Cysteine-rich secretory protein family; This is a large family of cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins (CAP) that are found in a wide range of organizms, including prokaryotes and non-vertebrate eukaryotes, The nine subfamilies of the mammalian CAP 'super'family include: the human glioma pathogenesis-related 1 (GLIPR1), Golgi associated pathogenesis related-1 (GAPR1) proteins, peptidase inhibitor 15 (PI15), peptidase inhibitor 16 (PI16), cysteine-rich secretory proteins (CRISPs), CRISP LCCL domain containing 1 (CRISPLD1), CRISP LCCL domain containing 2 (CRISPLD2), mannose receptor like and the R3H domain containing like proteins. Members are most often secreted and have an extracellular endocrine or paracrine function and are involved in processes including the regulation of extracellular matrix and branching morphogenesis, potentially as either proteases or protease inhibitors; in ion channel regulation in fertility; as tumour suppressor or pro-oncogenic genes in tissues including the prostate; and in cell-cell adhesion during fertilization. The overall protein structural conservation within the CAP 'super'family results in fundamentally similar functions for the CAP domain in all members, yet the diversity outside of this core region dramatically alters the target specificity and, thus, the biological consequences. The Ca++-chelating function would fit with the various signalling processes (e.g. the CRISP proteins) that members of this family are involved in, and also the sequence and structural evidence of a conserved pocket containing two histidines and a glutamate. It also may explain how Swiss:Q91055 blocks the Ca++ transporting ryanodine receptors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28573842    83 LRPASRMATLRWHEELAGLAKFALRRCDYID----DYCSNTDEFSYVSYIYGSTKWlqlekDPISVLDFVLQFWMDDVKG 158
Cdd:pfam00188   7 YRAAAGLPPLSWDNELAAAAQDHAKYCADNGshnhRSPYGGNIYARVVAAGYALGD-----AGPDSAEDAVDGWYDSPGT 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 28573842   159 CTMAHinaekpakdgqcrgyFTQLVQDLAAHVGCAMMlrkgQTSGLYQYGVLCHF 213
Cdd:pfam00188  82 YNCGH---------------RTNLLWPKSTKVGCAVA----KCGDGGTYYFVCNY 117

Cysteine-rich secretory protein family; This is a large family of cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins (CAP) that are found in a wide range of organizms, including prokaryotes and non-vertebrate eukaryotes, The nine subfamilies of the mammalian CAP 'super'family include: the human glioma pathogenesis-related 1 (GLIPR1), Golgi associated pathogenesis related-1 (GAPR1) proteins, peptidase inhibitor 15 (PI15), peptidase inhibitor 16 (PI16), cysteine-rich secretory proteins (CRISPs), CRISP LCCL domain containing 1 (CRISPLD1), CRISP LCCL domain containing 2 (CRISPLD2), mannose receptor like and the R3H domain containing like proteins. Members are most often secreted and have an extracellular endocrine or paracrine function and are involved in processes including the regulation of extracellular matrix and branching morphogenesis, potentially as either proteases or protease inhibitors; in ion channel regulation in fertility; as tumour suppressor or pro-oncogenic genes in tissues including the prostate; and in cell-cell adhesion during fertilization. The overall protein structural conservation within the CAP 'super'family results in fundamentally similar functions for the CAP domain in all members, yet the diversity outside of this core region dramatically alters the target specificity and, thus, the biological consequences. The Ca++-chelating function would fit with the various signalling processes (e.g. the CRISP proteins) that members of this family are involved in, and also the sequence and structural evidence of a conserved pocket containing two histidines and a glutamate. It also may explain how Swiss:Q91055 blocks the Ca++ transporting ryanodine receptors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28573842    83 LRPASRMATLRWHEELAGLAKFALRRCDYID----DYCSNTDEFSYVSYIYGSTKWlqlekDPISVLDFVLQFWMDDVKG 158
Cdd:pfam00188   7 YRAAAGLPPLSWDNELAAAAQDHAKYCADNGshnhRSPYGGNIYARVVAAGYALGD-----AGPDSAEDAVDGWYDSPGT 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 28573842   159 CTMAHinaekpakdgqcrgyFTQLVQDLAAHVGCAMMlrkgQTSGLYQYGVLCHF 213
Cdd:pfam00188  82 YNCGH---------------RTNLLWPKSTKVGCAVA----KCGDGGTYYFVCNY 117

CAP (cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins) domain of cysteine-rich secretory proteins; Cysteine-rich secretory proteins (CRISPs) are two-domain proteins with an evolutionary diverse and structurally conserved N-terminal CAP domain and a C-terminal cysteine-rich domain, which is comprised of a hinge and an ICR (ion channel regulator) region. CRISPs are involved in response to pathogens, fertilization, and sperm maturation. One member, Tex31 from the venom duct of Conus textile, has been shown to possess proteolytic activity sensitive to serine protease inhibitors. CRISP-1 has been shown to mediate gamete fusion by binding to the egg surface. Other members of the CRISP family secreted in the testis (CRISP2), epididymis (CRISP3-4), or during ejaculation (CRISP3), are also involved in sperm-egg interaction, supporting the existence of a functional redundancy and cooperation between homolog proteins ensuring the success of fertilization. The wider family of CAP domain containing proteins includes plant pathogenesis-related protein 1 (PR-1) and allergen 5 from vespid venom, among others.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28573842  69 NDFRNTVAkgqyPhlrPASRMATLRWHEELAGLAKFALRRCDYI-DDYCSNTDEFS------YVSyiYGSTKWlqlekdp 141
Cdd:cd05383  11 NALRRSVN----P---PASNMLKMSWNPEAAENAQRWANRCNFThSPPNGRTIPGIrcgeniFMS--SYPASW------- 74

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 28573842 142 isvlDFVLQFWMDDVKGCTMahinAEKPAKDGQCRGYFTQLVQDLAAHVGCAMMLRKGQTSglYQYGVLCHF 213
Cdd:cd05383  75 ----SEVIQAWYDEYKDFKY----GVGAKPPGSVTGHYTQVVWYSSYLVGCAVAYCPSQGS--LKYFYVCQY 136