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
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 221043490   4 WLLEGVPMRQAAVTSTSLTIKSVFTRSELKFSPQWSHHGKIVTCQLQDADGKFLSNDTVQLNV 66
Cdd:cd20938   36 WLLEGSPMRQAAVTSTSLTIKSVFTRSELKFQPKWSHHGKIVTCQLQDADGKVLSEDTVQLNV 98

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 221043490  163 TVQILHSPAVEGSQVEFLCMSLANPLPTnYTWYHNGKEMQGRTEEKV---------HIPKILPWHAGTYSCVAEN 228
Cdd:pfam13927   5 TVSPSSVTVREGETVTLTCEATGSPPPT-ITWYKNGEPISSGSTRSRslsgsnstlTISNVTRSDAGTYTCVASN 78

Second immunoglobulin domain of Cluster of Differentiation (CD) 22; member of the Constant 1 (C1)-set of IgSF domains; The members here are composed of the second immunoglobulin domain of clusters 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 C1-set of IgSF domains.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 221043490   4 WLLEGVPMRQAAVTSTSLTIKSVFTRSELKFSPQWSHHGKIVTCQLQDADGKFLSNDTVQLNV 66
Cdd:cd20938   36 WLLEGSPMRQAAVTSTSLTIKSVFTRSELKFQPKWSHHGKIVTCQLQDADGKVLSEDTVQLNV 98

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221043490    78 PSDAIVREGDSVTMTCEVSSSNPEYttVSWLKDGTSL----------KKQNTFTLNLREVTKDQSGKYCCQVSNDVGPGR 147
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPE--VTWYKQGGKLlaesgrfsvsRSGSTSTLTISNVTPEDSGTYTCAATNSSGSAS 78

                   ....*...
gi 221043490   148 SeEVFLQV 155
Cdd:smart00410  79 S-GTTLTV 85

CD80-like C2-set immunoglobulin domain; These domains belong to the immunoglobulin superfamily.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 221043490    4 WLLEGVPMRQAAVTSTSLTIKSVFTR-SELKFSPQWSHHGKIVTCQLQDADGKF 56
Cdd:pfam08205  34 WYLDGKPLEAAETSSEQDPESGLVTVtSELKLVPSRSDHGQSLTCQVSYGALRG 87

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 221043490  425 RVSMSPGDQ-VMEGKSATLTCESDANPPVShYTWFDWNNQSLPYHSQK---------LRLEPVKVQHSGAYWCQGTN 491
Cdd:pfam13927   3 VITVSPSSVtVREGETVTLTCEATGSPPPT-ITWYKNGEPISSGSTRSrslsgsnstLTISNVTRSDAGTYTCVASN 78

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 221043490 327 LNVQYAPRDVRVRKikplseihsGNSVSLQCDFSSSHPKEVQFFWEKNGRLLGKES--QLNFDSISPEDAGSYSCWVNNS 404
Cdd:cd20937    3 LEIKVTPSDAIVRE---------GDSVTMTCEVSSSNPEYTTVSWLKDGTSLKKQNtfTLNLREVTKDQSGKYCCQVSND 73

                         90
                 ....*....|....*
gi 221043490 405 IGQTASKAWTLEVLY 419
Cdd:cd20937   74 VGPGRSEEVFLQVQY 88

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221043490  338 VRKIKPLsEIHSGNSVSLQCDFSSSHPKEVQffWEKNGRLL-----------GKESQLNFDSISPEDAGSYSCWVNNSIG 406
Cdd:pfam07679   4 TQKPKDV-EVQEGESARFTCTVTGTPDPEVS--WFKDGQPLrssdrfkvtyeGGTYTLTISNVQPDDSGKYTCVATNSAG 80

                          90
                  ....*....|.
gi 221043490  407 QTASKAwTLEV 417
Cdd:pfam07679  81 EAEASA-ELTV 90

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221043490   171 AVEGSQVEFLCMSLANPLPTnYTWYHNGKEM---QGRTEEKV-------HIPKILPWHAGTYSCVAENILGTGQRgpGAE 240
Cdd:smart00410   6 VKEGESVTLSCEASGSPPPE-VTWYKQGGKLlaeSGRFSVSRsgststlTISNVTPEDSGTYTCAATNSSGSASS--GTT 82

