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 255918077 2182 CDYGWHKFQGQCYKYFAHRRTWDAAERECRLQGAHLTSILSHEEQMFVNRVGHDYQWIGLNDKMFEHDFRWTDGSTLQYE 2261
Cdd:cd03588     1 CEEGWDKFQGHCYRHFPDRETWEDAERRCREQQGHLSSIVTPEEQEFVNNNAQDYQWIGLNDRTIEGDFRWSDGHPLQFE 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 255918077 2262 NWRPNQPDSFFSAGEDCVVIIWHENGQWNDVPCNYHLTYTCKKG 2305
Cdd:cd03588    81 NWRPNQPDNFFATGEDCVVMIWHEEGEWNDVPCNYHLPFTCKKG 124

Link_domain_CSPGs_modules_2_4; this link domain is found in the second and fourth link modules of the chondroitin sulfate proteoglycan core protein (CSPG) aggrecan and, in the second 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. Aggrecan in addition contains a second globular domain (G2) having link modules 3 and 4 which 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 aggregan 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 255918077  251 DVFHLTVPSKFTFEEAAKECENQDARLATVGELQAAWRNGFDQCDYGWLSDASVRHPVTVARAQCGGGLLGVRTLYRFEN 330
Cdd:cd03520     1 EVFYATAPEKFTFQEARAECRSLGAVLATTGQLYAAWRQGLDQCDPGWLADGSVRYPISTPRPQCGGGLPGVRTLYRFPN 80

                          90
                  ....*....|....*.
gi 255918077  331 QTGFPPPDSRFDAYCF 346
Cdd:cd03520    81 QTGFPDPHSRFDAYCF 96

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 255918077 2140 DFDECHS-NPCRNGATCVDGFNTFRCLCLPSYVGALCE 2176
Cdd:cd00054     1 DIDECASgNPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38

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 255918077 2309 CGQPPVVENAKTFGKmKPRYEINSLIRYHCKDGFIQRHLPTIRCLGNGRWAIPKITC 2365
Cdd:cd00033     1 CPPPPVPENGTVTGS-KGSYSYGSTVTYSCNEGYTLVGSSTITCTENGGWSPPPPTC 56

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 255918077 2182 CDYGWHKFQGQCYKYFAHRRTWDAAERECRLQGAHLTSILSHEEQMFVNRVGHDYQWIGLNDKMFEHDFRWTDGSTLQYE 2261
Cdd:cd03588     1 CEEGWDKFQGHCYRHFPDRETWEDAERRCREQQGHLSSIVTPEEQEFVNNNAQDYQWIGLNDRTIEGDFRWSDGHPLQFE 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 255918077 2262 NWRPNQPDSFFSAGEDCVVIIWHENGQWNDVPCNYHLTYTCKKG 2305
Cdd:cd03588    81 NWRPNQPDNFFATGEDCVVMIWHEEGEWNDVPCNYHLPFTCKKG 124

Link_domain_CSPGs_modules_2_4; this link domain is found in the second and fourth link modules of the chondroitin sulfate proteoglycan core protein (CSPG) aggrecan and, in the second 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. Aggrecan in addition contains a second globular domain (G2) having link modules 3 and 4 which 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 aggregan 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 255918077  251 DVFHLTVPSKFTFEEAAKECENQDARLATVGELQAAWRNGFDQCDYGWLSDASVRHPVTVARAQCGGGLLGVRTLYRFEN 330
Cdd:cd03520     1 EVFYATAPEKFTFQEARAECRSLGAVLATTGQLYAAWRQGLDQCDPGWLADGSVRYPISTPRPQCGGGLPGVRTLYRFPN 80

                          90
                  ....*....|....*.
gi 255918077  331 QTGFPPPDSRFDAYCF 346
Cdd:cd03520    81 QTGFPDPHSRFDAYCF 96

Extracellular link domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255918077   150 VVFHYRAAtSRYTLNFEAAQKACLDVGAVIATPEQLFAAYEDGFEQCDAGWLADQTVRYPIRAPRVGCYGdkmGKAGVRT 229
Cdd:pfam00193    1 GVFHLESP-GRYKLTFQEAQAACAALGATLATPEQLYAAWKAGLDTCDAGWLADGTVRYPITTPRPNCGG---NMPGVRQ 76

