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Conserved domains on  [gi|1057503142|ref|NP_001317195|]
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grancalcin isoform a [Homo sapiens]

Protein Classification

EFh_PEF_grancalcin domain-containing protein( domain architecture ID 11610867)

EFh_PEF_grancalcin domain-containing protein

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
EFh_PEF_grancalcin cd16186
Penta-EF hand, calcium binding motifs, found in grancalcin; Grancalcin (GCA) is a cytosolic ...
 68-232 5.66e-128

Penta-EF hand, calcium binding motifs, found in grancalcin; Grancalcin (GCA) is a cytosolic Ca2+-binding protein specifically expressed in neutrophils and monocytes/macrophages. It displays a Ca2+-dependent translocation to granules and plasma membrane upon neutrophil activation, suggesting roles in granule-membrane fusion and degranulation of neutrophils. It may also play a role in the regulation of vesicle/granule exocytosis through the reversible binding of secretory vesicles and plasma membranes upon the presence of calcium. Moreover, GCA is involved in inflammation, as well as in the process of adhesion of neutrophils to fibronectin. It plays a key role in leukocyte-specific functions that are responsible for host defense, and affects the function of integrin receptors on immune cells through binding to L-plastin in the absence of calcium. Furthermore, GCA can strongly interact with sorcin to form a heterodimer, and further modulate the function of sorcin. GCA exists as homodimers in solution. It contains five EF-hand motifs attached to an N-terminal region of an approximately 50 residue-long segment rich in glycines and prolines. GCA binds two Ca2+ ions through its EF1 and EF3 hands.


:

Pssm-ID: 320061 [Multi-domain]  Cd Length: 165  Bit Score: 358.41  E-value: 5.66e-128
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142  68 SVYTYFSAVAGQDGEVDAEELQRCLTQSGINGTYSPFSLETCRIMIAMLDRDHTGKMGFNAFKELWAALNAWKENFMTVD 147
Cdd:cd16186     1 PMWGYFSAVAGQDGEVDAEELQRCLTQSGINGTYTPFSLETCRIMIAMLDRDHTGKMGFNEFKELWAALNAWKQNFMTVD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142 148 QDGSGTVEHHELRQAIGLMGYRLSPQTLTTIVKRYSKNGRIFFDDYVACCVKLRALTDFFRKRDHLQQGSANFIYDDFLQ 227
Cdd:cd16186    81 QDRSGTVEPHELRQAIGAMGYRLSPQTLTTIVKRYSKNGRIYFDDYVACCVKLRALTDFFRRRDHMQQGSVNFIYDDFLQ 160


                  ....*
gi 1057503142 228 GTMAI 232
Cdd:cd16186   161 CTMAI 165
 
Name Accession Description Interval E-value
EFh_PEF_grancalcin cd16186
Penta-EF hand, calcium binding motifs, found in grancalcin; Grancalcin (GCA) is a cytosolic ...
 68-232 5.66e-128

Penta-EF hand, calcium binding motifs, found in grancalcin; Grancalcin (GCA) is a cytosolic Ca2+-binding protein specifically expressed in neutrophils and monocytes/macrophages. It displays a Ca2+-dependent translocation to granules and plasma membrane upon neutrophil activation, suggesting roles in granule-membrane fusion and degranulation of neutrophils. It may also play a role in the regulation of vesicle/granule exocytosis through the reversible binding of secretory vesicles and plasma membranes upon the presence of calcium. Moreover, GCA is involved in inflammation, as well as in the process of adhesion of neutrophils to fibronectin. It plays a key role in leukocyte-specific functions that are responsible for host defense, and affects the function of integrin receptors on immune cells through binding to L-plastin in the absence of calcium. Furthermore, GCA can strongly interact with sorcin to form a heterodimer, and further modulate the function of sorcin. GCA exists as homodimers in solution. It contains five EF-hand motifs attached to an N-terminal region of an approximately 50 residue-long segment rich in glycines and prolines. GCA binds two Ca2+ ions through its EF1 and EF3 hands.


Pssm-ID: 320061 [Multi-domain]  Cd Length: 165  Bit Score: 358.41  E-value: 5.66e-128
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142  68 SVYTYFSAVAGQDGEVDAEELQRCLTQSGINGTYSPFSLETCRIMIAMLDRDHTGKMGFNAFKELWAALNAWKENFMTVD 147
Cdd:cd16186     1 PMWGYFSAVAGQDGEVDAEELQRCLTQSGINGTYTPFSLETCRIMIAMLDRDHTGKMGFNEFKELWAALNAWKQNFMTVD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142 148 QDGSGTVEHHELRQAIGLMGYRLSPQTLTTIVKRYSKNGRIFFDDYVACCVKLRALTDFFRKRDHLQQGSANFIYDDFLQ 227
Cdd:cd16186    81 QDRSGTVEPHELRQAIGAMGYRLSPQTLTTIVKRYSKNGRIYFDDYVACCVKLRALTDFFRRRDHMQQGSVNFIYDDFLQ 160


                  ....*
gi 1057503142 228 GTMAI 232
Cdd:cd16186   161 CTMAI 165
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
80-208 4.32e-04

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 39.39  E-value: 4.32e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142  80 DGEVDAEELQRcltqsgingtyspFSLETCRIMIAMLDRDHTGKMGFNAFKELWAALNAW------KENFMTVDQDGSGT 153
Cdd:COG5126    19 DGVLERDDFEA-------------LFRRLWATLFSEADTDGDGRISREEFVAGMESLFEAtvepfaRAAFDLLDTDGDGK 85

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1057503142 154 VEHHELRQAIGlmGYRLSPQTLTTIVKRYSKN--GRIFFDDYVAccvklrALTDFFR 208
Cdd:COG5126    86 ISADEFRRLLT--ALGVSEEEADELFARLDTDgdGKISFEEFVA------AVRDYYT 134
PTZ00183 PTZ00183
centrin; Provisional
 81-194 1.22e-03

centrin; Provisional


Pssm-ID: 185503 [Multi-domain]  Cd Length: 158  Bit Score: 38.13  E-value: 1.22e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142  81 GEVDAEELQRCLTQSGINgtyspFSLETCRIMIAMLDRDHTGKMGFNAFKELWAALNAWKEN-------FMTVDQDGSGT 153
Cdd:PTZ00183   32 GTIDPKELKVAMRSLGFE-----PKKEEIKQMIADVDKDGSGKIDFEEFLDIMTKKLGERDPreeilkaFRLFDDDKTGK 106

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1057503142 154 VEHHELRQAIGLMGYRLSPQTLTTIVKRYSKN--GRIFFDDYV 194
Cdd:PTZ00183  107 ISLKNLKRVAKELGETITDEELQEMIDEADRNgdGEISEEEFY 149
 
Name Accession Description Interval E-value
EFh_PEF_grancalcin cd16186
Penta-EF hand, calcium binding motifs, found in grancalcin; Grancalcin (GCA) is a cytosolic ...
 68-232 5.66e-128

Penta-EF hand, calcium binding motifs, found in grancalcin; Grancalcin (GCA) is a cytosolic Ca2+-binding protein specifically expressed in neutrophils and monocytes/macrophages. It displays a Ca2+-dependent translocation to granules and plasma membrane upon neutrophil activation, suggesting roles in granule-membrane fusion and degranulation of neutrophils. It may also play a role in the regulation of vesicle/granule exocytosis through the reversible binding of secretory vesicles and plasma membranes upon the presence of calcium. Moreover, GCA is involved in inflammation, as well as in the process of adhesion of neutrophils to fibronectin. It plays a key role in leukocyte-specific functions that are responsible for host defense, and affects the function of integrin receptors on immune cells through binding to L-plastin in the absence of calcium. Furthermore, GCA can strongly interact with sorcin to form a heterodimer, and further modulate the function of sorcin. GCA exists as homodimers in solution. It contains five EF-hand motifs attached to an N-terminal region of an approximately 50 residue-long segment rich in glycines and prolines. GCA binds two Ca2+ ions through its EF1 and EF3 hands.


