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Conserved domains on  [gi|2462515664|ref|XP_054195711|]
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1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-2 isoform X7 [Homo sapiens]

Protein Classification

EFh_PI-PLCeta2 and PI-PLCc_eta2 domain-containing protein( domain architecture ID 11598620)

protein containing domains PH_PLC_eta, EFh_PI-PLCeta2, PI-PLCc_eta2, and C2_PLC_like

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PI-PLCc_eta2 cd08633
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily ...
 412-814 2.53e-175

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-eta isozyme 2. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-eta represents a class of neuron-speific PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-eta2 is a neuron-specific enzyme and expressed in the brain. It may in part function downstream of G-protein-coupled receptors and play an important role in the formation and maintenance of the neuronal network in the postnatal brain.


:

Pssm-ID: 176570 [Multi-domain]  Cd Length: 254  Bit Score: 517.29  E-value: 2.53e-175
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  412 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 491
Cdd:cd08633      1 NQDMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  492 KYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLDLSSVSSEDATTLPSPQMLKGKILVKGKklpanisedaeeg 571
Cdd:cd08633     81 KYAFIKNEYPVILSIENHCSVPQQKKMAQYLTEILGDKLDLSSVISNDCTRLPSPEILKGKILVKGK------------- 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  572 evsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeedvesge 651
Cdd:cd08633        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  652 dagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmKLSRALSDLVKYTKSVATHDIEME 731
Cdd:cd08633    148 --------------------------------------------------------KLSRALSDLVKYTKSVRVHDIETE 171

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  732 AASSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKF 811
Cdd:cd08633    172 ATSSWQVSSFSETKAHQILQQKPAQYLRFNQRQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKF 251


                   ...
gi 2462515664  812 SAN 814
Cdd:cd08633    252 SAN 254
EFh_PI-PLCeta2 cd16221
EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also ...
 260-400 2.71e-99

EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-2, or phosphoinositide phospholipase C-like 4, or phospholipase C-like protein 4 (PLC-L4), or phospholipase C-eta-2 (PLC-eta2), is a neuron-specific PI-PLC that is most abundant in the brain, particularly in the hippocampus, habenula, olfactory bulb, cerebellum, and throughout the cerebral cortex. It is also expressed in the pituitary gland, pineal gland, retina, and lung, as well as in neuroendocrine cells. PI-PLC-eta2 has been implicated in the regulation of neuronal differentiation/maturation. It is required for retinoic acid-stimulated neurite growth. It may also in part function downstream of G-protein-coupled receptors and play an important role in the formation and maintenance of the neuronal network in the postnatal brain. Moreover, PI-PLC-eta2 acts as a Ca2+ sensor that shows a canonical EF-loop directing Ca2+-sensitivity and thus can amplify transient Ca2+ signals. Its activation can be triggered either by intracellular calcium mobilization or by G beta-gamma signaling. PI-PLC-eta2 contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. The C-terminal tail harbors a number of proline-rich motifs which may interact with SH3 (Src homology 3) domain-containing proteins, as well as many serine/threonine residues, suggesting possible regulation of interactions by protein kinases/phosphatases.


:

Pssm-ID: 320051 [Multi-domain]  Cd Length: 141  Bit Score: 311.87  E-value: 2.71e-99
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  260 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTDDHQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 339
Cdd:cd16221      1 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQKVKQMFKEADTDDNQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462515664  340 NHKDHLDAASLQRFLQVEQKMAGVTLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRSPA 400
Cdd:cd16221     81 NHKDHLDTNDLQRFLEVEQKMAGVTREHCLEIISQFEPCSENKQNGALGIDGFTNYMRSPA 141
PH_PLC_eta cd13364
Phospholipase C-eta (PLC-eta) pleckstrin homology (PH) domain; PLC-eta (PLCeta) consists of ...
 136-242 1.49e-55

Phospholipase C-eta (PLC-eta) pleckstrin homology (PH) domain; PLC-eta (PLCeta) consists of two enzymes, PLCeta1 and PLCeta2. They hydrolyze phosphatidylinositol 4,5-bisphosphate, are more sensitive to Ca2+ than other PLC isozymes, and involved in PKC activation in the brain and neuroendocrine systems. PLC-eta consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves by a variable linker, a C2 domain, and a C-terminal PDZ domain. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.involved in targeting proteins to the plasma membrane, but only a few (less than 10%) display strong specificity in binding inositol phosphates. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinases, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, cytoskeletal associated molecules, and in lipid associated enzymes.


:

Pssm-ID: 270170  Cd Length: 109  Bit Score: 187.87  E-value: 1.49e-55
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  136 MQEGMQMVKLRGGSKGLVRFYYLDEHRSCIRWRPSRKN-EKAKISIDSIQEVSEGRQSEVFQRYP-DGNFDPNCCFSIYH 213
Cdd:cd13364      1 MQEGSELVKVRSNSRQYRRFFYLDEDKSSIRWKPSKKKsEKAKIPISSIREVREGKTTDIFRSCDiSGDFPEECCFSIIY 80

                           90       100
                   ....*....|....*....|....*....
gi 2462515664  214 GSHRESLDLVSTSSEVARTWVTGLRYLMA 242
Cdd:cd13364     81 GEEYETLDLVASSPDEANIWITGLRYLMS 109
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 844-969 1.66e-51

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.


:

Pssm-ID: 175974 [Multi-domain]  Cd Length: 128  Bit Score: 176.96  E-value: 1.66e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  844 KKQLVLRIISGQQLPKPRDsmlgDRGEIIDPFVEVEIIGLPV-DCSREQTRVVDDNGFNPTWEETLVFMVHMPEIALVRF 922
Cdd:cd00275      1 PLTLTIKIISGQQLPKPKG----DKGSIVDPYVEVEIHGLPAdDSAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRF 76

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2462515664  923 LVWDHDPIGRDFIGQRTLAFSSMMPGYRHVYL-----EGMEEASIFVHVAVS 969
Cdd:cd00275     77 VVYDEDSGDDDFLGQACLPLDSLRQGYRHVPLldskgEPLELSTLFVHIDIT 128
PHA03247 super family cl33720
large tegument protein UL36; Provisional
 989-1175 2.21e-03

large tegument protein UL36; Provisional


The actual alignment was detected with superfamily member PHA03247:

Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 42.62  E-value: 2.21e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  989 PKPGSLDSHAAGRPPARPSVsqrilrrTASAPTKSQKPGRRGFPELVLGTRDTGSKGVADDVVPPGPGPAPEAPAQEGPG 1068
Cdd:PHA03247  2743 AVPAGPATPGGPARPARPPT-------TAGPPAPAPPAAPAAGPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPA 2815

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664 1069 SGSPRGKAPAAvAEKSPVRVRPLRVLDGPGPAGMAATcmkcvvgSCAGVNTGGLQRERPPSPGPASRQAAiRQQPRARAD 1148
Cdd:PHA03247  2816 AALPPAASPAG-PLPPPTSAQPTAPPPPPGPPPPSLP-------LGGSVAPGGDVRRRPPSRSPAAKPAA-PARPPVRRL 2886

                          170       180
                   ....*....|....*....|....*..
gi 2462515664 1149 SLGAPCCGLDPHAIPGRSREAPKGPGA 1175
Cdd:PHA03247  2887 ARPAVSRSTESFALPPDQPERPPQPQA 2913
PRK12323 super family cl46901
DNA polymerase III subunit gamma/tau;
32-117 9.87e-03

DNA polymerase III subunit gamma/tau;


The actual alignment was detected with superfamily member PRK14950:

Pssm-ID: 481241 [Multi-domain]  Cd Length: 585  Bit Score: 40.18  E-value: 9.87e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664   32 VCDALLAQAT---PRQGTPGAPGAERPQSSLLLPPVDGRPQLVIPASPSFQLLPPPTVlSPSMMAPPTAGPLPGPALPPE 108
Cdd:PRK14950   355 VIEALLVPVPapqPAKPTAAAPSPVRPTPAPSTRPKAAAAANIPPKEPVRETATPPPV-PPRPVAPPVPHTPESAPKLTR 433


                   ....*....
gi 2462515664  109 DPGPYPESR 117
Cdd:PRK14950   434 AAIPVDEKP 442
 
Name Accession Description Interval E-value
PI-PLCc_eta2 cd08633
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily ...
 412-814 2.53e-175

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-eta isozyme 2. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-eta represents a class of neuron-speific PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-eta2 is a neuron-specific enzyme and expressed in the brain. It may in part function downstream of G-protein-coupled receptors and play an important role in the formation and maintenance of the neuronal network in the postnatal brain.


Pssm-ID: 176570 [Multi-domain]  Cd Length: 254  Bit Score: 517.29  E-value: 2.53e-175
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  412 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 491
Cdd:cd08633      1 NQDMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  492 KYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLDLSSVSSEDATTLPSPQMLKGKILVKGKklpanisedaeeg 571
Cdd:cd08633     81 KYAFIKNEYPVILSIENHCSVPQQKKMAQYLTEILGDKLDLSSVISNDCTRLPSPEILKGKILVKGK------------- 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  572 evsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeedvesge 651
Cdd:cd08633        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  652 dagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmKLSRALSDLVKYTKSVATHDIEME 731
Cdd:cd08633    148 --------------------------------------------------------KLSRALSDLVKYTKSVRVHDIETE 171

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  732 AASSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKF 811
Cdd:cd08633    172 ATSSWQVSSFSETKAHQILQQKPAQYLRFNQRQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKF 251


                   ...
gi 2462515664  812 SAN 814
Cdd:cd08633    252 SAN 254
EFh_PI-PLCeta2 cd16221
EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also ...
 260-400 2.71e-99

EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-2, or phosphoinositide phospholipase C-like 4, or phospholipase C-like protein 4 (PLC-L4), or phospholipase C-eta-2 (PLC-eta2), is a neuron-specific PI-PLC that is most abundant in the brain, particularly in the hippocampus, habenula, olfactory bulb, cerebellum, and throughout the cerebral cortex. It is also expressed in the pituitary gland, pineal gland, retina, and lung, as well as in neuroendocrine cells. PI-PLC-eta2 has been implicated in the regulation of neuronal differentiation/maturation. It is required for retinoic acid-stimulated neurite growth. It may also in part function downstream of G-protein-coupled receptors and play an important role in the formation and maintenance of the neuronal network in the postnatal brain. Moreover, PI-PLC-eta2 acts as a Ca2+ sensor that shows a canonical EF-loop directing Ca2+-sensitivity and thus can amplify transient Ca2+ signals. Its activation can be triggered either by intracellular calcium mobilization or by G beta-gamma signaling. PI-PLC-eta2 contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. The C-terminal tail harbors a number of proline-rich motifs which may interact with SH3 (Src homology 3) domain-containing proteins, as well as many serine/threonine residues, suggesting possible regulation of interactions by protein kinases/phosphatases.


Pssm-ID: 320051 [Multi-domain]  Cd Length: 141  Bit Score: 311.87  E-value: 2.71e-99
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  260 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTDDHQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 339
Cdd:cd16221      1 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQKVKQMFKEADTDDNQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462515664  340 NHKDHLDAASLQRFLQVEQKMAGVTLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRSPA 400
Cdd:cd16221     81 NHKDHLDTNDLQRFLEVEQKMAGVTREHCLEIISQFEPCSENKQNGALGIDGFTNYMRSPA 141
PI-PLC-X pfam00388
Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...
 415-557 6.82e-84

Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to form a single structural unit.


Pssm-ID: 459795 [Multi-domain]  Cd Length: 142  Bit Score: 269.37  E-value: 6.82e-84
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  415 MTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINKYA 494
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462515664  495 FIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLdLSSVSSEDATTLPSPQMLKGKILVKG 557
Cdd:pfam00388   81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDML-YTPPLDDDLTELPSPEDLKGKILIKG 142
PLN02952 PLN02952
phosphoinositide phospholipase C
 329-954 5.18e-68

phosphoinositide phospholipase C


Pssm-ID: 178538 [Multi-domain]  Cd Length: 599  Bit Score: 241.06  E-value: 5.18e-68
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  329 RDLYLLMLTYSNHKDHLDAASLQRFLQVEQKMAGVTLESCQDIIEQFEpcpeNK-------SKGLLGIDGFTNYTRSPag 401
Cdd:PLN02952    38 DDVKDVFCKFSVGGGHMGADQLRRFLVLHQDELDCTLAEAQRIVEEVI----NRrhhvtryTRHGLNLDDFFHFLLYD-- 111

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  402 DIFNPEHHHVHQDMTQPLSHYFITSSHNTYLVGDQLMSQ-SRVDMYAwVLQAGCRCVEVDCWDGPDGEPI-VHHGYTLTS 479
Cdd:PLN02952   112 DLNGPITPQVHHDMTAPLSHYFIYTGHNSYLTGNQLSSDcSEVPIVK-ALQRGVRVIELDLWPGSTKDEIlVLHGRTLTT 190

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  480 KILFKDVIETINKYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLDLSsvSSEDATTLPSPQMLKGKILVKGKK 559
Cdd:PLN02952   191 PVPLIKCLKSIRDYAFSSSPYPVIITLEDHLTPDLQAKVAEMATQIFGQMLYYP--ESDSLVQFPSPESLKHRIIISTKP 268

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  560 lPANISEDaeegevsdedsadeidddckllNGDASTNRKrventakrkldslikeskirdcedpnnfsvSTLSPSGKlgR 639
Cdd:PLN02952   269 -PKEYLES----------------------SGPIVIKKK------------------------------NNVSPSGR--N 293

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  640 KSKAEEDVESGEDAGASrrngrlvvgsfsrrkkkgsklkkAASVEEGDEGQDSPGGQSRGATRQKKTM-----KLSRALS 714
Cdd:PLN02952   294 SSEETEEAQTLESMLFE-----------------------QEADSRSDSDQDDNKSGELQKPAYKRLItihagKPKGTLK 350

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  715 DLVKYtksvathdiemeAASSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVA 794
Cdd:PLN02952   351 DAMKV------------AVDKVRRLSLSEQELEKAATTNGQDVVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIA 418

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  795 LNYQSEGRMLQLNRAKFSANGGCGYVLKPGCMCQGVFNPNSEDP---LPgqLKKQLVLRIISGQQLPKPRDSMLGDRGEI 871
Cdd:PLN02952   419 FNMQGYGKSLWLMHGMFRANGGCGYLKKPDFLMKKGFHDEVFDPkkkLP--VKKTLKVKVYLGDGWRLDFSHTHFDSYSP 496

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  872 IDPFVEVEIIGLPVDCSREQTRVVDDNgFNPTWEETLVFMVHMPEIALVRFLVWDHDPIGR-DFIGQRTLAFSSMMPGYR 950
Cdd:PLN02952   497 PDFYTKMYIVGVPADNAKKKTKIIEDN-WYPAWNEEFSFPLTVPELALLRIEVREYDMSEKdDFGGQTCLPVSELRPGIR 575


                   ....
gi 2462515664  951 HVYL 954
Cdd:PLN02952   576 SVPL 579
PLCXc smart00148
Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ...
 415-558 4.96e-63

Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. These enzymes contain 2 regions (X and Y) which together form a TIM barrel-like structure containing the active site residues. Phospholipase C enzymes (PI-PLC) act as signal transducers that generate two second messengers, inositol-1,4,5-trisphosphate and diacylglycerol. The bacterial enzyme appears to be a homologue of the mammalian PLCs.


Pssm-ID: 197543 [Multi-domain]  Cd Length: 143  Bit Score: 210.60  E-value: 4.96e-63
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664   415 MTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINKYA 494
Cdd:smart00148    1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80

                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462515664   495 FIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLdLSSVSSEDATTLPSPQMLKGKILVKGK 558
Cdd:smart00148   81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDML-YTPPLTSSLEVLPSPEQLRGKILLKVR 143
PH_PLC_eta cd13364
Phospholipase C-eta (PLC-eta) pleckstrin homology (PH) domain; PLC-eta (PLCeta) consists of ...
 136-242 1.49e-55

Phospholipase C-eta (PLC-eta) pleckstrin homology (PH) domain; PLC-eta (PLCeta) consists of two enzymes, PLCeta1 and PLCeta2. They hydrolyze phosphatidylinositol 4,5-bisphosphate, are more sensitive to Ca2+ than other PLC isozymes, and involved in PKC activation in the brain and neuroendocrine systems. PLC-eta consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves by a variable linker, a C2 domain, and a C-terminal PDZ domain. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.involved in targeting proteins to the plasma membrane, but only a few (less than 10%) display strong specificity in binding inositol phosphates. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinases, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, cytoskeletal associated molecules, and in lipid associated enzymes.


Pssm-ID: 270170  Cd Length: 109  Bit Score: 187.87  E-value: 1.49e-55
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  136 MQEGMQMVKLRGGSKGLVRFYYLDEHRSCIRWRPSRKN-EKAKISIDSIQEVSEGRQSEVFQRYP-DGNFDPNCCFSIYH 213
Cdd:cd13364      1 MQEGSELVKVRSNSRQYRRFFYLDEDKSSIRWKPSKKKsEKAKIPISSIREVREGKTTDIFRSCDiSGDFPEECCFSIIY 80

                           90       100
                   ....*....|....*....|....*....
gi 2462515664  214 GSHRESLDLVSTSSEVARTWVTGLRYLMA 242
Cdd:cd13364     81 GEEYETLDLVASSPDEANIWITGLRYLMS 109
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 844-969 1.66e-51

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.


Pssm-ID: 175974 [Multi-domain]  Cd Length: 128  Bit Score: 176.96  E-value: 1.66e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  844 KKQLVLRIISGQQLPKPRDsmlgDRGEIIDPFVEVEIIGLPV-DCSREQTRVVDDNGFNPTWEETLVFMVHMPEIALVRF 922
Cdd:cd00275      1 PLTLTIKIISGQQLPKPKG----DKGSIVDPYVEVEIHGLPAdDSAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRF 76

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2462515664  923 LVWDHDPIGRDFIGQRTLAFSSMMPGYRHVYL-----EGMEEASIFVHVAVS 969
Cdd:cd00275     77 VVYDEDSGDDDFLGQACLPLDSLRQGYRHVPLldskgEPLELSTLFVHIDIT 128
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 846-954 9.66e-22

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 91.01  E-value: 9.66e-22
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664   846 QLVLRIISGQQLPKPrdsmlgDRGEIIDPFVEVEIIGLPVdcSREQTRVVDDNGfNPTWEETLVFMVHMPEIALVRFLVW 925
Cdd:smart00239    1 TLTVKIISARNLPPK------DKGGKSDPYVKVSLDGDPK--EKKKTKVVKNTL-NPVWNETFEFEVPPPELAELEIEVY 71

                            90       100       110
                    ....*....|....*....|....*....|
gi 2462515664   926 DHDPIGRD-FIGQRTLAFSSMMPGYRHVYL 954
Cdd:smart00239   72 DKDRFGRDdFIGQVTIPLSDLLLGGRHEKL 101
C2 pfam00168
C2 domain;
846-951 6.38e-20

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 85.83  E-value: 6.38e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  846 QLVLRIISGQQLPKPrdsmlgDRGEIIDPFVEVEIIGlpvDCSREQTRVVDdNGFNPTWEETLVFMVHMPEIALVRFLVW 925
Cdd:pfam00168    2 RLTVTVIEAKNLPPK------DGNGTSDPYVKVYLLD---GKQKKKTKVVK-NTLNPVWNETFTFSVPDPENAVLEIEVY 71

                           90       100
                   ....*....|....*....|....*..
gi 2462515664  926 DHDPIGRD-FIGQRTLAFSSMMPGYRH 951
Cdd:pfam00168   72 DYDRFGRDdFIGEVRIPLSELDSGEGL 98
EF-hand_like pfam09279
Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are ...
 321-405 1.53e-13

Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are predominantly found in phosphoinositide-specific phospholipase C. They adopt a structure consisting of a core of four alpha helices, in an EF like fold, and are required for functioning of the enzyme.