                           90
                   ....*....|....*.
gi 255918077   230 YGFRSPQ-ETYDVYCY 244
Cdd:pfam00193   77 YGFRDPLsERYDAYCY 92

Link (Hyaluronan-binding);

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255918077    148 DGVVFHYRAATsRYTLNFEAAQKACLDVGAVIATPEQLFAAYEDGFEQCDAGWLADQTVRYPIRAPRVGCYGdkmGKAGV 227
Cdd:smart00445    1 DGGVFHVEKNG-RYKLTFAEAREACRAQGATLATVGQLYAAWQDGFDTCDAGWLADGSVRYPIITPRPRCGG---NLPGV 76

                            90
                    ....*....|....*..
gi 255918077    228 RTYGFRSPQETYDVYCY 244
Cdd:smart00445   77 RQYGFPDPTSRYDAYCF 93

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 255918077   2182 CDYGWHKFQGQCYKYFAHRRTWDAAERECRLQGAHLTSILSHEEQMFV-----NRVGHDYQWIGLNDKMFEHDFRWTDGS 2256
Cdd:smart00034    1 CPSGWISYGGKCYKFSTEKKTWEDAQAFCQSLGGHLASIHSEAENDFVasllkNSGSSDYYWIGLSDPDSNGSWQWSDGS 80

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*...
gi 255918077   2257 -TLQYENWRPNQPDsffSAGEDCVViIWHENGQWNDVPCNYHLTYTCK 2303
Cdd:smart00034   81 gPVSYSNWAPGEPN---NSSGDCVV-LSTSGGKWNDVSCTSKLPFVCE 124

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 255918077 2140 DFDECHS-NPCRNGATCVDGFNTFRCLCLPSYVGALCE 2176
Cdd:cd00054     1 DIDECASgNPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38

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 255918077 2104 DRCKM-NPCLNGGTCYPTETSYVCTCVPGYSGDQCE 2138
Cdd:cd00054     3 DECASgNPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38

Calcium-binding EGF-like domain;

                            10        20        30
                    ....*....|....*....|....*....|....*....
gi 255918077   2140 DFDECHS-NPCRNGATCVDGFNTFRCLCLPSYV-GALCE 2176
Cdd:smart00179    1 DIDECASgNPCQNGGTCVNTVGSYRCECPPGYTdGRNCE 39

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 255918077   2309 CGQPPVVENAKTFGKmKPRYEINSLIRYHCKDGFIQRHLPTIRCLGNGRWAIPKITC 2365
Cdd:smart00032    1 CPPPPDIENGTVTSS-SGTYSYGDTVTYSCDPGYTLIGSSTITCLENGTWSPPPPTC 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
                   ....*....|....*....|....*....
gi 255918077  2144 CHSNPCRNGATCVDGFNTFRCLCLPSYVG 2172
Cdd:pfam00008    1 CAPNPCSNGGTCVDTPGGYTCICPEGYTG 29

C-type lectin-like protein; Provisional

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 255918077 2181 TCDYGWHKFQGQCYKYFAHRRTWDAAERECRLQGAHLTSILSHEEQMFVNRVGHDY-QWIGLNDKMFEHDFRWTDGST 2257
Cdd:PHA02642   87 TCPKGWIGFGYKCFYFSEDSKNWTFGNTFCTSLGATLVKVETEEELNFLKRYKDSSdHWIGLNRESSNHPWKWADNSN 164

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255918077     29 SPPVRGSLSGKVSLPCHFSTMPTLppsyntseflRIKWskievdkngkdLKETTVLVAQNGNIKIGQDYkgrvsvpthpe 108
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPP----------EVTW-----------YKQGGKLLAESGRFSVSRSG----------- 48

