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 56117838  52 YTKPPQCVDIPADLRLCHNVGYKKMVLPNLLEHETMAEVKQQASSWVPLLNKNCHAGTQVFLCSLFAPVCLDRPIYPCRW 131
Cdd:cd07443   1 YTKPPQCVDIPADLRLCHNVGYKKMVLPNLLDHETMAEVKQQASSWVPLLNKNCHKGTQVFLCSLFAPVCLDRPVYPCRW 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 56117838 132 LCEAVRDSCEPVMQFFGFYWPEMLKCDKFPEGDVCIAMTPPNAT 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 56117838  52 YTKPPQCVDIPADLRLCHNVGYKKMVLPNLLEHETMAEVKQQASSWVPLLNKNCHAGTQVFLCSLFAPVCLDRPIYPCRW 131
Cdd:cd07443   1 YTKPPQCVDIPADLRLCHNVGYKKMVLPNLLDHETMAEVKQQASSWVPLLNKNCHKGTQVFLCSLFAPVCLDRPVYPCRW 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 56117838 132 LCEAVRDSCEPVMQFFGFYWPEMLKCDKFPEGDVCIAMTPPNAT 175
Cdd:cd07443  81 LCEAVRDSCEPVMQFFGFYWPEMLKCDKFPEGEVCIAMTPPNAT 124

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 56117838 183 TTVCPPCDNELKS-EAIIEHLCASEFALRMKIKEVKKENGDKKIVPKKKKPL-KLGPIKKKDLKKLVLYLKNGADCPCHQ 260
Cdd:cd03580   1 PKVCPPCENEEESaKTLLDNFCASDFALKVKIKEISYENGDRKVIGEKKKEIlKQGPLKKKDLKKLVLWLKNGANCPCPQ 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 56117838 261 LDNLSHHFLIMGRKVKSQYLLTAIHKWDKKNKEFKNFMKKMKNHEC 306
Cdd:cd03580  81 LDNLNGVYLVMGRKVDGKLLLTSIYKWQKKNKEFKRAVRKWKKHKC 126

Netrin C-terminal Domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56117838    199 IEHLCASE--FALRMKIKEVKKENGDKKIVPKKKKPLKLGPIKKKDLKKLVLYLKNGADCPCHQLDNLSHHFLIMGRKV- 275
Cdd:smart00643   1 LEKACKSDvdYVYKVKVLSVEEEGGFDKYTVKILEVIKSGTDELVRGKNKLRVFISRASCRCPLLLKLGKSYLIMGKSGd 80

                           90       100       110
                   ....*....|....*....|....*....|....
gi 56117838    276 ------KSQYLLTA---IHKWDKKNK-EFKNFMK 299
Cdd:smart00643  81 lwdakgRGQYVLGKnswVEEWPTEEEcRLRRLQK 114

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 56117838  52 YTKPPQCVDIPADLRLCHNVGYKKMVLPNLLEHETMAEVKQQASSWVPLLNKNCHAGTQVFLCSLFAPVCLDRPIYPCRW 131
Cdd:cd07443   1 YTKPPQCVDIPADLRLCHNVGYKKMVLPNLLDHETMAEVKQQASSWVPLLNKNCHKGTQVFLCSLFAPVCLDRPVYPCRW 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 56117838 132 LCEAVRDSCEPVMQFFGFYWPEMLKCDKFPEGDVCIAMTPPNAT 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 56117838  58 CVDIPADLRLCHNVGYKKMVLPNLLEHETMAEVKQQASSWVPLLNKNCHAGTQVFLCSLFAPVCLDRPIYPCRWLCEAVR 137
Cdd:cd07453   3 CMRIPKSMALCYDIGYSEMRIPNLLEHETMAEVIQQSSSWLPLLARECHPDARIFLCSLFAPICWDRPIYPCRSLCEAVR 82

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 56117838 138 DSCEPVMQFFGFYWPEMLKCDKFPE-GDVCIAmtpPNATEASKPQGTTVCPPCDNE 192
Cdd:cd07453  83 SSCAPLMACYGYPWPEILHCDKFPVdHDLCIS---PQFIDTLSPERVKPRASCEDC 135

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56117838     61 IPADLRLCHNVGYKKMVLPNLLEHETMAEVKQQASSWVPLLNKNCHAGTQVFLCSLFAPVCLDR--PIYPCRWLCEAVRD 138
Cdd:smart00063   2 EPITIPLCKDLGYNLTSMPNLLGHTTQEEAGLELEQFHPLLNVQCSPDLRFFLCSVYAPICTEDlrPILPCRSLCEAARE 81

