NCBI Conserved Domain Search

Conserved domains on [gi|448262543|pdb|4GNK|B]

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Chain B, 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3

Protein Classification

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List of domain hits

Name

Accession

Description

Interval

E-value

PI-PLCc_beta3

cd08625

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3; This subfamily ...

317-694

8.04e-180

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: 528.86 E-value: 8.04e-180

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       317 STDMTQPLSAYFINSSHNTYLTAGQLAGTSSVEMYRQALLWGCRCVELDVWKGRPPEEEPFITHGFTMTTEVPLRDVLEA 396
Cdd:cd08625    1 SDDMNQPLSHYFINSSHNTYLTAGQLTGLSSVEMYRQVLLTGCRCIELDCWKGRPPEEEPFITHGFTMTTEIPFKDVIEA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       397 IAETAFKTSPYPVILSFENHVDSAKQQAKMAEYCRSIFGDALLIEPLDKYPLAPGVPLPSPQDLMGRILVKNKKrhrpsa 476
Cdd:cd08625   81 IAESAFKTSPYPVILSFENHVDSAKQQAKMAEYCRSIFGDALLIDPLDKYPLVPGVQLPSPQELMGKILVKNKK------ 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       477 ggpdsagrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglekpslepqkslgdeglnrgpyvlgpadr 556
Cdd:cd08625      --------------------------------------------------------------------------------

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       557 edeeedeeeeeqtdpkkpttdegtassevnateeMSTLVNYIEPVKFKSFEAARKRNKCFEMSSFVETKAMEQLTKSPME 636
Cdd:cd08625  155 ----------------------------------MSTLVNYIEPVKFKSFEAAAKRNKFFEMSSFVETKAMEQLTKSPME 200

                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|....*...
4GNK_B       637 FVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDVAMQLNAGVFEYN 694
Cdd:cd08625  201 FVEYNKKQLSRIYPKGTRVDSSNYMPQLFWNVGCQMVALNFQTLDLAMQLNMGVFEYN 258

EFh_PI-PLCbeta3

cd16210

EF-hand motif found in phosphoinositide phospholipase C beta 3 (PI-PLC-beta3); PI-PLC-beta3, ...

155-305

1.70e-100

EF-hand motif found in phosphoinositide phospholipase C beta 3 (PI-PLC-beta3); PI-PLC-beta3, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3, or phospholipase C-beta-3 (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. PI-PLC-beta3 associates with CXC chemokine receptor 2 (CXCR2) and Na+/H+ exchanger regulatory factor-1 (NHERF1) to form macromolecular complexes at the plasma membrane of pancreatic cancer cells, which functionally couple chemokine signaling to PI-PLC-beta3-mediated signaling cascade. Moreover, PI-PLC-beta3 directly interacts with the M3 muscarinic receptor (M3R), a prototypical G alpha-q-coupled receptor that promotes PI-PLC-beta3 localization to the plasma membrane. This binding can alter G alpha-q-dependent PLC activation. Furthermore, PI-PLC-beta3 inhibits the proliferation of hematopoietic stem cells (HSCs) and myeloid cells through the interaction of SH2-domain-containing protein phosphatase 1 (SHP-1) and signal transducer and activator of transcription 5 (Stat5), and the augment of the dephosphorylating activity of SHP-1 toward Stat5, leading to the inactivation of Stat5. It is also involved in atopic dermatitis (AD) pathogenesis via regulating the expression of periostin in fibroblasts and thymic stromal lymphopoietin (TSLP) in keratinocytes. In addition, PI-PLC-beta3 mediates the thrombin-induced Ca2+ response in glial cells. PI-PLC-beta3 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: 320040 Cd Length: 151 Bit Score: 315.32 E-value: 1.70e-100

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       155 RKAYTKLKLQVNQDGRIPVKNILKMFSADKKRVETALESCGLKFNRSESIRPDEFSLEIFERFLNKLCLRPDIDKILLEI 234
Cdd:cd16210    1 RKAYTKLKLQVNQDGRIPVKNILKMFSADKKRVETALESCGLKFNRSESIKPDEFTLEIFERFLNKLCLRPDIDKILLEI 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
4GNK_B       235 GAKGKPYLTLEQLMDFINQKQRDPRLNEVLYPPLRPSQARLLIEKYEPNQQFLERDQMSMEGFSRYLGGEE 305
Cdd:cd16210   81 GAKGKPYLTLEQLMDFINQKQRDPRLNEVLYPPLRPSQVRQLIEKYEPNQQFLERDQMSMEGFSRYLGGEE 151

PLC-beta_C

pfam08703

PLC-beta C terminal; This domain corresponds to the alpha helical C terminal domain of ...

1030-1203

7.94e-72

PLC-beta C terminal; This domain corresponds to the alpha helical C terminal domain of phospholipase C beta.

Pssm-ID: 462571 [Multi-domain] Cd Length: 176 Bit Score: 236.89 E-value: 7.94e-72

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1030 KRYQEFQNRQVQSLLELREAQVDAEAQRRLEHLRQALQRLREVVLDANTTQFKRLKEMNEREKKELQKILDRKRHNSISE 1109
Cdd:pfam08703    1 KQVRELKERLEQELLELREEQYEQEKKRKEQHLTEQIQKLKELAREKQAAELKALKESSESEKKEMKKKLERKRLESIQE 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1110 AKMRDKHK-KEAELT-EINRRHITESVNSIRRLEEAQKQRHDRLVAGQQQVLQQLAEEEPKLLAQLAQECQEQRARLPQE 1187
Cdd:pfam08703   81 AKKRTSDKaAQERLKkEINNSHIQEVVQSIKQLEEKQKRRQEKLEEKQAECLQQIKEEEPQLQAELNAEYEEKLKGLPAE 160

                          170
                   ....*....|....*.
4GNK_B        1188 IRRSLLGEMPEGLGDG 1203
Cdd:pfam08703  161 VRESVKSCLKEGFPDE 176

PH_PLC_beta

cd13361

Phospholipase C-beta (PLC-beta) pleckstrin homology (PH) domain; PLC-beta (PLCbeta) is ...

23-150

3.73e-62

Phospholipase C-beta (PLC-beta) pleckstrin homology (PH) domain; PLC-beta (PLCbeta) is regulated by heterotrimeric G protein-coupled receptors through their C2 domain and long C-terminal extension which forms an autoinhibitory helix. There are four isoforms: PLC-beta1-4. The PH domain of PLC-beta2 and PLC-beta3 plays a dual role, much like PLC-delta1, by binding to the plasma membrane, as well as the interaction site for the catalytic activator. However, PLC-beta binds to the lipid surface independent of PIP2. PLC-beta1 seems to play unspecified roles in cellular proliferation and differentiation. PLC-beta consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves, a C2 domain and a C-terminal PDZ. Members of the Rho GTPase family (e.g., Rac1, Rac2, Rac3, and cdc42) have been implicated in their activation by binding to an alternate site on the N-terminal PH domain. A basic amino acid region within the enzyme's long C-terminal tail appears to function as a Nuclear Localization Signal for import into 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.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: 270167 Cd Length: 127 Bit Score: 207.42 E-value: 3.73e-62

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        23 LRRGSKFIKWDEETSSRNLVTLRVDPNGFFLYWTGPNMEVDTLDISSIRDTRTGRYARLPKDPKIREVlGFGGPDARLEE 102
Cdd:cd13361    1 LLKGSKFDKWDEDSSLETPVTLKVDEYGFFLYWKSEGKETEVLDLSLIRDVRTGKYPKDPKDLKEREV-NVGGSDEDLED 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
4GNK_B       103 KLMTVVSGPDPVNTVFLNFMAVQDDTAKVWSEELFKLAMNILAQNASR 150
Cdd:cd13361   80 RTLTIVSGTDLVNISFINFVAESEEVAKIWTEGLFKLAHNLLANNASP 127

PLN02952 super family

cl31960

phosphoinositide phospholipase C

319-834

1.67e-60

phosphoinositide phospholipase C

The actual alignment was detected with superfamily member PLN02952:

Pssm-ID: 178538 [Multi-domain] Cd Length: 599 Bit Score: 219.10 E-value: 1.67e-60

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        319 DMTQPLSAYFINSSHNTYLTAGQLAGTSSVEMYRQALLWGCRCVELDVWKGRpPEEEPFITHGFTMTTEVPLRDVLEAIA 398
Cdd:PLN02952  124 DMTAPLSHYFIYTGHNSYLTGNQLSSDCSEVPIVKALQRGVRVIELDLWPGS-TKDEILVLHGRTLTTPVPLIKCLKSIR 202

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        399 ETAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLiepldkYPLAPG-VPLPSPQDLMGRILVKNKkrhrPSag 477
Cdd:PLN02952  203 DYAFSSSPYPVIITLEDHL-TPDLQAKVAEMATQIFGQMLY------YPESDSlVQFPSPESLKHRIIISTK----PP-- 269

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        478 gpdsagrKRPLEQSNSALSESSAATEPSSPQlGSPSSDscpglsngEEVGLEKPSLEPQ---KSLGDEGLNRGPYVLGPA 554
Cdd:PLN02952  270 -------KEYLESSGPIVIKKKNNVSPSGRN-SSEETE--------EAQTLESMLFEQEadsRSDSDQDDNKSGELQKPA 333

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        555 DRedeeedeeeeeqtdpKKPTTDEGTASSEVNatEEMSTLVNYIEPVkfksfeaarkrnkcfemsSFVETKAMEQLTKSP 634
Cdd:PLN02952  334 YK---------------RLITIHAGKPKGTLK--DAMKVAVDKVRRL------------------SLSEQELEKAATTNG 378

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        635 MEFVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDVAMQLNAGVFEYNGRSGYLLKPEFMRRP---DK 711
Cdd:PLN02952  379 QDVVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIAFNMQGYGKSLWLMHGMFRANGGCGYLKKPDFLMKKgfhDE 458

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        712 SFDPFTEVivdgIVANALRVKVISG----------QFLSDRKVGIYVEVDMFGLPVDTRRKyRTRTSQGNsFNPVWDEEp 781
Cdd:PLN02952  459 VFDPKKKL----PVKKTLKVKVYLGdgwrldfshtHFDSYSPPDFYTKMYIVGVPADNAKK-KTKIIEDN-WYPAWNEE- 531

                         490       500       510       520       530
                  ....*....|....*....|....*....|....*....|....*....|....*..
4GNK_B        782 FDFPKVVlPTLASLRIAAFE----EGGKFVGHRILPVSAIRSGYHYVCLRNEANQPL 834
Cdd:PLN02952  532 FSFPLTV-PELALLRIEVREydmsEKDDFGGQTCLPVSELRPGIRSVPLHDKKGEKL 587

DUF1154 super family

cl05918

Protein of unknown function (DUF1154); This family represents a small conserved region of ...

952-991

1.85e-03

Protein of unknown function (DUF1154); This family represents a small conserved region of unknown function within eukaryotic phospholipase C (EC:3.1.4.3). All members also contain pfam00387 and pfam00388.

The actual alignment was detected with superfamily member pfam06631:

Pssm-ID: 461969 Cd Length: 45 Bit Score: 37.24 E-value: 1.85e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
4GNK_B         952 PTPLDELRGHKALVKLRSRQERDLRELRKKHQRKAVTLTR 991
Cdd:pfam06631    6 PITLESLRQDKAYLKLLKKQQKELESLKKKHSKERSAMQK 45

PRK06975 super family

cl35524

bifunctional uroporphyrinogen-III synthetase/uroporphyrin-III C-methyltransferase; Reviewed

874-1067

4.90e-03

bifunctional uroporphyrinogen-III synthetase/uroporphyrin-III C-methyltransferase; Reviewed

The actual alignment was detected with superfamily member PRK06975:

Pssm-ID: 235899 [Multi-domain] Cd Length: 656 Bit Score: 41.24 E-value: 4.90e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        874 ARQLAALIGESEAQAGQETCQDTQSQQLGSQPSSNPTPSPldASPRRPPGPTTSPASTSLSSPGQRDDLIASILSEVAPT 953
Cdd:PRK06975  256 ERIVRAFLTWADAAAQPATAAPAPSRMTDTNDSKSVTSQP--AAAAAAPAPPPNPPATPPEPPARRGRGSAALWFVVVVL 333

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        954 PLDELRGHKALVKLRSRQERDLRELRKK---HQRKAVTLTRRLLDGLAQAQAEgrcrlrPGALggaadveDTKEGEDEAK 1030
Cdd:PRK06975  334 ACAAAVGGYALNRKVDRLDQELVQRQQAndaQTAELRVKTEQAQASVHQLDSQ------FAQL-------DGKLADAQSA 400

                         170       180       190
                  ....*....|....*....|....*....|....*..
4GNK_B       1031 ryQEFQNRQVQSLLELREAQVDAEAQRRLEHLRQALQ 1067
Cdd:PRK06975  401 --QQALEQQYQDLSRNRDDWMIAEVEQMLSSASQQLQ 435

Name

Accession

Description

Interval

E-value

PI-PLCc_beta3

cd08625

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3; This subfamily ...

317-694

8.04e-180

Pssm-ID: 176562 [Multi-domain] Cd Length: 258 Bit Score: 528.86 E-value: 8.04e-180

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       317 STDMTQPLSAYFINSSHNTYLTAGQLAGTSSVEMYRQALLWGCRCVELDVWKGRPPEEEPFITHGFTMTTEVPLRDVLEA 396
Cdd:cd08625    1 SDDMNQPLSHYFINSSHNTYLTAGQLTGLSSVEMYRQVLLTGCRCIELDCWKGRPPEEEPFITHGFTMTTEIPFKDVIEA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       397 IAETAFKTSPYPVILSFENHVDSAKQQAKMAEYCRSIFGDALLIEPLDKYPLAPGVPLPSPQDLMGRILVKNKKrhrpsa 476
Cdd:cd08625   81 IAESAFKTSPYPVILSFENHVDSAKQQAKMAEYCRSIFGDALLIDPLDKYPLVPGVQLPSPQELMGKILVKNKK------ 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       477 ggpdsagrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglekpslepqkslgdeglnrgpyvlgpadr 556
Cdd:cd08625      --------------------------------------------------------------------------------

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       557 edeeedeeeeeqtdpkkpttdegtassevnateeMSTLVNYIEPVKFKSFEAARKRNKCFEMSSFVETKAMEQLTKSPME 636
Cdd:cd08625  155 ----------------------------------MSTLVNYIEPVKFKSFEAAAKRNKFFEMSSFVETKAMEQLTKSPME 200

                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|....*...
4GNK_B       637 FVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDVAMQLNAGVFEYN 694
Cdd:cd08625  201 FVEYNKKQLSRIYPKGTRVDSSNYMPQLFWNVGCQMVALNFQTLDLAMQLNMGVFEYN 258

EFh_PI-PLCbeta3

cd16210

EF-hand motif found in phosphoinositide phospholipase C beta 3 (PI-PLC-beta3); PI-PLC-beta3, ...

155-305

1.70e-100

Pssm-ID: 320040 Cd Length: 151 Bit Score: 315.32 E-value: 1.70e-100

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       155 RKAYTKLKLQVNQDGRIPVKNILKMFSADKKRVETALESCGLKFNRSESIRPDEFSLEIFERFLNKLCLRPDIDKILLEI 234
Cdd:cd16210    1 RKAYTKLKLQVNQDGRIPVKNILKMFSADKKRVETALESCGLKFNRSESIKPDEFTLEIFERFLNKLCLRPDIDKILLEI 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
4GNK_B       235 GAKGKPYLTLEQLMDFINQKQRDPRLNEVLYPPLRPSQARLLIEKYEPNQQFLERDQMSMEGFSRYLGGEE 305
Cdd:cd16210   81 GAKGKPYLTLEQLMDFINQKQRDPRLNEVLYPPLRPSQVRQLIEKYEPNQQFLERDQMSMEGFSRYLGGEE 151

PI-PLC-X

pfam00388

Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...

320-468

1.39e-74

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: 243.18 E-value: 1.39e-74

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B         320 MTQPLSAYFINSSHNTYLTAGQLAGTSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAIAE 399
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDG--PDGEPVVYHGYTLTSKIPFRDVLEAIKD 78

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
4GNK_B         400 TAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIEPLDKyplaPGVPLPSPQDLMGRILVKN 468
Cdd:pfam00388   79 YAFVTSPYPVILSLENHC-SPEQQKKMAEILKEIFGDMLYTPPLDD----DLTELPSPEDLKGKILIKG 142

PLC-beta_C

pfam08703

PLC-beta C terminal; This domain corresponds to the alpha helical C terminal domain of ...

1030-1203

7.94e-72

PLC-beta C terminal; This domain corresponds to the alpha helical C terminal domain of phospholipase C beta.

Pssm-ID: 462571 [Multi-domain] Cd Length: 176 Bit Score: 236.89 E-value: 7.94e-72

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1030 KRYQEFQNRQVQSLLELREAQVDAEAQRRLEHLRQALQRLREVVLDANTTQFKRLKEMNEREKKELQKILDRKRHNSISE 1109
Cdd:pfam08703    1 KQVRELKERLEQELLELREEQYEQEKKRKEQHLTEQIQKLKELAREKQAAELKALKESSESEKKEMKKKLERKRLESIQE 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1110 AKMRDKHK-KEAELT-EINRRHITESVNSIRRLEEAQKQRHDRLVAGQQQVLQQLAEEEPKLLAQLAQECQEQRARLPQE 1187
Cdd:pfam08703   81 AKKRTSDKaAQERLKkEINNSHIQEVVQSIKQLEEKQKRRQEKLEEKQAECLQQIKEEEPQLQAELNAEYEEKLKGLPAE 160

                          170
                   ....*....|....*.
4GNK_B        1188 IRRSLLGEMPEGLGDG 1203
Cdd:pfam08703  161 VRESVKSCLKEGFPDE 176

PLCYc

smart00149

Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. ...

592-706

1.23e-65

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: 217.11 E-value: 1.23e-65

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B          592 STLVNYIEPVKFKSFEAARKRNKCFEMSSFVETKAMEQLTKSPMEFVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQ 671
Cdd:smart00149    1 SDLVIYCAPVKFRSFESAESKNPFYEMSSFSETKAKKLLKKSPTDFVRYNQRQLSRVYPKGTRVDSSNYNPQVFWNHGCQ 80

                            90       100       110
                    ....*....|....*....|....*....|....*
4GNK_B          672 LVALNFQTLDVAMQLNAGVFEYNGRSGYLLKPEFM 706
Cdd:smart00149   81 MVALNFQTPDKPMQLNQGMFRANGGCGYVLKPDFL 115

PH_PLC_beta

cd13361

Phospholipase C-beta (PLC-beta) pleckstrin homology (PH) domain; PLC-beta (PLCbeta) is ...

23-150

3.73e-62

Pssm-ID: 270167 Cd Length: 127 Bit Score: 207.42 E-value: 3.73e-62

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        23 LRRGSKFIKWDEETSSRNLVTLRVDPNGFFLYWTGPNMEVDTLDISSIRDTRTGRYARLPKDPKIREVlGFGGPDARLEE 102
Cdd:cd13361    1 LLKGSKFDKWDEDSSLETPVTLKVDEYGFFLYWKSEGKETEVLDLSLIRDVRTGKYPKDPKDLKEREV-NVGGSDEDLED 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
4GNK_B       103 KLMTVVSGPDPVNTVFLNFMAVQDDTAKVWSEELFKLAMNILAQNASR 150
Cdd:cd13361   80 RTLTIVSGTDLVNISFINFVAESEEVAKIWTEGLFKLAHNLLANNASP 127

PLN02952

phosphoinositide phospholipase C

319-834

1.67e-60

phosphoinositide phospholipase C

Pssm-ID: 178538 [Multi-domain] Cd Length: 599 Bit Score: 219.10 E-value: 1.67e-60

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        319 DMTQPLSAYFINSSHNTYLTAGQLAGTSSVEMYRQALLWGCRCVELDVWKGRpPEEEPFITHGFTMTTEVPLRDVLEAIA 398
Cdd:PLN02952  124 DMTAPLSHYFIYTGHNSYLTGNQLSSDCSEVPIVKALQRGVRVIELDLWPGS-TKDEILVLHGRTLTTPVPLIKCLKSIR 202

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        399 ETAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLiepldkYPLAPG-VPLPSPQDLMGRILVKNKkrhrPSag 477
Cdd:PLN02952  203 DYAFSSSPYPVIITLEDHL-TPDLQAKVAEMATQIFGQMLY------YPESDSlVQFPSPESLKHRIIISTK----PP-- 269

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        478 gpdsagrKRPLEQSNSALSESSAATEPSSPQlGSPSSDscpglsngEEVGLEKPSLEPQ---KSLGDEGLNRGPYVLGPA 554
Cdd:PLN02952  270 -------KEYLESSGPIVIKKKNNVSPSGRN-SSEETE--------EAQTLESMLFEQEadsRSDSDQDDNKSGELQKPA 333

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        555 DRedeeedeeeeeqtdpKKPTTDEGTASSEVNatEEMSTLVNYIEPVkfksfeaarkrnkcfemsSFVETKAMEQLTKSP 634
Cdd:PLN02952  334 YK---------------RLITIHAGKPKGTLK--DAMKVAVDKVRRL------------------SLSEQELEKAATTNG 378

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        635 MEFVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDVAMQLNAGVFEYNGRSGYLLKPEFMRRP---DK 711
Cdd:PLN02952  379 QDVVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIAFNMQGYGKSLWLMHGMFRANGGCGYLKKPDFLMKKgfhDE 458

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        712 SFDPFTEVivdgIVANALRVKVISG----------QFLSDRKVGIYVEVDMFGLPVDTRRKyRTRTSQGNsFNPVWDEEp 781
Cdd:PLN02952  459 VFDPKKKL----PVKKTLKVKVYLGdgwrldfshtHFDSYSPPDFYTKMYIVGVPADNAKK-KTKIIEDN-WYPAWNEE- 531

                         490       500       510       520       530
                  ....*....|....*....|....*....|....*....|....*....|....*..
4GNK_B        782 FDFPKVVlPTLASLRIAAFE----EGGKFVGHRILPVSAIRSGYHYVCLRNEANQPL 834
Cdd:PLN02952  532 FSFPLTV-PELALLRIEVREydmsEKDDFGGQTCLPVSELRPGIRSVPLHDKKGEKL 587

PH_14

pfam17787

PH domain; This entry corresponds to the PH domain found at the N-terminus of phospholipase C ...

