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 1258501065   8 WVFEHPETLYAWEGACVWIPCTYRALDGDLESFILFHNPEYNKATSKFDGTRLYESTKDGKVPSEQKRVQFLGDKNKNCT 87
Cdd:cd20929     1 WVFEHPETLYAWEGACVWIPCTYRALDGDLESFILFHNPEYNKATSKFDGTRLYESTKDGKVPSEQKRVQFLGDKNKNCT 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1258501065  88 LSIHPVHLADSGQLGLRMESKTEKWMERIHLAVS 121
Cdd:cd20929    81 LSIHPVHLNDSGQLGLRMESKTEKWMERIHLNVS 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 1258501065 226 PKLEIKVTPSDAIVREGDSVTMTCEVSSSNPEYTTVSWLKDGTSLKKQNTFTLNLREVTKDQSGKYCCQVSNDVGPGRSE 305
Cdd:cd20937     1 PKLEIKVTPSDAIVREGDSVTMTCEVSSSNPEYTTVSWLKDGTSLKKQNTFTLNLREVTKDQSGKYCCQVSNDVGPGRSE 80

                  ....*...
gi 1258501065 306 EVFLQVQY 313
Cdd:cd20937    81 EVFLQVQY 88

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 1258501065   8 WVFEHPETLYAWEGACVWIPCTYRALDGDLESFILFHNPEYNKATSKFDGTRLYESTKDGKVPSEQKRVQFLGDKNKNCT 87
Cdd:cd20929     1 WVFEHPETLYAWEGACVWIPCTYRALDGDLESFILFHNPEYNKATSKFDGTRLYESTKDGKVPSEQKRVQFLGDKNKNCT 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1258501065  88 LSIHPVHLADSGQLGLRMESKTEKWMERIHLAVS 121
Cdd:cd20929    81 LSIHPVHLNDSGQLGLRMESKTEKWMERIHLNVS 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 1258501065 226 PKLEIKVTPSDAIVREGDSVTMTCEVSSSNPEYTTVSWLKDGTSLKKQNTFTLNLREVTKDQSGKYCCQVSNDVGPGRSE 305
Cdd:cd20937     1 PKLEIKVTPSDAIVREGDSVTMTCEVSSSNPEYTTVSWLKDGTSLKKQNTFTLNLREVTKDQSGKYCCQVSNDVGPGRSE 80

                  ....*...
gi 1258501065 306 EVFLQVQY 313
Cdd:cd20937    81 EVFLQVQY 88

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1258501065 226 PKLEIKvtPSDAIVREGDSVTMTCEVSSsNPEyTTVSWLKDGTSLK---------KQNTFTLNLREVTKDQSGKYCCQVS 296
Cdd:pfam07679   1 PKFTQK--PKDVEVQEGESARFTCTVTG-TPD-PEVSWFKDGQPLRssdrfkvtyEGGTYTLTISNVQPDDSGKYTCVAT 76

                          90
                  ....*....|....*
gi 1258501065 297 NDVGpGRSEEVFLQV 311
Cdd:pfam07679  77 NSAG-EAEASAELTV 90

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 1258501065   8 WVFEHPETLYAWEGACVWIPCTYRALDGDLESFILFHNPEYNKATSKFDGTRLYESTKDGKVPSEQKRVQFLGDKNKNCT 87
Cdd:cd20929     1 WVFEHPETLYAWEGACVWIPCTYRALDGDLESFILFHNPEYNKATSKFDGTRLYESTKDGKVPSEQKRVQFLGDKNKNCT 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1258501065  88 LSIHPVHLADSGQLGLRMESKTEKWMERIHLAVS 121
Cdd:cd20929    81 LSIHPVHLNDSGQLGLRMESKTEKWMERIHLNVS 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 1258501065 226 PKLEIKVTPSDAIVREGDSVTMTCEVSSSNPEYTTVSWLKDGTSLKKQNTFTLNLREVTKDQSGKYCCQVSNDVGPGRSE 305
Cdd:cd20937     1 PKLEIKVTPSDAIVREGDSVTMTCEVSSSNPEYTTVSWLKDGTSLKKQNTFTLNLREVTKDQSGKYCCQVSNDVGPGRSE 80