Pssm-ID: 401279 [Multi-domain]  Cd Length: 85  Bit Score: 67.27  E-value: 1.53e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  321 FYKMMSTRRDLYLLMLTYSNHKDHLDAASLQRFLQVEQKMAGVTLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRSPA 400
Cdd:pfam09279    1 FYKMLTQREEIDEIFQEYSGDGQKLSLDELVDFLREEQREEDASPALALSLIERYEPSETAKKQHAMTKDGFLMYLCSPD 80


                   ....*
gi 2462515664  401 GDIFN 405
Cdd:pfam09279   81 GSIFN 85
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
250-321 1.55e-10

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 60.19  E-value: 1.55e-10
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462515664  250 LARRQRTRDQWLKQTFDEADKNGDGSLSIGEVLQLLHKLNVnlPRQRVKQMFREADTdDHQGTLGFEEFCAF 321
Cdd:COG5126     60 ESLFEATVEPFARAAFDLLDTDGDGKISADEFRRLLTALGV--SEEEADELFARLDT-DGDGKISFEEFVAA 128
PH_12 pfam16457
Pleckstrin homology domain;
128-241 6.42e-10

Pleckstrin homology domain;


Pssm-ID: 465123 [Multi-domain]  Cd Length: 128  Bit Score: 58.42  E-value: 6.42e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  128 VVERCMGAMQEGMQMVKLRGGSKGL-VRFYYLDEHRSCIRW---------RPSRKNEKAKISIDSIQEVSEGRQSEVF-- 195
Cdd:pfam16457    1 VKEQRLNCLLEGAWFPKVRGRRRKKkYRFCRLSPNRKVLHYgdfeekptvDPSLESLPEKIDLSDIKEVVTGKECPHVre 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 2462515664  196 QRYPDGNFDPNCCFSIYHGSH-RESLDLVSTSSEVARTWVTGLRYLM 241
Cdd:pfam16457   81 SGKKSKKTSSTLAFSLIYGADeYELLDFVAPSESVAAIWLDGLNMLL 127
PTZ00184 PTZ00184
calmodulin; Provisional
 250-328 2.18e-06

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 48.60  E-value: 2.18e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  250 LARRQRTRD--QWLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTDDhQGTLGFEEFCafyKMMST 327
Cdd:PTZ00184    73 MARKMKDTDseEEIKEAFKVFDRDGNGFISAAELRHVMTNLGEKLTDEEVDEMIREADVDG-DGQINYEEFV---KMMMS 148


                   .
gi 2462515664  328 R 328
Cdd:PTZ00184   149 K 149
PHA03247 PHA03247
large tegument protein UL36; Provisional
 989-1175 2.21e-03

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 42.62  E-value: 2.21e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  989 PKPGSLDSHAAGRPPARPSVsqrilrrTASAPTKSQKPGRRGFPELVLGTRDTGSKGVADDVVPPGPGPAPEAPAQEGPG 1068
Cdd:PHA03247  2743 AVPAGPATPGGPARPARPPT-------TAGPPAPAPPAAPAAGPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPA 2815

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664 1069 SGSPRGKAPAAvAEKSPVRVRPLRVLDGPGPAGMAATcmkcvvgSCAGVNTGGLQRERPPSPGPASRQAAiRQQPRARAD 1148
Cdd:PHA03247  2816 AALPPAASPAG-PLPPPTSAQPTAPPPPPGPPPPSLP-------LGGSVAPGGDVRRRPPSRSPAAKPAA-PARPPVRRL 2886

                          170       180
                   ....*....|....*....|....*..
gi 2462515664 1149 SLGAPCCGLDPHAIPGRSREAPKGPGA 1175
Cdd:PHA03247  2887 ARPAVSRSTESFALPPDQPERPPQPQA 2913
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
 297-325 4.05e-03

EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in pairs. Links between disease states and genes encoding EF-hands, particularly the S100 subclass, are emerging. Each motif consists of a 12 residue loop flanked on either side by a 12 residue alpha-helix. EF-hands undergo a conformational change unpon binding calcium ions.


Pssm-ID: 197492 [Multi-domain]  Cd Length: 29  Bit Score: 35.82  E-value: 4.05e-03
                            10        20
                    ....*....|....*....|....*....
gi 2462515664   297 VKQMFREADTdDHQGTLGFEEFCAFYKMM 325
Cdd:smart00054    2 LKEAFRLFDK-DGDGKIDFEEFKDLLKAL 29
PRK14950 PRK14950
DNA polymerase III subunits gamma and tau; Provisional
 32-117 9.87e-03

DNA polymerase III subunits gamma and tau; Provisional


Pssm-ID: 237864 [Multi-domain]  Cd Length: 585  Bit Score: 40.18  E-value: 9.87e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664   32 VCDALLAQAT---PRQGTPGAPGAERPQSSLLLPPVDGRPQLVIPASPSFQLLPPPTVlSPSMMAPPTAGPLPGPALPPE 108
Cdd:PRK14950   355 VIEALLVPVPapqPAKPTAAAPSPVRPTPAPSTRPKAAAAANIPPKEPVRETATPPPV-PPRPVAPPVPHTPESAPKLTR 433


                   ....*....
gi 2462515664  109 DPGPYPESR 117
Cdd:PRK14950   434 AAIPVDEKP 442
 
Name Accession Description Interval E-value
PI-PLCc_eta2 cd08633
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily ...
 412-814 2.53e-175

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-eta isozyme 2. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-eta represents a class of neuron-speific PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-eta2 is a neuron-specific enzyme and expressed in the brain. It may in part function downstream of G-protein-coupled receptors and play an important role in the formation and maintenance of the neuronal network in the postnatal brain.


Pssm-ID: 176570 [Multi-domain]  Cd Length: 254  Bit Score: 517.29  E-value: 2.53e-175
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  412 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 491
Cdd:cd08633      1 NQDMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  492 KYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLDLSSVSSEDATTLPSPQMLKGKILVKGKklpanisedaeeg 571
Cdd:cd08633     81 KYAFIKNEYPVILSIENHCSVPQQKKMAQYLTEILGDKLDLSSVISNDCTRLPSPEILKGKILVKGK------------- 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  572 evsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeedvesge 651
Cdd:cd08633        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  652 dagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmKLSRALSDLVKYTKSVATHDIEME 731
Cdd:cd08633    148 --------------------------------------------------------KLSRALSDLVKYTKSVRVHDIETE 171

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  732 AASSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKF 811
Cdd:cd08633    172 ATSSWQVSSFSETKAHQILQQKPAQYLRFNQRQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKF 251


                   ...
gi 2462515664  812 SAN 814
Cdd:cd08633    252 SAN 254
PI-PLCc_eta cd08594
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family ...
 412-814 1.55e-146

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-eta isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-eta represents a class of neuron-speific PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are two PI-PLC-eta isozymes (1-2), both neuron-specific enzymes. They function as calcium sensors that are activated by small increases in intracellular calcium concentrations. The PI-PLC-eta isozymes are also activated through GPCR stimulation. Aside from the PI-PLC-eta isozymes identified in mammals, their eukaryotic homologs are also present in this family.


Pssm-ID: 176536 [Multi-domain]  Cd Length: 227  Bit Score: 441.16  E-value: 1.55e-146
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  412 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 491
Cdd:cd08594      1 NQDMTQPLSHYFIASSHNTYLTGDQLLSQSRVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKILFRDVIETIN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  492 KYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLDLSSVSSEDATTLPSPQMLKGKILVKGKKlpanisedaeeg 571
Cdd:cd08594     81 KYAFIKNEYPVILSIENHCSVQQQKKMAQYLKEILGDKLDLSSVISGDSKQLPSPQSLKGKILIKGKK------------ 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  572 evsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeedvesge 651
Cdd:cd08594        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  652 dagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmklsralsdlvkytksvathdieme 731
Cdd:cd08594        --------------------------------------------------------------------------------

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  732 aassWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKF 811
Cdd:cd08594    149 ----WQVSSFSETRAHQIVQQKAAQFLRFNQRQLSRIYPSAYRIDSSNFNPQPYWNAGCQLVALNYQTEGRMLQLNRAKF 224


                   ...
gi 2462515664  812 SAN 814
Cdd:cd08594    225 RAN 227
PI-PLCc_eta1 cd08632
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta1; This subfamily ...
 412-814 4.66e-133

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-eta isozyme 1. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-eta represents a class of neuron-speific PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-eta1 is a neuron-specific enzyme and expressed in only nerve tissues such as the brain and spinal cord. It may perform a fundamental role in the brain.


Pssm-ID: 176569 [Multi-domain]  Cd Length: 253  Bit Score: 406.72  E-value: 4.66e-133
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  412 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 491
Cdd:cd08632      1 NQDMDQPLCNYFIASSHNTYLTGDQLLSQSKVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKITFRDVIETIN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  492 KYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLDLSSVSSEDATTLPSPQMLKGKILVKGKklpanisedaeeg 571
Cdd:cd08632     81 KYAFVKNEFPVILSIENHCSIQQQKKIAQYLKEIFGDKLDLSSVLTGDPKQLPSPQLLKGKILVKGK------------- 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  572 evsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeedvesge 651
Cdd:cd08632        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  652 dagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmKLSRALSDLVKYTKSVATHDIeME 731
Cdd:cd08632    148 --------------------------------------------------------KLCRDLSDLVVYTNSVAAQDI-VD 170

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  732 AASSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKF 811
Cdd:cd08632    171 DGSTGNVLSFSETRAHQLVQQKAEQFMTYNQKQLTRIYPSAYRIDSSNFNPLPYWNVGCQLVALNYQSEGRMMQLNRAKF 250


                   ...
gi 2462515664  812 SAN 814
Cdd:cd08632    251 MVN 253
PI-PLCc_eukaryota cd08558
Catalytic domain of eukaryotic phosphoinositide-specific phospholipase C and similar proteins; ...
 412-814 2.07e-129

Catalytic domain of eukaryotic phosphoinositide-specific phospholipase C and similar proteins; This family corresponds to the catalytic domain present in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) and similar proteins. The higher eukaryotic PI-PLCs play a critical role in most signal transduction pathways, controlling numerous cellular events such as cell growth, proliferation, excitation and secretion. They strictly require Ca2+ for the catalytic activity. They display a clear preference towards the hydrolysis of the more highly phosphorylated membrane phospholipids PI-analogues, phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol-4-phosphate (PIP), to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. The eukaryotic PI-PLCs have a multidomain organization that consists of a PLC catalytic core domain, and various regulatory domains, such as the pleckstrin homology (PH) domain, EF-hand motif, and C2 domain. The catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a linker region. The catalytic mechanism of eukaryotic PI-PLCs is based on general base and acid catalysis utilizing two well conserved histidines and consists of two steps, a phosphotransfer and a phosphodiesterase reaction. The mammalian PI-PLCs consist of 13 isozymes, which are classified into six-subfamilies, PI-PLC-delta (1,3 and 4), -beta(1-4), -gamma(1,2), -epsilon, -zeta, and -eta (1,2). Ca2+ is required for the activation of all forms of mammalian PI-PLCs, and the concentration of calcium influences substrate specificity. This family also includes metazoan phospholipase C related but catalytically inactive proteins (PRIP), which belong to a group of novel inositol trisphosphate binding proteins. Due to the replacement of critical catalytic residues, PRIP does not have PLC enzymatic activity.


Pssm-ID: 176501 [Multi-domain]  Cd Length: 226  Bit Score: 395.67  E-value: 2.07e-129
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  412 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 491
Cdd:cd08558      1 YQDMTQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGHTLTSKILFKDVIEAIK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  492 KYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLDLSSVSSEDaTTLPSPQMLKGKILVKGKKlpanisedaeeg 571
Cdd:cd08558     81 EYAFVTSPYPVILSLENHCSLEQQKKMAQILKEIFGDKLLTPPLDENP-VQLPSPEQLKGKILIKGKK------------ 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  572 evsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeedvesge 651
Cdd:cd08558        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  652 dagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmklsralsdlvkytksvathdieme 731
Cdd:cd08558        --------------------------------------------------------------------------------

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  732 aassWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKF 811
Cdd:cd08558    148 ----YHMSSFSETKALKLLKESPEEFVKYNKRQLSRVYPKGTRVDSSNYNPQPFWNAGCQMVALNYQTPDLPMQLNQGKF 223


                   ...
gi 2462515664  812 SAN 814
Cdd:cd08558    224 EQN 226
PI-PLCc_delta cd08593
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta; This subfamily ...
 412-814 1.29e-118

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This CD corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). PI-PLC-delta1 is relatively well characterized. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. Different PI-PLC-delta isozymes have different tissue distribution and different subcellular locations. PI-PLC-delta1 is mostly a cytoplasmic protein, PI-PLC-delta3 is located in the membrane, and PI-PLC-delta4 is predominantly detected in the cell nucleus. Aside from three PI-PLC-delta isozymes identified in mammals, some eukaryotic PI-PLC-delta homologs have been classified to this CD.


Pssm-ID: 176535 [Multi-domain]  Cd Length: 257  Bit Score: 368.59  E-value: 1.29e-118
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  412 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 491
Cdd:cd08593      1 YQDMTQPLSHYFIASSHNTYLLEDQLKGPSSTEAYIRALKKGCRCVELDCWDGPDGEPIIYHGHTLTSKILFKDVIQAIR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  492 KYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLdLSSVSSEDATTLPSPQMLKGKILVKGKKLpanisedaeeg 571
Cdd:cd08593     81 EYAFKVSPYPVILSLENHCSVEQQKVMAQHLKSILGDKL-LTQPLDGVLTALPSPEELKGKILVKGKKL----------- 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  572 evsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeedvesge 651
Cdd:cd08593        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  652 dagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmKLSRALSDLVKYTKSVATHDIE-- 729
Cdd:cd08593    149 --------------------------------------------------------KLAKELSDLVIYCKSVHFKSFEhs 172

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  730 MEAASSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRA 809
Cdd:cd08593    173 KENYHFYEMSSFSESKALKLAQESGNEFVRHNKRQLSRIYPAGLRTDSSNYDPQEMWNVGCQIVALNFQTPGEEMDLNDG 252


                   ....*
gi 2462515664  810 KFSAN 814
Cdd:cd08593    253 LFRQN 257
EFh_PI-PLCeta2 cd16221
EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also ...
 260-400 2.71e-99

EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-2, or phosphoinositide phospholipase C-like 4, or phospholipase C-like protein 4 (PLC-L4), or phospholipase C-eta-2 (PLC-eta2), is a neuron-specific PI-PLC that is most abundant in the brain, particularly in the hippocampus, habenula, olfactory bulb, cerebellum, and throughout the cerebral cortex. It is also expressed in the pituitary gland, pineal gland, retina, and lung, as well as in neuroendocrine cells. PI-PLC-eta2 has been implicated in the regulation of neuronal differentiation/maturation. It is required for retinoic acid-stimulated neurite growth. It may also in part function downstream of G-protein-coupled receptors and play an important role in the formation and maintenance of the neuronal network in the postnatal brain. Moreover, PI-PLC-eta2 acts as a Ca2+ sensor that shows a canonical EF-loop directing Ca2+-sensitivity and thus can amplify transient Ca2+ signals. Its activation can be triggered either by intracellular calcium mobilization or by G beta-gamma signaling. PI-PLC-eta2 contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. The C-terminal tail harbors a number of proline-rich motifs which may interact with SH3 (Src homology 3) domain-containing proteins, as well as many serine/threonine residues, suggesting possible regulation of interactions by protein kinases/phosphatases.


Pssm-ID: 320051 [Multi-domain]  Cd Length: 141  Bit Score: 311.87  E-value: 2.71e-99
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  260 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTDDHQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 339
Cdd:cd16221      1 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQKVKQMFKEADTDDNQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462515664  340 NHKDHLDAASLQRFLQVEQKMAGVTLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRSPA 400
Cdd:cd16221     81 NHKDHLDTNDLQRFLEVEQKMAGVTREHCLEIISQFEPCSENKQNGALGIDGFTNYMRSPA 141
PI-PLCc_PRIP_metazoa cd08597
Catalytic domain of metazoan phospholipase C related, but catalytically inactive protein; This ...
 412-814 8.02e-99

Catalytic domain of metazoan phospholipase C related, but catalytically inactive protein; This family corresponds to the catalytic domain present in metazoan phospholipase C related, but catalytically inactive proteins (PRIP), which belong to a group of novel Inositol 1,4,5-trisphosphate (InsP3) binding protein. PRIP has a primary structure and domain architecture, incorporating a pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain with highly conserved X- and Y-regions split by a linker sequence, and a C-terminal C2 domain, similar to phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11)-delta isoforms. Due to replacement of critical catalytic residues, PRIP do not have PLC enzymatic activity. PRIP consists of two subfamilies, PRIP-1(previously known as p130 or PLC-1), which is predominantly expressed in the brain, and PRIP-2 (previously known as PLC-2), which exhibits a relatively ubiquitous expression. Experiments show both, PRIP-1 and PRIP-2, are involved in InsP3-mediated calcium signaling pathway and GABA(A)receptor-mediated signaling pathway. In addition, PRIP-2 acts as a negative regulator of B-cell receptor signaling and immune responses.


Pssm-ID: 176539 [Multi-domain]  Cd Length: 260  Bit Score: 315.13  E-value: 8.02e-99
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  412 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 491
Cdd:cd08597      1 CQDMTQPLSHYFIASSHNTYLIEDQLRGPSSVEGYVRALQRGCRCVELDCWDGPNGEPVIYHGHTLTSKISFRSVIEAIN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  492 KYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLDLSSVsSEDATTLPSPQMLKGKILVKGKKLpanisedaeeg 571
Cdd:cd08597     81 EYAFVASEYPLILCIENHCSEKQQLVMAQYLKEIFGDKLYTEPP-NEGESYLPSPHDLKGKIIIKGKKL----------- 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  572 evsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeedvesge 651
Cdd:cd08597        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  652 dagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkKTMKLSRALSDLVKYTKSVATHDIEME 731
Cdd:cd08597    149 -----------------------------------------------------KRRKLCKELSDLVSLCKSVRFQDFPTS 175

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  732 AASS--WQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRA 809
Cdd:cd08597    176 AQNQkyWEVCSFSENLARRLANEFPEDFVNYNKKFLSRVYPSPMRVDSSNYNPQDFWNCGCQIVAMNYQTPGLMMDLNTG 255


                   ....*
gi 2462515664  810 KFSAN 814
Cdd:cd08597    256 KFLEN 260
EFh_PI-PLCeta cd16205
EF-hand motif found in phosphoinositide phospholipase C eta (PI-PLC-eta); PI-PLC-eta isozymes ...
 260-400 3.00e-95

EF-hand motif found in phosphoinositide phospholipase C eta (PI-PLC-eta); PI-PLC-eta isozymes represent a class of neuron-specific metazoan PI-PLCs that are most abundant in the brain, particularly in the hippocampus, habenula, olfactory bulb, cerebellum, and throughout the cerebral cortex. They are phosphatidylinositol 4,5-bisphosphate-hydrolyzing enzymes that are more sensitive to Ca2+ than other PI-PLC isozymes. They function as calcium sensors activated by small increases in intracellular calcium concentrations. They are also activated through G-protein-coupled receptor (GPCR) stimulation, and further mediate GPCR signalling pathways. PI-PLC-eta isozymes contain an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. The C-terminal tail harbors a number of proline-rich motifs which may interact with SH3 (Src homology 3) domain-containing proteins, as well as many serine/threonine residues, suggesting possible regulation of interactions by protein kinases/phosphatases. There are two PI-PLC-eta isozymes (1-2). Aside from the PI-PLC-eta isozymes identified in mammals, their eukaryotic homologs are also present in this family.


Pssm-ID: 320035 [Multi-domain]  Cd Length: 141  Bit Score: 300.84  E-value: 3.00e-95
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  260 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTDDHQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 339
Cdd:cd16205      1 WLKQTFEEADKNGDGLLSIGEILQLMHKLNVNLPRRKVRQMFKEADTDDNQGTLDFEEFCAFYKMMSTRRELYLLLLSYS 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462515664  340 NHKDHLDAASLQRFLQVEQKMAGVTLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRSPA 400
Cdd:cd16205     81 NKKDYLTLEDLARFLEVEQKMTNVTLEYCLDIIEKFEPSEENKKNGLLGIDGFTNYMRSPA 141
PI-PLCc_gamma cd08592
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family ...
 413-814 1.36e-93

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-gamma isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-gamma represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain.The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma, a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region is present within this linker region. There are two PI-PLC-gamma isozymes (1-2). They are activated by receptor and non-receptor tyrosine kinases due to the presence of two SH2 and a single SH3 domain within the linker region. Aside from the two PI-PLC-gamma isozymes identified in mammals, some eukaryotic PI-PLC-gamma homologs have been classified with this subfamily.


Pssm-ID: 176534 [Multi-domain]  Cd Length: 229  Bit Score: 299.73  E-value: 1.36e-93
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  413 QDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 492
Cdd:cd08592      2 QDMNNPLSHYWIASSHNTYLTGDQLSSESSLEAYARCLRMGCRCIELDCWDGPDGMPIIYHGHTLTSKIKFMDVLKTIKE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  493 YAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLdLSSVSSEDATTLPSPQMLKGKILVKGKKLpanisedaeege 572
Cdd:cd08592     82 HAFVTSEYPVILSIENHCSLPQQRNMAQAFKEVFGDML-LTQPVDRNADQLPSPNQLKRKIIIKHKKL------------ 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  573 vsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeedvesged 652
Cdd:cd08592        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  653 agasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmklsralsdlvkYTksvathdiEMea 732
Cdd:cd08592    149 ------------------------------------------------------------------FY--------EM-- 152

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  733 asswqvSSFSETKAHQIL-QQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKF 811
Cdd:cd08592    153 ------SSFPETKAEKYLnRQKGKIFLKYNRRQLSRVYPKGQRVDSSNYDPVPMWNCGSQMVALNFQTPDKPMQLNQALF 226


                   ...
gi 2462515664  812 SAN 814
Cdd:cd08592    227 MLN 229
PI-PLCc_beta cd08591
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily ...
 412-814 1.71e-93

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are four PLC-beta isozymes (1-4). They are activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. The beta-gamma subunits of heterotrimeric G proteins are known to activate the PLC-beta2 and -beta3 isozymes only. Aside from four PLC-beta isozymes identified in mammals, some eukaryotic PLC-beta homologs have been classified into this subfamily, such as NorpA and PLC-21 from Drosophila and PLC-beta from turkey, Xenopus, sponge, and hydra.


