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 1955742086  62 YTKEPQCVDIPTDLRLCHNVGYKKMRLPNLLDHETMPEVKQQAGSWVPLLAKRCHADTQVFLCSLFAPVCLDRPIYPCRS 141
Cdd:cd07444     1 YSKQPQCVDIPADLPLCHNVGYKRMRLPNLLEHESMAEVKQQASSWVPLLAKRCHADTQVFLCSLFAPVCLDRPIYPCRS 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1955742086 142 LCEAVRDSCAPVMETYGFPWPEMLTCDKFPIDNDLCIPIQFAGNQAT 188
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 1955742086  62 YTKEPQCVDIPTDLRLCHNVGYKKMRLPNLLDHETMPEVKQQAGSWVPLLAKRCHADTQVFLCSLFAPVCLDRPIYPCRS 141
Cdd:cd07444     1 YSKQPQCVDIPADLPLCHNVGYKRMRLPNLLEHESMAEVKQQASSWVPLLAKRCHADTQVFLCSLFAPVCLDRPIYPCRS 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1955742086 142 LCEAVRDSCAPVMETYGFPWPEMLTCDKFPIDNDLCIPIQFAGNQAT 188
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 1955742086   71 IPTDLRLCHNVGYKKMRLPNLLDHETMPEVKQQAGSWVPLLAKRCHADTQVFLCSLFAPVCLDR--PIYPCRSLCEAVRD 148
Cdd:smart00063   2 EPITIPLCKDLGYNLTSMPNLLGHTTQEEAGLELEQFHPLLNVQCSPDLRFFLCSVYAPICTEDlrPILPCRSLCEAARE 81

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1955742086  149 SCAPVMETYGFPWPEMLTCDKFPIDNDLCIPI 180
Cdd:smart00063  82 GCEPLMEKFGFPWPEFLRCDRFPVQEELCMDP 113

Sodium/calcium exchanger protein; This is a family of sodium/calcium exchanger integral membrane proteins. This family covers the integral membrane regions of the proteins. Sodium/calcium exchangers regulate intracellular Ca2+ concentrations in many cells; cardiac myocytes, epithelial cells, neurons retinal rod photoreceptors and smooth muscle cells. Ca2+ is moved into or out of the cytosol depending on Na+ concentration. In humans and rats there are 3 isoforms; NCX1 NCX2 and NCX3.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1955742086 187 ATPAPDTFASKVAAIQDQyADASIGNVTGSNAVNVFLGIGVAWSMAAIYHNSKGndFKVDpgslaFSVTLFTIFAFICVG 266
Cdd:pfam01699  46 GTSLPELVSSIIAALRGE-PDLALGNVIGSNIFNILLVLGLSALIGPVKVDSLL--LKLD-----LGVLLLVALLLLLLL 117

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1955742086 267 VLMYRRRpsiggelggPRTPKILTTMLFVSLWLLYILFSSL 307
Cdd:pfam01699 118 LLLLLPL---------FGRLSRFEGLVLLLLYIVYLVFQIV 149

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 1955742086  62 YTKEPQCVDIPTDLRLCHNVGYKKMRLPNLLDHETMPEVKQQAGSWVPLLAKRCHADTQVFLCSLFAPVCLDRPIYPCRS 141
Cdd:cd07444     1 YSKQPQCVDIPADLPLCHNVGYKRMRLPNLLEHESMAEVKQQASSWVPLLAKRCHADTQVFLCSLFAPVCLDRPIYPCRS 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1955742086 142 LCEAVRDSCAPVMETYGFPWPEMLTCDKFPIDNDLCIPIQFAGNQAT 188
Cdd:cd07444    81 LCEAVRDSCAPVMESYGFPWPEMLHCHKFPLDNDLCIAVQFGHLQAT 127

