C-type lectin (CTL)/C-type lectin-like (CTLD) domain; CLECT: C-type lectin (CTL)/C-type lectin-like (CTLD) domain; protein domains homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. This group is chiefly comprised of eukaryotic CTLDs, but contains some, as yet functionally uncharacterized, bacterial CTLDs. Many CTLDs are calcium-dependent carbohydrate binding modules; other CTLDs bind protein ligands, lipids, and inorganic surfaces, including CaCO3 and ice. Animal C-type lectins are involved in such functions as extracellular matrix organization, endocytosis, complement activation, pathogen recognition, and cell-cell interactions. For example: mannose-binding lectin and lung surfactant proteins A and D bind carbohydrates on surfaces (e.g. pathogens, allergens, necrotic, and apoptotic cells) and mediate functions associated with killing and phagocytosis; P (platlet)-, E (endothelial)-, and L (leukocyte)- selectins (sels) mediate the initial attachment, tethering, and rolling of lymphocytes on inflamed vascular walls enabling subsequent lymphocyte adhesion and transmigration. CTLDs may bind a variety of carbohydrate ligands including mannose, N-acetylglucosamine, galactose, N-acetylgalactosamine, and fucose. Several CTLDs bind to protein ligands, and only some of these binding interactions are Ca2+-dependent; including the CTLDs of Coagulation Factors IX/X (IX/X) and Von Willebrand Factor (VWF) binding proteins, and natural killer cell receptors. C-type lectins, such as lithostathine, and some type II antifreeze glycoproteins function in a Ca2+-independent manner to bind inorganic surfaces. Many proteins in this group contain a single CTLD; these CTLDs associate with each other through several different surfaces to form dimers, trimers, or tetramers, from which ligand-binding sites project in different orientations. Various vertebrate type 1 transmembrane proteins including macrophage mannose receptor, endo180, phospholipase A2 receptor, and dendritic and epithelial cell receptor (DEC205) have extracellular domains containing 8 or more CTLDs; these CTLDs remain in the parent model. In some members (IX/X and VWF binding proteins), a loop extends to the adjoining domain to form a loop-swapped dimer. A similar conformation is seen in the macrophage mannose receptor CRD4's putative non-sugar bound form of the domain in the acid environment of the endosome. Lineage specific expansions of CTLDs have occurred in several animal lineages including Drosophila melanogaster and Caenorhabditis elegans; these CTLDs also remain in the parent model.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1663448272 1127 CDHTWRKFQGHCYCYFAHRRSWEEAERDCRRRSGHLTSIHSWEEHNFISSFGHENTWIGLNDRIVEQDFQWTDNTGLQYE 1206
Cdd:cd03588      1 CEEGWDKFQGHCYRHFPDRETWEDAERRCREQQGHLSSIVTPEEQEFVNNNAQDYQWIGLNDRTIEGDFRWSDGHPLQFE 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1663448272 1207 NWRENQPDNFFAGGEDCVVLVSHETGKWNDVPCNYKLPYVCKK 1249
Cdd:cd03588     81 NWRPNQPDNFFATGEDCVVMIWHEEGEWNDVPCNYHLPFTCKK 123

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1663448272   32 KVSHQPVRVGLAEPVSLPCLFLLqgsiPPNPGERPDPPRIKWSKVQSATGQpEDLSVLVAKDNVVKISKNYEGRIALPGY 111
Cdd:cd05902      1 RVTAPPVRRPLSSSVLLPCVFTL----PPSASSPPEGPRIKWTKLSTSGGQ-QQRPVLVARDNVVRVAKAFQGRVSLPGY 75

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1663448272  112 PHHRENATLLFLSARASDAGLYRCEIVTGIHDEQDLVPLEVTGVVF 157
Cdd:cd05902     76 PKNRYNASLVLSRLRYSDSGTYRCEVVLGINDEQDTVPLEVTGVVF 121

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 1663448272 1085 DIDDCLS-NPCQNGGTCIDEINAFVCLCLPSYGGSLC 1120
Cdd:cd00054      1 DIDECASgNPCQNGGTCVNTVGSYRCSCPPGYTGRNC 37

EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very similar, but has 8 instead of 6 conserved cysteines. Includes some cytokine receptors. The EGF domain misses the N-terminus regions of the Ca2+ binding EGF domains (this is the main reason of discrepancy between swiss-prot domain start/end and Pfam). The family is hard to model due to many similar but different sub-types of EGF domains. Pfam certainly misses a number of EGF domains.