                   ...
gi 221043490   241 LDV 243
Cdd:smart00410  83 LTV 85

Second immunoglobulin domain of Cluster of Differentiation (CD) 22; member of the Constant 1 (C1)-set of IgSF domains; The members here are composed of the second immunoglobulin domain of clusters 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 C1-set of IgSF domains.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 221043490   4 WLLEGVPMRQAAVTSTSLTIKSVFTRSELKFSPQWSHHGKIVTCQLQDADGKFLSNDTVQLNV 66
Cdd:cd20938   36 WLLEGSPMRQAAVTSTSLTIKSVFTRSELKFQPKWSHHGKIVTCQLQDADGKVLSEDTVQLNV 98

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 221043490  78 PSDAIVREGDSVTMTCEVSSSnPEyTTVSWLKDGTSLKKQNT--------FTLNLREVTKDQSGKYCCQVSNDVGPGRSE 149
Cdd:cd20970    9 SFTVTAREGENATFMCRAEGS-PE-PEISWTRNGNLIIEFNTryivrengTTLTIRNIRRSDMGIYLCIASNGVPGSVEK 86

                 ....*.
gi 221043490 150 EVFLQV 155
Cdd:cd20970   87 RITLQV 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 221043490    78 PSDAIVREGDSVTMTCEVSSSNPEYttVSWLKDGTSL----------KKQNTFTLNLREVTKDQSGKYCCQVSNDVGPGR 147
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPE--VTWYKQGGKLlaesgrfsvsRSGSTSTLTISNVTPEDSGTYTCAATNSSGSAS 78

                   ....*...
gi 221043490   148 SeEVFLQV 155
Cdd:smart00410  79 S-GTTLTV 85

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 221043490   76 VTPSDAIVREGDSVTMTCEVSSSNPeYTTVSWLKDGTSL----------KKQNTFTLNLREVTKDQSGKYCCQVSNDVGP 145
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSASTGSP-GPDVTWSKEGGTLieslkvkhdnGRTTQSSLLISNVTKEDAGTYTCVVNNPGGS 79

                  ....
gi 221043490  146 GRSE 149
Cdd:pfam00047  80 ATLS 83

T-cell surface glycoprotein CD3 delta chain; This is an immunoglobulin-like domain. It is found on the T-cell surface glycoprotein CD3 delta chain. CD3delta and CD3epsilon complex together as part of the T-cell receptor complex.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 221043490   86 GDSVTMTCEVSSSNpeyttVSWLKDGTSLKKQNTFTLNLREVTKDQSGKYCCQVSNDVGPgrseevFLQVQY 157
Cdd:pfam16680   1 DGKVLLTCNSSSKS-----ITWLKDGKGIKSTNTKTLDLGKFSEDPRGLYQCQGEKKKSS------TLQVYY 61

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 221043490  89 VTMTCEVSSSNPeyTTVSWLKDGTSLK---------KQNTFTLNLREVTKDQSGKYCCQVSNDVGPGRSEEV 151
Cdd:cd00096    1 VTLTCSASGNPP--PTITWYKNGKPLPpssrdsrrsELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 221043490  163 TVQILHSPAVEGSQVEFLCMSLANPLPTnYTWYHNGKEMQGRTEEKV---------HIPKILPWHAGTYSCVAEN 228
Cdd:pfam13927   5 TVSPSSVTVREGETVTLTCEATGSPPPT-ITWYKNGEPISSGSTRSRslsgsnstlTISNVTRSDAGTYTCVASN 78

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 221043490 423 RLRVSMSPGDQVM-EGKSATLTCE-SDANPPVSHYTWFDWNNQSLPYHSQKLRLEPVKVQHSGAYWCQGTNGVGKGRSPL 500
Cdd:cd20937    2 KLEIKVTPSDAIVrEGDSVTMTCEvSSSNPEYTTVSWLKDGTSLKKQNTFTLNLREVTKDQSGKYCCQVSNDVGPGRSEE 81

