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 2217263570 105 VALLGGTAELLCPLSlwpgtvPK------EVRWLRSPFpqrSQAVHIFRDGKDQDEDLMPEYKGRTVLVRDA-QEGSVTL 177
Cdd:cd05713    11 LALVGEDAELPCHLS------PKmsaehmEVRWFRSQF---SPVVHLYRDGQDQEEEQMPEYRGRTELLKDAiAEGSVAL 81

                          90       100       110
                  ....*....|....*....|....*....|...
gi 2217263570 178 QILDVRLEDQGSYRCLIQVGNLSKEDTVILQVA 210
Cdd:cd05713    82 RIHNVRPSDEGQYTCFFRSGSFYEEATLELKVA 114

Immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG); The members here are composed of the immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG). MOG, a minor component of the myelin sheath, is an important CNS-specific autoantigen, linked to the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). It is a transmembrane protein having an extracellular Ig domain. MOG is expressed in the CNS on the outermost lamellae of the myelin sheath, and on the surface of oligodendrocytes, and may participate in the completion, compaction, and/or maintenance of myelin. This group also includes butyrophilin (BTN). BTN is the most abundant protein in bovine milk-fat globule membrane (MFGM).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217263570 105 VALLGGTAELLCPLSlwpgtvPK------EVRWLRSPFpqrSQAVHIFRDGKDQDEDLMPEYKGRTVLVRDA-QEGSVTL 177
Cdd:cd05713    11 LALVGEDAELPCHLS------PKmsaehmEVRWFRSQF---SPVVHLYRDGQDQEEEQMPEYRGRTELLKDAiAEGSVAL 81

                          90       100       110
                  ....*....|....*....|....*....|...
gi 2217263570 178 QILDVRLEDQGSYRCLIQVGNLSKEDTVILQVA 210
Cdd:cd05713    82 RIHNVRPSDEGQYTCFFRSGSFYEEATLELKVA 114

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217263570  111 TAELLCplSLWPGTVPK-EVRWLRSPfpQRSQAVHIFRDGKDQDEDLMPEYKGRTVLVRDAQEGSVTLQILDVRLEDQGS 189
Cdd:smart00406   1 SVTLSC--KFSGSTFSSyYVSWVRQP--PGKGLEWLGYIGSNGSSYYQESYKGRFTISKDTSKNDVSLTISNLRVEDTGT 76

                   ....*
gi 2217263570  190 YRCLI 194
Cdd:smart00406  77 YYCAV 81

Immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG); The members here are composed of the immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG). MOG, a minor component of the myelin sheath, is an important CNS-specific autoantigen, linked to the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). It is a transmembrane protein having an extracellular Ig domain. MOG is expressed in the CNS on the outermost lamellae of the myelin sheath, and on the surface of oligodendrocytes, and may participate in the completion, compaction, and/or maintenance of myelin. This group also includes butyrophilin (BTN). BTN is the most abundant protein in bovine milk-fat globule membrane (MFGM).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217263570 105 VALLGGTAELLCPLSlwpgtvPK------EVRWLRSPFpqrSQAVHIFRDGKDQDEDLMPEYKGRTVLVRDA-QEGSVTL 177
Cdd:cd05713    11 LALVGEDAELPCHLS------PKmsaehmEVRWFRSQF---SPVVHLYRDGQDQEEEQMPEYRGRTELLKDAiAEGSVAL 81

                          90       100       110
                  ....*....|....*....|....*....|...
gi 2217263570 178 QILDVRLEDQGSYRCLIQVGNLSKEDTVILQVA 210
Cdd:cd05713    82 RIHNVRPSDEGQYTCFFRSGSFYEEATLELKVA 114

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 2217263570 108 LGGTAELLCPLSLWPGTVPKEVRWLRSPFPQRSQAVHIFRDGKDQdedlMPEYKGRTVLVRDAQEGSVTLQILDVRLEDQ 187
Cdd:pfam07686  10 LGGSVTLPCTYSSSMSEASTSVYWYRQPPGKGPTFLIAYYSNGSE----EGVKKGRFSGRGDPSNGDGSLTIQNLTLSDS 85