Pssm-ID: 176533 [Multi-domain]  Cd Length: 257  Bit Score: 300.41  E-value: 1.71e-93
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  412 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDG--PDGEPIVHHGYTLTSKILFKDVIET 489
Cdd:cd08591      1 YQDMDQPLSHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLSGCRCIELDCWDGkgEDEEPIITHGKTMCTEILFKDVIEA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  490 INKYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKL---DLSSVSSEDATTLPSPQMLKGKILVKGKKlpanise 566
Cdd:cd08591     81 IAETAFKTSEYPVILSFENHCSSKQQAKMAEYCREIFGDLLltePLEKYPLEPGVPLPSPNDLKRKILIKNKK------- 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  567 daeegevsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeed 646
Cdd:cd08591        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  647 vesgedagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmklsraLSDLVKYTKSV--A 724
Cdd:cd08591    154 ------------------------------------------------------------------LSSLVNYIQPVkfQ 167

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  725 THDIEMEAASSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRML 804
Cdd:cd08591    168 GFEVAEKRNKHYEMSSFNESKGLGYLKKSPIEFVNYNKRQLSRIYPKGTRVDSSNYMPQIFWNAGCQMVALNFQTPDLPM 247

                          410
                   ....*....|
gi 2462515664  805 QLNRAKFSAN 814
Cdd:cd08591    248 QLNQGKFEYN 257
PI-PLCc_delta4 cd08631
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta4; This subfamily ...
 412-814 9.43e-93

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta4; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta4 isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This CD corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). Unlike PI-PLC-delta 1 and 3, a putative nuclear export sequence (NES) located in the EF-hand domain, which may be responsible transporting PI-PLC-delta1 and 3 from the cell nucleus, is not present in PI-PLC-delta4. Experiments show PI-PLC-delta4 is required for the acrosome reaction in fertilization.


Pssm-ID: 176568 [Multi-domain]  Cd Length: 258  Bit Score: 298.78  E-value: 9.43e-93
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  412 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 491
Cdd:cd08631      1 YQDMTQPLCHYFICSSHNTYLMEDQLRGQSSVEGYIRALKRGCRCVEVDVWDGPNGEPIVYHGHTFTSKILFKDVVAAVA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  492 KYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLDLSSVSSEDATTLPSPQMLKGKILVKGKKLpanisedaeeg 571
Cdd:cd08631     81 QYAFQVSDYPVILSLENHCGVEQQQTMAQHLTEILGEKLLSTTLDGVLPTQLPSPEELRGKILLKGKKI----------- 149

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  572 evsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeedvesge 651
Cdd:cd08631        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  652 dagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmKLSRALSDLVKYTKSVATHDIEME 731
Cdd:cd08631    150 --------------------------------------------------------RLSPELSDCVIYCKSVSFRSFTHS 173

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  732 AASS--WQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRA 809
Cdd:cd08631    174 REHYhfYEISSFTETKARKLIREAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQEMWNAGCQMVALNFQTAGLEMDLNDG 253


                   ....*
gi 2462515664  810 KFSAN 814
Cdd:cd08631    254 LFRQN 258
PI-PLCc_delta1 cd08629
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta1; This subfamily ...
 412-814 1.74e-87

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta1 isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This subfamily corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). PI-PLC-delta1 is relatively well characterized. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. Unlike PI-PLC-delta 4, PI-PLC-delta1 and 3 possess a putative nuclear export sequence (NES) located in the EF-hand domain, which may be responsible transporting PI-PLC-delta1and 3 from the cell nucleus. Experiments show PI-PLC-delta1 is essential for normal hair formation.


Pssm-ID: 176566 [Multi-domain]  Cd Length: 258  Bit Score: 284.23  E-value: 1.74e-87
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  412 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 491
Cdd:cd08629      1 YQDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVLRAIR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  492 KYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLdLSSVSSEDATTLPSPQMLKGKILVKGKKLpanisedaeeg 571
Cdd:cd08629     81 DYAFKASPYPVILSLENHCSLEQQRVMARHLRAILGPIL-LDQPLDGVTTSLPSPEQLKGKILLKGKKL----------- 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  572 evsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeedvesge 651
Cdd:cd08629        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  652 dagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmKLSRALSDLVKYTKSVATHDIE-- 729
Cdd:cd08629    149 --------------------------------------------------------KLVPELSDMIIYCKSVHFGGFSsp 172

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  730 -MEAASSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNR 808
Cdd:cd08629    173 gTSGQAFYEMASFSESRALRLLQESGNGFVRHNVSCLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYL 252


                   ....*.
gi 2462515664  809 AKFSAN 814
Cdd:cd08629    253 GCFQDN 258
PI-PLC-X pfam00388
Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...
 415-557 6.82e-84

Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to form a single structural unit.


Pssm-ID: 459795 [Multi-domain]  Cd Length: 142  Bit Score: 269.37  E-value: 6.82e-84
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  415 MTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINKYA 494
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462515664  495 FIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLdLSSVSSEDATTLPSPQMLKGKILVKG 557
Cdd:pfam00388   81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDML-YTPPLDDDLTELPSPEDLKGKILIKG 142
PI-PLCc_zeta cd08595
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-zeta; This family ...
 412-814 1.31e-83

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-zeta; This family corresponds to the catalytic domain presenting in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-zeta isozyme. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-zeta represents a class of sperm-specific PI-PLC that has an N-terminal EF-hand domain, a PLC catalytic core domain, and a C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There is one PLC-zeta isozyme (1). PLC-zeta plays a fundamental role in vertebrate fertilization by initiating intracellular calcium oscillations that trigger the embryo development. However, the mechanism of its activation still remains unclear. Aside from PI-PLC-zeta identified in mammals, its eukaryotic homologs have been classified with this family.


Pssm-ID: 176537 [Multi-domain]  Cd Length: 257  Bit Score: 273.35  E-value: 1.31e-83
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  412 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 491
Cdd:cd08595      1 YQDMDHPLSDYFISSSHNTYLVSDQLVGPSDLDGYVSALRKGCRCLEIDCWDGADNEPVVYHGYTLTSKILFKEVITTVE 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  492 KYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLDLSSVSSEDATTLPSPQMLKGKILVKGKKlpanisedaeeg 571
Cdd:cd08595     81 KYAFEKSDYPVVLSLENHCSTEQQEIMAHYLVSILGEKLLRAPIDDPATGELPSPEALKFKILVKNKK------------ 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  572 evsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeedvesge 651
Cdd:cd08595        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  652 dagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmKLSRALSDLVKYTKSVA----THD 727
Cdd:cd08595    149 --------------------------------------------------------KIAKALSDLVIYTKSEKfcsfTHS 172

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  728 IEMEaaSSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLN 807
Cdd:cd08595    173 RDNQ--HSYENNSIGENKARKLLKSSGADFVGHTQRFITRIYPKGTRASSSNYNPQEFWNVGCQMVALNFQTLGAPMDLQ 250


                   ....*..
gi 2462515664  808 RAKFSAN 814
Cdd:cd08595    251 NGKFLDN 257
PI-PLCc_delta3 cd08630
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta3; This subfamily ...
 412-814 1.90e-82

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta3; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta3 isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This family corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). Unlike PI-PLC-delta 4, PI-PLC-delta1 and 3 possess a putative nuclear export sequence (NES) located in the EF-hand domain, which may be responsible transporting PI-PLC-delta1 and 3 from the cell nucleus.


Pssm-ID: 176567 [Multi-domain]  Cd Length: 258  Bit Score: 270.35  E-value: 1.90e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  412 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 491
Cdd:cd08630      1 FQDMSQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVIQAVR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  492 KYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLDLSSVSSEDATTLPSPQMLKGKILVKGKKLpanisedaeeg 571
Cdd:cd08630     81 QHAFTASPYPVILSLENHCGLEQQAAMARHLQTILGDMLVTQPLDSLNPEELPSPEELKGRVLVKGKKL----------- 149

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  572 evsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeedvesge 651
Cdd:cd08630        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  652 dagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmKLSRALSDLVKYTKSVATHDIEM- 730
Cdd:cd08630    150 --------------------------------------------------------QISPELSALAVYCQATRLRTLEPa 173

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  731 -EAASSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRA 809
Cdd:cd08630    174 pVQPQPCQVSSLSERKAKKLIREAGNSFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLVALNFQTPGYEMDLNAG 253


                   ....*
gi 2462515664  810 KFSAN 814
Cdd:cd08630    254 RFLVN 258
PI-PLCc_gamma2 cd08628
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma2; This subfamily ...
 413-814 2.15e-80

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma2; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-gamma isozyme 2. PI-PLC is a signaling enzyme that hydrolyze the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-gamma represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma2, a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region is present within this linker region. PI-PLC-gamma2 is highly expressed in cells of hematopoietic origin. It is activated by receptor and non-receptor tyrosine kinases due to the presence of two SH2 and a single SH3 domain within the linker region. Unlike PI-PLC-gamma1, the activation of PI-PLC-gamma2 may require concurrent stimulation of PI 3-kinase.


Pssm-ID: 176565 [Multi-domain]  Cd Length: 254  Bit Score: 264.22  E-value: 2.15e-80
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  413 QDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 492
Cdd:cd08628      2 QDMNNPLSHYWISSSHNTYLTGDQLRSESSTEAYIRCLRMGCRCIELDCWDGPDGKPIIYHGWTRTTKIKFDDVVQAIKD 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  493 YAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLDLSSVSSEdATTLPSPQMLKGKILVKGKKLPANisedaeege 572
Cdd:cd08628     82 HAFVTSEYPVILSIEEHCSVEQQRHMAKVFKEVFGDKLLMKPLEAS-ADQLPSPTQLKEKIIIKHKKLIAI--------- 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  573 vsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeedvesged 652
Cdd:cd08628        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  653 agasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmklsrALSDLVKYTKSVATHDIEMEA 732
Cdd:cd08628    152 -----------------------------------------------------------ELSDLVVYCKPTSKTKDNLEN 172

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  733 ASSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKFS 812
Cdd:cd08628    173 PDFKEIRSFVETKAPSIIRQKPVQLLKYNRKGLTRVYPKGQRVDSSNYDPFRLWLCGSQMVALNFQTADKYMQLNHALFS 252


                   ..
gi 2462515664  813 AN 814
Cdd:cd08628    253 LN 254
PI-PLC1c_yeast cd08598
Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This ...
 413-814 4.38e-80

Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This family corresponds to the catalytic domain present in a group of putative phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) encoded by PLC1 genes from yeasts, which are homologs of the delta isoforms of mammalian PI-PLC in terms of overall sequence similarity and domain organization. Mammalian PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. The prototype of this CD is protein Plc1p encoded by PLC1 genes from Saccharomyces cerevisiae. Plc1p contains both highly conserved X- and Y- regions of PLC catalytic core domain, as well as a presumptive EF-hand like calcium binding motif. Experiments show that Plc1p displays calcium dependent catalytic properties with high similarity to those of the mammalian PLCs, and plays multiple roles in modulating the membrane/protein interactions in filamentation control. CaPlc1p encoded by CAPLC1 from the closely related yeast Candida albicans, an orthologue of S. cerevisiae Plc1p, is also included in this group. Like Plc1p, CaPlc1p has conserved presumptive catalytic domain, shows PLC activity when expressed in E. coli, and is involved in multiple cellular processes. There are two other gene copies of CAPLC1 in C. albicans, CAPLC2 (also named as PIPLC) and CAPLC3. Experiments show CaPlc1p is the only enzyme in C. albicans which functions as PLC. The biological functions of CAPLC2 and CAPLC3 gene products must be clearly different from CaPlc1p, but their exact roles remain unclear. Moreover, CAPLC2 and CAPLC3 gene products are more similar to extracellular bacterial PI-PLC than to the eukaryotic PI-PLC, and they are not included in this subfamily.


Pssm-ID: 176540 [Multi-domain]  Cd Length: 231  Bit Score: 262.57  E-value: 4.38e-80
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  413 QDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 492
Cdd:cd08598      2 EDLSRPLNEYFISSSHNTYLLGRQLAGDSSVEGYIRALQRGCRCVEIDVWDGDDGEPVVTHGYTLTSSVPFRDVCRAIKK 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  493 YAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLdLSSVSSEDATTLPSPQMLKGKILVKgkklpanisedaeege 572
Cdd:cd08598     82 YAFVTSPYPLILSLEVHCDAEQQERMVEIMKETFGDLL-VTEPLDGLEDELPSPEELRGKILIK---------------- 144

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  573 vsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeedvesged 652
Cdd:cd08598        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  653 agasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmklsralsdlVKYTKSVATHDIemea 732
Cdd:cd08598    145 ----------------------------------------------------------------VKKESKTPNHIF---- 156

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  733 asswqvsSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKFS 812
Cdd:cd08598    157 -------SLSERSLLKLLKDKRAALDKHNRRHLMRVYPSGTRISSSNFNPLPFWRAGVQMVALNWQTYDLGMQLNEAMFA 229


                   ..
gi 2462515664  813 AN 814
Cdd:cd08598    230 GS 231
PI-PLCc_beta4 cd08626
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta4; This subfamily ...
 412-814 9.27e-76

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta4; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozyme 4. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-beta4 is expressed in high concentrations in cerebellar Purkinje and granule cells, the median geniculate body, and the lateral geniculate nucleus. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension.


Pssm-ID: 176563 [Multi-domain]  Cd Length: 257  Bit Score: 251.22  E-value: 9.27e-76
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  412 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGP--DGEPIVHHGYTLTSKILFKDVIET 489
Cdd:cd08626      1 YQDMDQPLAHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLAGCRCIELDCWDGKgeDQEPIITHGKAMCTDILFKDVIQA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  490 INKYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKL---DLSSVSSEDATTLPSPQMLKGKILVKGKKlpanise 566
Cdd:cd08626     81 IKDTAFVTSDYPVILSFENHCSKPQQYKLAKYCEEIFGDLLltkPLESHPLEPGVPLPSPNKLKRKILIKNKR------- 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  567 daeegevsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeed 646
Cdd:cd08626        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  647 vesgedagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmklsraLSDLVKYTKSV--A 724
Cdd:cd08626    154 ------------------------------------------------------------------LSSLVNYAQPVkfQ 167

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  725 THDIEMEAASSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRML 804
Cdd:cd08626    168 GFDVAEERNIHFNMSSFNESVGLGYLKTSAIEFVNYNKRQMSRIYPKGTRVDSSNYMPQIFWNAGCQMVSLNFQTPDLGM 247

                          410
                   ....*....|
gi 2462515664  805 QLNRAKFSAN 814
Cdd:cd08626    248 QLNQGKFEYN 257
PI-PLCc_epsilon cd08596
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family ...
 413-814 7.44e-73

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-epsilon isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-epsilon represents a class of mammalian PI-PLC that has an N-terminal CDC25 homology domain with a guanyl-nucleotide exchange factor (GFF) activity, a pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and two predicted RA (Ras association) domains that are implicated in the binding of small GTPases, such as Ras or Rap, from the Ras family. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There is one PI-PLC-epsilon isozyme (1). PI-PLC-epsilon is activated by G alpha(12/13), G beta gamma, and activated members of Ras and Rho small GTPases. Aside from PI-PLC-epsilon identified in mammals, its eukaryotic homologs have been classified with this family.


Pssm-ID: 176538 [Multi-domain]  Cd Length: 254  Bit Score: 243.22  E-value: 7.44e-73
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  413 QDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 492
Cdd:cd08596      2 EDLQYPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLTGCRCVELDCWDGDDGMPIIYHGHTLTTKIPFKDVVEAINR 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  493 YAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLD---LSSVSSEDATTLPSPQMLKGKILVKGKKLPanisedae 569
Cdd:cd08596     82 SAFITSDYPVILSIENHCSLQQQRKMAEIFKTVFGEKLVtkfLFESDFSDDPSLPSPLQLKNKILLKNKKAP-------- 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  570 egevsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeedves 649
Cdd:cd08596        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  650 gedagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmklsrALSDLVKYTKSVATHDie 729
Cdd:cd08596    154 --------------------------------------------------------------ELSDLVIYCQAVKFPG-- 169

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  730 MEAASSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRA 809
Cdd:cd08596    170 LSTPKCYHISSLNENAAKRLCRRYPQKLVQHTRCQLLRTYPAATRIDSSNPNPLIFWLHGLQLVALNYQTDDLPMHLNAA 249


                   ....*
gi 2462515664  810 KFSAN 814
Cdd:cd08596    250 MFEAN 254
PI-PLCc_beta2 cd08624
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta2; This subfamily ...
 412-814 1.03e-71

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta2; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozyme 2. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-beta2 is expressed at highest levels in cells of hematopoietic origin. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. It is also activated by the beta-gamma subunits of heterotrimeric G proteins.


Pssm-ID: 176561 [Multi-domain]  Cd Length: 261  Bit Score: 240.34  E-value: 1.03e-71
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  412 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDG--PDGEPIVHHGYTLTSKILFKDVIET 489
Cdd:cd08624      1 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSPEMYRQVLLSGCRCVELDCWKGkpPDEEPIITHGFTMTTEILFKDAIEA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  490 INKYAFIKNEYPVILSIENHC-SVIQQKKMAQYLTDILGDKL---DLSSVSSEDATTLPSPQMLKGKILVKGKKLpanis 565
Cdd:cd08624     81 IAESAFKTSPYPVILSFENHVdSPKQQAKMAEYCRTIFGDMLltePLEKYPLKPGVPLPSPEDLRGKILIKNKKY----- 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  566 edaeegevsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaee 645
Cdd:cd08624        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  646 dvesgedagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmklsRALSDLVKYTKSVA- 724
Cdd:cd08624    156 -----------------------------------------------------------------EEMSSLVNYIQPTKf 170

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  725 -THDIEMEAASSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRM 803
Cdd:cd08624    171 vSFEFSAQKNRSYVISSFTELKAYDLLSKASVQFVEYNKRQMSRIYPKGTRMDSSNYMPQMFWNVGCQMVALNFQTMDLP 250

                          410
                   ....*....|.
gi 2462515664  804 LQLNRAKFSAN 814
Cdd:cd08624    251 MQQNMALFEFN 261
EFh_PI-PLCeta1 cd16220
EF-hand motif found in phosphoinositide phospholipase C eta 1 (PI-PLC-eta1); PI-PLC-eta1, also ...
 260-400 1.45e-71

EF-hand motif found in phosphoinositide phospholipase C eta 1 (PI-PLC-eta1); PI-PLC-eta1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-1, or phospholipase C-eta-1 (PLC-eta-1), or phospholipase C-like protein 3 (PLC-L3), is a neuron-specific PI-PLC that is most abundant in the brain, particularly in the hippocampus, habenula, olfactory bulb, cerebellum, and throughout the cerebral cortex. It is also expressed in the zona incerta and in the spinal cord. PI-PLC-eta1 may perform a fundamental role in the brain. It may also act in synergy with other PLC subtypes. For instance, it is activated via intracellular Ca2+ mobilization and then plays a role in the amplification of GPCR (G-protein-coupled receptor)-mediated PLC-beta signals. In addition, its activity can be stimulated by ionomycin. PI-PLC-eta1 contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. The C-terminal tail harbors a number of proline-rich motifs which may interact with SH3 (Src homology 3) domain-containing proteins, as well as many serine/threonine residues, suggesting possible regulation of interactions by protein kinases/phosphatases.


Pssm-ID: 320050 [Multi-domain]  Cd Length: 141  Bit Score: 234.92  E-value: 1.45e-71
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  260 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTDDHQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 339
Cdd:cd16220      1 WVKQTFEEADKNGDGLLNIEEIYQLMHKLNVNLPRRKVRQMFQEADTDENQGTLTFEEFCVFYKMMSLRRDLYLLLLSYS 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462515664  340 NHKDHLDAASLQRFLQVEQKMAGVTLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRSPA 400
Cdd:cd16220     81 DKKDHLTVEELAQFLKVEQKMNNVTTEYCLDIIKKFEVSEENKEQNVLGIEGFTNFMRSPA 141
PI-PLCc_gamma1 cd08627
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily ...
 413-814 3.83e-68

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-gamma isozyme 1. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-gamma represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma1, a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region is present within this linker region. PI-PLC-gamma1 is ubiquitously expressed. It is activated by receptor and non-receptor tyrosine kinases due to the presence of two SH2 and a single SH3 domain within the linker region.


