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 223462233  26 WTVDHPQTLFAWEGACIRIPCKYKTPLpkARLDNILLFQNYEFDKATKKFTGTVLYNATKTEKDPeselylSKQGRVTFL 105
Cdd:cd20929    1 WVFEHPETLYAWEGACVWIPCTYRALD--GDLESFILFHNPEYNKATSKFDGTRLYESTKDGKVP------SEQKRVQFL 72

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 223462233 106 GNRIDNCTLKIHPIRANDSGNLGLRMTAGTERWMEPIHLNVS 147
Cdd:cd20929   73 GDKNKNCTLSIHPVHLNDSGQLGLRMESKTEKWMERIHLNVS 114

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 223462233 257 PKLEIKVNPTE--VEKNNSVTMTCRVNSSNPKLRTVavSWFKDGRPLEDQELEQeqqmskLILHSVTKDMRGKYRCQASN 334
Cdd:cd20937    1 PKLEIKVTPSDaiVREGDSVTMTCEVSSSNPEYTTV--SWLKDGTSLKKQNTFT------LNLREVTKDQSGKYCCQVSN 72

                         90
                 ....*....|....*.
gi 223462233 335 DIGPGESEEVELTVHY 350
Cdd:cd20937   73 DVGPGRSEEVFLQVQY 88

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223462233   626 HVMEGKKATLSCESDANPPiSQYTWFDSSGQDLHSSG----------QKLRLEPLEVQHTGSYRCKGTNGIGTGESpPST 695
Cdd:smart00410   5 TVKEGESVTLSCEASGSPP-PEVTWYKQGGKLLAESGrfsvsrsgstSTLTISNVTPEDSGTYTCAATNSSGSASS-GTT 82

                   ...
gi 223462233   696 LTV 698
Cdd:smart00410  83 LTV 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
                 ....*....|....*....|....*....|....*....|...
gi 223462233 440 PKAVTTVIQSFTPILEGDSVTLVCRYNSSNPDVTSYRWNPQGS 482
Cdd:cd20937    1 PKLEIKVTPSDAIVREGDSVTMTCEVSSSNPEYTTVSWLKDGT 43

First immunoglobulin domain of Cluster of Differentiation (CD) 22; member of the V-set of IgSF domains; The members here are composed of the first 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 V-set of IgSF domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223462233  26 WTVDHPQTLFAWEGACIRIPCKYKTPLpkARLDNILLFQNYEFDKATKKFTGTVLYNATKTEKDPeselylSKQGRVTFL 105
Cdd:cd20929    1 WVFEHPETLYAWEGACVWIPCTYRALD--GDLESFILFHNPEYNKATSKFDGTRLYESTKDGKVP------SEQKRVQFL 72

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 223462233 106 GNRIDNCTLKIHPIRANDSGNLGLRMTAGTERWMEPIHLNVS 147
Cdd:cd20929   73 GDKNKNCTLSIHPVHLNDSGQLGLRMESKTEKWMERIHLNVS 114

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 223462233 257 PKLEIKVNPTE--VEKNNSVTMTCRVNSSNPKLRTVavSWFKDGRPLEDQELEQeqqmskLILHSVTKDMRGKYRCQASN 334
Cdd:cd20937    1 PKLEIKVTPSDaiVREGDSVTMTCEVSSSNPEYTTV--SWLKDGTSLKKQNTFT------LNLREVTKDQSGKYCCQVSN 72

                         90
                 ....*....|....*.
gi 223462233 335 DIGPGESEEVELTVHY 350
Cdd:cd20937   73 DVGPGRSEEVFLQVQY 88

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 223462233  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 223462233   364 AEEGQSVELICESLASPSATnYTWYHNR-KPIPGD---------TQEKLRIPKVSPWHAGNYSCLAENrlGHGKIDQEAK 433
Cdd:smart00410   6 VKEGESVTLSCEASGSPPPE-VTWYKQGgKLLAESgrfsvsrsgSTSTLTISNVTPEDSGTYTCAATN--SSGSASSGTT 82

                   ...
gi 223462233   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 223462233   626 HVMEGKKATLSCESDANPPiSQYTWFDSSGQDLHSSG----------QKLRLEPLEVQHTGSYRCKGTNGIGTGESpPST 695
Cdd:smart00410   5 TVKEGESVTLSCEASGSPP-PEVTWYKQGGKLLAESGrfsvsrsgstSTLTISNVTPEDSGTYTCAATNSSGSASS-GTT 82

                   ...
gi 223462233   696 LTV 698
Cdd:smart00410  83 LTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 223462233  618 RVSISPGDH-VMEGKKATLSCESDANPPiSQYTWF---------DSSGQDLHSSGQKLRLEPLEVQHTGSYRCKGTN 684
Cdd:pfam13927   3 VITVSPSSVtVREGETVTLTCEATGSPP-PTITWYkngepissgSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 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 223462233 532 LKVSPASEI-RAGQRVLLQCDFAESNPAEVRFFWKKNGSLV--QEGRYLSFGSVSPEDSGNYNCMVNNSIGETLSQAWNL 608
Cdd:cd20937    5 IKVTPSDAIvREGDSVTMTCEVSSSNPEYTTVSWLKDGTSLkkQNTFTLNLREVTKDQSGKYCCQVSNDVGPGRSEEVFL 84

