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 1753152462   1 MVLPNLLEHETMAEVKQQASSWVPLLNKNCHIGTQVFLCSLFAPVCLDRPIYPCRWLCEAVRDSCEPVMQFFGFYWPEML 80
Cdd:cd07443    25 MVLPNLLDHETMAEVKQQASSWVPLLNKNCHKGTQVFLCSLFAPVCLDRPVYPCRWLCEAVRDSCEPVMQFFGFYWPEML 104

                          90       100
                  ....*....|....*....|
gi 1753152462  81 KCDKFPEGDVCIAMTPPNAT 100
Cdd:cd07443   105 KCDKFPEGEVCIAMTPPNAT 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 1753152462   1 MVLPNLLEHETMAEVKQQASSWVPLLNKNCHIGTQVFLCSLFAPVCLDRPIYPCRWLCEAVRDSCEPVMQFFGFYWPEML 80
Cdd:cd07443    25 MVLPNLLDHETMAEVKQQASSWVPLLNKNCHKGTQVFLCSLFAPVCLDRPVYPCRWLCEAVRDSCEPVMQFFGFYWPEML 104

                          90       100
                  ....*....|....*....|
gi 1753152462  81 KCDKFPEGDVCIAMTPPNAT 100
Cdd:cd07443   105 KCDKFPEGEVCIAMTPPNAT 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 1753152462    1 MVLPNLLEHETMAEVKQQASSWVPLLNKNCHIGTQVFLCSLFAPVCLDR--PIYPCRWLCEAVRDSCEPVMQFFGFYWPE 78
Cdd:smart00063  17 TSMPNLLGHTTQEEAGLELEQFHPLLNVQCSPDLRFFLCSVYAPICTEDlrPILPCRSLCEAAREGCEPLMEKFGFPWPE 96

                           90
                   ....*....|....*..
gi 1753152462   79 MLKCDKFP-EGDVCIAM 94
Cdd:smart00063  97 FLRCDRFPvQEELCMDP 113

Netrin C-terminal Domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1753152462  124 IEHLCASE--FALRMKIKEVKKENGDKKIVPKKKKPLKLGPIKKKELKKLVLYLKNGADCPCHQLDNLSHHFLIMGRKV- 200
Cdd:smart00643   1 LEKACKSDvdYVYKVKVLSVEEEGGFDKYTVKILEVIKSGTDELVRGKNKLRVFISRASCRCPLLLKLGKSYLIMGKSGd 80

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1753152462  201 ------KSQYLLTA---IHKWDKKNK-EFKNFMK 224
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 1753152462   1 MVLPNLLEHETMAEVKQQASSWVPLLNKNCHIGTQVFLCSLFAPVCLDRPIYPCRWLCEAVRDSCEPVMQFFGFYWPEML 80
Cdd:cd07443    25 MVLPNLLDHETMAEVKQQASSWVPLLNKNCHKGTQVFLCSLFAPVCLDRPVYPCRWLCEAVRDSCEPVMQFFGFYWPEML 104

                          90       100
                  ....*....|....*....|
gi 1753152462  81 KCDKFPEGDVCIAMTPPNAT 100
Cdd:cd07443   105 KCDKFPEGEVCIAMTPPNAT 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 1753152462   1 MVLPNLLEHETMAEVKQQASSWVPLLNKNCHIGTQVFLCSLFAPVCLDRPIYPCRWLCEAVRDSCEPVMQFFGFYWPEML 80
Cdd:cd07453    21 MRIPNLLEHETMAEVIQQSSSWLPLLARECHPDARIFLCSLFAPICWDRPIYPCRSLCEAVRSSCAPLMACYGYPWPEIL 100

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1753152462  81 KCDKFPEG-DVCIAmtpPNATEASKPQGTTVCPPCDNE 117
Cdd:cd07453   101 HCDKFPVDhDLCIS---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 1753152462 108 TTVCPPCDNELKS-EAIIEHLCASEFALRMKIKEVKKENGDKKIVPKKKKPL-KLGPIKKKELKKLVLYLKNGADCPCHQ 185
Cdd:cd03580     1 PKVCPPCENEEESaKTLLDNFCASDFALKVKIKEISYENGDRKVIGEKKKEIlKQGPLKKKDLKKLVLWLKNGANCPCPQ 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1753152462 186 LDNLSHHFLIMGRKVKSQYLLTAIHKWDKKNKEFKNFMKKMKNHEC 231
Cdd:cd03580    81 LDNLNGVYLVMGRKVDGKLLLTSIYKWQKKNKEFKRAVRKWKKHKC 126

