Cysteine-rich domain of the secreted frizzled-related protein 5 (SFRP5), a regulator of Wnt activity; The cysteine-rich domain (CRD) is an essential part of the secreted frizzled-related Protein 5 (SFRP5), which regulates the activity of Wnt proteins, key players in a number of fundamental cellular processes such as embryogenesis and postnatal development. SFRPs antagonize the activation of Wnt signaling by binding to the CRD domains of frizzled (Fz) proteins, thereby preventing Wnt proteins from binding to these receptors. SFRPs are also known to have functions unrelated to Wnt, as enhancers of procollagen cleavage by the TLD proteinases. SFRPs and Fz proteins both contain CRD domains, but SFRPs lack the seven-pass transmembrane domain which is an integral part of Fzs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050367947  43 YTKQSQCVDIPSDLHLCHNVGYKKMRLPNLLDHETMPEVKQQASSWVPLLAKQCHRDTQLFLCSLFAPICLERPIYPCRS 122
Cdd:cd07444     1 YSKQPQCVDIPADLPLCHNVGYKRMRLPNLLEHESMAEVKQQASSWVPLLAKRCHADTQVFLCSLFAPVCLDRPIYPCRS 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1050367947 123 LCEVVRDSCAPVMESYGFPWPEMLNCNKFPLDNDLCITVQFGSKQVT 169
Cdd:cd07444    81 LCEAVRDSCAPVMESYGFPWPEMLHCHKFPLDNDLCIAVQFGHLQAT 127

Cysteine-rich domain of the secreted frizzled-related protein 5 (SFRP5), a regulator of Wnt activity; The cysteine-rich domain (CRD) is an essential part of the secreted frizzled-related Protein 5 (SFRP5), which regulates the activity of Wnt proteins, key players in a number of fundamental cellular processes such as embryogenesis and postnatal development. SFRPs antagonize the activation of Wnt signaling by binding to the CRD domains of frizzled (Fz) proteins, thereby preventing Wnt proteins from binding to these receptors. SFRPs are also known to have functions unrelated to Wnt, as enhancers of procollagen cleavage by the TLD proteinases. SFRPs and Fz proteins both contain CRD domains, but SFRPs lack the seven-pass transmembrane domain which is an integral part of Fzs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050367947  43 YTKQSQCVDIPSDLHLCHNVGYKKMRLPNLLDHETMPEVKQQASSWVPLLAKQCHRDTQLFLCSLFAPICLERPIYPCRS 122
Cdd:cd07444     1 YSKQPQCVDIPADLPLCHNVGYKRMRLPNLLEHESMAEVKQQASSWVPLLAKRCHADTQVFLCSLFAPVCLDRPIYPCRS 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1050367947 123 LCEVVRDSCAPVMESYGFPWPEMLNCNKFPLDNDLCITVQFGSKQVT 169
Cdd:cd07444    81 LCEAVRDSCAPVMESYGFPWPEMLHCHKFPLDNDLCIAVQFGHLQAT 127

NTR domain, Secreted frizzled-related protein (Sfrp) 1-like subfamily; composed of proteins similar to human Sfrp1, Sfrp2 and Sfrp5. Sfrps are soluble proteins containing an NTR domain C-terminal to a cysteine-rich Frizzled domain. They show diverse functions and are thought to work in Wnt signaling indirectly, as modulators or antagonists by binding Wnt ligands, and directly, via the Wnt receptor, Frizzled. They participate in regulating the patterning along the anteroposterior axis in vertebrates. Human Sfrp1 has been found frequently to be downregulated in breast cancer and is associated with disease progression and poor prognosis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050367947 174 TKICTQCEIEQKS-ETMRVQLCASDFVLRMRIKEVKIENGDRKLIAAQKKKKVLKAGKLkRKEFRKLVLYIKNAASCPCP 252
Cdd:cd03580     1 PKVCPPCENEEESaKTLLDNFCASDFALKVKIKEISYENGDRKVIGEKKKEILKQGPLK-KKDLKKLVLWLKNGANCPCP 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1050367947 253 QLDNLSGSFLIMGRKVDNKLILTAIYKWDKKSKDMKYAVNFMYSYPC 299
Cdd:cd03580    80 QLDNLNGVYLVMGRKVDGKLLLTSIYKWQKKNKEFKRAVRKWKKHKC 126