                  ....*..
gi 2217263570 188 GSYRCLI 194
Cdd:pfam07686  86 GTYTCAV 92

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 2217263570 105 VALLGGTAELLCPLSLWPGTVPKEVRWLRSpfpQRSQAVHIFRDGKDQDEDLMPEYKGRT-VLVRDAQEGSVTLQILDVR 183
Cdd:cd20984     8 AGNIGEDGILSCTFTPDIKLSDIVIQWLKE---GDSGLVHEFKEGKDELSRQSPMFRGRTsLFADQVHVGNASLRLKNVQ 84

                          90
                  ....*....|.
gi 2217263570 184 LEDQGSYRCLI 194
Cdd:cd20984    85 LTDAGTYLCII 95

Immunoglobulin variable domain (IgV) in Cluster of Differentiation (CD) 86; The members here are composed of the immunoglobulin variable region (IgV) in the Cluster of Differentiation (CD) 86). Glycoproteins B7-1 (also known as cluster of differentiation (CD) 80) and B7-2 (also known as CD86) are expressed on antigen-presenting cells and deliver the co-stimulatory signal through CD28 and CTLA-4 (also known as CD152) on T cells. signaling through CD28 augments the T-cell response, whereas CTLA-4 signaling attenuates it. The CTLA-4 and B7-2 monomers are both two-layer beta-sandwiches that display the chain topology characteristic of the immunoglobulin variable (V-type) domains present in antigen receptors. The front and back sheets of B7-2 are composed of AGFCC'C" and BED strands, respectively. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217263570 106 ALLGGTAELLCPLSLWPGTVPKE--VRWLRspfpQRSQAVHIFRDGKDQDEDLMPEYKGRTVLVRDaqegSVTLQILDVR 183
Cdd:cd16087     5 AYFNETAYLPCQFKNPQNISLSElvVFWQD----QKKLVLYELYLGKEKLDNVNSKYIGRTSFDQE----NWTLQLHNVQ 76

                          90
                  ....*....|..
gi 2217263570 184 LEDQGSYRCLIQ 195
Cdd:cd16087    77 IKDQGTYQCFIH 88

Immunoglobulin Variable (V) domain of the Coxsackievirus and Adenovirus Receptor (CAR), and similar proteins; The members here are composed of the Variable (V) domain of the Coxsackievirus and Adenovirus Receptor (CAR), and similar proteins. CAR, which is encoded by human CXADR gene, is a cell adhesion molecule of the Immunoglobulin (Ig) superfamily. The CAR acts as a type I membrane receptor for group B1-B6 coxsackie viruses and subgroup C adenoviruses. For instance, adenovirus interacts with the coxsackievirus and adenovirus receptor to enter epithelial airway cells. The CAR is also shown to be involved in physiological processes such as neuronal and heart development, epithelial tight junction integrity, and tumor suppression. The CAR is a component of the epithelial apical junction complex that may function as a homophilic cell adhesion molecule and is essential for tight junction integrity. The CAR is also involved in transepithelial migration of leukocytes through adhesive interactions with JAML a transmembrane protein of the plasma membrane of leukocytes. The interaction between both receptors also mediates the activation of gamma-delta T-cells, a subpopulation of T-cells residing in epithelia and involved in tissue homeostasis and repair. The CAR is composed of one V-set and one C2-set Ig module, a single transmembrane helix, and an intracellular domain. This group belongs to the V-set of IgSF domains, having A, B, E and D strands in one beta-sheet and A', G, F, C, C' and C" in the other

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217263570 109 GGTAELLCPLSLWPGTVPK-EVRWLRSPfPQRSQAVHIFRDGKDQDEDLMPEYKGRTVLVRDAQEGSVTLQILDVRLEDQ 187
Cdd:cd20960    15 GENVTLPCHHQLGLEDQGTlDIEWLLLP-SDKVEKVVITYSGDRVYNHYYPALKGRVAFTSNDLSGDASLNISNLKLSDT 93

