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 297374828 141 FPPHIQLPPEIQESQEVTLTCLLNFSCYGYPIQLQWLLEGVPMRQAAVTSTSLTIKSVFTRSELKFSPQWSHHGKIVTCQ 220
Cdd:cd20938    1 FQPHIQLPPEIQESQEVTLTCLLNFSCYGYPIQLQWLLEGSPMRQAAVTSTSLTIKSVFTRSELKFQPKWSHHGKIVTCQ 80

                         90
                 ....*....|....*...
gi 297374828 221 LQDADGKFLSNDTVQLNV 238
Cdd:cd20938   81 LQDADGKVLSEDTVQLNV 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 297374828   606 VMEGKSATLTCESDANPPVsHYTWFdWNNQSLPYHSQK-----------LRLEPVKVQHSGAYWCQGTNSVGKGRSPLsT 674
Cdd:smart00410   6 VKEGESVTLSCEASGSPPP-EVTWY-KQGGKLLAESGRfsvsrsgststLTISNVTPEDSGTYTCAATNSSGSASSGT-T 82

                   ...
gi 297374828   675 LTV 677
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        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297374828 499 LNVQYAPRDVRVRKikplseihsGNSVSLQCDFSSSHPKEVQFFWEKNGRLLGKES--QLNFDSISPEDAGSYSCWVNNS 576
Cdd:cd20937    3 LEIKVTPSDAIVRE---------GDSVTMTCEVSSSNPEYTTVSWLKDGTSLKKQNtfTLNLREVTKDQSGKYCCQVSND 73

                         90
                 ....*....|....*
gi 297374828 577 IGQTASKAWTLEVLY 591
Cdd:cd20937   74 VGPGRSEEVFLQVQY 88

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 297374828 141 FPPHIQLPPEIQESQEVTLTCLLNFSCYGYPIQLQWLLEGVPMRQAAVTSTSLTIKSVFTRSELKFSPQWSHHGKIVTCQ 220
Cdd:cd20938    1 FQPHIQLPPEIQESQEVTLTCLLNFSCYGYPIQLQWLLEGSPMRQAAVTSTSLTIKSVFTRSELKFQPKWSHHGKIVTCQ 80

                         90
                 ....*....|....*...
gi 297374828 221 LQDADGKFLSNDTVQLNV 238
Cdd:cd20938   81 LQDADGKVLSEDTVQLNV 98

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297374828  143 PHIQLPPEIQESQ--EVTLTCLlnfSCYGYP-IQLQWLLEGVPMRQAAVTSTSLTIKSVFTR-SELKFSPQWSHHGKIVT 218
Cdd:pfam08205   1 PTIEPPASLLEGEgpEVVATCS---SAGGKPaPRITWYLDGKPLEAAETSSEQDPESGLVTVtSELKLVPSRSDHGQSLT 77

                          90
                  ....*....|
gi 297374828  219 CQLQDADGKF 228
Cdd:pfam08205  78 CQVSYGALRG 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 297374828   250 PSDAIVREGDSVTMTCEVSSSNPEYttVSWLKDGTSL----------KKQNTFTLNLREVTKDQSGKYCCQVSNDVGPGR 319
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPE--VTWYKQGGKLlaesgrfsvsRSGSTSTLTISNVTPEDSGTYTCAATNSSGSAS 78

                   ....*...
gi 297374828   320 SeEVFLQV 327
Cdd:smart00410  79 S-GTTLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 297374828  335 TVQILHSPAVEGSQVEFLCMSLANPLPTnYTWYHNGKEMQGRTEEKV---------HIPKILPWHAGTYSCVAEN 400
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 297374828 595 RLRVSMSPGDQVM-EGKSATLTCE-SDANPPVSHYTWFDWNNQSLPYHSQKLRLEPVKVQHSGAYWCQGTNSVGKGRSPL 672
Cdd:cd20937    2 KLEIKVTPSDAIVrEGDSVTMTCEvSSSNPEYTTVSWLKDGTSLKKQNTFTLNLREVTKDQSGKYCCQVSNDVGPGRSEE 81