                 ....*..
gi 221043490 501 STLTVYY 507
Cdd:cd20937   82 VFLQVQY 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 221043490  83 VREGDSVTMTCEVSSSNpeyTTVSWLKDGTSLK-------KQNTFTLNLREVTKDQSGKYCCQVSNDVGPGRSEEVFLQV 155
Cdd:cd05740   12 VEDKDAVTLTCEPETQN---TSYLWWFNGQSLPvtprltlSNGNRTLTLLNVTREDAGAYQCEISNPVSANRSDPVTLDV 88

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. 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. The fourth Ig-like domain of hemolin 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 domains, members of the I-set have a discontinuous A strand but lack a C" strand. 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 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 221043490 171 AVEGSQVEFLCMSLANPLPTnYTWYHNGKEMQGRTEE-KVH-----IPKILPWHAGTYSCVAENILGTGQR 235
Cdd:cd20978   13 VKGGQDVTLPCQVTGVPQPK-ITWLHNGKPLQGPMERaTVEdgtltIINVQPEDTGYYGCVATNEIGDIYT 82

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 221043490 177 VEFLCMSLANPLPTnYTWYHNGKEMQGRTEEKV---------HIPKILPWHAGTYSCVAENILGT 232
Cdd:cd00096    1 VTLTCSASGNPPPT-ITWYKNGKPLPPSSRDSRrselgngtlTISNVTLEDSGTYTCVASNSAGG 64

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 221043490  169 SPAVEGSQVEFLCMSLANPLPtNYTWYHNGKEMQGRTeeKVHIPKILPWHAGTYSCVAENILGTGQRGP 237
Cdd:pfam13895   9 TVVTEGEPVTLTCSAPGNPPP-SYTWYKDGSAISSSP--NFFTLSVSAEDSGTYTCVARNGRGGKVSNP 74

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 221043490  340 KIKPLSEIHSGNSVSLQCdFSSSHPKEVQFFWEKNG-RLLGKE-----------SQLNFDSISPEDAGSYSCWVNNSIGQ 407
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTC-SASTGSPGPDVTWSKEGgTLIESLkvkhdngrttqSSLLISNVTKEDAGTYTCVVNNPGGS 79

                  ....*
gi 221043490  408 TASKA 412
Cdd:pfam00047  80 ATLST 84

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; 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. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 221043490  86 GDSVTMTCeVSSSNPEyTTVSWLKDGTSLKKQNT----------FTLNLREVTKDQSGKYCCQVSNDVG 144
Cdd:cd05729   19 ANKVRLEC-GAGGNPM-PNITWLKDGKEFKKEHRiggtkveekgWSLIIERAIPRDKGKYTCIVENEYG 85

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. 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 titin Z1z2 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 221043490 161 PSTVQILHSPAV-EGSQVEFLCMSLANPLPtNYTWYHNGKEMQGRTEEKVH---------IPKILPWHAGTYSCVAENIL 230
Cdd:cd20972    2 PQFIQKLRSQEVaEGSKVRLECRVTGNPTP-VVRWFCEGKELQNSPDIQIHqegdlhsliIAEAFEEDTGRYSCLATNSV 80

                 ..
gi 221043490 231 GT 232
Cdd:cd20972   81 GS 82

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); 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 like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221043490 333 PRDVRVRKI-KPLseihsGNSVSLQCdFSSSHPKEVqFFWEKNGRLL-------GKESQ--LNFDSISPEDAGSYSCWVN 402
Cdd:cd05856    6 PAKMRRRVIaRPV-----GSSVRLKC-VASGNPRPD-ITWLKDNKPLtppeigeNKKKKwtLSLKNLKPEDSGKYTCHVS 78

                 ....*
gi 221043490 403 NSIGQ 407
Cdd:cd05856   79 NRAGE 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 221043490 440 ATLTCESDANPPVShYTWFdWNNQSLP----------YHSQKLRLEPVKVQHSGAYWCQGTNGVGKGRS 498
Cdd:cd00096    1 VTLTCSASGNPPPT-ITWY-KNGKPLPpssrdsrrseLGNGTLTISNVTLEDSGTYTCVASNSAGGSAS 67