                 ....
gi 223462233 609 QVLY 612
Cdd:cd20937   85 QVQY 88

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223462233  153 PYIQMPSEIRESQS--VTLTCglnFSCFGY-DILLKWFLEDSEITSITSSVTSITSSvtssiKNVYTESKLTFQPKWTDH 229
Cdd:pfam08205   1 PTIEPPASLLEGEGpeVVATC---SSAGGKpAPRITWYLDGKPLEAAETSSEQDPES-----GLVTVTSELKLVPSRSDH 72

                          90
                  ....*....|
gi 223462233  230 GKSVKCQVQH 239
Cdd:pfam08205  73 GQSLTCQVSY 82

First immunoglobulin domain of Cluster of Differentiation (CD) 22; member of the V-set of IgSF domains; The members here are composed of the first 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 V-set of IgSF domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223462233  26 WTVDHPQTLFAWEGACIRIPCKYKTPLpkARLDNILLFQNYEFDKATKKFTGTVLYNATKTEKDPeselylSKQGRVTFL 105
Cdd:cd20929    1 WVFEHPETLYAWEGACVWIPCTYRALD--GDLESFILFHNPEYNKATSKFDGTRLYESTKDGKVP------SEQKRVQFL 72

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 223462233 106 GNRIDNCTLKIHPIRANDSGNLGLRMTAGTERWMEPIHLNVS 147
Cdd:cd20929   73 GDKNKNCTLSIHPVHLNDSGQLGLRMESKTEKWMERIHLNVS 114

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 223462233 257 PKLEIKVNPTE--VEKNNSVTMTCRVNSSNPKLRTVavSWFKDGRPLEDQELEQeqqmskLILHSVTKDMRGKYRCQASN 334
Cdd:cd20937    1 PKLEIKVTPSDaiVREGDSVTMTCEVSSSNPEYTTV--SWLKDGTSLKKQNTFT------LNLREVTKDQSGKYCCQVSN 72

                         90
                 ....*....|....*.
gi 223462233 335 DIGPGESEEVELTVHY 350
Cdd:cd20937   73 DVGPGRSEEVFLQVQY 88

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 223462233  364 AEEGQSVELICESLASPSATnYTWYHNRKPIPGDTQEK---------LRIPKVSPWHAGNYSCLAEN 421
Cdd:pfam13927  13 VREGETVTLTCEATGSPPPT-ITWYKNGEPISSGSTRSrslsgsnstLTISNVTRSDAGTYTCVASN 78

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223462233  257 PKLEIKVNPTEVEKNNSVTMTCRVnSSNPKLRtvaVSWFKDG---RPLEDQELEQEQQMSKLILHSVTKDMRGKYRCQAS 333
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTV-TGTPDPE---VSWFKDGqplRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAT 76

                          90
                  ....*....|....*
gi 223462233  334 NDIGpGESEEVELTV 348
Cdd:pfam07679  77 NSAG-EAEASAELTV 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 223462233   265 PTEVEKNNSVTMTCRVNSSNPklrtVAVSWFKDGR----PLEDQELEQEQQMSKLILHSVTKDMRGKYRCQASNDIGPGE 340
Cdd:smart00410   3 SVTVKEGESVTLSCEASGSPP----PEVTWYKQGGkllaESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSAS 78

                   ....*...
gi 223462233   341 SeEVELTV 348
Cdd:smart00410  79 S-GTTLTV 85

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 223462233  360 YPSPAEEGQSVELICESLASPSAtNYTWYHNRKPIPgDTQEKLrIPKVSPWHAGNYSCLAENRLG 424
Cdd:pfam13895   7 SPTVVTEGEPVTLTCSAPGNPPP-SYTWYKDGSAIS-SSPNFF-TLSVSAEDSGTYTCVARNGRG 68

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223462233  258 KLEIKVNPTEVEKNNSVTMTCRVnSSNPklrTVAVSWFKDGRPLEDQeleqeqqmSKLILHSVTKDMRGKYRCQASNDIG 337
Cdd:pfam13895   1 KPVLTPSPTVVTEGEPVTLTCSA-PGNP---PPSYTWYKDGSAISSS--------PNFFTLSVSAEDSGTYTCVARNGRG 68

                          90
                  ....*....|.
gi 223462233  338 PGESEEVELTV 348
Cdd:pfam13895  69 GKVSNPVELTV 79