Netrin C-terminal Domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050367947  194 CAS--DFVLRMRIKEVKIENGDRKLIAAQKKKKVLKAGKLKRKefrKLVLYIKNA-ASCPCPQLDNLSGSFLIMGRKVDN 270
Cdd:smart00643   5 CKSdvDYVYKVKVLSVEEEGGFDKYTVKILEVIKSGTDELVRG---KNKLRVFISrASCRCPLLLKLGKSYLIMGKSGDL 81

                           90       100
                   ....*....|....*....|....*
gi 1050367947  271 K-------LILTA---IYKWDKKSK 285
Cdd:smart00643  82 WdakgrgqYVLGKnswVEEWPTEEE 106

Cysteine-rich domain of the secreted frizzled-related protein 5 (SFRP5), a regulator of Wnt activity; The cysteine-rich domain (CRD) is an essential part of the secreted frizzled-related Protein 5 (SFRP5), which regulates the activity of Wnt proteins, key players in a number of fundamental cellular processes such as embryogenesis and postnatal development. SFRPs antagonize the activation of Wnt signaling by binding to the CRD domains of frizzled (Fz) proteins, thereby preventing Wnt proteins from binding to these receptors. SFRPs are also known to have functions unrelated to Wnt, as enhancers of procollagen cleavage by the TLD proteinases. SFRPs and Fz proteins both contain CRD domains, but SFRPs lack the seven-pass transmembrane domain which is an integral part of Fzs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050367947  43 YTKQSQCVDIPSDLHLCHNVGYKKMRLPNLLDHETMPEVKQQASSWVPLLAKQCHRDTQLFLCSLFAPICLERPIYPCRS 122
Cdd:cd07444     1 YSKQPQCVDIPADLPLCHNVGYKRMRLPNLLEHESMAEVKQQASSWVPLLAKRCHADTQVFLCSLFAPVCLDRPIYPCRS 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1050367947 123 LCEVVRDSCAPVMESYGFPWPEMLNCNKFPLDNDLCITVQFGSKQVT 169
Cdd:cd07444    81 LCEAVRDSCAPVMESYGFPWPEMLHCHKFPLDNDLCIAVQFGHLQAT 127

Cysteine-rich domain of the crescent protein; The cysteine-rich domain (CRD) is an essential part of the crescent protein, a member of the secreted frizzled-related protein (SFRP) family, which regulates convergent extension movements (CEMs) during gastrulation and neurulation. Xenopus laevis crescent efficiently forms inhibitory complexes with Wnt5a and Wnt11, but this effect is cancelled in the presence of another member of the SFRP family, Frzb1. A potential role for Crescent in head formation is to regulate a non-canonical Wnt pathway positively in the adjacent posterior mesoderm, and negatively in the overlying anterior neuroectoderm.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050367947  47 SQCVDIPSDLHLCHNVGYKKMRLPNLLDHETMPEVKQQASSWVPLLAKQCHRDTQLFLCSLFAPICLERPIYPCRSLCEV 126
Cdd:cd07453     1 SPCMRIPKSMALCYDIGYSEMRIPNLLEHETMAEVIQQSSSWLPLLARECHPDARIFLCSLFAPICWDRPIYPCRSLCEA 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1050367947 127 VRDSCAPVMESYGFPWPEMLNCNKFPLDNDLCITVQFGSKqvTQPPVTKICTQCEIE 183
Cdd:cd07453    81 VRSSCAPLMACYGYPWPEILHCDKFPVDHDLCISPQFIDT--LSPERVKPRASCEDC 135

Frizzled; Drosophila melanogaster frizzled mediates signalling that polarises a precursor cell along the anteroposterior axis. Homologues of the N-terminal region of frizzled exist either as transmembrane or secreted molecules. Frizzled homologues are reported to be receptors for the Wnt growth factors. (Not yet in MEDLINE: the FRI domain occurs in several receptor tyrosine kinases [Xu, Y.K. and Nusse, Curr. Biol. 8 R405-R406 (1998); Masiakowski, P. and Yanopoulos, G.D., Curr. Biol. 8, R407 (1998)].