18-147

5.35e-48

PH domain; This entry corresponds to the PH domain found at the N-terminus of phospholipase C enzymes.

Pssm-ID: 465506 Cd Length: 131 Bit Score: 167.17 E-value: 5.35e-48

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B          18 TVVETLRRGSKFIKWDEETSSRN-LVTLRVDPNGFFLYWTGPNMEVDTLDISSIRDTRTGRYARLPKDPKIREVLGFGGP 96
Cdd:pfam17787    1 EVPEKLQKGELFIKWDEESTVAEpNVLLKVDPKGFFLYWKSQGKEGEVLEITSIRDTRLGKFAKIPKDPKLREVLSMGGS 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
4GNK_B          97 DARLEEKLMTVVSGPDPVNTVFLNFMAVQDDTAKVWSEELFKLAMNILAQN 147
Cdd:pfam17787   81 DNSLEDKTLTVVSGTDMVNINFHNFVASNSEVAKNWAEGLRALAHNVLAAN 131

C2_PLC_like

cd00275

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...

729-844

8.72e-37

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: 134.98 E-value: 8.72e-37

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       729 LRVKVISGQFLSD------RKVGIYVEVDMFGLPVDTRRKYRTRTSQGNSFNPVWDEEpFDFPkVVLPTLASLRIAAFEE 802
Cdd:cd00275    4 LTIKIISGQQLPKpkgdkgSIVDPYVEVEIHGLPADDSAKFKTKVVKNNGFNPVWNET-FEFD-VTVPELAFLRFVVYDE 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
4GNK_B       803 GG---KFVGHRILPVSAIRSGYHYVCLRNEANQPLCLPALLIYTE 844
Cdd:cd00275   82 DSgddDFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHID 126

PLN02223

phosphoinositide phospholipase C

319-829

1.37e-24

phosphoinositide phospholipase C

Pssm-ID: 165867 [Multi-domain] Cd Length: 537 Bit Score: 109.73 E-value: 1.37e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        319 DMTQPLSAYFINSSHNTYLTAGQLAGTS-SVEMYRQALLWGCRCVELDVWkgrpPEEEPFITHGFTMTTEVPLR--DVLE 395
Cdd:PLN02223  107 DMHAPLSHYFIHTSLKSYFTGNNVFGKLySIEPIIDALEQGVRVVELDLL----PDGKDGICVRPKWNFEKPLElqECLD 182

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        396 AIAETAF-KTSPYPVILSFEnhvDSAKQ--QAKMAEYCRSIFGDALLIEPldkyPLAPGVPLPSPQDLMGRILVKNKkrh 472
Cdd:PLN02223  183 AIKEHAFtKCRSYPLIITFK---DGLKPdlQSKATQMIDQTFGDMVYHED----PQHSLEEFPSPAELQNKILISRR--- 252

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        473 rpsaggpdsagrkrpleqsnsalsessaatePSSPQLGSPSSDSCPGLSNGEEVglekpslepqkslgdeglNRGPyvlg 552
Cdd:PLN02223  253 -------------------------------PPKELLYAKADDGGVGVRNELEI------------------QEGP---- 279

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        553 padredeeedeeeeeqTDPkkpttdegtassevnateemstlvNYIEPVKFKSFEAARKRNKCFEMSSfvetKAMEQLTK 632
Cdd:PLN02223  280 ----------------ADK------------------------NYQSLVGFHAVEPRGMLQKALTGKA----DDIQQPGW 315

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        633 SPMEFVEYNKQQLSRIYPKGTRVDS-SNYMPQLFWNVGCQLVALNFQTLDVAMQLNAGVFEYNGRSGYLLKPEFMRR--P 709
Cdd:PLN02223  316 YERDIISFTQKKFLRTRPKKKNLLInAPYKPQRAWMHGAQLIALSRKDDKEKLWLMQGMFRANGGCGYVKKPDFLLNagP 395

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        710 DKSFDPftevIVDGIVANALRVKVISGQ-FLSD--RKVG------IYVEVDMFGLPVDtrRKYRTRTSQGNSFNPVWDEE 780
Cdd:PLN02223  396 SGVFYP----TENPVVVKILKVKIYMGDgWIVDfkKRIGrlskpdLYVRISIAGVPHD--EKIMKTTVKNNEWKPTWGEE 469

                         490       500       510       520       530
                  ....*....|....*....|....*....|....*....|....*....|...
4GNK_B        781 pFDFPkVVLPTLA--SLRIAAFE--EGGKFVGHRILPVSAIRSGYHYVCLRNE 829
Cdd:PLN02223  470 -FTFP-LTYPDLAliSFEVYDYEvsTADAFCGQTCLPVSELIEGIRAVPLYDE 520

smart00239

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...

729-826

2.05e-13

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: 67.51 E-value: 2.05e-13

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B          729 LRVKVISGQFLSDRKVG----IYVEVDMFGlpvDTRRKYRTRTSQgNSFNPVWDEEpFDFPkVVLPTLASLRIAAFEEGG 804
Cdd:smart00239    2 LTVKIISARNLPPKDKGgksdPYVKVSLDG---DPKEKKKTKVVK-NTLNPVWNET-FEFE-VPPPELAELEIEVYDKDR 75

                            90       100
                    ....*....|....*....|....*.
4GNK_B          805 ----KFVGHRILPVSAIRSGYHYVCL 826
Cdd:smart00239   76 fgrdDFIGQVTIPLSDLLLGGRHEKL 101

EF-hand_like

pfam09279

Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are ...

217-309

7.70e-09

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: 53.79 E-value: 7.70e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B         217 FLNKLCLRPDIDKILLEIGAKGKpYLTLEQLMDFINQKQRDPRLNevlypplrPSQARLLIEKYEPNQQFLERDQMSMEG 296
Cdd:pfam09279    1 FYKMLTQREEIDEIFQEYSGDGQ-KLSLDELVDFLREEQREEDAS--------PALALSLIERYEPSETAKKQHAMTKDG 71

                           90
                   ....*....|...
4GNK_B         297 FSRYLGGEENGIL 309
Cdd:pfam09279   72 FLMYLCSPDGSIF 84

COG4913

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

956-1185

5.85e-08

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

Pssm-ID: 443941 [Multi-domain] Cd Length: 1089 Bit Score: 57.23 E-value: 5.85e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       956 DELRG-HKALVKLRsRQERDLRELRKKHQRkavtlTRRLLDGLAQAQAEGRcRLRPgalggaadvedtkegEDEAKRYQE 1034
Cdd:COG4913  235 DDLERaHEALEDAR-EQIELLEPIRELAER-----YAAARERLAELEYLRA-ALRL---------------WFAQRRLEL 292

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B      1035 FQNRQVQSLLELREAQVD-AEAQRRLEHLRQALQRLREVVLDANTTQFKRLkemnEREKKELQKILDRKRHNS------I 1107
Cdd:COG4913  293 LEAELEELRAELARLEAElERLEARLDALREELDELEAQIRGNGGDRLEQL----EREIERLERELEERERRRarlealL 368

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B      1108 SEAKMRDKHkKEAELTEiNRRHITESVNSIRRLEEAQKQRHDRLVAGQQQVLQQLAEEE-------------P----KLL 1170
Cdd:COG4913  369 AALGLPLPA-SAEEFAA-LRAEAAALLEALEEELEALEEALAEAEAALRDLRRELRELEaeiaslerrksniParllALR 446

                        250
                 ....*....|....*
4GNK_B      1171 AQLAQECQEQRARLP 1185
Cdd:COG4913  447 DALAEALGLDEAELP 461

pfam00168

C2 domain;

729-823

7.15e-08

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 51.55 E-value: 7.15e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B         729 LRVKVISGQFLSDRKVGI----YVEVDMfglpVDTRRKYRTRTSQgNSFNPVWDEEpFDFPkVVLPTLASLRIAAFEEGG 804
Cdd:pfam00168    3 LTVTVIEAKNLPPKDGNGtsdpYVKVYL----LDGKQKKKTKVVK-NTLNPVWNET-FTFS-VPDPENAVLEIEVYDYDR 75

                           90       100
                   ....*....|....*....|...
4GNK_B         805 ----KFVGHRILPVSAIRSGYHY 823
Cdd:pfam00168   76 fgrdDFIGEVRIPLSELDSGEGL 98

SMC_prok_A

TIGR02169

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of ...

1020-1188

1.07e-06

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274009 [Multi-domain] Cd Length: 1164 Bit Score: 53.15 E-value: 1.07e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1020 EDTKEGEDEAKRYQEFQNRQVQSLLELREAQVDA-----EAQRRLEHLRQALQRLREVV--LDANTTQFKRLKEMNEREK 1092
Cdd:TIGR02169  681 ERLEGLKRELSSLQSELRRIENRLDELSQELSDAsrkigEIEKEIEQLEQEEEKLKERLeeLEEDLSSLEQEIENVKSEL 760

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1093 KELQKILDRKRhnsiseakmRDKHKKEAELTEINRRHITESVNSIRRLEEAQKQRHDRLVA---------GQQQVLQQLA 1163
Cdd:TIGR02169  761 KELEARIEELE---------EDLHKLEEALNDLEARLSHSRIPEIQAELSKLEEEVSRIEArlreieqklNRLTLEKEYL 831

                          170       180
                   ....*....|....*....|....*
4GNK_B        1164 EEEPKLLAQLAQECQEQRARLPQEI 1188
Cdd:TIGR02169  832 EKEIQELQEQRIDLKEQIKSIEKEI 856

PTZ00121

MAEBL; Provisional

956-1190

1.97e-05

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 49.37 E-value: 1.97e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        956 DELRGHKALVKLRSRQERDLRELRKKHQRKAVTLTRRLLDGLAQAQAEGRCRlrpgalgGAADVEDTKEGeDEAKRYQEF 1035
Cdd:PTZ00121 1486 DEAKKKAEEAKKKADEAKKAAEAKKKADEAKKAEEAKKADEAKKAEEAKKAD-------EAKKAEEKKKA-DELKKAEEL 1557

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       1036 QN-RQVQSLLELREAQVDAE-AQRRLEHLRQALQRLREVVLDANTTQFKRLKEMNEREKKELQKILDRKRHNSISEAKMR 1113
Cdd:PTZ00121 1558 KKaEEKKKAEEAKKAEEDKNmALRKAEEAKKAEEARIEEVMKLYEEEKKMKAEEAKKAEEAKIKAEELKKAEEEKKKVEQ 1637

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
4GNK_B       1114 DKHKKEAELTEINRRHITESVNSIRRLEEAQKQRHDRLVAGQqqvLQQLAEEEPKLLAQLAQECQEqrARLPQEIRR 1190
Cdd:PTZ00121 1638 LKKKEAEEKKKAEELKKAEEENKIKAAEEAKKAEEDKKKAEE---AKKAEEDEKKAAEALKKEAEE--AKKAEELKK 1709

DUF1154

pfam06631

Protein of unknown function (DUF1154); This family represents a small conserved region of ...

952-991

1.85e-03

Pssm-ID: 461969 Cd Length: 45 Bit Score: 37.24 E-value: 1.85e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
4GNK_B         952 PTPLDELRGHKALVKLRSRQERDLRELRKKHQRKAVTLTR 991
Cdd:pfam06631    6 PITLESLRQDKAYLKLLKKQQKELESLKKKHSKERSAMQK 45

PRK06975

bifunctional uroporphyrinogen-III synthetase/uroporphyrin-III C-methyltransferase; Reviewed

874-1067

4.90e-03

bifunctional uroporphyrinogen-III synthetase/uroporphyrin-III C-methyltransferase; Reviewed

Pssm-ID: 235899 [Multi-domain] Cd Length: 656 Bit Score: 41.24 E-value: 4.90e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        874 ARQLAALIGESEAQAGQETCQDTQSQQLGSQPSSNPTPSPldASPRRPPGPTTSPASTSLSSPGQRDDLIASILSEVAPT 953
Cdd:PRK06975  256 ERIVRAFLTWADAAAQPATAAPAPSRMTDTNDSKSVTSQP--AAAAAAPAPPPNPPATPPEPPARRGRGSAALWFVVVVL 333

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        954 PLDELRGHKALVKLRSRQERDLRELRKK---HQRKAVTLTRRLLDGLAQAQAEgrcrlrPGALggaadveDTKEGEDEAK 1030
Cdd:PRK06975  334 ACAAAVGGYALNRKVDRLDQELVQRQQAndaQTAELRVKTEQAQASVHQLDSQ------FAQL-------DGKLADAQSA 400

                         170       180       190
                  ....*....|....*....|....*....|....*..
4GNK_B       1031 ryQEFQNRQVQSLLELREAQVDAEAQRRLEHLRQALQ 1067
Cdd:PRK06975  401 --QQALEQQYQDLSRNRDDWMIAEVEQMLSSASQQLQ 435

Name

Accession

Description

Interval

E-value

PI-PLCc_beta3

cd08625

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3; This subfamily ...

317-694

8.04e-180

Pssm-ID: 176562 [Multi-domain] Cd Length: 258 Bit Score: 528.86 E-value: 8.04e-180

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       317 STDMTQPLSAYFINSSHNTYLTAGQLAGTSSVEMYRQALLWGCRCVELDVWKGRPPEEEPFITHGFTMTTEVPLRDVLEA 396
Cdd:cd08625    1 SDDMNQPLSHYFINSSHNTYLTAGQLTGLSSVEMYRQVLLTGCRCIELDCWKGRPPEEEPFITHGFTMTTEIPFKDVIEA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       397 IAETAFKTSPYPVILSFENHVDSAKQQAKMAEYCRSIFGDALLIEPLDKYPLAPGVPLPSPQDLMGRILVKNKKrhrpsa 476
Cdd:cd08625   81 IAESAFKTSPYPVILSFENHVDSAKQQAKMAEYCRSIFGDALLIDPLDKYPLVPGVQLPSPQELMGKILVKNKK------ 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       477 ggpdsagrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglekpslepqkslgdeglnrgpyvlgpadr 556
Cdd:cd08625      --------------------------------------------------------------------------------

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       557 edeeedeeeeeqtdpkkpttdegtassevnateeMSTLVNYIEPVKFKSFEAARKRNKCFEMSSFVETKAMEQLTKSPME 636
Cdd:cd08625  155 ----------------------------------MSTLVNYIEPVKFKSFEAAAKRNKFFEMSSFVETKAMEQLTKSPME 200

                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|....*...
4GNK_B       637 FVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDVAMQLNAGVFEYN 694
Cdd:cd08625  201 FVEYNKKQLSRIYPKGTRVDSSNYMPQLFWNVGCQMVALNFQTLDLAMQLNMGVFEYN 258

PI-PLCc_beta

cd08591

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily ...

317-694

3.30e-179

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: 527.29 E-value: 3.30e-179

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       317 STDMTQPLSAYFINSSHNTYLTAGQLAGTSSVEMYRQALLWGCRCVELDVWKGRPPEEEPFITHGFTMTTEVPLRDVLEA 396
Cdd:cd08591    1 YQDMDQPLSHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLSGCRCIELDCWDGKGEDEEPIITHGKTMCTEILFKDVIEA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       397 IAETAFKTSPYPVILSFENHVDSaKQQAKMAEYCRSIFGDALLIEPLDKYPLAPGVPLPSPQDLMGRILVKNKKrhrpsa 476
Cdd:cd08591   81 IAETAFKTSEYPVILSFENHCSS-KQQAKMAEYCREIFGDLLLTEPLEKYPLEPGVPLPSPNDLKRKILIKNKK------ 153

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       477 ggpdsagrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglekpslepqkslgdeglnrgpyvlgpadr 556
Cdd:cd08591      --------------------------------------------------------------------------------

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       557 edeeedeeeeeqtdpkkpttdegtassevnateeMSTLVNYIEPVKFKSFEAARKRNKCFEMSSFVETKAMEQLTKSPME 636
Cdd:cd08591  154 ----------------------------------LSSLVNYIQPVKFQGFEVAEKRNKHYEMSSFNESKGLGYLKKSPIE 199

                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|....*...
4GNK_B       637 FVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDVAMQLNAGVFEYN 694
Cdd:cd08591  200 FVNYNKRQLSRIYPKGTRVDSSNYMPQIFWNAGCQMVALNFQTPDLPMQLNQGKFEYN 257

PI-PLCc_beta2

cd08624

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta2; This subfamily ...

317-694

5.06e-148

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: 446.04 E-value: 5.06e-148

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       317 STDMTQPLSAYFINSSHNTYLTAGQLAGTSSVEMYRQALLWGCRCVELDVWKGRPPEEEPFITHGFTMTTEVPLRDVLEA 396
Cdd:cd08624    1 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSPEMYRQVLLSGCRCVELDCWKGKPPDEEPIITHGFTMTTEILFKDAIEA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       397 IAETAFKTSPYPVILSFENHVDSAKQQAKMAEYCRSIFGDALLIEPLDKYPLAPGVPLPSPQDLMGRILVKNKKrhrpsa 476
Cdd:cd08624   81 IAESAFKTSPYPVILSFENHVDSPKQQAKMAEYCRTIFGDMLLTEPLEKYPLKPGVPLPSPEDLRGKILIKNKK------ 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       477 ggpdsagrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglekpslepqkslgdeglnrgpyvlgpadr 556
Cdd:cd08624      --------------------------------------------------------------------------------

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       557 edeeedeeeeeqtdpkkpttdegtassevnaTEEMSTLVNYIEPVKFKSFEAARKRNKCFEMSSFVETKAMEQLTKSPME 636
Cdd:cd08624  155 -------------------------------YEEMSSLVNYIQPTKFVSFEFSAQKNRSYVISSFTELKAYDLLSKASVQ 203

                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|....*...
4GNK_B       637 FVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDVAMQLNAGVFEYN 694
Cdd:cd08624  204 FVEYNKRQMSRIYPKGTRMDSSNYMPQMFWNVGCQMVALNFQTMDLPMQQNMALFEFN 261

PI-PLCc_beta1

cd08623

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta1; This subfamily ...

317-694

2.88e-138

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: 420.64 E-value: 2.88e-138

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       317 STDMTQPLSAYFINSSHNTYLTAGQLAGTSSVEMYRQALLWGCRCVELDVWKGRPPEEEPFITHGFTMTTEVPLRDVLEA 396
Cdd:cd08623    1 NEDMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGRTAEEEPVITHGFTMTTEISFKEVIEA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       397 IAETAFKTSPYPVILSFENHVDSAKQQAKMAEYCRSIFGDALLIEPLDKYPLAPGVPLPSPQDLMGRILVKNKKrhrpsa 476
Cdd:cd08623   81 IAECAFKTSPFPILLSFENHVDSPKQQAKMAEYCRLIFGDALLMEPLEKYPLESGVPLPSPMDLMYKILVKNKK------ 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       477 ggpdsagrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglekpslepqkslgdeglnrgpyvlgpadr 556
Cdd:cd08623      --------------------------------------------------------------------------------

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       557 edeeedeeeeeqtdpkkpttdegtassevnateeMSTLVNYIEPVKFKSFEAARKRNKCFEMSSFVETKAMEQLTKSPME 636
Cdd:cd08623  155 ----------------------------------MSNLVNYIQPVKFESFEASKKRNKSFEMSSFVETKGLEQLTKSPVE 200

                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|....*...
4GNK_B       637 FVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDVAMQLNAGVFEYN 694
Cdd:cd08623  201 FVEYNKMQLSRIYPKGTRVDSSNYMPQLFWNAGCQMVALNFQTVDLSMQINMGMYEYN 258

PI-PLCc_eukaryota

cd08558

Catalytic domain of eukaryotic phosphoinositide-specific phospholipase C and similar proteins; ...

319-694

1.01e-126

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: 388.35 E-value: 1.01e-126

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       319 DMTQPLSAYFINSSHNTYLTAGQLAGTSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAIA 398
Cdd:cd08558    3 DMTQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDG--PDGEPVVYHGHTLTSKILFKDVIEAIK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       399 ETAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIEPLDKYPlapgVPLPSPQDLMGRILVKNKKRHrpsagg 478
Cdd:cd08558   81 EYAFVTSPYPVILSLENHC-SLEQQKKMAQILKEIFGDKLLTPPLDENP----VQLPSPEQLKGKILIKGKKYH------ 149

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       479 pdsagrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglekpslepqkslgdeglnrgpyvlgpadred 558
Cdd:cd08558      --------------------------------------------------------------------------------

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       559 eeedeeeeeqtdpkkpttdegtassevnateemstlvnyiepvkfksfeaarkrnkcfeMSSFVETKAMEQLTKSPMEFV 638
Cdd:cd08558  150 -----------------------------------------------------------MSSFSETKALKLLKESPEEFV 170

                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|....*.
4GNK_B       639 EYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDVAMQLNAGVFEYN 694
Cdd:cd08558  171 KYNKRQLSRVYPKGTRVDSSNYNPQPFWNAGCQMVALNYQTPDLPMQLNQGKFEQN 226

PI-PLCc_beta4

cd08626

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta4; This subfamily ...

