Second immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains; The members here are composed of the second immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs). Interactions between IgG and FcgammaR are important to the initiation of cellular and humoral response. IgG binding to FcgammaR leads to a cascade of signals and ultimately to functions such as antibody-dependent-cellular-cytotoxicity (ADCC), endocytosis, phagocytosis, release of inflammatory mediators, etc. FcgammaR has two Ig-like domains. This group also contains FcepsilonRI which binds IgE with high affinity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024383755 152 LLILQVPSHAVFEGELLQMQCRGWKVGSLAAVRFYRDGADITKPYtSAMQLSIPQAKAHHSGRYHCSADMHSYlslkRRE 231
Cdd:cd05753     1 WLLLQAPSAVVFEGEPLTLRCHGWKDKKVHKVTYYKDGKALKFSY-ENSNFSIPQATLSDSGSYHCSGTVRIK----RRS 75

                  ....*...
gi 2024383755 232 SQGLYISI 239
Cdd:cd05753    76 SESVNITV 83

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 2024383755 249 SVASSAEPLEGSPLNLSCITQLSPYRPHtVLWylFYGNSTVLQGP--------VTSSEYQVPAVGLMDTGFYSCAVRTES 320
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSASTGSPGPD-VTW--SKEGGTLIESLkvkhdngrTTQSSLLISNVTKEDAGTYTCVVNNPG 77

                  ....*...
gi 2024383755 321 SNVQKWSP 328
Cdd:pfam00047  78 GSATLSTS 85

Second immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains; The members here are composed of the second immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs). Interactions between IgG and FcgammaR are important to the initiation of cellular and humoral response. IgG binding to FcgammaR leads to a cascade of signals and ultimately to functions such as antibody-dependent-cellular-cytotoxicity (ADCC), endocytosis, phagocytosis, release of inflammatory mediators, etc. FcgammaR has two Ig-like domains. This group also contains FcepsilonRI which binds IgE with high affinity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024383755 152 LLILQVPSHAVFEGELLQMQCRGWKVGSLAAVRFYRDGADITKPYtSAMQLSIPQAKAHHSGRYHCSADMHSYlslkRRE 231
Cdd:cd05753     1 WLLLQAPSAVVFEGEPLTLRCHGWKDKKVHKVTYYKDGKALKFSY-ENSNFSIPQATLSDSGSYHCSGTVRIK----RRS 75

                  ....*...
gi 2024383755 232 SQGLYISI 239
Cdd:cd05753    76 SESVNITV 83

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2024383755 343 SLEVWPQEGQVMEGHRLVLHCSvATGTGSISFSWHREGSAEVLGRDSRYE---------IPSTQQSDNGQYYCMASN 410
Cdd:pfam13927   3 VITVSPSSVTVREGETVTLTCE-ATGSPPPTITWYKNGEPISSGSTRSRSlsgsnstltISNVTRSDAGTYTCVASN 78

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. 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. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024383755 352 QVMEGHRLVLHCSvATGTGSISFSWHREGSA--------EVLGRDSRYEIPSTQQSDNGQYYCMASNGDSPARS--LKVQ 421
Cdd:cd20970    13 TAREGENATFMCR-AEGSPEPEISWTRNGNLiiefntryIVRENGTTLTIRNIRRSDMGIYLCIASNGVPGSVEkrITLQ 91

                  .
gi 2024383755 422 V 422
Cdd:cd20970    92 V 92

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024383755   75 PPWSVIFQGESVTLRCQ--GPPVHKQQptaWYHNG----------KLLEHTETNTYRIQNARYKQNGRYECQ--SPGSTS 140
Cdd:smart00410   1 PPSVTVKEGESVTLSCEasGSPPPEVT---WYKQGgkllaesgrfSVSRSGSTSTLTISNVTPEDSGTYTCAatNSSGSA 77

