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 19353578  52 YTKPPQCVDIPVDLRLCHNVGYKKMVLPNLLEHETMAEVKQQASSWVPLLNKNCHMGTQVFLCSLFAPVCLDRPIYPCRW 131
Cdd:cd07443   1 YTKPPQCVDIPADLRLCHNVGYKKMVLPNLLDHETMAEVKQQASSWVPLLNKNCHKGTQVFLCSLFAPVCLDRPVYPCRW 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 19353578 132 LCEAVRDSCEPVMQFFGFYWPEMLKCDKFPEGDVCIAMTPPNTT 175
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 19353578  52 YTKPPQCVDIPVDLRLCHNVGYKKMVLPNLLEHETMAEVKQQASSWVPLLNKNCHMGTQVFLCSLFAPVCLDRPIYPCRW 131
Cdd:cd07443   1 YTKPPQCVDIPADLRLCHNVGYKKMVLPNLLDHETMAEVKQQASSWVPLLNKNCHKGTQVFLCSLFAPVCLDRPVYPCRW 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 19353578 132 LCEAVRDSCEPVMQFFGFYWPEMLKCDKFPEGDVCIAMTPPNTT 175
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 19353578     61 IPVDLRLCHNVGYKKMVLPNLLEHETMAEVKQQASSWVPLLNKNCHMGTQVFLCSLFAPVCLDR--PIYPCRWLCEAVRD 138
Cdd:smart00063   2 EPITIPLCKDLGYNLTSMPNLLGHTTQEEAGLELEQFHPLLNVQCSPDLRFFLCSVYAPICTEDlrPILPCRSLCEAARE 81

                           90       100       110
                   ....*....|....*....|....*....|..
gi 19353578    139 SCEPVMQFFGFYWPEMLKCDKFP-EGDVCIAM 169
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 19353578   200 EHLCA-SEFALRMKIKEVKKENGDKKIVPKKKKPLKLGpIKKKELKRLVLFLKNGaDCPCHQLdNLSHNFLIMGRKV--- 275
Cdd:pfam01759   1 KKACKgSDYVYKVKVLSVEEEGSFDKYTVKVKEVLKEG-TDKIQRGKVRLFLKRG-DCRCPQL-RLGKEYLIMGKVGdle 77

                          90       100
                  ....*....|....*....|....*....
gi 19353578   276 --------KSQYLLTAIHKWDKKNKEFKN 296
Cdd:pfam01759  78 grgryvldKNSWVEPWPTKWECKLRELQK 106

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 19353578  52 YTKPPQCVDIPVDLRLCHNVGYKKMVLPNLLEHETMAEVKQQASSWVPLLNKNCHMGTQVFLCSLFAPVCLDRPIYPCRW 131
Cdd:cd07443   1 YTKPPQCVDIPADLRLCHNVGYKKMVLPNLLDHETMAEVKQQASSWVPLLNKNCHKGTQVFLCSLFAPVCLDRPVYPCRW 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 19353578 132 LCEAVRDSCEPVMQFFGFYWPEMLKCDKFPEGDVCIAMTPPNTT 175
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 19353578  58 CVDIPVDLRLCHNVGYKKMVLPNLLEHETMAEVKQQASSWVPLLNKNCHMGTQVFLCSLFAPVCLDRPIYPCRWLCEAVR 137
Cdd:cd07453   3 CMRIPKSMALCYDIGYSEMRIPNLLEHETMAEVIQQSSSWLPLLARECHPDARIFLCSLFAPICWDRPIYPCRSLCEAVR 82

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 19353578 138 DSCEPVMQFFGFYWPEMLKCDKFPEG-DVCIAmtpPNTTEASKPQGTTVCPPCDNE 192
Cdd:cd07453  83 SSCAPLMACYGYPWPEILHCDKFPVDhDLCIS---PQFIDTLSPERVKPRASCEDC 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 19353578 183 TTVCPPCDNELKS-EAIIEHLCASEFALRMKIKEVKKENGDKKIVPKKKKPL-KLGPIKKKELKRLVLFLKNGADCPCHQ 260
Cdd:cd03580   1 PKVCPPCENEEESaKTLLDNFCASDFALKVKIKEISYENGDRKVIGEKKKEIlKQGPLKKKDLKKLVLWLKNGANCPCPQ 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 19353578 261 LDNLSHNFLIMGRKVKSQYLLTAIHKWDKKNKEFKNFMKRMKNHEC 306
Cdd:cd03580  81 LDNLNGVYLVMGRKVDGKLLLTSIYKWQKKNKEFKRAVRKWKKHKC 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 19353578  57 QCVDIPVDLRLCHNVGYKKMVLPNLLEHETMAEVKQQASSWVPLLNKNCHMGTQVFLCSLFAPVCLDRPIYPCRWLCEAV 136
Cdd:cd07452   8 KCVPIPPEMSMCQDVGYSEMRLPNLLGHTSMAEVVPKSADWQTLLHTGCHPHARTFLCSLFAPVCLDTFIQPCRSMCVAV 87

