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 830260054  29 PQKQYKVARGDNATLPCAFTPPPPAGSTTEITWKATPDVPGSPMidIIKFnsaTGMKVYKNY----KGRAGLTFDLTKGK 104
Cdd:cd20960    6 AQTEIKKVAGENVTLPCHHQLGLEDQGTLDIEWLLLPSDKVEKV--VITY---SGDRVYNHYypalKGRVAFTSNDLSGD 80

                         90       100
                 ....*....|....*....|
gi 830260054 105 ADLQLVRVTSADNRTYECHV 124
Cdd:cd20960   81 ASLNISNLKLSDTGTYQCKV 100

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 830260054  29 PQKQYKVARGDNATLPCAFTPPPPAGSTTEITWKATPDVPGSPMidIIKFnsaTGMKVYKNY----KGRAGLTFDLTKGK 104
Cdd:cd20960    6 AQTEIKKVAGENVTLPCHHQLGLEDQGTLDIEWLLLPSDKVEKV--VITY---SGDRVYNHYypalKGRVAFTSNDLSGD 80

                         90       100
                 ....*....|....*....|
gi 830260054 105 ADLQLVRVTSADNRTYECHV 124
Cdd:cd20960   81 ASLNISNLKLSDTGTYQCKV 100

Seventh 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 seventh 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 830260054 161 QDITLTCKSEeGTPTPTYKWQ--------SY-DVLNNPRPNPLKatdvNGVLSLYNISKDTSGFYVCTSTNEIRS 226
Cdd:cd20954   17 QDVMLHCQAD-GFPTPTVTWKkatgstpgEYkDLLYDPNVRILP----NGTLVFGHVQKENEGHYLCEAKNGIGS 86

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 830260054    30 QKQYKVARGDNATLPCAFTPPPPAgsttEITWKatpDVPGSPMIdiikfnsatgmkvyknYKGRAGLTFDltKGKADLQL 109
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPP----EVTWY---KQGGKLLA----------------ESGRFSVSRS--GSTSTLTI 55

                           90       100       110
                   ....*....|....*....|....*....|...
gi 830260054   110 VRVTSADNRTYECHVdvqEEEDGTLSDTANLIV 142
Cdd:smart00410  56 SNVTPEDSGTYTCAA---TNSSGSASSGTTLTV 85

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 830260054  29 PQKQYKVARGDNATLPCAFTPPPPAGSTTEITWKATPDVPGSPMidIIKFnsaTGMKVYKNY----KGRAGLTFDLTKGK 104
Cdd:cd20960    6 AQTEIKKVAGENVTLPCHHQLGLEDQGTLDIEWLLLPSDKVEKV--VITY---SGDRVYNHYypalKGRVAFTSNDLSGD 80

                         90       100
                 ....*....|....*....|
gi 830260054 105 ADLQLVRVTSADNRTYECHV 124
Cdd:cd20960   81 ASLNISNLKLSDTGTYQCKV 100

Seventh 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 seventh 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 830260054 161 QDITLTCKSEeGTPTPTYKWQ--------SY-DVLNNPRPNPLKatdvNGVLSLYNISKDTSGFYVCTSTNEIRS 226
Cdd:cd20954   17 QDVMLHCQAD-GFPTPTVTWKkatgstpgEYkDLLYDPNVRILP----NGTLVFGHVQKENEGHYLCEAKNGIGS 86

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 830260054 161 QDITLTCKSEeGTPTPTYKWqsyDVLNNP-RPNPLKATDVNGVLSLYNISKDTSGFYVCTSTNEIRSAKCNLTMAV 235
Cdd:cd05876   11 QSLVLECIAE-GLPTPTVKW---LRPSGPlPPDRVKYQNHNKTLQLLNVGESDDGEYVCLAENSLGSARHAYYVTV 82

Immunoglobulin (Ig)-like domain found in Perlecan and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in Perlecan. Perlecan is a large multi-domain heparin sulfate proteoglycan, important in tissue development and organogenesis. Perlecan can be represented as 5 major portions; its fourth major portion (domain IV) is a tandem repeat of immunoglobulin-like domains (Ig2-Ig15) which can vary in size due to alternative splicing. Perlecan binds many cellular and extracellular ligands. Its domain IV region has many binding sites. Some of these have been mapped at the level of individual Ig-like domains, including a site restricted to the Ig5 domain for heparin/sulfatide, a site restricted to the Ig3 domain for nidogen-1 and nidogen-2, a site restricted to Ig4-5 for fibronectin, and sites restricted to Ig2 and to Ig13-15 for fibulin-2. 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 830260054 162 DITLTCKSEEGTPTPTYKWQSYDvlnnpRPNPLKATDVNGVLSLYNISKDTSGFYVCTSTNEIRSAKCNLTM 233
Cdd:cd05754   18 DVSFICRAKSKSPAYTLVWTRVN-----GTLPSRAMDFNGILTIRNVQLSDAGTYVCTGSNMLDTDEATATL 84