Pssm-ID: 320061 [Multi-domain]  Cd Length: 165  Bit Score: 358.41  E-value: 5.66e-128
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142  68 SVYTYFSAVAGQDGEVDAEELQRCLTQSGINGTYSPFSLETCRIMIAMLDRDHTGKMGFNAFKELWAALNAWKENFMTVD 147
Cdd:cd16186     1 PMWGYFSAVAGQDGEVDAEELQRCLTQSGINGTYTPFSLETCRIMIAMLDRDHTGKMGFNEFKELWAALNAWKQNFMTVD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142 148 QDGSGTVEHHELRQAIGLMGYRLSPQTLTTIVKRYSKNGRIFFDDYVACCVKLRALTDFFRKRDHLQQGSANFIYDDFLQ 227
Cdd:cd16186    81 QDRSGTVEPHELRQAIGAMGYRLSPQTLTTIVKRYSKNGRIYFDDYVACCVKLRALTDFFRRRDHMQQGSVNFIYDDFLQ 160


                  ....*
gi 1057503142 228 GTMAI 232
Cdd:cd16186   161 CTMAI 165
EFh_PEF_Group_II_sorcin_like cd16181
Penta-EF hand, calcium binding motifs, found in sorcin, grancalcin, and similar proteins; The ...
 68-232 3.42e-121

Penta-EF hand, calcium binding motifs, found in sorcin, grancalcin, and similar proteins; The family corresponds to the second group of penta-EF hand (PEF) proteins that includes sorcin, grancalcin, and similar proteins. Sorcin, also termed 22 kDa Ca2+-binding protein, CP-22, or V19, is a soluble resistance-related calcium-binding protein that is expressed in normal mammalian tissues, such as the liver, lungs and heart. It contains a flexible glycine and proline-rich N-terminal extension and five EF-hand motifs that associate with membranes in a calcium-dependent manner. It may harbor three potential Ca2+ binding sites through its EF1, EF2 and EF3 hands. However, binding of only two Ca2+/monomer suffices to trigger the conformational change that exposes hydrophobic regions and leads to interaction with the respective targets. Sorcin forms homodimers through the association of the unpaired EF5 hand. Among the PEF proteins, sorcin is unique in that it contains potential phosphorylation sites by cAMP-dependent protein kinase (PKA), and it can form a tetramer at slightly acid pH values although remaining a stable dimer at neutral pH. Grancalcin (GCA) is a cytosolic Ca2+-binding protein specifically expressed in neutrophils and monocytes/macrophages. It can strongly interact with sorcin to form a heterodimer and further modulate the function of sorcin. GCA exists as homodimers in solution. It contains five EF-hand motifs attached to an N-terminal region of an approximately 50 residue-long segment rich in glycines and prolines. In contrast with sorcin, GCA binds two Ca2+ ions through its EF1 and EF3 hands.


Pssm-ID: 320056 [Multi-domain]  Cd Length: 165  Bit Score: 341.27  E-value: 3.42e-121
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142  68 SVYTYFSAVAGQDGEVDAEELQRCLTQSGINGTYSPFSLETCRIMIAMLDRDHTGKMGFNAFKELWAALNAWKENFMTVD 147
Cdd:cd16181     1 PLYGYFSAVAGQDGQIDADELQRCLTQSGISGNYQPFSLETCRLMIAMLDRDHSGKMGFNEFKELWAALNQWKTTFMQYD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142 148 QDGSGTVEHHELRQAIGLMGYRLSPQTLTTIVKRYSKNGRIFFDDYVACCVKLRALTDFFRKRDHLQQGSANFIYDDFLQ 227
Cdd:cd16181    81 RDRSGTVEPQELQQAIRSFGYNLSPQALNVIVKRYSKNGRITFDDFVACAVRLRALTDRFRRRDTQQNGTATFQYDDFIQ 160


                  ....*
gi 1057503142 228 GTMAI 232
Cdd:cd16181   161 VTMSI 165
EFh_PEF_sorcin cd16187
Penta-EF hand, calcium binding motifs, found in sorcin; Sorcin, also termed 22 kDa Ca2 ...
 69-232 9.82e-95

Penta-EF hand, calcium binding motifs, found in sorcin; Sorcin, also termed 22 kDa Ca2+-binding protein, CP-22, or V19, is a soluble resistance-related calcium-binding protein that is expressed in normal mammalian tissues, such as the liver, lungs and heart. The up-regulation of sorcin is correlated with a number of cancer types, including colorectal, gastric and breast cancer. It may represent a therapeutic target for reversing tumor multidrug resistance (MDR). Sorcin participates in the regulation of calcium homeostasis in cells and is necessary for the activation of mitosis and cytokinesis. It enhances metastasis and promotes epithelial-to-mesenchymal transition of colorectal cancer. Moreover, sorcin has been implicated in the regulation of intracellular Ca2+ cycling and cardiac excitation-contraction coupling. It displays the anti-apoptotic properties via the modulation of mitochondrial Ca2+ handling in cardiac myocytes. It can target and activate the sarcolemmal Na+/Ca2+ exchanger (NCX1) in cardiac muscle. Meanwhile, sorcin modulates cardiac L-type Ca2+ current by functional interaction with the alpha1C subunit. It also associates with calcium/calmodulin-dependent protein kinase IIdeltaC (CaMKIIdelta(C)) and further modulates ryanodine receptor (RyR) function in cardiac myocytes. Furthermore, sorcin may act as a Ca2+ sensor for glucose-induced nuclear translocation and the activation of carbohydrate-responsive element-binding protein (ChREBP)-dependent genes. As a mitochondrial chaperone TRAP1 interactor, sorcin involves in mitochondrial metabolism through the TRAP1 pathway. In addition, sorcin may regulate the inhibition of type I interferon response in cells through interacting with foot-and-mouth disease virus (FMDV) VP1. Sorcin contains a flexible glycine and proline-rich N-terminal extension and five EF-hand motifs that associate with membranes in a calcium-dependent manner. It may harbor three potential Ca2+ binding sites through its EF1, EF2 and EF3 hands. However, binding of only two Ca2+/monomer suffices to trigger the conformational change that exposes hydrophobic regions and leads to interaction with the respective targets. Sorcin forms homodimers through the association of the unpaired EF5 hand. Among the PEF proteins, sorcin is unique in that it contains potential phosphorylation sites by cAMP-dependent protein kinase (PKA), and it can form a tetramer at slightly acid pH values although remaining a stable dimer at neutral pH.


Pssm-ID: 320062 [Multi-domain]  Cd Length: 165  Bit Score: 274.48  E-value: 9.82e-95
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142  69 VYTYFSAVAGQDGEVDAEELQRCLTQSGINGTYSPFSLETCRIMIAMLDRDHTGKMGFNAFKELWAALNAWKENFMTVDQ 148
Cdd:cd16187     2 LYGYFAAVAGQDGQIDADELQRCLTQSGIAGGYKPFNLETCRLMISMLDRDMSGTMGFNEFKELWAVLNGWRQHFISFDS 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142 149 DGSGTVEHHELRQAIGLMGYRLSPQTLTTIVKRYSKNGRIFFDDYVACCVKLRALTDFFRKRDHLQQGSANFIYDDFLQG 228
Cdd:cd16187    82 DRSGTVDPQELQKALTTMGFRLSPQAVNSIAKRYSTNGKITFDDYIACCVKLRALTDSFRRRDTSQQGVVNFPYDDFIQC 161


                  ....
gi 1057503142 229 TMAI 232
Cdd:cd16187   162 VMSI 165
EFh_PEF cd15897
The penta-EF hand (PEF) family; The penta-EF hand (PEF) family contains a group of five ...
 68-231 5.73e-92