                           90       100       110
                   ....*....|....*....|....*....|..
gi 56117838    139 SCEPVMQFFGFYWPEMLKCDKFP-EGDVCIAM 169
Cdd:smart00063  82 GCEPLMEKFGFPWPEFLRCDRFPvQEELCMDP 113

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 56117838  57 QCVDIPADLRLCHNVGYKKMVLPNLLEHETMAEVKQQASSWVPLLNKNCHAGTQVFLCSLFAPVCLDRPIYPCRWLCEAV 136
Cdd:cd07452   8 KCVPIPPEMSMCQDVGYSEMRLPNLLGHTSMAEVVPKSADWQTLLHTGCHPHARTFLCSLFAPVCLDTFIQPCRSMCVAV 87

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 56117838 137 RDSCEPVMQFFGFYWPEMLKCDKFPEG-DVCIAMTPPNATEASKPQGTTVCPPC 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 56117838  62 PADLRLCHNVGYKKMVLPNLLEHETMAEVKQQASSWVPLLNKNCHAGTQVFLCSLFAPVC---LDRPIYPCRWLCEAVRD 138
Cdd:cd07448   6 PIRIEMCQGLGYNVTRMPNLVGHELQTDAELQLQTFTPLIQYGCSSQLKFFLCSVYVPMCtekVPVPIGPCRPLCLSVKK 85

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 56117838 139 SCEPVMQFFGFYWPEMLKCDKFP----EGDVCiaMTPPNATEA 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 56117838  62 PADLRLCHNVGYKKMVLPNLLEHETMAEVKQQASSWVPLLNKNCHAGTQVFLCSLFAPVC--LDRPIYPCRWLCEAVRDS 139
Cdd:cd07458   5 PITIPLCTDIPYNMTIFPNLLGHTKQEDAGLEVHQFYPLVKVQCSPDLKFFLCSVYAPVCtvLERPIPPCRSLCESARQG 84

                        90       100       110
                ....*....|....*....|....*....|..
gi 56117838 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 56117838  67 LCHNVGYKKMVLPNLLEHETMAEVKQQASSWVPLLNKNCHAGTQVFLCSLFAPVCL---DRPIYPCRWLCEAVRDSCEPV 143
Cdd:cd07456   9 MCKGIGYNMTYMPNQFNHDTQEEAGLEVHQFWPLVEIQCSPDLKFFLCSMYTPICLedyDKPLPPCRSVCERARDGCAPI 88

                        90       100
                ....*....|....*....|
gi 56117838 144 MQFFGFYWPEMLKCDKFPEG 163
Cdd:cd07456  89 MRQYGFAWPERMSCDALPEG 108

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 56117838  57 QCVDIPadlrLCHNVGYKKMVLPNLLEHETMAEVKQQASSWVPLLNKNCHAGTQVFLCSLFAPVCLDR---PIYPCRWLC 133
Cdd:cd07462   6 QPIEIP----MCKDIGYNMTRMPNLMGHENQREAAIQLHEFAPLVEYGCHSHLKFFLCSLYAPMCTEQvstPIPACRVMC 81

                        90       100
                ....*....|....*....|....*...
gi 56117838 134 EAVRDSCEPVMQFFGFYWPEMLKCDKFP 161
Cdd:cd07462  82 EQARLKCSPIMEQFNFKWPDSLDCSKLP 109

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 56117838  62 PADLRLCHNVGYKKMVLPNLLEHETMAEVKQQASSWVPLLNKNCHAGTQVFLCSLFAPVC--LDRPIYPCRWLCEAVRDS 139
Cdd:cd07466   7 PISIPLCTDIAYNQTIMPNLLGHTNQEDAGLEVHQFYPLVKVQCSPELKFFLCSMYAPVCtvLEQAIPPCRSLCERARQG 86

                        90       100       110
                ....*....|....*....|....*....|..
gi 56117838 140 CEPVMQFFGFYWPEMLKCDKFP---EGDVCIA 168
Cdd:cd07466  87 CEALMNKFGFQWPERLRCENFPvhgAGEICVG 118

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 56117838  54 KPPQCVDIPadLRLCHNVGYKKMVLPNLLEHETMAEVKQQASSWVPLLNKNCHAGTQVFLCSLFAPVCLD---RPIYPCR 130
Cdd:cd07461   1 KELQCQEIT--VPLCKGIGYNYTYMPNQFNHDTQDEAGLEVHQFWPLVEIQCSPDLKFFLCSMYTPICLEdykKPLPPCR 78