CRD_domain cysteine-rich domain, also known as Fz (frizzled) domain; CRD_FZ is an essential component of a number of cell surface receptors, which are involved in multiple signal transduction pathways, particularly in modulating the activity of the Wnt proteins, which play a fundamental role in the early development of metazoans. CRD is also found in secreted frizzled related proteins (SFRPs), which lack the transmembrane segment found in the frizzled protein. The CRD domain is also present in the alpha-1 chain of mouse type XVIII collagen, in carboxypeptidase Z, several receptor tyrosine kinases, and the mosaic transmembrane serine protease corin. The CRD domain is well conserved in metazoans - 10 frizzled proteins have been identified in mammals, 4 in Drosophila and 3 in Caenorhabditis elegans. CRD domains have also been identified in multiple tandem copies in a Dictyostelium discoideum protein. Very little is known about the mechanism by which CRD domains interact with their ligands. The domain contains 10 conserved cysteines.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1753152462   1 MVLPNLLEHETMAEVKQQASSWVPLLNKNCHIGTQVFLCSLFAPVCL---DRPIYPCRWLCEAVRDSCEPVMQFFGFYWP 77
Cdd:cd07066    18 TRFPNLLGHESQEEAEQELESFTPLVNSGCHPDLRFFLCSLYFPECTpdgDRPIPPCRSLCEEVRDSCEPLMLAFGFPWP 97

                          90       100
                  ....*....|....*....|..
gi 1753152462  78 EMLKCDKFPE---GDVCIAMTP 96
Cdd:cd07066    98 EPLDCDRFPDsneEGLCISPPG 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 1753152462   3 LPNLLEHETMAEVKQQASSWVPLLNKNCHIGTQVFLCSLFAPVC---LDRPIYPCRWLCEAVRDSCEPVMQFFGFYWPEM 79
Cdd:cd07448    22 MPNLVGHELQTDAELQLQTFTPLIQYGCSSQLKFFLCSVYVPMCtekVPVPIGPCRPLCLSVKKRCLPVLKEFGFPWPEA 101

                          90       100
                  ....*....|....*....|....*..
gi 1753152462  80 LKCDKFP----EGDVCiaMTPPNATEA 102
Cdd:cd07448   102 LNCSKFPpqnnHNHMC--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 1753152462   2 VLPNLLEHETMAEVKQQASSWVPLLNKNCHIGTQVFLCSLFAPVC--LDRPIYPCRWLCEAVRDSCEPVMQFFGFYWPEM 79
Cdd:cd07458    20 IFPNLLGHTKQEDAGLEVHQFYPLVKVQCSPDLKFFLCSVYAPVCtvLERPIPPCRSLCESARQGCEALMNKFGFQWPES 99

                          90
                  ....*....|....*..
gi 1753152462  80 LKCDKFPE---GDVCIA 93
Cdd:cd07458   100 LDCEKFPVhgaGDLCVG 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 1753152462   3 LPNLLEHETMAEVKQQASSWVPLLNKNCHIGTQVFLCSLFAPVCL---DRPIYPCRWLCEAVRDSCEPVMQFFGFYWPEM 79
Cdd:cd07456    20 MPNQFNHDTQEEAGLEVHQFWPLVEIQCSPDLKFFLCSMYTPICLedyDKPLPPCRSVCERARDGCAPIMRQYGFAWPER 99

                  ....*....
gi 1753152462  80 LKCDKFPEG 88
Cdd:cd07456   100 MSCDALPEG 108

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 1753152462   3 LPNLLEHETMAEVKQQASSWVPLLNKNCHIGTQVFLCSLFAPVCLD---RPIYPCRWLCEAVRDSCEPVMQFFGFYWPEM 79
Cdd:cd07460    23 MPNQFNHDTQDEAGLEVHQFWPLVEIQCSPDLRFFLCSMYTPICLPdyrKPLPPCRSVCERAKAGCSPLMRQYGFAWPER 102

                          90       100
                  ....*....|....*....|....*
gi 1753152462  80 LKCDKFPE-GDVCIAMTPPNATEAS 103
Cdd:cd07460   103 MNCDRLPVlGDPETLCMDYNRTEAT 127

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 1753152462   2 VLPNLLEHETMAEVKQQASSWVPLLNKNCHIGTQVFLCSLFAPVC--LDRPIYPCRWLCEAVRDSCEPVMQFFGFYWPEM 79
Cdd:cd07465    22 IMPNLLGHTNQEDAGLEVHQFYPLVKVQCSAELKFFLCSMYAPVCtvLEQALPPCRSLCERARQGCEALMNKFGFQWPDT 101

                          90       100
                  ....*....|....*....|....*....
gi 1753152462  80 LKCDKFP---EGDVCIAMtppNATEASKP 105
Cdd:cd07465   102 LRCEKFPvhgAGELCVGQ---NTSESGTP 127