The penta-EF hand (PEF) family; The penta-EF hand (PEF) family contains a group of five EF-hand calcium-binding proteins, including several classical calpain large catalytic subunits (CAPN1, 2, 3, 8, 9, 11, 12, 13, 14), two calpain small subunits (CAPNS1 and CAPNS2), as well as non-calpain PEF proteins, ALG-2 (apoptosis-linked gene 2, also termed programmed cell death protein 6, PDCD6), peflin, sorcin, and grancalcin. Based on the sequence similarity of EF1 hand, ALG-2 and peflin have been classified into group I PEF proteins. Calcium-dependent protease calpain subfamily members, sorcin and grancalcin, are group II PEF proteins. Calpains (EC 3.4.22.17) are calcium-activated intracellular cysteine proteases that play important roles in the degradation or functional modulation in a variety of substrates. They have been implicated in a number of physiological processes such as cell cycle progression, remodeling of cytoskeletal-cell membrane attachments, signal transduction, gene expression and apoptosis. ALG-2 is a pro-apoptotic factor that forms a homodimer in the cell or a heterodimer with its closest paralog peflin through their EF5s. Peflin is a 30-kD PEF protein with a longer N-terminal hydrophobic domain than any other member of the PEF family, and it contains nine nonapeptide (A/PPGGPYGGP) repeats. It exists only as a heterodimer with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+. ALG-2 interacts with various proteins in a Ca2+-dependent manner. Sorcin (for soluble resistance-related calcium binding protein) is a soluble resistance-related calcium-binding protein that participates in the regulation of calcium homeostasis in cells. Grancalcin is a cytosolic Ca2+-binding protein specifically expressed in neutrophils and monocytes/macrophages. It plays a key role in leukocyte-specific functions that are responsible for host defense. Grancalcin can form a heterodimer together with sorcin. Members in this family contain five EF-hand motifs attached to an N-terminal region of variable length containing one or more short Gly/Pro-rich sequences. These proteins form homodimers or heterodimers through pairing between the 5th EF-hands from the two molecules. Unlike calmodulin, the PEF domains do not undergo major conformational changes upon binding Ca2+.


Pssm-ID: 320054 [Multi-domain]  Cd Length: 165  Bit Score: 267.37  E-value: 5.73e-92
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142  68 SVYTYFSAVAGQDGEVDAEELQRCLTQSGINGTYSPFSLETCRIMIAMLDRDHTGKMGFNAFKELWAALNAWKENFMTVD 147
Cdd:cd15897     1 QLRNVFQAVAGDDGEISATELQQALSNVGWTHFDLGFSLETCRSMIAMMDRDHSGKLNFSEFKGLWNYIKAWQEIFRTYD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142 148 QDGSGTVEHHELRQAIGLMGYRLSPQTLTTIVKRYSK-NGRIFFDDYVACCVKLRALTDFFRKRDHLQQGSANFIYDDFL 226
Cdd:cd15897    81 TDGSGTIDSNELRQALSGAGYRLSEQTYDIIIRRYDRgRGNIDFDDFIQCCVRLQRLTDAFRRYDKDQDGQIQVNYDEFL 160


                  ....*
gi 1057503142 227 QGTMA 231
Cdd:cd15897   161 QGTMS 165
EFh_PEF_CalpA_B cd16196
Penta-EF hand, calcium binding motifs, found in Drosophila melanogaster calpain-A (CalpA), ...
 73-230 1.40e-55

Penta-EF hand, calcium binding motifs, found in Drosophila melanogaster calpain-A (CalpA), calpain-B (CalpB), and similar proteins; The family contains two calpains that have been found in Drosophila, CalpA and CalpB. CalpA, also termed calcium-activated neutral proteinase A (CANP A), or calpain-A catalytic subunit, is a Drosophila calpain homolog specifically expressed in a few neurons in the central nervous system, in scattered endocrine cells in the midgut, and in blood cells. CalpB, also termed calcium-activated neutral proteinase B (CANP B), contains calpain-B catalytic subunit 1 and calpain-B catalytic subunit 2. Both CalpA and CalpB are closely related to that of vertebrate calpains, and they share similar domain architecture, which consists of four domains: the N-terminal domain I, the catalytic domain II carrying the three active site residues, Cys, His and Asn, the Ca2+-regulated phospholipid-binding domain III, and penta-EF-hand Ca2+-binding domain IV. Besides, CalpA and CalpB display some distinguishing structural features that are not found in mammalian typical calpains. CalpA harbors a 76 amino acid long hydrophobic stretch inserted in domain IV, which may be involved in membrane attachment of this enzyme. CalpB has an unusually long N-terminal tail of 224 amino acids, which belongs to the class of intrinsically unstructured proteins (IUP) and may become ordered upon binding to target protein(s). Moreover, they do not need small regulatory subunits for their catalytic activity, and their proteolytic function is not regulated by an intrinsic inhibitor as the Drosophila genome contains neither regulatory subunit nor calpastatin orthologs. As a result, they may exist as a monomer or perhaps as a homo- or heterodimer together with a second large subunit. Furthermore, both CalpA and CalpB are dispensable for viability and fertility and do not share vital functions during Drosophila development. Phosphatidylinositol 4,5-diphosphate, phosphatidylinositol 4-monophosphate, phosphatidylinositol, and phosphatidic acid can stimulate the activity and the rate of activation of CalpA, but not CalpB. Calpain A modulates Toll responses by limited Cactus/IkappaB proteolysis. CalpB directly interacts with talin, an important component of the focal adhesion complex, and functions as an important modulator in border cell migration within egg chambers, which may act via the digestion of talin. CalpB can be phosphorylated by cAMP-dependent protein kinase (protein kinase A, PKA; EC 2.7.11.11) at Ser240 and Ser845, as well as by mitogen-activated protein kinase (ERK1 and ERK2; EC 2.7.11.24) at Thr747. The activation of the ERK pathway by extracellular signals results in the phosphorylation and activation of calpain B. In Schneider cells (S2), calpain B was mainly in the cytoplasm and upon a rise in Ca2+ the enzyme adhered to intracellular membranes.


Pssm-ID: 320071 [Multi-domain]  Cd Length: 167  Bit Score: 175.08  E-value: 1.40e-55
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142  73 FSAVAGQDGEVDAEELQRCLTQSGING-TYSPFSLETCRIMIAMLDRDHTGKMGFNAFKELWAALNAWKENFMTVDQDGS 151
Cdd:cd16196     6 FDKIAGEDMEIDAYELQDILNTAFKKDfPFDGFSLDACRSMVAMMDVDRSGKLGFEEFKKLWEDLRSWKRVFKLFDTDGS 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142 152 GTVEHHELRQAIGLMGYRLSPQTLTTIVKRYS-KNGRIFFDDYVACCVKLRALTDFFRKRDHLQQGSANFIYDDFLQGTM 230
Cdd:cd16196    86 GSFSSFELRNALNSAGFRLSNATLNALVLRYSnKDGRISFDDFIMCAVKLKTMFEIFKEKDPRGGGRATFNLDEFLESTM 165
EFh_PEF_Group_I cd16180
Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds ...
 81-232 8.51e-53

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


Pssm-ID: 320055 [Multi-domain]  Cd Length: 164  Bit Score: 167.71  E-value: 8.51e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142  81 GEVDAEELQRCLtqsgINGTYSPFSLETCRIMIAMLDRDHTGKMGFNAFKELWAALNAWKENFMTVDQDGSGTVEHHELR 160
Cdd:cd16180    15 GRISAKELQRAL----SNGDWTPFSIETVRLMINMFDRDRSGTINFDEFVGLWKYIQDWRRLFRRFDRDRSGSIDFNELQ 90

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1057503142 161 QAIGLMGYRLSPQTLTTIVKRYSKNGR--IFFDDYVACCVKLRALTDFFRKRDHLQQGSANFIYDDFLQGTMAI 232
Cdd:cd16180    91 NALSSFGYRLSPQFVQLLVRKFDRRRRgsISFDDFVEACVTLKRLTDAFRKYDTNRTGYATISYEDFLTMVLSI 164
EFh_PEF_peflin cd16184
EF-hand, calcium binding motif, found in peflin and similar proteins; Peflin, also termed ...
 69-232 5.09e-51

EF-hand, calcium binding motif, found in peflin and similar proteins; Peflin, also termed penta-EF hand (PEF) protein with a long N-terminal hydrophobic domain, or penta-EF hand domain-containing protein 1, is a ubiquitously expressed 30-kD PEF protein containing five EF-hand motifs in its C-terminal domain and a longer N-terminal hydrophobic domain (NHB domain) than any other member of the PEF family. The NHB domain harbors nine repeats of a nonapeptide (A/PPGGPYGGP). Peflin may modulate the function of ALG-2 in Ca2+ signaling. It exists only as a heterodimer with ALG-2, and binds two Ca2+ ions through its EF1 and EF3 hands. Its additional EF5 hand is unpaired and does not bind Ca2+ ion but mediates the heterodimerization with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+. In lower vertebrates, peflin may interact with transient receptor potential N (TRPN1), suggesting a potential role of peflin in fast transducer channel adaptation.


