Immunoglobulin (Ig)-like variable (V) domain of the Signal-Regulatory Protein (SIRP); The members here are composed of the immunoglobulin (Ig)-like domain of the Signal-Regulatory Protein (SIRP). The SIRPs belong to the "paired receptors" class of membrane proteins that comprise several genes coding for proteins with similar extracellular regions, but very different transmembrane/cytoplasmic regions with different (activating or inhibitory) signaling potentials. They are commonly on NK cells, but are also on many myeloid cells. Their extracellular region contains three immunoglobulin superfamily domains, a single V-set, and two C1-set IgSF domains. Their cytoplasmic tails that contain either ITIMs or transmembrane regions have positively charged residues that allow an association with adaptor proteins, such as DAP12/KARAP, containing ITAMs. There are 3 distinct SIRP members: alpha, beta, and gamma. SIRP alpha (also known as CD172a or SRC homology 2 domain-containing protein tyrosine phosphatase substrate 1/Shps-1) is a membrane receptor that interacts with a ligand CD47 expressed on many cells and gives an inhibitory signal through immunoreceptor tyrosine-based inhibition motifs in the cytoplasmic region that interact with phosphatases SHP-1 and SHP-2. SIRP beta has a short cytoplasmic region and associates with a transmembrane adapter protein DAP12 containing immunoreceptor tyrosine-based activation motifs to give an activating signal. SIRP gamma contains a very short cytoplasmic region lacking obvious signaling motifs, but also binds CD47 with much less affinity. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2JJV_A        5 QVIQPDKSISVAAGESATLHCTVTSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRISNITPA 84
Cdd:cd16097   1 QVIQPEKSVSVAAGESATLHCTVTSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRISNITPA 80

                        90       100       110
                ....*....|....*....|....*....|.
2JJV_A       85 DAGTYYCVKFRKGSPDHVEFKSGAGTELSVR 115
Cdd:cd16097  81 DAGTYYCVKFRKGSPDDVEFKSGAGTELSVR 111

Immunoglobulin (Ig)-like variable (V) domain of the Signal-Regulatory Protein (SIRP); The members here are composed of the immunoglobulin (Ig)-like domain of the Signal-Regulatory Protein (SIRP). The SIRPs belong to the "paired receptors" class of membrane proteins that comprise several genes coding for proteins with similar extracellular regions, but very different transmembrane/cytoplasmic regions with different (activating or inhibitory) signaling potentials. They are commonly on NK cells, but are also on many myeloid cells. Their extracellular region contains three immunoglobulin superfamily domains, a single V-set, and two C1-set IgSF domains. Their cytoplasmic tails that contain either ITIMs or transmembrane regions have positively charged residues that allow an association with adaptor proteins, such as DAP12/KARAP, containing ITAMs. There are 3 distinct SIRP members: alpha, beta, and gamma. SIRP alpha (also known as CD172a or SRC homology 2 domain-containing protein tyrosine phosphatase substrate 1/Shps-1) is a membrane receptor that interacts with a ligand CD47 expressed on many cells and gives an inhibitory signal through immunoreceptor tyrosine-based inhibition motifs in the cytoplasmic region that interact with phosphatases SHP-1 and SHP-2. SIRP beta has a short cytoplasmic region and associates with a transmembrane adapter protein DAP12 containing immunoreceptor tyrosine-based activation motifs to give an activating signal. SIRP gamma contains a very short cytoplasmic region lacking obvious signaling motifs, but also binds CD47 with much less affinity. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2JJV_A        5 QVIQPDKSISVAAGESATLHCTVTSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRISNITPA 84
Cdd:cd16097   1 QVIQPEKSVSVAAGESATLHCTVTSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRISNITPA 80

                        90       100       110
                ....*....|....*....|....*....|.
2JJV_A       85 DAGTYYCVKFRKGSPDHVEFKSGAGTELSVR 115
Cdd:cd16097  81 DAGTYYCVKFRKGSPDDVEFKSGAGTELSVR 111

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2JJV_A          11 KSISVAAGESATLHCTVTSLIPVGpIQWFRGagPGRELIYNQKeghfprvTTVSdltkRNNMDFSIRISNITPADAGTYY 90
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPE-VTWYKQ--GGKLLAESGR-------FSVS----RSGSTSTLTISNVTPEDSGTYT 67