                           10        20        30
                   ....*....|....*....|....*....|.
gi 1663448272 1051 CDNDPCLHGGTCQSSGNLSSCYCLPGFTGEN 1081
Cdd:pfam00008    1 CAPNPCSNGGTCVDTPGGYTCICPEGYTGKR 31

C-type lectin-like domain (CTLD) of the type found in chondroitin sulfate proteoglycan core proteins; CLECT_CSPGs: C-type lectin-like domain (CTLD) of the type found in chondroitin sulfate proteoglycan core proteins (CSPGs) in human and chicken aggrecan, frog brevican, and zebra fish dermacan. CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. In cartilage, aggrecan forms cartilage link protein stabilized aggregates with hyaluronan (HA). These aggregates contribute to the tissue's load bearing properties. Aggregates having other CSPGs substituting for aggrecan may contribute to the structural integrity of many different tissues. Xenopus brevican is expressed in the notochord and the brain during early embryogenesis. Zebra fish dermacan is expressed in dermal bones and may play a role in dermal bone development. CSPGs do contain LINK domain(s) which bind HA. These LINK domains are considered by one classification system to be a variety of CTLD, but are omitted from this hierarchical classification based on insignificant sequence similarity.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1663448272 1127 CDHTWRKFQGHCYCYFAHRRSWEEAERDCRRRSGHLTSIHSWEEHNFISSFGHENTWIGLNDRIVEQDFQWTDNTGLQYE 1206
Cdd:cd03588      1 CEEGWDKFQGHCYRHFPDRETWEDAERRCREQQGHLSSIVTPEEQEFVNNNAQDYQWIGLNDRTIEGDFRWSDGHPLQFE 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1663448272 1207 NWRENQPDNFFAGGEDCVVLVSHETGKWNDVPCNYKLPYVCKK 1249
Cdd:cd03588     81 NWRPNQPDNFFATGEDCVVMIWHEEGEWNDVPCNYHLPFTCKK 123

Immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), neurocan; The members here are composed of the immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), neurocan. In CSPGs, the Ig-like domain is followed by hyaluronan (HA)-binding tandem repeats, and a C-terminal region with epidermal growth factor-like, lectin-like, and complement regulatory protein-like domains. Separating these N- and C-terminal regions is a nonhomologous glycosaminoglycan attachment region. In cartilage, the CSPG aggrecan (not included in this group) forms cartilage link protein stabilized aggregates with HA. These aggregates contribute to the tissue's load bearing properties. Unlike aggrecan which is widely distributed in connective tissue and extracellular matrices, neurocan is localized almost exclusively in nervous tissue. Aggregates having other CSPGs substituting for aggrecan may contribute to the structural integrity of many different tissues. Members of the vertebrate HPLN (hyaluronan/HA and proteoglycan binding link) protein family are physically linked adjacent to CSPG genes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1663448272   32 KVSHQPVRVGLAEPVSLPCLFLLqgsiPPNPGERPDPPRIKWSKVQSATGQpEDLSVLVAKDNVVKISKNYEGRIALPGY 111
Cdd:cd05902      1 RVTAPPVRRPLSSSVLLPCVFTL----PPSASSPPEGPRIKWTKLSTSGGQ-QQRPVLVARDNVVRVAKAFQGRVSLPGY 75

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1663448272  112 PHHRENATLLFLSARASDAGLYRCEIVTGIHDEQDLVPLEVTGVVF 157
Cdd:cd05902     76 PKNRYNASLVLSRLRYSDSGTYRCEVVLGINDEQDTVPLEVTGVVF 121

Link (Hyaluronan-binding);

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1663448272   221 GKVFYATSPGR--LTFQMAQKHCLSRGAQLATTGQLYLAWQEGLDQCDPGWLADGSVRYPIRTPRKKCGGDEPGVRttyq 298
Cdd:smart00445    2 GGVFHVEKNGRykLTFAEAREACRAQGATLATVGQLYAAWQDGFDTCDAGWLADGSVRYPIITPRPRCGGNLPGVR---- 77

                            90       100
                    ....*....|....*....|
gi 1663448272   299 fsnRTGFPDPASKFDAYCYK 318
Cdd:smart00445   78 ---QYGFPDPTSRYDAYCFN 94

Link_domain_CSPGs_modules_1_3; this extracellular link domain is found in the first and third link modules of the chondroitin sulfate proteoglycan core protein (CSPG) aggrecan. In addition, it is found in the first link module of three other CSPGs: versican, neurocan, and brevican. The link domain is a hyaluronan (HA)-binding domain. CSPGs are characterized by an N-terminal globular domain (G1 domain) containing two contiguous link modules (modules 1 and 2). Both link modules of the G1 domain of aggrecan are involved in interaction with HA. In addition, aggrecan contains a second globular domain (G2) which contains link modules 3 and 4. G2 appears to lack HA-binding activity. In cartilage, aggrecan forms cartilage link protein stabilized aggregates with HA. These aggregates contribute to the tissue's load bearing properties. Aggregates having other CSPGs substituting for aggrecan may contribute to the structural integrity of many different tissues. Members of the vertebrate HPLN (hyaluronan/HA and proteoglycan binding link) protein family are physically linked adjacent to CSPG genes.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1663448272  155 VVFHYRAASNRYALTFSEAQKACEENSAVIASPAHLEEAFEDGYDNCDAGWLSDHTVRYPITLSRPG 221
Cdd:cd03517      1 VVFHYRDATARYALTFPRAQRACLDISAQIATPEQLLAAYEDGFEQCDAGWLADQTVRYPIQTPREG 67

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 1663448272 1085 DIDDCLS-NPCQNGGTCIDEINAFVCLCLPSYGGSLC 1120
Cdd:cd00054      1 DIDECASgNPCQNGGTCVNTVGSYRCSCPPGYTGRNC 37

Calcium-binding EGF-like domain;

                            10        20        30
                    ....*....|....*....|....*....|....*...
gi 1663448272  1085 DIDDCLS-NPCQNGGTCIDEINAFVCLCLPSY-GGSLC 1120
Cdd:smart00179    1 DIDECASgNPCQNGGTCVNTVGSYRCECPPGYtDGRNC 38

Domain abundant in complement control proteins; SUSHI repeat; short complement-like repeat (SCR); The complement control protein (CCP) modules (also known as short consensus repeats SCRs or SUSHI repeats) contain approximately 60 amino acid residues and have been identified in several proteins of the complement system. A missense mutation in seventh CCP domain causes deficiency of the b subunit of factor XIII.