Pssm-ID: 176564 [Multi-domain]  Cd Length: 229  Bit Score: 228.76  E-value: 3.83e-68
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  413 QDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 492
Cdd:cd08627      2 EEMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  493 YAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLdLSSVSSEDATTLPSPQMLKGKILVKGKKLpanisedaeege 572
Cdd:cd08627     82 HAFVTSEYPIILSIEDHCSIVQQRNMAQHFKKVFGDML-LTKPVDINADGLPSPNQLKRKILIKHKKL------------ 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  573 vsdedsadeidddckllngdastnrkrventakrkldslikeskIRDcedpnnfsvstlspsgklgrkskaeedvesged 652
Cdd:cd08627    149 --------------------------------------------YRD--------------------------------- 151

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  653 agasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmklsralsdlvkytksvathdiemea 732
Cdd:cd08627        --------------------------------------------------------------------------------

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  733 asswqVSSFSETKAHQILQQ-KPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKF 811
Cdd:cd08627    152 -----MSSFPETKAEKYVNRsKGKKFLQYNRRQLSRIYPKGQRLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALF 226


                   ...
gi 2462515664  812 SAN 814
Cdd:cd08627    227 MLG 229
PLN02952 PLN02952
phosphoinositide phospholipase C
 329-954 5.18e-68

phosphoinositide phospholipase C


Pssm-ID: 178538 [Multi-domain]  Cd Length: 599  Bit Score: 241.06  E-value: 5.18e-68
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  329 RDLYLLMLTYSNHKDHLDAASLQRFLQVEQKMAGVTLESCQDIIEQFEpcpeNK-------SKGLLGIDGFTNYTRSPag 401
Cdd:PLN02952    38 DDVKDVFCKFSVGGGHMGADQLRRFLVLHQDELDCTLAEAQRIVEEVI----NRrhhvtryTRHGLNLDDFFHFLLYD-- 111

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  402 DIFNPEHHHVHQDMTQPLSHYFITSSHNTYLVGDQLMSQ-SRVDMYAwVLQAGCRCVEVDCWDGPDGEPI-VHHGYTLTS 479
Cdd:PLN02952   112 DLNGPITPQVHHDMTAPLSHYFIYTGHNSYLTGNQLSSDcSEVPIVK-ALQRGVRVIELDLWPGSTKDEIlVLHGRTLTT 190

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  480 KILFKDVIETINKYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLDLSsvSSEDATTLPSPQMLKGKILVKGKK 559
Cdd:PLN02952   191 PVPLIKCLKSIRDYAFSSSPYPVIITLEDHLTPDLQAKVAEMATQIFGQMLYYP--ESDSLVQFPSPESLKHRIIISTKP 268

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  560 lPANISEDaeegevsdedsadeidddckllNGDASTNRKrventakrkldslikeskirdcedpnnfsvSTLSPSGKlgR 639
Cdd:PLN02952   269 -PKEYLES----------------------SGPIVIKKK------------------------------NNVSPSGR--N 293

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  640 KSKAEEDVESGEDAGASrrngrlvvgsfsrrkkkgsklkkAASVEEGDEGQDSPGGQSRGATRQKKTM-----KLSRALS 714
Cdd:PLN02952   294 SSEETEEAQTLESMLFE-----------------------QEADSRSDSDQDDNKSGELQKPAYKRLItihagKPKGTLK 350

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  715 DLVKYtksvathdiemeAASSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVA 794
Cdd:PLN02952   351 DAMKV------------AVDKVRRLSLSEQELEKAATTNGQDVVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIA 418

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  795 LNYQSEGRMLQLNRAKFSANGGCGYVLKPGCMCQGVFNPNSEDP---LPgqLKKQLVLRIISGQQLPKPRDSMLGDRGEI 871
Cdd:PLN02952   419 FNMQGYGKSLWLMHGMFRANGGCGYLKKPDFLMKKGFHDEVFDPkkkLP--VKKTLKVKVYLGDGWRLDFSHTHFDSYSP 496

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  872 IDPFVEVEIIGLPVDCSREQTRVVDDNgFNPTWEETLVFMVHMPEIALVRFLVWDHDPIGR-DFIGQRTLAFSSMMPGYR 950
Cdd:PLN02952   497 PDFYTKMYIVGVPADNAKKKTKIIEDN-WYPAWNEEFSFPLTVPELALLRIEVREYDMSEKdDFGGQTCLPVSELRPGIR 575


                   ....
gi 2462515664  951 HVYL 954
Cdd:PLN02952   576 SVPL 579
PI-PLCc_beta3 cd08625
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3; This subfamily ...
 414-814 1.94e-66

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozyme 3. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-beta3 is widely expressed at highest levels in brain, liver, and parotid gland. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. It is also activated by the beta-gamma subunits of heterotrimeric G proteins.


Pssm-ID: 176562 [Multi-domain]  Cd Length: 258  Bit Score: 224.93  E-value: 1.94e-66
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  414 DMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDG--PDGEPIVHHGYTLTSKILFKDVIETIN 491
Cdd:cd08625      3 DMNQPLSHYFINSSHNTYLTAGQLTGLSSVEMYRQVLLTGCRCIELDCWKGrpPEEEPFITHGFTMTTEIPFKDVIEAIA 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  492 KYAFIKNEYPVILSIENHC-SVIQQKKMAQYLTDILGDKL---DLSSVSSEDATTLPSPQMLKGKILVKGKKLPAnised 567
Cdd:cd08625     83 ESAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALlidPLDKYPLVPGVQLPSPQELMGKILVKNKKMST----- 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  568 aeegevsdedsadeidddckLLNGDASTNRKRVENTAKRKldslikeskirdcedpnnfsvstlspsgklgrkskaeedv 647
Cdd:cd08625    158 --------------------LVNYIEPVKFKSFEAAAKRN---------------------------------------- 177

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  648 esgedagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmklsralsdlvKYtksvathd 727
Cdd:cd08625    178 ----------------------------------------------------------------------KF-------- 179

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  728 iemeaassWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLN 807
Cdd:cd08625    180 --------FEMSSFVETKAMEQLTKSPMEFVEYNKKQLSRIYPKGTRVDSSNYMPQLFWNVGCQMVALNFQTLDLAMQLN 251


                   ....*..
gi 2462515664  808 RAKFSAN 814
Cdd:cd08625    252 MGVFEYN 258
PLCXc smart00148
Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ...
 415-558 4.96e-63

Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. These enzymes contain 2 regions (X and Y) which together form a TIM barrel-like structure containing the active site residues. Phospholipase C enzymes (PI-PLC) act as signal transducers that generate two second messengers, inositol-1,4,5-trisphosphate and diacylglycerol. The bacterial enzyme appears to be a homologue of the mammalian PLCs.


Pssm-ID: 197543 [Multi-domain]  Cd Length: 143  Bit Score: 210.60  E-value: 4.96e-63
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664   415 MTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINKYA 494
Cdd:smart00148    1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80

                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462515664   495 FIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLdLSSVSSEDATTLPSPQMLKGKILVKGK 558
Cdd:smart00148   81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDML-YTPPLTSSLEVLPSPEQLRGKILLKVR 143
PLN02228 PLN02228
Phosphoinositide phospholipase C
 334-954 2.15e-62

Phosphoinositide phospholipase C


Pssm-ID: 177873 [Multi-domain]  Cd Length: 567  Bit Score: 223.76  E-value: 2.15e-62
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  334 LMLTYSnHKDHLDAASLQRFLQVEQKMAGVTLESCQDIIEQFEPCPENKSKGLLGIDGFTNY----TRSPAgdifnPEHH 409
Cdd:PLN02228    29 LFEAYS-RNGKMSFDELLRFVSEVQGERHAGLDYVQDIFHSVKHHNVFHHHGLVHLNAFYRYlfsdTNSPL-----PMSG 102

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  410 HVHQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDG-EPIVHHGYTLTSKILFKDVIE 488
Cdd:PLN02228   103 QVHHDMKAPLSHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELDLWPNPSGnAAEVRHGRTLTSHEDLQKCLN 182

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  489 TINKYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKldLSSVSSEDATTLPSPQMLKGKILVKGKKLPANISEDA 568
Cdd:PLN02228   183 AIKDNAFQVSDYPVVITLEDHLPPNLQAQVAKMLTKTFRGM--LFRCTSESTKHFPSPEELKNKILISTKPPKEYLESKT 260

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  569 EEGEVSD----------EDSADEIDDDCKLLNGDASTNRKRVENTAKRKLDSLikeskiRDC--EDPNnfsvstlspsgK 636
Cdd:PLN02228   261 VQTTRTPtvketswkrvADAENKILEEYKDEESEAVGYRDLIAIHAANCKDPL------KDClsDDPE-----------K 323

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  637 LGRKSKAEEDVEsgedagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkkTMKLSRAlSDL 716
Cdd:PLN02228   324 PIRVSMDEQWLE---------------------------------------------------------TMVRTRG-TDL 345

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  717 VKYTksvathdiemeaasswqvssfsetkahqilqqkpaqylrfnQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALN 796
Cdd:PLN02228   346 VRFT-----------------------------------------QRNLVRIYPKGTRVDSSNYDPHVGWTHGAQMVAFN 384

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  797 YQSEGRMLQLNRAKFSANGGCGYVLKPGCMCQ--GVFNPNSEDPLPGQLKkqlvLRIISGQ--QLPKPRDSMlgDRGEII 872
Cdd:PLN02228   385 MQGHGKQLWIMQGMFRANGGCGYVKKPRILLDehTLFDPCKRLPIKTTLK----VKIYTGEgwDLDFHLTHF--DQYSPP 458

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  873 DPFVEVEIIGLPVDCSREQTRVVDDNGFnPTW-EETLVFMVHMPEIALVRFLVWDHDP-IGRDFIGQRTLAFSSMMPGYR 950
Cdd:PLN02228   459 DFFVKIGIAGVPRDTVSYRTETAVDQWF-PIWgNDEFLFQLRVPELALLWFKVQDYDNdTQNDFAGQTCLPLPELKSGVR 537


                   ....
gi 2462515664  951 HVYL 954
Cdd:PLN02228   538 AVRL 541
PI-PLCc_beta1 cd08623
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta1; This subfamily ...
 413-814 8.44e-61

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozyme 1. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-beta1 is expressed at highest levels in specific regions of the brain. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension.


Pssm-ID: 176560 [Multi-domain]  Cd Length: 258  Bit Score: 209.17  E-value: 8.44e-61
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  413 QDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDG--PDGEPIVHHGYTLTSKILFKDVIETI 490
Cdd:cd08623      2 EDMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGrtAEEEPVITHGFTMTTEISFKEVIEAI 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  491 NKYAFIKNEYPVILSIENHC-SVIQQKKMAQYLTDILGDKL---DLSSVSSEDATTLPSPQMLKGKILVKGKKlpanise 566
Cdd:cd08623     82 AECAFKTSPFPILLSFENHVdSPKQQAKMAEYCRLIFGDALlmePLEKYPLESGVPLPSPMDLMYKILVKNKK------- 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  567 daeegevsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeed 646
Cdd:cd08623        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  647 vesgedagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmklsraLSDLVKYTKSVATH 726
Cdd:cd08623    155 ------------------------------------------------------------------MSNLVNYIQPVKFE 168

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  727 DIEMEAA--SSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRML 804
Cdd:cd08623    169 SFEASKKrnKSFEMSSFVETKGLEQLTKSPVEFVEYNKMQLSRIYPKGTRVDSSNYMPQLFWNAGCQMVALNFQTVDLSM 248

                          410
                   ....*....|
gi 2462515664  805 QLNRAKFSAN 814
Cdd:cd08623    249 QINMGMYEYN 258
PLN02222 PLN02222
phosphoinositide phospholipase C 2
 350-954 2.98e-60

phosphoinositide phospholipase C 2


Pssm-ID: 177868 [Multi-domain]  Cd Length: 581  Bit Score: 217.98  E-value: 2.98e-60
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  350 LQRFLQVEQKMAGVTLESCQDIIeqfepcpeNKSKGLLG-----IDGFTNYTrspAGDIFNP-EHHHVHQDMTQPLSHYF 423
Cdd:PLN02222    45 LHRFLIDVQKQDKATREDAQSII--------NSASSLLHrnglhLDAFFKYL---FGDNNPPlALHEVHHDMDAPISHYF 113

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  424 ITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPI-VHHGYTLTSKILFKDVIETINKYAFIKNEYPV 502
Cdd:PLN02222   114 IFTGHNSYLTGNQLSSDCSEVPIIDALKKGVRVIELDIWPNSDKDDIdVLHGMTLTTPVGLIKCLKAIRAHAFDVSDYPV 193

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  503 ILSIENHCSVIQQKKMAQYLTDILGDKLdLSSVSSEDATTLPSPQMLKGKILVKGKKlpaniseDAEEGEVSDedsaDEI 582
Cdd:PLN02222   194 VVTLEDHLTPDLQSKVAEMVTEIFGEIL-FTPPVGESLKEFPSPNSLKKRIIISTKP-------PKEYKEGKD----DEV 261

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  583 DDDCKLLnGDastnrkrvENTAKRKLDSLIKESKIRDCEDPNnfsvstlspsgklGRKSKAEEDVESGEDAGASRRNGRL 662
Cdd:PLN02222   262 VQKGKDL-GD--------EEVWGREVPSFIQRNKSVDKNDSN-------------GDDDDDDDDGEDKSKKNAPPQYKHL 319

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  663 VvgsfsrrkkkgsklkkaaSVEEGdegqdSPGGqsrgatrqkktmklsrALSDLVKytksVATHDIEMEAASSWQVSSFS 742
Cdd:PLN02222   320 I------------------AIHAG-----KPKG----------------GITECLK----VDPDKVRRLSLSEEQLEKAA 356

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  743 ETKAHQILqqkpaqylRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKFSANGGCGYVLK 822
Cdd:PLN02222   357 EKYAKQIV--------RFTQHNLLRIYPKGTRVTSSNYNPLVGWSHGAQMVAFNMQGYGRSLWLMQGMFRANGGCGYIKK 428

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  823 PGCMCQG-----VFNPNSEDPLPGQLKkqLVLRIISGQQLPKPRDSMlgDRGEIIDPFVEVEIIGLPVDCSREQTRVVDD 897
Cdd:PLN02222   429 PDLLLKSgsdsdIFDPKATLPVKTTLR--VTIYMGEGWYFDFRHTHF--DQYSPPDFYTRVGIAGVPGDTVMKKTKTLED 504

                          570       580       590       600       610
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2462515664  898 NgFNPTWEETLVFMVHMPEIALVRFLVWDHDPIGR-DFIGQRTLAFSSMMPGYRHVYL 954
Cdd:PLN02222   505 N-WIPAWDEVFEFPLTVPELALLRLEVHEYDMSEKdDFGGQTCLPVWELSQGIRAFPL 561
PI-PLC-Y pfam00387
Phosphatidylinositol-specific phospholipase C, Y domain; This associates with pfam00388 to ...
 713-825 2.61e-57

Phosphatidylinositol-specific phospholipase C, Y domain; This associates with pfam00388 to form a single structural unit.


Pssm-ID: 459794  Cd Length: 114  Bit Score: 193.06  E-value: 2.61e-57
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  713 LSDLVKYTKSVATHDIEM-EAASSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQ 791
Cdd:pfam00387    1 LSDLVVYTQSVKFKSFSTpESKTPNHIFSFSESKALKLIKSSSAAFVKHNRRHLMRVYPKGTRVDSSNFNPQPFWNCGVQ 80

                           90       100       110
                   ....*....|....*....|....*....|....
gi 2462515664  792 MVALNYQSEGRMLQLNRAKFSANGGCGYVLKPGC 825
Cdd:pfam00387   81 MVALNWQTPDEGMQLNEGMFADNGGCGYVLKPEF 114
PLN02230 PLN02230
phosphoinositide phospholipase C 4
 330-954 2.38e-56

phosphoinositide phospholipase C 4


Pssm-ID: 177875 [Multi-domain]  Cd Length: 598  Bit Score: 206.86  E-value: 2.38e-56
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  330 DLYLLMLTYSNHKDHLDAASLQRFLQVEQKMAGVT-LESCQDIIEQFEPCPENKSKGL---LGIDGFTNYTRSPagDIFN 405
Cdd:PLN02230    30 DVRDLFEKYADGDAHMSPEQLQKLMAEEGGGEGETsLEEAERIVDEVLRRKHHIAKFTrrnLTLDDFNYYLFST--DLNP 107

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  406 PEHHHVHQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKD 485
Cdd:PLN02230   108 PIADQVHQNMDAPLSHYFIFTGHNSYLTGNQLSSNCSELPIADALRRGVRVVELDLWPRGTDDVCVKHGRTLTKEVKLGK 187

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  486 VIETINKYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLDLSsvSSEDATTLPSPQMLKGKILVKGKK----LP 561
Cdd:PLN02230   188 CLDSIKANAFAISKYPVIITLEDHLTPKLQFKVAKMITQTFGDMLYYH--DSEGCQEFPSPEELKEKILISTKPpkeyLE 265

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  562 ANISED---AEEGEVSDEDSADEIDDDCKLLNGDASTNRKRVENTAKrkldsliKESKIRDCEdpNNFSVSTLSPSGKlg 638
Cdd:PLN02230   266 ANDAKEkdnGEKGKDSDEDVWGKEPEDLISTQSDLDKVTSSVNDLNQ-------DDEERGSCE--SDTSCQLQAPEYK-- 334

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  639 rkskaeedvesgedagasrrngRLVvgsfsrrkkkgsklkkaaSVEEGdegqdSPGGQSRGATRQKKTmKLSRAlsdlvk 718
Cdd:PLN02230   335 ----------------------RLI------------------AIHAG-----KPKGGLRMALKVDPN-KIRRL------ 362

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  719 ytksvathdiemeaasswqvsSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQ 798
Cdd:PLN02230   363 ---------------------SLSEQLLEKAVASYGADVIRFTQKNFLRIYPKGTRFNSSNYKPQIGWMSGAQMIAFNMQ 421

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  799 SEGRMLQLNRAKFSANGGCGYVLKP------GCMCQGVFNPNSEDPlpgqlKKQLVLRIISGQQLPKPRDSMLGDRGEII 872
Cdd:PLN02230   422 GYGRALWLMEGMFRANGGCGYVKKPdflmdaGPNGQDFYPKDNSCP-----KKTLKVKVCMGDGWLLDFKKTHFDSYSPP 496

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  873 DPFVEVEIIGLPVDCSREQTRVVDDNgFNPTWEETLVFMVHMPEIALVRFLVWDHDPIGR-DFIGQRTLAFSSMMPGYRH 951
Cdd:PLN02230   497 DFFVRVGIAGAPVDEVMEKTKIEYDT-WTPIWNKEFIFPLAVPELALLRVEVHEHDINEKdDFGGQTCLPVSEIRQGIHA 575


                   ...
gi 2462515664  952 VYL 954
Cdd:PLN02230   576 VPL 578
PH_PLC_eta cd13364
Phospholipase C-eta (PLC-eta) pleckstrin homology (PH) domain; PLC-eta (PLCeta) consists of ...
 136-242 1.49e-55

Phospholipase C-eta (PLC-eta) pleckstrin homology (PH) domain; PLC-eta (PLCeta) consists of two enzymes, PLCeta1 and PLCeta2. They hydrolyze phosphatidylinositol 4,5-bisphosphate, are more sensitive to Ca2+ than other PLC isozymes, and involved in PKC activation in the brain and neuroendocrine systems. PLC-eta consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves by a variable linker, a C2 domain, and a C-terminal PDZ domain. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.involved in targeting proteins to the plasma membrane, but only a few (less than 10%) display strong specificity in binding inositol phosphates. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinases, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, cytoskeletal associated molecules, and in lipid associated enzymes.


Pssm-ID: 270170  Cd Length: 109  Bit Score: 187.87  E-value: 1.49e-55
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  136 MQEGMQMVKLRGGSKGLVRFYYLDEHRSCIRWRPSRKN-EKAKISIDSIQEVSEGRQSEVFQRYP-DGNFDPNCCFSIYH 213
Cdd:cd13364      1 MQEGSELVKVRSNSRQYRRFFYLDEDKSSIRWKPSKKKsEKAKIPISSIREVREGKTTDIFRSCDiSGDFPEECCFSIIY 80

                           90       100
                   ....*....|....*....|....*....
gi 2462515664  214 GSHRESLDLVSTSSEVARTWVTGLRYLMA 242
Cdd:cd13364     81 GEEYETLDLVASSPDEANIWITGLRYLMS 109
PI-PLCc_plant cd08599
Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family ...
 412-583 1.05e-54

Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family corresponds to the catalytic domain present in a group of phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11) encoded by PLC genes from higher plants, which are homologs of mammalian PI-PLC in terms of overall sequence similarity and domain organization. Mammalian PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. The domain arrangement of plant PI-PLCs is structurally similar to the mammalian PLC-zeta isoform, which lacks the N-terminal pleckstrin homology (PH) domain, but contains EF-hand like motifs (which are absent in a few plant PLCs), a PLC catalytic core domain with X- and Y- highly conserved regions split by a linker sequence, and a C2 domain. However, at the sequence level, the plant PI-PLCs are closely related to the mammalian PLC-delta isoform. Experiments show that plant PLCs display calcium dependent PLC catalytic properties, although they lack some of the N-terminal motifs found in their mammalian counterparts. A putative calcium binding site may be located at the region spanning the X- and Y- domains.