                        90       100       110
                ....*....|....*....|....*....|..
gi 56117838 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 56117838  62 PADLRLCHNVGYKKMVLPNLLEHETMAEVKQQASSWVPLLNKNCHAGTQVFLCSLFAPVCLD--RPIYPCRWLCEAVRDS 139
Cdd:cd07449   7 PITLRMCQDLPYNTTFMPNLLNHYDQQTAALAMEPFHPMVNLECSRDFRPFLCALYAPVCMEygRVTLPCRRLCQRAYSE 86

                        90       100
                ....*....|....*....|....*
gi 56117838 140 CEPVMQFFGFYWPEMLKCDKFPEGD 164
Cdd:cd07449  87 CSKLMEMFGVPWPEDMECSRFPDCD 111

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 56117838  62 PADLRLCHNVGYKKMVLPNLLEHETMAEVKQQASSWVPLLNKNCHAGTQVFLCSLFAPVCL----DRPIYPCRWLCEAVR 137
Cdd:cd07441   6 PVRIPMCKSMPWNMTKMPNHLHHSTQANAVLAIEQFEGLLGTQCSPDLLFFLCAMYAPICTidfqHEPIKPCKSVCERAR 85

                        90       100       110
                ....*....|....*....|....*....|....
gi 56117838 138 DSCEPVMQFFGFYWPEMLKCDKFPEGDVCIAMTP 171
Cdd:cd07441  86 AGCEPVLIRYRHTWPESLACEELPVYDRGVCISP 119

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 56117838  55 PPQCVDIPADLRLCHNVGYKKMVLPNLLEHETMAEVKQQASSWVPLLNKNCHAGTQVFLCSLFAPVCLDRPIY---PCRW 131
Cdd:cd07455   2 RPRCLPVPSSLPFCSRLGIRSFWLPNFLNHTSVEEVRAVLAEWAWLLESGCHPSLEWFFCLLLVPSCGGGPPPpppPCRQ 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 56117838 132 LCEAVRDSCEPVMQffGFYWPemLKCDKFPEGDV--CIAMTPP 172
Cdd:cd07455  82 FCEVLQDSCWNLLE--GGRLP--VACASLPEQEDgyCVLIGPP 120

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 56117838 200 EHLCASEFALRMKIKEVKKENGDKKIVPKKKKPLKLGPIkKKDLKKLVLYLKNGADCPCHQLDNLSHHFLIMGRKVKSQY 279
Cdd:cd03523   1 KAFCKSDYVVRAKIKEIKEENDDVKYEVKIIKIYKTGKA-KADKADLRFYYTAPACCPCHPILNPGREYLIMGKEEDSQG 79

                        90       100       110
                ....*....|....*....|....*....|
gi 56117838 280 LL-----TAIHKWDKKNKefknFMKKMKNH 304
Cdd:cd03523  80 GLvldplSFVEPWSPLSL----RQDRRLRE 105

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 56117838  56 PQCVDIpaDLRLCHNVGYKKMVLPNLLEHETMAEVKQQA-----SSWVPLLNKNCHAGTQVFLCSLFAPVCL-DRPIYPC 129
Cdd:cd07447   2 ATCTDL--LLSYCSDVSYTQTTFPNLLGHRSREVTEAGAeylllSVLHGLLGGECNPDIRLLGCSVLAPRCEnDKVIKPC 79

                        90       100       110
                ....*....|....*....|....*....|.
gi 56117838 130 RWLCEAVRDSCEPVMQFFGFYWPEMLKCDKF 160
Cdd:cd07447  80 RSTCEALRKRCSHAFDAIQMAWPYFLDCDRF 110

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 56117838  83 EHETMAEVKQQASSWVPLLN-KNCHAGTQVFLCSLFAPVCLDRPIY-PCRWLCEAVRDSCEPVMQFFGfyWPEMLKCDK 159
Cdd:cd07451  30 DSTTQEEVQEKLHLWSGLRNvPKCWAVIQPLLCALYMPKCENGKVElPSQEMCQATRGPCKIVENERG--WPDFLRCDN 106

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 56117838   200 EHLCA-SEFALRMKIKEVKKENGDKKIVPKKKKPLKLGpiKKKDLKKLVLYLKNGADCPCHQLdNLSHHFLIMGRKV--- 275
Cdd:pfam01759   1 KKACKgSDYVYKVKVLSVEEEGSFDKYTVKVKEVLKEG--TDKIQRGKVRLFLKRGDCRCPQL-RLGKEYLIMGKVGdle 77

                          90       100
                  ....*....|....*....|....*....
gi 56117838   276 --------KSQYLLTAIHKWDKKNKEFKN 296
Cdd:pfam01759  78 grgryvldKNSWVEPWPTKWECKLRELQK 106