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*..
gi 1663448272  1254 CGPPPLVENASPIGKKkEKYSVHSTIRYQCTEGFLQRHLPTIKCHVNGLWENPKVLC 1310
Cdd:smart00032    1 CPPPPDIENGTVTSSS-GTYSYGDTVTYSCDPGYTLIGSSTITCLENGTWSPPPPTC 56

EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very similar, but has 8 instead of 6 conserved cysteines. Includes some cytokine receptors. The EGF domain misses the N-terminus regions of the Ca2+ binding EGF domains (this is the main reason of discrepancy between swiss-prot domain start/end and Pfam). The family is hard to model due to many similar but different sub-types of EGF domains. Pfam certainly misses a number of EGF domains.

                           10        20        30
                   ....*....|....*....|....*....|.
gi 1663448272 1051 CDNDPCLHGGTCQSSGNLSSCYCLPGFTGEN 1081
Cdd:pfam00008    1 CAPNPCSNGGTCVDTPGGYTCICPEGYTGKR 31

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1663448272   37 PVRVGLAEPVSLPCLFllqgsippNPGERPDPPRIKWSKVQsaTGQPEDLSVLVAKDNVVKISKnyEGRIALPGYPHhRE 116
Cdd:pfam07686    5 EVTVALGGSVTLPCTY--------SSSMSEASTSVYWYRQP--PGKGPTFLIAYYSNGSEEGVK--KGRFSGRGDPS-NG 71

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1663448272  117 NATLLFLSARASDAGLYRCEIVT-GIHDEQDLVPLEVT 153
Cdd:pfam07686   72 DGSLTIQNLTLSDSGTYTCAVIPsGEGVFGKGTRLTVL 109

Calcium-binding EGF-like domain;

                            10        20        30
                    ....*....|....*....|....*....|....*..
gi 1663448272  1049 DPC-DNDPCLHGGTCQSSGNLSSCYCLPGFT-GENCE 1083
Cdd:smart00179    3 DECaSGNPCQNGGTCVNTVGSYRCECPPGYTdGRNCE 39

C-type lectin-like domain (CTLD) of the type found in chondroitin sulfate proteoglycan core proteins; CLECT_CSPGs: C-type lectin-like domain (CTLD) of the type found in chondroitin sulfate proteoglycan core proteins (CSPGs) in human and chicken aggrecan, frog brevican, and zebra fish dermacan. CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. In cartilage, aggrecan forms cartilage link protein stabilized aggregates with hyaluronan (HA). These aggregates contribute to the tissue's load bearing properties. Aggregates having other CSPGs substituting for aggrecan may contribute to the structural integrity of many different tissues. Xenopus brevican is expressed in the notochord and the brain during early embryogenesis. Zebra fish dermacan is expressed in dermal bones and may play a role in dermal bone development. CSPGs do contain LINK domain(s) which bind HA. These LINK domains are considered by one classification system to be a variety of CTLD, but are omitted from this hierarchical classification based on insignificant sequence similarity.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1663448272 1127 CDHTWRKFQGHCYCYFAHRRSWEEAERDCRRRSGHLTSIHSWEEHNFISSFGHENTWIGLNDRIVEQDFQWTDNTGLQYE 1206
Cdd:cd03588      1 CEEGWDKFQGHCYRHFPDRETWEDAERRCREQQGHLSSIVTPEEQEFVNNNAQDYQWIGLNDRTIEGDFRWSDGHPLQFE 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1663448272 1207 NWRENQPDNFFAGGEDCVVLVSHETGKWNDVPCNYKLPYVCKK 1249
Cdd:cd03588     81 NWRPNQPDNFFATGEDCVVMIWHEEGEWNDVPCNYHLPFTCKK 123

Immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), neurocan; The members here are composed of the immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), neurocan. In CSPGs, the Ig-like domain is followed by hyaluronan (HA)-binding tandem repeats, and a C-terminal region with epidermal growth factor-like, lectin-like, and complement regulatory protein-like domains. Separating these N- and C-terminal regions is a nonhomologous glycosaminoglycan attachment region. In cartilage, the CSPG aggrecan (not included in this group) forms cartilage link protein stabilized aggregates with HA. These aggregates contribute to the tissue's load bearing properties. Unlike aggrecan which is widely distributed in connective tissue and extracellular matrices, neurocan is localized almost exclusively in nervous tissue. Aggregates having other CSPGs substituting for aggrecan may contribute to the structural integrity of many different tissues. Members of the vertebrate HPLN (hyaluronan/HA and proteoglycan binding link) protein family are physically linked adjacent to CSPG genes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1663448272   32 KVSHQPVRVGLAEPVSLPCLFLLqgsiPPNPGERPDPPRIKWSKVQSATGQpEDLSVLVAKDNVVKISKNYEGRIALPGY 111
Cdd:cd05902      1 RVTAPPVRRPLSSSVLLPCVFTL----PPSASSPPEGPRIKWTKLSTSGGQ-QQRPVLVARDNVVRVAKAFQGRVSLPGY 75