Pssm-ID: 176541 [Multi-domain]  Cd Length: 228  Bit Score: 190.28  E-value: 1.05e-54
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  412 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 491
Cdd:cd08599      1 HHDMTAPLSHYFIFSSHNSYLTGNQLSSRSSTAPIIEALLRGCRVIELDLWPGGRGDICVLHGGTLTKPVKFEDCIKAIK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  492 KYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLDLSSvSSEDATTLPSPQMLKGKILV--KGKKLPANISEDAE 569
Cdd:cd08599     81 ENAFTASEYPVIITLENHLSPELQAKAAQILRETLGDKLFYPD-SEDLPEEFPSPEELKGKILIsdKPPVIRNSLSETQL 159

                          170
                   ....*....|....
gi 2462515664  570 EGEVSDEDSADEID 583
Cdd:cd08599    160 KKVIEGEHPTDLIE 173
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 844-969 1.66e-51

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.


Pssm-ID: 175974 [Multi-domain]  Cd Length: 128  Bit Score: 176.96  E-value: 1.66e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  844 KKQLVLRIISGQQLPKPRDsmlgDRGEIIDPFVEVEIIGLPV-DCSREQTRVVDDNGFNPTWEETLVFMVHMPEIALVRF 922
Cdd:cd00275      1 PLTLTIKIISGQQLPKPKG----DKGSIVDPYVEVEIHGLPAdDSAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRF 76

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2462515664  923 LVWDHDPIGRDFIGQRTLAFSSMMPGYRHVYL-----EGMEEASIFVHVAVS 969
Cdd:cd00275     77 VVYDEDSGDDDFLGQACLPLDSLRQGYRHVPLldskgEPLELSTLFVHIDIT 128
PLCYc smart00149
Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. ...
 714-826 1.18e-50

Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. These enzymes contain 2 regions (X and Y) which together form a TIM barrel-like structure containing the active site residues. Phospholipase C enzymes (PI-PLC) act as signal transducers that generate two second messengers, inositol-1,4,5-trisphosphate and diacylglycerol. The bacterial enzyme appears to be a homologue of the mammalian PLCs.


Pssm-ID: 128454 [Multi-domain]  Cd Length: 115  Bit Score: 174.35  E-value: 1.18e-50
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664   714 SDLVKYTKSVATHDIE--MEAASSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQ 791
Cdd:smart00149    1 SDLVIYCAPVKFRSFEsaESKNPFYEMSSFSETKAKKLLKKSPTDFVRYNQRQLSRVYPKGTRVDSSNYNPQVFWNHGCQ 80

                            90       100       110
                    ....*....|....*....|....*....|....*
gi 2462515664   792 MVALNYQSEGRMLQLNRAKFSANGGCGYVLKPGCM 826
Cdd:smart00149   81 MVALNFQTPDKPMQLNQGMFRANGGCGYVLKPDFL 115
PI-PLCc cd00137
Catalytic domain of prokaryotic and eukaryotic phosphoinositide-specific phospholipase C; This ...
 412-814 8.79e-47

Catalytic domain of prokaryotic and eukaryotic phosphoinositide-specific phospholipase C; This subfamily corresponds to the catalytic domain present in prokaryotic and eukaryotic phosphoinositide-specific phospholipase C (PI-PLC), which is a ubiquitous enzyme catalyzing the cleavage of the sn3-phosphodiester bond in the membrane phosphoinositides (phosphatidylinositol, PI; Phosphatidylinositol-4-phosphate, PIP; phosphatidylinositol 4,5-bisphosphate, PIP2) to yield inositol phosphates (inositol monosphosphate, InsP; inositol diphosphate, InsP2; inositol trisphosphate, InsP3) and diacylglycerol (DAG). The higher eukaryotic PI-PLCs (EC 3.1.4.11) have a multidomain organization that consists of a PLC catalytic core domain, and various regulatory domains. They play a critical role in most signal transduction pathways, controlling numerous cellular events, such as cell growth, proliferation, excitation and secretion. These PI-PLCs strictly require Ca2+ for their catalytic activity. They display a clear preference towards the hydrolysis of the more highly phosphorylated PI-analogues, PIP2 and PIP, to generate two important second messengers, InsP3 and DAG. InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. In contrast, bacterial PI-PLCs contain a single catalytic domain. Although their precise physiological function remains unclear, bacterial PI-PLCs may function as virulence factors in some pathogenic bacteria. They participate in Ca2+-independent PI metabolism. They are characterized as phosphatidylinositol-specific phospholipase C (EC 4.6.1.13) that selectively hydrolyze PI, not PIP or PIP2. The TIM-barrel type catalytic domain in bacterial PI-PLCs is very similar to the one in eukaryotic PI-PLCs, in which the catalytic domain is assembled from two highly conserved X- and Y-regions split by a divergent linker sequence. The catalytic mechanism of both prokaryotic and eukaryotic PI-PLCs is based on general base and acid catalysis utilizing two well conserved histidines, and consists of two steps, a phosphotransfer and a phosphodiesterase reaction. This superfamily also includes a distinctly different type of eukaryotic PLC, glycosylphosphatidylinositol-specific phospholipase C (GPI-PLC), an integral membrane protein characterized in the protozoan parasite Trypanosoma brucei. T. brucei GPI-PLC hydrolyzes the GPI-anchor on the variant specific glycoprotein (VSG), releasing dimyristyl glycerol (DMG), which may facilitate the evasion of the protozoan to the host#s immune system. It does not require Ca2+ for its activity and is more closely related to bacterial PI-PLCs, but not mammalian PI-PLCs.


Pssm-ID: 176497 [Multi-domain]  Cd Length: 274  Bit Score: 169.37  E-value: 8.79e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  412 HQDMTQPLSHYFITSSHNTYLVGDQL-----MSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTsKILFKDV 486
Cdd:cd00137      1 HHPDTQPLAHYSIPGTHDTYLTAGQFtikqvWGLTQTEMYRQQLLSGCRCVDIRCWDGKPEEPIIYHGPTFL-DIFLKEV 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  487 IETINKYAFIKNEYPVILSIENHCSVI--QQKKMAQYLTDILGDKldLSSVSSEDATTLPSPQMLKGKILVKGKKlpani 564
Cdd:cd00137     80 IEAIAQFLKKNPPETIIMSLKNEVDSMdsFQAKMAEYCRTIFGDM--LLTPPLKPTVPLPSLEDLRGKILLLNKK----- 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  565 sedaeegevsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvSTLSPSGklgrkskae 644
Cdd:cd00137    153 ----------------------------------------------------------------NGFSGPT--------- 159

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  645 edvesgedagasrrngrlvvgsfsrrkkkgsklkkaasveeGDEGQDSPGGQSRGATRQKktmklsralsdlvkytksva 724
Cdd:cd00137    160 -----------------------------------------GSSNDTGFVSFEFSTQKNR-------------------- 178

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  725 thdiemeaasSWQVSSFSETKAHQI----LQQKPAQYLRFNQQQLSRIYPS---------SYRVDSSNYNPQPFWN---A 788
Cdd:cd00137    179 ----------SYNISSQDEYKAYDDekvkLIKATVQFVDYNKNQLSRNYPSgtsggtawyYYAMDSNNYMPQMFWNanpA 248

                          410       420
                   ....*....|....*....|....*.
gi 2462515664  789 GCQMVALNYQSEGRMLQLNRAKFSAN 814
Cdd:cd00137    249 GCGIVILDFQTMDLPMQQYMAVIEFN 274
EFh_PRIP cd16206
EF-hand motif found in phospholipase C-related but catalytically inactive proteins (PRIP); ...
 260-399 4.79e-45

EF-hand motif found in phospholipase C-related but catalytically inactive proteins (PRIP); This family represents a class of metazoan phospholipase C related, but catalytically inactive proteins (PRIP), which belong to a group of novel inositol 1,4,5-trisphosphate (InsP3) binding protein. PRIP has a primary structure and domain architecture, incorporating a pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain with highly conserved X- and Y-regions split by a linker sequence, and a C-terminal C2 domain, similar to phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11)-delta isoforms. Due to replacement of critical catalytic residues, PRIP do not have PLC enzymatic activity. PRIP consists of two subfamilies, PRIP-1(also known as p130 or PLC-L1), which is predominantly expressed in the brain, and PRIP-2 (also known as PLC-L2), which exhibits a relatively ubiquitous expression. Experiments show both, PRIP-1 and PRIP-2, are involved in InsP3-mediated calcium signaling pathway and GABA(A)receptor-mediated signaling pathway. In addition, PRIP-2 acts as a negative regulator of B-cell receptor signaling and immune responses.


Pssm-ID: 320036 [Multi-domain]  Cd Length: 143  Bit Score: 159.30  E-value: 4.79e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  260 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFRE--ADTDDHQGTLGFEEFCAFYKMMSTRRDLYLLMLT 337
Cdd:cd16206      1 WLESVFEEADTNKSGFLDEEEAVQLIKQLNPGLSTSRIKQKLKElqKKKDGARGRVSSDEFVELFKELATRPEIYFLLVR 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462515664  338 YSNHKDHLDAASLQRFLQVEQKMAGVTLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRSP 399
Cdd:cd16206     81 YASNKDYLTVDDLMLFLEAEQGMTGVTKEKCLEIINKYEPSEEGREKGQLGIDGFTRYLLSE 142
EFh_PI-PLCdelta cd16202
EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta ...
 260-399 5.93e-42

EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta isozymes represent a class of metazoan PI-PLCs that are some of the most sensitive to calcium among all PLCs. Their activation is modulated by intracellular calcium ion concentration, phospholipids, polyamines, and other proteins, such as RhoAGAP. Like other PI-PLC isozymes, PI-PLC-delta isozymes contain a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1, 3 and 4). PI-PLC-delta1 is relatively well characterized. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. Different PI-PLC-delta isozymes have different tissue distribution and different subcellular locations. PI-PLC-delta1 is mostly a cytoplasmic protein, PI-PLC-delta3 is located in the membrane, and PI-PLC-delta4 is predominantly detected in the cell nucleus. PI-PLC-delta isozymes is evolutionarily conserved even in non-mammalian species, such as yeast, slime molds and plants.


Pssm-ID: 320032 [Multi-domain]  Cd Length: 140  Bit Score: 150.45  E-value: 5.93e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  260 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTDDhQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 339
Cdd:cd16202      1 WLKDQFRKADKNGDGKLSFKECKKLLKKLNVKVDKDYAKKLFQEADTSG-EDVLDEEEFVQFYNRLTKRPEIEELFKKYS 79

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  340 NHKDHLDAASLQRFLQVEQKMAGVTLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRSP 399
Cdd:cd16202     80 GDDEALTVEELRRFLQEEQKVKDVTLEWAEQLIETYEPSEDLKAQGLMSLDGFTLFLLSP 139
PH_PLC_ELMO1 cd01248
Phospholipase C and Engulfment and cell motility protein 1 pleckstrin homology domain; The ...
 136-241 1.65e-40

Phospholipase C and Engulfment and cell motility protein 1 pleckstrin homology domain; The C-terminal region of ELMO1, the PH domain and Pro-rich sequences, binds the SH3-containing region of DOCK2 forming a intermolecular five-helix bundle allowing for DOCK mediated Rac1 activation. ELMO1, a mammalian homolog of C. elegans CED-12, contains an N-terminal RhoG-binding region, a ELMO domain, a PH domain, and a C-terminal sequence with three PxxP motifs. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). All PLCs, except for PLCzeta, have a PH domain which is for most part N-terminally located, though lipid binding specificity is not conserved between them. In addition PLC gamma contains a split PH domain within its catalytic domain that is separated by 2 SH2 domains and a single SH3 domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269952  Cd Length: 108  Bit Score: 144.77  E-value: 1.65e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  136 MQEGMQMVKLRGGSKGLVRFYYLDEHRSCIRWRPSRK-NEKAKISIDSIQEVSEGRQSEVFQRYPDGN-FDPNCCFSIYH 213
Cdd:cd01248      1 LQQGTLLLKYREGSKPKERTFYLDPDGTRITWESSKKkSEKKSIDISDIKEIRPGKDTDGFKRKKKSNkPKEERCFSIIY 80

                           90       100
                   ....*....|....*....|....*...
gi 2462515664  214 GSHRESLDLVSTSSEVARTWVTGLRYLM 241
Cdd:cd01248     81 GSNNKTLDLVAPSEDEANLWVEGLRALL 108
EFh_PI-PLC cd15898
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
 260-400 5.87e-38

EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) isozymes; PI-PLC isozymes are signaling enzymes that hydrolyze the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. This family corresponds to the four EF-hand motifs containing PI-PLC isozymes, including PI-PLC-beta (1-4), -gamma (1-2), -delta (1,3,4), -epsilon (1), -zeta (1), eta (1-2). Lower eukaryotes such as yeast and slime molds contain only delta-type isozymes. In contrast, other types of isoforms present in higher eukaryotes. This family also includes 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase 1 (PLC1) from fungi. Some homologs from plants contain only two atypical EF-hand motifs and they are not included. All PI-PLC isozymes except sperm-specific PI-PLC-zeta share a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. PI-PLC-zeta lacks the PH domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Most of EF-hand motifs found in PI-PLCs consist of a helix-loop-helix structure, but lack residues critical to metal binding. Moreover, the EF-hand region of most of PI-PLCs may have an important regulatory function, but it has yet to be identified. However, PI-PLC-zeta is a key exception. It is responsible for Ca2+ oscillations in fertilized oocytes and exhibits a high sensitivity to Ca2+ mediated through its EF-hand domain. In addition, PI-PLC-eta2 shows a canonical EF-loop directing Ca2+-sensitivity and thus can amplify transient Ca2+ signals. Also it appears that PI-PLC-delta1 can regulate the binding of PH domain to PIP2 in a Ca2+-dependent manner through its functionally important EF-hand domains. PI-PLCs can be activated by a variety of extracellular ligands, such as growth factors, hormones, cytokines and lipids. Their activation has been implicated in tumorigenesis and/or metastasis linked to migration, proliferation, growth, inflammation, angiogenesis and actin cytoskeleton reorganization. PI-PLC-beta isozymes are activated by G-protein coupled receptor (GPCR) through different mechanisms. However, PI-PLC-gamma isozymes are activated by receptor tyrosine kinase (RTK), such as Rho and Ras GTPases. In contrast, PI-PLC-epsilon are activated by both GPCR and RTK. PI-PLC-delta1 and PLC-eta 1 are activated by GPCR-mediated calcium mobilization. The activation mechanism for PI-PLC-zeta remains unclear.


Pssm-ID: 320029 [Multi-domain]  Cd Length: 137  Bit Score: 138.57  E-value: 5.87e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  260 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTdDHQGTLGFEEFCAFYKMMSTRRDLYLLMLTY- 338
Cdd:cd15898      1 WLRRQWIKADKDGDGKLSLKEIKKLLKRLNIRVSEKELKKLFKEVDT-NGDGTLTFDEFEELYKSLTERPELEPIFKKYa 79

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462515664  339 SNHKDHLDAASLQRFLQVEQKMAgVTLESCQDIIEQFEPCPENKskgLLGIDGFTNYTRSPA 400
Cdd:cd15898     80 GTNRDYMTLEEFIRFLREEQGEN-VSEEECEELIEKYEPERENR---QLSFEGFTNFLLSPE 137
PLN02223 PLN02223
phosphoinositide phospholipase C
 412-954 1.53e-30

phosphoinositide phospholipase C


Pssm-ID: 165867 [Multi-domain]  Cd Length: 537  Bit Score: 128.22  E-value: 1.53e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  412 HQDMTQPLSHYFITSSHNTYLVGDQLMSQS-RVDMYAWVLQAGCRCVEVDCWdgPDGEP--IVHHGYTLTSKILFKDVIE 488
Cdd:PLN02223   105 HHDMHAPLSHYFIHTSLKSYFTGNNVFGKLySIEPIIDALEQGVRVVELDLL--PDGKDgiCVRPKWNFEKPLELQECLD 182

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  489 TINKYAFIK-NEYPVILSIENHCSVIQQKKMAQYLTDILGDKldlssVSSEDAT----TLPSPQMLKGKILVKgKKLPAn 563
Cdd:PLN02223   183 AIKEHAFTKcRSYPLIITFKDGLKPDLQSKATQMIDQTFGDM-----VYHEDPQhsleEFPSPAELQNKILIS-RRPPK- 255

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  564 isedaeegevsdedsadeidddcKLLNGDASTNRKRVENtakrkldslikESKIRD-CEDPNNFSV---STLSPSGKLgr 639
Cdd:PLN02223   256 -----------------------ELLYAKADDGGVGVRN-----------ELEIQEgPADKNYQSLvgfHAVEPRGML-- 299

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  640 kskaeEDVESGEDAGASRrngrlvvgsfsrrkkkgsklkkaasveegdegqdsPGGQSRgatrqkktmklsralsDLVKY 719
Cdd:PLN02223   300 -----QKALTGKADDIQQ-----------------------------------PGWYER----------------DIISF 323

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  720 TKSvathdiemeaasswqvssfsetkahQILQQKPaqylrfnQQQLSRIYPSsyrvdssnYNPQPFWNAGCQMVALNYQS 799
Cdd:PLN02223   324 TQK-------------------------KFLRTRP-------KKKNLLINAP--------YKPQRAWMHGAQLIALSRKD 363

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  800 EGRMLQLNRAKFSANGGCGYVLKPGCMCQ----GVFNPnSEDPLpgqLKKQLVLRIISGQ-----------QLPKPrdsm 864
Cdd:PLN02223   364 DKEKLWLMQGMFRANGGCGYVKKPDFLLNagpsGVFYP-TENPV---VVKILKVKIYMGDgwivdfkkrigRLSKP---- 435

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  865 lgdrgeiiDPFVEVEIIGLPVDCSREQTrVVDDNGFNPTWEETLVFMVHMPEIALVRFLVWDHDPIGRD-FIGQRTLAFS 943
Cdd:PLN02223   436 --------DLYVRISIAGVPHDEKIMKT-TVKNNEWKPTWGEEFTFPLTYPDLALISFEVYDYEVSTADaFCGQTCLPVS 506

                          570
                   ....*....|.
gi 2462515664  944 SMMPGYRHVYL 954
Cdd:PLN02223   507 ELIEGIRAVPL 517
EFh_PRIP1 cd16222
EF-hand motif found in phospholipase C-related but catalytically inactive protein 1 (PRIP-1); ...
 260-399 3.10e-28

EF-hand motif found in phospholipase C-related but catalytically inactive protein 1 (PRIP-1); PRIP-1, also termed phospholipase C-deleted in lung carcinoma, or inactive phospholipase C-like protein 1 (PLC-L1), or p130, is a novel inositol 1,4,5-trisphosphate (InsP3) binding protein that is predominantly expressed in the brain. It is involved in InsP3-mediated calcium signaling pathway and GABA(A)receptor-mediated signaling pathway. It interacts with the catalytic subunits of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A), and functions as a scaffold to regulate the activities and subcellular localizations of both PP1 and PP2A in phospho-dependent cellular signaling. It also promotes the translocation of phosphatases to lipid droplets to trigger the dephosphorylation of hormone-sensitive lipase (HSL) and perilipin A, thus reducing protein kinase A (PKA)-mediated lipolysis. Moreover, PRIP-1 plays an important role in insulin granule exocytosis through the association with GABAA-receptor-associated protein (GABARAP) to form a complex to regulate KIF5B-mediated insulin secretion. It also inhibits regulated exocytosis through direct interactions with syntaxin 1 and synaptosomal-associated protein 25 (SNAP-25) via its C2 domain. Furthermore, PRIP-1 has been implicated in the negative regulation of bone formation. PRIP-1 has a primary structure and domain architecture, incorporating a pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain with highly conserved X- and Y-regions split by a linker sequence, and a C-terminal C2 domain, similar to phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11)-delta isoforms. Due to replacement of critical catalytic residues, PRIP-1 does not have PLC enzymatic activity.


