Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad residues.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24640561  708 SAPGDWPWLVALFREDI-HVCDGTLITQDWVLTTEGCFQGQPRATWMAIVGAVRLSAKAPWTQRRRIIGMIKSPVEGSTA 786
Cdd:cd00190    7 AKIGSFPWQVSLQYTGGrHFCGGSLISPRWVLTAAHCVYSSAPSNYTVRLGSHDLSSNEGGGQVIKVKKVIVHPNYNPST 86

                         90       100
                 ....*....|....*....|....*...
gi 24640561  787 -----ALVRLETPVSYSDHVRPICLPDA 809
Cdd:cd00190   87 ydndiALLKLKRPVTLSDNVRPICLPSS 114

Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about 40 amino acids are present in the N-terminal of this multidomain membrane protein; other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement; the binding of calcium is required for in vitro formation of the native disulfide isomer and is necessary in establishing and maintaining the modular structure

                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 24640561  536 CSPNALYCGRGRaCVPRKARCDGKADCPDGADEKDC 571
Cdd:cd00112    1 CPPNEFRCANGR-CIPSSWVCDGEDDCGDGSDEENC 35

Fz domain; Also known as the CRD (cysteine rich domain), the C6 box in MuSK receptor. This domain of unknown function has been independently identified by several groups. The domain contains 10 conserved cysteines.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24640561    385 CSPLELSYCRQVGYNITTYPNLLGHASYEQLAED-----VIVFRELVDGECHREAYDFVCRLLQPPCdtHGSDLQPTPGQ 459
Cdd:pfam01392    1 CEPITLPMCLGLGYNATVFPNLLGHQTQEEAELSlaylvLSEFEPLVDLSCSPSLRLFLCSLYFPPC--TLGPSPKPVCP 78

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 24640561    460 ICREYCESFMAGCGGRLPQRFRQF-----FDCERFPES 492
Cdd:pfam01392   79 PCRSLCEEVRYGCEPLLEEAKFGFswpefLDCDSLPAD 116

Trypsin-like serine protease; Many of these are synthesised as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. A few, however, are active as single chain molecules, and others are inactive due to substitutions of the catalytic triad residues.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24640561     708 SAPGDWPWLVALFREDI-HVCDGTLITQDWVLTTEGCFQGQPRATWMAIVGAVRLSAKAPwTQRRRIIGMIKSPVEGSTA 786
Cdd:smart00020    8 ANIGSFPWQVSLQYGGGrHFCGGSLISPRWVLTAAHCVRGSDPSNIRVRLGSHDLSSGEE-GQVIKVSKVIIHPNYNPST 86

                            90       100       110
                    ....*....|....*....|....*....|
gi 24640561     787 -----ALVRLETPVSYSDHVRPICLPDALQ 811
Cdd:smart00020   87 ydndiALLKLKEPVTLSDNVRPICLPSSNY 116

Trypsin;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24640561    708 SAPGDWPWLVAL-FREDIHVCDGTLITQDWVLTTEGCFQGQPRatWMAIVGAVRLSAKAPWTQRRRIIGMIKSPVEGSTA 786
Cdd:pfam00089    7 AQPGSFPWQVSLqLSSGKHFCGGSLISENWVLTAAHCVSGASD--VKVVLGAHNIVLREGGEQKFDVEKIIVHPNYNPDT 84

                           90       100
                   ....*....|....*....|....*...
gi 24640561    787 -----ALVRLETPVSYSDHVRPICLPDA 809
Cdd:pfam00089   85 ldndiALLKLESPVTLGDTVRPICLPDA 112

Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about 40 amino acids are present in the N-terminal of this multidomain membrane protein; other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement; the binding of calcium is required for in vitro formation of the native disulfide isomer and is necessary in establishing and maintaining the modular structure

                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 24640561  536 CSPNALYCGRGRaCVPRKARCDGKADCPDGADEKDC 571
Cdd:cd00112    1 CPPNEFRCANGR-CIPSSWVCDGEDDCGDGSDEENC 35

Low-density lipoprotein receptor domain class A; Cysteine-rich repeat in the low-density lipoprotein (LDL) receptor that plays a central role in mammalian cholesterol metabolism. The N-terminal type A repeats in LDL receptor bind the lipoproteins. Other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement. Mutations in the LDL receptor gene cause familial hypercholesterolemia.

