Cysteine-rich domain of the secreted frizzled-related protein 1 (SFRP1), a regulator of Wnt activity; The cysteine-rich domain (CRD) is an essential part of the secreted frizzled-related protein 1 (SFRP1), 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 CRDs 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. SFRP1 is expressed in many tissues and is involved in the regulation of Wnt signaling in osteoblasts, leading to enhanced trabecular bone formation in adults; it has also been shown to control the growth of retinal ganglion cell axons and the elongation of the antero-posterior axis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 697821717   3 YAKPHQCVAIPADLRLCHSVGYDKMVLPNLLDHETMAEVKHQASSWVPLLNKNCHMGTQVFLCSLFAPVCLDRPVYPCRW 82
Cdd:cd07443    1 YTKPPQCVDIPADLRLCHNVGYKKMVLPNLLDHETMAEVKQQASSWVPLLNKNCHKGTQVFLCSLFAPVCLDRPVYPCRW 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 697821717  83 LCEAVRDSCEPVMQFFGFFWPEMLKCDQFPQDDVCIAMTAPNAT 126
Cdd:cd07443   81 LCEAVRDSCEPVMQFFGFYWPEMLKCDKFPEGEVCIAMTPPNAT 124

Cysteine-rich domain of the secreted frizzled-related protein 1 (SFRP1), a regulator of Wnt activity; The cysteine-rich domain (CRD) is an essential part of the secreted frizzled-related protein 1 (SFRP1), 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 CRDs 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. SFRP1 is expressed in many tissues and is involved in the regulation of Wnt signaling in osteoblasts, leading to enhanced trabecular bone formation in adults; it has also been shown to control the growth of retinal ganglion cell axons and the elongation of the antero-posterior axis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 697821717   3 YAKPHQCVAIPADLRLCHSVGYDKMVLPNLLDHETMAEVKHQASSWVPLLNKNCHMGTQVFLCSLFAPVCLDRPVYPCRW 82
Cdd:cd07443    1 YTKPPQCVDIPADLRLCHNVGYKKMVLPNLLDHETMAEVKQQASSWVPLLNKNCHKGTQVFLCSLFAPVCLDRPVYPCRW 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 697821717  83 LCEAVRDSCEPVMQFFGFFWPEMLKCDQFPQDDVCIAMTAPNAT 126
Cdd:cd07443   81 LCEAVRDSCEPVMQFFGFYWPEMLKCDKFPEGEVCIAMTPPNAT 124

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 697821717    12 IPADLRLCHSVGYDKMVLPNLLDHETMAEVKHQASSWVPLLNKNCHMGTQVFLCSLFAPVCLDR--PVYPCRWLCEAVRD 89
Cdd:smart00063   2 EPITIPLCKDLGYNLTSMPNLLGHTTQEEAGLELEQFHPLLNVQCSPDLRFFLCSVYAPICTEDlrPILPCRSLCEAARE 81

                           90       100       110
                   ....*....|....*....|....*....|..
gi 697821717    90 SCEPVMQFFGFFWPEMLKCDQFP-QDDVCIAM 120
Cdd:smart00063  82 GCEPLMEKFGFPWPEFLRCDRFPvQEELCMDP 113

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 697821717  151 EHLCA-SEFALKMTIKEVKKENGDKMIVPRKRKALKLGpIRKKNLKKLVLFLKNGaDCPCHQLdNLGQYFLIMGRQVKT- 228
Cdd:pfam01759   1 KKACKgSDYVYKVKVLSVEEEGSFDKYTVKVKEVLKEG-TDKIQRGKVRLFLKRG-DCRCPQL-RLGKEYLIMGKVGDLe 77

                  ....*...
gi 697821717  229 ---QYLLT 233
Cdd:pfam01759  78 grgRYVLD 85

Cysteine-rich domain of the secreted frizzled-related protein 1 (SFRP1), a regulator of Wnt activity; The cysteine-rich domain (CRD) is an essential part of the secreted frizzled-related protein 1 (SFRP1), 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 CRDs 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. SFRP1 is expressed in many tissues and is involved in the regulation of Wnt signaling in osteoblasts, leading to enhanced trabecular bone formation in adults; it has also been shown to control the growth of retinal ganglion cell axons and the elongation of the antero-posterior axis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 697821717   3 YAKPHQCVAIPADLRLCHSVGYDKMVLPNLLDHETMAEVKHQASSWVPLLNKNCHMGTQVFLCSLFAPVCLDRPVYPCRW 82
Cdd:cd07443    1 YTKPPQCVDIPADLRLCHNVGYKKMVLPNLLDHETMAEVKQQASSWVPLLNKNCHKGTQVFLCSLFAPVCLDRPVYPCRW 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 697821717  83 LCEAVRDSCEPVMQFFGFFWPEMLKCDQFPQDDVCIAMTAPNAT 126
Cdd:cd07443   81 LCEAVRDSCEPVMQFFGFYWPEMLKCDKFPEGEVCIAMTPPNAT 124