Pssm-ID: 320052 [Multi-domain]  Cd Length: 143  Bit Score: 111.11  E-value: 3.10e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  260 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTDDHQGT--LGFEEFCAFYKMMSTRRDLYLLMLT 337
Cdd:cd16222      1 WLSAVFEAADVDGYGIMLEDTAVELIKQLNPGIKEAKIRLKFKEIQKSKEKLTtrVTEEEFCEAYSELCTRPEVYFLLVQ 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462515664  338 YSNHKDHLDAASLQRFLQVEQKMAGVTLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRSP 399
Cdd:cd16222     81 ISKNKEYLDAKDLMLFLEAEQGMTHITEEMCLDIIRRYEPSQEGRLKGFLGIDGFTQYLLSS 142
EFh_PRIP2 cd16223
EF-hand motif found in phospholipase C-related but catalytically inactive protein 2 (PRIP-2); ...
 260-399 3.47e-26

EF-hand motif found in phospholipase C-related but catalytically inactive protein 2 (PRIP-2); PRIP-2, also termed phospholipase C-L2, or phospholipase C-epsilon-2 (PLC-epsilon-2), or inactive phospholipase C-like protein 2 (PLC-L2), is a novel inositol 1,4,5-trisphosphate (InsP3) binding protein that exhibits a relatively ubiquitous expression. It functions as a novel negative regulator of B-cell receptor (BCR) signaling and immune responses. PRIP-2 has a primary structure and domain architecture, incorporating a pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain with highly conserved X- and Y-regions split by a linker sequence, and a C-terminal C2 domain, similar to phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11)-delta isoforms. Due to replacement of critical catalytic residues, PRIP-2 does not have PLC enzymatic activity.


Pssm-ID: 320053 [Multi-domain]  Cd Length: 144  Bit Score: 105.37  E-value: 3.47e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  260 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFRE-ADTDDHQGT-LGFEEFCAFYKMMSTRRDLYLLMLT 337
Cdd:cd16223      1 WLSQMFVEADTDNVGHITLCRAVQFIKNLNPGLKTSKIELKFKElHKSKEKGGTeVTKEEFIEVFHELCTRPEIYFLLVQ 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462515664  338 YSNHKDHLDAASLQRFLQVEQKMAGVTLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRSP 399
Cdd:cd16223     81 FSSNKEFLDTKDLMMFLEAEQGMAHVTEEISLDIIHKYEPSKEGQEKGWLSLDGFTNYLMSP 142
EFh_PI-PLCdelta4 cd16219
EF-hand motif found in phosphoinositide phospholipase C delta 4 (PI-PLC-delta4); PI-PLC-delta4, ...
 260-399 2.64e-25

EF-hand motif found in phosphoinositide phospholipase C delta 4 (PI-PLC-delta4); PI-PLC-delta4, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4 (PLCD4), or phospholipase C-delta-4 (PLC-delta-4), is expressed in various tissues with the highest levels detected selectively in the brain, skeletal muscle, testis and kidney. It plays a significant role in cell growth, cell proliferation, tumorigenesis, and in an early stage of fertilization. PI-PLC-delta4 may function as a key enzyme in the regulation of PtdIns(4,5)P2 levels and Ca2+ metabolism in nuclei in response to growth factors, and its expression may be partially regulated by an increase in cytoplasmic Ca2+. Moreover, PI-PLC-delta4 binds glutamate receptor-interacting protein1 (GRIP1) in testis and is required for calcium mobilization essential for the zona pellucida-induced acrosome reaction in sperm. Overexpression or dysregulated expression of PLCdelta4 may initiate oncogenesis in certain tissues through upregulating erbB1/2 expression, extracellular signal-regulated kinase (ERK) signaling pathway, and proliferation in MCF-7 cells. PI-PLC-delta4 contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, and a C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unlike PI-PLC-delta 1 and 3, a putative nuclear export sequence (NES) located in the EF-hand domain, which may be responsible transporting PI-PLC-delta1 and 3 from the cell nucleus, is not present in PI-PLC-delta4.


Pssm-ID: 320049 [Multi-domain]  Cd Length: 140  Bit Score: 102.61  E-value: 2.64e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  260 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTDDhQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 339
Cdd:cd16219      1 WIRDWFQKADKNKDGRMNFKEVRDLLKMMNVDMNEEHALRLFQMADKSE-SGTLEGEEFVLFYKALTQREDVLKIFQDFS 79

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  340 NHKDHLDAASLQRFLQVEQKMAGVTLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRSP 399
Cdd:cd16219     80 ADGQKLTLLEFVDFLQQEQLERENTEELAMELIDRYEPSDTAKKLHALSIDGFLMYLCSP 139
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 846-954 9.66e-22

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 91.01  E-value: 9.66e-22
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664   846 QLVLRIISGQQLPKPrdsmlgDRGEIIDPFVEVEIIGLPVdcSREQTRVVDDNGfNPTWEETLVFMVHMPEIALVRFLVW 925
Cdd:smart00239    1 TLTVKIISARNLPPK------DKGGKSDPYVKVSLDGDPK--EKKKTKVVKNTL-NPVWNETFEFEVPPPELAELEIEVY 71

                            90       100       110
                    ....*....|....*....|....*....|
gi 2462515664   926 DHDPIGRD-FIGQRTLAFSSMMPGYRHVYL 954
Cdd:smart00239   72 DKDRFGRDdFIGQVTIPLSDLLLGGRHEKL 101
PH_PLC_delta cd13363
Phospholipase C-delta (PLC-delta) pleckstrin homology (PH) domain; The PLC-delta (PLCdelta) ...
 136-254 2.79e-21

Phospholipase C-delta (PLC-delta) pleckstrin homology (PH) domain; The PLC-delta (PLCdelta) consists of three family members, delta 1, 2, and 3. PLC-delta1 is the most well studied. PLC-delta is activated by high calcium levels generated by other PLC family members, and functions as a calcium amplifier within the cell. PLC-delta consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves, and a C-terminal C2 domain. The PH domain binds PIP2 and promotes activation of the catalytic core as well as tethering the enzyme to the plasma membrane. The C2 domain has been shown to mediate calcium-dependent phospholipid binding as well. The PH and C2 domains operate in concert as a "tether and fix" apparatus necessary for processive catalysis by the enzyme. Its leucine-rich nuclear export signal (NES) in its EF hand motif, as well as a Nuclear localization signal within its linker region allow PLC-delta 1 to actively translocate into and out of the nucleus. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270169  Cd Length: 117  Bit Score: 90.46  E-value: 2.79e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  136 MQEGMQMVKLRGGSKGLVRFYYLDEHRSCIrWRPSRK---NEKAKISIDSIQEVSEGRQSEVFQRYPDGnFDPNCCFSI- 211
Cdd:cd13363      1 LLQGSPLLKVRSRSWKKERFYKLQEDCKTV-WHESKKtrsNSKQTFSIEDIESVREGHQSEGLRKYAEA-FPEDRCFSIv 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 2462515664  212 YHGsHRESLDLVSTSSEVARTWVTGLRYLMAGIsdeDSLARRQ 254
Cdd:cd13363     79 FKG-RRKNLDLIAPSEEEAQRWVRGLEKLIARL---TNMSQRE 117
PI-PLCc_GDPD_SF cd08555
Catalytic domain of phosphoinositide-specific phospholipase C-like phosphodiesterases ...
 426-531 2.88e-21

Catalytic domain of phosphoinositide-specific phospholipase C-like phosphodiesterases superfamily; The PI-PLC-like phosphodiesterases superfamily represents the catalytic domains of bacterial phosphatidylinositol-specific phospholipase C (PI-PLC, EC 4.6.1.13), eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11), glycerophosphodiester phosphodiesterases (GP-GDE, EC 3.1.4.46), sphingomyelinases D (SMases D) (sphingomyelin phosphodiesterase D, EC 3.1.4.41) from spider venom, SMases D-like proteins, and phospholipase D (PLD) from several pathogenic bacteria, as well as their uncharacterized homologs found in organisms ranging from bacteria and archaea to metazoans, plants, and fungi. PI-PLCs are ubiquitous enzymes hydrolyzing the membrane lipid phosphoinositides to yield two important second messengers, inositol phosphates and diacylglycerol (DAG). GP-GDEs play essential roles in glycerol metabolism and catalyze the hydrolysis of glycerophosphodiesters to sn-glycerol-3-phosphate (G3P) and the corresponding alcohols that are major sources of carbon and phosphate. Both, PI-PLCs and GP-GDEs, can hydrolyze the 3'-5' phosphodiester bonds in different substrates, and utilize a similar mechanism of general base and acid catalysis with conserved histidine residues, which consists of two steps, a phosphotransfer and a phosphodiesterase reaction. This superfamily also includes Neurospora crassa ankyrin repeat protein NUC-2 and its Saccharomyces cerevisiae counterpart, Phosphate system positive regulatory protein PHO81, glycerophosphodiester phosphodiesterase (GP-GDE)-like protein SHV3 and SHV3-like proteins (SVLs). The residues essential for enzyme activities and metal binding are not conserved in these sequence homologs, which might suggest that the function of catalytic domains in these proteins might be distinct from those in typical PLC-like phosphodiesterases.


Pssm-ID: 176498 [Multi-domain]  Cd Length: 179  Bit Score: 92.50  E-value: 2.88e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  426 SSHNTYLVGDQlmsQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLT------SKILFKDVIETINKYAFiKNE 499
Cdd:cd08555      2 LSHRGYSQNGQ---ENTLEAFYRALDAGARGLELDVRLTKDGELVVYHGPTLDrttagiLPPTLEEVLELIADYLK-NPD 77

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 2462515664  500 YPVILSIENHCSV----IQQKKMAQYLTDILGDKLD 531
Cdd:cd08555     78 YTIILSLEIKQDSpeydEFLAKVLKELRVYFDYDLR 113
C2 pfam00168
C2 domain;
846-951 6.38e-20

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 85.83  E-value: 6.38e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  846 QLVLRIISGQQLPKPrdsmlgDRGEIIDPFVEVEIIGlpvDCSREQTRVVDdNGFNPTWEETLVFMVHMPEIALVRFLVW 925
Cdd:pfam00168    2 RLTVTVIEAKNLPPK------DGNGTSDPYVKVYLLD---GKQKKKTKVVK-NTLNPVWNETFTFSVPDPENAVLEIEVY 71

                           90       100
                   ....*....|....*....|....*..
gi 2462515664  926 DHDPIGRD-FIGQRTLAFSSMMPGYRH 951
Cdd:pfam00168   72 DYDRFGRDdFIGEVRIPLSELDSGEGL 98
EFh_ScPlc1p_like cd16207
EF-hand motif found in Saccharomyces cerevisiae phospholipase C-1 (ScPlc1p) and similar ...
 257-400 2.74e-19

EF-hand motif found in Saccharomyces cerevisiae phospholipase C-1 (ScPlc1p) and similar proteins; This family represents a group of putative phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) encoded by PLC1 genes from yeasts, which are homologs of the delta isoforms of mammalian PI-PLC in terms of overall sequence similarity and domain organization. Mammalian PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. The prototype of this family is protein Plc1p (also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase 1) encoded by PLC1 genes from Saccharomyces cerevisiae. ScPlc1p contains both highly conserved X- and Y- regions of PLC catalytic core domain, as well as a presumptive EF-hand like calcium binding motif. Experiments show that ScPlc1p displays calcium dependent catalytic properties with high similarity to those of the mammalian PLCs, and plays multiple roles in modulating the membrane/protein interactions in filamentation control. CaPlc1p encoded by CAPLC1 from the closely related yeast Candida albicans, an orthologue of S. cerevisiae Plc1p, is also included in this group. Like SCPlc1p, CaPlc1p has conserved presumptive catalytic domain, shows PLC activity when expressed in E. coli, and is involved in multiple cellular processes. There are two other gene copies of CAPLC1 in C. albicans, CAPLC2 (also named as PIPLC) and CAPLC3. Experiments show CaPlc1p is the only enzyme in C. albicans which functions as PLC. The biological functions of CAPLC2 and CAPLC3 gene products must be clearly different from CaPlc1p, but their exact roles remain unclear. Moreover, CAPLC2 and CAPLC3 gene products are more similar to extracellular bacterial PI-PLC than to the eukaryotic PI-PLC, and they are not included in this subfamily.


Pssm-ID: 320037 [Multi-domain]  Cd Length: 142  Bit Score: 85.38  E-value: 2.74e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  257 RDQWlKQTfDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTdDHQGTLGFEEFCAFYKMMSTRRDLYLLML 336
Cdd:cd16207      2 RIHW-KRA-DSKKQDGDERLDFEDVEKLCRRLHINCSESYLRELFDKADT-DKKGYLNFEEFQEFVKLLKRRKDIKAIFK 78

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462515664  337 TY-SNHKDHLDAASLQRFLQVEQKmAGVTLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRSPA 400
Cdd:cd16207     79 QLtKPGSDGLTLEEFLKFLRDVQK-EDVDRETWEKIFEKFARRIDDSDSLTMTLEGFTSFLLSSY 142
PH_PLC_plant-like cd13365
Plant-like Phospholipase C (PLC) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) was the ...
 127-242 5.30e-16

Plant-like Phospholipase C (PLC) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) was the second class of PLC discovered. PLC-gamma consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves internal to which is a PH domain split by two SH2 domains and a single SH3 domain, and a C-terminal C2 domain. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). This cd contains PLC members from fungi and plants. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270171  Cd Length: 115  Bit Score: 75.01  E-value: 5.30e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  127 PVVERCMGAMQEGMQMVKL--RGGSKglVRFYYLDEHRSCIRWRPSRKNEKAKISIDSIQEVSEGRQSEVFQRYPdGNFD 204
Cdd:cd13365      1 RDVIEAITQLKIGSYLLKYgrRGKPH--FRYFWLSPDELTLYWSSPKKGSEKRVRLSSVSRIIPGQRTVVFKRPP-PPGL 77

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 2462515664  205 PNCCFSIYHGSHRESLDLVSTSSEVARTWVTGLRYLMA 242
Cdd:cd13365     78 EEHSFSIIYADGERSLDLTCKDRQEFDTWFTGLRYLLS 115
EFh_PI-PLCdelta1 cd16217
EF-hand motif found in phosphoinositide phospholipase C delta 1 (PI-PLC-delta1); PI-PLC-delta1, ...
 260-399 5.34e-16

EF-hand motif found in phosphoinositide phospholipase C delta 1 (PI-PLC-delta1); PI-PLC-delta1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1 (PLCD1), or phospholipase C-III (PLC-III), or phospholipase C-delta-1 (PLC-delta-1), is present in high abundancy in the brain, heart, lung, skeletal muscle and testis. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. PI-PLC-delta1 is required for maintenance of homeostasis in skin and metabolic tissues. Moreover, it is essential in trophoblasts for placental development. Simultaneous loss of PI-PLC-delta1 may cause placental vascular defects, leading to embryonic lethality. PI-PLC-delta1 can be positively or negatively regulated by several binding partners, including p122/Rho GTPase activating protein (RhoGAP), Gha/Transglutaminase II, RalA, and calmodulin. It is involved in Alzheimer's disease and hypertension. Furthermore, PI-PLC-delta1 regulates cell proliferation and cell-cycle progression from G1- to S-phase by control of cyclin E-CDK2 activity and p27 levels. It can be activated by alpha1-adrenoreceptors (AR) in a calcium-dependent manner and may be important for G protein-coupled receptors (GPCR) responses in vascular smooth muscle (VSM). PI-PLC-delta1 may also be involved in noradrenaline (NA)-induced phosphatidylinositol-4,5-bisphosphate (PIP2) hydrolysis and modulate sustained contraction of mesenteric small arteries. In addition, it inhibits thermogenesis and induces lipid accumulation, and therefore contributes to the development of obesity. PI-PLC-delta1 contains a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-delta1 can regulate the binding of PH domain to PIP2 in a Ca2+-dependent manner through its functionally important EF-hand domains. In addition, PI-PLC-delta1 possesses a classical leucine-rich nuclear export sequence (NES) located in the EF hand motifs, as well as a nuclear localization signal within its linker region, both of which may be responsible for translocating PI-PLC-delta1 into and out of the cell nucleus.


Pssm-ID: 320047 [Multi-domain]  Cd Length: 139  Bit Score: 75.93  E-value: 5.34e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  260 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTDDhQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 339
Cdd:cd16217      1 WIHSCLRKADKNKDNKMSFKELKDFLKEINIEVDDDYAEKLFKECDKSK-SGFLEGEEIEEFYKLLTKREEIDVIFGEYA 79

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  340 NHKDHLDAASLQRFLQVEQKMAgVTLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRSP 399
Cdd:cd16217     80 KSDGTMSRNNLLNFLQEEQREE-VAPAYALSLIEKYEPDETAKAQRQMTKDGFLMYLLSP 138
PH_PLC_gamma cd13362
Phospholipase C-gamma (PLC-gamma) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is ...
 160-242 3.40e-15

Phospholipase C-gamma (PLC-gamma) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is activated by receptor and non-receptor tyrosine kinases due to the presence of its SH2 and SH3 domains. There are two main isoforms of PLC-gamma expressed in human specimens, PLC-gamma1 and PLC-gamma2. PLC-gamma consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves internal to which is a PH domain split by two SH2 domains and a single SH3 domain, and a C-terminal C2 domain. Only the first PH domain is present in this hierarchy. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270168  Cd Length: 121  Bit Score: 73.08  E-value: 3.40e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  160 EHRSCIRWRPSRKNEKAKISIDSIQEVSEGRQSEVFQRYPD--GNFDPNCCFSIYHGSH--RESLDLVSTSSEVARTWVT 235
Cdd:cd13362     26 ETRQVVWSRGGGKRAEGAVDIREIKEIRPGKNSKDFERWPDeaKKLDPSCCFVILYGTEfrLKTLSVAATSEEECDMWIK 105


                   ....*..
gi 2462515664  236 GLRYLMA 242
Cdd:cd13362    106 GLRYLVE 112
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 847-937 8.94e-15

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175973 [Multi-domain]  Cd Length: 102  Bit Score: 71.33  E-value: 8.94e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  847 LVLRIISGQQLPKPrdsmlgDRGEIIDPFVEVEIIGLpvdcSREQTRVVDDNgFNPTWEETLVFMVHMPEIALVRFLVWD 926
Cdd:cd00030      1 LRVTVIEARNLPAK------DLNGKSDPYVKVSLGGK----QKFKTKVVKNT-LNPVWNETFEFPVLDPESDTLTVEVWD 69

                           90
                   ....*....|..
gi 2462515664  927 HDPIGRD-FIGQ 937
Cdd:cd00030     70 KDRFSKDdFLGE 81
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 260-326 7.28e-14

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.


Pssm-ID: 238008 [Multi-domain]  Cd Length: 63  Bit Score: 67.19  E-value: 7.28e-14
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462515664  260 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTDDHqGTLGFEEFCafyKMMS 326
Cdd:cd00051      1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGD-GKIDFEEFL---ELMA 63
EF-hand_like pfam09279
Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are ...
 321-405 1.53e-13

Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are predominantly found in phosphoinositide-specific phospholipase C. They adopt a structure consisting of a core of four alpha helices, in an EF like fold, and are required for functioning of the enzyme.


Pssm-ID: 401279 [Multi-domain]  Cd Length: 85  Bit Score: 67.27  E-value: 1.53e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  321 FYKMMSTRRDLYLLMLTYSNHKDHLDAASLQRFLQVEQKMAGVTLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRSPA 400
Cdd:pfam09279    1 FYKMLTQREEIDEIFQEYSGDGQKLSLDELVDFLREEQREEDASPALALSLIERYEPSETAKKQHAMTKDGFLMYLCSPD 80


                   ....*
gi 2462515664  401 GDIFN 405
Cdd:pfam09279   81 GSIFN 85
EF-hand_7 pfam13499
EF-hand domain pair;
258-323 2.99e-13

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 65.74  E-value: 2.99e-13
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2462515664  258 DQWLKQTFDEADKNGDGSLSIGEVLQLLHKL--NVNLPRQRVKQMFREADTdDHQGTLGFEEFCAFYK 323
Cdd:pfam13499    1 EEKLKEAFKLLDSDGDGYLDVEELKKLLRKLeeGEPLSDEEVEELFKEFDL-DKDGRISFEEFLELYS 67
EFh_PI-PLCdelta3 cd16218
EF-hand motif found in phosphoinositide phospholipase C delta 3 (PI-PLC-delta3); PI-PLC-delta3, ...
 260-400 4.03e-13

EF-hand motif found in phosphoinositide phospholipase C delta 3 (PI-PLC-delta3); PI-PLC-delta3, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-3 (PLCD3), phospholipase C-delta-3 (PLC-delta-3), is expressed abundantly in brain, skeletal muscle and heart. PI-PLC-delta3 gene expression is down-regulation by cAMP and calcium. PI-PLC-delta3 acts as anchoring of myosin VI on plasma membrane, and further modulates Myosin IV expression and microvilli formation in enterocytes. It negatively regulates RhoA expression, inhibits RhoA/Rho kinase signaling, and plays an essential role in normal neuronal migration by promoting neuronal outgrowth in the developing brain. Moreover, PI-PLC-delta3 is essential in trophoblasts for placental development. Simultaneous loss of PI-PLC-delta3 may cause placental vascular defects, leading to embryonic lethality. PI-PLC-delta3 contains a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. In addition, PI-PLC-delta3 possesses a classical leucine-rich nuclear export sequence (NES) located in the EF hand motifs, which may be responsible transporting PI-PLC-delta3 from the cell nucleus.