                            10        20        30
                    ....*....|....*....|....*....|...
gi 24640561     536 CSPNALYCGRGRaCVPRKARCDGKADCPDGADE 568
Cdd:smart00192    2 CPPGEFQCDNGR-CIPSSWVCDGVDDCGDGSDE 33

Fz domain; Also known as the CRD (cysteine rich domain), the C6 box in MuSK receptor. This domain of unknown function has been independently identified by several groups. The domain contains 10 conserved cysteines.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24640561    385 CSPLELSYCRQVGYNITTYPNLLGHASYEQLAED-----VIVFRELVDGECHREAYDFVCRLLQPPCdtHGSDLQPTPGQ 459
Cdd:pfam01392    1 CEPITLPMCLGLGYNATVFPNLLGHQTQEEAELSlaylvLSEFEPLVDLSCSPSLRLFLCSLYFPPC--TLGPSPKPVCP 78

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 24640561    460 ICREYCESFMAGCGGRLPQRFRQF-----FDCERFPES 492
Cdd:pfam01392   79 PCRSLCEEVRYGCEPLLEEAKFGFswpefLDCDSLPAD 116

Trypsin-like serine protease; Many of these are synthesised as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. A few, however, are active as single chain molecules, and others are inactive due to substitutions of the catalytic triad residues.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24640561     708 SAPGDWPWLVALFREDI-HVCDGTLITQDWVLTTEGCFQGQPRATWMAIVGAVRLSAKAPwTQRRRIIGMIKSPVEGSTA 786
Cdd:smart00020    8 ANIGSFPWQVSLQYGGGrHFCGGSLISPRWVLTAAHCVRGSDPSNIRVRLGSHDLSSGEE-GQVIKVSKVIIHPNYNPST 86

                            90       100       110
                    ....*....|....*....|....*....|
gi 24640561     787 -----ALVRLETPVSYSDHVRPICLPDALQ 811
Cdd:smart00020   87 ydndiALLKLKEPVTLSDNVRPICLPSSNY 116

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 24640561  383 RRCSPLELSYCRQVGYNITTYPNLLGHASYEQLAEDVIVFRELVDGECHREAYDFVCRLLQPPCDTHGSDLQPtpgqiCR 462
Cdd:cd07458    1 GKCEPITIPLCTDIPYNMTIFPNLLGHTKQEDAGLEVHQFYPLVKVQCSPDLKFFLCSVYAPVCTVLERPIPP-----CR 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 24640561  463 EYCESFMAGCGGrLPQRFR----QFFDCERFPESTGTQSC 498
Cdd:cd07458   76 SLCESARQGCEA-LMNKFGfqwpESLDCEKFPVHGAGDLC 114

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 24640561  384 RCSPLELSYCRQVGYNITTYPNLLGHASYEQ--LAEDVIVFRELVDGECHREAYDFVCRLLQPPCDTHGSDLQPTPGQIC 461
Cdd:cd07888    1 QCEPITLELCMNLPYNTTRYPNYLGHRTQKEasISWESSLFPALVQTNCYKYLMFFACTILVPKCDPVTQQRIPPCRSLC 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 24640561  462 R---EYCESFMAGCGGRLPQRfrqfFDCERFP-ESTGTQSC 498
Cdd:cd07888   81 RnskERCESVLGIVGLQWPED----TDCAQFPeENSDNQTC 117

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 24640561  382 PRRCSPLELSYCRQVGYNITTYPNLLGHASYEQLAEDVIVFRELVDGECHREAYDFVCRLLQPPCdthgSDLQPTPGQIC 461
Cdd:cd07463    2 AAKCQPVVIPMCRGIGYNLTRMPNFLGHDSQREAAIKLNEFAPLVEYGCHVHLRFFLCSLYAPMC----TDQVSTSIPAC 77

                         90       100       110
                 ....*....|....*....|....*....|..
gi 24640561  462 REYCESFMAGCGGRLPQ---RFRQFFDCERFP 490
Cdd:cd07463   78 RPMCEQARQKCSPIMEQfnfGWPESLDCSRLP 109

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 24640561  385 CSPLELSYCRQVGYNITTYPNLLGHASYEQLAEDVIVFRELVDGECHREAYDFVCRLLQPPCDTHGSDLQPTPgQIC--- 461
Cdd:cd07464    5 CQPISIPLCTDIAYNQTIMPNLLGHTNQEDAGLEVHQFYPLVKVQCSLELRFFLCSMYAPVCTVLEQAIPPCR-SICera 83

