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 1974316043  45 YTKQSQCVDIPADLQLCHNVGYKRMRLPNLLEHDSMPEIKQQANSWVPLLAKRCHSDTQIFLCSLFTPVCLDQPIYPCRS 124
Cdd:cd07444     1 YSKQPQCVDIPADLPLCHNVGYKRMRLPNLLEHESMAEVKQQASSWVPLLAKRCHADTQVFLCSLFAPVCLDRPIYPCRS 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1974316043 125 LCEVVRDSCAPVMESYGFPWPDMLNCNKFPFDNDLCITVQFGNNQVT 171
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 1974316043  45 YTKQSQCVDIPADLQLCHNVGYKRMRLPNLLEHDSMPEIKQQANSWVPLLAKRCHSDTQIFLCSLFTPVCLDQPIYPCRS 124
Cdd:cd07444     1 YSKQPQCVDIPADLPLCHNVGYKRMRLPNLLEHESMAEVKQQASSWVPLLAKRCHADTQVFLCSLFAPVCLDRPIYPCRS 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1974316043 125 LCEVVRDSCAPVMESYGFPWPDMLNCNKFPFDNDLCITVQFGNNQVT 171
Cdd:cd07444    81 LCEAVRDSCAPVMESYGFPWPEMLHCHKFPLDNDLCIAVQFGHLQAT 127

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 1974316043   54 IPADLQLCHNVGYKRMRLPNLLEHDSMPEIKQQANSWVPLLAKRCHSDTQIFLCSLFTPVCLDQ--PIYPCRSLCEVVRD 131
Cdd:smart00063   2 EPITIPLCKDLGYNLTSMPNLLGHTTQEEAGLELEQFHPLLNVQCSPDLRFFLCSVYAPICTEDlrPILPCRSLCEAARE 81

                           90       100       110
                   ....*....|....*....|....*....|
gi 1974316043  132 SCAPVMESYGFPWPDMLNCNKFPFDNDLCI 161
Cdd:smart00063  82 GCEPLMEKFGFPWPEFLRCDRFPVQEELCM 111

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 1974316043 193 EQMCS-SDFVVKMHIKEIKKENGerRLVATQKKKKVLKVGpLKRKDTKKLVLYMKNaGTCPCPQLdDLSGSFLVMGRKV- 270
Cdd:pfam01759   1 KKACKgSDYVYKVKVLSVEEEGS--FDKYTVKVKEVLKEG-TDKIQRGKVRLFLKR-GDCRCPQL-RLGKEYLIMGKVGd 75

                          90       100       110
                  ....*....|....*....|....*....|
gi 1974316043 271 ---GGRLLV----LAIY---RWEKKNKEMK 290
Cdd:pfam01759  76 legRGRYVLdknsWVEPwptKWECKLRELQ 105

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 1974316043  45 YTKQSQCVDIPADLQLCHNVGYKRMRLPNLLEHDSMPEIKQQANSWVPLLAKRCHSDTQIFLCSLFTPVCLDQPIYPCRS 124
Cdd:cd07444     1 YSKQPQCVDIPADLPLCHNVGYKRMRLPNLLEHESMAEVKQQASSWVPLLAKRCHADTQVFLCSLFAPVCLDRPIYPCRS 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1974316043 125 LCEVVRDSCAPVMESYGFPWPDMLNCNKFPFDNDLCITVQFGNNQVT 171
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 1974316043  49 SQCVDIPADLQLCHNVGYKRMRLPNLLEHDSMPEIKQQANSWVPLLAKRCHSDTQIFLCSLFTPVCLDQPIYPCRSLCEV 128
Cdd:cd07453     1 SPCMRIPKSMALCYDIGYSEMRIPNLLEHETMAEVIQQSSSWLPLLARECHPDARIFLCSLFAPICWDRPIYPCRSLCEA 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1974316043 129 VRDSCAPVMESYGFPWPDMLNCNKFPFDNDLCITVQFgnNQVTQPPVSRICTQCEIE 185
Cdd:cd07453    81 VRSSCAPLMACYGYPWPEILHCDKFPVDHDLCISPQF--IDTLSPERVKPRASCEDC 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 1974316043 176 SRICTQCEIEHK-ADGIMEQMCSSDFVVKMHIKEIKKENGERRLVAtQKKKKVLKVGPLKRKDTKKLVLYMKNAGTCPCP 254
Cdd:cd03580     1 PKVCPPCENEEEsAKTLLDNFCASDFALKVKIKEISYENGDRKVIG-EKKKEILKQGPLKKKDLKKLVLWLKNGANCPCP 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1974316043 255 QLDDLSGSFLVMGRKVGGRLLVLAIYRWEKKNKEMKFAVKFMFSYPC 301
Cdd:cd03580    80 QLDNLNGVYLVMGRKVDGKLLLTSIYKWQKKNKEFKRAVRKWKKHKC 126