                            90       100       110
                    ....*....|....*....|....*....|....*....
gi 255918077    109 avGDASLTVVKLLASDAGLYRCDVMYGIEDTQDTVSLTV 147
Cdd:smart00410   49 --STSTLTISNVTPEDSGTYTCAATNSSGSASSGTTLTV 85

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 255918077 2182 CDYGWHKFQGQCYKYFAHRRTWDAAERECRLQGAHLTSILSHEEQMFVNRVGHDYQWIGLNDKMFEHDFRWTDGSTLQYE 2261
Cdd:cd03588     1 CEEGWDKFQGHCYRHFPDRETWEDAERRCREQQGHLSSIVTPEEQEFVNNNAQDYQWIGLNDRTIEGDFRWSDGHPLQFE 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 255918077 2262 NWRPNQPDSFFSAGEDCVVIIWHENGQWNDVPCNYHLTYTCKKG 2305
Cdd:cd03588    81 NWRPNQPDNFFATGEDCVVMIWHEEGEWNDVPCNYHLPFTCKKG 124

Immunoglobulin (Ig)-like domain of the aggrecan-like chondroitin sulfate proteoglycan core protein (CSPG); The members here are composed of the immunoglobulin (Ig)-like domain of the aggrecan-like chondroitin sulfate proteoglycan core proteins (CSPGs). Included in this group are the Ig domains of other CSPGs: 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. 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 255918077   26 VGKSPPVRGSLSGKVSLPCHFSTMPTLPPSYNTSEFLRIKWSKIEVDknGKDLKETTVLVAQNGNIKIGQDYKGRVSVPT 105
Cdd:cd05878     1 IPQSSPVRVLLGTSVTLPCYFIDPPHPVTPSTAPLAPRIKWSKVSVD--GKKEKEVVLLVATEGRVRVNSAYQGRVSLPN 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 255918077  106 HPEAVGDASLTVVKLLASDAGLYRCDVMYGIEDTQDTVSLTVDGVVF 152
Cdd:cd05878    79 YPAIPSDATLEVQSLRASDSGLYRCEVMHGIEDSQDTVELVVKGVVF 125

Link_domain_CSPGs_modules_2_4; this link domain is found in the second and fourth link modules of the chondroitin sulfate proteoglycan core protein (CSPG) aggrecan and, in the second 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. Aggrecan in addition contains a second globular domain (G2) having link modules 3 and 4 which 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 aggregan 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 255918077  251 DVFHLTVPSKFTFEEAAKECENQDARLATVGELQAAWRNGFDQCDYGWLSDASVRHPVTVARAQCGGGLLGVRTLYRFEN 330
Cdd:cd03520     1 EVFYATAPEKFTFQEARAECRSLGAVLATTGQLYAAWRQGLDQCDPGWLADGSVRYPISTPRPQCGGGLPGVRTLYRFPN 80

                          90
                  ....*....|....*.
gi 255918077  331 QTGFPPPDSRFDAYCF 346
Cdd:cd03520    81 QTGFPDPHSRFDAYCF 96

Extracellular link domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255918077   150 VVFHYRAAtSRYTLNFEAAQKACLDVGAVIATPEQLFAAYEDGFEQCDAGWLADQTVRYPIRAPRVGCYGdkmGKAGVRT 229
Cdd:pfam00193    1 GVFHLESP-GRYKLTFQEAQAACAALGATLATPEQLYAAWKAGLDTCDAGWLADGTVRYPITTPRPNCGG---NMPGVRQ 76

                           90
                   ....*....|....*.
gi 255918077   230 YGFRSPQ-ETYDVYCY 244
Cdd:pfam00193   77 YGFRDPLsERYDAYCY 92

Link (Hyaluronan-binding);

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255918077    148 DGVVFHYRAATsRYTLNFEAAQKACLDVGAVIATPEQLFAAYEDGFEQCDAGWLADQTVRYPIRAPRVGCYGdkmGKAGV 227
Cdd:smart00445    1 DGGVFHVEKNG-RYKLTFAEAREACRAQGATLATVGQLYAAWQDGFDTCDAGWLADGSVRYPIITPRPRCGG---NLPGV 76