319-694

9.87e-119

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: 368.71 E-value: 9.87e-119

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       319 DMTQPLSAYFINSSHNTYLTAGQLAGTSSVEMYRQALLWGCRCVELDVWKGRPPEEEPFITHGFTMTTEVPLRDVLEAIA 398
Cdd:cd08626    3 DMDQPLAHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLAGCRCIELDCWDGKGEDQEPIITHGKAMCTDILFKDVIQAIK 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       399 ETAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIEPLDKYPLAPGVPLPSPQDLMGRILVKNKKrhrpsagg 478
Cdd:cd08626   83 DTAFVTSDYPVILSFENHC-SKPQQYKLAKYCEEIFGDLLLTKPLESHPLEPGVPLPSPNKLKRKILIKNKR-------- 153

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       479 pdsagrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglekpslepqkslgdeglnrgpyvlgpadred 558
Cdd:cd08626      --------------------------------------------------------------------------------

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       559 eeedeeeeeqtdpkkpttdegtassevnateeMSTLVNYIEPVKFKSFEAARKRNKCFEMSSFVETKAMEQLTKSPMEFV 638
Cdd:cd08626  154 --------------------------------LSSLVNYAQPVKFQGFDVAEERNIHFNMSSFNESVGLGYLKTSAIEFV 201

                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|....*.
4GNK_B       639 EYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDVAMQLNAGVFEYN 694
Cdd:cd08626  202 NYNKRQMSRIYPKGTRVDSSNYMPQIFWNAGCQMVSLNFQTPDLGMQLNQGKFEYN 257

PI-PLCc_delta

cd08593

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta; This subfamily ...

319-694

7.89e-108

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: 339.31 E-value: 7.89e-108

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       319 DMTQPLSAYFINSSHNTYLTAGQLAGTSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAIA 398
Cdd:cd08593    3 DMTQPLSHYFIASSHNTYLLEDQLKGPSSTEAYIRALKKGCRCVELDCWDG--PDGEPIIYHGHTLTSKILFKDVIQAIR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       399 ETAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIEPLDkyplAPGVPLPSPQDLMGRILVKNKKRHrpsagg 478
Cdd:cd08593   81 EYAFKVSPYPVILSLENHC-SVEQQKVMAQHLKSILGDKLLTQPLD----GVLTALPSPEELKGKILVKGKKLK------ 149

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       479 pdsagrkrpleqsnsaLSessaatepsspqlgspssdscpglsngeevglekpslepqkslgdeglnrgpyvlgpadred 558
Cdd:cd08593  150 ----------------LA-------------------------------------------------------------- 151

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       559 eeedeeeeeqtdpkkpttdegtassevnatEEMSTLVNYIEPVKFKSFEAARKRNKCFEMSSFVETKAMEQLTKSPMEFV 638
Cdd:cd08593  152 ------------------------------KELSDLVIYCKSVHFKSFEHSKENYHFYEMSSFSESKALKLAQESGNEFV 201

                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|....*.
4GNK_B       639 EYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDVAMQLNAGVFEYN 694
Cdd:cd08593  202 RHNKRQLSRIYPAGLRTDSSNYDPQEMWNVGCQIVALNFQTPGEEMDLNDGLFRQN 257

EFh_PI-PLCbeta3

cd16210

EF-hand motif found in phosphoinositide phospholipase C beta 3 (PI-PLC-beta3); PI-PLC-beta3, ...

155-305

1.70e-100

Pssm-ID: 320040 Cd Length: 151 Bit Score: 315.32 E-value: 1.70e-100

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       155 RKAYTKLKLQVNQDGRIPVKNILKMFSADKKRVETALESCGLKFNRSESIRPDEFSLEIFERFLNKLCLRPDIDKILLEI 234
Cdd:cd16210    1 RKAYTKLKLQVNQDGRIPVKNILKMFSADKKRVETALESCGLKFNRSESIKPDEFTLEIFERFLNKLCLRPDIDKILLEI 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
4GNK_B       235 GAKGKPYLTLEQLMDFINQKQRDPRLNEVLYPPLRPSQARLLIEKYEPNQQFLERDQMSMEGFSRYLGGEE 305
Cdd:cd16210   81 GAKGKPYLTLEQLMDFINQKQRDPRLNEVLYPPLRPSQVRQLIEKYEPNQQFLERDQMSMEGFSRYLGGEE 151

PI-PLCc_PRIP_metazoa

cd08597

Catalytic domain of metazoan phospholipase C related, but catalytically inactive protein; This ...

319-694

3.84e-87

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: 283.16 E-value: 3.84e-87

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       319 DMTQPLSAYFINSSHNTYLTAGQLAGTSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAIA 398
Cdd:cd08597    3 DMTQPLSHYFIASSHNTYLIEDQLRGPSSVEGYVRALQRGCRCVELDCWDG--PNGEPVIYHGHTLTSKISFRSVIEAIN 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       399 ETAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIEPLDKyplaPGVPLPSPQDLMGRILVKNKKrhrpsagg 478
Cdd:cd08597   81 EYAFVASEYPLILCIENHC-SEKQQLVMAQYLKEIFGDKLYTEPPNE----GESYLPSPHDLKGKIIIKGKK-------- 147

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       479 pdsagrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevgLEKPSLepqkslgdeglnrgpyvlgpadred 558
Cdd:cd08597  148 -------------------------------------------------LKRRKL------------------------- 153

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       559 eeedeeeeeqtdpkkpttdegtassevnaTEEMSTLVNYIEPVKFKSFEAARKRNKCFEMSSFVETKAMEQLTKSPMEFV 638
Cdd:cd08597  154 -----------------------------CKELSDLVSLCKSVRFQDFPTSAQNQKYWEVCSFSENLARRLANEFPEDFV 204

                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|....*.
4GNK_B       639 EYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDVAMQLNAGVFEYN 694
Cdd:cd08597  205 NYNKKFLSRVYPSPMRVDSSNYNPQDFWNCGCQIVAMNYQTPGLMMDLNTGKFLEN 260

PI-PLC1c_yeast

cd08598

Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This ...

317-691

1.55e-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: 263.72 E-value: 1.55e-80

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       317 STDMTQPLSAYFINSSHNTYLTAGQLAGTSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEA 396
Cdd:cd08598    1 EEDLSRPLNEYFISSSHNTYLLGRQLAGDSSVEGYIRALQRGCRCVEIDVWDG--DDGEPVVTHGYTLTSSVPFRDVCRA 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       397 IAETAFKTSPYPVILSFENHVDSAkQQAKMAEYCRSIFGDALLIEPLDkyPLAPGvpLPSPQDLMGRILVKNKKrhrpsa 476
Cdd:cd08598   79 IKKYAFVTSPYPLILSLEVHCDAE-QQERMVEIMKETFGDLLVTEPLD--GLEDE--LPSPEELRGKILIKVKK------ 147

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       477 ggpdsagrkrpleqsnsalsessaatEPSSPqlgspssdscpglsngeevglekpslepqkslgdeglnrgpyvlgpadr 556
Cdd:cd08598  148 --------------------------ESKTP------------------------------------------------- 152

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       557 edeeedeeeeeqtdpkkpttdegtassevnateemstlvnyiepvkfksfeaarkrNKCFemsSFVETKAMEQLTKSPME 636
Cdd:cd08598  153 --------------------------------------------------------NHIF---SLSERSLLKLLKDKRAA 173

                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|....*
4GNK_B       637 FVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDVAMQLNAGVF 691
Cdd:cd08598  174 LDKHNRRHLMRVYPSGTRISSSNFNPLPFWRAGVQMVALNWQTYDLGMQLNEAMF 228

PI-PLCc_gamma

cd08592

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family ...

319-694

3.23e-79

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: 260.05 E-value: 3.23e-79

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       319 DMTQPLSAYFINSSHNTYLTAGQLAGTSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAIA 398
Cdd:cd08592    3 DMNNPLSHYWIASSHNTYLTGDQLSSESSLEAYARCLRMGCRCIELDCWDG--PDGMPIIYHGHTLTSKIKFMDVLKTIK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       399 ETAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIEPLDkyplAPGVPLPSPQDLMGRILVKNKKRHRpsagg 478
Cdd:cd08592   81 EHAFVTSEYPVILSIENHC-SLPQQRNMAQAFKEVFGDMLLTQPVD----RNADQLPSPNQLKRKIIIKHKKLFY----- 150

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       479 pdsagrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglekpslepqkslgdeglnrgpyvlgpadred 558
Cdd:cd08592      --------------------------------------------------------------------------------

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       559 eeedeeeeeqtdpkkpttdegtassevnateemstlvnyiepvkfksfeaarkrnkcfEMSSFVETKAMEQLTKS-PMEF 637
Cdd:cd08592  151 ----------------------------------------------------------EMSSFPETKAEKYLNRQkGKIF 172

                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|....*..
4GNK_B       638 VEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDVAMQLNAGVFEYN 694
Cdd:cd08592  173 LKYNRRQLSRVYPKGQRVDSSNYDPVPMWNCGSQMVALNFQTPDKPMQLNQALFMLN 229

PI-PLCc_zeta

cd08595

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-zeta; This family ...

319-694

7.42e-76

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: 251.78 E-value: 7.42e-76

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       319 DMTQPLSAYFINSSHNTYLTAGQLAGTSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAIA 398
Cdd:cd08595    3 DMDHPLSDYFISSSHNTYLVSDQLVGPSDLDGYVSALRKGCRCLEIDCWDG--ADNEPVVYHGYTLTSKILFKEVITTVE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       399 ETAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIEPLDKYPLApgvPLPSPQDLMGRILVKNKKRhrpsagg 478
Cdd:cd08595   81 KYAFEKSDYPVVLSLENHC-STEQQEIMAHYLVSILGEKLLRAPIDDPATG---ELPSPEALKFKILVKNKKK------- 149

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       479 pdsagrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglekpslepqkslgdeglnrgpYVLGpadred 558
Cdd:cd08595  150 ----------------------------------------------------------------------IAKA------ 153

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       559 eeedeeeeeqtdpkkpttdegtassevnateeMSTLVNYIEPVKFKSFEAARKRNKCFEMSSFVETKAMEQLTKSPMEFV 638
Cdd:cd08595  154 --------------------------------LSDLVIYTKSEKFCSFTHSRDNQHSYENNSIGENKARKLLKSSGADFV 201

                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|....*.
4GNK_B       639 EYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDVAMQLNAGVFEYN 694
Cdd:cd08595  202 GHTQRFITRIYPKGTRASSSNYNPQEFWNVGCQMVALNFQTLGAPMDLQNGKFLDN 257

PI-PLCc_delta4

cd08631

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta4; This subfamily ...

319-694

7.92e-76

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: 251.79 E-value: 7.92e-76

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       319 DMTQPLSAYFINSSHNTYLTAGQLAGTSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAIA 398
Cdd:cd08631    3 DMTQPLCHYFICSSHNTYLMEDQLRGQSSVEGYIRALKRGCRCVEVDVWDG--PNGEPIVYHGHTFTSKILFKDVVAAVA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       399 ETAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIEPLD-KYPlapgVPLPSPQDLMGRILVKNKKrhrpsag 477
Cdd:cd08631   81 QYAFQVSDYPVILSLENHC-GVEQQQTMAQHLTEILGEKLLSTTLDgVLP----TQLPSPEELRGKILLKGKK------- 148

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       478 gpdsagrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglekpslepqkslgdeglnrgpyvlgpadre 557
Cdd:cd08631      --------------------------------------------------------------------------------

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       558 deeedeeeeeqtdpkkpttdegtasseVNATEEMSTLVNYIEPVKFKSFEAARKRNKCFEMSSFVETKAMEQLTKSPMEF 637
Cdd:cd08631  149 ---------------------------IRLSPELSDCVIYCKSVSFRSFTHSREHYHFYEISSFTETKARKLIREAGNEF 201

                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|....*..
4GNK_B       638 VEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDVAMQLNAGVFEYN 694
Cdd:cd08631  202 VQHNTWQLSRVYPSGLRTDSSNYNPQEMWNAGCQMVALNFQTAGLEMDLNDGLFRQN 258

PI-PLCc_delta1

cd08629

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta1; This subfamily ...

319-694

1.20e-75

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: 251.11 E-value: 1.20e-75

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       319 DMTQPLSAYFINSSHNTYLTAGQLAGTSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAIA 398
Cdd:cd08629    3 DMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDG--PNQEPIIYHGYTFTSKILFCDVLRAIR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       399 ETAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIEPLDkyplAPGVPLPSPQDLMGRILVKNKKrhrpsagg 478
Cdd:cd08629   81 DYAFKASPYPVILSLENHC-SLEQQRVMARHLRAILGPILLDQPLD----GVTTSLPSPEQLKGKILLKGKK-------- 147

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       479 pdsagrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglekpslepqkslgdeglnrgpyvlgpadred 558
Cdd:cd08629      --------------------------------------------------------------------------------

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       559 eeedeeeeeqtdpkkpttdegtasseVNATEEMSTLVNYIEPVKFKSFEAARKRNKCF-EMSSFVETKAMEQLTKSPMEF 637
Cdd:cd08629  148 --------------------------LKLVPELSDMIIYCKSVHFGGFSSPGTSGQAFyEMASFSESRALRLLQESGNGF 201

                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|....*..
4GNK_B       638 VEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDVAMQLNAGVFEYN 694
Cdd:cd08629  202 VRHNVSCLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYLGCFQDN 258

PI-PLC-X

pfam00388

Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...

320-468

1.39e-74

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: 243.18 E-value: 1.39e-74

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B         320 MTQPLSAYFINSSHNTYLTAGQLAGTSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAIAE 399
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDG--PDGEPVVYHGYTLTSKIPFRDVLEAIKD 78

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
4GNK_B         400 TAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIEPLDKyplaPGVPLPSPQDLMGRILVKN 468
Cdd:pfam00388   79 YAFVTSPYPVILSLENHC-SPEQQKKMAEILKEIFGDMLYTPPLDD----DLTELPSPEDLKGKILIKG 142

PI-PLCc_delta3

cd08630

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta3; This subfamily ...

319-694

2.23e-73

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: 244.93 E-value: 2.23e-73

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       319 DMTQPLSAYFINSSHNTYLTAGQLAGTSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAIA 398
Cdd:cd08630    3 DMSQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEG--PGGEPVIYHGHTLTSKILFRDVIQAVR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       399 ETAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIEPLDKYPLApgvPLPSPQDLMGRILVKNKKrhrpsagg 478
Cdd:cd08630   81 QHAFTASPYPVILSLENHC-GLEQQAAMARHLQTILGDMLVTQPLDSLNPE---ELPSPEELKGRVLVKGKK-------- 148

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       479 pdsagrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglekpslepqkslgdeglnrgpyvlgpadred 558
Cdd:cd08630      --------------------------------------------------------------------------------

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       559 eeedeeeeEQTDPkkpttdegtassevnateEMSTLVNYIEPVKFKSFEAARKRNKCFEMSSFVETKAMEQLTKSPMEFV 638
Cdd:cd08630  149 --------LQISP------------------ELSALAVYCQATRLRTLEPAPVQPQPCQVSSLSERKAKKLIREAGNSFV 202

                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|....*.
4GNK_B       639 EYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDVAMQLNAGVFEYN 694
Cdd:cd08630  203 RHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLVALNFQTPGYEMDLNAGRFLVN 258

PI-PLCc_epsilon

cd08596

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family ...

319-694

7.30e-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: 7.30e-73

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       319 DMTQPLSAYFINSSHNTYLTAGQLAGTSSVEMYRQALLWGCRCVELDVWKGRppEEEPFITHGFTMTTEVPLRDVLEAIA 398
Cdd:cd08596    3 DLQYPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLTGCRCVELDCWDGD--DGMPIIYHGHTLTTKIPFKDVVEAIN 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       399 ETAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIEPLDKYPLAPGVPLPSPQDLMGRILVKNKKrhrpsagg 478
Cdd:cd08596   81 RSAFITSDYPVILSIENHC-SLQQQRKMAEIFKTVFGEKLVTKFLFESDFSDDPSLPSPLQLKNKILLKNKK-------- 151

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       479 pdsagrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglekpslepqkslgdeglnrgpyvlgpadred 558
Cdd:cd08596      --------------------------------------------------------------------------------

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       559 eeedeeeeeqtdpkkpttdegtassevnaTEEMSTLVNYIEPVKFKSFEAArkrnKCFEMSSFVETKAMEQLTKSPMEFV 638
Cdd:cd08596  152 -----------------------------APELSDLVIYCQAVKFPGLSTP----KCYHISSLNENAAKRLCRRYPQKLV 198

                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|....*.
4GNK_B       639 EYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDVAMQLNAGVFEYN 694
Cdd:cd08596  199 QHTRCQLLRTYPAATRIDSSNPNPLIFWLHGLQLVALNYQTDDLPMHLNAAMFEAN 254

PLC-beta_C

pfam08703

PLC-beta C terminal; This domain corresponds to the alpha helical C terminal domain of ...

1030-1203

7.94e-72

PLC-beta C terminal; This domain corresponds to the alpha helical C terminal domain of phospholipase C beta.

Pssm-ID: 462571 [Multi-domain] Cd Length: 176 Bit Score: 236.89 E-value: 7.94e-72

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1030 KRYQEFQNRQVQSLLELREAQVDAEAQRRLEHLRQALQRLREVVLDANTTQFKRLKEMNEREKKELQKILDRKRHNSISE 1109
Cdd:pfam08703    1 KQVRELKERLEQELLELREEQYEQEKKRKEQHLTEQIQKLKELAREKQAAELKALKESSESEKKEMKKKLERKRLESIQE 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1110 AKMRDKHK-KEAELT-EINRRHITESVNSIRRLEEAQKQRHDRLVAGQQQVLQQLAEEEPKLLAQLAQECQEQRARLPQE 1187
Cdd:pfam08703   81 AKKRTSDKaAQERLKkEINNSHIQEVVQSIKQLEEKQKRRQEKLEEKQAECLQQIKEEEPQLQAELNAEYEEKLKGLPAE 160

                          170
                   ....*....|....*.
4GNK_B        1188 IRRSLLGEMPEGLGDG 1203
Cdd:pfam08703  161 VRESVKSCLKEGFPDE 176

EFh_PI-PLCbeta

cd16200

EF-hand motif found in metazoan phosphoinositide-specific phospholipase C (PI-PLC)-beta ...

155-305

7.46e-71

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: 233.29 E-value: 7.46e-71

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       155 RKAYTKLKLQVNQDGRIPVKNILKMFSADK--KRVETALESCGLKFNRSESIRPDEFSLEIFERFLNKLCLRPDIDKILL 232
Cdd:cd16200    1 KKLYTKLKLSVNITGKIPVKNIIKCFSSDKkrKRVLKALKALGLPDGKNDEIDPEDFTFEKFFKLYNKLCPRPDIDEIFK 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
4GNK_B       233 EIGAKGKPYLTLEQLMDFINQKQRDPRLNEVLYPPLRPSQARLLIEKYEPNQQFLERDQMSMEGFSRYLGGEE 305
Cdd:cd16200   81 ELGGKRKPYLTLEQLVDFLNEEQRDPRLNEILFPFHTKEQAKKLIDKYEPNEKNKKKGQLTLEGFLRYLMSDE 153

EFh_PI-PLCbeta1

cd16208

EF-hand motif found in phosphoinositide phospholipase C beta 1 (PI-PLC-beta1); PI-PLC-beta1, ...

156-305

4.70e-69

EF-hand motif found in phosphoinositide phospholipase C beta 1 (PI-PLC-beta1); PI-PLC-beta1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1, or PLC-154, or phospholipase C-I (PLC-I), or phospholipase C-beta-1 (PLC-beta1), is expressed at highest levels in specific regions of the brain, as well as in the cardiovascular system. It has two splice variants, PI-PLC-beta1a and PI-PLC-beta1b, both of which are present within the nucleus. Nuclear PI-PLC-beta1 is a key molecule for nuclear inositide signaling, where it plays a role in cell cycle progression, proliferation and differentiation. It also contributes to generate cell-specific Ca2+ signals evoked by G protein-coupled receptor stimulation. PI-PLC-beta1 acts as an effector and a GTPase activating protein (GAP) specifically activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. It regulates neuronal activity in the cerebral cortex and hippocampus, and has been implicated for participations in diverse critical functions related to forebrain diseases such as schizophrenia. It may play an important role in maintenance of the status epilepticus, and in osteosarcoma-related signal transduction pathways. PI-PLC-beta1 also functions as a regulator of erythropoiesis in kinamycin F, a potent inducer of gamma-globin production in K562 cells. The G protein activation and the degradation of PI-PLC-beta1 can be regulated by the interaction of alpha-synuclein. As a result, it may reduce cell damage under oxidative stress. Moreover, PI-PLC-beta1 works as a new intermediate in the HIV-1 gp120-triggered phosphatidylcholine-specific phospholipase C (PC-PLC)-driven signal transduction pathway leading to cytoplasmic CCL2 secretion in macrophages. PI-PLC-beta1 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: 320038 Cd Length: 151 Bit Score: 228.22 E-value: 4.70e-69

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       156 KAYTKLKLQVNQDGRIPVKNILKMFSADKKRVETALESCGLKFNRSESIRPDEFSLEIFERFLNKLCLRPDIDKILLEIG 235
Cdd:cd16208    2 KAYTKLKLQVNPEGRIPVKNIYRLFSADRKRVETALEACNLPSSRNDSIPQEDFTPEVYRVFLNNLCPRPEIDHIFSEFG 81

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       236 AKGKPYLTLEQLMDFINQKQRDPRLNEVLYPPLRPSQARLLIEKYEPNQQFLERDQMSMEGFSRYLGGEE 305
Cdd:cd16208   82 AKSKPYLSVDQMTEFINSKQRDPRLNEILYPPLKQEQVQQLIEKYEPNSTLAKKGQISVDGFMRYLSGEE 151

PI-PLCc_eta

cd08594

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family ...