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1663448272  112 PHHRENATLLFLSARASDAGLYRCEIVTGIHDEQDLVPLEVTGVVF 157
Cdd:cd05902     76 PKNRYNASLVLSRLRYSDSGTYRCEVVLGINDEQDTVPLEVTGVVF 121

Extracellular link domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1663448272  222 KVFYATSPGR--LTFQMAQKHCLSRGAQLATTGQLYLAWQEGLDQCDPGWLADGSVRYPIRTPRKKCGGDEPGVRTtyqf 299
Cdd:pfam00193    1 GVFHLESPGRykLTFQEAQAACAALGATLATPEQLYAAWKAGLDTCDAGWLADGTVRYPITTPRPNCGGNMPGVRQ---- 76

                           90
                   ....*....|....*....
gi 1663448272  300 snrTGFPDP-ASKFDAYCY 317
Cdd:pfam00193   77 ---YGFRDPlSERYDAYCY 92

C-type lectin-like domain (CTLD) of the type found in CEL-1 from Cucumaria echinata and Echinoidin from Anthocidaris crassispina; CLECT_CEL-1_like: C-type lectin-like domain (CTLD) of the type found in CEL-1 from Cucumaria echinata and Echinoidin from Anthocidaris crassispina. CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. The CEL-1 CTLD binds three calcium ions and has a high specificity for N-acteylgalactosamine (GalNAc). CEL-1 exhibits strong cytotoxicity which is inhibited by GalNAc. This protein may play a role as a toxin defending against predation. Echinoidin is found in the coelomic fluid of the sea urchin and is specific for GalBeta1-3GalNAc. Echinoidin has a cell adhesive activity towards human cancer cells which is not mediated through the CTLD. Both CEL-1 and Echinoidin are multimeric proteins comprised of multiple dimers linked by disulfide bonds.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1663448272 1127 CDHTWRKFQGHCYCYFAHRRSWEEAERDCR-----RRSGHLTSIHSWEEHNFI------SSFGHENT--WIGLNDRIVEQ 1193
Cdd:cd03589      1 CPTFWTAFGGYCYRFFGDRLTWEEAELRCRsfsipGLIAHLVSIHSQEENDFVydlfesSRGPDTPYglWIGLHDRTSEG 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1663448272 1194 DFQWTDNTGLQYENWRENQPDNFFaGGEDCVVLVSHE--TGKWNDVPCNYKLPYVCK 1248
Cdd:cd03589     81 PFEWTDGSPVDFTKWAGGQPDNYG-GNEDCVQMWRRGdaGQSWNDMPCDAVFPYICK 136

Immunoglobulin (Ig)-like domain of chondroitin sulfate proteoglycans (CSPGs), human cartilage link protein (LP), and similar domains; The members here are composed of the immunoglobulin (Ig)-like domain similar to that found in chondroitin sulfate proteoglycans (CSPGs) and human cartilage link protein (LP). Included in this group are the CSPGs aggrecan, versican, and neurocan. In CSPGs, this Ig-like domain is followed by hyaluronan (HA)-binding tandem repeats, and a C-terminal region with epidermal growth factor-like, lectin-like, and complement regulatory protein-like domains. Separating these N- and C-terminal regions is a nonhomologous glycosaminoglycan attachment region. In cartilage, aggrecan forms cartilage link protein stabilized aggregates with hyaluronan (HA). These aggregates contribute to the tissue's load bearing properties. Aggrecan and versican have a wide distribution in connective tissue and extracellular matrices. Neurocan is localized almost exclusively in nervous tissue. Aggregates having other CSPGs substituting for aggrecan may contribute to the structural integrity of many different tissues. There is considerable evidence that HA-binding CSPGs are involved in developmental processes in the central nervous system. Members of the vertebrate HPLN (hyaluronan/HA and proteoglycan binding link) protein family are physically linked adjacent to CSPG genes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1663448272   37 PVRVGLAEPVSLPCLFLLQgsiPPNPGERPDPPRIKWSKVQSATGQPEDLSVLVAKDNVVKISKNYEGRIALPGYPHHRE 116
Cdd:cd05714      6 KVFSHLGGNVTLPCKFYRD---PTAFGSGIHKIRIKWTKLTSDSGYLKEVDVLVAMGNVVYHKKTYGGRVSVPLKPGSDS 82

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1663448272  117 NATLLFLSARASDAGLYRCEIVTGIHDEQDLVPLEVTGVVF 157
Cdd:cd05714     83 DASLVITDLTASDYGLYRCEVIEGIEDDQDVVALDVQGVVF 123