Pssm-ID: 320048 [Multi-domain]  Cd Length: 138  Bit Score: 67.85  E-value: 4.03e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  260 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADT------DDHQgtlgFEEFCAfyKMMStRRDLYL 333
Cdd:cd16218      1 WIHEYLRRADLNKDGKMSFEEIKDLLQMINIDLNEQYAYQLFKECDRsnddrlEEHE----IEEFCR--RLMQ-RPELEE 73

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462515664  334 LMLTYSNHKDHLDAASLQRFLQvEQKMAGvTLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRSPA 400
Cdd:cd16218     74 IFHQYSGEDCVLSAEELREFLK-DQGEDA-SLVHAKELIQTYELNEKAKQHQLMTLDGFTMYMLSKD 138
EFh_PI-PLCzeta cd16204
EF-hand motif found in phosphoinositide phospholipase C zeta 1 (PI-PLC-zeta1); PI-PLC-zeta1, ...
 273-398 7.57e-12

EF-hand motif found in phosphoinositide phospholipase C zeta 1 (PI-PLC-zeta1); PI-PLC-zeta1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase zeta-1, or phospholipase C-zeta-1 (PLC-zeta-1), or testis-development protein NYD-SP27, is only found in the testis. The sperm-specific PI-PLC plays a fundamental role in vertebrate fertilization by initiating intracellular calcium oscillations that trigger the embryo development. However, the mechanism of its activation still remains unclear. PI-PLC-zeta1 contains an N-terminal four atypical EF-hand motifs, a PLC catalytic core domain, and a C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unlike other PI-PLCs, PI-PLC-zeta is responsible for Ca2+ oscillations in fertilized oocytes and exhibits a high sensitivity to Ca2+ mediated through its EF-hand domain. There is only one PLC-zeta isozyme. Aside from PI-PLC-zeta identified in mammals, its eukaryotic homologs have been classified with this family.


Pssm-ID: 320034 [Multi-domain]  Cd Length: 142  Bit Score: 64.06  E-value: 7.57e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  273 DGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTDDhQGTLGFEEFCAFYKMMSTRRDLYLLMLTYSNHKDHLDAASLQR 352
Cdd:cd16204     16 KGKINLESTLKLLEKLDIPFDYIHVKYIFKKNDSFK-AGNITIEDFRAIYRAIAHRCEIHEIFNTYSENRKILSAPNLVG 94

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 2462515664  353 FLQVEQKMAGVTLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRS 398
Cdd:cd16204     95 FLKKEQFQDEADETIASELIAKYEPIEEVRKRKQMSFEGFIRYMTS 140
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
250-321 1.55e-10

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 60.19  E-value: 1.55e-10
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462515664  250 LARRQRTRDQWLKQTFDEADKNGDGSLSIGEVLQLLHKLNVnlPRQRVKQMFREADTdDHQGTLGFEEFCAF 321
Cdd:COG5126     60 ESLFEATVEPFARAAFDLLDTDGDGKISADEFRRLLTALGV--SEEEADELFARLDT-DGDGKISFEEFVAA 128
PH_12 pfam16457
Pleckstrin homology domain;
128-241 6.42e-10

Pleckstrin homology domain;


Pssm-ID: 465123 [Multi-domain]  Cd Length: 128  Bit Score: 58.42  E-value: 6.42e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  128 VVERCMGAMQEGMQMVKLRGGSKGL-VRFYYLDEHRSCIRW---------RPSRKNEKAKISIDSIQEVSEGRQSEVF-- 195
Cdd:pfam16457    1 VKEQRLNCLLEGAWFPKVRGRRRKKkYRFCRLSPNRKVLHYgdfeekptvDPSLESLPEKIDLSDIKEVVTGKECPHVre 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 2462515664  196 QRYPDGNFDPNCCFSIYHGSH-RESLDLVSTSSEVARTWVTGLRYLM 241
Cdd:pfam16457   81 SGKKSKKTSSTLAFSLIYGADeYELLDFVAPSESVAAIWLDGLNMLL 127
PI-PLCc_bacteria_like cd08557
Catalytic domain of bacterial phosphatidylinositol-specific phospholipase C and similar ...
 418-555 1.81e-08

Catalytic domain of bacterial phosphatidylinositol-specific phospholipase C and similar proteins; This subfamily corresponds to the catalytic domain present in bacterial phosphatidylinositol-specific phospholipase C (PI-PLC, EC 4.6.1.13) and their sequence homologs found in eukaryota. Bacterial PI-PLCs participate in Ca2+-independent PI metabolism, hydrolyzing the membrane lipid phosphatidylinositol (PI) to produce phosphorylated myo-inositol and diacylglycerol (DAG). Although their precise physiological function remains unclear, bacterial PI-PLCs may function as virulence factors in some pathogenic bacteria. Bacterial PI-PLCs contain a single TIM-barrel type catalytic domain. Its catalytic mechanism is based on general base and acid catalysis utilizing two well conserved histidines, and consists of two steps, a phosphotransfer and a phosphodiesterase reaction. Eukaryotic homologs in this family are named as phosphatidylinositol-specific phospholipase C X domain containing proteins (PI-PLCXD). They are distinct from the typical eukaryotic phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11), which have a multidomain organization that consists of a PLC catalytic core domain, and various regulatory domains. The catalytic core domain is assembled from two highly conserved X- and Y-regions split by a divergent linker sequence. In contrast, eukaryotic PI-PLCXDs contain a single TIM-barrel type catalytic domain, X domain, which is closely related to that of bacterial PI-PLCs. Although the biological function of eukaryotic PI-PLCXDs still remains unclear, it may be distinct from that of typical eukaryotic PI-PLCs. This family also includes a distinctly different type of eukaryotic PLC, glycosylphosphatidylinositol-specific phospholipase C (GPI-PLC), an integral membrane protein characterized in the protozoan parasite Trypanosoma brucei. T. brucei GPI-PLC hydrolyzes the GPI-anchor on the variant specific glycoprotein (VSG), releasing dimyristyl glycerol (DMG), which may facilitate the evasion of the protozoan to the host's immune system. It does not require Ca2+ for its activity and is more closely related to bacterial PI-PLCs, but not mammalian PI-PLCs.


Pssm-ID: 176500 [Multi-domain]  Cd Length: 271  Bit Score: 57.10  E-value: 1.81e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  418 PLSHYFITSSHNTYlvgDQLMSQSRVDMYAWV----------LQAGCRCVEVDCW-DGPDGEPIVHHGYTLTSKILFKDV 486
Cdd:cd08557      8 PLSQLSIPGTHNSY---AYTIDGNSPIVSKWSktqdlsitdqLDAGVRYLDLRVAyDPDDGDLYVCHGLFLLNGQTLEDV 84

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462515664  487 IETINkyAFIK---NEyPVILSIENHCSVI---QQKKMAQYLTDILGDKLDLSSVSSEDATTLpSpQMLKGKILV 555
Cdd:cd08557     85 LNEVK--DFLDahpSE-VVILDLEHEYGGDngeDHDELDALLRDVLGDPLYRPPVRAGGWPTL-G-ELRAGKRVL 154
EFh_PI-PLCbeta cd16200
EF-hand motif found in metazoan phosphoinositide-specific phospholipase C (PI-PLC)-beta ...
 280-399 6.90e-08

EF-hand motif found in metazoan phosphoinositide-specific phospholipase C (PI-PLC)-beta isozymes; PI-PLC-beta isozymes represent a class of metazoan PI-PLCs that hydrolyze the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) to propagate diverse intracellular responses that underlie the physiological action of many hormones, neurotransmitters, and growth factors (EC 3.1.4.11). They have been implicated in numerous processes relevant to central nervous system (CNS), including chemotaxis, cardiovascular function, neuronal signaling, and opioid sensitivity. Like other PI-PLC isozymes, PI-PLC-beta isozymes contain a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. Besides, they have a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are four PI-PLC-beta isozymes (1-4). PI-PLC-beta1 and PI-PLC-beta3 are expressed in a wide range of tissues and cell types, whereas PI-PLC-beta2 and PI-PLC-beta4 have been found only in hematopoietic and neuronal tissues, respectively. All PI-PLC-beta isozymes are activated by the heterotrimeric G protein alpha subunits of the Gq class through their C2 domain and long C-terminal extension. They are GTPase-activating proteins (GAPs) for these G alpha(q) proteins. PI-PLC-beta2 and PI-PLC-beta3 can also be activated by beta-gamma subunits of the G alpha(i/o) family of heterotrimeric G proteins and the small GTPases such as Rac and Cdc42. This family also includes two invertebrate homologs of PI-PLC-beta, PLC21 from cephalopod retina and No receptor potential A protein (NorpA) from Drosophila melanogaster.


Pssm-ID: 320030 [Multi-domain]  Cd Length: 153  Bit Score: 53.02  E-value: 6.90e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  280 EVLQLLHKLNvnLPRQRVKQMFREADTDDHqgtlgfeeFCAFYKMMSTRRDLYLLMLTYS-NHKDHLDAASLQRFLQVEQ 358
Cdd:cd16200     34 RVLKALKALG--LPDGKNDEIDPEDFTFEK--------FFKLYNKLCPRPDIDEIFKELGgKRKPYLTLEQLVDFLNEEQ 103

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 2462515664  359 ---KMAGV-----TLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRSP 399
Cdd:cd16200    104 rdpRLNEIlfpfhTKEQAKKLIDKYEPNEKNKKKGQLTLEGFLRYLMSD 152
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 844-937 1.11e-07

C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are believed to organize specialized sites of the plasma membrane called active zones. They also play a role in controlling neurotransmitter release, plasticity processes, as well as memory and learning. RIM contains an N-terminal zinc finger domain, a PDZ domain, and two C-terminal C2 domains (C2A, C2B). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology and do not bind Ca2+.


Pssm-ID: 175997 [Multi-domain]  Cd Length: 125  Bit Score: 51.86  E-value: 1.11e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  844 KKQLVLRIISGQQLPKPRDSMLGDrgeiidPFVEVEIIGLPVDCSREQTRVVDdNGFNPTWEETLVFMVHMPEIALVRFL 923
Cdd:cd04031     15 TSQLIVTVLQARDLPPRDDGSLRN------PYVKVYLLPDRSEKSKRRTKTVK-KTLNPEWNQTFEYSNVRRETLKERTL 87

                           90
                   ....*....|....*...
gi 2462515664  924 ---VWDHDPIG-RDFIGQ 937
Cdd:cd04031     88 evtVWDYDRDGeNDFLGE 105
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
257-330 1.23e-06

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 49.02  E-value: 1.23e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462515664  257 RDQWLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTdDHQGTLGFEEFCAFYKMMSTRRD 330
Cdd:COG5126     31 FRRLWATLFSEADTDGDGRISREEFVAGMESLFEATVEPFARAAFDLLDT-DGDGKISADEFRRLLTALGVSEE 103
EH cd00052
Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and ...
 262-319 1.25e-06

Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and signal transduction. The alignment contains a pair of EF-hand motifs, typically one of them is canonical and binds to Ca2+, while the other may not bind to Ca2+. A hydrophobic binding pocket is formed by residues from both EF-hand motifs. The EH domain binds to proteins containing NPF (class I), [WF]W or SWG (class II), or H[TS]F (class III) sequence motifs.


Pssm-ID: 238009 [Multi-domain]  Cd Length: 67  Bit Score: 46.83  E-value: 1.25e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2462515664  262 KQTFDEADKNGDGSLSIGEVLQLLhkLNVNLPRQRVKQMFREADTdDHQGTLGFEEFC 319
Cdd:cd00052      2 DQIFRSLDPDGDGLISGDEARPFL--GKSGLPRSVLAQIWDLADT-DKDGKLDKEEFA 56
PTZ00184 PTZ00184
calmodulin; Provisional
 250-328 2.18e-06

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 48.60  E-value: 2.18e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  250 LARRQRTRD--QWLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTDDhQGTLGFEEFCafyKMMST 327
Cdd:PTZ00184    73 MARKMKDTDseEEIKEAFKVFDRDGNGFISAAELRHVMTNLGEKLTDEEVDEMIREADVDG-DGQINYEEFV---KMMMS 148


                   .
gi 2462515664  328 R 328
Cdd:PTZ00184   149 K 149
EFh_PI-PLCgamma cd16201
EF-hand motif found in phosphoinositide phospholipase C gamma isozymes (PI-PLC-gamma); ...
 260-359 2.45e-06

EF-hand motif found in phosphoinositide phospholipase C gamma isozymes (PI-PLC-gamma); PI-PLC-gamma isozymes represent a class of metazoan PI-PLCs that hydrolyze the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) to propagate diverse intracellular responses that underlie the physiological action of many hormones, neurotransmitters, and growth factors. They can form a complex with the phosphorylated cytoplasmic domains of the immunoglobulin Ig-alpha and Ig-beta subunits of the B cell receptor (BCR), the membrane-tethered Src family kinase Lyn, phosphorylated spleen tyrosine kinase (Syk), the phosphorylated adaptor protein B-cell linker (BLNK), and activated Bruton's tyrosine kinase (Btk). Like other PI-PLC isozymes, PI-PLC-gamma isozymes contain a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma, a second PH domain, which is split by two SH2 (Src homology 2) domains, and one SH3 (Src homology 3) domain, are present within this linker. The SH2 and SH3 domains are responsible for the binding of phosphotyrosine-containing sequences and proline-rich sequences, respectively. There are two PI-PLC-gamma isozymes (1-2), both of which are activated by receptor and non-receptor tyrosine kinases due to the presence of SH2 and SH3 domains.


Pssm-ID: 320031 [Multi-domain]  Cd Length: 145  Bit Score: 48.34  E-value: 2.45e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  260 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTDdHQGTLGFEEFCAFY-------KMMSTRRDLY 332
Cdd:cd16201      1 WLRKEFYSMDRTRRETVTLKDLKAFLPRVNCKISTNKLREKFQEVDTR-RRGELGFDDFAQLYhklmfdqKIIEDFFKKY 79

                           90       100
                   ....*....|....*....|....*..
gi 2462515664  333 llmlTYSNHKDHLDAASLQRFLQVEQK 359
Cdd:cd16201     80 ----SYSSDGQTVTLEDFQRFLLEEQK 102
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
 831-951 4.07e-06

C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. There are several classes of Synaptotagmins. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175975 [Multi-domain]  Cd Length: 134  Bit Score: 47.58  E-value: 4.07e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  831 FNPNSEdplpgqlkkQLVLRIISGQQLPKPrdsmlgDRGEIIDPFVEVEIIGLPVDCSREQTRVVDDNgFNPTWEETLVF 910
Cdd:cd00276      9 YLPTAE---------RLTVVVLKARNLPPS------DGKGLSDPYVKVSLLQGGKKLKKKKTSVKKGT-LNPVFNEAFSF 72

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 2462515664  911 MV---HMPEIALVrFLVWDHDPIGRD-FIGQRTLAFSSMMPGYRH 951
Cdd:cd00276     73 DVpaeQLEEVSLV-ITVVDKDSVGRNeVIGQVVLGPDSGGEELEH 116
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
 873-942 6.33e-06

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha and gamma. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1(alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 175992 [Multi-domain]  Cd Length: 131  Bit Score: 46.87  E-value: 6.33e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462515664  873 DPFVEVEIIGLPVDCSREQTRVVDDNgFNPTWEETLVFMVHMPEiaLVRFL---VWDHDPIGR-DFIGqrTLAF 942
Cdd:cd04026     35 DPYVKLKLIPDPKNETKQKTKTIKKT-LNPVWNETFTFDLKPAD--KDRRLsieVWDWDRTTRnDFMG--SLSF 103
C2B_Ferlin cd04011
C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 846-933 6.34e-06

C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 175978 [Multi-domain]  Cd Length: 111  Bit Score: 46.42  E-value: 6.34e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  846 QLVLRIISGQQLPkprdsmlgdrGEIIDPFVEVEIIGlpvdcSREQTRVVDDNGfNPTWEETLVFMVHMP--EI--ALVR 921
Cdd:cd04011      5 QVRVRVIEARQLV----------GGNIDPVVKVEVGG-----QKKYTSVKKGTN-CPFYNEYFFFNFHESpdELfdKIIK 68

                           90
                   ....*....|..
gi 2462515664  922 FLVWDHDPIGRD 933
Cdd:cd04011     69 ISVYDSRSLRSD 80
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 846-957 8.29e-06

C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175976 [Multi-domain]  Cd Length: 133  Bit Score: 46.46  E-value: 8.29e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  846 QLVLRIISGQQLpKPRDSmlgdRGeIIDPFVEVEIigLP----VDCSREQTRVVDDNgFNPTWEETLVFMV----HMPEI 917
Cdd:cd04009     17 SLRVEILNARNL-LPLDS----NG-SSDPFVKVEL--LPrhlfPDVPTPKTQVKKKT-LFPLFDESFEFNVppeqCSVEG 87

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 2462515664  918 ALVRFLVWDHDPIGR-DFIGQRTLAFSSmMPGYRHVYLEGM 957
Cdd:cd04009     88 ALLLFTVKDYDLLGSnDFEGEAFLPLND-IPGVEDTSSAQG 127
EFh_PEF_ALG-2_like cd16185
EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein ...
 261-329 1.68e-05

EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein (ALG-2); The family includes some homologs of mammalian apoptosis-linked gene 2 protein (ALG-2) mainly found in lower eukaryotes, such as a parasitic protist Leishmarua major and a cellular slime mold Dictyostelium discoideum. These homologs contains five EF-hand motifs. Due to the presence of unfavorable residues at the Ca2+-coordinating positions, their non-canonical EF4 and EF5 hands may not bind Ca2+. Two Dictyostelium PEF proteins are the prototypes of this family. They may bind to cytoskeletal proteins and/or signal-transducing proteins localized to detergent-resistant membranes named lipid rafts, and occur as monomers or weak homo- or heterodimers like ALG-2. They can serve as a mediator for Ca2+ signaling-related Dictyostehum programmed cell death (PCD).


Pssm-ID: 320060 [Multi-domain]  Cd Length: 163  Bit Score: 46.44  E-value: 1.68e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462515664  261 LKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTdDHQGTLGFEEF---CAFykMMSTRR 329
Cdd:cd16185     68 MQNGFEQRDTSRSGRLDANEVHEALAASGFQLDPPAFQALFRKFDP-DRGGSLGFDDYielCIF--LASARN 136
EFh_PI-PLC21 cd16213
EF-hand motif found in phosphoinositide phospholipase PLC21 and similar proteins; The family ...
 313-395 2.35e-05

EF-hand motif found in phosphoinositide phospholipase PLC21 and similar proteins; The family includes invertebrate homologs of phosphoinositide phospholipase C beta (PI-PLC-beta) named PLC21 from cephalopod retina. It also includes PLC21 encoded by plc-21 gene, which is expressed in the central nervous system of Drosophila. Like beta-class of vertebrate PI-PLCs, PLC21 contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence.


Pssm-ID: 320043  Cd Length: 154  Bit Score: 45.76  E-value: 2.35e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  313 LGFEEFCAFYKMMSTRRDLYLLMLTYSN-HKDHLDAASLQRFLQVEQKMAGV--------TLESCQDIIEQFEPCPENKS 383
Cdd:cd16213     58 FTFEDFFNFYRRLTGRQEVEKIFDELGAkKKPYLTTEQFVDFLNKTQRDPRLneilypyaNPKRARDLINQYEPNKSFAK 137

                           90
                   ....*....|..
gi 2462515664  384 KGLLGIDGFTNY 395
Cdd:cd16213    138 KGHLSVEGFLRY 149
EFh_PI-PLCbeta4 cd16211
EF-hand motif found in phosphoinositide phospholipase C beta 4 (PI-PLC-beta4); PI-PLC-beta4, ...
 315-398 7.68e-05

EF-hand motif found in phosphoinositide phospholipase C beta 4 (PI-PLC-beta4); PI-PLC-beta4, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4, or phospholipase C-beta-4 (PLC-beta4), is expressed in high concentrations in cerebellar Purkinje and granule cells, the median geniculate body, and the lateral geniculate nucleus. It may play a critical role in linking anxiety behaviors and theta rhythm heterogeneity. PI-PLC-beta4 is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. It contributes to generate cell-specific Ca2+ signals evoked by G protein-coupled receptor stimulation. PI-PLC-beta4 functions as a downstream signaling molecule of type 1 metabotropic glutamate receptors (mGluR1s). The thalamic mGluR1-PI-PLC-beta4 cascade is essential for formalin-induced inflammatory pain by regulating the response of ventral posterolateral thalamic nucleus (VPL) neurons. Moreover, PI-PLC-beta4 is essential for long-term depression (LTD) in the rostral cerebellum, which may be required for the acquisition of the conditioned eyeblink response. Besides, PI-PLC-beta4 may play an important role in maintenance of the status epilepticus. The mutations of PI-PLC-beta4 has been identified as the major cause of autosomal dominant auriculocondylar syndrome (ACS). PI-PLC-beta4 contains a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. Besides, it has a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence.


