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 1211247042  46 YGKPPQCVDIPEDLRLCHNVGYNQMLLPNLLEHETMAEVKQQAGSWVPLVHKSCHPGTQVFLCSLFAPVCLERPIYPCRW 125
Cdd:cd07443     1 YTKPPQCVDIPADLRLCHNVGYKKMVLPNLLDHETMAEVKQQASSWVPLLNKNCHKGTQVFLCSLFAPVCLDRPVYPCRW 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1211247042 126 LCEAVRDGCTPIMESFGFPWPEMLTCDKFPQDDVCIAMTAPNAT 169
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 1211247042  46 YGKPPQCVDIPEDLRLCHNVGYNQMLLPNLLEHETMAEVKQQAGSWVPLVHKSCHPGTQVFLCSLFAPVCLERPIYPCRW 125
Cdd:cd07443     1 YTKPPQCVDIPADLRLCHNVGYKKMVLPNLLDHETMAEVKQQASSWVPLLNKNCHKGTQVFLCSLFAPVCLDRPVYPCRW 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1211247042 126 LCEAVRDGCTPIMESFGFPWPEMLTCDKFPQDDVCIAMTAPNAT 169
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 1211247042   55 IPEDLRLCHNVGYNQMLLPNLLEHETMAEVKQQAGSWVPLVHKSCHPGTQVFLCSLFAPVCLER--PIYPCRWLCEAVRD 132
Cdd:smart00063   2 EPITIPLCKDLGYNLTSMPNLLGHTTQEEAGLELEQFHPLLNVQCSPDLRFFLCSVYAPICTEDlrPILPCRSLCEAARE 81

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1211247042  133 GCTPIMESFGFPWPEMLTCDKFP-QDDVCIAM 163
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 1211247042 195 EHMCA-SEFAIRTKIKEVRREGmDRKVILQKRKKPLKLGNLKKnDLKKLVLYLKNGaDCPCQQLdNLGNTYLIMGRKVDT 273
Cdd:pfam01759   1 KKACKgSDYVYKVKVLSVEEEG-SFDKYTVKVKEVLKEGTDKI-QRGKVRLFLKRG-DCRCPQL-RLGKEYLIMGKVGDL 76

                          90       100       110
                  ....*....|....*....|....*....|
gi 1211247042 274 -----------QFLLTGIHKWDKSSKEFKK 292
Cdd:pfam01759  77 egrgryvldknSWVEPWPTKWECKLRELQK 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 1211247042  46 YGKPPQCVDIPEDLRLCHNVGYNQMLLPNLLEHETMAEVKQQAGSWVPLVHKSCHPGTQVFLCSLFAPVCLERPIYPCRW 125
Cdd:cd07443     1 YTKPPQCVDIPADLRLCHNVGYKKMVLPNLLDHETMAEVKQQASSWVPLLNKNCHKGTQVFLCSLFAPVCLDRPVYPCRW 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1211247042 126 LCEAVRDGCTPIMESFGFPWPEMLTCDKFPQDDVCIAMTAPNAT 169
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 1211247042 178 SPICPPCDNEMKT-DIILEHMCASEFAIRTKIKEVRREGMDRKVILQKRKKPLKLGNLKKNDLKKLVLYLKNGADCPCQQ 256
Cdd:cd03580     1 PKVCPPCENEEESaKTLLDNFCASDFALKVKIKEISYENGDRKVIGEKKKEILKQGPLKKKDLKKLVLWLKNGANCPCPQ 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1211247042 257 LDNLGNTYLIMGRKVDTQFLLTGIHKWDKSSKEFKKAIKKLKTHKC 302
Cdd:cd03580    81 LDNLNGVYLVMGRKVDGKLLLTSIYKWQKKNKEFKRAVRKWKKHKC 126