C-type lectin (CTL) or carbohydrate-recognition domain (CRD); Many of these domains function as calcium-dependent carbohydrate binding modules.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1663448272  1127 CDHTWRKFQGHCYCYFAHRRSWEEAERDCRRRSGHLTSIHSWEEHNFISSF-----GHENTWIGLNDRIVEQDFQWTDNT 1201
Cdd:smart00034    1 CPSGWISYGGKCYKFSTEKKTWEDAQAFCQSLGGHLASIHSEAENDFVASLlknsgSSDYYWIGLSDPDSNGSWQWSDGS 80

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*...
gi 1663448272  1202 GL-QYENWRENQPDNffaGGEDCVVLvSHETGKWNDVPCNYKLPYVCK 1248
Cdd:smart00034   81 GPvSYSNWAPGEPNN---SSGDCVVL-STSGGKWNDVSCTSKLPFVCE 124

Link_domain_CSPGs_modules_1_3; this extracellular link domain is found in the first and third link modules of the chondroitin sulfate proteoglycan core protein (CSPG) aggrecan. In addition, it is found in the first link module of three other CSPGs: versican, neurocan, and brevican. The link domain is a hyaluronan (HA)-binding domain. CSPGs are characterized by an N-terminal globular domain (G1 domain) containing two contiguous link modules (modules 1 and 2). Both link modules of the G1 domain of aggrecan are involved in interaction with HA. In addition, aggrecan contains a second globular domain (G2) which contains link modules 3 and 4. G2 appears to lack HA-binding activity. In cartilage, aggrecan forms cartilage link protein stabilized aggregates with HA. These aggregates contribute to the tissue's load bearing properties. Aggregates having other CSPGs substituting for aggrecan may contribute to the structural integrity of many different tissues. Members of the vertebrate HPLN (hyaluronan/HA and proteoglycan binding link) protein family are physically linked adjacent to CSPG genes.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1663448272  155 VVFHYRAASNRYALTFSEAQKACEENSAVIASPAHLEEAFEDGYDNCDAGWLSDHTVRYPITLSRPG 221
Cdd:cd03517      1 VVFHYRDATARYALTFPRAQRACLDISAQIATPEQLLAAYEDGFEQCDAGWLADQTVRYPIQTPREG 67

The link domain is a hyaluronan (HA)-binding domain. It functions to mediate adhesive interactions during inflammatory leukocyte homing and tumor metastasis. It is found in the CD44 receptor and in human TSG-6. TSG-6 is the protein product of the tumor necrosis factor-stimulated gene-6. TSG-6 has a strong anti-inflammatory effect in models of acute inflammation and autoimmune arthritis and plays an essential role in female fertility. This group also contains the link domains of the chondroitin sulfate proteoglycan core proteins (CSPG) including aggrecan, versican, neurocan, and brevican and the link domains of the vertebrate HAPLN (HA and proteoglycan binding link) protein family. In cartilage, aggrecan forms cartilage link protein stabilized aggregates with HA. These aggregates contribute to the tissue's load bearing properties. Aggregates in which other CSPGs substitute for aggregan might contribute to the structural integrity of many different tissues. Members of the vertebrate HPLN gene family are physically linked adjacent to CSPG genes. TSG-6 contains a single link module which supports high affinity binding with HA. The functional HA-binding domain of CD44 is an extended domain comprised of a link module flanked with N-and C- extensions. These extensions are essential for folding and functional activity. CSPGs are characterized by an N-terminal globular domain (G1 domain) containing two contiguous link modules (modules 1 and 2). Both link modules of the G1 domain of the CSPG aggrecan are involved in interaction with HA. Aggrecan in addition contains a second globular domain (G2) which contains link modules 3 and 4 which lack HA-binding activity. HAPLNs contain two contiguous link modules.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1663448272  222 KVFYATSP-GR--LTFQMAQKHCLSRGAQLATTGQLYLAWQEGLDQCDPGWLADGSVRYPIRTPRKKCGGDEPGVRTtyq 298
Cdd:cd01102      1 VVFHLESQnGRykLTFAEAALACKARGAHLATPGQLEAAWQDGFDVCTAGWLADGSVRYPIVTSRPNCGGRNPGVRS--- 77

                           90
                   ....*....|....*....
gi 1663448272  299 fsnrTGFPDPASKFDAYCY 317
Cdd:cd01102     78 ----YGNPAPSGRYDAYCF 92

Immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), versican; The members here are composed of the immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), versican. In CSPGs, the Ig-like domain is followed by hyaluronan (HA)-binding tandem repeats, and a C-terminal region with epidermal growth factor-like, lectin-like, and complement regulatory protein-like domains. Separating these N- and C-terminal regions is a nonhomologous glycosaminoglycan attachment region. In cartilage, the CSPG aggrecan (not included in this group) forms cartilage link protein stabilized aggregates with HA. These aggregates contribute to the tissue's load bearing properties. Like aggrecan, versican has a wide distribution in connective tissue and extracellular matrices. Aggregates having other CSPGs substituting for aggrecan may contribute to the structural integrity of many different tissues. Members of the vertebrate HPLN (hyaluronan/HA and proteoglycan binding link) protein family are physically linked adjacent to CSPG genes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1663448272   34 SHQPVRVGLAEPVSLPCLFLLQGSIPPNPGERPDPPRIKWSKVQSATG--QPEDLSVLVAKDNVVKISKNYEGRIALPGY 111
Cdd:cd05901      3 KSSRVHGSLSGSVVLPCRFSTLPTLPPSYNITSEFLRIKWTKIQVDKNgkDHKETTVLVAQNGIIKIGQEYMGRVSVPSH 82