                 ....*..
gi 297374828 673 STLTVYY 679
Cdd:cd20937   82 VFLQVQY 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 297374828 343 AVEGSQVEFLCMSLANPLPTnYTWYHNGKEMQGRTEE-KVH-----IPKILPWHAGTYSCVAENILGTGQR 407
Cdd:cd20978   13 VKGGQDVTLPCQVTGVPQPK-ITWLHNGKPLQGPMERaTVEdgtltIINVQPEDTGYYGCVATNEIGDIYT 82

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 297374828   522 GNSVSLQCDFSSSHPKEVQFFWEK------NGRLLGKESQ----LNFDSISPEDAGSYSCWVNNSIGQTASKAwTLEV 589
Cdd:smart00410   9 GESVTLSCEASGSPPPEVTWYKQGgkllaeSGRFSVSRSGststLTISNVTPEDSGTYTCAATNSSGSASSGT-TLTV 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 297374828 141 FPPHIQLPPEIQESQEVTLTCLLNFSCYGYPIQLQWLLEGVPMRQAAVTSTSLTIKSVFTRSELKFSPQWSHHGKIVTCQ 220
Cdd:cd20938    1 FQPHIQLPPEIQESQEVTLTCLLNFSCYGYPIQLQWLLEGSPMRQAAVTSTSLTIKSVFTRSELKFQPKWSHHGKIVTCQ 80

                         90
                 ....*....|....*...
gi 297374828 221 LQDADGKFLSNDTVQLNV 238
Cdd:cd20938   81 LQDADGKVLSEDTVQLNV 98

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297374828  143 PHIQLPPEIQESQ--EVTLTCLlnfSCYGYP-IQLQWLLEGVPMRQAAVTSTSLTIKSVFTR-SELKFSPQWSHHGKIVT 218
Cdd:pfam08205   1 PTIEPPASLLEGEgpEVVATCS---SAGGKPaPRITWYLDGKPLEAAETSSEQDPESGLVTVtSELKLVPSRSDHGQSLT 77

                          90
                  ....*....|
gi 297374828  219 CQLQDADGKF 228
Cdd:pfam08205  78 CQVSYGALRG 87

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 297374828 250 PSDAIVREGDSVTMTCEVSSSnPEyTTVSWLKDGTSLKKQNT--------FTLNLREVTKDQSGKYCCQVSNDVGPGRSE 321
Cdd:cd20970    9 SFTVTAREGENATFMCRAEGS-PE-PEISWTRNGNLIIEFNTryivrengTTLTIRNIRRSDMGIYLCIASNGVPGSVEK 86

                 ....*.
gi 297374828 322 EVFLQV 327
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 297374828   250 PSDAIVREGDSVTMTCEVSSSNPEYttVSWLKDGTSL----------KKQNTFTLNLREVTKDQSGKYCCQVSNDVGPGR 319
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPE--VTWYKQGGKLlaesgrfsvsRSGSTSTLTISNVTPEDSGTYTCAATNSSGSAS 78

                   ....*...
gi 297374828   320 SeEVFLQV 327
Cdd:smart00410  79 S-GTTLTV 85

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 297374828 143 PHIQLPPEIQESQEVTLTCLLNFSCYGYPIQLQWL-LEGVPMRQaaVTSTSLTIKSVFTRSELKFSPQWSHHGKIVTCQL 221
Cdd:cd20987    1 PNIHVPEELEAGQEVTLTCSVPDNCPALSPEFSWLgAALTPLPP--VLGRLEEEGTTTHSSVLTFTPRPEDHGTNLTCQV 78

                         90
                 ....*....|....*.
gi 297374828 222 QDADGKFLSNDTVQLN 237
Cdd:cd20987   79 KFPGATVTTERTIQLN 94

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297374828   606 VMEGKSATLTCESDANPPVsHYTWFdWNNQSLPYHSQK-----------LRLEPVKVQHSGAYWCQGTNSVGKGRSPLsT 674
Cdd:smart00410   6 VKEGESVTLSCEASGSPPP-EVTWY-KQGGKLLAESGRfsvsrsgststLTISNVTPEDSGTYTCAATNSSGSASSGT-T 82