319-694

1.07e-67

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: 227.38 E-value: 1.07e-67

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       319 DMTQPLSAYFINSSHNTYLTAGQLAGTSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAIA 398
Cdd:cd08594    3 DMTQPLSHYFIASSHNTYLTGDQLLSQSRVDMYARVLQAGCRCVEVDCWDG--PDGEPVVHHGYTLTSKILFRDVIETIN 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       399 ETAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLiepLDKYPLAPGVPLPSPQDLMGRILVKNKKrhrpsagg 478
Cdd:cd08594   81 KYAFIKNEYPVILSIENHC-SVQQQKKMAQYLKEILGDKLD---LSSVISGDSKQLPSPQSLKGKILIKGKK-------- 148

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       479 pdsagrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglekpslepqkslgdeglnrgpyvlgpadred 558
Cdd:cd08594      --------------------------------------------------------------------------------

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       559 eeedeeeeeqtdpkkpttdegtassevnateemstlvnyiepvkfksfeaarkrnkcFEMSSFVETKAMEQLTKSPMEFV 638
Cdd:cd08594  149 ---------------------------------------------------------WQVSSFSETRAHQIVQQKAAQFL 171

                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|....*.
4GNK_B       639 EYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDVAMQLNAGVFEYN 694
Cdd:cd08594  172 RFNQRQLSRIYPSAYRIDSSNFNPQPYWNAGCQLVALNYQTEGRMLQLNRAKFRAN 227

PI-PLCc_gamma2

cd08628

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma2; This subfamily ...

319-694

1.04e-66

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: 225.70 E-value: 1.04e-66

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       319 DMTQPLSAYFINSSHNTYLTAGQLAGTSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAIA 398
Cdd:cd08628    3 DMNNPLSHYWISSSHNTYLTGDQLRSESSTEAYIRCLRMGCRCIELDCWDG--PDGKPIIYHGWTRTTKIKFDDVVQAIK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       399 ETAFKTSPYPVILSFENHVDsAKQQAKMAEYCRSIFGDALLIEPLDkyplAPGVPLPSPQDLMGRILVKNKKRhrpsagg 478
Cdd:cd08628   81 DHAFVTSEYPVILSIEEHCS-VEQQRHMAKVFKEVFGDKLLMKPLE----ASADQLPSPTQLKEKIIIKHKKL------- 148

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       479 pdsagrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglekpslepqkslgdeglnrgpyvlgpadred 558
Cdd:cd08628      --------------------------------------------------------------------------------

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       559 eeedeeeeeqtdpkkpttdegtassevnATEEMSTLVNYIEPvkfKSFEAARKRNKCF-EMSSFVETKAMEQLTKSPMEF 637
Cdd:cd08628  149 ----------------------------IAIELSDLVVYCKP---TSKTKDNLENPDFkEIRSFVETKAPSIIRQKPVQL 197

                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|....*..
4GNK_B       638 VEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDVAMQLNAGVFEYN 694
Cdd:cd08628  198 LKYNRKGLTRVYPKGQRVDSSNYDPFRLWLCGSQMVALNFQTADKYMQLNHALFSLN 254

PLCYc

smart00149

Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. ...

592-706

1.23e-65

Pssm-ID: 128454 [Multi-domain] Cd Length: 115 Bit Score: 217.11 E-value: 1.23e-65

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B          592 STLVNYIEPVKFKSFEAARKRNKCFEMSSFVETKAMEQLTKSPMEFVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQ 671
Cdd:smart00149    1 SDLVIYCAPVKFRSFESAESKNPFYEMSSFSETKAKKLLKKSPTDFVRYNQRQLSRVYPKGTRVDSSNYNPQVFWNHGCQ 80

                            90       100       110
                    ....*....|....*....|....*....|....*
4GNK_B          672 LVALNFQTLDVAMQLNAGVFEYNGRSGYLLKPEFM 706
Cdd:smart00149   81 MVALNFQTPDKPMQLNQGMFRANGGCGYVLKPDFL 115

PI-PLCc_eta2

cd08633

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily ...

319-694

1.77e-65

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: 222.22 E-value: 1.77e-65

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       319 DMTQPLSAYFINSSHNTYLTAGQLAGTSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAIA 398
Cdd:cd08633    3 DMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDG--PDGEPIVHHGYTLTSKILFKDVIETIN 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       399 ETAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALliePLDKYPLAPGVPLPSPQDLMGRILVKNKKRHRpsagg 478
Cdd:cd08633   81 KYAFIKNEYPVILSIENHC-SVPQQKKMAQYLTEILGDKL---DLSSVISNDCTRLPSPEILKGKILVKGKKLSR----- 151

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       479 pdsagrkrpleqsnsALSEssaatepsspqlgspssdscpglsngeevglekpslepqkslgdeglnrgpyvlgpadred 558
Cdd:cd08633  152 ---------------ALSD------------------------------------------------------------- 155

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       559 eeedeeeeeqtdpkkpttdegtassevnateemstLVNYIEPVKFKSFEAarKRNKCFEMSSFVETKAMEQLTKSPMEFV 638
Cdd:cd08633  156 -----------------------------------LVKYTKSVRVHDIET--EATSSWQVSSFSETKAHQILQQKPAQYL 198

                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|....*.
4GNK_B       639 EYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDVAMQLNAGVFEYN 694
Cdd:cd08633  199 RFNQRQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKFSAN 254

PI-PLCc

cd00137

Catalytic domain of prokaryotic and eukaryotic phosphoinositide-specific phospholipase C; This ...

319-694

2.33e-65

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: 222.52 E-value: 2.33e-65

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       319 DMTQPLSAYFINSSHNTYLTAGQLA-----GTSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTtEVPLRDV 393
Cdd:cd00137    3 PDTQPLAHYSIPGTHDTYLTAGQFTikqvwGLTQTEMYRQQLLSGCRCVDIRCWDG--KPEEPIIYHGPTFL-DIFLKEV 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       394 LEAIAETAFKTSPYPVILSFENHVDSA-KQQAKMAEYCRSIFGDALLIEPLDkyplaPGVPLPSPQDLMGRILVKNKKrh 472
Cdd:cd00137   80 IEAIAQFLKKNPPETIIMSLKNEVDSMdSFQAKMAEYCRTIFGDMLLTPPLK-----PTVPLPSLEDLRGKILLLNKK-- 152

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       473 rpsaggpdsagrkrpleqsnsalsesSAATEPSspqlgspssdscpGLSNGEEVGLEKPSLEPQKSlgdeglnrgpyvlg 552
Cdd:cd00137  153 --------------------------NGFSGPT-------------GSSNDTGFVSFEFSTQKNRS-------------- 179

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       553 padredeeedeeeeeqtdpkkpttdegtassevnateemstlvnyiepvkfksfeaarkrnkcFEMSSFVETKAME---- 628
Cdd:cd00137  180 ---------------------------------------------------------------YNISSQDEYKAYDdekv 196

                        330       340       350       360       370       380       390
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
4GNK_B       629 QLTKSPMEFVEYNKQQLSRIYPKGTRV---------DSSNYMPQLFWN---VGCQLVALNFQTLDVAMQLNAGVFEYN 694
Cdd:cd00137  197 KLIKATVQFVDYNKNQLSRNYPSGTSGgtawyyyamDSNNYMPQMFWNanpAGCGIVILDFQTMDLPMQQYMAVIEFN 274

PH_PLC_beta

cd13361

Phospholipase C-beta (PLC-beta) pleckstrin homology (PH) domain; PLC-beta (PLCbeta) is ...

23-150

3.73e-62

Pssm-ID: 270167 Cd Length: 127 Bit Score: 207.42 E-value: 3.73e-62

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        23 LRRGSKFIKWDEETSSRNLVTLRVDPNGFFLYWTGPNMEVDTLDISSIRDTRTGRYARLPKDPKIREVlGFGGPDARLEE 102
Cdd:cd13361    1 LLKGSKFDKWDEDSSLETPVTLKVDEYGFFLYWKSEGKETEVLDLSLIRDVRTGKYPKDPKDLKEREV-NVGGSDEDLED 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
4GNK_B       103 KLMTVVSGPDPVNTVFLNFMAVQDDTAKVWSEELFKLAMNILAQNASR 150
Cdd:cd13361   80 RTLTIVSGTDLVNISFINFVAESEEVAKIWTEGLFKLAHNLLANNASP 127

EFh_PI-PLC21

cd16213

EF-hand motif found in phosphoinositide phospholipase PLC21 and similar proteins; The family ...

155-305

1.32e-61

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: 207.15 E-value: 1.32e-61

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       155 RKAYTKLKLQVNQDGRIPVKNILKMFSA---DKKRVETALESCGLKFNRSESIRPDEFSLEIFERFLNKLCLRPDIDKIL 231
Cdd:cd16213    1 EKAYTKLTLQTDKEGKIPVKNIVKMFAQhkdDRKRVEKALEAIGLPSGKNDAIDPKKFTFEDFFNFYRRLTGRQEVEKIF 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
4GNK_B       232 LEIGAKGKPYLTLEQLMDFINQKQRDPRLNEVLYPPLRPSQARLLIEKYEPNQQFLERDQMSMEGFSRYLGGEE 305
Cdd:cd16213   81 DELGAKKKPYLTTEQFVDFLNKTQRDPRLNEILYPYANPKRARDLINQYEPNKSFAKKGHLSVEGFLRYLMSED 154

PI-PLCc_eta1

cd08632

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta1; This subfamily ...

319-694

1.19e-60

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: 208.35 E-value: 1.19e-60

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       319 DMTQPLSAYFINSSHNTYLTAGQLAGTSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAIA 398
Cdd:cd08632    3 DMDQPLCNYFIASSHNTYLTGDQLLSQSKVDMYARVLQAGCRCVEVDCWDG--PDGEPVVHHGYTLTSKITFRDVIETIN 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       399 ETAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDAL-LIEPLDKYPLApgvpLPSPQDLMGRILVKNKKRHRpsag 477
Cdd:cd08632   81 KYAFVKNEFPVILSIENHC-SIQQQKKIAQYLKEIFGDKLdLSSVLTGDPKQ----LPSPQLLKGKILVKGKKLCR---- 151

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       478 gpdsagrkrpleqsnsALSESSAATEpsspqlgSPSSDSCpglsngeevglekpslepqkslgdeglnrgpyvlgpadre 557
Cdd:cd08632  152 ----------------DLSDLVVYTN-------SVAAQDI---------------------------------------- 168

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       558 deeedeeeeeqtdpkkptTDEGTASSEVnateemstlvnyiepvkfksfeaarkrnkcfemsSFVETKAMEQLTKSPMEF 637
Cdd:cd08632  169 ------------------VDDGSTGNVL----------------------------------SFSETRAHQLVQQKAEQF 196

                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|....*..
4GNK_B       638 VEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDVAMQLNAGVFEYN 694
Cdd:cd08632  197 MTYNQKQLTRIYPSAYRIDSSNFNPLPYWNVGCQLVALNYQSEGRMMQLNRAKFMVN 253

PLN02952

phosphoinositide phospholipase C

319-834

1.67e-60

phosphoinositide phospholipase C

Pssm-ID: 178538 [Multi-domain] Cd Length: 599 Bit Score: 219.10 E-value: 1.67e-60

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        319 DMTQPLSAYFINSSHNTYLTAGQLAGTSSVEMYRQALLWGCRCVELDVWKGRpPEEEPFITHGFTMTTEVPLRDVLEAIA 398
Cdd:PLN02952  124 DMTAPLSHYFIYTGHNSYLTGNQLSSDCSEVPIVKALQRGVRVIELDLWPGS-TKDEILVLHGRTLTTPVPLIKCLKSIR 202

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        399 ETAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLiepldkYPLAPG-VPLPSPQDLMGRILVKNKkrhrPSag 477
Cdd:PLN02952  203 DYAFSSSPYPVIITLEDHL-TPDLQAKVAEMATQIFGQMLY------YPESDSlVQFPSPESLKHRIIISTK----PP-- 269

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        478 gpdsagrKRPLEQSNSALSESSAATEPSSPQlGSPSSDscpglsngEEVGLEKPSLEPQ---KSLGDEGLNRGPYVLGPA 554
Cdd:PLN02952  270 -------KEYLESSGPIVIKKKNNVSPSGRN-SSEETE--------EAQTLESMLFEQEadsRSDSDQDDNKSGELQKPA 333

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        555 DRedeeedeeeeeqtdpKKPTTDEGTASSEVNatEEMSTLVNYIEPVkfksfeaarkrnkcfemsSFVETKAMEQLTKSP 634
Cdd:PLN02952  334 YK---------------RLITIHAGKPKGTLK--DAMKVAVDKVRRL------------------SLSEQELEKAATTNG 378

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        635 MEFVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDVAMQLNAGVFEYNGRSGYLLKPEFMRRP---DK 711
Cdd:PLN02952  379 QDVVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIAFNMQGYGKSLWLMHGMFRANGGCGYLKKPDFLMKKgfhDE 458

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        712 SFDPFTEVivdgIVANALRVKVISG----------QFLSDRKVGIYVEVDMFGLPVDTRRKyRTRTSQGNsFNPVWDEEp 781
Cdd:PLN02952  459 VFDPKKKL----PVKKTLKVKVYLGdgwrldfshtHFDSYSPPDFYTKMYIVGVPADNAKK-KTKIIEDN-WYPAWNEE- 531

                         490       500       510       520       530
                  ....*....|....*....|....*....|....*....|....*....|....*..
4GNK_B        782 FDFPKVVlPTLASLRIAAFE----EGGKFVGHRILPVSAIRSGYHYVCLRNEANQPL 834
Cdd:PLN02952  532 FSFPLTV-PELALLRIEVREydmsEKDDFGGQTCLPVSELRPGIRSVPLHDKKGEKL 587

PLCXc

smart00148

Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ...

320-469

2.28e-60

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: 202.90 E-value: 2.28e-60

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B          320 MTQPLSAYFINSSHNTYLTAGQLAGTSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAIAE 399
Cdd:smart00148    1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDG--PDGEPVIYHGHTFTLPIKLSEVLEAIKD 78

                            90       100       110       120       130       140       150
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B          400 TAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIEPLDKYPLapgvPLPSPQDLMGRILVKNK 469
Cdd:smart00148   79 FAFVTSPYPVILSLENHC-SPDQQAKMAQMFKEIFGDMLYTPPLTSSLE----VLPSPEQLRGKILLKVR 143

PI-PLC-Y

pfam00387

Phosphatidylinositol-specific phospholipase C, Y domain; This associates with pfam00388 to ...

591-705

1.72e-59

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

Pssm-ID: 459794 Cd Length: 114 Bit Score: 199.22 E-value: 1.72e-59

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B         591 MSTLVNYIEPVKFKSFEAArKRNKCFEMSSFVETKAMEQLTKSPMEFVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGC 670
Cdd:pfam00387    1 LSDLVVYTQSVKFKSFSTP-ESKTPNHIFSFSESKALKLIKSSSAAFVKHNRRHLMRVYPKGTRVDSSNFNPQPFWNCGV 79

                           90       100       110
                   ....*....|....*....|....*....|....*
4GNK_B         671 QLVALNFQTLDVAMQLNAGVFEYNGRSGYLLKPEF 705
Cdd:pfam00387   80 QMVALNWQTPDEGMQLNEGMFADNGGCGYVLKPEF 114

PI-PLCc_gamma1

cd08627

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily ...

319-694

5.56e-58

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: 199.87 E-value: 5.56e-58

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       319 DMTQPLSAYFINSSHNTYLTAGQLAGTSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAIA 398
Cdd:cd08627    3 EMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDG--PDGMPVIYHGHTLTTKIKFSDVLHTIK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       399 ETAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIEPLDKYplAPGvpLPSPQDLMGRILVKNKKRHRpsagg 478
Cdd:cd08627   81 EHAFVTSEYPIILSIEDHC-SIVQQRNMAQHFKKVFGDMLLTKPVDIN--ADG--LPSPNQLKRKILIKHKKLYR----- 150

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       479 pdsagrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglekpslepqkslgdeglnrgpyvlgpadred 558
Cdd:cd08627      --------------------------------------------------------------------------------

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       559 eeedeeeeeqtdpkkpttdegtassevnateemstlvnyiepvkfksfeaarkrnkcfEMSSFVETKAMEQLTKSP-MEF 637
Cdd:cd08627  151 ----------------------------------------------------------DMSSFPETKAEKYVNRSKgKKF 172

                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|....*..
4GNK_B       638 VEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDVAMQLNAGVFEYN 694
Cdd:cd08627  173 LQYNRRQLSRIYPKGQRLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALFMLG 229

PLN02222

phosphoinositide phospholipase C 2

286-829

3.97e-56

phosphoinositide phospholipase C 2

Pssm-ID: 177868 [Multi-domain] Cd Length: 581 Bit Score: 205.65 E-value: 3.97e-56

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        286 FLERDQMSMEGFSRYLGGEENGilPLEALDLSTDMTQPLSAYFINSSHNTYLTAGQLAGTSSVEMYRQALLWGCRCVELD 365
Cdd:PLN02222   73 LLHRNGLHLDAFFKYLFGDNNP--PLALHEVHHDMDAPISHYFIFTGHNSYLTGNQLSSDCSEVPIIDALKKGVRVIELD 150

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        366 VWKGRpPEEEPFITHGFTMTTEVPLRDVLEAIAETAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIEPLDK 445
Cdd:PLN02222  151 IWPNS-DKDDIDVLHGMTLTTPVGLIKCLKAIRAHAFDVSDYPVVVTLEDHL-TPDLQSKVAEMVTEIFGEILFTPPVGE 228

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        446 YPLApgvpLPSPQDLMGRILVKNKKRHRPSAGGPDSAGRKrpleqsnsalsessaatepsspqlgspssdsCPGLSNGEE 525
Cdd:PLN02222  229 SLKE----FPSPNSLKKRIIISTKPPKEYKEGKDDEVVQK-------------------------------GKDLGDEEV 273

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        526 VGLEKPS-LEPQKSLGDEGLNrgpyvlGPADredeeedeeeeeqtdpkkPTTDEGTASSEVNATEEMSTLVNyIEPVKFK 604
Cdd:PLN02222  274 WGREVPSfIQRNKSVDKNDSN------GDDD------------------DDDDDGEDKSKKNAPPQYKHLIA-IHAGKPK 328

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        605 S-----FEAARKRNKCFEMSSFVETKAMEQLTKSPMEFVEYNkqqLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQT 679
Cdd:PLN02222  329 GgitecLKVDPDKVRRLSLSEEQLEKAAEKYAKQIVRFTQHN---LLRIYPKGTRVTSSNYNPLVGWSHGAQMVAFNMQG 405

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        680 LDVAMQLNAGVFEYNGRSGYLLKPEFMRRPDKS---FDPFTEVIVDgivaNALRVKVISGQ----------FLSDRKVGI 746
Cdd:PLN02222  406 YGRSLWLMQGMFRANGGCGYIKKPDLLLKSGSDsdiFDPKATLPVK----TTLRVTIYMGEgwyfdfrhthFDQYSPPDF 481

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        747 YVEVDMFGLPVDTRRKyRTRTSQGNsFNPVWDeEPFDFPKVVlPTLASLRIAAFE----EGGKFVGHRILPVSAIRSGYH 822
Cdd:PLN02222  482 YTRVGIAGVPGDTVMK-KTKTLEDN-WIPAWD-EVFEFPLTV-PELALLRLEVHEydmsEKDDFGGQTCLPVWELSQGIR 557


                  ....*..
4GNK_B        823 YVCLRNE 829
Cdd:PLN02222  558 AFPLHSR 564

PLN02228

Phosphoinositide phospholipase C

286-832

2.32e-54

Phosphoinositide phospholipase C

Pssm-ID: 177873 [Multi-domain] Cd Length: 567 Bit Score: 200.26 E-value: 2.32e-54

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        286 FLERDQMSMEGFSRYLGGEENGILPLEAlDLSTDMTQPLSAYFINSSHNTYLTAGQLAGTSSVEMYRQALLWGCRCVELD 365
Cdd:PLN02228   75 FHHHGLVHLNAFYRYLFSDTNSPLPMSG-QVHHDMKAPLSHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELD 153

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        366 VWKGrPPEEEPFITHGFTMTTEVPLRDVLEAIAETAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIEPLDK 445
Cdd:PLN02228  154 LWPN-PSGNAAEVRHGRTLTSHEDLQKCLNAIKDNAFQVSDYPVVITLEDHL-PPNLQAQVAKMLTKTFRGMLFRCTSES 231

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        446 YPLapgvpLPSPQDLMGRILVKNKKrhrpsaggpdsagrkrPLEQSNSALSESSaatepSSPQLGSPSSDScpgLSNGEE 525
Cdd:PLN02228  232 TKH-----FPSPEELKNKILISTKP----------------PKEYLESKTVQTT-----RTPTVKETSWKR---VADAEN 282

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        526 VGLEKPSLEPQKSLGDEGLnrgpYVLGPADRedeEEDEEEEEQTDPKKPTtdegtassEVNATEEmstlvnyiepvkfks 605
Cdd:PLN02228  283 KILEEYKDEESEAVGYRDL----IAIHAANC---KDPLKDCLSDDPEKPI--------RVSMDEQ--------------- 332

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        606 feaarkrnkcfemssFVETKAMeqlTKSPmEFVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDVAMQ 685
Cdd:PLN02228  333 ---------------WLETMVR---TRGT-DLVRFTQRNLVRIYPKGTRVDSSNYDPHVGWTHGAQMVAFNMQGHGKQLW 393

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        686 LNAGVFEYNGRSGYLLKPEFMRRPDKSFDPFTEVIVDgivaNALRVKVISGQ----------FLSDRKVGIYVEVDMFGL 755
Cdd:PLN02228  394 IMQGMFRANGGCGYVKKPRILLDEHTLFDPCKRLPIK----TTLKVKIYTGEgwdldfhlthFDQYSPPDFFVKIGIAGV 469

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        756 PVDTrRKYRTRTSQGNSFnPVWDEEPFDFPKVVlPTLASLRIAAFE----EGGKFVGHRILPVSAIRSGYHYVCLRNEAN 831
Cdd:PLN02228  470 PRDT-VSYRTETAVDQWF-PIWGNDEFLFQLRV-PELALLWFKVQDydndTQNDFAGQTCLPLPELKSGVRAVRLHDRAG 546


                  .
4GNK_B        832 Q 832
Cdd:PLN02228  547 K 547

PI-PLCc_plant

cd08599

Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family ...