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 830260054    30 QKQYKVARGDNATLPCAFTPPPPAgsttEITWKatpDVPGSPMIdiikfnsatgmkvyknYKGRAGLTFDltKGKADLQL 109
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPP----EVTWY---KQGGKLLA----------------ESGRFSVSRS--GSTSTLTI 55

                           90       100       110
                   ....*....|....*....|....*....|...
gi 830260054   110 VRVTSADNRTYECHVdvqEEEDGTLSDTANLIV 142
Cdd:smart00410  56 SNVTPEDSGTYTCAA---TNSSGSASSGTTLTV 85

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 830260054 161 QDITLTCKSEeGTPTPTYKWqsydvLNNPRP---NPLKATDVNGVLSLYNISKDTSGFYVCTSTNEI 224
Cdd:cd20978   17 QDVTLPCQVT-GVPQPKITW-----LHNGKPlqgPMERATVEDGTLTIINVQPEDTGYYGCVATNEI 77

Immunoglobulin Variable (IgV) domain of Programmed death ligand 1 (PD-L1); The members here are composed of the immunoglobulin variable (IgV) domain of Programmed death ligand 1 (PD-L1; also known as Cluster of Differentiation 274 (CD274)). PD-L1 is a cell-surface ligand that competes with PD-L2 for binding to the immunosuppressive receptor programmed death-1 (PD-1). PD-1 is a member of the B7 family that plays an important role in negatively regulating immune responses upon interaction with its two ligands, PD-L1 or PD-L2. Like PD-L2, PD-L1 interacts with PD-1 and suppresses T cell proliferation and cytokine production. The PD-1 receptor is expressed on the surface of activated T cells, while PD-L1 is expressed on cancer cells. When PD-1 and PD-L1 bind together, they form a molecular shield protecting tumor cells from being destroyed by the immune system. Thus, inhibiting the binding of PD-L1 to PD-1 with an antibody leads to killing of tumor cells by T cells. PD-1 inhibitors (such as Pembrolizumab, Nivolumab, and Cemiplimab) and PD-L1 inhibitors (such as Atezolizumab, Avelumab, and Durvalumab ) are an emerging class of immunotherapy that stimulate lymphocytes against tumor cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 830260054  26 VDIPQKQYKVARGDNATLPCAFTPPPPAGSTTEITWKATPDVpgspmiDIIKF-NSATGMKV-YKNYKGRAGLTFD-LTK 102
Cdd:cd20947    1 VTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYWEMEDK------NIIQFvHGEEDLKVqHSSYRQRARLLKDqLSL 74

                         90       100
                 ....*....|....*....|
gi 830260054 103 GKADLQLVRVTSADNRTYEC 122
Cdd:cd20947   75 GNAALQITDVKLQDAGVYRC 94

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 830260054  161 QDITLTCKSEEGTPTPTYKWQSYD-VLNNPRPNPLKATDV-NGVLSLYNISKDTSGFYVCTSTN 222
Cdd:pfam00047  12 DSATLTCSASTGSPGPDVTWSKEGgTLIESLKVKHDNGRTtQSSLLISNVTKEDAGTYTCVVNN 75

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 830260054    40 NATLPCAFTPPPPagSTTEITW-KATPDVPGSPMIdiikFNSATGMKVYKN-YKGRAGLTFDLTKGKADLQLVRVTSADN 117
Cdd:smart00406   1 SVTLSCKFSGSTF--SSYYVSWvRQPPGKGLEWLG----YIGSNGSSYYQEsYKGRFTISKDTSKNDVSLTISNLRVEDT 74

                   ....*
gi 830260054   118 RTYEC 122
Cdd:smart00406  75 GTYYC 79

Immunoglobulin (Ig)-like domain of chondroitin sulfate proteoglycans (CSPGs), human cartilage link protein (LP), and similar domains; The members here are composed of the immunoglobulin (Ig)-like domain similar to that found in chondroitin sulfate proteoglycans (CSPGs) and human cartilage link protein (LP). Included in this group are the CSPGs aggrecan, versican, and neurocan. In CSPGs, this Ig-like domain is followed by hyaluronan (HA)-binding tandem repeats, and a C-terminal region with epidermal growth factor-like, lectin-like, and complement regulatory protein-like domains. Separating these N- and C-terminal regions is a nonhomologous glycosaminoglycan attachment region. In cartilage, aggrecan forms cartilage link protein stabilized aggregates with hyaluronan (HA). These aggregates contribute to the tissue's load bearing properties. Aggrecan and versican have a wide distribution in connective tissue and extracellular matrices. Neurocan is localized almost exclusively in nervous tissue. Aggregates having other CSPGs substituting for aggrecan may contribute to the structural integrity of many different tissues. There is considerable evidence that HA-binding CSPGs are involved in developmental processes in the central nervous system. Members of the vertebrate HPLN (hyaluronan/HA and proteoglycan binding link) protein family are physically linked adjacent to CSPG genes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 830260054  36 ARGDNATLPCAFT-PPPPAGSTTE---ITW-KATPDVPGSPMIDIIkFNSATGMKVYKNYKGRAGL-TFDLTKGKADLQL 109
Cdd:cd05714   10 HLGGNVTLPCKFYrDPTAFGSGIHkirIKWtKLTSDSGYLKEVDVL-VAMGNVVYHKKTYGGRVSVpLKPGSDSDASLVI 88