                            90
                    ....*....|....*..
gi 255918077    228 RTYGFRSPQETYDVYCY 244
Cdd:smart00445   77 RQYGFPDPTSRYDAYCF 93

C-type lectin-like domain (CTLD) of the type found in human dendritic cell (DC)-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) and the related receptor, DC-SIGN receptor (DC-SIGNR); CLECT_DC-SIGN_like: C-type lectin-like domain (CTLD) of the type found in human dendritic cell (DC)-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) and the related receptor, DC-SIGN receptor (DC-SIGNR). This group also contains proteins similar to hepatic asialoglycoprotein receptor (ASGP-R) and langerin in human. These proteins are type II membrane proteins with a CTLD ectodomain. CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. DC-SIGN is thought to mediate the initial contact between dendritic cells and resting T cells, and may also mediate the rolling of DCs on epithelium. DC-SIGN and DC-SIGNR bind to oligosaccharides present on human tissues, as well as, on pathogens including parasites, bacteria, and viruses. DC-SIGN and DC-SIGNR bind to HIV enhancing viral infection of T cells. DC-SIGN and DC-SIGNR are homotetrameric, and contain four CTLDs stabilized by a coiled coil of alpha helices. The hepatic ASGP-R is an endocytic recycling receptor which binds and internalizes desialylated glycoproteins having a terminal galactose or N-acetylgalactosamine residues on their N-linked carbohydrate chains, via the clathrin-coated pit mediated endocytic pathway, and delivers them to lysosomes for degradation. It has been proposed that glycoproteins bearing terminal Sia (sialic acid) alpha2, 6GalNAc and Sia alpha2, 6Gal are endogenous ligands for ASGP-R and that ASGP-R participates in regulating the relative concentration of serum glycoproteins bearing alpha 2,6-linked Sia. The human ASGP-R is a hetero-oligomer composed of two subunits, both of which are found within this group. Langerin is expressed in a subset of dendritic leukocytes, the Langerhans cells (LC). Langerin induces the formation of Birbeck Granules (BGs) and associates with these BGs following internalization. Langerin binds, in a calcium-dependent manner, to glyco-conjugates containing mannose and related sugars mediating their uptake and degradation. Langerin molecules oligomerize as trimers with three CTLDs held together by a coiled-coil of alpha helices.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255918077 2182 CDYGWHKFQGQCYkYFAH-RRTWDAAERECRLQGAHLTSILSHEEQMFVNR--VGHDYQWIGLNDKMFEHDFRWTDGSTL 2258
Cdd:cd03590     1 CPTNWKSFQSSCY-FFSTeKKSWEESRQFCEDMGAHLVIINSQEEQEFISKilSGNRSYWIGLSDEETEGEWKWVDGTPL 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 255918077 2259 Q--YENWRPNQPDSFFSAGEDCVViIWHENGQWNDVPCNYHLTYTCKK 2304
Cdd:cd03590    80 NssKTFWHPGEPNNWGGGGEDCAE-LVYDSGGWNDVPCNLEYRWICEK 126

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 255918077 2193 CYKYFAHRRTWDAAERECRLQGAHLTSILSHEEQMFV----NRVGHDYQWIGLNDKMFEHDFRWTDGST-LQYENWRPNQ 2267
Cdd:cd00037     2 CYKFSTEKLTWEEAQEYCRSLGGHLASIHSEEENDFLasllKKSSSSDVWIGLNDLSSEGTWKWSDGSPlVDYTNWAPGE 81

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 255918077 2268 PDSffSAGEDCVVIIWHENGQWNDVPCNYHLTYTCKK 2304
Cdd:cd00037    82 PNP--GGSEDCVVLSSSSDGKWNDVSCSSKLPFICEK 116