Pssm-ID: 320041  Cd Length: 153  Bit Score: 44.33  E-value: 7.68e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  315 FEEFCAFYKMMSTRRDLYLLMLTYS-NHKDHLDAASLQRFLQVEQKMAGVT--------LESCQDIIEQFEPCPENKSKG 385
Cdd:cd16211     59 FEKFYELYHKICPRTDIEELFKKINgDKKDYLTVDQLISFLNEHQRDPRLNeilfpfydRKRVMQIIETYEVDEEFKKKE 138

                           90
                   ....*....|...
gi 2462515664  386 LLGIDGFTNYTRS 398
Cdd:cd16211    139 QLSSDGFCRYLMS 151
EFh_PEF_ALG-2_like cd16185
EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein ...
 261-327 9.69e-05

EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein (ALG-2); The family includes some homologs of mammalian apoptosis-linked gene 2 protein (ALG-2) mainly found in lower eukaryotes, such as a parasitic protist Leishmarua major and a cellular slime mold Dictyostelium discoideum. These homologs contains five EF-hand motifs. Due to the presence of unfavorable residues at the Ca2+-coordinating positions, their non-canonical EF4 and EF5 hands may not bind Ca2+. Two Dictyostelium PEF proteins are the prototypes of this family. They may bind to cytoskeletal proteins and/or signal-transducing proteins localized to detergent-resistant membranes named lipid rafts, and occur as monomers or weak homo- or heterodimers like ALG-2. They can serve as a mediator for Ca2+ signaling-related Dictyostehum programmed cell death (PCD).


Pssm-ID: 320060 [Multi-domain]  Cd Length: 163  Bit Score: 44.13  E-value: 9.69e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462515664  261 LKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTdDHQGTLGFEEFCAFYKMMST 327
Cdd:cd16185      2 LRQWFRAVDRDRSGSIDVNELQKALAGGGLLFSLATAEKLIRMFDR-DGNGTIDFEEFAALHQFLSN 67
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
261-375 1.09e-04

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 43.63  E-value: 1.09e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  261 LKQTFDEADKNGDGSLSIGEVLQLLHklnvnlprQRVKQMFREADTdDHQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS- 339
Cdd:COG5126      7 LDRRFDLLDADGDGVLERDDFEALFR--------RLWATLFSEADT-DGDGRISREEFVAGMESLFEATVEPFARAAFDl 77

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 2462515664  340 ---NHKDHLDAASLQRFLQVeqkmAGVTLESCQDIIEQF 375
Cdd:COG5126     78 ldtDGDGKISADEFRRLLTA----LGVSEEEADELFARL 112
C2A_Synaptotagmin-7 cd08386
C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 847-951 1.53e-04

C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176032 [Multi-domain]  Cd Length: 125  Bit Score: 42.70  E-value: 1.53e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  847 LVLRIISGQQLPKPrdsmlgDRGEIIDPFVEVEIigLPVDCSREQTRVVDDNgFNPTWEETLVFMVHMPEIALVRFL--- 923
Cdd:cd08386     18 LTLKILKAVELPAK------DFSGTSDPFVKIYL--LPDKKHKLETKVKRKN-LNPHWNETFLFEGFPYEKLQQRVLylq 88

                           90       100       110
                   ....*....|....*....|....*....|....
gi 2462515664  924 VWDH------DPIGRDFIGQRTLAFSSMMPGYRH 951
Cdd:cd08386     89 VLDYdrfsrnDPIGEVSLPLNKVDLTEEQTFWKD 122
EF-hand_10 pfam14788
EF hand;
276-325 1.74e-04

EF hand;


Pssm-ID: 405477  Cd Length: 50  Bit Score: 40.48  E-value: 1.74e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2462515664  276 LSIGEVLQLLHKLNVNLPRQRVKQMFREADTdDHQGTLGFEEFCAFYKMM 325
Cdd:pfam14788    2 MSFKELKNFLRLINIEVDDSYARKLFQKCDT-SQSGRLEGEEIEEFYKLL 50
EFh_PEF_Group_I cd16180
Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds ...
 261-323 2.40e-04

Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds to Group I PEF proteins that have been found not only in higher animals but also in lower animals, plants, fungi and protists. Group I PEF proteins include apoptosis-linked gene 2 protein (ALG-2), peflin and similar proteins. ALG-2, also termed programmed cell death protein 6 (PDCD6), is a widely expressed calcium-binding modulator protein associated with cell proliferation and death, as well as cell survival. It forms a homodimer in the cell or a heterodimer with its closest paralog peflin. Among the PEF proteins, ALG-2 can bind three Ca2+ ions through its EF1, EF3, and EF5 hands, where it is unique in that its EF5 hand binds Ca2+ ion in a canonical coordination. Peflin is a ubiquitously expressed 30-kD PEF protein containing five EF-hand motifs in its C-terminal domain and a longer N-terminal hydrophobic domain (NHB domain) than any other member of the PEF family. The NHB domain harbors nine repeats of a nonapeptide (A/PPGGPYGGP). Peflin may modulate the function of ALG-2 in Ca2+ signaling. It exists only as a heterodimer with ALG-2, and binds two Ca2+ ions through its EF1 and EF3 hands. Its additional EF5 hand is unpaired and does not bind Ca2+ ion but mediates the heterodimerization with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+.


Pssm-ID: 320055 [Multi-domain]  Cd Length: 164  Bit Score: 42.90  E-value: 2.40e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462515664  261 LKQTFDEADKNGDGSLSIGEvLQLLHKLNVNLPRQR--VKQMFREADTDDHqGTLGFEEFCAFYK 323
Cdd:cd16180      2 LRRIFQAVDRDRSGRISAKE-LQRALSNGDWTPFSIetVRLMINMFDRDRS-GTINFDEFVGLWK 64
EFh_PI-PLCgamma1_like cd16216
EF-hand motif found in 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1-like ...
 260-361 2.52e-04

EF-hand motif found in 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1-like proteins; This family corresponds to a small group of uncharacterized 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1-like (PI-PLC-gamma1-like) proteins. Although their biological function remains unclear, they shows high sequence similarity with other phosphoinositide phospholipase C gamma proteins. They contain a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. A second PH domain, which is split by two SH2 (Src homology 2) domains, and one SH3 (Src homology 3) domain, are present within this linker.


Pssm-ID: 320046  Cd Length: 150  Bit Score: 42.61  E-value: 2.52e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  260 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRV---KQMFREADTDdhqgtLGFEEFCAFYK--MMSTRRDLyLL 334
Cdd:cd16216      1 WLRKQFDGMDRSREGSITVKDLKALLPQVNYRVPNMRFlrdKLVEVEARSE-----LTFPHFIQFYKnlMFDAQKSI-IE 74

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 2462515664  335 MLTYSNHKDHLDAASL--------QRFLQVEQKMA 361
Cdd:cd16216     75 QLELSFPLRNVDRPELcqislydfQKFLQHDQKES 109
C2A_MCTP_PRT_plant cd04022
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 847-966 2.87e-04

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 175989 [Multi-domain]  Cd Length: 127  Bit Score: 41.94  E-value: 2.87e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  847 LVLRIISGQQLPkPRDSMLGdrgeiIDPFVEVEIiglpvDCSREQTRVVDDNgFNPTWEETLVFMVHMPEIALVRFL--- 923
Cdd:cd04022      2 LVVEVVDAQDLM-PKDGQGS-----SSAYVELDF-----DGQKKRTRTKPKD-LNPVWNEKLVFNVSDPSRLSNLVLevy 69

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 2462515664  924 VWDH--DPIGRDFIGQRTLAFSSMMPGYRHVYLE-GMEEASIFVHV 966
Cdd:cd04022     70 VYNDrrSGRRRSFLGRVRISGTSFVPPSEAVVQRyPLEKRGLFSRV 115
C2_SRC2_like cd04051
C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production ...
 847-976 5.30e-04

C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production is a response to pathogen infiltration. The initial response of increased Ca2+ concentrations are coupled to downstream signal transduction pathways via calcium binding proteins. SRC2 contains a single C2 domain which localizes to the plasma membrane and is involved in Ca2+ dependent protein binding. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176016 [Multi-domain]  Cd Length: 125  Bit Score: 41.06  E-value: 5.30e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  847 LVLRIISGQQL--PKPRDSMlgdrgeiiDPFVEVEIIGLpvdcSREQTRVVDDNGFNPTWEETLVFMVHMPEI----ALV 920
Cdd:cd04051      2 LEITIISAEDLknVNLFGKM--------KVYAVVWIDPS----HKQSTPVDRDGGTNPTWNETLRFPLDERLLqqgrLAL 69

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2462515664  921 RFLVWDHDPIGRD-FIGQRTLAFSSMMPGYrhvyleGMEEASIFVHVAVSDISGKVK 976
Cdd:cd04051     70 TIEVYCERPSLGDkLIGEVRVPLKDLLDGA------SPAGELRFLSYQLRRPSGKPQ 120
C2A_Rabphilin_Doc2 cd04035
C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 842-936 8.11e-04

C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176000 [Multi-domain]  Cd Length: 123  Bit Score: 40.73  E-value: 8.11e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  842 QLKKQLVLRIISGQQLpKPRDSmlgdrGEIIDPFVEVEIIGLPVDCSREQTRVVDdNGFNPTWEETLVFMVHMPEIA--- 918
Cdd:cd04035     12 PANSALHCTIIRAKGL-KAMDA-----NGLSDPYVKLNLLPGASKATKLRTKTVH-KTRNPEFNETLTYYGITEEDIqrk 84

                           90
                   ....*....|....*...
gi 2462515664  919 LVRFLVWDHDPIGRDFIG 936
Cdd:cd04035     85 TLRLLVLDEDRFGNDFLG 102
C2A_Synaptotagmin-15-17 cd08390
C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a ...
 842-932 9.35e-04

C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176036 [Multi-domain]  Cd Length: 123  Bit Score: 40.32  E-value: 9.35e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  842 QLKKQLVLRIISGQQLPkPRDSMLGDRgeiiDPFVEVEIigLPVDCSREQTRVVDDnGFNPTWEETLVFMVHMPEI--AL 919
Cdd:cd08390     11 LEEEQLTVSLIKARNLP-PRTKDVAHC----DPFVKVCL--LPDERRSLQSKVKRK-TQNPNFDETFVFQVSFKELqrRT 82

                           90
                   ....*....|....*....
gi 2462515664  920 VRFLVWD------HDPIGR 932
Cdd:cd08390     83 LRLSVYDvdrfsrHCIIGH 101
C2A_fungal cd04041
C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C ...
 866-929 9.46e-04

C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C (PKC). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176006 [Multi-domain]  Cd Length: 111  Bit Score: 39.94  E-value: 9.46e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  866 GDRGEI-IDPFVEVEI--IGLPVDCsreqTRVVDDNgFNPTWEETLVFMVHMPEIAL---VRFLVWDHDP 929
Cdd:cd04041     16 ADFGTGsSDPYVTASFakFGKPLYS----TRIIRKD-LNPVWEETWFVLVTPDEVKAgerLSCRLWDSDR 80
PTZ00184 PTZ00184
calmodulin; Provisional
 262-328 9.87e-04

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 40.90  E-value: 9.87e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462515664  262 KQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTDDHqGTLGFEEFCAfykMMSTR 328
Cdd:PTZ00184    14 KEAFSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGN-GTIDFPEFLT---LMARK 76
C2_plant_PLD cd04015
C2 domain present in plant phospholipase D (PLD); PLD hydrolyzes terminal phosphodiester bonds ...
 849-936 1.51e-03

C2 domain present in plant phospholipase D (PLD); PLD hydrolyzes terminal phosphodiester bonds in diester glycerophospholipids resulting in the degradation of phospholipids. In vitro PLD transfers phosphatidic acid to primary alcohols. In plants PLD plays a role in germination, seedling growth, phosphatidylinositol metabolism, and changes in phospholipid composition. There is a single Ca(2+)/phospholipid-binding C2 domain in PLD. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175982 [Multi-domain]  Cd Length: 158  Bit Score: 40.75  E-value: 1.51e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  849 LRIISGQQLPKPRDSMLGDRGEII--DPFVEVEIIGLPVdcsrEQTRVVDDNGfNPTWEET-LVFMVHMpeIALVRFLVW 925
Cdd:cd04015     33 FSKLVGCSEPTLKRPSSHRHVGKItsDPYATVDLAGARV----ARTRVIENSE-NPVWNESfHIYCAHY--ASHVEFTVK 105

                           90
                   ....*....|.
gi 2462515664  926 DHDPIGRDFIG 936
Cdd:cd04015    106 DNDVVGAQLIG 116
PHA03247 PHA03247
large tegument protein UL36; Provisional
 989-1175 2.21e-03

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 42.62  E-value: 2.21e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  989 PKPGSLDSHAAGRPPARPSVsqrilrrTASAPTKSQKPGRRGFPELVLGTRDTGSKGVADDVVPPGPGPAPEAPAQEGPG 1068
Cdd:PHA03247  2743 AVPAGPATPGGPARPARPPT-------TAGPPAPAPPAAPAAGPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPA 2815

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664 1069 SGSPRGKAPAAvAEKSPVRVRPLRVLDGPGPAGMAATcmkcvvgSCAGVNTGGLQRERPPSPGPASRQAAiRQQPRARAD 1148
Cdd:PHA03247  2816 AALPPAASPAG-PLPPPTSAQPTAPPPPPGPPPPSLP-------LGGSVAPGGDVRRRPPSRSPAAKPAA-PARPPVRRL 2886

                          170       180
                   ....*....|....*....|....*..
gi 2462515664 1149 SLGAPCCGLDPHAIPGRSREAPKGPGA 1175
Cdd:PHA03247  2887 ARPAVSRSTESFALPPDQPERPPQPQA 2913
EFh_PEF_Group_I cd16180
Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds ...
 258-327 2.30e-03

Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds to Group I PEF proteins that have been found not only in higher animals but also in lower animals, plants, fungi and protists. Group I PEF proteins include apoptosis-linked gene 2 protein (ALG-2), peflin and similar proteins. ALG-2, also termed programmed cell death protein 6 (PDCD6), is a widely expressed calcium-binding modulator protein associated with cell proliferation and death, as well as cell survival. It forms a homodimer in the cell or a heterodimer with its closest paralog peflin. Among the PEF proteins, ALG-2 can bind three Ca2+ ions through its EF1, EF3, and EF5 hands, where it is unique in that its EF5 hand binds Ca2+ ion in a canonical coordination. Peflin is a ubiquitously expressed 30-kD PEF protein containing five EF-hand motifs in its C-terminal domain and a longer N-terminal hydrophobic domain (NHB domain) than any other member of the PEF family. The NHB domain harbors nine repeats of a nonapeptide (A/PPGGPYGGP). Peflin may modulate the function of ALG-2 in Ca2+ signaling. It exists only as a heterodimer with ALG-2, and binds two Ca2+ ions through its EF1 and EF3 hands. Its additional EF5 hand is unpaired and does not bind Ca2+ ion but mediates the heterodimerization with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+.


Pssm-ID: 320055 [Multi-domain]  Cd Length: 164  Bit Score: 40.20  E-value: 2.30e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462515664  258 DQWlKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTDDhQGTLGFEEF---CAFYKMMST 327
Cdd:cd16180     67 QDW-RRLFRRFDRDRSGSIDFNELQNALSSFGYRLSPQFVQLLVRKFDRRR-RGSISFDDFveaCVTLKRLTD 137
C2_putative_Elicitor-responsive_gene cd04049
C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive ...
 872-940 2.37e-03

C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive proteins are triggered in response to specific elicitor molecules such as glycolproteins, peptides, carbohydrates and lipids. A host of defensive responses are also triggered resulting in localized cell death. Antimicrobial secondary metabolites, such as phytoalexins, or defense-related proteins, including pathogenesis-related (PR) proteins are also produced. There is a single C2 domain present here. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-II topology.


Pssm-ID: 176014 [Multi-domain]  Cd Length: 124  Bit Score: 39.24  E-value: 2.37e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2462515664  872 IDPFVEVEiiglpvdCsREQTR---VVDDNGFNPTWEETLVFMVHMPEIALVRFL---VWDHDPI-GRDFIGQRTL 940
Cdd:cd04049     22 IDPYVIIQ-------C-RTQERkskVAKGDGRNPEWNEKFKFTVEYPGWGGDTKLilrIMDKDNFsDDDFIGEATI 89
C2B_SLP_1-2-3-4 cd04020
C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically ...
 872-936 2.58e-03

C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175987 [Multi-domain]  Cd Length: 162  Bit Score: 40.00  E-value: 2.58e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462515664  872 IDPFVEVEIigLPVDC--SREQTRVVDDNGfNPTWEETLVFMVHMPE---IALVRFLVWDHDPIGR-DFIG 936
Cdd:cd04020     48 SDSFVKCYL--LPDKSkkSKQKTPVVKKSV-NPVWNHTFVYDGVSPEdlsQACLELTVWDHDKLSSnDFLG 115
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
 297-325 4.05e-03

EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in pairs. Links between disease states and genes encoding EF-hands, particularly the S100 subclass, are emerging. Each motif consists of a 12 residue loop flanked on either side by a 12 residue alpha-helix. EF-hands undergo a conformational change unpon binding calcium ions.


Pssm-ID: 197492 [Multi-domain]  Cd Length: 29  Bit Score: 35.82  E-value: 4.05e-03
                            10        20
                    ....*....|....*....|....*....
gi 2462515664   297 VKQMFREADTdDHQGTLGFEEFCAFYKMM 325
Cdd:smart00054    2 LKEAFRLFDK-DGDGKIDFEEFKDLLKAL 29
EF-hand_1 pfam00036
EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering ...
 261-288 4.31e-03

EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering/transport proteins. The first group is the largest and includes the most well-known members of the family such as calmodulin, troponin C and S100B. These proteins typically undergo a calcium-dependent conformational change which opens a target binding site. The latter group is represented by calbindin D9k and do not undergo calcium dependent conformational changes.


Pssm-ID: 425435 [Multi-domain]  Cd Length: 29  Bit Score: 35.84  E-value: 4.31e-03
                           10        20
                   ....*....|....*....|....*...
gi 2462515664  261 LKQTFDEADKNGDGSLSIGEVLQLLHKL 288
Cdd:pfam00036    2 LKEIFRLFDKDGDGKIDFEEFKELLKKL 29
EF-hand_1 pfam00036
EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering ...
 296-325 5.96e-03

EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering/transport proteins. The first group is the largest and includes the most well-known members of the family such as calmodulin, troponin C and S100B. These proteins typically undergo a calcium-dependent conformational change which opens a target binding site. The latter group is represented by calbindin D9k and do not undergo calcium dependent conformational changes.


Pssm-ID: 425435 [Multi-domain]  Cd Length: 29  Bit Score: 35.45  E-value: 5.96e-03
                           10        20        30
                   ....*....|....*....|....*....|
gi 2462515664  296 RVKQMFREADTdDHQGTLGFEEFCAFYKMM 325
Cdd:pfam00036    1 ELKEIFRLFDK-DGDGKIDFEEFKELLKKL 29
EF-hand_6 pfam13405
EF-hand domain;
260-289 6.17e-03

EF-hand domain;


Pssm-ID: 463869 [Multi-domain]  Cd Length: 30  Bit Score: 35.62  E-value: 6.17e-03
                           10        20        30
                   ....*....|....*....|....*....|
gi 2462515664  260 WLKQTFDEADKNGDGSLSIGEVLQLLHKLN 289
Cdd:pfam13405    1 ELREAFKLFDKDGDGKISLEELRKALRSLG 30
C2A_Copine cd04048
C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
 851-937 6.76e-03

C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176013 [Multi-domain]  Cd Length: 120  Bit Score: 37.93  E-value: 6.76e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664  851 IISGQQLPKPrdsmlgDRGEIIDPFVEVEIIGLPVDCSRE--QTRVVDDNgFNPTWEETLVFMVHMPEIALVRFLVWDHD 928
Cdd:cd04048      6 SISCRNLLDK------DVLSKSDPFVVVYVKTGGSGQWVEigRTEVIKNN-LNPDFVTTFTVDYYFEEVQKLRFEVYDVD 78

                           90
                   ....*....|....
gi 2462515664  929 PIGR-----DFIGQ 937
Cdd:cd04048     79 SKSKdlsdhDFLGE 92
PRK14950 PRK14950
DNA polymerase III subunits gamma and tau; Provisional
 32-117 9.87e-03

DNA polymerase III subunits gamma and tau; Provisional


Pssm-ID: 237864 [Multi-domain]  Cd Length: 585  Bit Score: 40.18  E-value: 9.87e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515664   32 VCDALLAQAT---PRQGTPGAPGAERPQSSLLLPPVDGRPQLVIPASPSFQLLPPPTVlSPSMMAPPTAGPLPGPALPPE 108
Cdd:PRK14950   355 VIEALLVPVPapqPAKPTAAAPSPVRPTPAPSTRPKAAAAANIPPKEPVRETATPPPV-PPRPVAPPVPHTPESAPKLTR 433


                   ....*....
gi 2462515664  109 DPGPYPESR 117
Cdd:PRK14950   434 AAIPVDEKP 442
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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