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050367947   52 IPSDLHLCHNVGYKKMRLPNLLDHETMPEVKQQASSWVPLLAKQCHRDTQLFLCSLFAPICLER--PIYPCRSLCEVVRD 129
Cdd:smart00063   2 EPITIPLCKDLGYNLTSMPNLLGHTTQEEAGLELEQFHPLLNVQCSPDLRFFLCSVYAPICTEDlrPILPCRSLCEAARE 81

                           90       100       110
                   ....*....|....*....|....*....|
gi 1050367947  130 SCAPVMESYGFPWPEMLNCNKFPLDNDLCI 159
Cdd:smart00063  82 GCEPLMEKFGFPWPEFLRCDRFPVQEELCM 111

Cysteine-rich domain of the sizzled protein; The cysteine-rich domain (CRD) is an essential part of the sizzled protein, which regulates bone morphogenetic protein (Bmp) signaling by stabilizing chordin, and plays a critical role in the patterning of vertebrate and invertebrate embryos. Sizzled also functions in the ventral region as a Wnt inhibitor and modulates canonical Wnt signaling. Sizzled proteins belong to the secreted frizzled-related protein family (SFRP), and have be identified in the genomes of birds, fishes and frogs, but not mammals.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050367947  47 SQCVDIPSDLHLCHNVGYKKMRLPNLLDHETMPEVKQQASSWVPLLAKQCHRDTQLFLCSLFAPICLERPIYPCRSLCEV 126
Cdd:cd07452     7 TKCVPIPPEMSMCQDVGYSEMRLPNLLGHTSMAEVVPKSADWQTLLHTGCHPHARTFLCSLFAPVCLDTFIQPCRSMCVA 86

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1050367947 127 VRDSCAPVMESYGFPWPEMLNCNKFPLDNDLCIT-----VQFGSKQVTQPPvtkiCTQC 180
Cdd:cd07452    87 VRDSCAPVLACHGHSWPESLDCDRFPAGEDMCLAslskeYQYFYKEFPKPA----CQSC 141

Cysteine-rich Wnt-binding domain of the frizzled 4 (Fz4) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 4 (Fz4) receptor, and is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and the Ca(2+) modulating signaling pathway. CRD containing Fzs have been found in diverse species from amoebas to mammals. 10 different frizzled proteins are found in vertebrata. Frizzled 4 (Fz4) activates the Ca(2+)/calmodulin-dependent protein kinase II and protein kinase C of the Wnt/Ca(2+) signaling pathway during retinal angiogenesis. Mutations in Fz4 lead to familial exudative vitreoretinopathy (FEVR), a hereditary ocular disorder characterized by failure of the peripheral retinal vascularization. In addition, the interplay between Fz4 and norrin as a receptor-ligand pair plays an important role in vascular development in the retina and inner ear in a Wnt-independent manner.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050367947  53 PSDLHLCHNVGYKKMRLPNLLDHETMPEVKQQASSWVPLLAKQCHRDTQLFLCSLFAPIC---LERPIYPCRSLCEVVRD 129
Cdd:cd07448     6 PIRIEMCQGLGYNVTRMPNLVGHELQTDAELQLQTFTPLIQYGCSSQLKFFLCSVYVPMCtekVPVPIGPCRPLCLSVKK 85

                          90       100
                  ....*....|....*....|....*..
gi 1050367947 130 SCAPVMESYGFPWPEMLNCNKFPLDND 156
Cdd:cd07448    86 RCLPVLKEFGFPWPEALNCSKFPPQNN 112

Cysteine-rich Wnt-binding domain (CRD) of receptors similar to frizzled 9; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 9 (Fz9) and frizzled 10 (Fz10) receptors, and similar proteins. This domain is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and Ca(2+) modulating signaling pathway. The CRD domain is well conserved in metazoans - 10 frizzled proteins have been identified in mammals, 4 in Drosophila and 3 in Caenorhabditis elegans. Very little is known about the mechanism by which CRD domains interact with their ligands. The domain contains 10 conserved cysteines.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050367947  48 QCVDIPsdlhLCHNVGYKKMRLPNLLDHETMPEVKQQASSWVPLLAKQCHRDTQLFLCSLFAPICLER---PIYPCRSLC 124
Cdd:cd07457     4 ERITIP----MCQGIGYNMTRMPNLLGHESQSEAAISIHEFAPLVQYGCAEHLRFFLCSLYAPMCTEQvsiPIPACRSMC 79

