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 74762141 278 ASSNKVKSGDDISVLCTVLGEPDVEVEFTWIFPGQKDERPVTIQdtwRLIHRGLGHTTRISqSVITVEDFETIDAGYYIC 357
Cdd:cd05742   9 AEPTVLPQGETLVLNCTANVNLNEVVDFQWTYPSEKEGKLALLK---PDIKVDWSEPGEFV-STLTIPEATLKDSGTYTC 84

                        90
                ....*....|....*
gi 74762141 358 TAQNLQGQTTVATTV 372
Cdd:cd05742  85 AARSGVMKKEKQTSV 99

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and similar proteins; member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and related proteins. The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members: VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1) and VEGFR-3 (Flt-4). VEGF-A interacts with both VEGFR-1 and VEGFR-2. VEGFR-1 binds strongest to VEGF; VEGF-2 binds more weakly. VEGFR-3 appears not to bind VEGF, but binds other members of the VEGF family (VEGF-C and -D). VEGFRs bind VEGFs with high affinity with the IG-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic, and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth. This group also contains alpha-type platelet-derived growth factor receptor precursor (PDGFR)-alpha (CD140a), and PDGFR-beta (CD140b). PDGFRs alpha and beta have an extracellular component with five Ig-like domains, a transmembrane segment, and a cytoplasmic portion that has protein tyrosine kinase activity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74762141 278 ASSNKVKSGDDISVLCTVLGEPDVEVEFTWIFPGQKDERPVTIQdtwRLIHRGLGHTTRISqSVITVEDFETIDAGYYIC 357
Cdd:cd05742   9 AEPTVLPQGETLVLNCTANVNLNEVVDFQWTYPSEKEGKLALLK---PDIKVDWSEPGEFV-STLTIPEATLKDSGTYTC 84

                        90
                ....*....|....*
gi 74762141 358 TAQNLQGQTTVATTV 372
Cdd:cd05742  85 AARSGVMKKEKQTSV 99

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74762141    283 VKSGDDISVLCTVLGEPDVEVefTWIFPGQKderPVTIQDTWRLIHRGLGHTTRISQsvITVEDfetidAGYYICTAQNL 362
Cdd:smart00410   6 VKEGESVTLSCEASGSPPPEV--TWYKQGGK---LLAESGRFSVSRSGSTSTLTISN--VTPED-----SGTYTCAATNS 73

                           90
                   ....*....|.
gi 74762141    363 QGQTTVATTVE 373
Cdd:smart00410  74 SGSASSGTTLT 84

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 74762141    79 KPAATLSLLAGQTVELRCKGSR------IGWSYPAylDTFKDSRLSVKQNERYGQ--LTLVNSTSADTGEFSC 143
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSASTgspgpdVTWSKEG--GTLIESLKVKHDNGRTTQssLLISNVTKEDAGTYTC 71

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and similar proteins; member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and related proteins. The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members: VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1) and VEGFR-3 (Flt-4). VEGF-A interacts with both VEGFR-1 and VEGFR-2. VEGFR-1 binds strongest to VEGF; VEGF-2 binds more weakly. VEGFR-3 appears not to bind VEGF, but binds other members of the VEGF family (VEGF-C and -D). VEGFRs bind VEGFs with high affinity with the IG-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic, and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth. This group also contains alpha-type platelet-derived growth factor receptor precursor (PDGFR)-alpha (CD140a), and PDGFR-beta (CD140b). PDGFRs alpha and beta have an extracellular component with five Ig-like domains, a transmembrane segment, and a cytoplasmic portion that has protein tyrosine kinase activity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74762141 278 ASSNKVKSGDDISVLCTVLGEPDVEVEFTWIFPGQKDERPVTIQdtwRLIHRGLGHTTRISqSVITVEDFETIDAGYYIC 357
Cdd:cd05742   9 AEPTVLPQGETLVLNCTANVNLNEVVDFQWTYPSEKEGKLALLK---PDIKVDWSEPGEFV-STLTIPEATLKDSGTYTC 84