319-694

2.70e-52

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: 183.34 E-value: 2.70e-52

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       319 DMTQPLSAYFINSSHNTYLTAGQLAGTSSVEMYRQALLWGCRCVELDVWKGRppEEEPFITHGFTMTTEVPLRDVLEAIA 398
Cdd:cd08599    3 DMTAPLSHYFIFSSHNSYLTGNQLSSRSSTAPIIEALLRGCRVIELDLWPGG--RGDICVLHGGTLTKPVKFEDCIKAIK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       399 ETAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIEPldkyPLAPGVPLPSPQDLMGRILVknkkrhrpsagg 478
Cdd:cd08599   81 ENAFTASEYPVIITLENHL-SPELQAKAAQILRETLGDKLFYPD----SEDLPEEFPSPEELKGKILI------------ 143

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       479 pdsagrkrpleqsnsalsessaatepsspqlgspsSDSCPGLSNgeevglekpslepqkslgdeglnrgpyvlgpadred 558
Cdd:cd08599  144 -----------------------------------SDKPPVIRN------------------------------------ 152

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       559 eeedeeeeeqtdpkkpttdegtassevNATEemSTLVNYIEpvkfksfeaarkrnkcfemssfvetkameqlTKSPMEFV 638
Cdd:cd08599  153 ---------------------------SLSE--TQLKKVIE-------------------------------GEHPTDLI 172

                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|....*.
4GNK_B       639 EYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDVAMQLNAGVFEYN 694
Cdd:cd08599  173 EFTQKNLLRVYPAGLRITSSNYDPMLAWMHGAQMVALNMQGYDRPLWLNRGKFRAN 228

EFh_PI-PLCbeta2

cd16209

EF-hand motif found in phosphoinositide phospholipase C beta 2 (PI-PLC-beta2); PI-PLC-beta2, ...

156-305

4.92e-52

EF-hand motif found in phosphoinositide phospholipase C beta 2 (PI-PLC-beta2); PI-PLC-beta2, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2, or phospholipase C-beta-2 (PLC-beta2), is expressed at highest levels in cells of hematopoietic origin. It is activated by the heterotrimeric G protein alpha q subunits (G alpha(q)) through their C2 domain and long C-terminal extension. It is also activated by the beta-gamma subunits of heterotrimeric G proteins. PI-PLC-beta2 has two cellular binding partners, alpha- and gamma-synuclein. The binding of either alpha- and gamma-synuclein inhibits PI-PLC-beta2 activity through preventing the binding of its activator G alpha(q). However, the binding of gamma-synuclein to PI-PLC-beta2 does not affect its binding to G beta(gamma) subunits or small G proteins, but enhances these signals. Meanwhile, gamma-synuclein may protect PI-PLC-beta2 from protease degradation and contribute to its over-expression in breast cancer. In leukocytes, the G beta(gamma)-mediated activation of PI-PLC-beta2 can be promoted by a scaffolding protein WDR26, which is also required for the translocation of PI-PLC-beta2 from the cytosol to the membrane in polarized leukocytes. PI-PLC-beta2 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: 320039 Cd Length: 151 Bit Score: 179.69 E-value: 4.92e-52

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       156 KAYTKLKLQVNQDGRIPVKNILKMFSADKKRVETALESCGLKFNRSESIRPDEFSLEIFERFLNKLCLRPDIDKILLEIG 235
Cdd:cd16209    2 KIYVKLKMQLNSEGKIPVKNFFQMFPADRKRVEAALSACHLPKGKNDAINPEDFPEAVFKTFLMQLCPRPEIDEIFTSYH 81

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       236 AKGKPYLTLEQLMDFINQKQRDPRLNEVLYPPLRPSQARLLIEKYEPNQQFLERDQMSMEGFSRYLGGEE 305
Cdd:cd16209   82 AKAKPYMTKEHLTKFINKKQRDSRLNEELFPPARPDQVQGLIEKYEPSGINAQRGQLSPEGMVWFLCGPE 151

PH_14

pfam17787

PH domain; This entry corresponds to the PH domain found at the N-terminus of phospholipase C ...

18-147

5.35e-48

PH domain; This entry corresponds to the PH domain found at the N-terminus of phospholipase C enzymes.

Pssm-ID: 465506 Cd Length: 131 Bit Score: 167.17 E-value: 5.35e-48

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B          18 TVVETLRRGSKFIKWDEETSSRN-LVTLRVDPNGFFLYWTGPNMEVDTLDISSIRDTRTGRYARLPKDPKIREVLGFGGP 96
Cdd:pfam17787    1 EVPEKLQKGELFIKWDEESTVAEpNVLLKVDPKGFFLYWKSQGKEGEVLEITSIRDTRLGKFAKIPKDPKLREVLSMGGS 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
4GNK_B          97 DARLEEKLMTVVSGPDPVNTVFLNFMAVQDDTAKVWSEELFKLAMNILAQN 147
Cdd:pfam17787   81 DNSLEDKTLTVVSGTDMVNINFHNFVASNSEVAKNWAEGLRALAHNVLAAN 131

PLN02230

phosphoinositide phospholipase C 4

289-828

7.92e-44

phosphoinositide phospholipase C 4

Pssm-ID: 177875 [Multi-domain] Cd Length: 598 Bit Score: 169.50 E-value: 7.92e-44

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        289 RDQMSMEGFSRYLGGEEngILPLEALDLSTDMTQPLSAYFINSSHNTYLTAGQLAGTSSVEMYRQALLWGCRCVELDVW- 367
Cdd:PLN02230   88 RRNLTLDDFNYYLFSTD--LNPPIADQVHQNMDAPLSHYFIFTGHNSYLTGNQLSSNCSELPIADALRRGVRVVELDLWp 165

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        368 KGrppEEEPFITHGFTMTTEVPLRDVLEAIAETAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIEPLDKYP 447
Cdd:PLN02230  166 RG---TDDVCVKHGRTLTKEVKLGKCLDSIKANAFAISKYPVIITLEDHL-TPKLQFKVAKMITQTFGDMLYYHDSEGCQ 241

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        448 lapgvPLPSPQDLMGRILVKNKKrhrpsaggpdsagrkrPLEqsnsaLSESSAATEPSSPQLGSPSSDSCPGLSNGEEVG 527
Cdd:PLN02230  242 -----EFPSPEELKEKILISTKP----------------PKE-----YLEANDAKEKDNGEKGKDSDEDVWGKEPEDLIS 295

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        528 LEKPSLEPQKSLGDeglnrgpyvlgpadredeeedeeeeEQTDPKKPTTDEGTASSEVNATEEMSTLVNYIEPVKFKSFE 607
Cdd:PLN02230  296 TQSDLDKVTSSVND-------------------------LNQDDEERGSCESDTSCQLQAPEYKRLIAIHAGKPKGGLRM 350

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        608 AARKRNKCFEMSSFVETKAMEQLTKSPMEFVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDVAMQLN 687
Cdd:PLN02230  351 ALKVDPNKIRRLSLSEQLLEKAVASYGADVIRFTQKNFLRIYPKGTRFNSSNYKPQIGWMSGAQMIAFNMQGYGRALWLM 430

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        688 AGVFEYNGRSGYLLKPEFMRRPDKSFDPFTEVIvDGIVANALRVKVISG----------QFLSDRKVGIYVEVDMFGLPV 757
Cdd:PLN02230  431 EGMFRANGGCGYVKKPDFLMDAGPNGQDFYPKD-NSCPKKTLKVKVCMGdgwlldfkktHFDSYSPPDFFVRVGIAGAPV 509

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        758 D-----TRRKYRTRTsqgnsfnPVWDEEpFDFPkVVLPTLASLRIAAFE----EGGKFVGHRILPVSAIRSGYHYVCLRN 828
Cdd:PLN02230  510 DevmekTKIEYDTWT-------PIWNKE-FIFP-LAVPELALLRVEVHEhdinEKDDFGGQTCLPVSEIRQGIHAVPLFN 580

EFh_PI-PLCbeta4

cd16211

EF-hand motif found in phosphoinositide phospholipase C beta 4 (PI-PLC-beta4); PI-PLC-beta4, ...

155-305

1.74e-40

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: 146.80 E-value: 1.74e-40

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       155 RKAYTKLKLQVNQDGRIPVKNILKMFSADK--KRVETALESCGLKFNRSESIRPDEFSLEIFERFLNKLCLRPDIDKILL 232
Cdd:cd16211    1 KKHWMRLCFLVNPNGKIPVRSITRTFASGKteKIVFQSLKELGLPSGKNDEIEPEAFTFEKFYELYHKICPRTDIEELFK 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
4GNK_B       233 EIGAKGKPYLTLEQLMDFINQKQRDPRLNEVLYPPLRPSQARLLIEKYEPNQQFLERDQMSMEGFSRYLGGEE 305
Cdd:cd16211   81 KINGDKKDYLTVDQLISFLNEHQRDPRLNEILFPFYDRKRVMQIIETYEVDEEFKKKEQLSSDGFCRYLMSDE 153

C2_PLC_like

cd00275

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...

729-844

8.72e-37

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 134.98 E-value: 8.72e-37

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       729 LRVKVISGQFLSD------RKVGIYVEVDMFGLPVDTRRKYRTRTSQGNSFNPVWDEEpFDFPkVVLPTLASLRIAAFEE 802
Cdd:cd00275    4 LTIKIISGQQLPKpkgdkgSIVDPYVEVEIHGLPADDSAKFKTKVVKNNGFNPVWNET-FEFD-VTVPELAFLRFVVYDE 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
4GNK_B       803 GG---KFVGHRILPVSAIRSGYHYVCLRNEANQPLCLPALLIYTE 844
Cdd:cd00275   82 DSgddDFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHID 126

EFh_NorpA_like

cd16212

EF-hand motif found in Drosophila melanogaster No receptor potential A protein (NorpA) and ...

155-305

1.04e-33

EF-hand motif found in Drosophila melanogaster No receptor potential A protein (NorpA) and similar proteins; NorpA, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase, is an eye-specific phosphoinositide phospholipase C (PI-PLC) encoded by norpA gene in Drosophila. It is expressed predominantly in photoreceptors and plays an essential role in the phototransduction pathway of Drosophila. A mutation within the norpA gene can render the fly blind without affecting any of the obvious structures of the eye. Like beta-class of vertebrate PI-PLCs, NorpA 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: 320042 [Multi-domain] Cd Length: 153 Bit Score: 127.28 E-value: 1.04e-33

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       155 RKAYTKLKLQVNQDGRIPVKNILKMFSADK--KRVETALESCGLKFNRSESIRPDEFSLEIFERFLNKLCLRPDIDKILL 232
Cdd:cd16212    1 KKHWMRLGFMVDSGGKIPVKHIARTFASGKteKLVYQCLAEMGLPSGKGDSIEKEDFTFEKFYALYHKICPRNDIEELFT 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
4GNK_B       233 EIGAKGKPYLTLEQLMDFINQKQRDPRLNEVLYPPLRPSQARLLIEKYEPNQQFLERDQMSMEGFSRYLGGEE 305
Cdd:cd16212   81 SITKGKGEHISLAQLINFMNDKQRDPRLNEILYPLYDEKRCTEIIKAYEQNEENIKNKRMSKDGFIRYLMSDE 153

PLN02223

phosphoinositide phospholipase C

319-829

1.37e-24

phosphoinositide phospholipase C

Pssm-ID: 165867 [Multi-domain] Cd Length: 537 Bit Score: 109.73 E-value: 1.37e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        319 DMTQPLSAYFINSSHNTYLTAGQLAGTS-SVEMYRQALLWGCRCVELDVWkgrpPEEEPFITHGFTMTTEVPLR--DVLE 395
Cdd:PLN02223  107 DMHAPLSHYFIHTSLKSYFTGNNVFGKLySIEPIIDALEQGVRVVELDLL----PDGKDGICVRPKWNFEKPLElqECLD 182

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        396 AIAETAF-KTSPYPVILSFEnhvDSAKQ--QAKMAEYCRSIFGDALLIEPldkyPLAPGVPLPSPQDLMGRILVKNKkrh 472
Cdd:PLN02223  183 AIKEHAFtKCRSYPLIITFK---DGLKPdlQSKATQMIDQTFGDMVYHED----PQHSLEEFPSPAELQNKILISRR--- 252

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        473 rpsaggpdsagrkrpleqsnsalsessaatePSSPQLGSPSSDSCPGLSNGEEVglekpslepqkslgdeglNRGPyvlg 552
Cdd:PLN02223  253 -------------------------------PPKELLYAKADDGGVGVRNELEI------------------QEGP---- 279

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        553 padredeeedeeeeeqTDPkkpttdegtassevnateemstlvNYIEPVKFKSFEAARKRNKCFEMSSfvetKAMEQLTK 632
Cdd:PLN02223  280 ----------------ADK------------------------NYQSLVGFHAVEPRGMLQKALTGKA----DDIQQPGW 315

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        633 SPMEFVEYNKQQLSRIYPKGTRVDS-SNYMPQLFWNVGCQLVALNFQTLDVAMQLNAGVFEYNGRSGYLLKPEFMRR--P 709
Cdd:PLN02223  316 YERDIISFTQKKFLRTRPKKKNLLInAPYKPQRAWMHGAQLIALSRKDDKEKLWLMQGMFRANGGCGYVKKPDFLLNagP 395

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        710 DKSFDPftevIVDGIVANALRVKVISGQ-FLSD--RKVG------IYVEVDMFGLPVDtrRKYRTRTSQGNSFNPVWDEE 780
Cdd:PLN02223  396 SGVFYP----TENPVVVKILKVKIYMGDgWIVDfkKRIGrlskpdLYVRISIAGVPHD--EKIMKTTVKNNEWKPTWGEE 469

                         490       500       510       520       530
                  ....*....|....*....|....*....|....*....|....*....|...
4GNK_B        781 pFDFPkVVLPTLA--SLRIAAFE--EGGKFVGHRILPVSAIRSGYHYVCLRNE 829
Cdd:PLN02223  470 -FTFP-LTYPDLAliSFEVYDYEvsTADAFCGQTCLPVSELIEGIRAVPLYDE 520

EFh_PI-PLC

cd15898

EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...

155-305

3.23e-21

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: 90.80 E-value: 3.23e-21

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       155 RKAYTKLKLQVNQDGRIPVKNILKMFSADKKRV---ETALESCGLKFNRSESIRPDEFsleifERFLNKLCLRPDIDKIL 231
Cdd:cd15898    1 WLRRQWIKADKDGDGKLSLKEIKKLLKRLNIRVsekELKKLFKEVDTNGDGTLTFDEF-----EELYKSLTERPELEPIF 75

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
4GNK_B       232 LEIGAKGKPYLTLEQLMDFINQKQrdprlnevlYPPLRPSQARLLIEKYEPNqqfLERDQMSMEGFSRYLGGEE 305
Cdd:cd15898   76 KKYAGTNRDYMTLEEFIRFLREEQ---------GENVSEEECEELIEKYEPE---RENRQLSFEGFTNFLLSPE 137

PI-PLCc_GDPD_SF

cd08555

Catalytic domain of phosphoinositide-specific phospholipase C-like phosphodiesterases ...

330-439

1.89e-19

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: 87.11 E-value: 1.89e-19

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       330 NSSHNTYLTAGQlagTSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVP------LRDVLEAIAETAFk 403
Cdd:cd08555    1 VLSHRGYSQNGQ---ENTLEAFYRALDAGARGLELDVRLT--KDGELVVYHGPTLDRTTAgilpptLEEVLELIADYLK- 74

                         90       100       110
                 ....*....|....*....|....*....|....*....
4GNK_B       404 TSPYPVILSFENHVDSA---KQQAKMAEYCRSIFGDALL 439
Cdd:cd08555   75 NPDYTIILSLEIKQDSPeydEFLAKVLKELRVYFDYDLR 113

EFh_PI-PLCdelta

cd16202

EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta ...

165-301

1.40e-13

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: 69.18 E-value: 1.40e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       165 VNQDGRI---PVKNILKM--FSADKKRVETAlescglkFNRSESIRPDEFSLEIFERFLNKLCLRPDIDKILLEIgAKGK 239
Cdd:cd16202   11 KNGDGKLsfkECKKLLKKlnVKVDKDYAKKL-------FQEADTSGEDVLDEEEFVQFYNRLTKRPEIEELFKKY-SGDD 82

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
4GNK_B       240 PYLTLEQLMDFINQKQRDPRLNevlypplrPSQARLLIEKYEPNQQFLERDQMSMEGFSRYL 301
Cdd:cd16202   83 EALTVEELRRFLQEEQKVKDVT--------LEWAEQLIETYEPSEDLKAQGLMSLDGFTLFL 136

smart00239

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...

729-826

2.05e-13

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 67.51 E-value: 2.05e-13

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B          729 LRVKVISGQFLSDRKVG----IYVEVDMFGlpvDTRRKYRTRTSQgNSFNPVWDEEpFDFPkVVLPTLASLRIAAFEEGG 804
Cdd:smart00239    2 LTVKIISARNLPPKDKGgksdPYVKVSLDG---DPKEKKKTKVVK-NTLNPVWNET-FEFE-VPPPELAELEIEVYDKDR 75

                            90       100
                    ....*....|....*....|....*.
4GNK_B          805 ----KFVGHRILPVSAIRSGYHYVCL 826
Cdd:smart00239   76 fgrdDFIGQVTIPLSDLLLGGRHEKL 101

PH_PLC_ELMO1

cd01248

Phospholipase C and Engulfment and cell motility protein 1 pleckstrin homology domain; The ...

23-139

1.79e-11

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: 61.95 E-value: 1.79e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        23 LRRGSKFIKWDEEtSSRNLVTLRVDPNGFFLYWTGP--NMEVDTLDISSIRDTRTGRYARLPKDpkirevlgFGGPDARL 100
Cdd:cd01248    1 LQQGTLLLKYREG-SKPKERTFYLDPDGTRITWESSkkKSEKKSIDISDIKEIRPGKDTDGFKR--------KKKSNKPK 71

                         90       100       110
                 ....*....|....*....|....*....|....*....
4GNK_B       101 EEKLMTVVSGPdpvNTVFLNFMAVQDDTAKVWSEELFKL 139
Cdd:cd01248   72 EERCFSIIYGS---NNKTLDLVAPSEDEANLWVEGLRAL 107

EF-hand_like

pfam09279

Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are ...

217-309

7.70e-09

Pssm-ID: 401279 [Multi-domain] Cd Length: 85 Bit Score: 53.79 E-value: 7.70e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B         217 FLNKLCLRPDIDKILLEIGAKGKpYLTLEQLMDFINQKQRDPRLNevlypplrPSQARLLIEKYEPNQQFLERDQMSMEG 296
Cdd:pfam09279    1 FYKMLTQREEIDEIFQEYSGDGQ-KLSLDELVDFLREEQREEDAS--------PALALSLIERYEPSETAKKQHAMTKDG 71

                           90
                   ....*....|...
4GNK_B         297 FSRYLGGEENGIL 309
Cdd:pfam09279   72 FLMYLCSPDGSIF 84

EFh_PI-PLCdelta4

cd16219

EF-hand motif found in phosphoinositide phospholipase C delta 4 (PI-PLC-delta4); PI-PLC-delta4, ...

