Immunoglobulin (Ig)-like domain of human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) domains 2, 4, and 6, and similar domains; The members here are composed of the second, fourth, and sixth immunoglobulin (Ig)-like domains in human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) protein subfamily. The CEA family is a group of anchored or secreted glycoproteins expressed by epithelial cells, leukocytes, endothelial cells, and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. This group represents the CEACAM subfamily. CEACAM1 has many important cellular functions; it is a cell adhesion molecule and a signaling molecule that regulates the growth of tumor cells, an angiogenic factor, and a receptor for bacterial and viral pathogens, including mouse hepatitis virus (MHV). In mice, four isoforms of CEACAM1 generated by alternative splicing have either two [D1, D4] or four [D1-D4] Ig-like domains on the cell surface.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317305 146 KPSISSNNSNPVEDKDAVAFTCEPETQDTTYLWWINNQSLPVSPRLQLSNGNRTLTLLSVTRNDTGPYECEIQNPVSANR 225
Cdd:cd05740    1 KPFISSNNSNPVEDKDAVTLTCEPETQNTSYLWWFNGQSLPVTPRLTLSNGNRTLTLLNVTREDAGAYQCEISNPVSANR 80

                 ....*...
gi 296317305 226 SDPVTLNV 233
Cdd:cd05740   81 SDPVTLDV 88

Immunoglobulin (Ig)-like domain of human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) domains 2, 4, and 6, and similar domains; The members here are composed of the second, fourth, and sixth immunoglobulin (Ig)-like domains in human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) protein subfamily. The CEA family is a group of anchored or secreted glycoproteins expressed by epithelial cells, leukocytes, endothelial cells, and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. This group represents the CEACAM subfamily. CEACAM1 has many important cellular functions; it is a cell adhesion molecule and a signaling molecule that regulates the growth of tumor cells, an angiogenic factor, and a receptor for bacterial and viral pathogens, including mouse hepatitis virus (MHV). In mice, four isoforms of CEACAM1 generated by alternative splicing have either two [D1, D4] or four [D1-D4] Ig-like domains on the cell surface.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317305 146 KPSISSNNSNPVEDKDAVAFTCEPETQDTTYLWWINNQSLPVSPRLQLSNGNRTLTLLSVTRNDTGPYECEIQNPVSANR 225
Cdd:cd05740    1 KPFISSNNSNPVEDKDAVTLTCEPETQNTSYLWWFNGQSLPVTPRLTLSNGNRTLTLLNVTREDAGAYQCEISNPVSANR 80

                 ....*...
gi 296317305 226 SDPVTLNV 233
Cdd:cd05740   81 SDPVTLDV 88

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 296317305   38 TESMPFNVAEGKEVLLLVHNLPQ---QLFGYSWYKGERVDGNRQ-IVGYAIGTQQATPGPANSGRETI-YPNASLLIQNV 112
Cdd:pfam07686   1 QTPREVTVALGGSVTLPCTYSSSmseASTSVYWYRQPPGKGPTFlIAYYSNGSEEGVKKGRFSGRGDPsNGDGSLTIQNL 80

                          90       100
                  ....*....|....*....|....*....
gi 296317305  113 TQNDTGFYTLQVIKSDLVNEEATGQFHVY 141
Cdd:pfam07686  81 TLSDSGTYTCAVIPSGEGVFGKGTRLTVL 109

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 296317305   244 PSDTYYRPGANLSLSCYAASNPPAQYSWL------------INGTFQQSTQELFIPNITVNNSGSYTCHANNS 304
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYkqggkllaesgrFSVSRSGSTSTLTISNVTPEDSGTYTCAATNS 73

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317305   157 VEDKDAVAFTCEPETQDTTYLWWINN--QSLPVSPRLQLSN--GNRTLTLLSVTRNDTGPYECEIQNPvSANRSDPVTLN 232
Cdd:smart00410   6 VKEGESVTLSCEASGSPPPEVTWYKQggKLLAESGRFSVSRsgSTSTLTISNVTPEDSGTYTCAATNS-SGSASSGTTLT 84

