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 150421670  47 YSKPPQCLDIPADLPLCHTVGYKRMRLPNLLEHESLAEVKQQASSWLPLLAKRCHSDTQVFLCSLFAPVCLDRPIYPCRS 126
Cdd:cd07444    1 YSKQPQCVDIPADLPLCHNVGYKRMRLPNLLEHESMAEVKQQASSWVPLLAKRCHADTQVFLCSLFAPVCLDRPIYPCRS 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 150421670 127 LCEAVRAGCAPLMEAYGFPWPEMLHCHKFPLDNDLCIAVQFGHLPAT 173
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 150421670  47 YSKPPQCLDIPADLPLCHTVGYKRMRLPNLLEHESLAEVKQQASSWLPLLAKRCHSDTQVFLCSLFAPVCLDRPIYPCRS 126
Cdd:cd07444    1 YSKQPQCVDIPADLPLCHNVGYKRMRLPNLLEHESMAEVKQQASSWVPLLAKRCHADTQVFLCSLFAPVCLDRPIYPCRS 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 150421670 127 LCEAVRAGCAPLMEAYGFPWPEMLHCHKFPLDNDLCIAVQFGHLPAT 173
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 150421670    56 IPADLPLCHTVGYKRMRLPNLLEHESLAEVKQQASSWLPLLAKRCHSDTQVFLCSLFAPVCLDR--PIYPCRSLCEAVRA 133
Cdd:smart00063   2 EPITIPLCKDLGYNLTSMPNLLGHTTQEEAGLELEQFHPLLNVQCSPDLRFFLCSVYAPICTEDlrPILPCRSLCEAARE 81

                           90       100       110
                   ....*....|....*....|....*....|.
gi 150421670   134 GCAPLMEAYGFPWPEMLHCHKFPLDNDLCIA 164
Cdd:smart00063  82 GCEPLMEKFGFPWPEFLRCDRFPVQEELCMD 112

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 150421670  195 EQMCS-SDFVVKMRIKEIKIENGDRKLI---------GAQkkkkllkpgplkRKDTKRLVLHMKNGAgCPCPQLDsLAGS 264
Cdd:pfam01759   1 KKACKgSDYVYKVKVLSVEEEGSFDKYTvkvkevlkeGTD------------KIQRGKVRLFLKRGD-CRCPQLR-LGKE 66

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 150421670  265 FLVMGRKVD-----------GQLLLMAVYRWDKKNKEMK 292
Cdd:pfam01759  67 YLIMGKVGDlegrgryvldkNSWVEPWPTKWECKLRELQ 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 150421670  47 YSKPPQCLDIPADLPLCHTVGYKRMRLPNLLEHESLAEVKQQASSWLPLLAKRCHSDTQVFLCSLFAPVCLDRPIYPCRS 126
Cdd:cd07444    1 YSKQPQCVDIPADLPLCHNVGYKRMRLPNLLEHESMAEVKQQASSWVPLLAKRCHADTQVFLCSLFAPVCLDRPIYPCRS 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 150421670 127 LCEAVRAGCAPLMEAYGFPWPEMLHCHKFPLDNDLCIAVQFGHLPAT 173
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 150421670  53 CLDIPADLPLCHTVGYKRMRLPNLLEHESLAEVKQQASSWLPLLAKRCHSDTQVFLCSLFAPVCLDRPIYPCRSLCEAVR 132
Cdd:cd07453    3 CMRIPKSMALCYDIGYSEMRIPNLLEHETMAEVIQQSSSWLPLLARECHPDARIFLCSLFAPICWDRPIYPCRSLCEAVR 82

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 150421670 133 AGCAPLMEAYGFPWPEMLHCHKFPLDNDLCIAVQFghLPATAPPVTKICAQCEME 187
Cdd:cd07453   83 SSCAPLMACYGYPWPEILHCDKFPVDHDLCISPQF--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 150421670 178 TKICAQCEMEH-SADGLMEQMCSSDFVVKMRIKEIKIENGDRKLIGAQKKKKLLKPGPLkRKDTKRLVLHMKNGAGCPCP 256
Cdd:cd03580    1 PKVCPPCENEEeSAKTLLDNFCASDFALKVKIKEISYENGDRKVIGEKKKEILKQGPLK-KKDLKKLVLWLKNGANCPCP 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 150421670 257 QLDSLAGSFLVMGRKVDGQLLLMAVYRWDKKNKEMKFAVKFMFSYPC 303
Cdd:cd03580   80 QLDNLNGVYLVMGRKVDGKLLLTSIYKWQKKNKEFKRAVRKWKKHKC 126