                         90
                 ....*....|....*
gi 830260054 110 VRVTSADNRTYECHV 124
Cdd:cd05714   89 TDLTASDYGLYRCEV 103

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 830260054  37 RGDNATLPCAFTPPPPAgSTTEITWKATPDvpgSPMIDIIKFNSATGMKVYKNYKGRAGLTFD-LTKGKADLQLVRVTSA 115
Cdd:cd20984   11 IGEDGILSCTFTPDIKL-SDIVIQWLKEGD---SGLVHEFKEGKDELSRQSPMFRGRTSLFADqVHVGNASLRLKNVQLT 86

                 ....*....
gi 830260054 116 DNRTYECHV 124
Cdd:cd20984   87 DAGTYLCII 95

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). 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 830260054 153 IEGKTEYFQditltCKSEeGTPTPTYKWQSYDVLNNPRPNPLKATDVNGVLSLY--NISKDTSGFYVCTSTNEIRSAKCN 230
Cdd:cd05744   13 QEGRLCRFD-----CKVS-GLPTPDLFWQLNGKPVRPDSAHKMLVRENGRHSLIiePVTKRDAGIYTCIARNRAGENSFN 86

                 ....*
gi 830260054 231 LTMAV 235
Cdd:cd05744   87 AELVV 91

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 830260054  161 QDITLTCKSEeGTPTPTYKWQSYDVLNNPRPNPLkatdvngvlsLYNISKDTSGFYVCTSTNE---IRSAKCNLT 232
Cdd:pfam13895  15 EPVTLTCSAP-GNPPPSYTWYKDGSAISSSPNFF----------TLSVSAEDSGTYTCVARNGrggKVSNPVELT 78

CD19 (Cluster of Differentiation 19), a unique double immunoglobulin (Ig)-fold domain; CD19, also known as B-Lymphocyte Surface Antigen B4, T-Cell Surface Antigen Leu-12, and CVID3, is a transmembrane receptor present on various types of B cells, including progenitor, naive, and memory B cells, as well as plasmablasts. Until recently, it was believed to comprise two extracellular immunoglobulin (Ig) structural domains arranged in tandem with C2 topology. However, recent crystal structures have shown that the CD19 extracellular domain contains a unique double Ig domain that is responsible for its binding to proteins such as CD21, CD81, and CD225, which regulate B cell activation and survival. A recent analysis of the CD19 extracellular domain sequence reveals two "Ig domains", but the structure demonstrates that these two domains are not folded independently and connected in tandem. Rather, they fold together as one intertwined domain that can be referred to as a "double Ig" domain. Each of the two regular Ig domain sequences has a noticeably short linker that forms a loop between strands C' and D, rather than allowing the formation of a C" strand. Additionally, the two Ig-domain sequences are separated by a long linker that is structured as a small insertion domain, enabling both Ig sequences to fold together as a unique double Ig-domain. The CD19 domain comprises four "protodomains": two formed by A'B-CC' strands and two by DE-FG strands that interdigitate to form a novel double Ig fold. When analyzing this double Ig domain in terms of the usual Ig-fold, A'B-CC' protodomain of the first Ig sequence combines with DE-FG protodomain of the second, and vice versa. Hence, the second combined Ig fold is inverted, with DE-FG protodomain of the first Ig sequence combining with A'B-CC' protodomain of the second Ig sequence and in that order, as if it were a circular permutation, obtained only through structural folding.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 830260054  34 KVARGDNATLPCAftPPPPAGSTTEITWKATPdvPGSPMIDIikfnsatgmkvykNYKGRaGLTFDLTKGKADLQLVRVT 113
Cdd:cd23997    4 TVAEGSTLWLPCL--VPPSDGPRGPLTWSRGH--PKTPLLSL-------------ELGSP-GLWVLVGPLGILLLLPNVS 65

                         90
                 ....*....|
gi 830260054 114 SADNRTYECH 123
Cdd:cd23997   66 AQMGGFYLCE 75