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 1955742086  62 YTKEPQCVDIPTDLRLCHNVGYKKMRLPNLLDHETMPEVKQQAGSWVPLLAKRCHADTQVFLCSLFAPVCLDRPIYPCRS 141
Cdd:cd07443     1 YTKPPQCVDIPADLRLCHNVGYKKMVLPNLLDHETMAEVKQQASSWVPLLNKNCHKGTQVFLCSLFAPVCLDRPVYPCRW 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1955742086 142 LCEAVRDSCAPVMETYGFPWPEMLTCDKFPIDnDLCI 178
Cdd:cd07443    81 LCEAVRDSCEPVMQFFGFYWPEMLKCDKFPEG-EVCI 116

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 1955742086  68 CVDIPTDLRLCHNVGYKKMRLPNLLDHETMPEVKQQAGSWVPLLAKRCHADTQVFLCSLFAPVCLDRPIYPCRSLCEAVR 147
Cdd:cd07453     3 CMRIPKSMALCYDIGYSEMRIPNLLEHETMAEVIQQSSSWLPLLARECHPDARIFLCSLFAPICWDRPIYPCRSLCEAVR 82

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1955742086 148 DSCAPVMETYGFPWPEMLTCDKFPIDNDLCIPIQF 182
Cdd:cd07453    83 SSCAPLMACYGYPWPEILHCDKFPVDHDLCISPQF 117

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 1955742086  67 QCVDIPTDLRLCHNVGYKKMRLPNLLDHETMPEVKQQAGSWVPLLAKRCHADTQVFLCSLFAPVCLDRPIYPCRSLCEAV 146
Cdd:cd07452     8 KCVPIPPEMSMCQDVGYSEMRLPNLLGHTSMAEVVPKSADWQTLLHTGCHPHARTFLCSLFAPVCLDTFIQPCRSMCVAV 87

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1955742086 147 RDSCAPVMETYGFPWPEMLTCDKFPIDNDLCI 178
Cdd:cd07452    88 RDSCAPVLACHGHSWPESLDCDRFPAGEDMCL 119

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 1955742086  72 PTDLRLCHNVGYKKMRLPNLLDHETMPEVKQQAGSWVPLLAKRCHADTQVFLCSLFAPVC---LDRPIYPCRSLCEAVRD 148
Cdd:cd07448     6 PIRIEMCQGLGYNVTRMPNLVGHELQTDAELQLQTFTPLIQYGCSSQLKFFLCSVYVPMCtekVPVPIGPCRPLCLSVKK 85

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1955742086 149 SCAPVMETYGFPWPEMLTCDKFPIDND---LCIP 179
Cdd:cd07448    86 RCLPVLKEFGFPWPEALNCSKFPPQNNhnhMCME 119

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 1955742086  72 PTDLRLCHNVGYKKMRLPNLLDHETMPEVKQQAGSWVPLLAKRCHADTQVFLCSLFAPVC--LDRPIYPCRSLCEAVRDS 149
Cdd:cd07458     5 PITIPLCTDIPYNMTIFPNLLGHTKQEDAGLEVHQFYPLVKVQCSPDLKFFLCSVYAPVCtvLERPIPPCRSLCESARQG 84

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1955742086 150 CAPVMETYGFPWPEMLTCDKFPIDN--DLCI 178
Cdd:cd07458    85 CEALMNKFGFQWPESLDCEKFPVHGagDLCV 115

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 1955742086  77 LCHNVGYKKMRLPNLLDHETMPEVKQQAGSWVPLLAKRCHADTQVFLCSLFAPVCL---DRPIYPCRSLCEAVRDSCAPV 153
Cdd:cd07456     9 MCKGIGYNMTYMPNQFNHDTQEEAGLEVHQFWPLVEIQCSPDLKFFLCSMYTPICLedyDKPLPPCRSVCERARDGCAPI 88

                          90       100
                  ....*....|....*....|....*...
gi 1955742086 154 METYGFPWPEMLTCDKFP---IDNDLCI 178
Cdd:cd07456    89 MRQYGFAWPERMSCDALPeggDPDNLCM 116