Pssm-ID: 320059 [Multi-domain]  Cd Length: 165  Bit Score: 163.20  E-value: 5.09e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142  69 VYTYFSAV-AGQDGEVDAEELQRCLTqsgiNGTYSPFSLETCRIMIAMLDRDHTGKMGFNAFKELWAALNAWKENFMTVD 147
Cdd:cd16184     2 VQQWFQAVdRDRSGKISAKELQQALV----NGNWSHFNDETCRLMIGMFDKDKSGTIDIYEFQALWNYIQQWKQVFQQFD 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142 148 QDGSGTVEHHELRQAIGLMGYRLSPQTLTTIVKRYS--KNGRIFFDDYVACCVKLRALTDFFRKRDHLQQGSANFIYDDF 225
Cdd:cd16184    78 RDRSGSIDENELHQALSQMGYRLSPQFVQFLVSKYDprARRSLTLDQFIQVCVQLQSLTDAFRQRDTQMTGTITISYEDF 157


                  ....*..
gi 1057503142 226 LqgTMAI 232
Cdd:cd16184   158 L--TMAL 162
EFh_PEF_Group_II_CAPN_like cd16182
Penta-EF hand, calcium binding motifs, found in PEF calpain family; The PEF calpain family ...
 73-230 6.08e-48

Penta-EF hand, calcium binding motifs, found in PEF calpain family; The PEF calpain family belongs to the second group of penta-EF hand (PEF) proteins. It includes classical (also called conventional or typical) calpain (referring to a calcium-dependent papain-like enzymes, EC 3.4.22.17) large catalytic subunits (CAPN1, 2, 3, 8, 9, 11, 12, 13, 14) and two calpain small subunits (CAPNS1 and CAPNS2), which are largely confined to animals (metazoans). These PEF-containing are nonlysosomal intracellular calcium-activated intracellular cysteine proteases that play important roles in the degradation or functional modulation in a variety of substrates in response to calcium signalling. The classical mu- and m-calpains are heterodimers consisting of homologous but a distinct (large) L-subunit/chain (CAPN1 or CAPN2) and a common (small) S-subunit/chain (CAPNS1 or CAPNS2). These L-subunits (CAPN1 and CAPN2) and S-subunit CAPNS1 are ubiquitously found in all tissues. Other calpains likely consist of an isolated L-subunit/chain alone. Many of them, such as CAPNS2, CAPN3 (in skeletal muscle, or lens), CAPN8 (in stomach), CAPN9 (in digestive tracts), CAPN11 (in testis), CAPN12 (in follicles), are tissue-specific and have specific functions in distinct organs. The L-subunits of similar structure (called CALPA and B) also have been found in Drosophila melanogaster. The S-subunit seems to have a chaperone-like function for proper folding of the L-subunit. The catalytic L-subunits contain a short N-terminal anchor helix, followed by a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain. The S-subunits only have the PEF domain following an N-terminal Gly-rich hydrophobic domain. The calpains undergo a rearrangement of the protein backbone upon Ca2+-binding.


Pssm-ID: 320057 [Multi-domain]  Cd Length: 167  Bit Score: 155.46  E-value: 6.08e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142  73 FSAVAGQDGEVDAEELQRCLTQSGINGTYSP--FSLETCRIMIAMLDRDHTGKMGFNAFKELWAALNAWKENFMTVDQDG 150
Cdd:cd16182     6 FEKLAGEDEEIDAVELQKLLNASLLKDMPKFdgFSLETCRSLIALMDTNGSGRLDLEEFKTLWSDLKKWQAIFKKFDTDR 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142 151 SGTVEHHELRQAIGLMGYRLSPQTLTTIVKRYS-KNGRIFFDDYVACCVKLRALTDFFRKRDHLQQGSANFIYDDFLQGT 229
Cdd:cd16182    86 SGTLSSYELRKALESAGFHLSNKVLQALVLRYAdSTGRITFEDFVSCLVRLKTAFETFSALDKKNEGVIPLTLEEWLLLT 165


                  .
gi 1057503142 230 M 230
Cdd:cd16182   166 L 166
EFh_PEF_ALG-2 cd16183
EF-hand, calcium binding motif, found in apoptosis-linked gene 2 protein (ALG-2) and similar ...
 69-227 1.32e-47

EF-hand, calcium binding motif, found in apoptosis-linked gene 2 protein (ALG-2) and similar proteins; ALG-2, also termed programmed cell death protein 6 (PDCD6), or probable calcium-binding protein ALG-2, is one of the prototypic members of the penta EF-hand protein family. It is a widely expressed calcium-binding modulator protein associated with cell proliferation and death, as well as cell survival. ALG-2 acts as a pro-apoptotic factor participating in T cell receptor-, Fas-, and glucocorticoid-induced programmed cell death, and also serves as a useful molecular marker for the prognosis of cancers. Moreover, ALG-2 functions as a calcium ion sensor at endoplasmic reticulum (ER) exit sites, and modulates ER-stress-stimulated cell death and neuronal apoptosis during organ formation. Furthermore, ALG-2 can mediate the pro-apoptotic activity of cisplatin or tumor necrosis factor alpha (TNFalpha) through the down-regulation of nuclear factor-kappaB (NF-kappaB) expression. It also inhibits angiogenesis through PI3K/mTOR/p70S6K pathway by interacting of vascular endothelial growth factor receptor-2 (VEGFR-2). In addition, nuclear ALG-2 may participate in the post-transcriptional regulation of Inositol Trisphosphate Receptor Type 1 (IP3R1) pre-mRNA at least in part by interacting with CHERP (Ca2+ homeostasis endoplasmic reticulum protein) calcium-dependently. ALG-2 contains five serially repeated EF-hand motifs and interacts with various proteins, including ALG-2-interacting protein X (Alix), Fas, annexin XI, death-associated protein kinase 1 (DAPk1), Tumor susceptibility gene 101 (TSG101), Sec31A, phospholipid scramblase 3 (PLSCR3), the P-body component PATL1, and endosomal sorting complex required for transport (ESCRT)-III-related protein IST1, in a calcium-dependent manner. It forms a homodimer in the cell or a heterodimer with its closest paralog peflin. Among the PEF proteins, ALG-2 can bind three Ca2+ ions through its EF1, EF3, and EF5 hands, where it is unique in that its EF5 hand binds Ca2+ ion in a canonical coordination.


