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 6677895   36 KRSNCKPIPANLQLCHGIEYQNMRLPNLLGHETMKEVLEQAGAWIPLVMKQCHPDTKKFLCSLFAPVCLDDLDETIQPCH 115
Cdd:cd07446   1 KKSNCKPIPANMLLCHGIEYTNMRLPNLLGHETMKEVLQQAGSWIPLVQKQCHPDTKKFLCSLFAPVCLDDLDEAIQPCR 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 6677895  116 SLCVQVKDRCAPVMSAFGFPWPDMLECDRFPQDNDLCIPLASSDHLLP 163
Cdd:cd07446  81 SLCEAVKDGCAPVMSAFGFPWPDMLDCTRFPLDNDLCIPPAGSDHLLP 128

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 6677895   36 KRSNCKPIPANLQLCHGIEYQNMRLPNLLGHETMKEVLEQAGAWIPLVMKQCHPDTKKFLCSLFAPVCLDDLDETIQPCH 115
Cdd:cd07446   1 KKSNCKPIPANMLLCHGIEYTNMRLPNLLGHETMKEVLQQAGSWIPLVQKQCHPDTKKFLCSLFAPVCLDDLDEAIQPCR 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 6677895  116 SLCVQVKDRCAPVMSAFGFPWPDMLECDRFPQDNDLCIPLASSDHLLP 163
Cdd:cd07446  81 SLCEAVKDGCAPVMSAFGFPWPDMLDCTRFPLDNDLCIPPAGSDHLLP 128

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 6677895      43 IPANLQLCHGIEYQNMRLPNLLGHETMKEVLEQAGAWIPLVMKQCHPDTKKFLCSLFAPVCLDDLDeTIQPCHSLCVQVK 122
Cdd:smart00063   2 EPITIPLCKDLGYNLTSMPNLLGHTTQEEAGLELEQFHPLLNVQCSPDLRFFLCSVYAPICTEDLR-PILPCRSLCEAAR 80

                           90       100       110
                   ....*....|....*....|....*....|..
gi 6677895     123 DRCAPVMSAFGFPWPDMLECDRFPQDNDLCIP 154
Cdd:smart00063  81 EGCEPLMEKFGFPWPEFLRCDRFPVQEELCMD 112

Netrin C-terminal Domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6677895     186 METLCK--NDFALKIKVKEITYINRDTKIilETKSKTIYKLnGVSERDLKKSVLWLKDS-LQCTCEEMNDINAPYLVMGQ 262
Cdd:smart00643   1 LEKACKsdVDYVYKVKVLSVEEEGGFDKY--TVKILEVIKS-GTDELVRGKNKLRVFISrASCRCPLLLKLGKSYLIMGK 77

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 6677895     263 -------KQGGELVITS---VKRWQKGQ-REFKRISR 288
Cdd:smart00643  78 sgdlwdaKGRGQYVLGKnswVEEWPTEEeCRLRRLQK 114

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 6677895   36 KRSNCKPIPANLQLCHGIEYQNMRLPNLLGHETMKEVLEQAGAWIPLVMKQCHPDTKKFLCSLFAPVCLDDLDETIQPCH 115
Cdd:cd07446   1 KKSNCKPIPANMLLCHGIEYTNMRLPNLLGHETMKEVLQQAGSWIPLVQKQCHPDTKKFLCSLFAPVCLDDLDEAIQPCR 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 6677895  116 SLCVQVKDRCAPVMSAFGFPWPDMLECDRFPQDNDLCIPLASSDHLLP 163
Cdd:cd07446  81 SLCEAVKDGCAPVMSAFGFPWPDMLDCTRFPLDNDLCIPPAGSDHLLP 128

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 6677895  169 PKVCEACKTKNEDDNDIMETLCKNDFALKIKVKEITYINRDTKIILETKsKTIYKLNGVSERDLKKSVLWLKDSLQCTCE 248
Cdd:cd03580   1 PKVCPPCENEEESAKTLLDNFCASDFALKVKIKEISYENGDRKVIGEKK-KEILKQGPLKKKDLKKLVLWLKNGANCPCP 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 6677895  249 EMNDINAPYLVMGQKQGGELVITSVKRWQKGQREFKRISRSIRKLQC 295
Cdd:cd03580  80 QLDNLNGVYLVMGRKVDGKLLLTSIYKWQKKNKEFKRAVRKWKKHKC 126

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 6677895   38 SNCKPIPANLQLCHGIEYQNMRLPNLLGHETMKEVLEQAGAWIPLVMKQCHPDTKKFLCSLFAPVCLDDLdetIQPCHSL 117
Cdd:cd07453   1 SPCMRIPKSMALCYDIGYSEMRIPNLLEHETMAEVIQQSSSWLPLLARECHPDARIFLCSLFAPICWDRP---IYPCRSL 77