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 24640561  462 REYCESFMAGCGGRLPQRFRqffdCERFPESTGTQSCHQKPH 503
Cdd:cd07464   84 RQGCEALMNKFGFQWPERLR----CENFPRHGAEQICVGQNH 121

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 24640561  385 CSPLELSYCRQVGYNITTYPNLLGHASYEQLAEDVIVFRELVDGECHREAYDFVCRLLQPPCDTHGSDLQPtpgqiCREY 464
Cdd:cd07466    5 CQPISIPLCTDIAYNQTIMPNLLGHTNQEDAGLEVHQFYPLVKVQCSPELKFFLCSMYAPVCTVLEQAIPP-----CRSL 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 24640561  465 CESFMAGC-------GGRLPQRFRqffdCERFPESTGTQSC 498
Cdd:cd07466   80 CERARQGCealmnkfGFQWPERLR----CENFPVHGAGEIC 116

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 24640561  385 CSPLELSYCRQVGYNITTYPNLLGHASYEQLAEDVIVFRELVDGECHREAYDFVCRLLQPPCDTHGSDLQPtpgqiCREY 464
Cdd:cd07449    5 CEPITLRMCQDLPYNTTFMPNLLNHYDQQTAALAMEPFHPMVNLECSRDFRPFLCALYAPVCMEYGRVTLP-----CRRL 79

                         90       100       110
                 ....*....|....*....|....*....|.
gi 24640561  465 CESFMAGCgGRLPQRF----RQFFDCERFPE 491
Cdd:cd07449   80 CQRAYSEC-SKLMEMFgvpwPEDMECSRFPD 109

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 24640561  383 RRCSPLELSYCRQVGYNITTYPNLLGHASYEQLAEDVIVFRELVDGECHREAYDFVCRLLQPPCdthgSDLQPTPGQICR 462
Cdd:cd07448    2 RRCEPIRIEMCQGLGYNVTRMPNLVGHELQTDAELQLQTFTPLIQYGCSSQLKFFLCSVYVPMC----TEKVPVPIGPCR 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 24640561  463 EYCESFMAGCggrLP--QRF----RQFFDCERFP-ESTGTQSCHQKPH 503
Cdd:cd07448   78 PLCLSVKKRC---LPvlKEFgfpwPEALNCSKFPpQNNHNHMCMEGPG 122

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 24640561  387 PLELSYCRQVGYNITTYPNLLGHASYEQLAEDVIVFRELVDGECHREAYDFVCRLLQPPC-DTHgsdLQPtpgqiCREYC 465
Cdd:cd07452   13 PPEMSMCQDVGYSEMRLPNLLGHTSMAEVVPKSADWQTLLHTGCHPHARTFLCSLFAPVClDTF---IQP-----CRSMC 84

                         90       100       110
                 ....*....|....*....|....*....|..
gi 24640561  466 ESFMAGCGGRLP---QRFRQFFDCERFPESTG 494
Cdd:cd07452   85 VAVRDSCAPVLAchgHSWPESLDCDRFPAGED 116

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 24640561  383 RRCSPLELSYCRQVGYNITTYPNLLGHASYEQLAEDVIVFRELVDGECHREAYDFVCRLLQPPC-DTHGSDLQPtpgqiC 461
Cdd:cd07461    3 LQCQEITVPLCKGIGYNYTYMPNQFNHDTQDEAGLEVHQFWPLVEIQCSPDLKFFLCSMYTPIClEDYKKPLPP-----C 77

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 24640561  462 REYCESFMAGC-------GGRLPQRFRqffdCERFPE 491
Cdd:cd07461   78 RSVCERAKAGCaplmrqyGFPWPDRMR----CDLLPE 110

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 24640561  385 CSPLELSYCRQVGYNITTYPNLLGHASYEQLAEDVIVFRELVDGECHREAYDFVCRLLQPPC--DTHgsdlQPTPGqiCR 462
Cdd:cd07460    5 CQEITVPMCKGIGYNLTYMPNQFNHDTQDEAGLEVHQFWPLVEIQCSPDLRFFLCSMYTPIClpDYR----KPLPP--CR 78

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 24640561  463 EYCESFMAGC-------GGRLPQRfrqfFDCERFPE 491
Cdd:cd07460   79 SVCERAKAGCsplmrqyGFAWPER----MNCDRLPV 110

