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 2203400233 151 FQPYIQMPSEIRESQSVTLTCGLNFSCFGYDILLKWFLEDSEitsitsSVTSITSSVTSSIKNVYTESKLTFQPKWTDHG 230
Cdd:cd20938     1 FQPHIQLPPEIQESQEVTLTCLLNFSCYGYPIQLQWLLEGSP------MRQAAVTSTSLTIKSVFTRSELKFQPKWSHHG 74

                          90       100
                  ....*....|....*....|....
gi 2203400233 231 KSVKCQVQHSS-KVLSERTVRLDV 253
Cdd:cd20938    75 KIVTCQLQDADgKVLSEDTVQLNV 98

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2203400233 364 AEEGQSVELICESLASPSATnYTWYHNRKPIPGDTQEK---------LRIPKVSPWHAGNYSCLAEN 421
Cdd:pfam13927  13 VREGETVTLTCEATGSPPPT-ITWYKNGEPISSGSTRSrslsgsnstLTISNVTRSDAGTYTCVASN 78

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2203400233  539 EIRAGQRVLLQCDFAESNPAEVRFFWKKNGSLVQEGRY----------LSFGSVSPEDSGNYNCMVNNSIGETLSQAwNL 608
Cdd:smart00410   5 TVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFsvsrsgststLTISNVTPEDSGTYTCAATNSSGSASSGT-TL 83

                   ..
gi 2203400233  609 QV 610
Cdd:smart00410  84 TV 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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2203400233 151 FQPYIQMPSEIRESQSVTLTCGLNFSCFGYDILLKWFLEDSEitsitsSVTSITSSVTSSIKNVYTESKLTFQPKWTDHG 230
Cdd:cd20938     1 FQPHIQLPPEIQESQEVTLTCLLNFSCYGYPIQLQWLLEGSP------MRQAAVTSTSLTIKSVFTRSELKFQPKWSHHG 74

                          90       100
                  ....*....|....*....|....
gi 2203400233 231 KSVKCQVQHSS-KVLSERTVRLDV 253
Cdd:cd20938    75 KIVTCQLQDADgKVLSEDTVQLNV 98

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2203400233 257 PKLEIKVNPTEVEKNNSVTMTCRVNSSNPklrtVAVSWFKDGRPLEDQELEQEQQM---SKLILHSVTKDMRGKYRCQAS 333
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPP----PTITWYKNGEPISSGSTRSRSLSgsnSTLTISNVTRSDAGTYTCVAS 77

                  .
gi 2203400233 334 N 334
Cdd:pfam13927  78 N 78

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 2203400233 370 VELICESLASPSATnYTWYHNRKPIPGDTQEK---------LRIPKVSPWHAGNYSCLAENRLG 424
Cdd:cd00096     1 VTLTCSASGNPPPT-ITWYKNGKPLPPSSRDSrrselgngtLTISNVTLEDSGTYTCVASNSAG 63

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2203400233  265 PTEVEKNNSVTMTCRVNSSNPklrtVAVSWFKDGR----PLEDQELEQEQQMSKLILHSVTKDMRGKYRCQASNDIGPGE 340
Cdd:smart00410   3 SVTVKEGESVTLSCEASGSPP----PEVTWYKQGGkllaESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSAS 78

                   ....*...
gi 2203400233  341 SeEVELTV 348
Cdd:smart00410  79 S-GTTLTV 85

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2203400233  539 EIRAGQRVLLQCDFAESNPAEVRFFWKKNGSLVQEGRY----------LSFGSVSPEDSGNYNCMVNNSIGETLSQAwNL 608
Cdd:smart00410   5 TVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFsvsrsgststLTISNVTPEDSGTYTCAATNSSGSASSGT-TL 83

                   ..
gi 2203400233  609 QV 610
Cdd:smart00410  84 TV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2203400233 531 VLKVSPASEI-RAGQRVLLQCDfAESNPaEVRFFWKKNGSLVQEGRY-----------LSFGSVSPEDSGNYNCMVNN 596
Cdd:pfam13927   3 VITVSPSSVTvREGETVTLTCE-ATGSP-PPTITWYKNGEPISSGSTrsrslsgsnstLTISNVTRSDAGTYTCVASN 78