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 150421670  52 QCLDIPadLPLCHTVGYKRMRLPNLLEHESLAEVKQQASSWLPLLAKRCHSDTQVFLCSLFAPVCL---DRPIYPCRSLC 128
Cdd:cd07066    1 KCEPIP--LPLCRGLPYNTTRFPNLLGHESQEEAEQELESFTPLVNSGCHPDLRFFLCSLYFPECTpdgDRPIPPCRSLC 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 150421670 129 EAVRAGCAPLMEAYGFPWPEMLHCHKFPLDN--DLCIAVQ 166
Cdd:cd07066   79 EEVRDSCEPLMLAFGFPWPEPLDCDRFPDSNeeGLCISPP 118

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 150421670  57 PADLPLCHTVGYKRMRLPNLLEHESLAEVKQQASSWLPLLAKRCHSDTQVFLCSLFAPVC---LDRPIYPCRSLCEAVRA 133
Cdd:cd07448    6 PIRIEMCQGLGYNVTRMPNLVGHELQTDAELQLQTFTPLIQYGCSSQLKFFLCSVYVPMCtekVPVPIGPCRPLCLSVKK 85

                         90       100
                 ....*....|....*....|....*..
gi 150421670 134 GCAPLMEAYGFPWPEMLHCHKFPLDND 160
Cdd:cd07448   86 RCLPVLKEFGFPWPEALNCSKFPPQNN 112

Fz domain; Also known as the CRD (cysteine rich domain), the C6 box in MuSK receptor. This domain of unknown function has been independently identified by several groups. The domain contains 10 conserved cysteines.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150421670   53 CLDIpaDLPLCHTVGYKRMRLPNLLEHESLAEVKQQA-----SSWLPLLAKRCHSDTQVFLCSLFAPVC-----LDRPIY 122
Cdd:pfam01392   1 CEPI--TLPMCLGLGYNATVFPNLLGHQTQEEAELSLaylvlSEFEPLVDLSCSPSLRLFLCSLYFPPCtlgpsPKPVCP 78

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 150421670  123 PCRSLCEAVRAGCAPLME--AYGFPWPEMLHCHKFP 156
Cdd:pfam01392  79 PCRSLCEEVRYGCEPLLEeaKFGFSWPEFLDCDSLP 114

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 150421670  57 PADLPLCHTVGYKRMRLPNLLEHESLAEVKQQASSWLPLLAKRCHSDTQVFLCSLFAPVCLDR---PIYPCRSLCEAVRA 133
Cdd:cd07457    5 RITIPMCQGIGYNMTRMPNLLGHESQSEAAISIHEFAPLVQYGCAEHLRFFLCSLYAPMCTEQvsiPIPACRSMCEQARD 84

                         90       100       110
                 ....*....|....*....|....*....|....
gi 150421670 134 GCAPLMEAYGFPWPEMLHCHKFPLDND---LCIA 164
Cdd:cd07457   85 KCSPIMEQFSFSWPDSLDCDRLPRKNDpkdLCME 118

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 9 (Fz9) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 9 (Fz9) 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. Fz9 may play a signaling role in lymphoid development and maturation, particularly at points where B cells undergo self-renewal prior to further differentiation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150421670  57 PADLPLCHTVGYKRMRLPNLLEHESLAEVKQQASSWLPLLAKRCHSDTQVFLCSLFAPVCLDR---PIYPCRSLCEAVRA 133
Cdd:cd07463    7 PVVIPMCRGIGYNLTRMPNFLGHDSQREAAIKLNEFAPLVEYGCHVHLRFFLCSLYAPMCTDQvstSIPACRPMCEQARQ 86

                         90       100       110
                 ....*....|....*....|....*....|...
gi 150421670 134 GCAPLMEAYGFPWPEMLHCHKFPLDND---LCI 163
Cdd:cd07463   87 KCSPIMEQFNFGWPESLDCSRLPTRNDpnaLCM 119

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 150421670  57 PADLPLCHTVGYKRMRLPNLLEHESLAEVKQQASSWLPLLAKRCHSDTQVFLCSLFAPVCLDR---PIYPCRSLCEAVRA 133
Cdd:cd07462    7 PIEIPMCKDIGYNMTRMPNLMGHENQREAAIQLHEFAPLVEYGCHSHLKFFLCSLYAPMCTEQvstPIPACRVMCEQARL 86

                         90       100       110
                 ....*....|....*....|....*....|...
gi 150421670 134 GCAPLMEAYGFPWPEMLHCHKFPLDND---LCI 163
Cdd:cd07462   87 KCSPIMEQFNFKWPDSLDCSKLPNKNDpnyLCM 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 150421670  57 PADLPLCHTVGYKRMRLPNLLEHESLAEVKQQASSWLPLLAKRCHSDTQVFLCSLFAPVC--LDRPIYPCRSLCEAVRAG 134
Cdd:cd07465    7 PISIPLCTDIAYNQTIMPNLLGHTNQEDAGLEVHQFYPLVKVQCSAELKFFLCSMYAPVCtvLEQALPPCRSLCERARQG 86