                           90       100
                   ....*....|....*....|....
2JJV_A          91 CVkfrkGSPDHVEFKSgaGTELSV 114
Cdd:smart00410  68 CA----ATNSSGSASS--GTTLTV 85

Immunoglobulin (Ig)-like variable (V) domain of the Signal-Regulatory Protein (SIRP); The members here are composed of the immunoglobulin (Ig)-like domain of the Signal-Regulatory Protein (SIRP). The SIRPs belong to the "paired receptors" class of membrane proteins that comprise several genes coding for proteins with similar extracellular regions, but very different transmembrane/cytoplasmic regions with different (activating or inhibitory) signaling potentials. They are commonly on NK cells, but are also on many myeloid cells. Their extracellular region contains three immunoglobulin superfamily domains, a single V-set, and two C1-set IgSF domains. Their cytoplasmic tails that contain either ITIMs or transmembrane regions have positively charged residues that allow an association with adaptor proteins, such as DAP12/KARAP, containing ITAMs. There are 3 distinct SIRP members: alpha, beta, and gamma. SIRP alpha (also known as CD172a or SRC homology 2 domain-containing protein tyrosine phosphatase substrate 1/Shps-1) is a membrane receptor that interacts with a ligand CD47 expressed on many cells and gives an inhibitory signal through immunoreceptor tyrosine-based inhibition motifs in the cytoplasmic region that interact with phosphatases SHP-1 and SHP-2. SIRP beta has a short cytoplasmic region and associates with a transmembrane adapter protein DAP12 containing immunoreceptor tyrosine-based activation motifs to give an activating signal. SIRP gamma contains a very short cytoplasmic region lacking obvious signaling motifs, but also binds CD47 with much less affinity. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2JJV_A        5 QVIQPDKSISVAAGESATLHCTVTSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRISNITPA 84
Cdd:cd16097   1 QVIQPEKSVSVAAGESATLHCTVTSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRISNITPA 80

                        90       100       110
                ....*....|....*....|....*....|.
2JJV_A       85 DAGTYYCVKFRKGSPDHVEFKSGAGTELSVR 115
Cdd:cd16097  81 DAGTYYCVKFRKGSPDDVEFKSGAGTELSVR 111

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2JJV_A          8 QPDKSISVAAGESATLHCTVTSLI--PVGPIQWFR---GAGPGRELI-YNQKEGHFPRVTTVSDLTKRNNMDFSIRISNI 81
Cdd:pfam07686   1 QTPREVTVALGGSVTLPCTYSSSMseASTSVYWYRqppGKGPTFLIAyYSNGSEEGVKKGRFSGRGDPSNGDGSLTIQNL 80

                          90       100       110
                  ....*....|....*....|....*....|....
2JJV_A         82 TPADAGTYYCVKFRKGspdhvEFKSGAGTELSVR 115
Cdd:pfam07686  81 TLSDSGTYTCAVIPSG-----EGVFGKGTRLTVL 109

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2JJV_A          11 KSISVAAGESATLHCTVTSLIPVGpIQWFRGagPGRELIYNQKeghfprvTTVSdltkRNNMDFSIRISNITPADAGTYY 90
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPE-VTWYKQ--GGKLLAESGR-------FSVS----RSGSTSTLTISNVTPEDSGTYT 67

                           90       100
                   ....*....|....*....|....
2JJV_A          91 CVkfrkGSPDHVEFKSgaGTELSV 114
Cdd:smart00410  68 CA----ATNSSGSASS--GTTLTV 85

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2JJV_A          20 SATLHCTV-TSLIPVGPIQWFRgAGPGREL---IYNQKEGHF-------PRVTTVSDLTKRnnmDFSIRISNITPADAGT 88
Cdd:smart00406   1 SVTLSCKFsGSTFSSYYVSWVR-QPPGKGLewlGYIGSNGSSyyqesykGRFTISKDTSKN---DVSLTISNLRVEDTGT 76