                   .
gi 296317305   233 V 233
Cdd:smart00410  85 V 85

Immunoglobulin (Ig)-like domain of human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) domains 2, 4, and 6, and similar domains; The members here are composed of the second, fourth, and sixth immunoglobulin (Ig)-like domains in human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) protein subfamily. The CEA family is a group of anchored or secreted glycoproteins expressed by epithelial cells, leukocytes, endothelial cells, and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. This group represents the CEACAM subfamily. CEACAM1 has many important cellular functions; it is a cell adhesion molecule and a signaling molecule that regulates the growth of tumor cells, an angiogenic factor, and a receptor for bacterial and viral pathogens, including mouse hepatitis virus (MHV). In mice, four isoforms of CEACAM1 generated by alternative splicing have either two [D1, D4] or four [D1-D4] Ig-like domains on the cell surface.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317305 146 KPSISSNNSNPVEDKDAVAFTCEPETQDTTYLWWINNQSLPVSPRLQLSNGNRTLTLLSVTRNDTGPYECEIQNPVSANR 225
Cdd:cd05740    1 KPFISSNNSNPVEDKDAVTLTCEPETQNTSYLWWFNGQSLPVTPRLTLSNGNRTLTLLNVTREDAGAYQCEISNPVSANR 80

                 ....*...
gi 296317305 226 SDPVTLNV 233
Cdd:cd05740   81 SDPVTLDV 88

Fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains; member of the C2-set IgSF domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains. The CEA family is a group of anchored or secreted glycoproteins, expressed by epithelial cells, leukocytes, endothelial cells and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), also known as CD66e (Cluster of Differentiation 66e), is a cell surface glycoprotein that plays a role in cell adhesion, intracellular signaling and tumor progression. Diseases associated with CEACAM5 include lung cancer and rectum cancer. 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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 296317305 243 SPSDTYYRPGANLSLSCYAASNPPAQYSWLINGTFQQSTQELFIPNITVNNSGSYTCHANNSVTGCNRTTVKTIIV 318
Cdd:cd20948    1 SPSDTYYLSGENLNLSCHAASNPPAQYSWTINGTFQTSSQELFLPAITENNEGTYTCSAHNSLTGKNISLVLSVTV 76

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 296317305  240 PTISPSDTYYRPGANLSLSCYAASNPPAQYSWLINGTFQQSTQELFIPNITVNNSGSYTCHANNSVTGCNRTTVkTIIV 318
Cdd:pfam13895   2 PVLTPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAISSSPNFFTLSVSAEDSGTYTCVARNGRGGKVSNPV-ELTV 79

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 296317305   244 PSDTYYRPGANLSLSCYAASNPPAQYSWL------------INGTFQQSTQELFIPNITVNNSGSYTCHANNS 304
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYkqggkllaesgrFSVSRSGSTSTLTISNVTPEDSGTYTCAATNS 73

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 296317305  146 KPSISSNNSNP-VEDKDAVAFTCEPETQDTTYLWWINNQSLPVSPRLQ---LSNGNRTLTLLSVTRNDTGPYECEIQN 219
Cdd:pfam13927   1 KPVITVSPSSVtVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRsrsLSGSNSTLTISNVTRSDAGTYTCVASN 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 296317305 243 SPSDTYYRPGANLSLSCYAASNPPAQYSWLING----------TFQQSTQELFIPNITVNNSGSYTCHANNSVTG 307
Cdd:cd20970    8 PSFTVTAREGENATFMCRAEGSPEPEISWTRNGnliiefntryIVRENGTTLTIRNIRRSDMGIYLCIASNGVPG 82

Fourth 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 fourth 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 296317305 250 RPGANLSLSCYAASNPPAQYSWLINGT-------FQQS---TQE------LFIPNITVNNSGSYTCHANNSV 305
Cdd:cd20956   14 QPGPSVSLKCVASGNPLPQITWTLDGFpipesprFRVGdyvTSDgdvvsyVNISSVRVEDGGEYTCTATNDV 85

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317305 163 VAFTCEPE-TQDTTYLWWINNQSLPVSPRL--QLSNGNRTLTLLSVTRNDTGPYECEIQNPVSANRSDPV 229
Cdd:cd00096    1 VTLTCSASgNPPPTITWYKNGKPLPPSSRDsrRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