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 1974316043  49 SQCVDIPADLQLCHNVGYKRMRLPNLLEHDSMPEIKQQANSWVPLLAKRCHSDTQIFLCSLFTPVCLDQPIYPCRSLCEV 128
Cdd:cd07452     7 TKCVPIPPEMSMCQDVGYSEMRLPNLLGHTSMAEVVPKSADWQTLLHTGCHPHARTFLCSLFAPVCLDTFIQPCRSMCVA 86

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1974316043 129 VRDSCAPVMESYGFPWPDMLNCNKFPFDNDLCIT 162
Cdd:cd07452    87 VRDSCAPVLACHGHSWPESLDCDRFPAGEDMCLA 120

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 1974316043  55 PADLQLCHNVGYKRMRLPNLLEHDSMPEIKQQANSWVPLLAKRCHSDTQIFLCSLFTPVC---LDQPIYPCRSLCEVVRD 131
Cdd:cd07448     6 PIRIEMCQGLGYNVTRMPNLVGHELQTDAELQLQTFTPLIQYGCSSQLKFFLCSVYVPMCtekVPVPIGPCRPLCLSVKK 85

                          90       100
                  ....*....|....*....|....*..
gi 1974316043 132 SCAPVMESYGFPWPDMLNCNKFPFDND 158
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 1974316043  55 PADLQLCHNVGYKRMRLPNLLEHDSMPEIKQQANSWVPLLAKRCHSDTQIFLCSLFTPVCLDQ---PIYPCRSLCEVVRD 131
Cdd:cd07457     5 RITIPMCQGIGYNMTRMPNLLGHESQSEAAISIHEFAPLVQYGCAEHLRFFLCSLYAPMCTEQvsiPIPACRSMCEQARD 84

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1974316043 132 SCAPVMESYGFPWPDMLNCNKFPFDND---LCI 161
Cdd:cd07457    85 KCSPIMEQFSFSWPDSLDCDRLPRKNDpkdLCM 117

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 1974316043  47 KQSQCVDIPadLQLCHNVGYKRMRLPNLLEHDSMPEIKQQANSWVPLLAKRCHSDTQIFLCSLFTPVCLD---QPIYPCR 123
Cdd:cd07461     1 KELQCQEIT--VPLCKGIGYNYTYMPNQFNHDTQDEAGLEVHQFWPLVEIQCSPDLKFFLCSMYTPICLEdykKPLPPCR 78

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1974316043 124 SLCEVVRDSCAPVMESYGFPWPDMLNCNKFP 154
Cdd:cd07461    79 SVCERAKAGCAPLMRQYGFPWPDRMRCDLLP 109

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 1974316043  60 LCHNVGYKRMRLPNLLEHDSMPEIKQQANSWVPLLAKRCHSDTQIFLCSLFTPVCL---DQPIYPCRSLCEVVRDSCAPV 136
Cdd:cd07456     9 MCKGIGYNMTYMPNQFNHDTQEEAGLEVHQFWPLVEIQCSPDLKFFLCSMYTPICLedyDKPLPPCRSVCERARDGCAPI 88

                          90       100
                  ....*....|....*....|....*...
gi 1974316043 137 MESYGFPWPDMLNCNKFP---FDNDLCI 161
Cdd:cd07456    89 MRQYGFAWPERMSCDALPeggDPDNLCM 116

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 1974316043  60 LCHNVGYKRMRLPNLLEHDSMPEIKQQANSWVPLLAKRCHSDTQIFLCSLFTPVCLD---QPIYPCRSLCEVVRDSCAPV 136
Cdd:cd07460    12 MCKGIGYNLTYMPNQFNHDTQDEAGLEVHQFWPLVEIQCSPDLRFFLCSMYTPICLPdyrKPLPPCRSVCERAKAGCSPL 91

                          90       100
                  ....*....|....*....|....*...
gi 1974316043 137 MESYGFPWPDMLNCNKFPFDND---LCI 161
Cdd:cd07460    92 MRQYGFAWPERMNCDRLPVLGDpetLCM 119

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 7 (Fz7) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 7 (Fz7) 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 Fz7 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 1974316043  55 PADLQLCHNVGYKRMRLPNLLEHDSMPEIKQQANSWVPLLAKRCHSDTQIFLCSLFTPVC--LDQPIYPCRSLCEVVRDS 132
Cdd:cd07466     7 PISIPLCTDIAYNQTIMPNLLGHTNQEDAGLEVHQFYPLVKVQCSPELKFFLCSMYAPVCtvLEQAIPPCRSLCERARQG 86

                          90       100
                  ....*....|....*....|..
gi 1974316043 133 CAPVMESYGFPWPDMLNCNKFP 154
Cdd:cd07466    87 CEALMNKFGFQWPERLRCENFP 108