166-305

9.92e-09

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: 55.24 E-value: 9.92e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       166 NQDGRI---PVKNILKMFSADKKRvETALEScglkFNRSESIRPDEFSLEIFERFLNKLCLRPDIDKILLEIGAKGKPyL 242
Cdd:cd16219   12 NKDGRMnfkEVRDLLKMMNVDMNE-EHALRL----FQMADKSESGTLEGEEFVLFYKALTQREDVLKIFQDFSADGQK-L 85

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
4GNK_B       243 TLEQLMDFINQKQRDPRLNEVLypplrpsqARLLIEKYEPNQQFLERDQMSMEGFSRYLGGEE 305
Cdd:cd16219   86 TLLEFVDFLQQEQLERENTEEL--------AMELIDRYEPSDTAKKLHALSIDGFLMYLCSPE 140

COG4913

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

956-1185

5.85e-08

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

Pssm-ID: 443941 [Multi-domain] Cd Length: 1089 Bit Score: 57.23 E-value: 5.85e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       956 DELRG-HKALVKLRsRQERDLRELRKKHQRkavtlTRRLLDGLAQAQAEGRcRLRPgalggaadvedtkegEDEAKRYQE 1034
Cdd:COG4913  235 DDLERaHEALEDAR-EQIELLEPIRELAER-----YAAARERLAELEYLRA-ALRL---------------WFAQRRLEL 292

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B      1035 FQNRQVQSLLELREAQVD-AEAQRRLEHLRQALQRLREVVLDANTTQFKRLkemnEREKKELQKILDRKRHNS------I 1107
Cdd:COG4913  293 LEAELEELRAELARLEAElERLEARLDALREELDELEAQIRGNGGDRLEQL----EREIERLERELEERERRRarlealL 368

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B      1108 SEAKMRDKHkKEAELTEiNRRHITESVNSIRRLEEAQKQRHDRLVAGQQQVLQQLAEEE-------------P----KLL 1170
Cdd:COG4913  369 AALGLPLPA-SAEEFAA-LRAEAAALLEALEEELEALEEALAEAEAALRDLRRELRELEaeiaslerrksniParllALR 446

                        250
                 ....*....|....*
4GNK_B      1171 AQLAQECQEQRARLP 1185
Cdd:COG4913  447 DALAEALGLDEAELP 461

pfam00168

C2 domain;

729-823

7.15e-08

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 51.55 E-value: 7.15e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B         729 LRVKVISGQFLSDRKVGI----YVEVDMfglpVDTRRKYRTRTSQgNSFNPVWDEEpFDFPkVVLPTLASLRIAAFEEGG 804
Cdd:pfam00168    3 LTVTVIEAKNLPPKDGNGtsdpYVKVYL----LDGKQKKKTKVVK-NTLNPVWNET-FTFS-VPDPENAVLEIEVYDYDR 75

                           90       100
                   ....*....|....*....|...
4GNK_B         805 ----KFVGHRILPVSAIRSGYHY 823
Cdd:pfam00168   76 fgrdDFIGEVRIPLSELDSGEGL 98

EFh_ScPlc1p_like

cd16207

EF-hand motif found in Saccharomyces cerevisiae phospholipase C-1 (ScPlc1p) and similar ...

198-301

5.24e-07

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: 50.33 E-value: 5.24e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       198 FNRSESIRPDEFSLEIFERFLNKLCLRPDIDKILLEIGAKGKPYLTLEQLMDFINQKQRDprlnevlypPLRPSQARLLI 277
Cdd:cd16207   44 FDKADTDKKGYLNFEEFQEFVKLLKRRKDIKAIFKQLTKPGSDGLTLEEFLKFLRDVQKE---------DVDRETWEKIF 114

                         90       100
                 ....*....|....*....|....
4GNK_B       278 EKYEPNQQFLERDQMSMEGFSRYL 301
Cdd:cd16207  115 EKFARRIDDSDSLTMTLEGFTSFL 138

EFh_PI-PLCdelta1

cd16217

EF-hand motif found in phosphoinositide phospholipase C delta 1 (PI-PLC-delta1); PI-PLC-delta1, ...

212-305

8.19e-07

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: 49.74 E-value: 8.19e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       212 EIfERFLNKLCLRPDIDKILLEIgAKGKPYLTLEQLMDFINQKQRDPrlnevlyppLRPSQARLLIEKYEPNQQFLERDQ 291
Cdd:cd16217   57 EI-EEFYKLLTKREEIDVIFGEY-AKSDGTMSRNNLLNFLQEEQREE---------VAPAYALSLIEKYEPDETAKAQRQ 125

                         90
                 ....*....|....
4GNK_B       292 MSMEGFSRYLGGEE 305
Cdd:cd16217  126 MTKDGFLMYLLSPE 139

SMC_prok_A

TIGR02169

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of ...

1020-1188

1.07e-06

Pssm-ID: 274009 [Multi-domain] Cd Length: 1164 Bit Score: 53.15 E-value: 1.07e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1020 EDTKEGEDEAKRYQEFQNRQVQSLLELREAQVDA-----EAQRRLEHLRQALQRLREVV--LDANTTQFKRLKEMNEREK 1092
Cdd:TIGR02169  681 ERLEGLKRELSSLQSELRRIENRLDELSQELSDAsrkigEIEKEIEQLEQEEEKLKERLeeLEEDLSSLEQEIENVKSEL 760

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1093 KELQKILDRKRhnsiseakmRDKHKKEAELTEINRRHITESVNSIRRLEEAQKQRHDRLVA---------GQQQVLQQLA 1163
Cdd:TIGR02169  761 KELEARIEELE---------EDLHKLEEALNDLEARLSHSRIPEIQAELSKLEEEVSRIEArlreieqklNRLTLEKEYL 831

                          170       180
                   ....*....|....*....|....*
4GNK_B        1164 EEEPKLLAQLAQECQEQRARLPQEI 1188
Cdd:TIGR02169  832 EKEIQELQEQRIDLKEQIKSIEKEI 856

TPH

pfam13868

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of ...

961-1183

1.13e-06

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of eukaryotic proteins. Trichoplein or mitostatin, was first defined as a meiosis-specific nuclear structural protein. It has since been linked with mitochondrial movement. It is associated with the mitochondrial outer membrane, and over-expression leads to reduction in mitochondrial motility whereas lack of it enhances mitochondrial movement. The activity appears to be mediated through binding the mitochondria to the actin intermediate filaments (IFs). The family is in the trichohyalin-plectin-homology domain.

Pssm-ID: 464007 [Multi-domain] Cd Length: 341 Bit Score: 52.23 E-value: 1.13e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B         961 HKALVKLRSRQERDLRELRKKHQRKAVTLTRRLLDGLAQAQAEGRCRLRpgalggaADVEDTKEGEDEAKRYQEFQNRQV 1040
Cdd:pfam13868   31 KKRIKAEEKEEERRLDEMMEEERERALEEEEEKEEERKEERKRYRQELE-------EQIEEREQKRQEEYEEKLQEREQM 103

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1041 QSLLElreaQVDAEAQRRLEHLRQALQRLREVVLDANTTQFKRLKEMNEREKKELQKILdrkrhnsiseAKMRDKHKKEA 1120
Cdd:pfam13868  104 DEIVE----RIQEEDQAEAEEKLEKQRQLREEIDEFNEEQAEWKELEKEEEREEDERIL----------EYLKEKAEREE 169

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
4GNK_B        1121 ELTEinrrhitesvnSIRRLEEAQKQRHDRLVAGQQQVLQQLAEEEpKLLAQLAQECQEQRAR 1183
Cdd:pfam13868  170 EREA-----------EREEIEEEKEREIARLRAQQEKAQDEKAERD-ELRAKLYQEEQERKER 220

Smc

COG1196

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning]; ...

947-1190

2.04e-06

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 52.25 E-value: 2.04e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       947 LSEVAPTPLDELRGHKALVKLRSRQERDLRELRKKHQRkavtLTRRLLDGLAQAQAEGRcRLRPGALGGAADVEDTKEGE 1026
Cdd:COG1196  536 YEAALEAALAAALQNIVVEDDEVAAAAIEYLKAAKAGR----ATFLPLDKIRARAALAA-ALARGAIGAAVDLVASDLRE 610

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B      1027 DEAKRYQEFQNRQVQSLLELREAQVDAEAQRRLEHLRQALQRLREVVLD-ANTTQFKRLKEMNEREKKELQKILDRKrhn 1105
Cdd:COG1196  611 ADARYYVLGDTLLGRTLVAARLEAALRRAVTLAGRLREVTLEGEGGSAGgSLTGGSRRELLAALLEAEAELEELAER--- 687

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B      1106 sisEAKMRDKHKKEAELTEINRRHITESVNSIRRLEEAQKQRHDRLVAGQQQVLQQLAEEEPKLLAQLA---------QE 1176
Cdd:COG1196  688 ---LAEEELELEEALLAEEEEERELAEAEEERLEEELEEEALEEQLEAEREELLEELLEEEELLEEEALeelpeppdlEE 764

                        250
                 ....*....|....
4GNK_B      1177 CQEQRARLPQEIRR 1190
Cdd:COG1196  765 LERELERLEREIEA 778

cd00030

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...

729-797

4.68e-06

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: 46.29 E-value: 4.68e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
4GNK_B       729 LRVKVISGQFLSDRKVGI----YVEVDmfglpVDTRRKYRTRTSQgNSFNPVWDEEpFDFPkVVLPTLASLRI 797
Cdd:cd00030    1 LRVTVIEARNLPAKDLNGksdpYVKVS-----LGGKQKFKTKVVK-NTLNPVWNET-FEFP-VLDPESDTLTV 65

EFh_PI-PLCzeta

cd16204

EF-hand motif found in phosphoinositide phospholipase C zeta 1 (PI-PLC-zeta1); PI-PLC-zeta1, ...

198-305

4.94e-06

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: 47.50 E-value: 4.94e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       198 FNRSESIRPDEFSLEIFERFLNKLCLRPDIDKILlEIGAKGKPYLTLEQLMDFINQKQRDPRLNEvlypplrpSQARLLI 277
Cdd:cd16204   44 FKKNDSFKAGNITIEDFRAIYRAIAHRCEIHEIF-NTYSENRKILSAPNLVGFLKKEQFQDEADE--------TIASELI 114

                         90       100
                 ....*....|....*....|....*...
4GNK_B       278 EKYEPNQQFLERDQMSMEGFSRYLGGEE 305
Cdd:cd16204  115 AKYEPIEEVRKRKQMSFEGFIRYMTSED 142

ARGLU

pfam15346

Arginine and glutamate-rich 1; ARGLU, arginine and glutamate-rich 1 protein family, is ...

1026-1169

6.14e-06

Arginine and glutamate-rich 1; ARGLU, arginine and glutamate-rich 1 protein family, is required for the oestrogen-dependent expression of ESR1 target genes. It functions in cooperation with MED1. The family of proteins is found in eukaryotes.

Pssm-ID: 405931 [Multi-domain] Cd Length: 151 Bit Score: 47.35 E-value: 6.14e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1026 EDEAKRYQEFQNRQVQSLLELREAQVDAEAQRRLEHLRQALQRLREVVLDANTTQF---KRLKEMNER-EKKELQKILdR 1101
Cdd:pfam15346   10 EETARRVEEAVAKRVEEELEKRKDEIEAEVERRVEEARKIMEKQVLEELEREREAEleeERRKEEEERkKREELERIL-E 88

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
4GNK_B        1102 KRHNSISEAKMRDKHKKEAELTEINRRHitesvNSIRRLEEAQKQRHDRlvagQQQVLQQLAEEEPKL 1169
Cdd:pfam15346   89 ENNRKIEEAQRKEAEERLAMLEEQRRMK-----EERQRREKEEEEREKR----EQQKILNKKNSRPKL 147

Smc

COG1196

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning]; ...

955-1190

6.24e-06

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 50.71 E-value: 6.24e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       955 LDELRGHkaLVKLR--SRQERDLRELRKKHQRKAVTLTRRLLDGLAQAQAEGRCRLRpgALGGAADVEDTKEGEDEAKRy 1032
Cdd:COG1196  195 LGELERQ--LEPLErqAEKAERYRELKEELKELEAELLLLKLRELEAELEELEAELE--ELEAELEELEAELAELEAEL- 269

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B      1033 QEFQNRQVQSLLELREAQVD-AEAQRRLEHLRQALQRLREVvLDANTTQFKRLKEMNEREKKELQKILDRKrhnsISEAK 1111
Cdd:COG1196  270 EELRLELEELELELEEAQAEeYELLAELARLEQDIARLEER-RRELEERLEELEEELAELEEELEELEEEL----EELEE 344

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B      1112 MRDKHKKEAELTEINRRHITESVNSIRRLEEAQKQRHDRLVAGQQQVLQQLAEEEPKL--LAQLAQECQEQRARLPQEIR 1189
Cdd:COG1196  345 ELEEAEEELEEAEAELAEAEEALLEAEAELAEAEEELEELAEELLEALRAAAELAAQLeeLEEAEEALLERLERLEEELE 424


                 .
4GNK_B      1190 R 1190
Cdd:COG1196  425 E 425

EFh_PRIP2

cd16223

EF-hand motif found in phospholipase C-related but catalytically inactive protein 2 (PRIP-2); ...

162-301

6.47e-06

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: 47.21 E-value: 6.47e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       162 KLQVNQDGRIPVKNILKMFSADKKRVETAleSCGLKF---NRSESIRPDEFSLEIFERFLNKLCLRPDIDKILLEIGAKg 238
Cdd:cd16223    8 EADTDNVGHITLCRAVQFIKNLNPGLKTS--KIELKFkelHKSKEKGGTEVTKEEFIEVFHELCTRPEIYFLLVQFSSN- 84

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
4GNK_B       239 KPYLTLEQLMDFINQKQRDPRLNEvlypplrpsQARL-LIEKYEPNQQFLERDQMSMEGFSRYL 301
Cdd:cd16223   85 KEFLDTKDLMMFLEAEQGMAHVTE---------EISLdIIHKYEPSKEGQEKGWLSLDGFTNYL 139

YhaN

COG4717

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

967-1181

8.28e-06

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

Pssm-ID: 443752 [Multi-domain] Cd Length: 641 Bit Score: 50.15 E-value: 8.28e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       967 LRSRQERDLRELRKKHQRKavtlTRRLLDGLAQAQAEgrcrlrpgalggaadvedTKEGEDEAKRYQEFQNRQVQSLLEL 1046
Cdd:COG4717   47 LLERLEKEADELFKPQGRK----PELNLKELKELEEE------------------LKEAEEKEEEYAELQEELEELEEEL 104

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B      1047 REAQVD-AEAQRRLEHLRQALQRLR--------EVVLDANTTQFKRLKEmNEREKKELQKILDRKRhNSISEAKmRDKHK 1117
Cdd:COG4717  105 EELEAElEELREELEKLEKLLQLLPlyqelealEAELAELPERLEELEE-RLEELRELEEELEELE-AELAELQ-EELEE 181

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
4GNK_B      1118 KEAELTEINRRHITESVNSIRRLEEAQKQRHDRLVAGQQQvLQQLAEEEPKLLAQLAQECQEQR 1181
Cdd:COG4717  182 LLEQLSLATEEELQDLAEELEELQQRLAELEEELEEAQEE-LEELEEELEQLENELEAAALEER 244

EFh_PRIP

cd16206

EF-hand motif found in phospholipase C-related but catalytically inactive proteins (PRIP); ...

210-305

9.88e-06

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: 46.43 E-value: 9.88e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       210 SLEIFERFLNKLCLRPDIDKILLEIgAKGKPYLTLEQLMDFINQKQRDPRLNEvlypplrpSQARLLIEKYEPNQQFLER 289
Cdd:cd16206   57 SSDEFVELFKELATRPEIYFLLVRY-ASNKDYLTVDDLMLFLEAEQGMTGVTK--------EKCLEIINKYEPSEEGREK 127

                         90
                 ....*....|....*.
4GNK_B       290 DQMSMEGFSRYLGGEE 305
Cdd:cd16206  128 GQLGIDGFTRYLLSEE 143

EFh_PI-PLCdelta3

cd16218

EF-hand motif found in phosphoinositide phospholipase C delta 3 (PI-PLC-delta3); PI-PLC-delta3, ...

166-301

1.32e-05

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: 46.28 E-value: 1.32e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       166 NQDGRIP---VKNILKMFSADKKRVETAL--ESCglkfNRSESIRPDEfsLEIfERFLNKLCLRPDIDKILLEIGAKGKp 240
Cdd:cd16218   12 NKDGKMSfeeIKDLLQMINIDLNEQYAYQlfKEC----DRSNDDRLEE--HEI-EEFCRRLMQRPELEEIFHQYSGEDC- 83

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
4GNK_B       241 YLTLEQLMDFINQKQRDPRLnevlypplrpSQARLLIEKYEPNQQFLERDQMSMEGFSRYL 301
Cdd:cd16218   84 VLSAEELREFLKDQGEDASL----------VHAKELIQTYELNEKAKQHQLMTLDGFTMYM 134

PTZ00121

MAEBL; Provisional

956-1190

1.97e-05

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 49.37 E-value: 1.97e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        956 DELRGHKALVKLRSRQERDLRELRKKHQRKAVTLTRRLLDGLAQAQAEGRCRlrpgalgGAADVEDTKEGeDEAKRYQEF 1035
Cdd:PTZ00121 1486 DEAKKKAEEAKKKADEAKKAAEAKKKADEAKKAEEAKKADEAKKAEEAKKAD-------EAKKAEEKKKA-DELKKAEEL 1557

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       1036 QN-RQVQSLLELREAQVDAE-AQRRLEHLRQALQRLREVVLDANTTQFKRLKEMNEREKKELQKILDRKRHNSISEAKMR 1113
Cdd:PTZ00121 1558 KKaEEKKKAEEAKKAEEDKNmALRKAEEAKKAEEARIEEVMKLYEEEKKMKAEEAKKAEEAKIKAEELKKAEEEKKKVEQ 1637

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
4GNK_B       1114 DKHKKEAELTEINRRHITESVNSIRRLEEAQKQRHDRLVAGQqqvLQQLAEEEPKLLAQLAQECQEqrARLPQEIRR 1190
Cdd:PTZ00121 1638 LKKKEAEEKKKAEELKKAEEENKIKAAEEAKKAEEDKKKAEE---AKKAEEDEKKAAEALKKEAEE--AKKAEELKK 1709

DUF5401

pfam17380

Family of unknown function (DUF5401); This is a family of unknown function found in ...

1016-1191

2.18e-05

Family of unknown function (DUF5401); This is a family of unknown function found in Chromadorea.

Pssm-ID: 375164 [Multi-domain] Cd Length: 722 Bit Score: 48.97 E-value: 2.18e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1016 AADVEDTKEGEDEAKRYQEFQNRQVQSLLELREAQV-DAEAQRRLEHLRQALQRLREVVLDANTTQFKRLKEMNER---- 1090
Cdd:pfam17380  371 AMEISRMRELERLQMERQQKNERVRQELEAARKVKIlEEERQRKIQQQKVEMEQIRAEQEEARQREVRRLEEERARemer 450

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1091 ---EKKELQKILDRKRHNSISEAKMR---DKHKKEAELTEINRRHITESVNSIRRLEEAQKQRHDRLVAGQQQVLQQ-LA 1163
Cdd:pfam17380  451 vrlEEQERQQQVERLRQQEEERKRKKlelEKEKRDRKRAEEQRRKILEKELEERKQAMIEEERKRKLLEKEMEERQKaIY 530

                          170       180       190
                   ....*....|....*....|....*....|.
4GNK_B        1164 EEEPKLLAQLAQECQ---EQRARLPQEIRRS 1191
Cdd:pfam17380  531 EEERRREAEEERRKQqemEERRRIQEQMRKA 561

PTZ00121

MAEBL; Provisional

956-1190

2.20e-05

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 48.98 E-value: 2.20e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        956 DELRghKALVKLRSRQERDLRELRKKHQRKAVTLTRRlldglaqaqAEGRcrlRPGALGGAADVEDTKEG--EDEAKRYQ 1033
Cdd:PTZ00121 1537 DEAK--KAEEKKKADELKKAEELKKAEEKKKAEEAKK---------AEED---KNMALRKAEEAKKAEEAriEEVMKLYE 1602

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       1034 EFQNRQVQSLLELREAQVDAEAQRRLEHLRQALQrlrevvldanttQFKRLKEMNEREKKELQKILDRKRHNSISEAKMR 1113
Cdd:PTZ00121 1603 EEKKMKAEEAKKAEEAKIKAEELKKAEEEKKKVE------------QLKKKEAEEKKKAEELKKAEEENKIKAAEEAKKA 1670

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       1114 DKHKKEAE---LTEINRRHITESVNsiRRLEEAQK-QRHDRLVAGQQQVLQQL--AEEEPKLLAQLAQECQEQRARLPQE 1187
Cdd:PTZ00121 1671 EEDKKKAEeakKAEEDEKKAAEALK--KEAEEAKKaEELKKKEAEEKKKAEELkkAEEENKIKAEEAKKEAEEDKKKAEE 1748


                  ...
4GNK_B       1188 IRR 1190
Cdd:PTZ00121 1749 AKK 1751

DUF5401

pfam17380

Family of unknown function (DUF5401); This is a family of unknown function found in ...

1026-1198

3.17e-05

Family of unknown function (DUF5401); This is a family of unknown function found in Chromadorea.