                  ....*
gi 2217263570 188 GSYRC 192
Cdd:cd20960    94 GTYQC 98

Immunoglobulin Variable region-containing chitin-binding proteins; an immunoglobulin V-set domain; The members here are composed of the immunoglobulin variable (IgV) region-containing chitin-binding proteins (VCBPs). VCBPs are secreted, immune-type molecules that have been identified in both amphioxus and sea squirt (Ciona intestinalis). VCBPs, which consist of a leader peptide, two tandem N-terminal immunoglobulin V-type domains and a single C-terminal chitin-binding domain, belong to a multigene family encoding secreted proteins. The VCBPs were identified first in the cephalochordate Branchiostoma floridae and show structural similarities with V-type domains of immunoglobulins and T cell receptors, suggesting that VCBPs represent a unique gut-associated form of innate immune proteins. 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, such as, T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as, 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. 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, having A, B, E and D strands in one beta-sheet and A', G, F, C, C' and C" in the other.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217263570 105 VALLGGTAELLCPLSLWPGTVPKEVRWLRSPFPQRSQAV----HIFRDGKDQDEDLMPEYKGRTVLVRDAQEgsvTLQIL 180
Cdd:cd20963    13 DPTWGNRVELPCSYTISPAAQPPTITWLKGISVDRAEVVfkgfKYWNETSSSGEVYFGDYAGRASVASLTQP---TLVLT 89

                          90       100
                  ....*....|....*....|...
gi 2217263570 181 DVRLEDQGSYRCliQVGNLSKED 203
Cdd:cd20963    90 DLKFDDWGRYWC--RVANWSQRD 110

Immunoglobulin variable (IgV)-like domain in complement receptor of the immunoglobulin superfamily (CRIg); The members here are composed of the immunoglobulin variable (IgV) region of the complement receptor of the immunoglobulin superfamily (CRIg). The N-terminal domain of CRIg (also known as Z39Ig and V-set and Ig domain-containing 4 (VSIG4) belongs to the IgV family of immunoglobulin-like domains while the C-terminal domain of CRIg belongs to the IgC family of immunoglobulin-like domains. Like all members of this family, the CRIg domain contains two beta-sheets: one composed of strands A', G, F, C, C' and C", and the other of strands B, E and D. The complement system is an important part of the innate immune system and is required for removal of pathogens from the bloodstream. After exposure to pathogens, the third component of the complement system, C3, is cleaved to C3b which, after recruitment of factor B, initiates formation of the alternative pathway convertases. CRIg, a complement receptor expressed on macrophages, binds to C3b and iC3b mediating phagocytosis of the particles. It is also a potent inhibitor of the alternative pathway convertases and a negative regulator of T cell activation. 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, such as, T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as, 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217263570 110 GTAELLCPLSLWPGTVPKEVRWLrspFPQRSQAVHIF-RDGKDqDEDLMPEYKGRTVLVRDAqEGSVTLQILDVRLEDQG 188
Cdd:cd16089    15 GSVNLPCTYVPEEGYTQVLVKWL---VQRDSDPVTIFlRDSSG-DHIQQAKYRGRLEVSKDT-PGDVSLQLDTLEMDDRG 89

                          90       100
                  ....*....|....*....|....*.
gi 2217263570 189 SYRCLI----QVGNLSK-EDTVILQV 209
Cdd:cd16089    90 HYTCQVtwqtPDGNLIVrEKTTELRV 115