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 24640561  385 CSPLELSYCRQVGYNITTYPNLLGHASYEQLAEDVIVFRELVDGECHREAYDFVCRLLQPPCDTHGSDLQPtpgqiCREY 464
Cdd:cd07450    5 CEPITVPRCLKMPYNMTFFPNLMGHYDQDIAAVEMEPFLPLANLRCSPNVHTFLCQAFVPTCTEQIHVVRP-----CREL 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 24640561  465 CESFMAGC-------GGRLPQRfrqfFDCERFPESTGTQSCHQKPH 503
Cdd:cd07450   80 CEKVYSDCkklidtfGISWPEE----LECDRLQYCDETVPDTADPH 121

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 24640561  384 RCSPLELSYCRQVGYNITTYPNLLGHASYEQLAEDVIVFRELVDGECHREAYDFVCRLLQPPCdthgSDLQPTPGQICRE 463
Cdd:cd07454    4 KCIPIDIELCKDLPYNYTYFPNTILHNDQHTLQTHTEHFKPLMKTKCHPHIHFFICSVFAPMC----PIGMPQAVTSCKS 79

                         90       100       110
                 ....*....|....*....|....*....|
gi 24640561  464 YCESFMAGCGGRLPQ---RFRQFFDCERFP 490
Cdd:cd07454   80 VCEQVKADCFSILEEfgiGWPEPLNCAQFP 109

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 24640561  385 CSPLELSYCRQVGYNITTYPNLLGHASYEQLAEDVIVFRELVDGECHREAYDFVCRLLQPPCDThgsDLQPTPGQICREY 464
Cdd:cd07441    4 CEPVRIPMCKSMPWNMTKMPNHLHHSTQANAVLAIEQFEGLLGTQCSPDLLFFLCAMYAPICTI---DFQHEPIKPCKSV 80

                 ....*...
gi 24640561  465 CESFMAGC 472
Cdd:cd07441   81 CERARAGC 88

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 24640561  387 PLELSYCRQVGYNITTYPNLLGHASYEQLAEDVIVFRELVDGECHREAYDFVCRLLQPPCdthgsdlQPTPGQICREYCE 466
Cdd:cd07443   11 PADLRLCHNVGYKKMVLPNLLDHETMAEVKQQASSWVPLLNKNCHKGTQVFLCSLFAPVC-------LDRPVYPCRWLCE 83

                         90       100       110
                 ....*....|....*....|....*....|..
gi 24640561  467 SFMAGC-------GGRLPQRFRqffdCERFPE 491
Cdd:cd07443   84 AVRDSCepvmqffGFYWPEMLK----CDKFPE 111

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 24640561  387 PLELSYCRQVGYNITTYPNLLGHASYEQLAEDVIVFRELVDGECHREAYDFVCRLLQPPCdtHGSDLQPtpgqiCREYCE 466
Cdd:cd07453    7 PKSMALCYDIGYSEMRIPNLLEHETMAEVIQQSSSWLPLLARECHPDARIFLCSLFAPIC--WDRPIYP-----CRSLCE 79

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24640561  467 SFMAGCGGRLP---QRFRQFFDCERFPESTGTqschqkphCVSDMQSNVQSPRLCDGYADCPD 526
Cdd:cd07453   80 AVRSSCAPLMAcygYPWPEILHCDKFPVDHDL--------CISPQFIDTLSPERVKPRASCED 134

Glucosidase II beta subunit-like; The sequences found in this family are similar to a region found in the beta-subunit of glucosidase II, which is also known as protein kinase C substrate 80K-H (PRKCSH). The enzyme catalyzes the sequential removal of two alpha-1,3-linked glucose residues in the second step of N-linked oligosaccharide processing. The beta subunit is required for the solubility and stability of the heterodimeric enzyme, and is involved in retaining the enzyme within the endoplasmic reticulum.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24640561    503 HCVSDMQSNVQSPRLCDGYADCPDLSDERSCAFCSPNALYC---GRGRACVPRKARCDGKAD---CPDGADEKD------ 570
Cdd:pfam12999   39 KCLNHSEIKLSFDQVNDDYCDCPDGSDEPGTNACSNGKFYCaneGFIPGYIPSFKVDDGVCDydiCCDGSDEALgkcpnk 118

                           90
                   ....*....|..
gi 24640561    571 CLSIAPLAADLL 582
Cdd:pfam12999  119 CGEIARQFEEYL 130