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 1753152462   3 LPNLLEHETMAEVKQQASSWVPLLNKNCHIGTQVFLCSLFAPVCLD---RPIYPCRWLCEAVRDSCEPVMQFFGFYWPEM 79
Cdd:cd07461    23 MPNQFNHDTQDEAGLEVHQFWPLVEIQCSPDLKFFLCSMYTPICLEdykKPLPPCRSVCERAKAGCAPLMRQYGFPWPDR 102

                  ....*...
gi 1753152462  80 LKCDKFPE 87
Cdd:cd07461   103 MRCDLLPE 110

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 1753152462   3 LPNLLEHETMAEVKQQASSWVPLLNKNCHIGTQVFLCSLFAPVC----LDRPIYPCRWLCEAVRDSCEPVMQFFGFYWPE 78
Cdd:cd07442    23 MPNHLHHSTQENAVLAIEQYEELVDTGCSPVLPFFLCAMYAPICtlefLYDPIKPCRSVCQRARDGCEPIMRRYNHSWPE 102

                          90
                  ....*....|....*...
gi 1753152462  79 MLKCDKFPEGDVCIAMTP 96
Cdd:cd07442   103 SLACDDLPVYDRGVCISP 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 1753152462 125 EHLCASEFALRMKIKEVKKENGDKKIVPKKKKPLKLGPIkKKELKKLVLYLKNGADCPCHQLDNLSHHFLIMGRKVKSQY 204
Cdd:cd03523     1 KAFCKSDYVVRAKIKEIKEENDDVKYEVKIIKIYKTGKA-KADKADLRFYYTAPACCPCHPILNPGREYLIMGKEEDSQG 79

                          90       100       110
                  ....*....|....*....|....*....|
gi 1753152462 205 LL-----TAIHKWDKKNKefknFMKKMKNH 229
Cdd:cd03523    80 GLvldplSFVEPWSPLSL----RQDRRLRE 105

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 1753152462   4 PNLLEHETMAEVKQQASSWVPLLNKNCHIGTQVFLCSLFAPVCLDR--PIYPCRWLCEAVRDSCEPVMQFFGFYWPEMLK 81
Cdd:cd07450    24 PNLMGHYDQDIAAVEMEPFLPLANLRCSPNVHTFLCQAFVPTCTEQihVVRPCRELCEKVYSDCKKLIDTFGISWPEELE 103

                          90       100
                  ....*....|....*....|....
gi 1753152462  82 CDKFPEGDVCIAMTPPNATEASKP 105
Cdd:cd07450   104 CDRLQYCDETVPDTADPHTEFSSP 127

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 1753152462   4 PNLLEHETMAE--VKQQASSWVPLLNKNCHIGTQVFLCSLFAPVC---LDRPIYPCRWLCEAVRDSCEPVMQFFGFYWPE 78
Cdd:cd07888    21 PNYLGHRTQKEasISWESSLFPALVQTNCYKYLMFFACTILVPKCdpvTQQRIPPCRSLCRNSKERCESVLGIVGLQWPE 100

                  ....*....
gi 1753152462  79 MLKCDKFPE 87
Cdd:cd07888   101 DTDCAQFPE 109

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 1753152462  29 NCHIGTQVFLCSLFAPVCL----DRP-IYPCRWLCEAVRDSCEPVMQFFGFYWPEMLKCDKF 85
Cdd:cd07445    48 SCYQHIMLFGCSLALPECIsdgdDRHgLLPCRSFCEAAKEGCEPVLGMVNASWPDFLRCSQF 109

Netrin C-terminal Domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1753152462  124 IEHLCASE--FALRMKIKEVKKENGDKKIVPKKKKPLKLGPIKKKELKKLVLYLKNGADCPCHQLDNLSHHFLIMGRKV- 200
Cdd:smart00643   1 LEKACKSDvdYVYKVKVLSVEEEGGFDKYTVKILEVIKSGTDELVRGKNKLRVFISRASCRCPLLLKLGKSYLIMGKSGd 80

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1753152462  201 ------KSQYLLTA---IHKWDKKNK-EFKNFMK 224
Cdd:smart00643  81 lwdakgRGQYVLGKnswVEEWPTEEEcRLRRLQK 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.

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gi 1753152462   8 EHETMAEVKQQASSWVPLLN-KNCHIGTQVFLCSLFAPVCLDRPIY-PCRWLCEAVRDSCEPVMQFFGfyWPEMLKCDK 84
Cdd:cd07451    30 DSTTQEEVQEKLHLWSGLRNvPKCWAVIQPLLCALYMPKCENGKVElPSQEMCQATRGPCKIVENERG--WPDFLRCDN 106