                  ....*...
gi 1258501065 306 EVFLQVQY 313
Cdd:cd20937    81 EVFLQVQY 88

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 1258501065 234 PSDAIVREGDSVTMTCEVSSSnPEyTTVSWLKDGTSLKKQNT--------FTLNLREVTKDQSGKYCCQVSNDVGPGRSE 305
Cdd:cd20970     9 SFTVTAREGENATFMCRAEGS-PE-PEISWTRNGNLIIEFNTryivrengTTLTIRNIRRSDMGIYLCIASNGVPGSVEK 86

                  ....*.
gi 1258501065 306 EVFLQV 311
Cdd:cd20970    87 RITLQV 92

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1258501065 227 KLEIKVTPSDAIVREGDSVTMTCEVSSSNPEytTVSWLKDGTSLK---------KQNTFTLNLREVTKDQSGKYCCQVSN 297
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEATGSPPP--TITWYKNGEPISsgstrsrslSGSNSTLTISNVTRSDAGTYTCVASN 78

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1258501065 233 TPSDAIVREGDSVTMTCEVsSSNPEYtTVSWLKDGTSLKK-QNTFTLNlreVTKDQSGKYCCQVSNDVGPGRSEEVFLQV 311
Cdd:pfam13895   5 TPSPTVVTEGEPVTLTCSA-PGNPPP-SYTWYKDGSAISSsPNFFTLS---VSAEDSGTYTCVARNGRGGKVSNPVELTV 79

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 1258501065 231 KVTPSDAIVREGDSVTMTCEVSSSNPEyTTVSWLKDGTSLKKQNTF-------TLNLREVTKDQSGKYCCQVSNDVGPGR 303
Cdd:cd05724     1 RVEPSDTQVAVGEMAVLECSPPRGHPE-PTVSWRKDGQPLNLDNERvrivddgNLLIAEARKSDEGTYKCVATNMVGERE 79

                  ....*...
gi 1258501065 304 SEEVFLQV 311
Cdd:cd05724    80 SRAARLSV 87

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 1258501065 127 PHIQLPPEIQESQEVTLTCLLAFSCYGYPIQLQWL-LEGVPMRQaaVTSTSLTIKSVFTRSELKFSPQWSHHGKIVTCQL 205
Cdd:cd20987     1 PNIHVPEELEAGQEVTLTCSVPDNCPALSPEFSWLgAALTPLPP--VLGRLEEEGTTTHSSVLTFTPRPEDHGTNLTCQV 78

                          90
                  ....*....|....*.
gi 1258501065 206 QDADGKFLSADTVQLN 221
Cdd:cd20987    79 KFPGATVTTERTIQLN 94

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 1258501065 239 VREGDSVTMTCEVSSSNpeyTTVSWLKDGTSLK-------KQNTFTLNLREVTKDQSGKYCCQVSNDVGPGRSEEVFLQV 311
Cdd:cd05740    12 VEDKDAVTLTCEPETQN---TSYLWWFNGQSLPvtprltlSNGNRTLTLLNVTREDAGAYQCEISNPVSANRSDPVTLDV 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 1258501065 241 EGDSVTMTCEVSSSnPEYTTVSWLKDGTSLKKQNTfTLNLREVTKDQSGKYCCQVSndvGPGRSEEVFLQV 311
Cdd:cd05752    14 QGEKVTLTCQGFYS-PEQNSTQWYHNGTLISSTSS-SYRIVAATVNDSGEYRCQTQ---GSSLSDPVHLEV 79

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 1258501065 233 TPSDAIVREGDSVTMTCEVSSSNPeYTTVSWL--KDG-------------------------TSLKKQNTFTLNLREVTK 285
Cdd:cd00099     4 SPRSLSVQEGESVTLSCEVSSSFS-STYIYWYrqKPGqgpefliylssskgktkggvpgrfsGSRDGTSSFSLTISNLQP 82

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1258501065 286 DQSGKYCCQVSndVGPGRSEEVFlqvqyAGGTK 318
Cdd:cd00099    83 EDSGTYYCAVS--ESGGTDKLTF-----GSGTR 108

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 1258501065 234 PSDAIVREGDSVTMTCEvSSSNPEyTTVSWLKDGTSLKKQNTFTLNLREVTKDQS----------------GKYCCQVSN 297
Cdd:cd07693     7 PSDLIVSKGDPATLNCK-AEGRPT-PTIQWLKNGQPLETDKDDPRSHRIVLPSGSlfflrvvhgrkgrsdeGVYVCVAHN 84