Cysteine-rich domain of the secreted frizzled-related protein 2 (SFRP2), a regulator of Wnt activity; The cysteine-rich-domain (CRD) is an essential part of the secreted frizzled related protein 2 (SFRP2), 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 CRD domains of frizzled (Fz) proteins, thereby preventing Wnt proteins from binding to these receptors. SFRPs and Fz proteins both contain CRD domains, but SFRPs lack the seven-pass transmembrane domain which is an integral part of Fzs. As a Wnt antagonist, SFRP2 regulates Nkx2.2 expression in the ventral spinal cord and anteroposterior axis elongation. SFRP2 also has a Wnt-independent function as an enhancer of procollagen cleavage by the TLD proteinases. SFRP2 binds both procollagen and TLD, thus facilitating the enzymatic reaction by bringing together the proteinase and its substrate.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1211247042  48 KPPQCVDIPEDLRLCHNVGYNQMLLPNLLEHETMAEVKQQAGSWVPLVHKSCHPGTQVFLCSLFAPVC---LERPIYPCR 124
Cdd:cd07446     1 KKSNCKPIPANMLLCHGIEYTNMRLPNLLGHETMKEVLQQAGSWIPLVQKQCHPDTKKFLCSLFAPVClddLDEAIQPCR 80

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1211247042 125 WLCEAVRDGCTPIMESFGFPWPEMLTCDKFPQD-DVCI 161
Cdd:cd07446    81 SLCEAVKDGCAPVMSAFGFPWPDMLDCTRFPLDnDLCI 118

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 1211247042  51 QCVDIPEDLrlCHNVGYNQMLLPNLLEHETMAEVKQQAGSWVPLVHKSCHPGTQVFLCSLFAPVCLE---RPIYPCRWLC 127
Cdd:cd07066     1 KCEPIPLPL--CRGLPYNTTRFPNLLGHESQEEAEQELESFTPLVNSGCHPDLRFFLCSLYFPECTPdgdRPIPPCRSLC 78

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1211247042 128 EAVRDGCTPIMESFGFPWPEMLTCDKFPQ---DDVCIA 162
Cdd:cd07066    79 EEVRDSCEPLMLAFGFPWPEPLDCDRFPDsneEGLCIS 116

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 1211247042  56 PEDLRLCHNVGYNQMLLPNLLEHETMAEVKQQAGSWVPLVHKSCHPGTQVFLCSLFAPVC---LERPIYPCRWLCEAVRD 132
Cdd:cd07448     6 PIRIEMCQGLGYNVTRMPNLVGHELQTDAELQLQTFTPLIQYGCSSQLKFFLCSVYVPMCtekVPVPIGPCRPLCLSVKK 85

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1211247042 133 GCTPIMESFGFPWPEMLTCDKFP----QDDVCiaMTAPNATEA 171
Cdd:cd07448    86 RCLPVLKEFGFPWPEALNCSKFPpqnnHNHMC--MEGPGDEEV 126

Cysteine-rich Wnt-binding domain (CRD) of receptors similar to frizzled 9; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 9 (Fz9) and frizzled 10 (Fz10) receptors, and similar proteins. This domain is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and Ca(2+) modulating signaling pathway. The CRD domain is well conserved in metazoans - 10 frizzled proteins have been identified in mammals, 4 in Drosophila and 3 in Caenorhabditis elegans. Very little is known about the mechanism by which CRD domains interact with their ligands. The domain contains 10 conserved cysteines.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1211247042  51 QCVDIPedlrLCHNVGYNQMLLPNLLEHETMAEVKQQAGSWVPLVHKSCHPGTQVFLCSLFAPVCLER---PIYPCRWLC 127
Cdd:cd07457     4 ERITIP----MCQGIGYNMTRMPNLLGHESQSEAAISIHEFAPLVQYGCAEHLRFFLCSLYAPMCTEQvsiPIPACRSMC 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1211247042 128 EAVRDGCTPIMESFGFPWPEMLTCDKFPQ--DDVCIAMTAPN 167
Cdd:cd07457    80 EQARDKCSPIMEQFSFSWPDSLDCDRLPRknDPKDLCMEAPN 121