                   ...
2JJV_A          89 YYC 91
Cdd:smart00406  77 YYC 79

Immunoglobulin (Ig)-like domain of protein zero (P0) and similar proteins; The members here are composed of the immunoglobulin (Ig) domain of protein zero (P0), a myelin membrane adhesion molecule. P0 accounts for over 50% of the total protein in peripheral nervous system (PNS) myelin. P0 is a single-pass transmembrane glycoprotein with a highly basic intracellular domain and an extracellular Ig domain. The extracellular domain of P0 (P0-ED) is similar to the Ig variable domain, carrying one acceptor sequence for N-linked glycosylation. P0 plays a role in membrane adhesion in the spiral wraps of the myelin sheath. The intracellular domain is thought to mediate membrane apposition of the cytoplasmic faces and may, through electrostatic interactions, interact directly with lipid headgroups. It is thought that homophilic interactions of the P0 extracellular domain mediate membrane juxtaposition in the extracellular space of PNS myelin. This group also contains the Ig domain of sodium channel subunit beta-2 (SCN2B), and of epithelial V-like antigen 1 (EVA). EVA, also known as myelin protein zero-like 2, is an adhesion molecule, which may play a role in structural organization of the thymus and early lymphocyte development. SCN2B subunits play a role in determining sodium channel density and function in neurons,and in control of electrical excitability in the brain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2JJV_A       10 DKSISVAAGESATLHCTVTSLIPVG---PIQW-FR--GAGPGREL-------IYNQKEGHFP-RVTTVSDLTKRnnmDFS 75
Cdd:cd05715   6 PRELNVLNGSDVRLTCTFTSCYTVGdafSVTWtYQpeGGNTTESMfhyskgkPYILKVGRFKdRVSWAGNPSKK---DAS 82

                        90       100
                ....*....|....*....|....*..
2JJV_A       76 IRISNITPADAGTYYCvkFRKGSPDHV 102
Cdd:cd05715  83 IVISNLQFSDNGTYTC--DVKNPPDIV 107

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2JJV_A          5 QVIQPDKSISVAAGESATLHCTVTSlIPVGPIQWFRGagpGRELiynqKEGHFPRVTTVSDLTkrnnmdfSIRISNITPA 84
Cdd:pfam07679   2 KFTQKPKDVEVQEGESARFTCTVTG-TPDPEVSWFKD---GQPL----RSSDRFKVTYEGGTY-------TLTISNVQPD 66

                  ....*...
2JJV_A         85 DAGTYYCV 92
Cdd:pfam07679  67 DSGKYTCV 74

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2JJV_A         11 KSISVAAGESATLHCTVTSLIPVGPIQWFRGagpGRELIYNQKEGHFPRVTTVSDLTkrnnmdfsirISNITPADAGTYY 90
Cdd:pfam00047   4 PTVTVLEGDSATLTCSASTGSPGPDVTWSKE---GGTLIESLKVKHDNGRTTQSSLL----------ISNVTKEDAGTYT 70

                          90
                  ....*....|....*.
2JJV_A         91 CVKFRKGSPDHVEFKS 106
Cdd:pfam00047  71 CVVNNPGGSATLSTSL 86

Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) beta chain; The members here are composed of the immunoglobulin (Ig) variable domain of the beta chain of alpha/beta T-cell antigen receptors (TCRs). TCRs mediate antigen recognition by T lymphocytes, and are composed of alpha and beta, or gamma and delta, polypeptide chains with variable (V) and constant (C) regions. This group includes the variable domain of the alpha chain of alpha/beta TCRs. Alpha/beta TCRs recognize antigen as peptide fragments presented by major histocompatibility complex (MHC) molecules. The variable domain of TCRs is responsible for antigen recognition, and is located at the N-terminus of the receptor. Gamma/delta TCRs recognize intact protein antigens directly without antigen processing and recognize MHC independently of the bound peptide. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2JJV_A        6 VIQPDKSISVAAGESATLHCTVTSLIPVgpIQWFR-GAGPGRELIYNQKEGHFPRVTTVS----DLTKRNNMDFSIRISN 80
Cdd:cd05899   1 VTQSPRYLIKRRGQSVTLRCSQKSGHDN--MYWYRqDPGKGLQLLFYSYGGGLNEEGDLPgdrfSASRPSLTRSSLTIKS 78