                          90
                  ....*....|....
gi 1258501065 298 DVGPGRSEEVFLQV 311
Cdd:cd07693    85 SLGEAVSRNASLEV 98

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. 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, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -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, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -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 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. The fifth Ig-like domain of Robo 1 and 2 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. 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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1258501065 230 IKVTPSDAIVREGDSVTMTCEVSSSnpEYTTVSWLKDGTSL-------KKQNTFTLNLREVTKDQSGKYCCQVSNDVG 300
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCQATGE--PVPTISWLKDGVPLlgkderiTTLENGSLQIKGAEKSDTGEYTCVALNLSG 77

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 1258501065 232 VTPSDAIVREGDSVTMTCEVSSSNPeyTTVSWLKDGTSLKKQ---------NTFTLNLREVTKDQSGKYCCQVSNDVGPg 302
Cdd:cd20949     4 ENAYVTTVKEGQSATILCEVKGEPQ--PNVTWHFNGQPISASvadmskyriLADGLLINKVTQDDTGEYTCRAYQVNSI- 80

                  ....*....
gi 1258501065 303 RSEEVFLQV 311
Cdd:cd20949    81 ASDMQERTV 89

Immunoglobulin C1-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1258501065 124 PFPPhiqlPPEiQESQEVTLTCLLafscYGY---PIQLQWLLEGVPMRQAAVTSTSLTIK--SVFTRSELKFSPQWSHHG 198
Cdd:pfam07654   3 VFPP----SPE-ELGKPNTLTCLV----TGFyppDITVTWLKNGQEVTEGVKTTPPSPNSdwTYQLSSYLTVTPSDWESG 73

                  ....*.
gi 1258501065 199 KIVTCQ 204
Cdd:pfam07654  74 DEYTCR 79

Immunoglobulin Variable (IgV) domain at the N-terminus of CD33 and related Siglecs (sialic acid-binding Ig-like lectins); The members here are composed of the immunoglobulin (Ig) domain at the N-terminus of Cluster of Differentiation (CD) 33 and related Siglecs (sialic acid-binding Ig-like lectins). Siglec refers to a structurally related protein family that specifically recognizes sialic acid in oligosaccharide chains of glycoproteins and glycolipids. Siglecs are type I transmembrane proteins, 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, the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1258501065   8 WVFEHPETLYAWEGACVWIPCTYraldgdlesfilFHNPEYNKATSK-----FDGTRLYE------STKDGKVPSE-QKR 75
Cdd:cd05712     1 WGLQMPKSVTVQEGLCVLIPCSF------------SYPADYWVSNPVhgywyRGGPYPKYrppvatNNRTREVHEStQGR 68

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1258501065  76 VQFLGD-KNKNCTLSIHPVHLADSGQLGLRME 106
Cdd:cd05712    69 FRLLGDpGKKNCSLSISDARPEDSGKYFFRVE 100

Second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 - Necl-4; member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 or CADM3), Necl-2 (also known as CADM1), Necl-3 (also known as CADM2) and Necl-4 (also known as CADM4). These nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1 and Necl-2 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues, and is a putative tumour suppressor gene, which is downregulated in aggressive neuroblastoma. Necl-3 has been shown to accumulate in tissues of the central and peripheral nervous system, where it is expressed in ependymal cells and myelinated axons. It is observed at the interface between the axon shaft and the myelin sheath. Necl-4 is expressed on Schwann cells, and plays a key part in initiating peripheral nervous system (PNS) myelination. Necl-4 participates in cell-cell adhesion and is proposed to play a role in tumor suppression.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1258501065 239 VREGDSVTMTCEVSSSNPEyTTVSWLKDGTSLK---------KQNTFT----LNLREVTKDQSGKYCCQVSNDVGPGRSE 305
Cdd:cd05761    16 VVEGDEITLTCTTSGSKPA-ADIRWFKNDKELKgvkevqesgAGKTFTvtstLRFRVDRDDDGVAVICRVDHESLTSTPK 94

                  .
gi 1258501065 306 E 306
Cdd:cd05761    95 Q 95

Fifth 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 fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1258501065 242 GDSVTMTCEVSSsnpeY--TTVSWLKDGTSL---KKQNTF---TLNLREVTKDQ-SGKYCCQVSNDVGPGRSEEVFLQV 311
Cdd:cd20958    15 GQTLRLHCPVAG----YpiSSITWEKDGRRLplnHRQRVFpngTLVIENVQRSSdEGEYTCTARNQQGQSASRSVFVKV 89