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 255918077  150 VVFHYRAATSRYTLNFEAAQKACLDVGAVIATPEQLFAAYEDGFEQCDAGWLADQTVRYPIRAPRVGCYGDkmgKAGVRT 229
Cdd:cd01102     1 VVFHLESQNGRYKLTFAEAALACKARGAHLATPGQLEAAWQDGFDVCTAGWLADGSVRYPIVTSRPNCGGR---NPGVRS 77

                          90
                  ....*....|....*
gi 255918077  230 YGFRSPQETYDVYCY 244
Cdd:cd01102    78 YGNPAPSGRYDAYCF 92

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 255918077  252 VFHLTV---PSKFTFEEAAKECENQDARLATVGELQAAWRNGFDQCDYGWLSDASVRHPVTVARAQCGGGLLGVRTLyrf 328
Cdd:cd01102     2 VFHLESqngRYKLTFAEAALACKARGAHLATPGQLEAAWQDGFDVCTAGWLADGSVRYPIVTSRPNCGGRNPGVRSY--- 78

                          90
                  ....*....|....*...
gi 255918077  329 enqtGFPPPDSRFDAYCF 346
Cdd:cd01102    79 ----GNPAPSGRYDAYCF 92

Link_domain_HAPLN_module_2; this link domain is found in the second 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255918077  252 VFHLTVPSKFTFEEAAKECENQDARLATVGELQAAWR-NGFDQCDYGWLSDASVRHPVTVARAQCGGGLLGVRTLyrfen 330
Cdd:cd03519     2 VFYLLHPGKLTFSEAVAACQRDGAQIAKVGQLFAAWKfHGLDRCDAGWLADGSVRYPISRPRPRCGPLEPGVRSF----- 76

                          90
                  ....*....|....*..
gi 255918077  331 qtGFPPPDSR-FDAYCF 346
Cdd:cd03519    77 --GFPDKKHKlYGVYCY 91

Lectin C-type domain; This family includes both long and short form C-type

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255918077  2200 RRTWDAAERECRLQGAHLTSILSHEEQMFVNRVGHDYQ---WIGLNDKMFEHDFRWTDGSTLQYENWRPNQPDSffSAGE 2276
Cdd:pfam00059    1 SKTWDEAREACRKLGGHLVSINSAEELDFLSSTLKKSNkyfWIGLTDRKNEGTWKWVDGSPVNYTNWAPEPNNN--GENE 78

                           90       100
                   ....*....|....*....|....*...
gi 255918077  2277 DCVVIIWhENGQWNDVPCNYHLTYTCKK 2304
Cdd:pfam00059   79 DCVELSS-SSGKWNDENCNSKNPFVCEK 105

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 255918077   31 PVRGSLSGKVSLPCHFSTMPTLPPSYNTSEFL--RIKWSKIEVDKngkdlkETTVLVAQNGNIKIGQDYKGRVSVPTHPE 108
Cdd:cd05900     6 PLRVVLGSSLLIPCYFQDPIAKDPGAPTVAPLspRIKWSFISKEK------ESVLLVATEGKVRVNTEYLDRVSLPNYPA 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 255918077  109 AVGDASLTVVKLLASDAGLYRCDVMYGIEDTQDTVSLTVDGVVF 152
Cdd:cd05900    80 IPSDATLEITELRSNDSGTYRCEVMHGIEDNYDTVEVQVKGIVF 123