Pssm-ID: 320058 [Multi-domain]  Cd Length: 165  Bit Score: 154.72  E-value: 1.32e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142  69 VYTYFSAV-AGQDGEVDAEELQRCLtqsgINGTYSPFSLETCRIMIAMLDRDHTGKMGFNAFKELWAALNAWKENFMTVD 147
Cdd:cd16183     2 LWNVFQRVdKDRSGQISATELQQAL----SNGTWTPFNPETVRLMIGMFDRDNSGTINFQEFAALWKYITDWQNCFRSFD 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142 148 QDGSGTVEHHELRQAIGLMGYRLSPQTLTTIVKRYSKNGR--IFFDDYVACCVKLRALTDFFRKRDHLQQGSANFIYDDF 225
Cdd:cd16183    78 RDNSGNIDKNELKQALTSFGYRLSDQFYDILVRKFDRQGRgtIAFDDFIQCCVVLQTLTDSFRRYDTDQDGWIQISYEQF 157


                  ..
gi 1057503142 226 LQ 227
Cdd:cd16183   158 LE 159
EFh_PEF_CAPN11 cd16193
Penta-EF hand, calcium binding motifs, found in calpain-11 (CAPN11); CAPN11, also termed ...
 73-230 2.20e-31

Penta-EF hand, calcium binding motifs, found in calpain-11 (CAPN11); CAPN11, also termed calcium-activated neutral proteinase 11 (CANP 11), is a mammalian orthologue of micro/m calpain. It is one of the calpain large subunits that appears to be exclusively expressed in certain cells of the testis. It may be involved in regulating calcium-dependent signal transduction events during meiosis and sperm functional processes. CAPN11 contains a short N-terminal anchor helix, followed by a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain.


Pssm-ID: 320068 [Multi-domain]  Cd Length: 169  Bit Score: 113.09  E-value: 2.20e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142  73 FSAVAGQDGEVDAEELQRCLTQSGI---NGTYSPFSLETCRIMIAMLDRDHTGKMGFNAFKELWAALNAWKENFMTVDQD 149
Cdd:cd16193     6 FKIVANEDKEVDMYELQKLLNRMAIkfkSFKTKGFSLDVCRRMINLMDKDGSGKLGLHEFKILWKKIKKWMEIFKECDQD 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142 150 GSGTVEHHELRQAIGLMGYRLSPQTLTTIVKRYSKNGRIF-FDDYVACCVKLRALTDFFRKRDHLQQGSANFIYDDFLQG 228
Cdd:cd16193    86 RSGNLNSYEMRLAIEKAGIKMNNRVTEVVVARYADDNMIVdFDSFINCFLRLKAMFAFFLSMDTKKTGSICLSINQWLQI 165


                  ..
gi 1057503142 229 TM 230
Cdd:cd16193   166 TM 167
EFh_PEF_CAPN9 cd16192
Penta-EF hand, calcium binding motifs, found in calpain-9 (CAPN9); CAPN9, also termed ...
 71-232 5.64e-31

Penta-EF hand, calcium binding motifs, found in calpain-9 (CAPN9); CAPN9, also termed digestive tract-specific calpain, or new calpain 4 (nCL-4), or protein CG36, is a calpain large subunit predominantly expressed in gastrointestinal tract. It plays a physiological role in the suppression of tumorigenesis. It acts as an important biomolecule link for the regression of colorectal cancer via intracellular calcium homeostasis. CAPN9 may also play a critical role in lumen formation. Moreover, CAPN9, together with CAPN8, forms an active protease complex, G-calpain, in which both proteins are essential for stability and activity. The G-Calpain has been implicated in gastric mucosal defense. Furthermore, down-regulation of calpain 9 has been linked to hypertensive heart and kidney disease in salt-sensitive Dahl rats. CAPN9 contains a short N-terminal anchor helix, followed by a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain.


Pssm-ID: 320067 [Multi-domain]  Cd Length: 169  Bit Score: 112.20  E-value: 5.64e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142  71 TYFSAVAGQDGEVDAEELQRCLT---QSGINGTYSPFSLETCRIMIAMLDRDHTGKMGFNAFKELWAALNAWKENFMTVD 147
Cdd:cd16192     4 KLFEQISGEDLEISAEELQYVLNavlARTKEIKFKKLSLLSCKNIISLMDTSGNGKLGFSEFKVFWDKLKKWIGLFLKYD 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142 148 QDGSGTVEHHELRQAIGLMGYRLSPQTLTTIVKRYSKNG-RIFFDDYVACCVKLRALTDFFRKRDHLQQGSANFIYDDFL 226
Cdd:cd16192    84 ADRSGTMSSYELRSALKAAGFQLNNQLLQLIVLRYADDYlQIDFDDFLNCLVRLENSFRVFQALDTKNTGEISLNMLEFI 163


                  ....*.
gi 1057503142 227 QGTMAI 232
Cdd:cd16192   164 LLTMNI 169
EFh_PEF_CPNS1_2 cd16188
Penta-EF hand, calcium binding motifs, found in calcium-dependent protease small subunit ...
 73-230 1.18e-29

Penta-EF hand, calcium binding motifs, found in calcium-dependent protease small subunit CAPNS1 and CAPNS2; CAPNS1, also termed calpain small subunit 1 (CSS1), or calcium-activated neutral proteinase small subunit (CANP small subunit), or calcium-dependent protease small subunit (CDPS), or calpain regulatory subunit, is a common 28-kDa regulatory calpain subunit encoded by the calpain small 1 (Capns1, also known as Capn4) gene. It acts as a binding partner to form a heterodimer with the 80 kDa calpain large catalytic subunit and is required in maintaining the activity of calpain. CAPNS1 plays a significant role in tumor progression of human cancer, and functions as a potential therapeutic target in human hepatocellular carcinoma (HCC), nasopharyngeal carcinoma (NPC), glioma, and clear cell renal cell carcinoma (ccRCC). It may be involved in regulating migration and cell survival through binding to the SH3 domain of Ras GTPase-activating protein (RasGAP). It may also modulate Akt/FoxO3A signaling and apoptosis through PP2A. CAPNS1 contains an N-terminal glycine rich domain and a C-terminal PEF-hand domain. CAPNS2, also termed calpain small subunit 2 (CSS2), is a novel tissue-specific 30 kDa calpain small subunit that lacks two oligo-Gly stretches characteristic of the N-terminal Gly-rich domain of CAPNS1. CAPNS2 acts as a chaperone for the calpain large subunit, and appears to be the functional equivalent of CAPNS1. However, CAPNS2 binds the large subunit much more weakly than CAPNS1 and it does not undergo the autolytic conversion typical of CAPNS1.


Pssm-ID: 320063 [Multi-domain]  Cd Length: 169  Bit Score: 108.68  E-value: 1.18e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142  73 FSAVAGQDGEVDAEEL----QRCLTQSGINGTySPFSLETCRIMIAMLDRDHTGKMGFNAFKELWAALNAWKENFMTVDQ 148
Cdd:cd16188     6 FVQLAGDDMEVSATELmnilNKVVTRHPDLKT-DGFGIDTCRSMVAVMDSDTTGKLGFEEFKYLWNNIKKWQGIYKQFDT 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142 149 DGSGTVEHHELRQAIGLMGYRLSPQTLTTIVKRYS-KNGRIFFDDYVACCVKLRALTDFFRKRDHLQQGSANFIYDDFLQ 227
Cdd:cd16188    85 DRSGTIGSQELPGAFEAAGFHLNEQLYQMIIRRYSdEDGNMDFDNFISCLVRLDAMFRAFKSLDKDGTGQIQVNIQEWLQ 164


                  ...
gi 1057503142 228 GTM 230
Cdd:cd16188   165 LTM 167
EFh_PEF_CAPN13_14 cd16195
Penta-EF hand, calcium binding motifs, found in calpain-13 (CAPN13), calpain-14 (CAPN14), and ...
 77-211 6.88e-28

Penta-EF hand, calcium binding motifs, found in calpain-13 (CAPN13), calpain-14 (CAPN14), and similar proteins; CAPN13, also termed calcium-activated neutral proteinase 13 (CANP 13), a 63.6 kDa calpain large subunit that exhibits a restricted tissue distribution with low levels of expression detected only in human testis and lung. In calpain family, CAPN13 is most closely related to calpain-14 (CAPN14). CAPN14, also termed calcium-activated neutral proteinase 14 (CANP 14), is a 76.7 kDa calpain large subunit that is most highly expressed in the oesophagus. Its expression and calpain activity can be induced by IL-13. Both CAPN13 and CAPN14 contain a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain.