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 697821717   9 CVAIPADLRLCHSVGYDKMVLPNLLDHETMAEVKHQASSWVPLLNKNCHMGTQVFLCSLFAPVCLDRPVYPCRWLCEAVR 88
Cdd:cd07453    3 CMRIPKSMALCYDIGYSEMRIPNLLEHETMAEVIQQSSSWLPLLARECHPDARIFLCSLFAPICWDRPIYPCRSLCEAVR 82

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 697821717  89 DSCEPVMQFFGFFWPEMLKCDQFPQD-DVCIamtAPNATEVSRPKGTTVCPPCDNE 143
Cdd:cd07453   83 SSCAPLMACYGYPWPEILHCDKFPVDhDLCI---SPQFIDTLSPERVKPRASCEDC 135

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 697821717 134 TTVCPPCDNEMKS-EAIVEHLCASEFALKMTIKEVKKENGDKMIVPR-KRKALKLGPIRKKNLKKLVLFLKNGADCPCHQ 211
Cdd:cd03580    1 PKVCPPCENEEESaKTLLDNFCASDFALKVKIKEISYENGDRKVIGEkKKEILKQGPLKKKDLKKLVLWLKNGANCPCPQ 80

                         90       100       110
                 ....*....|....*....|....*....|
gi 697821717 212 LDNLGQYFLIMGRQVKTQYLLTAIYKWDKK 241
Cdd:cd03580   81 LDNLNGVYLVMGRKVDGKLLLTSIYKWQKK 110

CRD_domain cysteine-rich domain, also known as Fz (frizzled) domain; CRD_FZ is an essential component of a number of cell surface receptors, which are involved in multiple signal transduction pathways, particularly in modulating the activity of the Wnt proteins, which play a fundamental role in the early development of metazoans. CRD is also found in secreted frizzled related proteins (SFRPs), which lack the transmembrane segment found in the frizzled protein. The CRD domain is also present in the alpha-1 chain of mouse type XVIII collagen, in carboxypeptidase Z, several receptor tyrosine kinases, and the mosaic transmembrane serine protease corin. The CRD domain is well conserved in metazoans - 10 frizzled proteins have been identified in mammals, 4 in Drosophila and 3 in Caenorhabditis elegans. CRD domains have also been identified in multiple tandem copies in a Dictyostelium discoideum protein. 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 697821717   8 QCVAIPadLRLCHSVGYDKMVLPNLLDHETMAEVKHQASSWVPLLNKNCHMGTQVFLCSLFAPVCL---DRPVYPCRWLC 84
Cdd:cd07066    1 KCEPIP--LPLCRGLPYNTTRFPNLLGHESQEEAEQELESFTPLVNSGCHPDLRFFLCSLYFPECTpdgDRPIPPCRSLC 78

                         90       100       110
                 ....*....|....*....|....*....|.
gi 697821717  85 EAVRDSCEPVMQFFGFFWPEMLKCDQFPQDD 115
Cdd:cd07066   79 EEVRDSCEPLMLAFGFPWPEPLDCDRFPDSN 109

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 697821717  13 PADLRLCHSVGYDKMVLPNLLDHETMAEVKHQASSWVPLLNKNCHMGTQVFLCSLFAPVC---LDRPVYPCRWLCEAVRD 89
Cdd:cd07448    6 PIRIEMCQGLGYNVTRMPNLVGHELQTDAELQLQTFTPLIQYGCSSQLKFFLCSVYVPMCtekVPVPIGPCRPLCLSVKK 85

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 697821717  90 SCEPVMQFFGFFWPEMLKCDQFP----QDDVCiaMTAPNATEV 128
Cdd:cd07448   86 RCLPVLKEFGFPWPEALNCSKFPpqnnHNHMC--MEGPGDEEV 126

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 697821717  13 PADLRLCHSVGYDKMVLPNLLDHETMAEVKHQASSWVPLLNKNCHMGTQVFLCSLFAPVCLDR---PVYPCRWLCEAVRD 89
Cdd:cd07457    5 RITIPMCQGIGYNMTRMPNLLGHESQSEAAISIHEFAPLVQYGCAEHLRFFLCSLYAPMCTEQvsiPIPACRSMCEQARD 84