                   ....*...
gi 2024383755  141 SNSVTLSV 148
Cdd:smart00410  78 SSGTTLTV 85

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2024383755  258 EGSPLNLSCitQLSPYRPHTVLWY------LFYGNSTVLQGPVTSSEYQVPAVGLMDTGFYSCAVRTESSNVQK 325
Cdd:smart00410   8 EGESVTLSC--EASGSPPPEVTWYkqggklLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASS 79

Second immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains; The members here are composed of the second immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs). Interactions between IgG and FcgammaR are important to the initiation of cellular and humoral response. IgG binding to FcgammaR leads to a cascade of signals and ultimately to functions such as antibody-dependent-cellular-cytotoxicity (ADCC), endocytosis, phagocytosis, release of inflammatory mediators, etc. FcgammaR has two Ig-like domains. This group also contains FcepsilonRI which binds IgE with high affinity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024383755 152 LLILQVPSHAVFEGELLQMQCRGWKVGSLAAVRFYRDGADITKPYtSAMQLSIPQAKAHHSGRYHCSADMHSYlslkRRE 231
Cdd:cd05753     1 WLLLQAPSAVVFEGEPLTLRCHGWKDKKVHKVTYYKDGKALKFSY-ENSNFSIPQATLSDSGSYHCSGTVRIK----RRS 75

                  ....*...
gi 2024383755 232 SQGLYISI 239
Cdd:cd05753    76 SESVNITV 83

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2024383755 343 SLEVWPQEGQVMEGHRLVLHCSvATGTGSISFSWHREGSAEVLGRDSRYE---------IPSTQQSDNGQYYCMASN 410
Cdd:pfam13927   3 VITVSPSSVTVREGETVTLTCE-ATGSPPPTITWYKNGEPISSGSTRSRSlsgsnstltISNVTRSDAGTYTCVASN 78

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024383755  71 LTMDPPWSVIFQGESVTLRCQGPpvhkQQPTA---WYHNGKLLEhTETNTYrIQNARYKQNGRYECQ---SPGSTSSNSV 144
Cdd:pfam13895   2 PVLTPSPTVVTEGEPVTLTCSAP----GNPPPsytWYKDGSAIS-SSPNFF-TLSVSAEDSGTYTCVarnGRGGKVSNPV 75

                  ....
gi 2024383755 145 TLSV 148
Cdd:pfam13895  76 ELTV 79

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. 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. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024383755 352 QVMEGHRLVLHCSvATGTGSISFSWHREGSA--------EVLGRDSRYEIPSTQQSDNGQYYCMASNGDSPARS--LKVQ 421
Cdd:cd20970    13 TAREGENATFMCR-AEGSPEPEISWTRNGNLiiefntryIVRENGTTLTIRNIRRSDMGIYLCIASNGVPGSVEkrITLQ 91

                  .
gi 2024383755 422 V 422
Cdd:cd20970    92 V 92

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2024383755  71 LTMDPPWSVIFQGESVTLRCQ--GPPvhkqQPT-AWYHNGKLLEHTET---------NTYRIQNARYKQNGRYECQ 134
Cdd:pfam13927   4 ITVSPSSVTVREGETVTLTCEatGSP----PPTiTWYKNGEPISSGSTrsrslsgsnSTLTISNVTRSDAGTYTCV 75

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024383755   75 PPWSVIFQGESVTLRCQ--GPPVHKQQptaWYHNG----------KLLEHTETNTYRIQNARYKQNGRYECQ--SPGSTS 140
Cdd:smart00410   1 PPSVTVKEGESVTLSCEasGSPPPEVT---WYKQGgkllaesgrfSVSRSGSTSTLTISNVTPEDSGTYTCAatNSSGSA 77

                   ....*...
gi 2024383755  141 SNSVTLSV 148
Cdd:smart00410  78 SSGTTLTV 85

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. 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 2024383755 348 PQEGQVMEGHRLVLHCSvATGTGSISFSWHREGSAEVLGRDSRYE--------IPSTQQS-----DNGQYYCMASNGDSP 414
Cdd:cd05722     8 PSDIVAMRGGPVVLNCS-AESDPPPKIEWKKDGVLLNLVSDERRQqlpngsllITSVVHSkhnkpDEGFYQCVAQNESLG 86