Pssm-ID: 375164 [Multi-domain] Cd Length: 722 Bit Score: 48.20 E-value: 3.17e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1026 EDEAKRYQEFQNRQVQSLLELREAQVDAEAQRRLEHLRQALQRLRE---------------VVLDANTTQFKRLKEM--- 1087
Cdd:pfam17380  304 EKEEKAREVERRRKLEEAEKARQAEMDRQAAIYAEQERMAMERERElerirqeerkrelerIRQEEIAMEISRMRELerl 383

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1088 -------NEREKKEL-----QKILDRKRHNSISEaKMRDKHKKEAELTEINRRHitesvnsIRRLEEAQKQRHDRL---- 1151
Cdd:pfam17380  384 qmerqqkNERVRQELeaarkVKILEEERQRKIQQ-QKVEMEQIRAEQEEARQRE-------VRRLEEERAREMERVrlee 455

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
4GNK_B        1152 VAGQQQV--LQQLAEEEPKLLAQLAQEcQEQRARLPQEIRRSLLGEMPE 1198
Cdd:pfam17380  456 QERQQQVerLRQQEEERKRKKLELEKE-KRDRKRAEEQRRKILEKELEE 503

sbcc

TIGR00618

exonuclease SbcC; All proteins in this family for which functions are known are part of an ...

968-1192

3.68e-05

exonuclease SbcC; All proteins in this family for which functions are known are part of an exonuclease complex with sbcD homologs. This complex is involved in the initiation of recombination to regulate the levels of palindromic sequences in DNA. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 129705 [Multi-domain] Cd Length: 1042 Bit Score: 48.04 E-value: 3.68e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B         968 RSRQERDLRELRKKHQrKAVTLTRRLldGLAQAQAEGRCRLRPGALGGAADVEDTKEGEDEAKRYQEFQNRQVQSLLELR 1047
Cdd:TIGR00618  255 QLKKQQLLKQLRARIE-ELRAQEAVL--EETQERINRARKAAPLAAHIKAVTQIEQQAQRIHTELQSKMRSRAKLLMKRA 331

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1048 EAQVDAEAQRRLEHLRQALQRLREVVLDANTTQfKRLKEMNEREKKELQKIldRKRHNSISEAKMRDKHKKEAELTEINR 1127
Cdd:TIGR00618  332 AHVKQQSSIEEQRRLLQTLHSQEIHIRDAHEVA-TSIREISCQQHTLTQHI--HTLQQQKTTLTQKLQSLCKELDILQRE 408

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
4GNK_B        1128 RHITESVNSIRRLEEAQKqrhdrLVAGQQQVLQQLAEEEPKLLAQLAQECQEQRARLPQEIRRSL 1192
Cdd:TIGR00618  409 QATIDTRTSAFRDLQGQL-----AHAKKQQELQQRYAELCAAAITCTAQCEKLEKIHLQESAQSL 468

TPH

pfam13868

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of ...

966-1195

3.96e-05

Pssm-ID: 464007 [Multi-domain] Cd Length: 341 Bit Score: 47.22 E-value: 3.96e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B         966 KLRSRQERDLRELRKKHQRKavtltRRLLDGLAQAQAEgrcrlrpgalggaadVEDTKEGEDEAKRYQEFQNRQVQSLLE 1045
Cdd:pfam13868  106 IVERIQEEDQAEAEEKLEKQ-----RQLREEIDEFNEE---------------QAEWKELEKEEEREEDERILEYLKEKA 165

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1046 LREAQVDAEAQRRLEHLRQALQRLREVVLDANTTQ-------FKRLKEMNERE--KKELQKILDRKR-HNSISEA---KM 1112
Cdd:pfam13868  166 EREEEREAEREEIEEEKEREIARLRAQQEKAQDEKaerdelrAKLYQEEQERKerQKEREEAEKKARqRQELQQAreeQI 245

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1113 RDKHK---KEAELTEINRRHITESVNSIRRLEEAQKQ-RHDRLVAGQQQVLQQLAE----------EEPKLLAQLAQECQ 1178
Cdd:pfam13868  246 ELKERrlaEEAEREEEEFERMLRKQAEDEEIEQEEAEkRRMKRLEHRRELEKQIEEreeqraaereEELEEGERLREEEA 325

                          250
                   ....*....|....*..
4GNK_B        1179 EQRARLpQEIRRSLLGE 1195
Cdd:pfam13868  326 ERRERI-EEERQKKLKE 341

Borrelia_P83

pfam05262

Borrelia P83/100 protein; This family consists of several Borrelia P83/P100 antigen proteins.

1020-1176

3.98e-05

Borrelia P83/100 protein; This family consists of several Borrelia P83/P100 antigen proteins.

Pssm-ID: 114011 [Multi-domain] Cd Length: 489 Bit Score: 47.69 E-value: 3.98e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1020 EDTKEGEDEAKRYQEFQNRQVQSLLELREAQVDAEAQRRleHLRQALQRLREVVLDANTTQFKRLKEMNEREKKELQKil 1099
Cdd:pfam05262  210 EDAKRAQQLKEELDKKQIDADKAQQKADFAQDNADKQRD--EVRQKQQEAKNLPKPADTSSPKEDKQVAENQKREIEK-- 285

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1100 drkrhnSISEAKMRD---KHKKEAELTEINRRHITESVNSIRRLEEAQKQRHDrlVAGQQQVLQQLAEEEPKLLAQLAQE 1176
Cdd:pfam05262  286 ------AQIEIKKNDeeaLKAKDHKAFDLKQESKASEKEAEDKELEAQKKREP--VAEDLQKTKPQVEAQPTSLNEDAID 357

EFh_PI-PLCeta

cd16205

EF-hand motif found in phosphoinositide phospholipase C eta (PI-PLC-eta); PI-PLC-eta isozymes ...

162-301

4.78e-05

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: 44.68 E-value: 4.78e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       162 KLQVNqdgrIPVKNILKMFsadkKRVETALESCGLKFnrsesirpDEFSleifeRFLNKLCLRPDIDKILLEIGAKgKPY 241
Cdd:cd16205   28 KLNVN----LPRRKVRQMF----KEADTDDNQGTLDF--------EEFC-----AFYKMMSTRRELYLLLLSYSNK-KDY 85

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       242 LTLEQLMDFINQKQRdprLNEVlypPLRPSQArlLIEKYEPNQQFLERDQMSMEGFSRYL 301
Cdd:cd16205   86 LTLEDLARFLEVEQK---MTNV---TLEYCLD--IIEKFEPSEENKKNGLLGIDGFTNYM 137

DUF4659

pfam15558

Domain of unknown function (DUF4659); This family of proteins is found in eukaryotes. Proteins ...

1043-1192

6.91e-05

Domain of unknown function (DUF4659); This family of proteins is found in eukaryotes. Proteins in this family are typically between 427 and 674 amino acids in length. There are two completely conserved residues (D and I) that may be functionally important.

Pssm-ID: 464768 [Multi-domain] Cd Length: 374 Bit Score: 46.57 E-value: 6.91e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1043 LLELREAQVDAEaQRRLEHLRQALQRLREvvldanttqfKRLKEMNEREKKELQKiLDRKRHNSISEAKMRDKHKKEAEL 1122
Cdd:pfam15558   14 LARHKEEQRMRE-LQQQAALAWEELRRRD----------QKRQETLERERRLLLQ-QSQEQWQAEKEQRKARLGREERRR 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
4GNK_B        1123 TEINRRHITESVNSIRRLEEAQ-KQRHDRLvagqqqvlqqlaeEEPKLLAQLAQECQEQRARLPQEIRRSL 1192
Cdd:pfam15558   82 ADRREKQVIEKESRWREQAEDQeNQRQEKL-------------ERARQEAEQRKQCQEQRLKEKEEELQAL 139

COG4913

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

1039-1190

7.06e-05

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

Pssm-ID: 443941 [Multi-domain] Cd Length: 1089 Bit Score: 47.22 E-value: 7.06e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B      1039 QVQSLLELREAQVDAEAQRR-LEHLRQALQRLREVVLDANttQFKRLKEM-----NEREKKELQKILDRKRHN------S 1106
Cdd:COG4913  233 HFDDLERAHEALEDAREQIElLEPIRELAERYAAARERLA--ELEYLRAAlrlwfAQRRLELLEAELEELRAElarleaE 310

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B      1107 ISEAKmRDKHKKEAELTEINRRHITESVNSIRRLE------EAQKQRHDRLVAGQQQVLQQLAEEEP---KLLAQLAQEC 1177
Cdd:COG4913  311 LERLE-ARLDALREELDELEAQIRGNGGDRLEQLEreierlERELEERERRRARLEALLAALGLPLPasaEEFAALRAEA 389

                        170
                 ....*....|...
4GNK_B      1178 QEQRARLPQEIRR 1190
Cdd:COG4913  390 AALLEALEEELEA 402

DUF4670

pfam15709

Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins ...

1030-1190

9.03e-05

Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins in this family are typically between 373 and 763 amino acids in length.

Pssm-ID: 464815 [Multi-domain] Cd Length: 522 Bit Score: 46.48 E-value: 9.03e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1030 KRYQEFQNRQVQSLLELRE---AQVDAEAQRRLEHLRQALQRLREvvldanttqfKRLKEMNEREKKELQKILDRKRHNS 1106
Cdd:pfam15709  354 RREQEEQRRLQQEQLERAEkmrEELELEQQRRFEEIRLRKQRLEE----------ERQRQEEEERKQRLQLQAAQERARQ 423

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1107 ISEAKMRdkhkkeaELTEINRRHITESVNSIRRLEEAQKQRHDRLvAGQQQVLQQLAEEEpKLLAQLAQECQEQRARLPQ 1186
Cdd:pfam15709  424 QQEEFRR-------KLQELQRKKQQEEAERAEAEKQRQKELEMQL-AEEQKRLMEMAEEE-RLEYQRQKQEAEEKARLEA 494


                   ....
4GNK_B        1187 EIRR 1190
Cdd:pfam15709  495 EERR 498

SMC_prok_A

TIGR02169

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of ...

1049-1190

1.08e-04

Pssm-ID: 274009 [Multi-domain] Cd Length: 1164 Bit Score: 46.60 E-value: 1.08e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1049 AQVDAEAQRRLEHLRQALQRLREV--VLDANTTQFKRLKEmnEREKKELQKILDRKrhnsiseakmrdkhKKEAELTEIn 1126
Cdd:TIGR02169  166 AEFDRKKEKALEELEEVEENIERLdlIIDEKRQQLERLRR--EREKAERYQALLKE--------------KREYEGYEL- 228

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
4GNK_B        1127 rrhitesVNSIRRLeEAQKQRHDRLVAGQQQVLQQLAEEepklLAQLAQECQEQRARLPQEIRR 1190
Cdd:TIGR02169  229 -------LKEKEAL-ERQKEAIERQLASLEEELEKLTEE----ISELEKRLEEIEQLLEELNKK 280

YhaN

COG4717

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

1043-1190

1.44e-04

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

Pssm-ID: 443752 [Multi-domain] Cd Length: 641 Bit Score: 45.91 E-value: 1.44e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B      1043 LLELREAQVD-AEAQRRLEHLRQALQRLREVvldanttqfKRLKEMNEREKKELQKILDRKRHNSISEAKMRDKHKKEAE 1121
Cdd:COG4717   70 LKELKELEEElKEAEEKEEEYAELQEELEEL---------EEELEELEAELEELREELEKLEKLLQLLPLYQELEALEAE 140

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
4GNK_B      1122 LTEINRR--HITESVNSIRRLEEAQKQRHDRLVAGQQQV---LQQLAEEEPKLLAQLA---QECQEQRARLPQEIRR 1190
Cdd:COG4717  141 LAELPERleELEERLEELRELEEELEELEAELAELQEELeelLEQLSLATEEELQDLAeelEELQQRLAELEEELEE 217

EFh_PRIP1

cd16222

EF-hand motif found in phospholipase C-related but catalytically inactive protein 1 (PRIP-1); ...

212-305

1.97e-04

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: 42.93 E-value: 1.97e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       212 EIFERFLNKLCLRPDIDKILLEIgAKGKPYLTLEQLMDFINQKQRDPRLNEvlypplrpSQARLLIEKYEPNQQFLERDQ 291
Cdd:cd16222   59 EEFCEAYSELCTRPEVYFLLVQI-SKNKEYLDAKDLMLFLEAEQGMTHITE--------EMCLDIIRRYEPSQEGRLKGF 129

                         90
                 ....*....|....
4GNK_B       292 MSMEGFSRYLGGEE 305
Cdd:cd16222  130 LGIDGFTQYLLSSE 143

EnvC

COG4942

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, ...

993-1190

3.86e-04

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 443969 [Multi-domain] Cd Length: 377 Bit Score: 44.37 E-value: 3.86e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       993 LLDGLAQAQAEGRCRLRpgalggaADVEDTKEGEDEAKRYQEFQNRQVQSLLELREAQVD--AEAQRRLEHLRQALQRLR 1070
Cdd:COG4942   10 LLALAAAAQADAAAEAE-------AELEQLQQEIAELEKELAALKKEEKALLKQLAALERriAALARRIRALEQELAALE 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B      1071 EVvLDANTTQFKRLKEMNEREKKELQKILD--------------------------RKRHNSISEAKMRDKHKKEAELTE 1124
Cdd:COG4942   83 AE-LAELEKEIAELRAELEAQKEELAELLRalyrlgrqpplalllspedfldavrrLQYLKYLAPARREQAEELRADLAE 161

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
4GNK_B      1125 IN--RRHITESVNSIRRLEEAQKQRHDRL---VAGQQQVLQQLAEEEPKLLAQLAQEcQEQRARLPQEIRR 1190
Cdd:COG4942  162 LAalRAELEAERAELEALLAELEEERAALealKAERQKLLARLEKELAELAAELAEL-QQEAEELEALIAR 231

Myosin_tail_1

pfam01576

Myosin tail; The myosin molecule is a multi-subunit complex made up of two heavy chains and ...

964-1187

3.86e-04

Myosin tail; The myosin molecule is a multi-subunit complex made up of two heavy chains and four light chains it is a fundamental contractile protein found in all eukaryote cell types. This family consists of the coiled-coil myosin heavy chain tail region. The coiled-coil is composed of the tail from two molecules of myosin. These can then assemble into the macromolecular thick filament. The coiled-coil region provides the structural backbone the thick filament.

Pssm-ID: 460256 [Multi-domain] Cd Length: 1081 Bit Score: 44.78 E-value: 3.86e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B         964 LVKLRSRQ---ERDLRELRKKHQRkaVTLTRRLLDGLAQAQA-------EGRCRLrpgalggAADVEDTKE--------G 1025
Cdd:pfam01576   14 LQKVKERQqkaESELKELEKKHQQ--LCEEKNALQEQLQAETelcaeaeEMRARL-------AARKQELEEilhelesrL 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1026 EDEAKRYQEFQN--RQVQSLLELREAQVDAEaqrrlEHLRQALQrLREVVLDAnttqfkRLKEMNE-------------R 1090
Cdd:pfam01576   85 EEEEERSQQLQNekKKMQQHIQDLEEQLDEE-----EAARQKLQ-LEKVTTEA------KIKKLEEdillledqnsklsK 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1091 EKKELQKILDRKRHNSISE---AKM--RDKHKKEAELTEINRRHITESvNSIRRLEEAQKQRHDRLVAGQQQV--LQQLA 1163
Cdd:pfam01576  153 ERKLLEERISEFTSNLAEEeekAKSlsKLKNKHEAMISDLEERLKKEE-KGRQELEKAKRKLEGESTDLQEQIaeLQAQI 231

                          250       260
                   ....*....|....*....|....*..
4GNK_B        1164 EEepkLLAQLAQ---ECQEQRARLPQE 1187
Cdd:pfam01576  232 AE---LRAQLAKkeeELQAALARLEEE 255

Smc

COG1196

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning]; ...

959-1190

4.70e-04

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 44.54 E-value: 4.70e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       959 RGHKALVKLRSRQER-----DLR-ELRK-----KHQRKAVTLTRRLLDGLAQAQAEGRCRLRpgalggaADVEDTKEGED 1027
Cdd:COG1196  173 RKEEAERKLEATEENlerleDILgELERqleplERQAEKAERYRELKEELKELEAELLLLKL-------RELEAELEELE 245

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B      1028 EAKRYQEFQNRQVQSLLELREAQVdAEAQRRLEHLRQALQRLREVVLDANTT------QFKRLKEMNEREKKELQKILDR 1101
Cdd:COG1196  246 AELEELEAELEELEAELAELEAEL-EELRLELEELELELEEAQAEEYELLAElarleqDIARLEERRRELEERLEELEEE 324

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B      1102 KRHNsisEAKMRDKHKKEAELTEINRRHITESVNSIRRLEEAQKQRhDRLVAGQQQVLQQLAEEEpKLLAQLAQECQEQR 1181
Cdd:COG1196  325 LAEL---EEELEELEEELEELEEELEEAEEELEEAEAELAEAEEAL-LEAEAELAEAEEELEELA-EELLEALRAAAELA 399


                 ....*....
4GNK_B      1182 ARLPQEIRR 1190
Cdd:COG1196  400 AQLEELEEA 408

PI-PLCc_bacteria_like

cd08557

Catalytic domain of bacterial phosphatidylinositol-specific phospholipase C and similar ...

317-442

6.11e-04

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: 43.24 E-value: 6.11e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       317 STDMTQPLSAYFINSSHN--TYLTAGQLAGTSSVEMY-----RQALLWGCRCVELDVWKgRPPEEEPFITHGFTMTTEVP 389
Cdd:cd08557    2 ALLDDLPLSQLSIPGTHNsyAYTIDGNSPIVSKWSKTqdlsiTDQLDAGVRYLDLRVAY-DPDDGDLYVCHGLFLLNGQT 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
4GNK_B       390 LRDVLEAIAetAF-KTSPY-PVILSFENHV--DSAKQQAKMAEYCRSIFGDALLIEP 442
Cdd:cd08557   81 LEDVLNEVK--DFlDAHPSeVVILDLEHEYggDNGEDHDELDALLRDVLGDPLYRPP 135

PDCD7

pfam16021

Programmed cell death protein 7;

984-1183

6.43e-04

Programmed cell death protein 7;

Pssm-ID: 464979 [Multi-domain] Cd Length: 305 Bit Score: 43.18 E-value: 6.43e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B         984 RKAVTLTRRLLDGLAQAQAEgrcrLRpgalggaADVEDTKEGEDEAKRYQEFQNRQVQSLLELREAQVDAEAQRRLEhlR 1063
Cdd:pfam16021    7 RQALYSAARLVSRLETLCLE----LR-------ENVEDDSVWSESYSRAAELKHELQEKLLLLEDPELLESLKRKLE--R 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1064 QALQRLREvvldanttqfKRLKEMNEREKK-------ELQKILD---RKRHNSISEAKMRDKHKKEAE--LTEINRRH-- 1129
Cdd:pfam16021   74 RQKKRLRR----------KRRKEERKEEKKeeqerraEREAKIDkwrRKQIQEVEEKKRERELKLAADavLSEVRKKQad 143

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
4GNK_B        1130 ITESVNSIRRLEEAQKQRH----------------------DRLVAGQQQVLQQLAEEEPKLLAQLAQECQEQRAR 1183
Cdd:pfam16021  144 AKRMLDILRSLEKLRKLRKeaarrkgikpesecdeafeshlEKLRSVWKKRTEEYSAEEKALKVMLEGEQEEERKR 219

SMC_prok_B

TIGR02168

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...

1054-1190

7.75e-04

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 43.89 E-value: 7.75e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1054 EAQRRLEHLRQALQRLREVV--LDAN----------TTQFKRLKEmnerEKKELQKILDRKRHNSIsEAKMRDKHKKEAE 1121
Cdd:TIGR02168  176 ETERKLERTRENLDRLEDILneLERQlkslerqaekAERYKELKA----ELRELELALLVLRLEEL-REELEELQEELKE 250

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
4GNK_B        1122 LTEINRRHITESVNSIRRLEEAQKQRH--DRLVAGQQQVLQQLAEEEPKLLAQLaQECQEQRARLPQEIRR 1190
Cdd:TIGR02168  251 AEEELEELTAELQELEEKLEELRLEVSelEEEIEELQKELYALANEISRLEQQK-QILRERLANLERQLEE 320

PRK12704

phosphodiesterase; Provisional

1023-1188

8.89e-04

phosphodiesterase; Provisional

Pssm-ID: 237177 [Multi-domain] Cd Length: 520 Bit Score: 43.23 E-value: 8.89e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       1023 KEGEDEAKRYQEFQNRQVQSLLELREAQVDAEAQRRLEHLRQALQRL--REVVLDanttqfkRLKEMNEREKKELQKild 1100
Cdd:PRK12704   45 EEAKKEAEAIKKEALLEAKEEIHKLRNEFEKELRERRNELQKLEKRLlqKEENLD-------RKLELLEKREEELEK--- 114

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       1101 rkrHNSISEAKMRDKHKKEAELTEINRRHITEsvnsirrLEEaqkqrhdrlVAGqqqvlqqLAEEEPK--LLAQLAQECQ 1178
Cdd:PRK12704  115 ---KEKELEQKQQELEKKEEELEELIEEQLQE-------LER---------ISG-------LTAEEAKeiLLEKVEEEAR 168

                         170
                  ....*....|
4GNK_B       1179 EQRARLPQEI 1188
Cdd:PRK12704  169 HEAAVLIKEI 178

sbcc

TIGR00618

exonuclease SbcC; All proteins in this family for which functions are known are part of an ...