Seventh 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 seventh 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 221043490  75 KVTPSDAIVREGDSVTMTCEVSSSNPeyTTVSWLKD-GTS-------LKKQNTF-----TLNLREVTKDQSGKYCCQVSN 141
Cdd:cd20954    5 IVEPVDANVAAGQDVMLHCQADGFPT--PTVTWKKAtGSTpgeykdlLYDPNVRilpngTLVFGHVQKENEGHYLCEAKN 82

                         90
                 ....*....|....
gi 221043490 142 DVGPGRSEEVFLQV 155
Cdd:cd20954   83 GIGSGLSKVIFLKV 96

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 221043490 432 DQVMEGKSA-TLTCESDANppVSHYTWFdWNNQSLPYH--------SQKLRLEPVKVQHSGAYWCQGTNGVGKGRSPLST 502
Cdd:cd05740    9 SNPVEDKDAvTLTCEPETQ--NTSYLWW-FNGQSLPVTprltlsngNRTLTLLNVTREDAGAYQCEISNPVSANRSDPVT 85

                 ....
gi 221043490 503 LTVY 506
Cdd:cd05740   86 LDVI 89

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221043490 340 KIKPL--SEIHSGNSVSLQCDFSSSHPkEVQFFWEKNGRLLG-------------KESQLNFDSISPEDAGSYSCWVNNS 404
Cdd:cd05750    2 KLKEMksQTVQEGSKLVLKCEATSENP-SPRYRWFKDGKELNrkrpknikirnkkKNSELQINKAKLEDSGEYTCVVENI 80

                 ....*...
gi 221043490 405 IGQTASKA 412
Cdd:cd05750   81 LGKDTVTG 88

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221043490  345 SEIHSGNSVSLQCDFSSSHPKEVQffWEKNGRLL-----------GKESQLNFDSISPEDAGSYSCWVNN 403
Cdd:pfam13927  11 VTVREGETVTLTCEATGSPPPTIT--WYKNGEPIssgstrsrslsGSNSTLTISNVTRSDAGTYTCVASN 78

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221043490 161 PSTVQILHSPAVEGSQVEFLCMSLA-NPLPTnYTWYHNGKEM-----------QGRTEEKVHIPKILPWHAGTYSCVAEN 228
Cdd:cd05750    1 PKLKEMKSQTVQEGSKLVLKCEATSeNPSPR-YRWFKDGKELnrkrpknikirNKKKNSELQINKAKLEDSGEYTCVVEN 79

                 ...
gi 221043490 229 ILG 231
Cdd:cd05750   80 ILG 82

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221043490  78 PSDAIVREGDSVTMTCEvSSSNPEyTTVSWLKDGTSLKKQNTFTLNLREVTKDQS----------------GKYCCQVSN 141
Cdd:cd07693    7 PSDLIVSKGDPATLNCK-AEGRPT-PTIQWLKNGQPLETDKDDPRSHRIVLPSGSlfflrvvhgrkgrsdeGVYVCVAHN 84

                         90
                 ....*....|....
gi 221043490 142 DVGPGRSEEVFLQV 155
Cdd:cd07693   85 SLGEAVSRNASLEV 98

Immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1; The members here are composed of the immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. NRG-1 belongs to the neuregulin gene family which is comprised of four genes. This group represents NRG-1. NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, and heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. The NRG-1 protein binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. NRG-1 has multiple functions, for example, in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221043490 337 RVRKIKPlSEIHSGNSVSLQCDFSSSHPKeVQFFWEKNGRLLG--------------KESQLNFDSISPEDAGSYSCWVN 402
Cdd:cd05895    2 KLKEMKS-QEVAAGSKLVLRCETSSEYPS-LRFKWFKNGKEINrknkpenikiqkkkKKSELRINKASLADSGEYMCKVS 79

                         90
                 ....*....|
gi 221043490 403 NSIGQTASKA 412
Cdd:cd05895   80 SKLGNDSASA 89

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 221043490  72 LEIKVTPSDAIVREGDSVTMTCEVSSsNPEYTtVSWLKDGTSL----KKQNTF--TLNLREVTKDQSGKYCCQVSNDV 143
Cdd:cd20957    2 LSATIDPPVQTVDFGRTAVFNCSVTG-NPIHT-VLWMKDGKPLghssRVQILSedVLVIPSVKREDKGMYQCFVRNDG 77