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 2203400233 633 ATLSCESDANPPIsQYTWF---------DSSGQDLHSSGQKLRLEPLEVQHTGSYRCKGTNGIGTGES 691
Cdd:cd00096     1 VTLTCSASGNPPP-TITWYkngkplppsSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSAS 67

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
                  ....*....|....*....|....*....|....*....|...
gi 2203400233 440 PKAVTTVIQSFTPILEGDSVTLVCRYNSSNPDVTSYRWNPQGS 482
Cdd:cd20937     1 PKLEIKVTPSDAIVREGDSVTMTCEVSSSNPEYTTVSWLKDGT 43

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2203400233 151 FQPYIQMPSEIRESQSVTLTCGLNFSCFGYDILLKWFLEDSEitsitsSVTSITSSVTSSIKNVYTESKLTFQPKWTDHG 230
Cdd:cd20938     1 FQPHIQLPPEIQESQEVTLTCLLNFSCYGYPIQLQWLLEGSP------MRQAAVTSTSLTIKSVFTRSELKFQPKWSHHG 74

                          90       100
                  ....*....|....*....|....
gi 2203400233 231 KSVKCQVQHSS-KVLSERTVRLDV 253
Cdd:cd20938    75 KIVTCQLQDADgKVLSEDTVQLNV 98

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2203400233 257 PKLEIKVNPTEVEKNNSVTMTCRVNSSNPklrtVAVSWFKDGRPLEDQELEQEQQM---SKLILHSVTKDMRGKYRCQAS 333
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPP----PTITWYKNGEPISSGSTRSRSLSgsnSTLTISNVTRSDAGTYTCVAS 77

                  .
gi 2203400233 334 N 334
Cdd:pfam13927  78 N 78

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 2203400233 370 VELICESLASPSATnYTWYHNRKPIPGDTQEK---------LRIPKVSPWHAGNYSCLAENRLG 424
Cdd:cd00096     1 VTLTCSASGNPPPT-ITWYKNGKPLPPSSRDSrrselgngtLTISNVTLEDSGTYTCVASNSAG 63

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2203400233  364 AEEGQSVELICESLASPSATnYTWYHNR-KPIPGD---------TQEKLRIPKVSPWHAGNYSCLAENrlGHGKIDQEAK 433
Cdd:smart00410   6 VKEGESVTLSCEASGSPPPE-VTWYKQGgKLLAESgrfsvsrsgSTSTLTISNVTPEDSGTYTCAATN--SSGSASSGTT 82

                   ...
gi 2203400233  434 LDV 436
Cdd:smart00410  83 LTV 85

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2203400233  626 HVMEGKKATLSCESDANPPiSQYTWFDSSGQDLHSSG----------QKLRLEPLEVQHTGSYRCKGTNGIGTGESpPST 695
Cdd:smart00410   5 TVKEGESVTLSCEASGSPP-PEVTWYKQGGKLLAESGrfsvsrsgstSTLTISNVTPEDSGTYTCAATNSSGSASS-GTT 82

                   ...
gi 2203400233  696 LTV 698
Cdd:smart00410  83 LTV 85

Immunoglobulin (Ig)-like domain at the C-terminus of semaphorins; The members here are composed of the immunoglobulin (Ig)-like domain in semaphorins. Semaphorins are transmembrane protein that have important roles in a variety of tissues. Functionally, semaphorins were initially characterized for their importance in the development of the nervous system and in axonal guidance. Later they have been found to be important for the formation and functioning of the cardiovascular, endocrine, gastrointestinal, hepatic, immune, musculoskeletal, renal, reproductive, and respiratory systems. Semaphorins function through binding to their receptors and transmembrane semaphorins also serves as receptors themselves. Although molecular mechanism of semaphorins is poorly understood, the Ig-like domains may be involved in ligand binding or dimerization.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2203400233 366 EGQSVELICEslASPSATNYTWYHNRKPIPGDTQEKLR--------IPKVSPWHAGNYSCLAENrlgHGKIDQEAKLDVH 437
Cdd:cd04979    10 EGDTVILSCS--VKSNNAPVTWIHNGKKVPRYRSPRLVlktergllIRSAQEADAGVYECHSGE---RVLGSTLRSVTLH 84