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 223462233 274 VTMTCRVnSSNPKLRtvaVSWFKDGRPLEDQELEQEQQM---SKLILHSVTKDMRGKYRCQASNDIGPGESEEV 344
Cdd:cd00096    1 VTLTCSA-SGNPPPT---ITWYKNGKPLPPSSRDSRRSElgnGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 223462233  531 VLKVSPASEI-RAGQRVLLQCDfAESNPaEVRFFWKKNGSLVQEGRY-----------LSFGSVSPEDSGNYNCMVNN 596
Cdd:pfam13927   3 VITVSPSSVTvREGETVTLTCE-ATGSP-PPTITWYKNGEPISSGSTrsrslsgsnstLTISNVTRSDAGTYTCVASN 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 223462233 532 LKVSPASEI-RAGQRVLLQCDFAESNPAEVRFFWKKNGSLV--QEGRYLSFGSVSPEDSGNYNCMVNNSIGETLSQAWNL 608
Cdd:cd20937    5 IKVTPSDAIvREGDSVTMTCEVSSSNPEYTTVSWLKDGTSLkkQNTFTLNLREVTKDQSGKYCCQVSNDVGPGRSEEVFL 84

                 ....
gi 223462233 609 QVLY 612
Cdd:cd20937   85 QVQY 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223462233  533 KVSPASEIRAGQRVLLQCdFAESNPAEVRFFWKKNGSLVQEGRY------------LSFGSVSPEDSGNYNCMVNNSIGE 600
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTC-SASTGSPGPDVTWSKEGGTLIESLKvkhdngrttqssLLISNVTKEDAGTYTCVVNNPGGS 79

                  .
gi 223462233  601 T 601
Cdd:pfam00047  80 A 80

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 223462233 532 LKVSPASEIRAGQRVLLQCDFAESNPAeVRFFWKKNGSLVQEGR-------------YLSFGSVSPEDSGNYNCMVNNSI 598
Cdd:cd05750    3 LKEMKSQTVQEGSKLVLKCEATSENPS-PRYRWFKDGKELNRKRpknikirnkkknsELQINKAKLEDSGEYTCVVENIL 81

                 .
gi 223462233 599 G 599
Cdd:cd05750   82 G 82

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 223462233  366 EGQSVELICESLASPSATNYTWYHNRKPIP----------GDTQEKLRIPKVSPWHAGNYSCLAENRLGHG 426
Cdd:pfam00047  10 EGDSATLTCSASTGSPGPDVTWSKEGGTLIeslkvkhdngRTTQSSLLISNVTKEDAGTYTCVVNNPGGSA 80

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223462233 526 PRDVKVLKvspaseiraGQRVLLQCDFAESNPaEVRFFWKKNGS---LVQEGRY-LSFGS-----VSPEDSGNYNCMVNN 596
Cdd:cd05724    4 PSDTQVAV---------GEMAVLECSPPRGHP-EPTVSWRKDGQplnLDNERVRiVDDGNlliaeARKSDEGTYKCVATN 73

                         90
                 ....*....|....
gi 223462233 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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 223462233 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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 223462233 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223462233 616 RLRVSISPGDHVM-EGKKATLSCE-SDANPPISQYTWFDSSGQDLHSSGQKLRLEPLEVQHTGSYRCKGTNGIGTGESPP 693
Cdd:cd20937    2 KLEIKVTPSDAIVrEGDSVTMTCEvSSSNPEYTTVSWLKDGTSLKKQNTFTLNLREVTKDQSGKYCCQVSNDVGPGRSEE 81

                 ....*..
gi 223462233 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223462233 262 KVNP--TEVEKNNSVTMTCRVNSSNPklrTVAVSWFKDGRP-LEDQELEQEQQMSKLILHSVTKDMRGKYRCQASNDIGP 338
Cdd:cd05724    1 RVEPsdTQVAVGEMAVLECSPPRGHP---EPTVSWRKDGQPlNLDNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGE 77

                         90
                 ....*....|
gi 223462233 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223462233 621 ISPGDH-VMEGKKATLSCESDANPPiSQYTWFDSSG------QDLhSSGQKLRLEP---LEVQHT-----GSYRCKGTNG 685
Cdd:cd20954    6 VEPVDAnVAAGQDVMLHCQADGFPT-PTVTWKKATGstpgeyKDL-LYDPNVRILPngtLVFGHVqkeneGHYLCEAKNG 83

                         90
                 ....*....|...
gi 223462233 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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 223462233 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223462233 525 APRDVKVLKvspASEIRAGQRVLLQCDFAESNPAEVRFFWK-------KNGSLVQEGRYLSF--GSVSPEDSGNYNCMVN 595
Cdd:cd20972    1 PPQFIQKLR---SQEVAEGSKVRLECRVTGNPTPVVRWFCEgkelqnsPDIQIHQEGDLHSLiiAEAFEEDTGRYSCLAT 77

                         90
                 ....*....|
gi 223462233 596 NSIGETLSQA 605
Cdd:cd20972   78 NSVGSDTTSA 87