                          90
                  ....*....|.
gi 2024383755 415 ---ARSLKVQV 422
Cdd:cd05722    87 sivSRTARVTV 97

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. 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. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024383755  72 TMDPPWSVIFQGESVTLRC--QGPPVHKqqpTAWYHNGKLLEHTE------TNTYRIQNARYKQNGRYEC 133
Cdd:cd20957     5 TIDPPVQTVDFGRTAVFNCsvTGNPIHT---VLWMKDGKPLGHSSrvqilsEDVLVIPSVKREDKGMYQC 71

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. 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. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2024383755 342 VSLEVWPQEGQVMEGHRLVLHCSVaTGTGSISFSWHREGSAevLGRDSRYE--------IPSTQQSDNGQYYCMASN 410
Cdd:cd20957     2 LSATIDPPVQTVDFGRTAVFNCSV-TGNPIHTVLWMKDGKP--LGHSSRVQilsedvlvIPSVKREDKGMYQCFVRN 75

Sixth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the sixth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. 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 2024383755 349 QEGQVMEGHRLVLHCSVATGTGSISFSWHREGSA--EVLG--------RDSRYEIPSTQQSDNGQYYCMASNgdsPARSL 418
Cdd:cd20959    10 GEGAAQVGMRAQLHCGVPGGDLPLNIRWTLDGQPisDDLGitvsrlgrRSSILSIDSLEASHAGNYTCHARN---SAGSA 86

                  .
gi 2024383755 419 K 419
Cdd:cd20959    87 S 87

Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024383755  71 LTMDPPWSVIFQGESVTLRCQGPPVHKQQPT-AWYHNGKLLEHTETNT-YR------------IQNARYKQNGRYEC--Q 134
Cdd:cd04970     5 ITLAPSNADITVGENATLQCHASHDPTLDLTfTWSFNGVPIDLEKIEGhYRrrygkdsngdleIVNAQLKHAGRYTCtaQ 84

                          90
                  ....*....|....
gi 2024383755 135 SPGSTSSNSVTLSV 148
Cdd:cd04970    85 TVVDSDSASATLVV 98

Immunoglobulin (Ig)-like domain found in Leukocyte Ig-like receptors, Natural killer inhibitory receptors (KIRs) and similar domains; member of Immunoglobulin Constant-2 set of IgSF domains; The members here are composed of the first and second immunoglobulin (Ig)-like domains found in Leukocyte Ig-like receptors (LILRs), Natural killer inhibitory receptors (KIRs, also known as also known as cluster of differentiation (CD) 158), and similar proteins. This group includes LILRB1 (also known as LIR-1), LILRA5 (also known as LIR9), an activating natural cytotoxicity receptor NKp46, the immune-type receptor glycoprotein VI (GPVI), and the IgA-specific receptor Fc-alphaRI (also known as cluster of differentiation (CD) 89). LILRs are a family of immunoreceptors expressed on expressed on T and B cells, on monocytes, dendritic cells, and subgroups of natural killer (NK) cells. The human LILR family contains nine proteins (LILRA1-3, and 5, and LILRB1-5). From functional assays, and as the cytoplasmic domains of various LILRs, for example LILRB1, LILRB2 (also known as LIR-2), and LILRB3 (also known as LIR-3) contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs), it is thought that LIR proteins are inhibitory receptors. Of the eight LIR family proteins, only LILRB1, and LILRB2, show detectable binding to class I MHC molecules; ligands for the other members have yet to be determined. The extracellular portions of the different LIR proteins contain different numbers of Ig-like domains for example, four in the case of LILRB1, and LILRB2, and two in the case of LILRB4 (also known as LIR-5). The activating natural cytotoxicity receptor NKp46 is expressed in natural killer cells, and is organized as an extracellular portion having two Ig-like extracellular domains, a transmembrane domain, and a small cytoplasmic portion. GPVI, which also contains two Ig-like domains, participates in the processes of collagen-mediated platelet activation and arterial thrombus formation. Fc-alphaRI is expressed on monocytes, eosinophils, neutrophils, and macrophages; it mediates IgA-induced immune effector responses such as phagocytosis, antibody-dependent cell-mediated cytotoxicity and respiratory burst. Killer cell immunoglobulin-like receptors (KIRs; also known as CD158 for human KIR) are transmembrane glycoproteins expressed by natural killer cells and subsets of T cells. KIRs are a family of highly polymorphic activating and inhibitory receptors that serve as key regulators of human NK cell function. The KIR proteins are classified by the number of extracellular immunoglobulin domains (2D or 3D) and by whether they have a long (L) or short (S) cytoplasmic domain. KIR proteins with the long cytoplasmic domain transduce inhibitory signals upon ligand binding via an immune tyrosine-based inhibitory motif (ITIM), while KIR proteins with the short cytoplasmic domain lack the ITIM motif and instead associate with the TYRO protein tyrosine kinase binding protein to transduce activating signals. The major ligands for KIR are MHC class I (HLA-A, -B or -C) molecules.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024383755  76 PWSVIFQGESVTLRCQGPPvhkqqPTAWYHNGKLLEHTETNTYR-----------IQNARYKQNGRYECQSPGST----S 140
Cdd:cd16843     8 PSSVVPLGENVTIRCQGPP-----EAVLFQLYKEGNSLSQGTVRekepqnkaefyIPHMDRNHAGRYRCRYRSGTlwseP 82