CH3 domain (third constant Ig domain of the heavy chain) in immunoglobulin heavy alpha, gamma, and delta chains, and CH4 domain (fourth constant Ig domain of the heavy chain) in immunoglobulin heavy alpha, epsilon, and mu chains; member of the C1-set of I; The members here are composed of the third and fourth immunoglobulin constant domain (IgC) of alpha, delta, gamma and alpha, epsilon, and mu heavy chains, respectively. This domain is found on the Fc fragment. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. There are two types of light chains: kappa and lambda; each is composed of a constant domain and a variable domain. There are five types of heavy chains: alpha, delta, epsilon, gamma, and mu, all consisting of a variable domain (VH) with three (alpha, delta and gamma) or four (epsilon and mu) constant domains (CH1 to CH4). Ig molecules are modular proteins, in which the variable and constant domains have clear, conserved sequence patterns.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1258501065 234 PSDAIVREGDSVTMTCEVSSSNPEYTTVSWLKDGTSLKKQNTFT 277
Cdd:cd05768     8 PPEEELSLNETVTLTCLVKGFYPEDIFVSWLQNGEPLPSADYKT 51

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1258501065 229 EIKVTPSDAIVREGDSVTMTCEVSS-SNPEyttVSWLKDG----TSLKKQ-----NTFTLNLREVTKDQSGKYCCQVSND 298
Cdd:cd05736     2 VIRVYPEFQAKEPGVEASLRCHAEGiPLPR---VQWLKNGmdinPKLSKQltliaNGSELHISNVRYEDTGAYTCIAKNE 78

                  ..
gi 1258501065 299 VG 300
Cdd:cd05736    79 GG 80

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 1258501065 233 TPSDAIVREGDSVTMTCEvSSSNPEyTTVSWLKDGTSLkkQNTFTLNLREVTKDQSGKYCCQVSNDVG 300
Cdd:cd20948     1 SPSDTYYLSGENLNLSCH-AASNPP-AQYSWTINGTFQ--TSSQELFLPAITENNEGTYTCSAHNSLT 64

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1258501065 231 KVTPSDAIVREGDSVTMTCEVSSSNPeyTTVSW--LKDGTSLKKQNTFTLN------------LREVTKDQSGKYCCQVS 296
Cdd:cd05734     5 VVQPNDQDGIYGKAVVLNCSADGYPP--PTIVWkhSKGSGVPQFQHIVPLNgriqllsngsllIKHVLEEDSGYYLCKVS 82

                          90
                  ....*....|....*
gi 1258501065 297 NDVGPGRSEEVFLQV 311
Cdd:cd05734    83 NDVGADISKSMYLTV 97

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1258501065 233 TPSDAIVR-EGDSVTMTCEVsSSNPEyTTVSWLKDG--------TSLKKQNTFTLNlrEVTKDQSGKYCCQVSNDVGPGR 303
Cdd:cd20978     6 KPEKNVVVkGGQDVTLPCQV-TGVPQ-PKITWLHNGkplqgpmeRATVEDGTLTII--NVQPEDTGYYGCVATNEIGDIY 81

                  ....*...
gi 1258501065 304 SeEVFLQV 311
Cdd:cd20978    82 T-ETLLHV 88

Immunoglobulin (Ig)-like domain of Cluster of Differentiation (CD) 3 gamma and delta chains; member of the C1-set of IgSF domains; The members here are composed of immunoglobulin (Ig)-like domain of Cluster of Differentiation (CD) 3 gamma and delta chains. CD3 is a T cell surface receptor that is associated with alpha/beta T cell receptors (TCRs). The CD3 complex consists of one gamma, one delta, two epsilon, and two zeta chains. The CD3 subunits form heterodimers as gamma/epsilon, delta/epsilon, and zeta/zeta. The gamma, delta, and epsilon chains each contain an extracellular Ig domain, whereas the extracellular domains of the zeta chains are very small and have unknown structure. The CD3 domain participates in intracellular signaling once the TCR has bound an MHC/antigen complex.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1258501065 242 GDSVTMTCEVSSSnpeyttVSWLKDGTSLKKQNTFTLNLREVTKDQSGKYCCQVSNDVgpgrseEVFLQVQY 313
Cdd:cd07691     6 EDKVFLKCNSASS------ITWKKGTEGIEASDKTDLDLGSRINDPRGTYQCKGSENK------EKTLQVHY 65