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1050367947 125 EVVRDSCAPVMESYGFPWPEMLNCNKFPLDND---LCI 159
Cdd:cd07457    80 EQARDKCSPIMEQFSFSWPDSLDCDRLPRKNDpkdLCM 117

Cysteine-rich Wnt-binding domain (CRD) of receptors similar to frizzled 5; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 5 (Fz5) and frizzled 8 (Fz8) receptors, and similar proteins. This domain is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and Ca(2+) modulating signaling pathway. The CRD domain is well conserved in metazoans - 10 frizzled proteins have been identified in mammals, 4 in Drosophila and 3 in Caenorhabditis elegans. Very little is known about the mechanism by which CRD domains interact with their ligands. The domain contains 10 conserved cysteines.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050367947  58 LCHNVGYKKMRLPNLLDHETMPEVKQQASSWVPLLAKQCHRDTQLFLCSLFAPICLE---RPIYPCRSLCEVVRDSCAPV 134
Cdd:cd07456     9 MCKGIGYNMTYMPNQFNHDTQEEAGLEVHQFWPLVEIQCSPDLKFFLCSMYTPICLEdydKPLPPCRSVCERARDGCAPI 88

                          90       100
                  ....*....|....*....|....*...
gi 1050367947 135 MESYGFPWPEMLNCNKFPL---DNDLCI 159
Cdd:cd07456    89 MRQYGFAWPERMSCDALPEggdPDNLCM 116

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 8 (Fz8) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 8 (Fz8) receptor, and is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and Ca(2+) modulating signaling pathway. CRD containing Fzs have been found in diverse species from amoebas to mammals. 10 different frizzled proteins are found in vertebrata. Xenopus Fz8 is important in Wnt/beta-catenin signaling pathways controlling the transcriptional activation of target genes Siamois and Xnr3 in the animal caps of late blastula.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050367947  45 KQSQCVDIPsdLHLCHNVGYKKMRLPNLLDHETMPEVKQQASSWVPLLAKQCHRDTQLFLCSLFAPICLE---RPIYPCR 121
Cdd:cd07461     1 KELQCQEIT--VPLCKGIGYNYTYMPNQFNHDTQDEAGLEVHQFWPLVEIQCSPDLKFFLCSMYTPICLEdykKPLPPCR 78

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1050367947 122 SLCEVVRDSCAPVMESYGFPWPEMLNCNKFP 152
Cdd:cd07461    79 SVCERAKAGCAPLMRQYGFPWPDRMRCDLLP 109

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 5 (Fz5) receptor.proteins; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 5 (Fz5) receptor, and is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and Ca(2+) modulating signaling pathway. CRD containing Fzs have been found in diverse species from amoebas to mammals. 10 different frizzled proteins are found in vertebrata. Fz5 plays critical regulating roles in the yolk sac and placental angiogenesis, in the maturation of the Paneth cell phenotype, in governing the neural potential of progenitors in the developing retina, and in neuronal survival in the parafascicular nucleus.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050367947  58 LCHNVGYKKMRLPNLLDHETMPEVKQQASSWVPLLAKQCHRDTQLFLCSLFAPICL---ERPIYPCRSLCEVVRDSCAPV 134
Cdd:cd07460    12 MCKGIGYNLTYMPNQFNHDTQDEAGLEVHQFWPLVEIQCSPDLRFFLCSMYTPICLpdyRKPLPPCRSVCERAKAGCSPL 91

                          90       100
                  ....*....|....*....|....*...
gi 1050367947 135 MESYGFPWPEMLNCNKFPLDND---LCI 159
Cdd:cd07460    92 MRQYGFAWPERMNCDRLPVLGDpetLCM 119

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 1 (Fz1) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 1 (Fz1) receptor, and is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and Ca(2+) modulating signaling pathway. CRD containing Fzs have been found in diverse species from amoebas to mammals. 10 different frizzled proteins are found in vertebrata.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050367947  53 PSDLHLCHNVGYKKMRLPNLLDHETMPEVKQQASSWVPLLAKQCHRDTQLFLCSLFAPIC--LERPIYPCRSLCEVVRDS 130
Cdd:cd07465     7 PISIPLCTDIAYNQTIMPNLLGHTNQEDAGLEVHQFYPLVKVQCSAELKFFLCSMYAPVCtvLEQALPPCRSLCERARQG 86