                         90       100       110
                 ....*....|....*....|....*....|..
gi 150421670 135 CAPLMEAYGFPWPEMLHCHKFPLD--NDLCIA 164
Cdd:cd07465   87 CEALMNKFGFQWPDTLRCEKFPVHgaGELCVG 118

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 150421670  57 PADLPLCHTVGYKRMRLPNLLEHESLAEVKQQASSWLPLLAKRCHSDTQVFLCSLFAPVCL----DRPIYPCRSLCEAVR 132
Cdd:cd07441    6 PVRIPMCKSMPWNMTKMPNHLHHSTQANAVLAIEQFEGLLGTQCSPDLLFFLCAMYAPICTidfqHEPIKPCKSVCERAR 85

                         90       100       110
                 ....*....|....*....|....*....|...
gi 150421670 133 AGCAPLMEAYGFPWPEMLHCHKFPL-DNDLCIA 164
Cdd:cd07441   86 AGCEPVLIRYRHTWPESLACEELPVyDRGVCIS 118

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 150421670  56 IPADLPLCHTVGYKRMRLPNLLEHESLAEVKQQASSWLPLLAKRCHSDTQVFLCSLFAPVCLDR---PIYPCRSLCEAVR 132
Cdd:cd07454    6 IPIDIELCKDLPYNYTYFPNTILHNDQHTLQTHTEHFKPLMKTKCHPHIHFFICSVFAPMCPIGmpqAVTSCKSVCEQVK 85

                         90       100       110
                 ....*....|....*....|....*....|.
gi 150421670 133 AGCAPLMEAYGFPWPEMLHCHKFPLDNDLCI 163
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 150421670  50 PPQCLDIPADLPLCHTVGYKRMRLPNLLEHESLAEVKQQASSWLPLLAKRCHSDTQVFLCSLFAPVCLDRPIY---PCRS 126
Cdd:cd07455    2 RPRCLPVPSSLPFCSRLGIRSFWLPNFLNHTSVEEVRAVLAEWAWLLESGCHPSLEWFFCLLLVPSCGGGPPPpppPCRQ 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 150421670 127 LCEAVRAGCAPLMEAYGFPwpemLHCHKFPLDND-LCIAVQF 167
Cdd:cd07455   82 FCEVLQDSCWNLLEGGRLP----VACASLPEQEDgYCVLIGP 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 150421670  51 PQCLDIpaDLPLCHTVGYKRMRLPNLLEHESLAEVKQQASSWL-----PLLAKRCHSDTQVFLCSLFAPVCL-DRPIYPC 124
Cdd:cd07447    2 ATCTDL--LLSYCSDVSYTQTTFPNLLGHRSREVTEAGAEYLLlsvlhGLLGGECNPDIRLLGCSVLAPRCEnDKVIKPC 79

                         90       100       110
                 ....*....|....*....|....*....|.
gi 150421670 125 RSLCEAVRAGCAPLMEAYGFPWPEMLHCHKF 155
Cdd:cd07447   80 RSTCEALRKRCSHAFDAIQMAWPYFLDCDRF 110

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 150421670 198 CSSDFVVKMRIKEIKIENGDRKligAQKKKKLLKPGPLKRKDTKRLVLHMKNGAGCPCPQLDSLAGSFLVMGRKVD--GQ 275
Cdd:cd03523    4 CKSDYVVRAKIKEIKEENDDVK---YEVKIIKIYKTGKAKADKADLRFYYTAPACCPCHPILNPGREYLIMGKEEDsqGG 80

                         90       100
                 ....*....|....*....|
gi 150421670 276 LLLM---AVYRWDKKNKEMK 292
Cdd:cd03523   81 LVLDplsFVEPWSPLSLRQD 100

Netrin C-terminal Domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150421670   194 MEQMCSS--DFVVKMRIKEIKIENGDRKLI---------GaqkkkkllkpgpLKRKDTKRLVLHMKNG-AGCPCPQLDSL 261
Cdd:smart00643   1 LEKACKSdvDYVYKVKVLSVEEEGGFDKYTvkileviksG------------TDELVRGKNKLRVFISrASCRCPLLLKL 68

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 150421670   262 AGSFLVMGRKVD-------GQLLLMA---VYRWDKKNK 289
Cdd:smart00643  69 GKSYLIMGKSGDlwdakgrGQYVLGKnswVEEWPTEEE 106

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150421670  78 EHESLAEVKQQASSWLPL-LAKRCHSDTQVFLCSLFAPVCLDRPIY-PCRSLCEAVRAGCAPLMEAYGfpWPEMLHCHKF 155
Cdd:cd07451   30 DSTTQEEVQEKLHLWSGLrNVPKCWAVIQPLLCALYMPKCENGKVElPSQEMCQATRGPCKIVENERG--WPDFLRCDND 107

                 ....*..
gi 150421670 156 PLDNDLC 162
Cdd:cd07451  108 RFPPRGC 114