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 19353578 137 RDSCEPVMQFFGFYWPEMLKCDKFPEG-DVCIAMTPPNTTEASKPQGTTVCPPC 189
Cdd:cd07452  88 RDSCAPVLACHGHSWPESLDCDRFPAGeDMCLASLSKEYQYFYKEFPKPACQSC 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 19353578  62 PVDLRLCHNVGYKKMVLPNLLEHETMAEVKQQASSWVPLLNKNCHMGTQVFLCSLFAPVC---LDRPIYPCRWLCEAVRD 138
Cdd:cd07448   6 PIRIEMCQGLGYNVTRMPNLVGHELQTDAELQLQTFTPLIQYGCSSQLKFFLCSVYVPMCtekVPVPIGPCRPLCLSVKK 85

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 19353578 139 SCEPVMQFFGFYWPEMLKCDKFP----EGDVCiaMTPPNTTEA 177
Cdd:cd07448  86 RCLPVLKEFGFPWPEALNCSKFPpqnnHNHMC--MEGPGDEEV 126

Cysteine-rich Wnt-binding domain (CRD) of receptors similar to frizzled 1; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 1 (Fz1), frizzled 2 (Fz2), and frizzled 7 (Fz7) 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 19353578  62 PVDLRLCHNVGYKKMVLPNLLEHETMAEVKQQASSWVPLLNKNCHMGTQVFLCSLFAPVC--LDRPIYPCRWLCEAVRDS 139
Cdd:cd07458   5 PITIPLCTDIPYNMTIFPNLLGHTKQEDAGLEVHQFYPLVKVQCSPDLKFFLCSVYAPVCtvLERPIPPCRSLCESARQG 84

                        90       100       110
                ....*....|....*....|....*....|..
gi 19353578 140 CEPVMQFFGFYWPEMLKCDKFPE---GDVCIA 168
Cdd:cd07458  85 CEALMNKFGFQWPESLDCEKFPVhgaGDLCVG 116

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 19353578  61 IPVDLRLCHNVGYKKMVLPNLLEHETMAEVKQQASSWVPLLNKNCHMGTQVFLCSLFAPVCL---DRPIYPCRWLCEAVR 137
Cdd:cd07456   3 EEITIPMCKGIGYNMTYMPNQFNHDTQEEAGLEVHQFWPLVEIQCSPDLKFFLCSMYTPICLedyDKPLPPCRSVCERAR 82

                        90       100
                ....*....|....*....|....*.
gi 19353578 138 DSCEPVMQFFGFYWPEMLKCDKFPEG 163
Cdd:cd07456  83 DGCAPIMRQYGFAWPERMSCDALPEG 108

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 19353578  62 PVDLRLCHNVGYKKMVLPNLLEHETMAEVKQQASSWVPLLNKNCHMGTQVFLCSLFAPVC--LDRPIYPCRWLCEAVRDS 139
Cdd:cd07465   7 PISIPLCTDIAYNQTIMPNLLGHTNQEDAGLEVHQFYPLVKVQCSAELKFFLCSMYAPVCtvLEQALPPCRSLCERARQG 86

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 19353578 140 CEPVMQFFGFYWPEMLKCDKFP---EGDVCIAMtppNTTEASKP 180
Cdd:cd07465  87 CEALMNKFGFQWPDTLRCEKFPvhgAGELCVGQ---NTSESGTP 127

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 19353578  62 PVDLRLCHNVGYKKMVLPNLLEHETMAEVKQQASSWVPLLNKNCHMGTQVFLCSLFAPVCLDR---PIYPCRWLCEAVRD 138
Cdd:cd07462   7 PIEIPMCKDIGYNMTRMPNLMGHENQREAAIQLHEFAPLVEYGCHSHLKFFLCSLYAPMCTEQvstPIPACRVMCEQARL 86

                        90       100
                ....*....|....*....|...
gi 19353578 139 SCEPVMQFFGFYWPEMLKCDKFP 161
Cdd:cd07462  87 KCSPIMEQFNFKWPDSLDCSKLP 109

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 19353578  54 KPPQCVDIPVDLrlCHNVGYKKMVLPNLLEHETMAEVKQQASSWVPLLNKNCHMGTQVFLCSLFAPVCLD---RPIYPCR 130
Cdd:cd07461   1 KELQCQEITVPL--CKGIGYNYTYMPNQFNHDTQDEAGLEVHQFWPLVEIQCSPDLKFFLCSMYTPICLEdykKPLPPCR 78