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 1974316043  54 IPADLQLCHNVGYKRMRLPNLLEHDSMPEIKQQANSWVPLLAKRCHSDTQIFLCSLFTPVCLDQ---PIYPCRSLCEVVR 130
Cdd:cd07454     6 IPIDIELCKDLPYNYTYFPNTILHNDQHTLQTHTEHFKPLMKTKCHPHIHFFICSVFAPMCPIGmpqAVTSCKSVCEQVK 85

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1974316043 131 DSCAPVMESYGFPWPDMLNCNKFPFDNDLCI 161
Cdd:cd07454    86 ADCFSILEEFGIGWPEPLNCAQFPDPPELCM 116

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 1974316043  50 QCVDIPadlqLCHNVGYKRMRLPNLLEHDSMPEIKQQANSWVPLLAKRCHSDTQIFLCSLFTPVC----LDQPIYPCRSL 125
Cdd:cd07442     6 EAVRIP----MCRHMPWNITRMPNHLHHSTQENAVLAIEQYEELVDTGCSPVLPFFLCAMYAPICtlefLYDPIKPCRSV 81

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1974316043 126 CEVVRDSCAPVMESYGFPWPDMLNCNKFP-FDNDLCIT 162
Cdd:cd07442    82 CQRARDGCEPIMRRYNHSWPESLACDDLPvYDRGVCIS 119

NTR_like domain; a beta barrel with an oligosaccharide/oligonucleotide-binding fold found in netrins, complement proteins, tissue inhibitors of metalloproteases (TIMP), and procollagen C-proteinase enhancers (PCOLCE), amongst others. In netrins, the domain plays a role in controlling axon branching in neural development, while the common function of these modules in TIMPs appears to be binding to metzincins. A subset of this family is also known as the C345C domain because it occurs as a C-terminal domain in complement C3, C4 and C5. In C5, the domain interacts with various partners during the formation of the membrane attack complex.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1974316043 196 CSSDFVVKMHIKEIKKENGERRLVAtqKKKKVLKVGPLKrKDTKKLVLYMKNAGTCPCPQLDDLSGSFLVMGRKVGGR-L 274
Cdd:cd03523     4 CKSDYVVRAKIKEIKEENDDVKYEV--KIIKIYKTGKAK-ADKADLRFYYTAPACCPCHPILNPGREYLIMGKEEDSQgG 80

                          90       100
                  ....*....|....*....|
gi 1974316043 275 LVL----AIYRWEKKNKEMK 290
Cdd:cd03523    81 LVLdplsFVEPWSPLSLRQD 100

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 1974316043  55 PADLQLCHNVGYKRMRLPNLLEHDSMPE--IKQQANSWVPLLAKRCHSDTQIFLCSLFTPVC---LDQPIYPCRSLCEVV 129
Cdd:cd07888     4 PITLELCMNLPYNTTRYPNYLGHRTQKEasISWESSLFPALVQTNCYKYLMFFACTILVPKCdpvTQQRIPPCRSLCRNS 83

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1974316043 130 RDSCAPVMESYGFPWPDMLNCNKFP---FDNDLCIT 162
Cdd:cd07888    84 KERCESVLGIVGLQWPEDTDCAQFPeenSDNQTCLL 119

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 1974316043 193 EQMCS-SDFVVKMHIKEIKKENGerRLVATQKKKKVLKVGpLKRKDTKKLVLYMKNaGTCPCPQLdDLSGSFLVMGRKV- 270
Cdd:pfam01759   1 KKACKgSDYVYKVKVLSVEEEGS--FDKYTVKVKEVLKEG-TDKIQRGKVRLFLKR-GDCRCPQL-RLGKEYLIMGKVGd 75

                          90       100       110
                  ....*....|....*....|....*....|
gi 1974316043 271 ---GGRLLV----LAIY---RWEKKNKEMK 290
Cdd:pfam01759  76 legRGRYVLdknsWVEPwptKWECKLRELQ 105

Netrin C-terminal Domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1974316043  192 MEQMCSS--DFVVKMHIKEIKKENGERRLvaTQKKKKVLKVGpLKRKDTKKLVLYMKNAG-TCPCPQLDDLSGSFLVMGR 268
Cdd:smart00643   1 LEKACKSdvDYVYKVKVLSVEEEGGFDKY--TVKILEVIKSG-TDELVRGKNKLRVFISRaSCRCPLLLKLGKSYLIMGK 77

                   ..
gi 1974316043  269 KV 270
Cdd:smart00643  78 SG 79

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 1974316043  98 CHSDTQIFLCSLFTPVCLDQP-----IYPCRSLCEVVRDSCAPVMESYGFPWPDMLNCNKF 153
Cdd:cd07445    49 CYQHIMLFGCSLALPECISDGddrhgLLPCRSFCEAAKEGCEPVLGMVNASWPDFLRCSQF 109