                  ....*...
gi 2024383755 141 SNSVTLSV 148
Cdd:cd16843    83 SDPLELVV 90

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024383755 249 SVASSAEPLEGSPLNLSCITQLSPYRPHtVLWylFYGNSTVLQGP--------VTSSEYQVPAVGLMDTGFYSCAVRTES 320
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSASTGSPGPD-VTW--SKEGGTLIESLkvkhdngrTTQSSLLISNVTKEDAGTYTCVVNNPG 77

                  ....*...
gi 2024383755 321 SNVQKWSP 328
Cdd:pfam00047  78 GSATLSTS 85

Third immunoglobulin domain in Cluster of Differentiation (CD) 22; member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain in Cluster of Differentiation (CD) 22 (also known as Siglec-2). CD22, a sialic-acid binding immunoglobulin type-lectin (Siglec) family member, is an inhibitory co-receptor of the B-cell receptor (BCR). The inhibitory function of CD22 and its restricted expression on B cells makes CD22 an attractive target against dysregulated B cells that cause autoimmune diseases and B-cell-derived cancers. CD22 plays a vital role in establishing a baseline level of B-cell inhibition, and thus is an important determinant of homeostasis in humoral immunity. Siglecs are primarily expressed on immune cells and recognize sialic acid-containing glycan ligands. Siglecs are organized as an extracellular module composed of Ig-like domains (an N-terminal variable set of Ig-like carbohydrate recognition domains, and 1 to 16 constant Ig-like domains), followed by transmembrane and short cytoplasmic domains. Human Siglecs are classified into two subgroups, one subgroup is comprised of sialoadhesin (Siglec-1), CD22 (Siglec-2), and MAG (Siglec-4, myelin-associated glycoprotein), the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11. 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. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

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gi 2024383755 342 VSLEVWPQEGQVMEGHRLVLHCSVATGTGS-ISFSWHREGSAEVLGRDSRYEIPSTQQSDNGQYYCMASNGDSPARSLKV 420
Cdd:cd20937     3 LEIKVTPSDAIVREGDSVTMTCEVSSSNPEyTTVSWLKDGTSLKKQNTFTLNLREVTKDQSGKYCCQVSNDVGPGRSEEV 82

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gi 2024383755 421 QVTV 424
Cdd:cd20937    83 FLQV 86