First immunoglobulin (Ig) domain of contactin-2; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module by contacts between IG domains 1 and 4, and domains 2 and 3. 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-2 is also expressed in retinal amacrine cells in the developing chick retina, corresponding to the period of formation and maturation of AC processes. This group belongs to the I-set of IgSF domains.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 296317305 244 PSDTYYRPGA---NLSLSCYAASNPPAQYSWLINGT---------FQQSTQELFIPN-ITVNNSGSYTCHANNSV 305
Cdd:cd05850    9 PSSTLFPEGSaeeKVTLACRARASPPATYRWKMNGTelkmepdsrYRLVAGNLVISNpVKAKDAGSYQCLASNRR 83

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 296317305  157 VEDKDAVAFTCEPETQD--TTYLWWINNQSLPVSPRLQLSNGNRT---LTLLSVTRNDTGPYECEIQNPVS 222
Cdd:pfam00047   8 VLEGDSATLTCSASTGSpgPDVTWSKEGGTLIESLKVKHDNGRTTqssLLISNVTKEDAGTYTCVVNNPGG 78

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 296317305  161 DAVAFTC----EPETQDTtylWWINNQSLPVSPRLQLSN--GNRTLTLLSVTRNDTGPYECEIQNPVSANRSDpVTLNV 233
Cdd:pfam07679  16 ESARFTCtvtgTPDPEVS---WFKDGQPLRSSDRFKVTYegGTYTLTISNVQPDDSGKYTCVATNSAGEAEAS-AELTV 90

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 296317305 242 ISPSDTYYRPGANLSLSCYAASNPP--AQYSWLINGTF--QQSTQELFIPNITVNNSGSYTCHANNSV 305
Cdd:cd20937    7 VTPSDAIVREGDSVTMTCEVSSSNPeyTTVSWLKDGTSlkKQNTFTLNLREVTKDQSGKYCCQVSNDV 74

IL-1 receptor-like protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317305 106 SLLIQNVTQNDTGFYTLQvIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFtcEPETQDTTYLWWINNQSL 185
Cdd:PHA02826  99 NLWIGNVINIDEGIYICT-ISSGNICEESTIRLTFDSGTINYQFNSGKDSKLHCYGTDGI--SSTFKDYTLTWYKNGNIV 175

                         90       100       110
                 ....*....|....*....|....*....|..
gi 296317305 186 PVSPRLQLSNGNRTLTLLSVTRNDTGPYECEI 217
Cdd:PHA02826 176 LYTDRIQLRNNNSTLVIKSATHDDSGIYTCNL 207

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first 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. This group belongs to the I-set of IgSF domains.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 296317305 244 PSDTYYRPGA---NLSLSCYAASNPPAQYSWLINGT----FQQSTQELFIPNITVNN------SGSYTCHANNSV 305
Cdd:cd04967    8 PDDTIFPEDSdekKVALNCRARANPVPSYRWLMNGTeidlESDYRYSLVDGTLVISNpskakdAGHYQCLATNTV 82

Second 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 second immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. 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 296317305 237 PDTPTISPSDTYYRPGA-NLSLSCYAASNPPAQYSW--LINGT-----------FQQSTQELFIPNITVNNSGSYTCHAN 302
Cdd:cd20953    2 PKIPGLSKSQPLTVSSAsSIALLCPAQGYPAPSFRWykFIEGTtrkqavvlndrVKQVSGTLIIKDAVVEDSGKYLCVVN 81

                         90
                 ....*....|....
gi 296317305 303 NSVTGCNRTTVKTI 316
Cdd:cd20953   82 NSVGGESVETVLTV 95

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317305 145 PKPSISSNNSNP-VEDKDAVAFTCEPETQD---TTYLWWINNQSLPVSPRLqlsngnrTLTLLSVTRNDTGPYECEIQNP 220
Cdd:cd20937    1 PKLEIKVTPSDAiVREGDSVTMTCEVSSSNpeyTTVSWLKDGTSLKKQNTF-------TLNLREVTKDQSGKYCCQVSND 73