                        90       100       110
                ....*....|....*....|....*....|....
2JJV_A       81 ITPADAGTYYCVKFRKGSPDHVEFksGAGTELSV 114
Cdd:cd05899  79 AEPEDSAVYLCASSLGGGADEAYF--GPGTRLTV 110

Immunoglobulin (Ig) lambda light chain variable (V) domain; The members here are composed of the immunoglobulin (Ig) light chain, lambda type, variable (V) domain. 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 composed of a constant domain (CL) and a variable domain (VL). There are five types of heavy chains (alpha, gamma, delta, epsilon, and mu), which determines the type of immunoglobulin formed: IgA, IgG, IgD, IgE, and IgM, respectively. In higher vertebrates, there are two types of light chain, designated kappa and lambda, which seem to be functionally identical, and can associate with any of the heavy chains. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2JJV_A        6 VIQPdKSISVAAGESATLHCTVTSL-IPVGPIQWF--RGAGPGRELIY---NQKEGHFPRVTTVSDLTKRnnmdfSIRIS 79
Cdd:cd04984   2 LTQP-SSLSVSPGETVTITCTGSSGnISGNYVNWYqqKPGSAPRYLIYedkHRPSGIPDRFSGSKSGNTA-----SLTIS 75

                        90       100       110
                ....*....|....*....|....*....|....*
2JJV_A       80 NITPADAGTYYCvkfrkGSPDHVEFKSGAGTELSV 114
Cdd:cd04984  76 GAQTEDEADYYC-----QVWDSNSYVFGGGTKLTV 105

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2JJV_A        6 VIQPDKSISVAAGESATLHCTVtSLIPVGPIQWFRGagpGRELIYNQKEGHFPRVT-TVSDLTKRnnmdfsirisnitpA 84
Cdd:cd20958   3 FIRPMGNLTAVAGQTLRLHCPV-AGYPISSITWEKD---GRRLPLNHRQRVFPNGTlVIENVQRS--------------S 64

                ....*...
2JJV_A       85 DAGTYYCV 92
Cdd:cd20958  65 DEGEYTCT 72

Immunoglobulin (Ig) variable (V) domain of Cluster of Differentiation (CD) 8 beta chain; The members here are composed of the immunoglobulin (Ig)-like domain in Cluster of Differentiation (CD) 8 beta. The CD8 glycoprotein plays an essential role in the control of T-cell selection, maturation, and the T-cell receptor (TCR)-mediated response to peptide antigen. CD8 is comprised of alpha and beta subunits and is expressed as either an alpha/alpha or alpha/beta dimer. Both dimeric isoforms can serve as a coreceptor for T cell activation and differentiation, however they have distinct physiological roles, different cellular distributions, unique binding partners, etc. Each CD8 subunit is comprised of an extracellular domain containing a V-type Ig-like domain, a single pass transmembrane portion, and a short intracellular domain. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2JJV_A        7 IQPDKSISVAAGESATLHCTVTSLIPVGPIQWFR---------------------GAGPGRELIYNQKeghfpRVTTVSD 65
Cdd:cd07700   2 LQTPGSLLVQTNQTVKMSCEAKTSPKNTRIYWLRqrqapskdshfeflaswdpskGIVYGEGVDQEKL-----IILSDSD 76

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
2JJV_A       66 LTKrnnmdFSIRISNITPADAGTYYCVKFrkGSPdhvEFKSGAGTELSV 114
Cdd:cd07700  77 SSR-----YILSLMSVKPEDSGTYFCMTV--GSP---ELIFGTGTKLSV 115

Third 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 third 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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2JJV_A        7 IQPDKSISVAAGESATLHCTVTSlIPVGPIQWFRgagpgreliynqKEGHFPRVTTvsdltkRNNMDFSIRISNITPADA 86
Cdd:cd05725   1 VKRPQNQVVLVDDSAEFQCEVGG-DPVPTVRWRK------------EDGELPKGRY------EILDDHSLKIRKVTAGDM 61

                ....*.
2JJV_A       87 GTYYCV 92
Cdd:cd05725  62 GSYTCV 67

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2JJV_A        7 IQPdKSISVAAGESATLHCTVTSLIPVGPIQWFRGagpGRELIYNQkeghfPRVTTVSDltkrnnmdFSIRISNITPADA 86
Cdd:cd05724   2 VEP-SDTQVAVGEMAVLECSPPRGHPEPTVSWRKD---GQPLNLDN-----ERVRIVDD--------GNLLIAEARKSDE 64