Cysteine-rich Wnt-binding domain (CRD) of receptors similar to frizzled 5; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 5 (Fz5) and frizzled 8 (Fz8) receptors, and similar proteins. This domain is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and Ca(2+) modulating signaling pathway. The CRD domain is well conserved in metazoans - 10 frizzled proteins have been identified in mammals, 4 in Drosophila and 3 in Caenorhabditis elegans. Very little is known about the mechanism by which CRD domains interact with their ligands. The domain contains 10 conserved cysteines.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1211247042  61 LCHNVGYNQMLLPNLLEHETMAEVKQQAGSWVPLVHKSCHPGTQVFLCSLFAPVCLE---RPIYPCRWLCEAVRDGCTPI 137
Cdd:cd07456     9 MCKGIGYNMTYMPNQFNHDTQEEAGLEVHQFWPLVEIQCSPDLKFFLCSMYTPICLEdydKPLPPCRSVCERARDGCAPI 88

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1211247042 138 MESFGFPWPEMLTCDKFPQ--DDVCIAMTAPN 167
Cdd:cd07456    89 MRQYGFAWPERMSCDALPEggDPDNLCMDRNN 120

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 10 (Fz10) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 10 (Fz10) receptor, and is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and Ca(2+) modulating signaling pathway. CRD containing Fzs have been found in diverse species from amoebas to mammals. 10 different frizzled proteins are found in vertebrata. The cellular functon of Fz10 is unknown.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1211247042  51 QCVDIPedlrLCHNVGYNQMLLPNLLEHETMAEVKQQAGSWVPLVHKSCHPGTQVFLCSLFAPVCLER---PIYPCRWLC 127
Cdd:cd07462     6 QPIEIP----MCKDIGYNMTRMPNLMGHENQREAAIQLHEFAPLVEYGCHSHLKFFLCSLYAPMCTEQvstPIPACRVMC 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1211247042 128 EAVRDGCTPIMESFGFPWPEMLTCDKFP--QDDVCIAMTAPN 167
Cdd:cd07462    82 EQARLKCSPIMEQFNFKWPDSLDCSKLPnkNDPNYLCMEAPN 123

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 1211247042  48 KPPQCVDIpeDLRLCHNVGYNQMLLPNLLEHETMAEVKQQAGSWVPLVHKSCHPGTQVFLCSLFAPVCL---ERPIYPCR 124
Cdd:cd07460     1 KALVCQEI--TVPMCKGIGYNLTYMPNQFNHDTQDEAGLEVHQFWPLVEIQCSPDLRFFLCSMYTPICLpdyRKPLPPCR 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1211247042 125 WLCEAVRDGCTPIMESFGFPWPEMLTCDKFPQ--DDVCIAMTApNATEAT 172
Cdd:cd07460    79 SVCERAKAGCSPLMRQYGFAWPERMNCDRLPVlgDPETLCMDY-NRTEAT 127

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 2 (Fz2) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 2 (Fz2) receptor, and is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and Ca(2+) modulating signaling pathway. CRD containing Fzs have been found in diverse species from amoebas to mammals. 10 different frizzled proteins are found in vertebrata. Fz2 is involved in the Wnt/beta-catenin signaling pathway and in the activation of protein kinase C and calcium/calmodulin-dependent protein kinase (CaM kinase).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1211247042  56 PEDLRLCHNVGYNQMLLPNLLEHETMAEVKQQAGSWVPLVHKSCHPGTQVFLCSLFAPVC--LERPIYPCRWLCEAVRDG 133
Cdd:cd07464     7 PISIPLCTDIAYNQTIMPNLLGHTNQEDAGLEVHQFYPLVKVQCSLELRFFLCSMYAPVCtvLEQAIPPCRSICERARQG 86

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1211247042 134 CTPIMESFGFPWPEMLTCDKFPQ---DDVCIA 162
Cdd:cd07464    87 CEALMNKFGFQWPERLRCENFPRhgaEQICVG 118

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 1211247042  56 PEDLRLCHNVGYNQMLLPNLLEHETMAEVKQQAGSWVPLVHKSCHPGTQVFLCSLFAPVCLE--RPIYPCRWLCEAVRDG 133
Cdd:cd07449     7 PITLRMCQDLPYNTTFMPNLLNHYDQQTAALAMEPFHPMVNLECSRDFRPFLCALYAPVCMEygRVTLPCRRLCQRAYSE 86