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 6677895  118 CVQVKDRCAPVMSAFGFPWPDMLECDRFPQDNDLCIPLASSDHLLPATEEAPKVCEAC 175
Cdd:cd07453  78 CEAVRSSCAPLMACYGYPWPEILHCDKFPVDHDLCISPQFIDTLSPERVKPRASCEDC 135

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 6677895   40 CKPIPanLQLCHGIEYQNMRLPNLLGHETMKEVLEQAGAWIPLVMKQCHPDTKKFLCSLFAPVCLDDLDETIQPCHSLCV 119
Cdd:cd07066   2 CEPIP--LPLCRGLPYNTTRFPNLLGHESQEEAEQELESFTPLVNSGCHPDLRFFLCSLYFPECTPDGDRPIPPCRSLCE 79

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 6677895  120 QVKDRCAPVMSAFGFPWPDMLECDRFPQDN--DLCIP 154
Cdd:cd07066  80 EVRDSCEPLMLAFGFPWPEPLDCDRFPDSNeeGLCIS 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 6677895   40 CKPIpaNLQLCHGIEYQNMRLPNLLGHETMKEVLEQAGAWIPLVMKQCHPDTKKFLCSLFAPVCLDDLDETIQPCHSLCV 119
Cdd:cd07448   4 CEPI--RIEMCQGLGYNVTRMPNLVGHELQTDAELQLQTFTPLIQYGCSSQLKFFLCSVYVPMCTEKVPVPIGPCRPLCL 81

                        90       100       110
                ....*....|....*....|....*....|.
gi 6677895  120 QVKDRCAPVMSAFGFPWPDMLECDRFPQDND 150
Cdd:cd07448  82 SVKKRCLPVLKEFGFPWPEALNCSKFPPQNN 112

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 6677895   40 CKPIpaNLQLCHGIEYQNMRLPNLLGHETMKEVLEQAGAWIPLVMKQCHPDTKKFLCSLFAPVCLDDLDETIQPCHSLCV 119
Cdd:cd07456   2 CEEI--TIPMCKGIGYNMTYMPNQFNHDTQEEAGLEVHQFWPLVEIQCSPDLKFFLCSMYTPICLEDYDKPLPPCRSVCE 79

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 6677895  120 QVKDRCAPVMSAFGFPWPDMLECDRFPQ---DNDLCI 153
Cdd:cd07456  80 RARDGCAPIMRQYGFAWPERMSCDALPEggdPDNLCM 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 6677895   36 KRSNCKPIpaNLQLCHGIEYQNMRLPNLLGHETMKEVLEQAGAWIPLVMKQCHPDTKKFLCSLFAPVCLDDLDETIQPCH 115
Cdd:cd07461   1 KELQCQEI--TVPLCKGIGYNYTYMPNQFNHDTQDEAGLEVHQFWPLVEIQCSPDLKFFLCSMYTPICLEDYKKPLPPCR 78

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 6677895  116 SLCVQVKDRCAPVMSAFGFPWPDMLECDRFPQDND---LCIPLASSD 159
Cdd:cd07461  79 SVCERAKAGCAPLMRQYGFPWPDRMRCDLLPEQGNpdtLCMDYNRTD 125

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 6677895   40 CKPIpaNLQLCHGIEYQNMRLPNLLGHETMKEVLEQAGAWIPLVMKQCHPDTKKFLCSLFAPVCLDDLDETIQPCHSLCV 119
Cdd:cd07463   5 CQPV--VIPMCRGIGYNLTRMPNFLGHDSQREAAIKLNEFAPLVEYGCHVHLRFFLCSLYAPMCTDQVSTSIPACRPMCE 82

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 6677895  120 QVKDRCAPVMSAFGFPWPDMLECDRFPQDND---LCI 153
Cdd:cd07463  83 QARQKCSPIMEQFNFGWPESLDCSRLPTRNDpnaLCM 119

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 6677895   40 CKPIpaNLQLCHGIEYQNMRLPNLLGHETMKEVLEQAGAWIPLVMKQCHPDTKKFLCSLFAPVCLDDLDETIQPCHSLCV 119
Cdd:cd07462   5 CQPI--EIPMCKDIGYNMTRMPNLMGHENQREAAIQLHEFAPLVEYGCHSHLKFFLCSLYAPMCTEQVSTPIPACRVMCE 82

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 6677895  120 QVKDRCAPVMSAFGFPWPDMLECDRFPQDND---LCI 153
Cdd:cd07462  83 QARLKCSPIMEQFNFKWPDSLDCSKLPNKNDpnyLCM 119

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 6677895   40 CKPIpaNLQLCHGIEYQNMRLPNLLGHETMKEVLEQAGAWIPLVMKQCHPDTKKFLCSLFAPVClDDLDETIQPCHSLCV 119
Cdd:cd07465   5 CQPI--SIPLCTDIAYNQTIMPNLLGHTNQEDAGLEVHQFYPLVKVQCSAELKFFLCSMYAPVC-TVLEQALPPCRSLCE 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 6677895  120 QVKDRCAPVMSAFGFPWPDMLECDRFPQD--NDLCIPLASSDHLLP 163
Cdd:cd07465  82 RARQGCEALMNKFGFQWPDTLRCEKFPVHgaGELCVGQNTSESGTP 127