Immunoglobulin variable (IgV) domain of B7-H6; The members here are composed of the immunoglobulin variable (IgV) domain of B7-H6 (also known as NCR3LG1). B7-H6 contains one IgV domain and one IgC domain (IgV-IgC) and belongs to the B7-family, which consists of structurally related cell-surface protein ligands which bind to receptors on lymphocytes that regulate immune responses. B7-H6 is a ligand of NKp30, which is a member of CD28 family and an activating receptor of natural killer (NK) cells. The expression of NKp30 has been found in most of NK cells, which is involved in the process of tumor cell killing and interaction with antigen presenting cells (APCs) such as dendritic cells. Studies showed that NK cells eliminate B7-H6-expressing tumor cells either directly via cytotoxicity or indirectly by cytokine secretion. For instance, chimeric NKp30-expressing T cells responded to B7-H6(+) tumor cells and those T cells produced IFN-gamma and killed B7-H6-expressing tumor cells in vivo. B7-H6 mRNA is not found in normal cells, while high expression of B7-H6 is found in certain type tumor cells, such as lymphoma, leukemia, ovarian cancer, brain tumors, breast cancers, and various sarcomas. Since B7-H6 can bind NKp30 to exert anti-tumor effects by NK cells, which are able to recognize the difference between cancer cells and normal cells, B7-H6 may serve as a promising target for cancer immunotherapy.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217263570 100 AGKFHVALLGGTAELLCPLslwPGTVPKEVR-----WLRSPfPQRSQAVHIFRDGKDQDEDLMPeykGRTVLVRDAQEGS 174
Cdd:cd20981     7 AGGTQITPLNDNVTIFCNI---FYSQPLNITsmgitWFRKS-LTFDKEVKVFEFFGDHQKAFRP---GAIVSPWRLKSGD 79

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2217263570 175 VTLQILDVRLEDQGSYRCLIQVGNLSKEDTVILQV 209
Cdd:cd20981    80 ASLQLPGVQLEEAGEYRCEVVVTPLKAQGTVQLEV 114

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2217263570 131 WLR-SPFPQRSQAVHIfrdgKDQDEDLMPEYKGRTVLVRDAQEGSVTLQILDVRLEDQGSYR 191
Cdd:cd05712    39 WYRgGPYPKYRPPVAT----NNRTREVHESTQGRFRLLGDPGKKNCSLSISDARPEDSGKYF 96

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 2217263570 112 AELLCPLSlwpGTVPKEVRWlrspfpqrsqavhiFRDGKDQDEDLMPEykgrtvlvRDAQEGSVTLQILDVRLEDQGSYR 191
Cdd:cd00096     1 VTLTCSAS---GNPPPTITW--------------YKNGKPLPPSSRDS--------RRSELGNGTLTISNVTLEDSGTYT 55

                  .
gi 2217263570 192 C 192
Cdd:cd00096    56 C 56

Immunoglobulin (Ig)-like domain in the polymeric Ig receptor (pIgR) and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain in the polymeric Ig receptor (pIgR) and similar proteins. pIgR delivers dimeric IgA and pentameric IgM to mucosal secretions. Polymeric immunoglobulin (pIgs) are the first defense against pathogens and toxins. IgA and IgM can form polymers via an 18-residue extension at their C-termini referred to as the tailpiece. pIgR transports pIgs across mucosal epithelia into mucosal secretions. Human pIgR is a glycosylated type I transmembrane protein, comprised of a 620-residue extracellular region, a 23-residue transmembrane region, and a 103-residue cytoplasmic tail. The extracellular region contains five domains that share sequence similarity with Ig variable (v) regions. This group also contains the Ig-like extracellular domains of other receptors such as NK cell receptor Nkp44 and myeloid receptors, among others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217263570 104 HVALLGGTAELLCPLSLWPGTVPKevRWLRSpfpqrsqavhifRDGKDQDEDLMPEY--KGRTVLVRDAQEGSVTLQILD 181
Cdd:cd05716     7 VTGVEGGSVTIQCPYPPKYASSRK--YWCKW------------GSEGCQTLVSSEGVvpGGRISLTDDPDNGVFTVTLNQ 72

                          90       100
                  ....*....|....*....|....*...
gi 2217263570 182 VRLEDQGSYRCLI-QVGNLSKEDTVILQ 208
Cdd:cd05716    73 LRKEDAGWYWCGVgDDGDRGLTVQVKLV 100