                   ...
gi 297374828   675 LTV 677
Cdd:smart00410  83 LTV 85

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 297374828  258 GDSVTMTCEVSSSNpeyttVSWLKDGTSLKKQNTFTLNLREVTKDQSGKYCCQVSNDVGPgrseevFLQVQY 329
Cdd:pfam16680   1 DGKVLLTCNSSSKS-----ITWLKDGKGIKSTNTKTLDLGKFSEDPRGLYQCQGEKKKSS------TLQVYY 61

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 297374828  335 TVQILHSPAVEGSQVEFLCMSLANPLPTnYTWYHNGKEMQGRTEEKV---------HIPKILPWHAGTYSCVAEN 400
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 297374828 595 RLRVSMSPGDQVM-EGKSATLTCE-SDANPPVSHYTWFDWNNQSLPYHSQKLRLEPVKVQHSGAYWCQGTNSVGKGRSPL 672
Cdd:cd20937    2 KLEIKVTPSDAIVrEGDSVTMTCEvSSSNPEYTTVSWLKDGTSLKKQNTFTLNLREVTKDQSGKYCCQVSNDVGPGRSEE 81

                 ....*..
gi 297374828 673 STLTVYY 679
Cdd:cd20937   82 VFLQVQY 88

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 297374828 499 LNVQYAPRDVRVRKikplseihsGNSVSLQCDFSSSHPKEVQFFWEKNGRLLGKES--QLNFDSISPEDAGSYSCWVNNS 576
Cdd:cd20937    3 LEIKVTPSDAIVRE---------GDSVTMTCEVSSSNPEYTTVSWLKDGTSLKKQNtfTLNLREVTKDQSGKYCCQVSND 73

                         90
                 ....*....|....*
gi 297374828 577 IGQTASKAWTLEVLY 591
Cdd:cd20937   74 VGPGRSEEVFLQVQY 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 297374828 343 AVEGSQVEFLCMSLANPLPTnYTWYHNGKEMQGRTEE-KVH-----IPKILPWHAGTYSCVAENILGTGQR 407
Cdd:cd20978   13 VKGGQDVTLPCQVTGVPQPK-ITWLHNGKPLQGPMERaTVEdgtltIINVQPEDTGYYGCVATNEIGDIYT 82

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 297374828  341 SPAVEGSQVEFLCMSLANPLPtNYTWYHNGKEMQGRTeeKVHIPKILPWHAGTYSCVAENILGTGQRGP 409
Cdd:pfam13895   9 TVVTEGEPVTLTCSAPGNPPP-SYTWYKDGSAISSSP--NFFTLSVSAEDSGTYTCVARNGRGGKVSNP 74

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 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" strands in the other.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297374828 249 TPSDAIVREGDSVTMTCEVSSSNPeYTTVSWL--KDG-------------------------TSLKKQNTFTLNLREVTK 301
Cdd:cd00099    4 SPRSLSVQEGESVTLSCEVSSSFS-STYIYWYrqKPGqgpefliylssskgktkggvpgrfsGSRDGTSSFSLTISNLQP 82

                         90
                 ....*....|.
gi 297374828 302 DQSGKYCCQVS 312
Cdd:cd00099   83 EDSGTYYCAVS 93

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 297374828  512 KIKPLSEIHSGNSVSLQCdFSSSHPKEVQFFWEKNG-RLLGKE-----------SQLNFDSISPEDAGSYSCWVNNSIGQ 579
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTC-SASTGSPGPDVTWSKEGgTLIESLkvkhdngrttqSSLLISNVTKEDAGTYTCVVNNPGGS 79

                  ....*
gi 297374828  580 TASKA 584
Cdd:pfam00047  80 ATLST 84

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 297374828 333 PSTVQILHSPAV-EGSQVEFLCMSLANPLPtNYTWYHNGKEMQGRTEEKVH---------IPKILPWHAGTYSCVAENIL 402
Cdd:cd20972    2 PQFIQKLRSQEVaEGSKVRLECRVTGNPTP-VVRWFCEGKELQNSPDIQIHqegdlhsliIAEAFEEDTGRYSCLATNSV 80

                 ..
gi 297374828 403 GT 404
Cdd:cd20972   81 GS 82

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 297374828 515 PLSEIHSGNSVSLQCdFSSSHPKeVQFFWEKNGRLLGKESQLNFDSISPEDAGSYSCWVNNSIG 578
Cdd:cd20948    3 SDTYYLSGENLNLSC-HAASNPP-AQYSWTINGTFQTSSQELFLPAITENNEGTYTCSAHNSLT 64