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1663448272  112 PHHRENATLLFLSARASDAGLYRCEIVTGIHDEQDLVPLEVTGVVF 157
Cdd:cd05901     83 PEDQGDASLTIVKLRASDAGVYRCEVMHGIEDTQDTVSLDVSGVVF 128

Link_domain_HAPLN_module_1; this link domain is found in the first link module of proteins similar to the vertebrate HAPLN (hyaluronan/HA and proteoglycan binding link) protein family which includes cartilage link protein. The link domain is a HA-binding domain. HAPLNs contain two contiguous link modules. Both link modules of cartilage link protein are involved in interaction with HA. In cartilage, a chondroitin sulfate proteoglycan core protein (CSPG) aggrecan forms cartilage link protein stabilized aggregates with HA. These aggregates contribute to the tissue's load bearing properties. Aggregates with other CSPGs substituting for aggregan may contribute to the structural integrity of many different tissues. Members of the vertebrate HAPLN gene family are physically linked adjacent to CSPG genes.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1663448272  155 VVFHYRAASNRYALTFSEAQKACEENSAVIASPAHLEEAFEDGYDNCDAGWLSDHTVRYPITLSRPGKVFYATSPG 230
Cdd:cd03518      1 VVFPYQPRLGRYNLNFHEAQQACEEQDATLASFEQLYQAWTEGLDWCNAGWLSDGTVQYPITKPREPCGGKRTVPG 76

Immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), aggrecan; The members here are composed of the immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), aggrecan. In CSPGs, the Ig-like domain is followed by hyaluronan (HA)-binding tandem repeats, and a C-terminal region with epidermal growth factor-like, lectin-like, and complement regulatory protein-like domains. Separating these N- and C-terminal regions is a nonhomologous glycosaminoglycan attachment region. In cartilage, aggrecan forms cartilage link protein stabilized aggregates with HA. These aggregates contribute to the tissue's load bearing properties. Aggrecan has a wide distribution in connective tissue and extracellular matrices. Members of the vertebrate HPLN (hyaluronan/HA and proteoglycan binding link) protein family are physically linked adjacent to CSPG genes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1663448272   37 PVRVGLAEPVSLPCLFLL-QGSIPPNPGERPDPPRIKWSKVQSATgqpeDLSVLVAKDNVVKISKNYEGRIALPGYPHHR 115
Cdd:cd05900      6 PLRVVLGSSLLIPCYFQDpIAKDPGAPTVAPLSPRIKWSFISKEK----ESVLLVATEGKVRVNTEYLDRVSLPNYPAIP 81

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1663448272  116 ENATLLFLSARASDAGLYRCEIVTGIHDEQDLVPLEVTGVVF 157
Cdd:cd05900     82 SDATLEITELRSNDSGTYRCEVMHGIEDNYDTVEVQVKGIVF 123

C-type lectin-like domain (CTLD) of the type found in the type 1 transmembrane proteins: P(platlet)-, E(endothelial)-, and L(leukocyte)- selectins (sels); CLECT_selectins_like: C-type lectin-like domain (CTLD) of the type found in the type 1 transmembrane proteins: P(platlet)-, E(endothelial)-, and L(leukocyte)- selectins (sels). CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. P- E- and L-sels are cell adhesion receptors that mediate the initial attachment, tethering, and rolling of lymphocytes on inflamed vascular walls enabling subsequent lymphocyte adhesion and transmigration. L- sel is expressed constitutively on most leukocytes. P-sel is stored in the Weibel-Palade bodies of endothelial cells and in the alpha granules of platlets. E- sels are present on endothelial cells. Following platelet and/or endothelial cell activation P- sel is rapidly translocated to the cell surface and E-sel expression is induced. The initial step in leukocyte migration involves interactions of selectins with fucosylated, sialylated, and sulfated carbohydrate moieties on target ligands displayed on glycoprotein scaffolds on endothelial cells and leucocytes. A major ligand of P- E- and L-sels is PSGL-1 (P-sel glycoprotein ligand). Interactions of E- and P- sels with tumor cells may promote extravasation of cancer cells. Regulation of L-sel and P-sel function includes proteolytic shedding of the most extracellular portion (containing the CTLD) from the cell surface. Increased levels of the soluble form of P-sel in the plasma have been found in a number of diseases including coronary disease and diabetes. E- and P- sel also play roles in the development of synovial inflammation in inflammatory arthritis. Platelet P-sel, but not endothelial P-sel, plays a role in the inflammatory response and neointimal formation after arterial injury. Selectins may also function as signal-transducing receptors.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1663448272 1145 RRSWEEAERDCRRRSGHLTSIHSWEE----HNFISSFGHENTWIGLNDRIVEQDFQWTDNTGLQYENWRENQPDNffAGG 1220
Cdd:cd03592      9 KMTFNEAVKYCKSRGTDLVAIQNAEEnallNGFALKYNLGYYWIDGNDINNEGTWVDTDKKELEYKNWAPGEPNN--GRN 86