                ....*.
2JJV_A       87 GTYYCV 92
Cdd:cd05724  65 GTYKCV 70

Immunoglobulin Variable (IgV) domain of T cell Immunoglobulin Domain and Mucin Domain 3 (Tim-3), and similar domains; The members here are composed of the immunoglobulin variable (IgV) domain of T cell immunoglobulin domain and mucin domain 3 (Tim-3; also known as Hepatitis A virus cellular receptor 2 (HAVcr-2) and Cluster of Differentiation 366 (CD366)) and similar proteins. TIM-3 is a checkpoint inhibitor in immune responses to tumors, as well as involved in chronic viral infections. Thus, Tim-3 has emerged as one of most promising immune checkpoint targets for cancer immunotherapy. Tim-3 is highly expressed on Th1 lymphocytes and CD11b(+) macrophages and is upregulated on activated T and myeloid cells. TIM-3 regulates macrophage, activation and inhibits Th1 mediated immune responses to promote immunological tolerance. There are three TIM family members in humans (TIM-1, TIM-3, and TIM-4) and eight members in mice (TIM-1 to TIM-8). The IgV domain of human TIM-3 has been shown to bind ligands such as carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1), high mobility group protein B1 (HMGB1)and galectin-9 (GAL9). The binding of GAL9 to TIM-3 can negatively regulate Th1 immune response, enhance immune tolerance and inhibit anti#tumor immunity. Dysregulation of the TIM-3/GAL9 pathway is implicated in numerous chronic autoimmune diseases, such as multiple sclerosis and systemic lupus erythematosus.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2JJV_A       12 SISVAAGESATLHCTVTSLIPVG--PIQWFRGAGP----GRELIYNqkEGHfpRVT--TVSDLTKRNNM---DFSIRISN 80
Cdd:cd20982   2 EYRAEVGHNAYLPCSYTTAAPGNlvPVCWGKGACPvsycGNVLLRT--DER--DVTyqKSSRYQLKGDFskgDVSLTIEN 77

                        90
                ....*....|..
2JJV_A       81 ITPADAGTYYCV 92
Cdd:cd20982  78 VTLADSGIYCCR 89

Immunoglobulin Variable (IgV) domain of B7-H4; The members here are composed of the immunoglobulin variable (IgV) domain of B7-H4 (also known as B7-S1, B7x, or Vtcn1). B7-H4 is one of the B7 family of immune-regulatory ligands that act as negative regulators of T cell function; it contains one IgV domain and one IgC domain. The B7-family consists of structurally related cell-surface protein ligands, which bind to receptors on lymphocytes that regulate immune responses. The binding of B7-H4 to unidentified receptors results in the inhibition of TCR-mediated T cell proliferation, cell-cycle progression and IL-2 production. As a co-inhibitory molecule, B7-H4 is widely expressed in tumor tissues and its expression is significantly associated with poor prognosis in human cancers such as glioma, pancreatic cancer, oral squamous cell carcinoma, renal cell carcinoma, and lung cancer.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2JJV_A       18 GESATLHCTVTSLIPVGP--IQWFRGAGPGreLIYNQKEGHfprvttvSDLTKRNNM---------------DFSIRISN 80
Cdd:cd20984  12 GEDGILSCTFTPDIKLSDivIQWLKEGDSG--LVHEFKEGK-------DELSRQSPMfrgrtslfadqvhvgNASLRLKN 82

                        90
                ....*....|..
2JJV_A       81 ITPADAGTYYCV 92
Cdd:cd20984  83 VQLTDAGTYLCI 94

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.

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2JJV_A        7 IQPDKSISVAAGESATLHCTVTSLIPVGPIQWFRGagpGRELiyNQKEGHFPRVttvsdltkRNNMDFS-IRISNITPAD 85
Cdd:cd05750   3 LKEMKSQTVQEGSKLVLKCEATSENPSPRYRWFKD---GKEL--NRKRPKNIKI--------RNKKKNSeLQINKAKLED 69

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2JJV_A       86 AGTYYCV 92
Cdd:cd05750  70 SGEYTCV 76