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1050367947 131 CAPVMESYGFPWPEMLNCNKFPLD--NDLCI 159
Cdd:cd07465    87 CEALMNKFGFQWPDTLRCEKFPVHgaGELCV 117

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 3 (Fz3) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 3 (Fz3) receptor, and is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and Ca(2+) modulating signaling pathway. CRD containing Fzs have been found in diverse species from amoebas to mammals. 10 different frizzled proteins are found in vertebrata. Fz3 plays a vital role in the anterior-posterior guidance of commissural axons. Knockout mice without Fz3 show defects in fiber tracts in the rostral CNS.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050367947  53 PSDLHLCHNVGYKKMRLPNLLDHETMPEVKQQASSWVPLLAKQCHRDTQLFLCSLFAPICLE--RPIYPCRSLCEVVRDS 130
Cdd:cd07449     7 PITLRMCQDLPYNTTFMPNLLNHYDQQTAALAMEPFHPMVNLECSRDFRPFLCALYAPVCMEygRVTLPCRRLCQRAYSE 86

                          90       100
                  ....*....|....*....|..
gi 1050367947 131 CAPVMESYGFPWPEMLNCNKFP 152
Cdd:cd07449    87 CSKLMEMFGVPWPEDMECSRFP 108

Cysteine-rich domain of the secreted frizzled-related protein 3 (SFRP3, alias FRZB), a Wnt antagonist; The cysteine-rich domain (CRD) is an essential part of the secreted frizzled-related protein 3 (SFRP3, alias FRZB), which plays important roles in embryogenesis and postnatal development as an antagonist of Wnt proteins, key players in a number of fundamental cellular processes. SFRPs antagonize the activation of Wnt signaling by binding to the CRD domains of frizzled proteins (Fz), thereby preventing Wnt proteins from binding to these receptors. SFRPs are also known to have functions unrelated to Wnt, as enhancers of procollagen cleavage by the TLD proteinases. SFRPs and Fz proteins both contain CRD domains, but SFRPs lack the seven-pass transmembrane domain which is an integral part of Fzs. SFRP3 regulates Wnt signaling activity in bone development and homeostasis. It is also involved in the control of planar cell polarity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050367947  53 PSDLHLCHNVGYKKMRLPNLLDHETMPEVKQQASSWVPLLAKQCHRDTQLFLCSLFAPICL----ERPIYPCRSLCEVVR 128
Cdd:cd07441     6 PVRIPMCKSMPWNMTKMPNHLHHSTQANAVLAIEQFEGLLGTQCSPDLLFFLCAMYAPICTidfqHEPIKPCKSVCERAR 85

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1050367947 129 DSCAPVMESYGFPWPEMLNCNKFPL-DNDLCIT 160
Cdd:cd07441    86 AGCEPVLIRYRHTWPESLACEELPVyDRGVCIS 118

Cysteine-rich domain of the variant 3 of collagen XVIII (V3C18 ); The cysteine-rich domain (CRD) is an essential part of the variant 3 of collagen XVIII (V3C18), which regulates major cellular functions such as the differential epithelial morphogenesis of early lung and kidney development. V3C18 is a 170 kD protein, which is proteolotically processed into the CRD-containing 50 kD glucoprotein precursor that binds Wnt3a through its CRD domain and suppresses the Wnt3a-induced stabilization of beta catenin. Full-length V3C18 is unable to inhibit Wnt signaling.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050367947  47 SQCVDIPSDLHLCHNVGYKKMRLPNLLDHETMPEVKQQASSWVPLLAKQCHRDTQLFLCSLFAPICLERPIY---PCRSL 123
Cdd:cd07455     3 PRCLPVPSSLPFCSRLGIRSFWLPNFLNHTSVEEVRAVLAEWAWLLESGCHPSLEWFFCLLLVPSCGGGPPPpppPCRQF 82

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1050367947 124 CEVVRDSCAPVMESYGFPwpemLNCNKFPLDND 156
Cdd:cd07455    83 CEVLQDSCWNLLEGGRLP----VACASLPEQED 111