Pssm-ID: 320070 [Multi-domain]  Cd Length: 168  Bit Score: 103.82  E-value: 6.88e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142  77 AGQDGEVDAEELQRCLTQ---SGINGTYSPFSLETCRIMIAMLDRDHTGKMGFNAFKELWAALNAWKENFMTVDQDGSGT 153
Cdd:cd16195    10 ADQGGELDAEQLQKLLNEnllKGLAGSGGGFSLDACRSMVALMDLSVNGRLSLEEFSRLWKKLRKYKDIFQKADVSKSGF 89

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1057503142 154 VEHHELRQAIGLMGYRLSPQTLTTIVKRYS-KNGRIFFDDYVACCVKLRALTDFFRKRD 211
Cdd:cd16195    90 LSLSELRNAIQAAGIRVSDDLLNLMALRYGdSSGRISFESFICLMLRLECMAKIFRNLS 148
EFh_PEF_ALG-2_like cd16185
EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein ...
 73-232 1.62e-27

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


Pssm-ID: 320060 [Multi-domain]  Cd Length: 163  Bit Score: 102.68  E-value: 1.62e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142  73 FSAV-AGQDGEVDAEELQRCLTQSGINgtyspFSLETCRIMIAMLDRDHTGKMGFNAFKELWAALNAWKENFMTVDQDGS 151
Cdd:cd16185     6 FRAVdRDRSGSIDVNELQKALAGGGLL-----FSLATAEKLIRMFDRDGNGTIDFEEFAALHQFLSNMQNGFEQRDTSRS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142 152 GTVEHHELRQAIGLMGYRLSPQTLTTIVKRY--SKNGRIFFDDYVACCVKLRALTDFFRKRDHLQQGSANFIYDDFLQGT 229
Cdd:cd16185    81 GRLDANEVHEALAASGFQLDPPAFQALFRKFdpDRGGSLGFDDYIELCIFLASARNLFQAFDRQRTGRVTLDFNQFVYAA 160


                  ...
gi 1057503142 230 MAI 232
Cdd:cd16185   161 ANL 163
EFh_PEF_CAPN1_like cd16189
Penta-EF hand, calcium binding motifs, found in mu-type calpain (CAPN1), m-type calpain (CAPN2) ...
 73-227 2.16e-27

Penta-EF hand, calcium binding motifs, found in mu-type calpain (CAPN1), m-type calpain (CAPN2), and similar proteins; The family includes mu-type calpain (CAPN1) and m-type calpain (CAPN2), both of which are ubiquitously expressed 80-kDa Ca2+-dependent intracellular cysteine proteases that contain a short N-terminal anchor helix, followed by a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain. The catalytic subunit CAPN1 or CAPN2 in complex with a regulatory subunit encoded by CAPNS1 forms a mu- or m-calpain heterodimer, respectively.


Pssm-ID: 320064 [Multi-domain]  Cd Length: 168  Bit Score: 102.82  E-value: 2.16e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142  73 FSAVAGQDGEVDAEELQRCL-------TQSGINGtyspFSLETCRIMIAMLDRDHTGKMGFNAFKELWAALNAWKENFMT 145
Cdd:cd16189     6 FTQLAGEDSEISAFELQTILnkvlskrKDIKTDG----FSLETCRNMVNLLDKDGSGKLGLVEFQILWTKIQKYLKIYKK 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142 146 VDQDGSGTVEHHELRQAIGLMGYRLSPQTLTTIVKRYSKNGRIF-FDDYVACCVKLRALTDFFRKRDHLQQGsanFIYDD 224
Cdd:cd16189    82 FDTDGSGTMSSYEMRLALEEAGFKLNNQLHQVLVARYADQELTIdFDNFVRCLVRLELLFKIFKQLDKDNTG---TIELD 158


                  ...
gi 1057503142 225 FLQ 227
Cdd:cd16189   159 LIQ 161
EFh_PEF_CAPN2 cd16199
Penta-EF hand, calcium binding motifs, found in m-type calpain (CAPN2); CAPN2, also termed ...
 73-230 4.59e-27

Penta-EF hand, calcium binding motifs, found in m-type calpain (CAPN2); CAPN2, also termed millimolar-calpain (m-calpain), or calpain-2 catalytic subunit, or calcium-activated neutral proteinase 2 (CANP 2), or calpain large polypeptide L2, or calpain-2 large subunit, is a ubiquitously expressed 80-kDa Ca2+-dependent intracellular cysteine protease that contains a short N-terminal anchor helix, followed by a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain. The catalytic subunit CAPN2 in complex with a regulatory subunit encoded by CAPNS1 forms an m-calpain heterodimer. CAPN2 acts as the key protease responsible for N-methyl-d-aspartic acid (NMDA)-induced cytoplasmic polyadenylation element-binding protein 3 (CPEB3) degradation in neurons. It cleaves several components of the focal adhesion complex, such as FAK and talin, triggering disassembly of the complex at the rear of the cell. The stimulation of CAPN2 activity is required for Golgi antiapoptotic proteins (GAAPs) to promote cleavage of FA kinase (FAK), cell spreading, and enhanced migration. calpain 2 is also involved in the onset of glial differentiation. It regulates proliferation, survival, migration, and tumorigenesis of breast cancer cells through a PP2A-Akt-FoxO-p27(Kip1) signaling cascade. Its expression is associated with response to platinum based chemotherapy, progression-free and overall survival in ovarian cancer. Moreover, CAPN2 may play a role in fundamental mitotic functions, such as the maintenance of sister chromatid cohesion. The activation of CAPN2 plays an essential role in hippocampal synaptic plasticity and in learning and memory. In the eye, CAPN2, together with a lens-specific variant of CAPN3, is responsible for proteolytic cleavages of alpha and beta-crystallin. Overactivated alpha and beta-crystallin can lead to cataract formation. Sometimes, CAPN2 compensates for loss of CAPN1, and both calpain isoforms are involved in AngII-induced aortic aneurysm formation. The main phosphorylation sites in m-calpain are Ser50 and Ser369/Thr370.


Pssm-ID: 320074 [Multi-domain]  Cd Length: 168  Bit Score: 101.90  E-value: 4.59e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142  73 FSAVAGQDGEVDAEELQRCLTQ--SGINGTYSP-FSLETCRIMIAMLDRDHTGKMGFNAFKELWAALNAWKENFMTVDQD 149
Cdd:cd16199     6 FAQLAGEDAEISAFELQTILRRvlAKREDIKSDgFSIETCKIMVDMLDSDGSGKLGLKEFYILWTKIQKYQKIYREIDVD 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142 150 GSGTVEHHELRQAIGLMGYRLSPQTLTTIVKRYSKNGRIF-FDDYVACCVKLRALTDFFRKRDHLQQGSANFIYDDFLQG 228
Cdd:cd16199    86 RSGTMNSYEMRKALEEAGFKLPCQLHQVIVARFADDDLIIdFDNFVRCLVRLETLFKIFKQLDPENTGTIELDLISWLSF 165


                  ..
gi 1057503142 229 TM 230
Cdd:cd16199   166 SV 167
EFh_PEF_CAPN1 cd16198
Penta-EF hand, calcium binding motifs, found in mu-type calpain (CAPN1); CAPN1, also termed ...
 71-230 9.36e-27

Penta-EF hand, calcium binding motifs, found in mu-type calpain (CAPN1); CAPN1, also termed calpain-1 80-kDa catalytic subunit, or calpain-1 large subunit, or micromolar-calpain (muCANP), or calcium-activated neutral proteinase 1 (CANP 1), or cell proliferation-inducing gene 30 protein, is a ubiquitously expressed 80-kDa Ca2+-dependent intracellular cysteine protease that contains a short N-terminal anchor helix, followed by a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain. The catalytic subunit CAPN1 in complex with a regulatory subunit encoded by CAPNS1 forms a mu-calpain heterodimer. CAPN1 plays a central role in postmortem proteolysis and meat tenderization processes, as well as in regulation of proliferation and survival of skeletal satellite cells. It also acts as a novel regulator in IgE-mediated mast cell activation and could serve as a potential therapeutic target for the management of allergic inflammation. Moreover, CAPN1 is involved in neutrophil motility and functions as a potential target for intervention in inflammatory disease. It also facilitates age-associated aortic wall calcification and fibrosis through the regulation of matrix metalloproteinase 2 activity in vascular smooth muscle cells, and thus plays a role in hypertension and atherosclerosis. The proteolytic cleavage of beta-amyloid precursor protein and tau protein by CAPN1 may be involved in plaque formation. Furthermore, CAPN1 is activated in the brains of individuals with Alzheimer's disease. It is involved in the maintenance of a proliferative neural stem cell pool. The activation and macrophage inflammation of CAPN1 in hypercholesterolemic nephropathy is promoted by nicotinic acetylcholine receptor alpha1 (nAChRalpha1). In addition, CAPN1 displays a functional role in hemostasis, as well as in sickle cell disease.