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 697821717  90 SCEPVMQFFGFFWPEMLKCDQFPQ--DDVCIAMTAPN 124
Cdd:cd07457   85 KCSPIMEQFSFSWPDSLDCDRLPRknDPKDLCMEAPN 121

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 697821717  18 LCHSVGYDKMVLPNLLDHETMAEVKHQASSWVPLLNKNCHMGTQVFLCSLFAPVCL---DRPVYPCRWLCEAVRDSCEPV 94
Cdd:cd07456    9 MCKGIGYNMTYMPNQFNHDTQEEAGLEVHQFWPLVEIQCSPDLKFFLCSMYTPICLedyDKPLPPCRSVCERARDGCAPI 88

                         90       100       110
                 ....*....|....*....|....*....|..
gi 697821717  95 MQFFGFFWPEMLKCDQFPQ--DDVCIAMTAPN 124
Cdd:cd07456   89 MRQYGFAWPERMSCDALPEggDPDNLCMDRNN 120

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 10 (Fz10) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 10 (Fz10) 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. The cellular functon of Fz10 is unknown.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 697821717   8 QCVAIPadlrLCHSVGYDKMVLPNLLDHETMAEVKHQASSWVPLLNKNCHMGTQVFLCSLFAPVCLDR---PVYPCRWLC 84
Cdd:cd07462    6 QPIEIP----MCKDIGYNMTRMPNLMGHENQREAAIQLHEFAPLVEYGCHSHLKFFLCSLYAPMCTEQvstPIPACRVMC 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 697821717  85 EAVRDSCEPVMQFFGFFWPEMLKCDQFP--QDDVCIAMTAPN 124
Cdd:cd07462   82 EQARLKCSPIMEQFNFKWPDSLDCSKLPnkNDPNYLCMEAPN 123

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 2 (Fz2) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 2 (Fz2) 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. Fz2 is involved in the Wnt/beta-catenin signaling pathway and in the activation of protein kinase C and calcium/calmodulin-dependent protein kinase (CaM kinase).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 697821717  13 PADLRLCHSVGYDKMVLPNLLDHETMAEVKHQASSWVPLLNKNCHMGTQVFLCSLFAPVC--LDRPVYPCRWLCEAVRDS 90
Cdd:cd07464    7 PISIPLCTDIAYNQTIMPNLLGHTNQEDAGLEVHQFYPLVKVQCSLELRFFLCSMYAPVCtvLEQAIPPCRSICERARQG 86

                         90       100       110
                 ....*....|....*....|....*....|..
gi 697821717  91 CEPVMQFFGFFWPEMLKCDQFPQ---DDVCIA 119
Cdd:cd07464   87 CEALMNKFGFQWPERLRCENFPRhgaEQICVG 118

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 697821717  18 LCHSVGYDKMVLPNLLDHETMAEVKHQASSWVPLLNKNCHMGTQVFLCSLFAPVCLD---RPVYPCRWLCEAVRDSCEPV 94
Cdd:cd07460   12 MCKGIGYNLTYMPNQFNHDTQDEAGLEVHQFWPLVEIQCSPDLRFFLCSMYTPICLPdyrKPLPPCRSVCERAKAGCSPL 91

                         90
                 ....*....|....*...
gi 697821717  95 MQFFGFFWPEMLKCDQFP 112
Cdd:cd07460   92 MRQYGFAWPERMNCDRLP 109

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 697821717  13 PADLRLCHSVGYDKMVLPNLLDHETMAEVKHQASSWVPLLNKNCHMGTQVFLCSLFAPVCLD--RPVYPCRWLCEAVRDS 90
Cdd:cd07449    7 PITLRMCQDLPYNTTFMPNLLNHYDQQTAALAMEPFHPMVNLECSRDFRPFLCALYAPVCMEygRVTLPCRRLCQRAYSE 86

                         90       100
                 ....*....|....*....|....*
gi 697821717  91 CEPVMQFFGFFWPEMLKCDQFPQDD 115
Cdd:cd07449   87 CSKLMEMFGVPWPEDMECSRFPDCD 111

Cysteine-rich domain of the secreted frizzled-related protein 4 (SFRP4), a Wnt antagonist; The cysteine-rich domain (CRD) is an essential part of the secreted frizzled-related Protein 4 (SFRP4), 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 CRDs 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 697821717   6 PHQCVAIPadlrLCHSVGYDKMVLPNLLDHETMAEVKHQASSWVPLLNKNCHMGTQVFLCSLFAPVC----LDRPVYPCR 81
Cdd:cd07442    4 PCEAVRIP----MCRHMPWNITRMPNHLHHSTQENAVLAIEQYEELVDTGCSPVLPFFLCAMYAPICtlefLYDPIKPCR 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 697821717  82 WLCEAVRDSCEPVMQFFGFFWPEMLKCDQFPQDD--VCIAMTA 122
Cdd:cd07442   80 SVCQRARDGCEPIMRRYNHSWPESLACDDLPVYDrgVCISPEA 122