This is the extracellular link domain of the type found in human TSG-6. The link domain is a hyaluronan (HA)-binding domain. TSG-6 is the protein product of tumor necrosis factor-stimulated gene-6. TSG-6 is up-regulated in inflammatory lesions and in the ovary during ovulation. It has a strong anti-inflammatory and chondroprotective effect in models of acute inflammation and autoimmune arthritis and plays an essential role in female fertility. Also included in this group are the stabilins: stabilin-1 (FEEL-1, CLEVER-1) and stabilin-2 (FEEL-2). Stabilin-2 functions as the major liver and lymph node-scavenging receptor for HA and related glycosaminoglycans. Stabilin-2 is a scavenger receptor with a broad range of ligands including advanced glycation end (AGE) products, acetylated low density lipoprotein and procollagen peptides. In contrast, stabilin-1 does not bind HA, but binds acetylated low density lipoprotein and AGEs with lower affinity. As AGEs accumulate in vascular tissues during aging and diabetes, these receptors may be implicated in the pathologies of these states. Both stabilins are present in the early endocytic pathway in hepatic sinusoidal epithelium associating with clathrin/AP-2. Stabilin-1 is expressed in macrophages. Stabilin-2 is absent from the latter. In macrophages: stabilin-1 is involved in trafficking between early/sorting endosomes and the trans-Golgi network. Stabilin-1 has also been implicated in angiogenesis and possibly leucocyte trafficking. Both stabilins bind gram-positive and gram-negative bacteria. TSG-6 and stabilins contain a single link module which supports high affinity binding to HA.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255918077  151 VFHYRAATSRYTLNFEAAQKACLDVGAVIATPEQLFAAYEDGFEQCDAGWLADQTVRYPIRAPRVGCyGDkmGKAGVRTY 230
Cdd:cd03515     2 VFHLRSRSGKYKLTYTEAKAACEAEGAHLATYSQLSAAQQLGFHLCAAGWLAKGRVGYPIVFPSANC-GF--GHVGIVDY 78

                          90
                  ....*....|....*
gi 255918077  231 GFR-SPQETYDVYCY 244
Cdd:cd03515    79 GPRlNLSERWDAYCY 93

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 255918077 2194 YKYFAHRRTWDAAERECRLQGAHLTSILSHEEQMFVN----RVGHDYQWIGLNDKMFEhdFRW--TDGSTLQYENWRPNQ 2267
Cdd:cd03592     3 YHYSTEKMTFNEAVKYCKSRGTDLVAIQNAEENALLNgfalKYNLGYYWIDGNDINNE--GTWvdTDKKELEYKNWAPGE 80

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 255918077 2268 PDSffSAGEDCVVIIWHENGQWNDVPCNYHLTYTC 2302
Cdd:cd03592    81 PNN--GRNENCLEIYIKDNGKWNDEPCSKKKSAIC 113

C-type lectin-like domain (CTLD) of the type found in human collectins including lung surfactant proteins A and D, mannose- or mannan binding lectin (MBL), and CL-L1 (collectin liver 1); CLECT_collectin_like: C-type lectin-like domain (CTLD) of the type found in human collectins including lung surfactant proteins A and D, mannose- or mannan binding lectin (MBL), and CL-L1 (collectin liver 1). CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. The CTLDs of these collectins bind carbohydrates on surfaces (e.g. pathogens, allergens, necrotic, or apoptotic cells) and mediate functions associated with killing and phagocytosis. MBPs recognize high mannose oligosaccharides in a calcium dependent manner, bind to a broad range of pathogens, and trigger cell killing by activating the complement pathway. MBP also acts directly as an opsonin. SP-A and SP-D in addition to functioning as host defense components, are components of pulmonary surfactant which play a role in surfactant homeostasis. Pulmonary surfactant is a phospholipid-protein complex which reduces the surface tension within the lungs. SP-A binds the major surfactant lipid: dipalmitoylphosphatidylcholine (DPPC). SP-D binds two minor components of surfactant that contain sugar moieties: glucosylceramide and phosphatidylinositol (PI). MBP and SP-A, -D monomers are homotrimers with an N-terminal collagen region and three CTLDs. Multiple homotrimeric units associate to form supramolecular complexes. MBL deficiency results in an increased susceptibility to a large number of different infections and to inflammatory disease, such as rheumatoid arthritis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255918077 2195 KYFA---HRRTWDAAERECRLQGAHLTSILSHEE----QMFVNRvGHDYQWIGLNDKMFEHDFRWTDGSTLQYENWRPNQ 2267
Cdd:cd03591     2 KIFVtngEEKNFDDAQKLCSEAGGTLAMPRNAAEnaaiASYVKK-GNTYAFIGITDLETEGQFVYLDGGPLTYTNWKPGE 80