                         90
                 ....*....|....*
gi 296317305 221 VSANRSDPVTLNVTY 235
Cdd:cd20937   74 VGPGRSEEVFLQVQY 88

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 296317305  242 ISPSDTYYRPGANLSLSC-YAASNPPAQYSWLINGTF------------QQSTQELFIPNITVNNSGSYTCHANNS 304
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCsASTGSPGPDVTWSKEGGTlieslkvkhdngRTTQSSLLISNVTKEDAGTYTCVVNNP 76

Sixth immunoglobulin (Ig) domain of contactin-2; The members here are composed of the sixth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module by contacts between IG domains 1 and 4, and domains 2 and 3. 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-2 is also expressed in retinal amacrine cells (AC) in the developing chick retina, corresponding to the period of formation and maturation of AC processes.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317305 241 TISPSDTYYRPGANLSLSCYAASNPPAQ--YSWLING---------------TFQQSTQELFIPNITVNNSGSYTCHANN 303
Cdd:cd05854    6 TLAPSSADINQGENLTLQCHASHDPTMDltFTWSLDDfpidldkpnghyrrmEVKETIGDLVIVNAQLSHAGTYTCTAQT 85

                 ..
gi 296317305 304 SV 305
Cdd:cd05854   86 VV 87

Immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan, also known as HSPG2, and similar proteins. Perlecan consists of five domains: domain I has three putative heparan sulfate attachment sites, domain II has four LDL receptor-like repeats, and one Ig-like repeat, domain III resembles the short arm of laminin chains, domain IV has multiple Ig-like repeats (21 repeats in human perlecan), and domain V resembles the globular G domain of the laminin A chain and internal repeats of EGF. Perlecan may participate in a variety of biological functions including cell binding, LDL-metabolism, basement membrane assembly and selective permeability, calcium binding, and growth- and neurite-promoting activities.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317305 163 VAFTCEPETQDTTYL-WWINNQSLPVSPRLQL--SNGNRTLTLLSVTRNDTGPYECEIQN 219
Cdd:cd05743    4 VEFTCVATGVPTPIInWRLNWGHVPDSARVSItsEGGYGTLTIRDVKESDQGAYTCEAIN 63

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.

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                 ....*....|....*....|....*....|....*....|....*..
gi 296317305 175 TYLWWINNQSLPVSPRLQLSNGNRtLTLLSVTRNDTGPYECEIQNPV 221
Cdd:cd20957   32 TVLWMKDGKPLGHSSRVQILSEDV-LVIPSVKREDKGMYQCFVRNDG 77

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

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317305  220 PVSANRSDPVTLNVTYGPDTPTISPSDTYYR--PGANLSLSCYAASN------PPAQYSWliNGTFQQSTQELFIPNITV 291
Cdd:pfam07686   5 EVTVALGGSVTLPCTYSSSMSEASTSVYWYRqpPGKGPTFLIAYYSNgseegvKKGRFSG--RGDPSNGDGSLTIQNLTL 82

                          90
                  ....*....|...
gi 296317305  292 NNSGSYTCHANNS 304
Cdd:pfam07686  83 SDSGTYTCAVIPS 95

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 296317305 251 PGAN-LSLSCYAASNPPAQYSWLING------------TFQQSTQELFIPNITVNNSGSYTCHANNSVTGCNRT 311
Cdd:cd05857   17 PAANtVKFRCPAAGNPTPTMRWLKNGkefkqehriggyKVRNQHWSLIMESVVPSDKGNYTCVVENEYGSINHT 90

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317305 146 KPSISSNNSNPVEDKDAVAFTCEPETQDTTYLWWINNQSLPVSPRLQLSNGNRT-LTLLSVTRNDTGPYECEIQNPVSAN 224
Cdd:cd16843    1 KPFLSAEPSSVVPLGENVTIRCQGPPEAVLFQLYKEGNSLSQGTVREKEPQNKAeFYIPHMDRNHAGRYRCRYRSGTLWS 80

                         90
                 ....*....|
gi 296317305 225 R-SDPVTLNV 233
Cdd:cd16843   81 EpSDPLELVV 90