                           90       100
                   ....*....|....*....|....*..
gi 1663448272 1221 EDCVVLVSHETGKWNDVPCNYKLPYVC 1247
Cdd:cd03592     87 ENCLEIYIKDNGKWNDEPCSKKKSAIC 113

Immunoglobulin (Ig)-like domain of human cartilage link protein (LP), and similar domains; The members here are composed of the immunoglobulin (Ig)-like domain similar to that found in human cartilage link protein (LP; also called hyaluronan and proteoglycan link protein). In cartilage, chondroitin-keratan sulfate proteoglycan (CSPG), aggrecan, forms cartilage link protein stabilized aggregates with hyaluronan (HA). These aggregates contribute to the tissue's load bearing properties. Aggregates having other CSPGs substituting for aggrecan may contribute to the structural integrity of many different tissues. Members of the vertebrate HPLN (hyaluronan/HA and proteoglycan binding link) protein family are physically linked adjacent to CSPG genes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1663448272   46 VSLPCLFLLQGSIPPNPGERpdpprIKWSKVQSATGQPEDlsVLVAKDNVVKISKNYEGRIALPGypHHRENATLLFLSA 125
Cdd:cd05877     15 VTLPCRYHYEPELSAPRKIR-----VKWTKLEVDYAKEED--VLVAIGTRHKSYGSYQGRVFLRR--ADDLDASLVITDL 85

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1663448272  126 RASDAGLYRCEIVTGIHDEQDLVPLEVTGVVF 157
Cdd:cd05877     86 RLEDYGRYRCEVIDGLEDESVVVALRLRGVVF 117

C-type lectin-like domain (CTLD) of the type found in the human proteins, eosinophil major basic protein (EMBP) and prepro major basic protein homolog (MBPH); CLECT_EMBP_like: C-type lectin-like domain (CTLD) of the type found in the human proteins, eosinophil major basic protein (EMBP) and prepro major basic protein homolog (MBPH). CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. Eosinophils and basophils carry out various functions in allergic, parasitic, and inflammatory diseases. EMBP is stored in eosinophil crystalloid granules and is released upon degranulation. EMBP is also expressed in basophils. The proform of EMBP is expressed in placental X cells and breast tissue and increases significantly during human pregnancy. EMBP has cytotoxic properties and damages bacteria and mammalian cells, in vitro, as well as, helminth parasites. EMBP deposition has been observed in the inflamed tissue of allergy patients in a variety of diseases including asthma, atopic dermatitis, and rhinitis. In addition to its cytotoxic functions, EMBP activates cells and stimulates cytokine production. EMBP has been shown to bind the proteoglycan heparin. The binding site is similar to the carbohydrate binding site of other classical CTLD, such as mannose-binding protein (MBP1), however, heparin binding to EMBP is calcium ion independent. MBPH has reduced potency in cytotoxic and cytostimulatory assays compared with EMBP.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1663448272 1136 GHCYCYFAHRRSWEEAERDCRR-RSGHLTSIHSWEEHNFISSF-GHEN---TWIG--LNDRIVEQDFQWTDNTGLQYENW 1208
Cdd:cd03598      1 GRCYRFVKSPRTFRDAQVICRRcYRGNLASIHSFAFNYRVQRLvSTLNqaqVWIGgiITGKGRCRRFSWVDGSVWNYAYW 80

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1663448272 1209 RENQPDNffaGGEDCVVLVSHEtGKWNDVPCNYKLPYVC 1247
Cdd:cd03598     81 APGQPGN---RRGHCVELCTRG-GHWRRAHCKLRRPFIC 115

C-type lectin-like domain (CTLD) of the type found in the human type-1A transmembrane proteins chondrolectin (CHODL) and layilin; CLECT_chondrolectin_like: C-type lectin-like domain (CTLD) of the type found in the human type-1A transmembrane proteins chondrolectin (CHODL) and layilin. CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. CHODL is predominantly expressed in muscle cells and is associated with T-cell maturation. Various alternatively spliced isoforms have been of CHODL have been identified. The transmembrane form of CHODL is localized in the ER-Golgi apparatus. Layilin is widely expressed in different cell types. The extracellular CTLD of layilin binds hyaluronan (HA), a major constituent of the extracellular matrix (ECM). The cytoplasmic tail of layilin binds various members of the band 4.1/ERM superfamily (talin, radixin, and merlin). The ERM proteins are cytoskeleton-membrane linker molecules which link actin to receptors in the plasma membrane. Layilin co-localizes in with talin in membrane ruffles and may mediate signals from the ECM to the cell cytoskeleton.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1663448272 1132 RKFQGHCY--CYF---AHRRSWEEAERDCRRRSGHLTSIHSWEEHNFISSFGHE------NTWIGL---NDRIVEQD--- 1194
Cdd:cd03595      6 RGTEKPCYkiAYFqdsRRRLNFEEARQACREDGGELLSIESENEQKLIERFIQTlrasdgDFWIGLrrsSQYNVTSSacs 85