One of two cysteine-rich domains of the corin protein, a type II transmembrane serine protease ; The cysteine-rich domain (CRD) is an essential component of corin, a type II transmembrane serine protease which functions as the convertase of the pro-atrial natriuretic peptide (pro-ANP) in the heart. Corin contains two CRDs in its extracellular region, which play an important role in recognition of the physiological substrate, pro-ANP. This model characterizes the second (C-terminal) CRD.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050367947  53 PSDLHLCHNVGYKKMRLPNLLDHETMPE--VKQQASSWVPLLAKQCHRDTQLFLCSLFAPIC---LERPIYPCRSLCEVV 127
Cdd:cd07888     4 PITLELCMNLPYNTTRYPNYLGHRTQKEasISWESSLFPALVQTNCYKYLMFFACTILVPKCdpvTQQRIPPCRSLCRNS 83

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1050367947 128 RDSCAPVMESYGFPWPEMLNCNKFP---LDNDLCIT 160
Cdd:cd07888    84 KERCESVLGIVGLQWPEDTDCAQFPeenSDNQTCLL 119

Cysteine-rich domain of carboxypeptidase Z, a member of the carboxypeptidase E family; The cysteine-rich-domain (CRD) is an essential part of carboxypeptidase Z, a member of the carboxypeptidase E family of metallocarboxypeptidases. This is a group of Zn-dependent enzymes implicated in the intra- and extracellular processing of proteins. Carboxypeptidase Z removes C-terminal basic amino acid residues from its substrates, particularly arginine. The CRD acts as a ligand-binding domain for Wnts involved in developmental processes. CPZ binds and may process Wnt-4, CPZ has also been found to enhance the induction of the homeobox gene Cdx1. During vertebrate embryogenesis, the CRD of CPZ upregulates Pax3, a Wnt reporter gene essential for patterning of somites and limb development.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050367947  48 QCVDIpsDLHLCHNVGYKKMRLPNLLDHETMPEVKQQA-----SSWVPLLAKQCHRDTQLFLCSLFAPICL-ERPIYPCR 121
Cdd:cd07447     3 TCTDL--LLSYCSDVSYTQTTFPNLLGHRSREVTEAGAeylllSVLHGLLGGECNPDIRLLGCSVLAPRCEnDKVIKPCR 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 1050367947 122 SLCEVVRDSCAPVMESYGFPWPEMLNCNKF 151
Cdd:cd07447    81 STCEALRKRCSHAFDAIQMAWPYFLDCDRF 110

One of two cysteine-rich domains of the corin protein, a type II transmembrane serine protease ; The cysteine-rich domain (CRD) is an essential component of corin, a type II transmembrane serine protease which functions as the convertase of the pro-atrial natriuretic peptide (pro-ANP) in the heart. Corin contains two CRDs in its extracellular region, which play an important role in recognition of the physiological substrate, pro-ANP. This model characterizes the first (N-terminal) CRD.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1050367947  96 CHRDTQLFLCSLFAPICL-----ERPIYPCRSLCEVVRDSCAPVMESYGFPWPEMLNCNKF 151
Cdd:cd07445    49 CYQHIMLFGCSLALPECIsdgddRHGLLPCRSFCEAAKEGCEPVLGMVNASWPDFLRCSQF 109

UNC-6/NTR/C345C module; Sequence similarity between netrin UNC-6 and C345C complement protein family members, and hence the existence of the UNC-6 module, was first reported in. Subsequently, many additional members of the family were identified on the basis of sequence similarity between the C-terminal domains of netrins, complement proteins C3, C4, C5, secreted frizzled-related proteins, and type I pro-collagen C-proteinase enhancer proteins (PCOLCEs), which are homologous with the N-terminal domains of tissue inhibitors of metalloproteinases (TIMPs). The TIMPs are classified as a separate family in Pfam (pfam00965). This expanded domain family has been named as the NTR module.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050367947 194 CA-SDFVLRMRIKEVKIENGDRKLIAAqkKKKVLKAGKLKRKEfRKLVLYIKNaASCPCPQLdNLSGSFLIMGRKVDNK- 271
Cdd:pfam01759   4 CKgSDYVYKVKVLSVEEEGSFDKYTVK--VKEVLKEGTDKIQR-GKVRLFLKR-GDCRCPQL-RLGKEYLIMGKVGDLEg 78

                          90       100
                  ....*....|....*....|....*..
gi 1050367947 272 ----------LILTAIYKWDKKSKDMK 288
Cdd:pfam01759  79 rgryvldknsWVEPWPTKWECKLRELQ 105