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 6677895   40 CKPIpaNLQLCHGIEYQNMRLPNLLGHETMKEVLEQAGAWIPLVMKQCHPDTKKFLCSLFAPVCLDDLDETIqPCHSLCV 119
Cdd:cd07449   5 CEPI--TLRMCQDLPYNTTFMPNLLNHYDQQTAALAMEPFHPMVNLECSRDFRPFLCALYAPVCMEYGRVTL-PCRRLCQ 81

                        90       100
                ....*....|....*....|....*...
gi 6677895  120 QVKDRCAPVMSAFGFPWPDMLECDRFPQ 147
Cdd:cd07449  82 RAYSECSKLMEMFGVPWPEDMECSRFPD 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 second (C-terminal) CRD.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6677895   39 NCKPIpaNLQLCHGIEYQNMRLPNLLGHETMKE--VLEQAGAWIPLVMKQCHPDTKKFLCSLFAPVCLDDLDETIQPCHS 116
Cdd:cd07888   1 QCEPI--TLELCMNLPYNTTRYPNYLGHRTQKEasISWESSLFPALVQTNCYKYLMFFACTILVPKCDPVTQQRIPPCRS 78

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 6677895  117 LCVQVKDRCAPVMSAFGFPWPDMLECDRFP---QDNDLCI 153
Cdd:cd07888  79 LCRNSKERCESVLGIVGLQWPEDTDCAQFPeenSDNQTCL 118

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 6677895   38 SNCKPIpaNLQLCHGIEYQNMRLPNLLGHETMKEVLEQAGAWIPLVMKQCHPDTKKFLCSLFAPVCLDDLD-ETIQPCHS 116
Cdd:cd07441   2 ASCEPV--RIPMCKSMPWNMTKMPNHLHHSTQANAVLAIEQFEGLLGTQCSPDLLFFLCAMYAPICTIDFQhEPIKPCKS 79

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 6677895  117 LCVQVKDRCAPVMSAFGFPWPDMLECDRFP-QDNDLCI 153
Cdd:cd07441  80 VCERARAGCEPVLIRYRHTWPESLACEELPvYDRGVCI 117

Netrin C-terminal Domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6677895     186 METLCK--NDFALKIKVKEITYINRDTKIilETKSKTIYKLnGVSERDLKKSVLWLKDS-LQCTCEEMNDINAPYLVMGQ 262
Cdd:smart00643   1 LEKACKsdVDYVYKVKVLSVEEEGGFDKY--TVKILEVIKS-GTDELVRGKNKLRVFISrASCRCPLLLKLGKSYLIMGK 77

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 6677895     263 -------KQGGELVITS---VKRWQKGQ-REFKRISR 288
Cdd:smart00643  78 sgdlwdaKGRGQYVLGKnswVEEWPTEEeCRLRRLQK 114

Cysteine-rich domain of carboxypeptidase Z, a member of the carboxypeptidase E family; The cysteine-rich-domain (CRD) is an essential part of carboxypeptidase Z, a member of the carboxypeptidase E family of metallocarboxypeptidases. This is a group of Zn-dependent enzymes implicated in the intra- and extracellular processing of proteins. Carboxypeptidase Z removes C-terminal basic amino acid residues from its substrates, particularly arginine. The CRD acts as a ligand-binding domain for Wnts involved in developmental processes. CPZ binds and may process Wnt-4, CPZ has also been found to enhance the induction of the homeobox gene Cdx1. During vertebrate embryogenesis, the CRD of CPZ upregulates Pax3, a Wnt reporter gene essential for patterning of somites and limb development.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6677895   46 NLQLCHGIEYQNMRLPNLLGHETmKEVLEQAGAWI------PLVMKQCHPDTKKFLCSLFAPVCldDLDETIQPCHSLCV 119
Cdd:cd07447   8 LLSYCSDVSYTQTTFPNLLGHRS-REVTEAGAEYLllsvlhGLLGGECNPDIRLLGCSVLAPRC--ENDKVIKPCRSTCE 84

                        90       100
                ....*....|....*....|....*.
gi 6677895  120 QVKDRCAPVMSAFGFPWPDMLECDRF 145
Cdd:cd07447  85 ALRKRCSHAFDAIQMAWPYFLDCDRF 110

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 6677895  187 ETLCKNDFALKIKVKEITYINRDTKIilETKSKTIYKlNGVSERDLKKSVLWLKDSLQCTCEEMNDINAPYLVMGQKQG- 265
Cdd:cd03523   1 KAFCKSDYVVRAKIKEIKEENDDVKY--EVKIIKIYK-TGKAKADKADLRFYYTAPACCPCHPILNPGREYLIMGKEEDs 77

                ....*...
gi 6677895  266 -GELVITS 272
Cdd:cd03523  78 qGGLVLDP 85