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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 547896       39 PASLMVSLGEDAHFQCPHNSSNNANVTWWRVLHGNYTWPPEFLGPGEDPNGTLIIQNVNKSHGGIYVCRVQegNESYQQS 118
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAT--NSSGSAS 78

                   ....*..
gi 547896      119 CGTYLRV 125
Cdd:smart00410  79 SGTTLTV 85

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 547896       39 PASLMVSLGEDAHFQCPHNSSNNANVTWWRVLHGNYTWPPEFLGPGEDPNGTLIIQNVNKSHGGIYVCRVQegNESYQQS 118
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAT--NSSGSAS 78

                   ....*..
gi 547896      119 CGTYLRV 125
Cdd:smart00410  79 SGTTLTV 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
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 547896    50 AHFQCPHNSSNNANVTWWRVLHGNyTWPPEFLGPGEDPNGTLIIQNVNKSHGGIYVCRVQ 109
Cdd:cd00096   1 VTLTCSASGNPPPTITWYKNGKPL-PPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVAS 59

Immunoreceptor tyrosine-based activation motif; T cell receptor (TCR) is a complex multi-protein cell surface receptor composed of the ligand-sensing TCR heterodimer and three signaling subunits. These signaling subunits contain cytoplasmic immunoreceptor tyrosine-based activation motifs (ITAMs) with a consensus sequence of YxxL/Ix6-12YxxL/I. The two tyrosines are phosphorylated by a Src kinase, Lck or Fyn. Binding of the dually phosphorylated ITAM peptide reorients the two SH2 domains relative to each other, destabilizing inhibitory interactions made by the linker connecting the SH2 and kinase domains.

                          10        20
                  ....*....|....*....|
gi 547896     185 ENLYEGLNLDDCSMYEDISR 204
Cdd:pfam02189   1 DQLYQPLNKRDDDTYSHLGM 20

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 547896       39 PASLMVSLGEDAHFQCPHNSSNNANVTWWRVLHGNYTWPPEFLGPGEDPNGTLIIQNVNKSHGGIYVCRVQegNESYQQS 118
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAT--NSSGSAS 78

                   ....*..
gi 547896      119 CGTYLRV 125
Cdd:smart00410  79 SGTTLTV 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
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 547896    50 AHFQCPHNSSNNANVTWWRVLHGNyTWPPEFLGPGEDPNGTLIIQNVNKSHGGIYVCRVQ 109
Cdd:cd00096   1 VTLTCSASGNPPPTITWYKNGKPL-PPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVAS 59

Sixth immunoglobulin (Ig) domain of contactin-2; The members here are composed of the sixth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module by contacts between IG domains 1 and 4, and domains 2 and 3. 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-2 is also expressed in retinal amacrine cells (AC) in the developing chick retina, corresponding to the period of formation and maturation of AC processes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 547896    39 PASLMVSLGEDAHFQC--PHNSSNNANVTWwrVLHGnytWPPEFLGPG--------EDPNGTLIIQNVNKSHGGIYVCRV 108
Cdd:cd05854   9 PSSADINQGENLTLQChaSHDPTMDLTFTW--SLDD---FPIDLDKPNghyrrmevKETIGDLVIVNAQLSHAGTYTCTA 83

                        90       100
                ....*....|....*....|.
gi 547896   109 QEGNESYQQScgTYLRVRQPP 129
Cdd:cd05854  84 QTVVDSASAS--ATLVVRGPP 102

Immunoglobulin variable domain (IgV) Cluster of Differentiation (CD) 79B; The members here are composed of the immunoglobulin variable domain (IgV) of the Cluster of Differentiation (CD) 79B (also known as CD79b molecule, immunoglobulin-associated beta (Ig-beta), and B29). The B lymphocyte antigen receptor is a multimeric complex that includes the antigen-specific component, surface immunoglobulin (Ig). Surface Ig non-covalently associates with two other proteins, Ig-alpha and Ig-beta, which are necessary for expression and function of the B-cell antigen receptor. This gene encodes the Ig-beta protein of the B-cell antigen component. Alternatively spliced transcript variants encoding different isoforms have been described. Members of the IgV family 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. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 547896    33 LWMHkvPASLMVSLGEDAHFQCPHNSSnnANVTWWRVlHGNYTWPPEFLGPG---EDPNG---TLIIQNVNKSHGGIYVC 106
Cdd:cd16096   1 IWQH--PRFAAKKRSSMVKFHCYTNYS--GVMTWFRK-KGNQRPQELFPEDGrisQTQNGsvyTLTIQNIQYEDNGIYFC 75

                        90       100
                ....*....|....*....|.
gi 547896   107 RVQEGNESYQ--QSCGTYLRV 125
Cdd:cd16096  76 QQKCNSTEPDvtDGCGTELLV 96

Immunoreceptor tyrosine-based activation motif; Motif that may be dually phosphorylated on tyrosine that links antigen receptors to downstream signalling machinery.