958-1193

1.34e-03

Pssm-ID: 129705 [Multi-domain] Cd Length: 1042 Bit Score: 43.03 E-value: 1.34e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B         958 LRGHkaLVKLRSRQERDLRELRKKHQRKAVTLTRRLLDGLAQAQAEGRCRLRPGALGGAADV--EDTKEGEDEAKRYQEF 1035
Cdd:TIGR00618  422 LQGQ--LAHAKKQQELQQRYAELCAAAITCTAQCEKLEKIHLQESAQSLKEREQQLQTKEQIhlQETRKKAVVLARLLEL 499

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1036 QNRQ---VQSLLELREAQVDAE----AQRRLEHLRQALQRLREVV------LDANTTQFKRLKEMNEREKKELQKILDRK 1102
Cdd:TIGR00618  500 QEEPcplCGSCIHPNPARQDIDnpgpLTRRMQRGEQTYAQLETSEedvyhqLTSERKQRASLKEQMQEIQQSFSILTQCD 579

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1103 RHNSISEAKMRDKHKKEAELTEINRRH-ITESVNSIRRLEEAQKQRHDRLVAgqqQVLQQLAEEEPKLLAQLAQECQEqr 1181
Cdd:TIGR00618  580 NRSKEDIPNLQNITVRLQDLTEKLSEAeDMLACEQHALLRKLQPEQDLQDVR---LHLQQCSQELALKLTALHALQLT-- 654

                          250
                   ....*....|...
4GNK_B        1182 arLPQE-IRRSLL 1193
Cdd:TIGR00618  655 --LTQErVREHAL 665

PTZ00121

MAEBL; Provisional

965-1191

1.53e-03

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 43.21 E-value: 1.53e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        965 VKLRSRQERDLRELRKK--HQRKAVTLTRRLLDGLAQAQAEGRCRLRPGAlggaadvEDTKEGEDEAKRYQEFQNRQVQS 1042
Cdd:PTZ00121 1423 AKKKAEEKKKADEAKKKaeEAKKADEAKKKAEEAKKAEEAKKKAEEAKKA-------DEAKKKAEEAKKADEAKKKAEEA 1495

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       1043 LLELREAQVDAEAQRRLEHLRQALQRlrevvldanttqfkrlkemneREKKELQKILDRKRHNSISEAKmrdkHKKEAEl 1122
Cdd:PTZ00121 1496 KKKADEAKKAAEAKKKADEAKKAEEA---------------------KKADEAKKAEEAKKADEAKKAE----EKKKAD- 1549

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       1123 tEINRRHITESVNSIRRLEEAQKQRHDRLVAGQQ------------QVLQQLAEEEPKLLAQLAQECQEQRARlPQEIRR 1190
Cdd:PTZ00121 1550 -ELKKAEELKKAEEKKKAEEAKKAEEDKNMALRKaeeakkaeeariEEVMKLYEEEKKMKAEEAKKAEEAKIK-AEELKK 1627


                  .
4GNK_B       1191 S 1191
Cdd:PTZ00121 1628 A 1628

Hmw_CFAP97

pfam13879

Hemingway/CFA97; Drosophila Hemingway (Hmw) is required for motile cilia function and sperm ...

1066-1170

1.61e-03

Hemingway/CFA97; Drosophila Hemingway (Hmw) is required for motile cilia function and sperm flagella assembly. The human orthologue, known as cilia- and flagella-associated protein 97 (CFAP97) or KIAA1430, localizes to the primary cilium. Another member of this family is the uncharacterized protein CFAP97D1/2 (CFAP97 domain-containing protein 1/2).

Pssm-ID: 464014 Cd Length: 100 Bit Score: 39.26 E-value: 1.61e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1066 LQRLREVVLDANTTQFKRLKEMNEREKKELQKILDRKRHNSISEAKMrdkhkkeaelTEINRRHITESVNSIRRLEEAQK 1145
Cdd:pfam13879    1 LNKLKNAKPTVDNKAPPHLSLKLKKLQFEEERLAEIERENQILLEKI----------SRIMRRKGKVDKNSLSTQSYSSK 70

                           90       100
                   ....*....|....*....|....*.
4GNK_B        1146 QRHDRLVAGQQQV-LQQLAEEEPKLL 1170
Cdd:pfam13879   71 TRPKSLNAENRKReLLRIEEENQKLL 96

PTZ00121

MAEBL; Provisional

998-1191

1.65e-03

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 42.82 E-value: 1.65e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        998 AQAQAEGRCRLRPGALGGAADVEDTKEGEDEAKRYQEFqnRQVQSLLELREAQvDAEAQRRLEHLRQAlQRLREVVLDAN 1077
Cdd:PTZ00121 1096 AFGKAEEAKKTETGKAEEARKAEEAKKKAEDARKAEEA--RKAEDARKAEEAR-KAEDAKRVEIARKA-EDARKAEEARK 1171

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       1078 TTQFKRLKEmnEREKKELQKILDRKRHNSISEAKMRDKHKKEAELTEINRRHITESVNSIRRLEEAQKQRHDRLVAGQQQ 1157
Cdd:PTZ00121 1172 AEDAKKAEA--ARKAEEVRKAEELRKAEDARKAEAARKAEEERKAEEARKAEDAKKAEAVKKAEEAKKDAEEAKKAEEER 1249

                         170       180       190
                  ....*....|....*....|....*....|....*..
4GNK_B       1158 VLQQLAEEEPKLLAQLAQECQEQRA---RLPQEIRRS 1191
Cdd:PTZ00121 1250 NNEEIRKFEEARMAHFARRQAAIKAeeaRKADELKKA 1286

DUF1154

pfam06631

Protein of unknown function (DUF1154); This family represents a small conserved region of ...

952-991

1.85e-03

Pssm-ID: 461969 Cd Length: 45 Bit Score: 37.24 E-value: 1.85e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
4GNK_B         952 PTPLDELRGHKALVKLRSRQERDLRELRKKHQRKAVTLTR 991
Cdd:pfam06631    6 PITLESLRQDKAYLKLLKKQQKELESLKKKHSKERSAMQK 45

MukB

COG3096

Chromosome condensin MukBEF, ATPase and DNA-binding subunit MukB [Cell cycle control, cell ...

998-1187

2.37e-03

Chromosome condensin MukBEF, ATPase and DNA-binding subunit MukB [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 442330 [Multi-domain] Cd Length: 1470 Bit Score: 42.25 E-value: 2.37e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       998 AQAQAEGRCRLRPGALGGAADvedtkegedeakRYQEFQNRQ---VQSLLELREAQVDAEAQRRlEHlRQALQRLREVVL 1074
Cdd:COG3096  421 ALEKARALCGLPDLTPENAED------------YLAAFRAKEqqaTEEVLELEQKLSVADAARR-QF-EKAYELVCKIAG 486

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B      1075 DANTTQ-FKRLKEMnEREKKELQKILDRKrhNSIseakmrdkhkkEAELTEINRRhiTESVNSIRRLEEAQKQRHDRLVA 1153
Cdd:COG3096  487 EVERSQaWQTAREL-LRRYRSQQALAQRL--QQL-----------RAQLAELEQR--LRQQQNAERLLEEFCQRIGQQLD 550

                        170       180       190
                 ....*....|....*....|....*....|....*.
4GNK_B      1154 GQQQVLQQLAEEEPKL--LAQLAQECQEQRARLPQE 1187
Cdd:COG3096  551 AAEELEELLAELEAQLeeLEEQAAEAVEQRSELRQQ 586

YscO

pfam07321

Type III secretion protein YscO; This family contains the bacterial type III secretion protein ...

974-1112

2.42e-03

Type III secretion protein YscO; This family contains the bacterial type III secretion protein YscO, which is approximately 150 residues long. YscO has been shown to be required for high-level expression and secretion of the anti-host proteins V antigen and Yops in Yersinia pestis.

Pssm-ID: 399954 [Multi-domain] Cd Length: 148 Bit Score: 39.69 E-value: 2.42e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B         974 DLRELRKKHQRKAVTLTRRLLDGLAQAQAEGRCRLrpgalggaADVEDTKEGEdEAKRYQEFQNRQV---------QSLL 1044
Cdd:pfam07321    6 RVKHLREDRAEKAVKRQEQALAAARAAHQQAQASL--------QDYRAWRPQE-EQRLYAEIQGKLVllkelekvkQQVA 76

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
4GNK_B        1045 ELREAQVD-----AEAQRRLEHLRQALQRLREVVLDANTTQFKrLKEMNEREKKELQKILDRKRHNSISEAKM 1112
Cdd:pfam07321   77 LLRENEADlekqvAEARQQLEAEREALRQARQALAEARRAVEK-FAELVRLVQAEELRQQERQEEQELEEFAE 148

EFh_PI-PLCepsilon

cd16203

EF-hand motif found in phosphoinositide phospholipase C epsilon 1 (PI-PLC-epsilon1); ...

242-301

3.23e-03

EF-hand motif found in phosphoinositide phospholipase C epsilon 1 (PI-PLC-epsilon1); PI-PLC-epsilon1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1, or pancreas-enriched phospholipase C, or phospholipase C-epsilon-1 (PLC-epsilon-1), is dominant in connective tissues and brain. It has been implicated in carcinogenesis, such as in bladder and intestinal tumor, oesophageal squamous cell carcinoma, gastric adenocarcinoma, murine skin cancer, head and neck cancer. PI-PLC-epsilon1 contains an N-terminal CDC25 homology domain with a guanyl-nucleotide exchange factor (GFF) activity, a pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, a C2 domain, and at least one and perhaps two C-terminal 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 only one PI-PLC-epsilon isozyme. It is directly activated by G alpha(12/13), G beta gamma, and activated members of Ras and Rho small GTPases.

Pssm-ID: 320033 Cd Length: 174 Bit Score: 40.00 E-value: 3.23e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       242 LTLEQLMDFINQKQRDPRLNEvlypplrpsQARLLIEKYEPNQQFLERDQMSMEGFSRYL 301
Cdd:cd16203  120 LTISQLKDFLENHQMEHITEE---------EAIKIIQRHEPDPILRSKNCLSFEGFARYL 170

SMC_prok_B

TIGR02168

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...

971-1195

3.26e-03

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 41.97 E-value: 3.26e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B         971 QERDLRELRKKHQRkavtltrrlLDGLAQAQAEGRCRLRpgalggaADVEDTKEGEDEAKRYQEFQNRQVQSL-LELREA 1049
Cdd:TIGR02168  801 LREALDELRAELTL---------LNEEAANLRERLESLE-------RRIAATERRLEDLEEQIEELSEDIESLaAEIEEL 864

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1050 QVD-AEAQRRLEHL---RQALQRLREVVLDANTTQFKRLKEMnEREKKELQKILDRKRHnSISEAKMRdkhkkEAELtEI 1125
Cdd:TIGR02168  865 EELiEELESELEALlneRASLEEALALLRSELEELSEELREL-ESKRSELRRELEELRE-KLAQLELR-----LEGL-EV 936

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1126 NRRHITESVNSirrleeaqkqrhdrlvagQQQVLQQLAEEEPKLLAQLAQECQEQRARLPQEIRRslLGE 1195
Cdd:TIGR02168  937 RIDNLQERLSE------------------EYSLTLEEAEALENKIEDDEEEARRRLKRLENKIKE--LGP 986

COG4372

Uncharacterized protein, contains DUF3084 domain [Function unknown];

1028-1192

4.83e-03

Uncharacterized protein, contains DUF3084 domain [Function unknown];

Pssm-ID: 443500 [Multi-domain] Cd Length: 370 Bit Score: 40.66 E-value: 4.83e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B      1028 EAKRYQEFQNRQVQSLLELREAQVDAEAQRRLEHLRQALQRLREVvLDANTTQFKRLKEMNEREKKELQKILDR--KRHN 1105
Cdd:COG4372    9 GKARLSLFGLRPKTGILIAALSEQLRKALFELDKLQEELEQLREE-LEQAREELEQLEEELEQARSELEQLEEEleELNE 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B      1106 SISEAKMRDKhKKEAELTEIN------RRHITESVNSIRRLE------EAQKQRHDRLVAGQQQVLQQLAEEEPKLLAQL 1173
Cdd:COG4372   88 QLQAAQAELA-QAQEELESLQeeaeelQEELEELQKERQDLEqqrkqlEAQIAELQSEIAEREEELKELEEQLESLQEEL 166

                        170
                 ....*....|....*....
4GNK_B      1174 AQECQEQRARLPQEIRRSL 1192
Cdd:COG4372  167 AALEQELQALSEAEAEQAL 185

C2C_MCTP_PRT_plant

cd04019

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...

729-817

4.83e-03

C2 domain third 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 third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 175986 [Multi-domain] Cd Length: 150 Bit Score: 38.80 E-value: 4.83e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       729 LRVKVISGQ--FLSD--RKVGIYVEVDMfGLPVdtrrkYRTRTSQGNSFNPVWDE-------EPFDFPKVVlptlaSL-- 795
Cdd:cd04019    2 LRVTVIEAQdlVPSDknRVPEVFVKAQL-GNQV-----LRTRPSQTRNGNPSWNEelmfvaaEPFEDHLIL-----SVed 70

                         90       100
                 ....*....|....*....|..
4GNK_B       796 RIAAFEEGgkFVGHRILPVSAI 817
Cdd:cd04019   71 RVGPNKDE--PLGRAVIPLNDI 90

PRK06975

bifunctional uroporphyrinogen-III synthetase/uroporphyrin-III C-methyltransferase; Reviewed

874-1067

4.90e-03

bifunctional uroporphyrinogen-III synthetase/uroporphyrin-III C-methyltransferase; Reviewed

Pssm-ID: 235899 [Multi-domain] Cd Length: 656 Bit Score: 41.24 E-value: 4.90e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        874 ARQLAALIGESEAQAGQETCQDTQSQQLGSQPSSNPTPSPldASPRRPPGPTTSPASTSLSSPGQRDDLIASILSEVAPT 953
Cdd:PRK06975  256 ERIVRAFLTWADAAAQPATAAPAPSRMTDTNDSKSVTSQP--AAAAAAPAPPPNPPATPPEPPARRGRGSAALWFVVVVL 333

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        954 PLDELRGHKALVKLRSRQERDLRELRKK---HQRKAVTLTRRLLDGLAQAQAEgrcrlrPGALggaadveDTKEGEDEAK 1030
Cdd:PRK06975  334 ACAAAVGGYALNRKVDRLDQELVQRQQAndaQTAELRVKTEQAQASVHQLDSQ------FAQL-------DGKLADAQSA 400

                         170       180       190
                  ....*....|....*....|....*....|....*..
4GNK_B       1031 ryQEFQNRQVQSLLELREAQVDAEAQRRLEHLRQALQ 1067
Cdd:PRK06975  401 --QQALEQQYQDLSRNRDDWMIAEVEQMLSSASQQLQ 435

sbcc

TIGR00618

exonuclease SbcC; All proteins in this family for which functions are known are part of an ...

1026-1187

5.30e-03

Pssm-ID: 129705 [Multi-domain] Cd Length: 1042 Bit Score: 41.11 E-value: 5.30e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1026 EDEAKRYQEFQNRQVQSLLELREAQVDAEAQRRLEH-LRQALQRLREVvldanTTQFKRLKEMNERekkelqkiLDRKRH 1104
Cdd:TIGR00618  225 EKELKHLREALQQTQQSHAYLTQKREAQEEQLKKQQlLKQLRARIEEL-----RAQEAVLEETQER--------INRARK 291

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1105 NS----ISEAKMRDKHKKEAELTEINRRhITESVNSIRRLEEAQKQRHDrlVAGQQQVLQQLAEEEpKLLAQLAQECQEQ 1180
Cdd:TIGR00618  292 AAplaaHIKAVTQIEQQAQRIHTELQSK-MRSRAKLLMKRAAHVKQQSS--IEEQRRLLQTLHSQE-IHIRDAHEVATSI 367


                   ....*..
4GNK_B        1181 RARLPQE 1187
Cdd:TIGR00618  368 REISCQQ 374

YhaN

COG4717

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

949-1190

6.02e-03

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

Pssm-ID: 443752 [Multi-domain] Cd Length: 641 Bit Score: 40.91 E-value: 6.02e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       949 EVAPTPLDELRGHKALVKLRSRQERDLRELRKKHQRKAVTLTRRLLDGLAQAQAegrcrlrpgALGGAADVEDTKEGED- 1027
Cdd:COG4717  298 ASLGKEAEELQALPALEELEEEELEELLAALGLPPDLSPEELLELLDRIEELQE---------LLREAEELEEELQLEEl 368

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B      1028 EAKRYQEFQNRQVQSLLELREAQVDAEAQRRLEHLRQALQR-----LREVVLDANTTQFKRLKEMNEREKKELQKIldrk 1102
Cdd:COG4717  369 EQEIAALLAEAGVEDEEELRAALEQAEEYQELKEELEELEEqleelLGELEELLEALDEEELEEELEELEEELEEL---- 444

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B      1103 rhnsisEAKMRDKHKKEAELteinrRHITESVNSIRRLEEAQKQRHDrlvagQQQVLQQLAEE--EPKLLAQLAQECQE- 1179
Cdd:COG4717  445 ------EEELEELREELAEL-----EAELEQLEEDGELAELLQELEE-----LKAELRELAEEwaALKLALELLEEAREe 508

                        250
                 ....*....|..
4GNK_B      1180 -QRARLPQEIRR 1190
Cdd:COG4717  509 yREERLPPVLER 520

MAT1

pfam06391

CDK-activating kinase assembly factor MAT1; MAT1 is an assembly/targeting factor for ...

1018-1168

6.69e-03

CDK-activating kinase assembly factor MAT1; MAT1 is an assembly/targeting factor for cyclin-dependent kinase-activating kinase (CAK), which interacts with the transcription factor TFIIH. The domain found to the N-terminal side of this domain is a C3HC4 RING finger.

Pssm-ID: 461894 [Multi-domain] Cd Length: 202 Bit Score: 39.15 E-value: 6.69e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1018 DVEDTKEgedEAKRYQEfQNRQVQSLLELREAQVDAEAQRRLEHLRQALQRLREVVLDAnttqfkrlkEMNEREKKEL-- 1095
Cdd:pfam06391   62 DVEETEK---KIEQYEK-ENKDLILKNKMKLSQEEEELEELLELEKREKEERRKEEKQE---------EEEEKEKKEKak 128

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
4GNK_B        1096 QKILDRKRHNSISEAKMRDKHKKEAELTEINRRHITESVNsiRRLEEAQKQRHDRLVAGQQQVLQQlaEEEPK 1168
Cdd:pfam06391  129 QELIDELMTSNKDAEEIIAQHKKTAKKRKSERRRKLEELN--RVLEQKPTQFSTGIKFGQLPVPKI--EEGPL 197

COG4913

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

956-1190

7.05e-03

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

Pssm-ID: 443941 [Multi-domain] Cd Length: 1089 Bit Score: 40.67 E-value: 7.05e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B       956 DELRGHKALVKLRSRQERDLRELRKKHQRKAVTLTRRL-LDGLAQAQAEGRCRLRpGALGGAADVEDTKEGEDEAKRYQE 1034
Cdd:COG4913  624 EELAEAEERLEALEAELDALQERREALQRLAEYSWDEIdVASAEREIAELEAELE-RLDASSDDLAALEEQLEELEAELE 702

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B      1035 fQNRQVQSLLELREAQVDAEAQRRLEHLRQALQRLREVVLDANTTQFKRLKEMNERE-KKELQKILDRKRHNSISEAKmR 1113
Cdd:COG4913  703 -ELEEELDELKGEIGRLEKELEQAEEELDELQDRLEAAEDLARLELRALLEERFAAAlGDAVERELRENLEERIDALR-A 780

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B      1114 DKHKKEAELTEINRRHITE----------SVNSIRR-LEEAQKQRHDRLVAGQQQVLQQLAEEEPKLLAQLAQECQEQRA 1182
Cdd:COG4913  781 RLNRAEEELERAMRAFNREwpaetadldaDLESLPEyLALLDRLEEDGLPEYEERFKELLNENSIEFVADLLSKLRRAIR 860


                 ....*...
4GNK_B      1183 RLPQEIRR 1190
Cdd:COG4913  861 EIKERIDP 868

TPH

pfam13868

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of ...

1016-1183

9.53e-03

Pssm-ID: 464007 [Multi-domain] Cd Length: 341 Bit Score: 39.90 E-value: 9.53e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1016 AADVEDTKEGEDEAKRYQEFQNRQVQSLLELREAQVDAEAQRRLEHLRQALQRLREVVLDaNTTQFKRLKEMNEREKKEL 1095
Cdd:pfam13868   25 DAQIAEKKRIKAEEKEEERRLDEMMEEERERALEEEEEKEEERKEERKRYRQELEEQIEE-REQKRQEEYEEKLQEREQM 103

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4GNK_B        1096 QKILDRKRHNSISEAKMRDKHKKEA--ELTEINRRHIT-------ESVNSIRRLEEAQKQRHDRLVAGQQQVLQQLAEEE 1166
Cdd:pfam13868  104 DEIVERIQEEDQAEAEEKLEKQRQLreEIDEFNEEQAEwkelekeEEREEDERILEYLKEKAEREEEREAEREEIEEEKE 183

                          170
                   ....*....|....*..
4GNK_B        1167 pKLLAQLAQECQEQRAR 1183
Cdd:pfam13868  184 -REIARLRAQQEKAQDE 199

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