                          90       100
                  ....*....|....*....|....*
gi 1211247042 134 CTPIMESFGFPWPEMLTCDKFPQDD 158
Cdd:cd07449    87 CSKLMEMFGVPWPEDMECSRFPDCD 111

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 1211247042  55 IPEDLRLCHNVGYNQMLLPNLLEHETMAEVKQQAGSWVPLVHKSCHPGTQVFLCSLFAPVC---LERPIYPCRWLCEAVR 131
Cdd:cd07454     6 IPIDIELCKDLPYNYTYFPNTILHNDQHTLQTHTEHFKPLMKTKCHPHIHFFICSVFAPMCpigMPQAVTSCKSVCEQVK 85

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1211247042 132 DGCTPIMESFGFPWPEMLTCDKFP-QDDVCI 161
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 1211247042  62 CHNVGYNQMLLPNLLEHETMAEVKQQAGSWVPLVHKSCHPGTQVFLCSLFAPVCLER--PIYPCRWLCEAVRDGCTPIME 139
Cdd:cd07450    13 CLKMPYNMTFFPNLMGHYDQDIAAVEMEPFLPLANLRCSPNVHTFLCQAFVPTCTEQihVVRPCRELCEKVYSDCKKLID 92

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1211247042 140 SFGFPWPEMLTCDKFPQDDVCIAMTAPNATEATKP 174
Cdd:cd07450    93 TFGISWPEELECDRLQYCDETVPDTADPHTEFSSP 127

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 1211247042  56 PEDLRLCHNVGYNQMLLPNLLEHETMAEVKQQAGSWVPLVHKSCHPGTQVFLCSLFAPVCL----ERPIYPCRWLCEAVR 131
Cdd:cd07441     6 PVRIPMCKSMPWNMTKMPNHLHHSTQANAVLAIEQFEGLLGTQCSPDLLFFLCAMYAPICTidfqHEPIKPCKSVCERAR 85

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1211247042 132 DGCTPIMESFGFPWPEMLTCDKFPQDD--VCIAMTA 165
Cdd:cd07441    86 AGCEPVLIRYRHTWPESLACEELPVYDrgVCISPEA 121

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 1211247042  56 PEDLRLCHNVGYNQMLLPNLLEHETMAE--VKQQAGSWVPLVHKSCHPGTQVFLCSLFAPVC---LERPIYPCRWLCEAV 130
Cdd:cd07888     4 PITLELCMNLPYNTTRYPNYLGHRTQKEasISWESSLFPALVQTNCYKYLMFFACTILVPKCdpvTQQRIPPCRSLCRNS 83

                          90       100
                  ....*....|....*....|....*...
gi 1211247042 131 RDGCTPIMESFGFPWPEMLTCDKFPQDD 158
Cdd:cd07888    84 KERCESVLGIVGLQWPEDTDCAQFPEEN 111

Netrin C-terminal Domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1211247042  194 LEHMCASE--FAIRTKIKEVRREGMDRKVILQKrKKPLKLGNLKKnDLKKLVLYLKNG-ADCPCQQLDNLGNTYLIMGRK 270
Cdd:smart00643   1 LEKACKSDvdYVYKVKVLSVEEEGGFDKYTVKI-LEVIKSGTDEL-VRGKNKLRVFISrASCRCPLLLKLGKSYLIMGKS 78

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1211247042  271 VDT-------QFLL---TGIHKWD----KSSKEFKK 292
Cdd:smart00643  79 GDLwdakgrgQYVLgknSWVEEWPteeeCRLRRLQK 114

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 1211247042  77 EHETMAEVKQQAGSWVPLVH-KSCHPGTQVFLCSLFAPVCLERPIY-PCRWLCEAVRDGCTpIMESFGFpWPEMLTCDK 153
Cdd:cd07451    30 DSTTQEEVQEKLHLWSGLRNvPKCWAVIQPLLCALYMPKCENGKVElPSQEMCQATRGPCK-IVENERG-WPDFLRCDN 106