                           10        20
                   ....*....|....*....|.
gi 547896      185 ENLYEGLNLDDCSMYEDISRG 205
Cdd:smart00077   1 DQLYQPLNKRQRDTYSDLNTR 21

Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 547896    39 PASLMVSLGEDAHFQC--PHNSSNNANVTWwrVLHGnytWPPEFLGP--------GEDPNGTLIIQNVNKSHGGIYVCRV 108
Cdd:cd04970   9 PSNADITVGENATLQChaSHDPTLDLTFTW--SFNG---VPIDLEKIeghyrrryGKDSNGDLEIVNAQLKHAGRYTCTA 83

                        90       100
                ....*....|....*....|.
gi 547896   109 QEGNESYQQSCGtyLRVRQPP 129
Cdd:cd04970  84 QTVVDSDSASAT--LVVRGPP 102

Immunoglobulin (Ig)-like domain of Programmed Cell Death 1 (PD1); The members here are composed of the immunoglobulin (Ig)-like domain of Programmed Cell Death 1 (PD1; also known as CD279/cluster of differentiation 279). PD1 is a cell surface receptor that is expressed on T cells and pro-B cells. The protein's structure includes an extracellular IgV domain followed by a transmembrane region and an intracellular tail. Activation of CD4+ T cells, CD8+ T cells, NKT cells, B cells, and monocytes induces PD-1 expression, immediately after which it binds two distinct ligands, PD-L1 (also known as B7-H1 or CD274/cluster of differentiation 274) and PD-L2, also known as B7-DC. PD-1 plays an important role in down regulating the immune system by preventing the activation of T-cells, reducing autoimmunity and promoting self-tolerance. The inhibitory effect of PD-1 is accomplished by promoting apoptosis in antigen specific T-cells in lymph nodes while simultaneously reducing apoptosis in regulatory T cells. A class of drugs that target PD-1, known as the PD-1 inhibitors, activate the immune system to attack tumors and treat cancer. Comparisons between the mouse PD-1 (mPD-1) and human PD-1 (hPD-1) reveals that unlike the mPD-1 which has a conventional IgSF V-set domain, hPD-1 lacks a C" strand, and instead the C' and D strands are connected by a long and flexible loop. In addition, the BC loop is not stabilized by disulfide bonding to the F strand of the ligand binding beta sheet. These differences result in different binding affinities of human and mouse PD-1 for their ligands.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 547896    39 PASLMVSLGEDAHFQCP-HNSSNNANVTWWRVLHGNYT-----WPPEFLGPGED--------PNG-----TLIIQNVNKS 99
Cdd:cd16088   6 PALLVVTEGANATFTCSfSNTSESFVLNWYRLSPSNQTdklaaFPEDRSQPGQDwrfrvtqlPNGrdfhmSVVRARRNDS 85

                ....*..
gi 547896   100 hgGIYVC 106
Cdd:cd16088  86 --GTYLC 90

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth 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 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, 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, and 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 Slit2 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 547896    39 PASLMVSLGEDAHFQCPHNSSNNANVTWWRVLHGNYTWPPEFLGPGE----DPNGTLIIQNVNKSHGGIYVCR 107
Cdd:cd05726   6 PRDQVVALGRTVTFQCETKGNPQPAIFWQKEGSQNLLFPYQPPQPSSrfsvSPTGDLTITNVQRSDVGYYICQ 78

Immunoreceptor tyrosine-based activation motif; T cell receptor (TCR) is a complex multi-protein cell surface receptor composed of the ligand-sensing TCR heterodimer and three signaling subunits. These signaling subunits contain cytoplasmic immunoreceptor tyrosine-based activation motifs (ITAMs) with a consensus sequence of YxxL/Ix6-12YxxL/I. The two tyrosines are phosphorylated by a Src kinase, Lck or Fyn. Binding of the dually phosphorylated ITAM peptide reorients the two SH2 domains relative to each other, destabilizing inhibitory interactions made by the linker connecting the SH2 and kinase domains.

                          10        20
                  ....*....|....*....|
gi 547896     185 ENLYEGLNLDDCSMYEDISR 204
Cdd:pfam02189   1 DQLYQPLNKRDDDTYSHLGM 20

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 547896      37 KVPASLMVSLGEDAHFQC-------PHnssnnanVTWWR---VL----HGNYTWppeflgpgEDPNGTLIIQNVNKSHGG 102
Cdd:pfam07679   5 QKPKDVEVQEGESARFTCtvtgtpdPE-------VSWFKdgqPLrssdRFKVTY--------EGGTYTLTISNVQPDDSG 69

                          90       100
                  ....*....|....*....|...
gi 547896     103 IYVCRVQegNESYQQSCGTYLRV 125
Cdd:pfam07679  70 KYTCVAT--NSAGEAEASAELTV 90