                  ...
gi 2203400233 438 YAP 440
Cdd:cd04979    85 VLE 87

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2203400233  539 EIRAGQRVLLQCDFAESNPAEVRFFWKKNGSLVQEGRY----------LSFGSVSPEDSGNYNCMVNNSIGETLSQAwNL 608
Cdd:smart00410   5 TVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFsvsrsgststLTISNVTPEDSGTYTCAATNSSGSASSGT-TL 83

                   ..
gi 2203400233  609 QV 610
Cdd:smart00410  84 TV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2203400233 618 RVSISPGDH-VMEGKKATLSCESDANPPiSQYTWF---------DSSGQDLHSSGQKLRLEPLEVQHTGSYRCKGTN 684
Cdd:pfam13927   3 VITVSPSSVtVREGETVTLTCEATGSPP-PTITWYkngepissgSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. 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 this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus 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 2203400233 364 AEEGQSVELICESLASPsATNYTWYHNRKPIPGDTQE--------KLRIPKVSPWHAGNYSCLAENRLghGKIDQEAKLD 435
Cdd:cd20976    13 AVEGQDFVAQCSARGKP-VPRITWIRNAQPLQYAADRstceagvgELHIQDVLPEDHGTYTCLAKNAA--GQVSCSAWVT 89

                  .
gi 2203400233 436 V 436
Cdd:cd20976    90 V 90

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 2203400233 364 AEEGQSVELICESLASPSATnYTWYHNRKPIPGD------TQEKLRIPKVSPWHAGNYSCLAENRlgHGKIDQEAKLDV 436
Cdd:cd20978    13 VKGGQDVTLPCQVTGVPQPK-ITWLHNGKPLQGPmeratvEDGTLTIINVQPEDTGYYGCVATNE--IGDIYTETLLHV 88

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2203400233 626 HVMEGKKATLSCESDANPPISqYTWFdSSGQDLHSSGQKLRLEPlEVQHTGSYRCKGTNGIGTGESPPSTLTV 698
Cdd:pfam13895  10 VVTEGEPVTLTCSAPGNPPPS-YTWY-KDGSAISSSPNFFTLSV-SAEDSGTYTCVARNGRGGKVSNPVELTV 79

Second immunoglobulin domain of Cluster of Differentiation (CD) 33 and related Siglecs; member of the C2-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig) domain of Cluster of Differentiation (CD) 33 (also known as sialic-acid binding immunoglobulin type-lectin 3 (Siglec-3)) and related Siglecs. CD33, a Siglec family member, is a well-known immunotherapeutic target in acute myeloid leukemia (AML). It is an inhibitory sialoadhesin expressed in human leukocytes of the myeloid lineage and some lymphoid subsets, including natural killer (NK) cells. 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. CD33 (Siglec-3) is the smallest Siglec member. It preferentially binds to alpha2-6- and alpha2-3-sialylated glycans and strongly binds to sialylated ligands on leukemic cell lines. 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. This group includes CD33-related Siglecs which belong to the C2-set of IgSF domains. Unlike the C1-set, the C2-set structures do not have a D strand.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2203400233 153 PYIQMPSEIRESQSVTLTCGLNFSCFGYDILLKWfledseiTSITSSVTSITSSVTSSIKNVYTESKLTFQPKWTDHGKS 232
Cdd:cd20987     1 PNIHVPEELEAGQEVTLTCSVPDNCPALSPEFSW-------LGAALTPLPPVLGRLEEEGTTTHSSVLTFTPRPEDHGTN 73

                          90       100
                  ....*....|....*....|.
gi 2203400233 233 VKCQVQHSSKVLS-ERTVRLD 252
Cdd:cd20987    74 LTCQVKFPGATVTtERTIQLN 94

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2203400233 530 KVLKVSPASEIRAGQRVLLQCDFAESNPAEVRffWKKNGSLVQEGRY-----------LSFGSVSPEDSGNYNCMVNNSI 598
Cdd:pfam07679   2 KFTQKPKDVEVQEGESARFTCTVTGTPDPEVS--WFKDGQPLRSSDRfkvtyeggtytLTISNVQPDDSGKYTCVATNSA 79