Pssm-ID: 320073 [Multi-domain]  Cd Length: 169  Bit Score: 101.03  E-value: 9.36e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142  71 TYFSAVAGQDGEVDAEELQRCLTQS-------GINGtyspFSLETCRIMIAMLDRDHTGKMGFNAFKELWAALNAWKENF 143
Cdd:cd16198     4 NLFRQLAGEDMEISVFELKTILNRIiskhkdlRTDG----FSLESCRSMVNLMDKDGNGKLGLVEFNILWNKIRNYLTIF 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142 144 MTVDQDGSGTVEHHELRQAIGLMGYRLSPQTLTTIVKRYSK-NGRIFFDDYVACCVKLRALTDFFRKRDHLQQGSANFIY 222
Cdd:cd16198    80 RKFDLDKSGSMSAYEMRLALESAGFKLNNRLHQVIVARYADpNLAIDFDNFVCCLVRLETMFRFFKQLDTEETGTIEMDL 159


                  ....*...
gi 1057503142 223 DDFLQGTM 230
Cdd:cd16198   160 FEWLQLTM 167
EFh_PEF_CAPN3 cd16190
Calcium-activated neutral; CAPN3, also termed calcium-activated neutral proteinase 3 (CANP 3), ...
 73-230 1.33e-26

Calcium-activated neutral; CAPN3, also termed calcium-activated neutral proteinase 3 (CANP 3), or calpain L3, or calpain p94, or muscle-specific calcium-activated neutral protease 3, or new calpain 1 (nCL-1), is a calpain large subunit that is mainly expressed in skeletal muscle, or lens. The skeletal muscle-specific CAPN3 are pathologically associated with limb girdle muscular dystrophy type 2A (LGMD2A). Its autolytic activity can be positively regulated by calmodulin (CaM), a known transducer of the calcium signal. CAPN3 is also involved in human melanoma tumorigenesis and progression. It impairs cell proliferation and stimulates oxidative stress-mediated cell death in melanoma cells. Moreover, it plays an important role in sarcomere remodeling and mitochondrial protein turnover. Furthermore, the phosphorylated skeletal muscle-specific CAPN3 acts as a myofibril structural component and may participate in myofibril-based signaling pathways. In the eye, the lens-specific CAPN3, together with CAPN2, is responsible for proteolytic cleavages of alpha and beta-crystallin. Overactivated alpha and beta-crystallin can lead to cataract formation. CAPN3 exists as a homodimer, rather than a heterodimer with the calpain small subunit. It may also form heterodimers with other calpain large subunits. CAPN3 contains a long N-terminal region, followed by a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain. Ca2+ binding at EF5 of the CAPN3 PEF domain is a distinct feature not observed in other calpain isoforms.


Pssm-ID: 320065 [Multi-domain]  Cd Length: 169  Bit Score: 100.70  E-value: 1.33e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142  73 FSAVAGQDGEVDAEELQRCLTQSgINGTYS----PFSLETCRIMIAMLDRDHTGKMGFNAFKELWAALNAWKENFMTVDQ 148
Cdd:cd16190     6 FQQIAGDDMEISADELRSVLNRV-VKKHKDlkteGFTLESCRSMIALMDTDGSGKLNLQEFRHLWNKIKQWQKIFKRYDT 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142 149 DGSGTVEHHELRQAIGLMGYRLSPQTLTTIVKRYS-KNGRIFFDDYVACCVKLRALTDFFRKRDHLQQGSANFIYDDFLQ 227
Cdd:cd16190    85 DKSGTINSYEMRNAVNDAGFRLNNQLYDIITMRYAdKHMNIDFDSFICCFVRLEGMFRAFHAFDKDGDGIIKLNVLEWLQ 164


                  ...
gi 1057503142 228 GTM 230
Cdd:cd16190   165 LTM 167
EFh_PEF_CAPN8 cd16191
Penta-EF hand, calcium binding motifs, found in calpain-8 (CAPN8); CAPN8, also termed new ...
 71-216 3.08e-26

Penta-EF hand, calcium binding motifs, found in calpain-8 (CAPN8); CAPN8, also termed new calpain 2 (nCL-2), or stomach-specific M-type calpain, is a calpain large subunit predominantly expressed in the stomach. It appears to be involved in membrane trafficking in the gastric surface mucus cells (pit cells), via its location at the Golgi and interaction with the beta-subunit of coatomer complex (beta-COP) of vesicles derived from the Golgi. Moreover, CAPN8, together with CAPN9, forms an active protease complex, G-calpain, in which both proteins are essential for stability and activity. The G-Calpain has been implicated in gastric mucosal defense. CAPN8 exists as both a monomer and homo-oligomer, but not as a heterodimer with the conventional calpain regulatory subunit (30K). The monomer and homodimer forms predominate. CAPN8 contains a short N-terminal anchor helix, followed by a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain.


Pssm-ID: 320066 [Multi-domain]  Cd Length: 168  Bit Score: 99.86  E-value: 3.08e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142  71 TYFSAVAGQDGEVDAEELQRCLTQSGINGT---YSPFSLETCRIMIAMLDRDHTGKMGFNAFKELWAALNAWKENFMTVD 147
Cdd:cd16191     4 NIFQKLAGKKCEVTANELQTILNRVLSKRKdikSDGFTINTCREMISLLDTDGTGTLGLVEFRILWMKIQKYLAIYKKVD 83

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142 148 QDGSGTVEHHELRQAIGLMGYRLSPQTLTTIVKRYSKNG-RIFFDDYVACCVKLRALTDFFRKRDHLQQG 216
Cdd:cd16191    84 SDRSGTIDAHEMRNALQEAGFTLNNKIQQSIVQRYASNKlTINFDGFIACMIRLETLFKMFQLLDKDKSG 153
EFh_PEF_CAPN12 cd16194
Penta-EF hand, calcium binding motifs, found in calpain-12 (CAPN12); CAPN12, also termed ...
 73-216 5.10e-26

Penta-EF hand, calcium binding motifs, found in calpain-12 (CAPN12); CAPN12, also termed calcium-activated neutral proteinase 12 (CANP 12), is a calpain large subunit mainly expressed in the cortex of the hair follicle. It may affect apoptosis regulation. CAPN12 contains a short N-terminal anchor helix, followed by a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain.