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1663448272 1195 --FQWTDNTGLQYENWRENQPDnffAGGEDCVVLVSHETG----------KWNDVPCNYKLPYVCK 1248
Cdd:cd03595     86 slYYWLDGSISTFRNWYVDEPS---CGSEVCVVMYHQPSApagqggpylfQWNDDNCNMKNNFICK 148

C-type lectin (CTL)/C-type lectin-like (CTLD) domain subgroup 1; a subgroup of protein domains homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins; CLECT_1: C-type lectin (CTL)/C-type lectin-like (CTLD) domain subgroup 1; a subgroup of protein domains homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. Many CTLDs are calcium-dependent carbohydrate binding modules; other CTLDs bind protein ligands, lipids, and inorganic surfaces including CaCO3 and ice. Animal C-type lectins are involved in such functions as extracellular matrix organization, endocytosis, complement activation, pathogen recognition, and cell-cell interactions. CTLDs may bind a variety of carbohydrate ligands including mannose, N-acetylglucosamine, galactose, N-acetylgalactosamine, and fucose. CTLDs associate with each other through several different surfaces to form dimers, trimers, or tetramers from which ligand-binding sites project in different orientations. In some CTLDs a loop extends to the adjoining domain to form a loop-swapped dimer.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1663448272 1145 RRSWEEAERDCRRRSGHLTSIHSWEEHNFISSFGHENT---WIGLNDRIveQDFQWTDNTGLQYENWRENQPDnffaGGE 1221
Cdd:cd03602      9 SKTWSEAQQYCRENYTDLATVQNQEDNALLSNLSRVSNsaaWIGLYRDV--DSWRWSDGSESSFRNWNTFQPF----GQG 82

                           90       100
                   ....*....|....*....|....*.
gi 1663448272 1222 DCVVLVSheTGKWNDVPCNYKLPYVC 1247
Cdd:cd03602     83 DCATMYS--SGRWYAALCSALKPFIC 106

Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system; SUSHI repeats (short complement-like repeat, SCR) are abundant in complement control proteins. The complement control protein (CCP) modules (also known as short consensus repeats SCRs or SUSHI repeats) contain approximately 60 amino acid residues and have been identified in several proteins of the complement system. Typically, 2 to 4 modules contribute to a binding site, implying that the orientation of the modules to each other is critical for function.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1663448272 1254 CGPPPLVENASPIGKKkEKYSVHSTIRYQCTEGFLQRHLPTIKCHVNGLWENPKVLC 1310
Cdd:cd00033      1 CPPPPVPENGTVTGSK-GSYSYGSTVTYSCNEGYTLVGSSTITCTENGGWSPPPPTC 56

C-type lectin-like domain (CTLD) of the type found in human thrombomodulin(TM), Endosialin, C14orf27, and C1qR; CLECT_thrombomodulin_like: C-type lectin-like domain (CTLD) of the type found in human thrombomodulin(TM), Endosialin, C14orf27, and C1qR. CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. In these thrombomodulin-like proteins the residues involved in coordinating Ca2+ in the classical MBP-A CTLD are not conserved. TM exerts anti-fibrinolytic and anti-inflammatory activity. TM also regulates blood coagulation in the anticoagulant protein C pathway. In this pathway, the procoagulant properties of thrombin (T) are lost when it binds TM. TM also plays a key role in tumor biology. It is expressed on endothelial cells and on several type of tumor cell including squamous cell carcinoma. Loss of TM expression correlates with advanced stage and poor prognosis. Loss of function of TM function may be associated with arterial or venous thrombosis and with late fetal loss. Soluble molecules of TM retaining the CTLD are detected in human plasma and urine where higher levels indicate injury and/or enhanced turnover of the endothelium. C1qR is expressed on endothelial cells and stem cells. It is also expressed on monocots and neutrophils, where it is subject to ectodomain shedding. Soluble forms of C1qR retaining the CTLD is detected in human plasma. C1qR modulates the phagocytosis of apoptotic cells in vivo. C1qR-deficient mice are defective in clearance of apoptotic cells in vivo. The cytoplasmic tail of C1qR, C-terminal to the CTLD of CD93, contains a PDZ binding domain which interacts with the PDZ domain-containing adaptor protein, GIPC. The juxtamembrane region of this tail interacts with the ezrin/radixin/moesin family. Endosialin functions in the growth and progression of abdominal tumors and is expressed in the stroma of several tumors.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1663448272 1135 QGHCYCYFAHRRSWEEAERDCRRRSGHLTSIHSWEEHNFISSF----------GHENTWIGLNDRIVE--------QDFQ 1196
Cdd:cd03600      3 SDACYTLHPQKLTFLEAQRSCIELGGNLATVRSGEEADVVSLLlaagpgrhgrGSLRLWIGLQREPRQcsdpslplRGFS 82

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1663448272 1197 W-TDNTGLQYENW-RENQPDnffAGGEDCVVL----VSHETGKWNDVPCNYKLP-YVCK 1248
Cdd:cd03600     83 WvTGDQDTDFSNWlQEPAGT---CTSPRCVALsaagSTPDNLKWKDGPCSARADgYLCK 138