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297374828 343 AVEGSQVEFLCMSLANPLPtNYTWYHNGKEMQGRTEE--------KVHIPKILPWHAGTYSCVAENILGT 404
Cdd:cd20976   13 AVEGQDFVAQCSARGKPVP-RITWIRNAQPLQYAADRstceagvgELHIQDVLPEDHGTYTCLAKNAAGQ 81

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 297374828 604 DQVMEGKSA-TLTCESDANppVSHYTWFdWNNQSLPYH--------SQKLRLEPVKVQHSGAYWCQGTNSVGKGRSPLST 674
Cdd:cd05740    9 SNPVEDKDAvTLTCEPETQ--NTSYLWW-FNGQSLPVTprltlsngNRTLTLLNVTREDAGAYQCEISNPVSANRSDPVT 85

                 ....
gi 297374828 675 LTVY 678
Cdd:cd05740   86 LDVI 89

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 297374828 525 VSLQCDFSSSHPKEVQffWEKNGRLL-----------GKESQLNFDSISPEDAGSYSCWVNNSIGQTASK 583
Cdd:cd00096    1 VTLTCSASGNPPPTIT--WYKNGKPLppssrdsrrseLGNGTLTISNVTLEDSGTYTCVASNSAGGSASA 68

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 297374828 342 PAVEGSQVEFLCMSLANPLPTnYTWYH-----NGKEMQGRTEEKVHIPKILPWHAGTYSCVAENILG 403
Cdd:cd04968   12 YALKGQTVTLECFALGNPVPQ-IKWRKvdgspSSQWEITTSEPVLEIPNVQFEDEGTYECEAENSRG 77

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 297374828  515 PLSEIHSGNSVSLQCDFSSshPKEVQFFWEKNGRLLGKESQLNFDSISPEDAGSYSCWVNNSIGQTASKAWTLEV 589
Cdd:pfam13895   7 SPTVVTEGEPVTLTCSAPG--NPPPSYTWYKDGSAISSSPNFFTLSVSAEDSGTYTCVARNGRGGKVSNPVELTV 79

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 297374828 512 KIKPL--SEIHSGNSVSLQCDFSSSHPkEVQFFWEKNGRLLG-------------KESQLNFDSISPEDAGSYSCWVNNS 576
Cdd:cd05750    2 KLKEMksQTVQEGSKLVLKCEATSENP-SPRYRWFKDGKELNrkrpknikirnkkKNSELQINKAKLEDSGEYTCVVENI 80

                 ....*...
gi 297374828 577 IGQTASKA 584
Cdd:cd05750   81 LGKDTVTG 88

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 297374828 598 VSMSPG-DQVMEGKSATLTCEsDANPPVSHYTWFDWNNQSLPYHSQKLRLEPVKVQHSGAYWCQgtnsvgKGRSPLS 673
Cdd:cd05752    3 VSLDPPwTTVFQGEKVTLTCQ-GFYSPEQNSTQWYHNGTLISSTSSSYRIVAATVNDSGEYRCQ------TQGSSLS 72

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 297374828 250 PSDAIVREGDSVTMTCEvSSSNPEyTTVSWLKDGTSLKKQNTFTLNLREVTKDQS----------------GKYCCQVSN 313
Cdd:cd07693    7 PSDLIVSKGDPATLNCK-AEGRPT-PTIQWLKNGQPLETDKDDPRSHRIVLPSGSlfflrvvhgrkgrsdeGVYVCVAHN 84

                         90
                 ....*....|....
gi 297374828 314 DVGPGRSEEVFLQV 327
Cdd:cd07693   85 SLGEAVSRNASLEV 98

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. 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. The Ig-like domain of the Twitchin is a member of the I-set 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. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297374828 248 VTPSDAIVREGDSVTMTCEVSSSNPeyTTVSWLKDGTSLKKQ---------NTFTLNLREVTKDQSGKYCCQVSNDVGPg 318
Cdd:cd20949    4 ENAYVTTVKEGQSATILCEVKGEPQ--PNVTWHFNGQPISASvadmskyriLADGLLINKVTQDDTGEYTCRAYQVNSI- 80