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 1955742086  67 QCVDIPtdlrLCHNVGYKKMRLPNLLDHETMPEVKQQAGSWVPLLAKRCHADTQVFLCSLFAPVCLDR---PIYPCRSLC 143
Cdd:cd07463     6 QPVVIP----MCRGIGYNLTRMPNFLGHDSQREAAIKLNEFAPLVEYGCHVHLRFFLCSLYAPMCTDQvstSIPACRPMC 81

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1955742086 144 EAVRDSCAPVMETYGFPWPEMLTCDKFPIDND---LCI 178
Cdd:cd07463    82 EQARQKCSPIMEQFNFGWPESLDCSRLPTRNDpnaLCM 119

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 1955742086  64 KEPQCVDIptDLRLCHNVGYKKMRLPNLLDHETMPEVKQQAGSWVPLLAKRCHADTQVFLCSLFAPVCLD---RPIYPCR 140
Cdd:cd07460     1 KALVCQEI--TVPMCKGIGYNLTYMPNQFNHDTQDEAGLEVHQFWPLVEIQCSPDLRFFLCSMYTPICLPdyrKPLPPCR 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1955742086 141 SLCEAVRDSCAPVMETYGFPWPEMLTCDKFPIDND---LCI 178
Cdd:cd07460    79 SVCERAKAGCSPLMRQYGFAWPERMNCDRLPVLGDpetLCM 119

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 7 (Fz7) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 7 (Fz7) receptor, and is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and Ca(2+) modulating signaling pathway. CRD containing Fzs have been found in diverse species from amoebas to mammals. 10 different frizzled proteins are found in vertebrata. Xenopus Fz7 is important in Wnt/beta-catenin signaling pathways controlling the transcriptional activation of target genes Siamois and Xnr3 in the animal caps of late blastula.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1955742086  72 PTDLRLCHNVGYKKMRLPNLLDHETMPEVKQQAGSWVPLLAKRCHADTQVFLCSLFAPVC--LDRPIYPCRSLCEAVRDS 149
Cdd:cd07466     7 PISIPLCTDIAYNQTIMPNLLGHTNQEDAGLEVHQFYPLVKVQCSPELKFFLCSMYAPVCtvLEQAIPPCRSLCERARQG 86

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1955742086 150 CAPVMETYGFPWPEMLTCDKFPID--NDLCI 178
Cdd:cd07466    87 CEALMNKFGFQWPERLRCENFPVHgaGEICV 117

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 1955742086  72 PTDLRLCHNVGYKKMRLPNLLDHETMPEVKQQAGSWVPLLAKRCHADTQVFLCSLFAPVCLD--RPIYPCRSLCEAVRDS 149
Cdd:cd07449     7 PITLRMCQDLPYNTTFMPNLLNHYDQQTAALAMEPFHPMVNLECSRDFRPFLCALYAPVCMEygRVTLPCRRLCQRAYSE 86

                          90       100
                  ....*....|....*....|..
gi 1955742086 150 CAPVMETYGFPWPEMLTCDKFP 171
Cdd:cd07449    87 CSKLMEMFGVPWPEDMECSRFP 108

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 1955742086  67 QCVDIPtdlrLCHNVGYKKMRLPNLLDHETMPEVKQQAGSWVPLLAKRCHADTQVFLCSLFAPVC----LDRPIYPCRSL 142
Cdd:cd07442     6 EAVRIP----MCRHMPWNITRMPNHLHHSTQENAVLAIEQYEELVDTGCSPVLPFFLCAMYAPICtlefLYDPIKPCRSV 81

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1955742086 143 CEAVRDSCAPVMETYGFPWPEMLTCDKFPI-DNDLCI 178
Cdd:cd07442    82 CQRARDGCEPIMRRYNHSWPESLACDDLPVyDRGVCI 118