Cysteine-rich domain (CRD) of LIN_17; A cysteine-rich domain (CRD) is an essential component of a number of cell surface receptors, which are involved in multiple signal transduction pathways, particularly in modulating the activity of the Wnt proteins, which play a fundamental role in the early development of metazoans. CRD is also found in secreted frizzled related proteins (SFRPs), which lack the transmembrane segment found in the frizzled protein. The CRD domain is also present in the alpha-1 chain of mouse type XVIII collagen, in carboxypeptidase Z, several receptor tyrosine kinases, and the mosaic transmembrane serine protease corin. The CRD domain is well conserved in metazoans - 10 frizzled proteins have been identified in mammals, 4 in Drosophila and 3 in Caenorhabditis elegans. CRD domains have also been identified in multiple tandem copies in a Dictyostelium discoideum protein. Very little is known about the mechanism by which CRD domains interact with their ligands. The domain contains 10 conserved cysteines. The protein lin-17 is involved in cell type specification during Caenorhabditis elegans vulval development.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 697821717  12 IPADLRLCHSVGYDKMVLPNLLDHETMAEVKHQASSWVPLLNKNCHMGTQVFLCSLFAPVCLDR---PVYPCRWLCEAVR 88
Cdd:cd07454    6 IPIDIELCKDLPYNYTYFPNTILHNDQHTLQTHTEHFKPLMKTKCHPHIHFFICSVFAPMCPIGmpqAVTSCKSVCEQVK 85

                         90       100       110
                 ....*....|....*....|....*....|.
gi 697821717  89 DSCEPVMQFFGFFWPEMLKCDQFP-QDDVCI 118
Cdd:cd07454   86 ADCFSILEEFGIGWPEPLNCAQFPdPPELCM 116

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 697821717   6 PHQCVAIPADLRLCHSVGYDKMVLPNLLDHETMAEVKHQASSWVPLLNKNCHMGTQVFLCSLFAPVCLDRPVY---PCRW 82
Cdd:cd07455    2 RPRCLPVPSSLPFCSRLGIRSFWLPNFLNHTSVEEVRAVLAEWAWLLESGCHPSLEWFFCLLLVPSCGGGPPPpppPCRQ 81

                 ....*....
gi 697821717  83 LCEAVRDSC 91
Cdd:cd07455   82 FCEVLQDSC 90

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 697821717  151 EHLCA-SEFALKMTIKEVKKENGDKMIVPRKRKALKLGpIRKKNLKKLVLFLKNGaDCPCHQLdNLGQYFLIMGRQVKT- 228
Cdd:pfam01759   1 KKACKgSDYVYKVKVLSVEEEGSFDKYTVKVKEVLKEG-TDKIQRGKVRLFLKRG-DCRCPQL-RLGKEYLIMGKVGDLe 77

                  ....*...
gi 697821717  229 ---QYLLT 233
Cdd:pfam01759  78 grgRYVLD 85

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 697821717  55 NCHMGTQVFLCSLFAPVCL----DRP-VYPCRWLCEAVRDSCEPVMQFFGFFWPEMLKCDQF 111
Cdd:cd07445   48 SCYQHIMLFGCSLALPECIsdgdDRHgLLPCRSFCEAAKEGCEPVLGMVNASWPDFLRCSQF 109

Cysteine-rich domain of the smoothened receptor (Smo) integral membrane protein; The cysteine-rich domain (CRD) is part of the smoothened receptor (Smo), an integral membrane protein and one of the key players in the Hedgehog (Hh) signaling pathway, critical for development, cell growth and migration, as well as stem cell maintenance. The CRD of Smo is conserved in vertebrates and can also be identified in invertebrates. The precise function of the CRD in Smo is unknown. Mutations in the Drosophila CRD disrupt Smo activity in vivo, while deletion of the CRD in mammalian cells does not seem to affect the activity of overexpressed Smo.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 697821717  34 DHETMAEVKHQASSWVPLLN-KNCHMGTQVFLCSLFAPVCLDRPVY-PCRWLCEAVRDSCEPVmqFFGFFWPEMLKCD 109
Cdd:cd07451   30 DSTTQEEVQEKLHLWSGLRNvPKCWAVIQPLLCALYMPKCENGKVElPSQEMCQATRGPCKIV--ENERGWPDFLRCD 105