Pssm-ID: 320069 [Multi-domain]  Cd Length: 169  Bit Score: 99.18  E-value: 5.10e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142  73 FSAVAGQDGEVDAEELQRCLTQSGINGTYSP---FSLETCRIMIAMLDRDHTGKMGFNAFKELWAALNAWKENFMTVDQD 149
Cdd:cd16194     6 FQELAGEDEEINASELQKILSIALERAHTSKpreFGLRTCRQLIQCFDHGQNGKLALEEFQQLWGYLLEWQAIFTKFDED 85

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1057503142 150 GSGTVEHHELRQAIGLMGYRLSPQTLTTIVKRYSKNG-RIFFDDYVACcvkLRALTDFFRK-RDHLQQG 216
Cdd:cd16194    86 TSGTMDSYELRLALNAAGFHLNNQLTETLTSRYRDSRlRVDFESFLSC---LAHLTCIFCQcSQHDDGG 151
EFh_PEF_CalpC cd16197
Penta-EF hand, calcium binding motifs, found in Drosophila melanogaster calpain-C (CalpC) and ...
 86-217 7.99e-16

Penta-EF hand, calcium binding motifs, found in Drosophila melanogaster calpain-C (CalpC) and similar proteins; CalpC, also termed calcium-activated neutral proteinase homolog C (CANP C), is a catalytically inactive homolog of CalpA and CalpB found in Drosophila. It is strongly expressed in the salivary glands. In contrast with CalpA and CalpB, both of which are closely related to that of vertebrate calpains, and they share similar domain architecture, which consists of four domains: the N-terminal domain I, the catalytic domain II carrying the three active site residues, Cys, His and Asn, the Ca2+-regulated phospholipid-binding domain III, and penta-EF-hand Ca2+-binding domain IV. CalpC is a truncated calpain form missing domain I and about 20 residues from domain II. Moreover, due to all three mutated active site residues (Cys to Arg, His to Val and Asn to Ser), it may not have proteolytic activity.


Pssm-ID: 320072 [Multi-domain]  Cd Length: 166  Bit Score: 72.14  E-value: 7.99e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142  86 EELQRCLTQSGINGTYSpfsLETCRIMIAMLDRDHTGKMGFNAFKELWAALNAWKENFMTVDQDGSGTVEHHELRQAIGL 165
Cdd:cd16197    23 ELLEACLPNDYIKSCAN---IDVCRQVVLLMDNSGLGRLKFQDFKDFMCSLKWWQGVFKMHTKEKTGILRAERLRDALED 99

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1057503142 166 MGYRLSPQTLTTIVKRY-SKNGRIFFDDYVACCVKLRALTDFFRKRDHLQQGS 217
Cdd:cd16197   100 VGFQLNTDVLSILILRYmRKDGTLRFGDFVSAVLHLTAAFGSFEKKDPLQNGF 152
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 79-134 7.67e-05

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


Pssm-ID: 238008 [Multi-domain]  Cd Length: 63  Bit Score: 39.45  E-value: 7.67e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1057503142  79 QDGEVDAEELQRCLtqsgiNGTYSPFSLETCRIMIAMLDRDHTGKMGFNAFKELWA 134
Cdd:cd00051    13 GDGTISADELKAAL-----KSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 109-163 8.06e-05

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


Pssm-ID: 238008 [Multi-domain]  Cd Length: 63  Bit Score: 39.45  E-value: 8.06e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1057503142 109 CRIMIAMLDRDHTGKMGFNAFKELWAALNA------WKENFMTVDQDGSGTVEHHELRQAI 163
Cdd:cd00051     2 LREAFRLFDKDGDGTISADELKAALKSLGEglseeeIDEMIREVDKDGDGKIDFEEFLELM 62
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
80-208 4.32e-04

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 39.39  E-value: 4.32e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142  80 DGEVDAEELQRcltqsgingtyspFSLETCRIMIAMLDRDHTGKMGFNAFKELWAALNAW------KENFMTVDQDGSGT 153
Cdd:COG5126    19 DGVLERDDFEA-------------LFRRLWATLFSEADTDGDGRISREEFVAGMESLFEAtvepfaRAAFDLLDTDGDGK 85

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1057503142 154 VEHHELRQAIGlmGYRLSPQTLTTIVKRYSKN--GRIFFDDYVAccvklrALTDFFR 208
Cdd:COG5126    86 ISADEFRRLLT--ALGVSEEEADELFARLDTDgdGKISFEEFVA------AVRDYYT 134
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 140-195 8.88e-04

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


Pssm-ID: 238008 [Multi-domain]  Cd Length: 63  Bit Score: 36.76  E-value: 8.88e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1057503142 140 KENFMTVDQDGSGTVEHHELRQAIGLMGYRLSPQTLTTIVKRYSKN--GRIFFDDYVA 195
Cdd:cd00051     3 REAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDgdGKIDFEEFLE 60
PTZ00183 PTZ00183
centrin; Provisional
 81-194 1.22e-03

centrin; Provisional


Pssm-ID: 185503 [Multi-domain]  Cd Length: 158  Bit Score: 38.13  E-value: 1.22e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1057503142  81 GEVDAEELQRCLTQSGINgtyspFSLETCRIMIAMLDRDHTGKMGFNAFKELWAALNAWKEN-------FMTVDQDGSGT 153
Cdd:PTZ00183   32 GTIDPKELKVAMRSLGFE-----PKKEEIKQMIADVDKDGSGKIDFEEFLDIMTKKLGERDPreeilkaFRLFDDDKTGK 106

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1057503142 154 VEHHELRQAIGLMGYRLSPQTLTTIVKRYSKN--GRIFFDDYV 194
Cdd:PTZ00183  107 ISLKNLKRVAKELGETITDEELQEMIDEADRNgdGEISEEEFY 149
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
79-134 2.43e-03

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 37.08  E-value: 2.43e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1057503142  79 QDGEVDAEELQRCLTQSGIngtyspfSLETCRIMIAMLDRDHTGKMGFNAFKELWA 134
Cdd:COG5126    82 GDGKISADEFRRLLTALGV-------SEEEADELFARLDTDGDGKISFEEFVAAVR 130
EFh_SPARC_FSTL1 cd16233
EF-hand, extracellular calcium-binding (EC) motif, found in follistatin-related protein 1 ...
 63-129 5.65e-03

EF-hand, extracellular calcium-binding (EC) motif, found in follistatin-related protein 1 (FRP-1); FRP-1, also termed follistatin-like protein 1 (fstl-1), TGF-beta-stimulated clone 36 (TSC-36/Flik), or TGF-beta inducible protein, is a secreted glycoprotein that is overexpressed in certain inflammatory diseases and has been implicated in many autoimmune diseases. FRP-1 functions as an important proinflammatory factor in the pathogenesis of osteoarthritis (OA) by activating the canonical NF-kappaB-mediated inflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6), and enhancing fibroblast like synoviocytes proliferation. It also acts as a critical mediator of collagen-induced arthritis (CIA), juvenile rheumatoid arthritis (JRA), as well as Lyme arthritis observed after Borrelia burgdorferi infection. Meanwhile, it enhances nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome-mediated IL-1beta secretion from monocytes and macrophages. Moreover, FRP-1 shows critical functions in the nervous system. It differentially regulates transforming growth factor beta (TGF-beta) and bone morphogenetic protein (BMP) signaling, leading to epithelial injury and fibroblast activation. Furthermore, FRP-1 functions as a cardiokine with cardioprotective properties. It may play a potential role in ischemic stroke through decreasing neuronal apoptosis and improving neurological deficits via disco-interacting protein 2 homolog A (DIP2A)/Akt pathway after middle cerebral artery occlusion (MCAO). Plasma FRP-1 is elevated in Kawasaki disease (KD) and thus may play a possible role in the formation of coronary artery aneurysm (CAA). FRP-1 contains a follistatin-like (FS) domain, an extracellular calcium-binding (EC) domain including a pair of EF hands, and a von Willebrand factor type C (VWC) domain. The EC domain does not undergo characteristic structural changes upon calcium addition or depletion and therefore is not a functional calcium binding domain.


Pssm-ID: 320012  Cd Length: 114  Bit Score: 35.51  E-value: 5.65e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1057503142  63 SSAGDSVYTYFSAVAGQDGEVDAEELQRCLTQ--SGINGTYSPfSLETCRI--------MIAMLDRDHTGKMGFNAF 129
Cdd:cd16233    31 SSYSDILDKYFKKYDNGDSQLDSNELLKFVEQneTATNLTLYQ-DEETNKLlrglcvdaLIELSDENADWKLNFEEF 106
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

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