                        90       100       110
                ....*....|....*....|....*....|..
gi 19353578 131 WLCEAVRDSCEPVMQFFGFYWPEMLKCDKFPE 162
Cdd:cd07461  79 SVCERAKAGCAPLMRQYGFPWPDRMRCDLLPE 110

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 19353578  62 PVDLRLCHNVGYKKMVLPNLLEHETMAEVKQQASSWVPLLNKNCHMGTQVFLCSLFAPVCLD--RPIYPCRWLCEAVRDS 139
Cdd:cd07449   7 PITLRMCQDLPYNTTFMPNLLNHYDQQTAALAMEPFHPMVNLECSRDFRPFLCALYAPVCMEygRVTLPCRRLCQRAYSE 86

                        90       100
                ....*....|....*....|....*
gi 19353578 140 CEPVMQFFGFYWPEMLKCDKFPEGD 164
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 19353578  55 PPQCVDIPvdlrLCHNVGYKKMVLPNLLEHETMAEVKQQASSWVPLLNKNCHMGTQVFLCSLFAPVC----LDRPIYPCR 130
Cdd:cd07442   4 PCEAVRIP----MCRHMPWNITRMPNHLHHSTQENAVLAIEQYEELVDTGCSPVLPFFLCAMYAPICtlefLYDPIKPCR 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 19353578 131 WLCEAVRDSCEPVMQFFGFYWPEMLKCDKFPEGDVCIAMTP 171
Cdd:cd07442  80 SVCQRARDGCEPIMRRYNHSWPESLACDDLPVYDRGVCISP 120

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 19353578  61 IPVDLRLCHNVGYKKMVLPNLLEHETMAEVKQQASSWVPLLNKNCHMGTQVFLCSLFAPVCLDR---PIYPCRWLCEAVR 137
Cdd:cd07454   6 IPIDIELCKDLPYNYTYFPNTILHNDQHTLQTHTEHFKPLMKTKCHPHIHFFICSVFAPMCPIGmpqAVTSCKSVCEQVK 85

                        90       100       110
                ....*....|....*....|....*....|.
gi 19353578 138 DSCEPVMQFFGFYWPEMLKCDKFP-EGDVCI 167
Cdd:cd07454  86 ADCFSILEEFGIGWPEPLNCAQFPdPPELCM 116

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 6 (Fz6) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 6 (Fz6) 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. Frizzled 6 (Fz6) is expressed in the skin and hair follicles and controls hair patterning in mammals using a Fz-dependent tissue polarity system, which is similar to the one that patterns the Drosophila cuticle.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19353578  62 PVDLRLCHNVGYKKMVLPNLLEHETMAEVKQQASSWVPLLNKNCHMGTQVFLCSLFAPVCLDR--PIYPCRWLCEAVRDS 139
Cdd:cd07450   7 PITVPRCLKMPYNMTFFPNLMGHYDQDIAAVEMEPFLPLANLRCSPNVHTFLCQAFVPTCTEQihVVRPCRELCEKVYSD 86

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 19353578 140 CEPVMQFFGFYWPEMLKCDKFPEGDVCIAMTPPNTTEASKP 180
Cdd:cd07450  87 CKKLIDTFGISWPEELECDRLQYCDETVPDTADPHTEFSSP 127

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.

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gi 19353578  56 PQCVDIpvDLRLCHNVGYKKMVLPNLLEHETMAEVKQQA-----SSWVPLLNKNCHMGTQVFLCSLFAPVCL-DRPIYPC 129
Cdd:cd07447   2 ATCTDL--LLSYCSDVSYTQTTFPNLLGHRSREVTEAGAeylllSVLHGLLGGECNPDIRLLGCSVLAPRCEnDKVIKPC 79

                        90       100       110
                ....*....|....*....|....*....|.
gi 19353578 130 RWLCEAVRDSCEPVMQFFGFYWPEMLKCDKF 160
Cdd:cd07447  80 RSTCEALRKRCSHAFDAIQMAWPYFLDCDRF 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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 19353578 104 NCHMGTQVFLCSLFAPVCL----DRP-IYPCRWLCEAVRDSCEPVMQFFGFYWPEMLKCDKF 160
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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 19353578  83 EHETMAEVKQQASSWVPLLN-KNCHMGTQVFLCSLFAPVCLDRPIY-PCRWLCEAVRDSCEPVMQFFGfyWPEMLKCDK 159
Cdd:cd07451  30 DSTTQEEVQEKLHLWSGLRNvPKCWAVIQPLLCALYMPKCENGKVElPSQEMCQATRGPCKIVENERG--WPDFLRCDN 106