Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119631029  32 VQQTEMSQTVSTGESIILSCSVPDTLPNGPVLWFKGTGPNRKLIYNFKQGNFPRVKEIGDTTKPGNTDFSTRIREISLAD 111
Cdd:cd16097    2 VIQPEKSVSVAAGESATLHCTVTSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRISNITPAD 81

                         90       100
                 ....*....|....*....|....*....
gi 119631029 112 AGTYYCVKFIKGRAIK-EYQSGRGTQVFV 139
Cdd:cd16097   82 AGTYYCVKFRKGSPDDvEFKSGAGTELSV 110

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119631029  32 VQQTEMSQTVSTGESIILSCSVPDTLPNGPVLWFKGTGPNRKLIYNFKQGNFPRVKEIGDTTKPGNTDFSTRIREISLAD 111
Cdd:cd16097    2 VIQPEKSVSVAAGESATLHCTVTSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRISNITPAD 81

                         90       100
                 ....*....|....*....|....*....
gi 119631029 112 AGTYYCVKFIKGRAIK-EYQSGRGTQVFV 139
Cdd:cd16097   82 AGTYYCVKFRKGSPDDvEFKSGAGTELSV 110

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119631029    38 SQTVSTGESIILSCSVPDTlPNGPVLWFKGTGpnRKLIYNfkqgnfPRVKEIGDttkpgNTDFSTRIREISLADAGTYYC 117
Cdd:smart00410   3 SVTVKEGESVTLSCEASGS-PPPEVTWYKQGG--KLLAES------GRFSVSRS-----GSTSTLTISNVTPEDSGTYTC 68

                   .
gi 119631029   118 V 118
Cdd:smart00410  69 A 69

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119631029  32 VQQTEMSQTVSTGESIILSCSVPDTLPNGPVLWFKGTGPNRKLIYNFKQGNFPRVKEIGDTTKPGNTDFSTRIREISLAD 111
Cdd:cd16097    2 VIQPEKSVSVAAGESATLHCTVTSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRISNITPAD 81

                         90       100
                 ....*....|....*....|....*....
gi 119631029 112 AGTYYCVKFIKGRAIK-EYQSGRGTQVFV 139
Cdd:cd16097   82 AGTYYCVKFRKGSPDDvEFKSGAGTELSV 110

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119631029   34 QTEMSQTVSTGESIILSCSVPDTLPNGP--VLWFKGTGPN--RKLIYNFKQGNFPRVKEIGDT--TKPGNTDFSTRIREI 107
Cdd:pfam07686   1 QTPREVTVALGGSVTLPCTYSSSMSEAStsVYWYRQPPGKgpTFLIAYYSNGSEEGVKKGRFSgrGDPSNGDGSLTIQNL 80

                          90       100       110
                  ....*....|....*....|....*....|...
gi 119631029  108 SLADAGTYYCVKFIKGraikEYQSGRGTQVFVT 140
Cdd:pfam07686  81 TLSDSGTYTCAVIPSG----EGVFGKGTRLTVL 109

Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) gamma chain; The members here are composed of the immunoglobulin (Ig) variable (V) domain of the gamma chain of gamma/delta T-cell receptors (TCRs). TCRs mediate antigen recognition by T lymphocytes, and are heterodimers consisting of alpha and beta chains or gamma and delta chains. Each chain contains a variable (V) and a constant (C) region. The majority of T cells contain alpha/beta TCRs, but a small subset contain gamma/delta TCRs. Alpha/beta TCRs recognize antigens as peptide fragments presented by major histocompatibility complex (MHC) molecules. Gamma/delta TCRs recognize intact protein antigens directly without antigen processing and recognize MHC independently of the bound peptide. Gamma/delta T cells can also be stimulated by non-peptide antigens such as small phosphate- or amine-containing compounds. The variable domain of gamma/delta TCRs is responsible for antigen recognition and is located at the N-terminus of the receptor. Members of this group contain the standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119631029  32 VQQTEMSQTVSTGESIILSCSVPDT-LPNGPVLWFK---GTGPNRkLIY------NFKQGNFPRVKEigDTTKPGNTDFS 101
Cdd:cd04982    1 LEQPQLSITREESKSVTISCKVSGIdFSTTYIHWYRqkpGQALER-LLYvsstsaVRKDSGKTKNKF--EARKDVGKSTS 77

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 119631029 102 T-RIREISLADAGTYYCvkfikgrAIKEYQSGRGTQVF 138
Cdd:cd04982   78 TlTITNLEKEDSATYYC-------AYWESGSGYYIKVF 108

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119631029  36 EM-SQTVSTGESIILSCSVPDTLPNGPVLWFK-GTGPNRKLIYNFKQGNfprvkeigdttKPGNTDFstRIREISLADAG 113
Cdd:cd05750    5 EMkSQTVQEGSKLVLKCEATSENPSPRYRWFKdGKELNRKRPKNIKIRN-----------KKKNSEL--QINKAKLEDSG 71

                 ....*
gi 119631029 114 TYYCV 118
Cdd:cd05750   72 EYTCV 76

Immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1; The members here are composed of the immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. NRG-1 belongs to the neuregulin gene family which is comprised of four genes. This group represents NRG-1. NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, and heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. The NRG-1 protein binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. NRG-1 has multiple functions, for example, in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119631029  36 EM-SQTVSTGESIILSCSVPDTLPNGPVLWFKGTgpnrkliynfkqgnfprvKEIGDTTKPGNTDF-------STRIREI 107
Cdd:cd05895    5 EMkSQEVAAGSKLVLRCETSSEYPSLRFKWFKNG------------------KEINRKNKPENIKIqkkkkksELRINKA 66

                         90
                 ....*....|
gi 119631029 108 SLADAGTYYC 117
Cdd:cd05895   67 SLADSGEYMC 76

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119631029  44 GESIILSCS-VPDTLPNGPVLWFKGTGpNRKLIYNFKQGN----------FPRVKEIGDTTKPGNTdfSTRIREISLADA 112
Cdd:cd20984   12 GEDGILSCTfTPDIKLSDIVIQWLKEG-DSGLVHEFKEGKdelsrqspmfRGRTSLFADQVHVGNA--SLRLKNVQLTDA 88

                         90       100
                 ....*....|....*....|.
gi 119631029 113 GTYYCVKFI---KGRAIKEYQ 130
Cdd:cd20984   89 GTYLCIISNskgTGNANMEYK 109

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119631029  38 SQTVSTGESIILSCSVP-DTLPNgpVLWFKgtgpnrkliynfKQGNFPRVK-EIGDttkpgntDFSTRIREISLADAGTY 115
Cdd:cd05725    6 NQVVLVDDSAEFQCEVGgDPVPT--VRWRK------------EDGELPKGRyEILD-------DHSLKIRKVTAGDMGSY 64

                 ...
gi 119631029 116 YCV 118
Cdd:cd05725   65 TCV 67