                  ..
gi 2203400233 599 GE 600
Cdd:pfam07679  80 GE 81

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the 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 (Slit-1,Slit-2, Slit-3), 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 Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 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 Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2203400233 526 PRDVKVLKvspaseiraGQRVLLQCDFAESNPaEVRFFWKKNGS---LVQEGRY-LSFGS-----VSPEDSGNYNCMVNN 596
Cdd:cd05724     4 PSDTQVAV---------GEMAVLECSPPRGHP-EPTVSWRKDGQplnLDNERVRiVDDGNlliaeARKSDEGTYKCVATN 73

                          90
                  ....*....|....
gi 2203400233 597 SIGETLSQAWNLQV 610
Cdd:cd05724    74 MVGERESRAARLSV 87

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2203400233 633 ATLSCESDANPPIsQYTWF---------DSSGQDLHSSGQKLRLEPLEVQHTGSYRCKGTNGIGTGES 691
Cdd:cd00096     1 VTLTCSASGNPPP-TITWYkngkplppsSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSAS 67

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2203400233 534 VSPASEIRAGQRVLLQCdFAESNPAeVRFFWKKNGSLVQEGRYLSFGSVSPEDSGNYNCMVNNSIG 599
Cdd:cd20948     1 SPSDTYYLSGENLNLSC-HAASNPP-AQYSWTINGTFQTSSQELFLPAITENNEGTYTCSAHNSLT 64

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 2203400233 616 RLRVSISPGDHVM-EGKKATLSCE-SDANPPISQYTWFDSSGQDLHSSGQKLRLEPLEVQHTGSYRCKGTNGIGTGESPP 693
Cdd:cd20937     2 KLEIKVTPSDAIVrEGDSVTMTCEvSSSNPEYTTVSWLKDGTSLKKQNTFTLNLREVTKDQSGKYCCQVSNDVGPGRSEE 81

                  ....*..
gi 2203400233 694 STLTVYY 700
Cdd:cd20937    82 VFLQVQY 88

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the 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 (Slit-1,Slit-2, Slit-3), 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 Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 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 Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2203400233 262 KVNP--TEVEKNNSVTMTCRVNSSNPklrTVAVSWFKDGRP-LEDQELEQEQQMSKLILHSVTKDMRGKYRCQASNDIGP 338
Cdd:cd05724     1 RVEPsdTQVAVGEMAVLECSPPRGHP---EPTVSWRKDGQPlNLDNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGE 77

                          90
                  ....*....|
gi 2203400233 339 GESEEVELTV 348
Cdd:cd05724    78 RESRAARLSV 87

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2203400233 621 ISPGDH-VMEGKKATLSCESDANPPiSQYTWFDSSG------QDLhSSGQKLRLEP---LEVQHT-----GSYRCKGTNG 685
Cdd:cd20954     6 VEPVDAnVAAGQDVMLHCQADGFPT-PTVTWKKATGstpgeyKDL-LYDPNVRILPngtLVFGHVqkeneGHYLCEAKNG 83

                          90
                  ....*....|...
gi 2203400233 686 IGTGESPPSTLTV 698
Cdd:cd20954    84 IGSGLSKVIFLKV 96

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2203400233 631 KKATLSCESDANPPISqYTWFDSSGQ-DLHSS-------GQKLRLEPLEVQHTGSYRCKGTNGIGTGESPPSTLTVYY 700
Cdd:cd04967    20 KKVALNCRARANPVPS-YRWLMNGTEiDLESDyryslvdGTLVISNPSKAKDAGHYQCLATNTVGSVLSREATLQFGY 96

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2203400233 525 APRDVKVLKvspASEIRAGQRVLLQCDFAESNPAEVRFFWK-------KNGSLVQEGRYLSF--GSVSPEDSGNYNCMVN 595
Cdd:cd20972     1 PPQFIQKLR---SQEVAEGSKVRLECRVTGNPTPVVRWFCEgkelqnsPDIQIHQEGDLHSLiiAEAFEEDTGRYSCLAT 77