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 1955742086  66 PQCVDIPTDLRLCHNVGYKKMRLPNLLDHETMPEVKQQAGSWVPLLAKRCHADTQVFLCSLFAPVCLDRPIY---PCRSL 142
Cdd:cd07455     3 PRCLPVPSSLPFCSRLGIRSFWLPNFLNHTSVEEVRAVLAEWAWLLESGCHPSLEWFFCLLLVPSCGGGPPPpppPCRQF 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1955742086 143 CEAVRDSCAPVMETYGFPwpemLTCDKFPIDND-LCIPIQFA 183
Cdd:cd07455    83 CEVLQDSCWNLLEGGRLP----VACASLPEQEDgYCVLIGPP 120

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 1955742086  72 PTDLRLCHNVGYKKMRLPNLLDHETMPE--VKQQAGSWVPLLAKRCHADTQVFLCSLFAPVC---LDRPIYPCRSLCEAV 146
Cdd:cd07888     4 PITLELCMNLPYNTTRYPNYLGHRTQKEasISWESSLFPALVQTNCYKYLMFFACTILVPKCdpvTQQRIPPCRSLCRNS 83

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1955742086 147 RDSCAPVMETYGFPWPEMLTCDKFPIDNdlcipiqfAGNQATPAPD 192
Cdd:cd07888    84 KERCESVLGIVGLQWPEDTDCAQFPEEN--------SDNQTCLLPD 121

Sodium/calcium exchanger protein; This is a family of sodium/calcium exchanger integral membrane proteins. This family covers the integral membrane regions of the proteins. Sodium/calcium exchangers regulate intracellular Ca2+ concentrations in many cells; cardiac myocytes, epithelial cells, neurons retinal rod photoreceptors and smooth muscle cells. Ca2+ is moved into or out of the cytosol depending on Na+ concentration. In humans and rats there are 3 isoforms; NCX1 NCX2 and NCX3.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1955742086 187 ATPAPDTFASKVAAIQDQyADASIGNVTGSNAVNVFLGIGVAWSMAAIYHNSKGndFKVDpgslaFSVTLFTIFAFICVG 266
Cdd:pfam01699  46 GTSLPELVSSIIAALRGE-PDLALGNVIGSNIFNILLVLGLSALIGPVKVDSLL--LKLD-----LGVLLLVALLLLLLL 117

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1955742086 267 VLMYRRRpsiggelggPRTPKILTTMLFVSLWLLYILFSSL 307
Cdd:pfam01699 118 LLLLLPL---------FGRLSRFEGLVLLLLYIVYLVFQIV 149

One of two cysteine-rich domains of the corin protein, a type II transmembrane serine protease ; The cysteine-rich domain (CRD) is an essential component of corin, a type II transmembrane serine protease which functions as the convertase of the pro-atrial natriuretic peptide (pro-ANP) in the heart. Corin contains two CRDs in its extracellular region, which play an important role in recognition of the physiological substrate, pro-ANP. This model characterizes the first (N-terminal) CRD.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1955742086 115 CHADTQVFLCSLFAPVCL----DRP-IYPCRSLCEAVRDSCAPVMETYGFPWPEMLTCDKF 170
Cdd:cd07445    49 CYQHIMLFGCSLALPECIsdgdDRHgLLPCRSFCEAAKEGCEPVLGMVNASWPDFLRCSQF 109

Ca2+/Na+ antiporter [Inorganic ion transport and metabolism];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1955742086 187 ATPAPDTFASKVAAIQDQyADASIGNVTGSNAVNVFLGIGVAwsmAAIYhnskgnDFKVDPGSLAFSVTLFTIFAFICVG 266
Cdd:COG0530    30 GTSLPELAVSVTAALDGS-PDIAVGNVVGSNIANILLILGLA---ALIR------PLAVDRRVLRRDLPFLLLASLLLLA 99

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1955742086 267 VLMyrrrpsiggelggPRTPKILTTMLFVSLWLLYILFS 305
Cdd:COG0530   100 LLL-------------DGTLSRIDGVILLLLYVLYLYYL 125