                        90
                ....*....|....*
gi 74762141 358 TAQNLQGQTTVATTV 372
Cdd:cd05742  85 AARSGVMKKEKQTSV 99

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74762141   271 PPSTTILASSNKVKSGDDISVLCTVLGEPdvEVEFTWIFPGQKDERPVTIQDTwrlihrglghtTRISQSVITVEDFETI 350
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEATGSP--PPTITWYKNGEPISSGSTRSRS-----------LSGSNSTLTISNVTRS 67

                          90
                  ....*....|.
gi 74762141   351 DAGYYICTAQN 361
Cdd:pfam13927  68 DAGTYTCVASN 78

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74762141   272 PSTTILASSNKVKSGDDISVLCTVLGEPDVEVefTWifpgQKDERPVTIQDTWRLIHRGLGHTTRISQsvITVEDfetid 351
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEV--SW----FKDGQPLRSSDRFKVTYEGGTYTLTISN--VQPDD----- 67

                          90       100
                  ....*....|....*....|..
gi 74762141   352 AGYYICTAQNLQGQTTVATTVE 373
Cdd:pfam07679  68 SGKYTCVATNSAGEAEASAELT 89

First immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-2; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-2 (OCAM/mamFas II, RNCAM). NCAM-2 is organized similarly to NCAM-1, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. 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 74762141 275 TILASSNKVKSGDDISVLCTVLGEPDvevEFTWIFPgqKDERPVTIQdtwRLIHRGLGHTTRIsqsviTVEDFETIDAGY 354
Cdd:cd05866   4 SISLSKVELSVGESKFFTCTAIGEPE---SIDWYNP--QGEKIVSSQ---RVVVQKEGVRSRL-----TIYNANIEDAGI 70

                        90
                ....*....|....*...
gi 74762141 355 YICTAQNLQGQTTVATTV 372
Cdd:cd05866  71 YRCQATDAKGQTQEATVV 88

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. 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 Ig I1 domain of the titin I-band 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. 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 hemolymph protein hemolin, 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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74762141 272 PSTTILASSNKVKSGDDISVLCTVLGEPDVEVefTWIFPGQKDERPVTIQDTWrlIHRGLG-HTTRISQsvITVEdfeti 350
Cdd:cd20951   1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEV--KWYKNGVPIDPSSIPGKYK--IESEYGvHVLHIRR--VTVE----- 69

                        90       100
                ....*....|....*....|...
gi 74762141 351 DAGYYICTAQNLQGQTTVATTVE 373
Cdd:cd20951  70 DSAVYSAVAKNIHGEASSSASVV 92

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 74762141 293 CTVLGEPDVEVefTWifpgQKDERPVTIQDTWRLIHRGLGHTTRISQsvITVEDfetidAGYYICTAQNLQGQTTVATT 371
Cdd:cd00096   5 CSASGNPPPTI--TW----YKNGKPLPPSSRDSRRSELGNGTLTISN--VTLED-----SGTYTCVASNSAGGSASASV 70

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. 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. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. 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 hemolymph protein hemolin, 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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74762141 271 PPSTTILASSNKVKSGDDISVLCTVLGEPDVEVefTWIfpgqKDERPVTIQDTWRLIHRGLGHttrisqsvITVEDFETI 350
Cdd:cd20976   1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRI--TWI----RNAQPLQYAADRSTCEAGVGE--------LHIQDVLPE 66

                        90       100
                ....*....|....*....|..
gi 74762141 351 DAGYYICTAQNLQGQTTVATTV 372
Cdd:cd20976  67 DHGTYTCLAKNAAGQVSCSAWV 88

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. 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 Ig-like domain of the Twitchin is a member of the I-set 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. 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 hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74762141 275 TILASSNKVKSGDDISVLCTVLGEPDVEVefTWIFPGQKDERPVTIQDTWRLIHRGLgHTTRISQSvitvedfetiDAGY 354
Cdd:cd20949   3 TENAYVTTVKEGQSATILCEVKGEPQPNV--TWHFNGQPISASVADMSKYRILADGL-LINKVTQD----------DTGE 69

                        90
                ....*....|
gi 74762141 355 YICTAQNLQG 364
Cdd:cd20949  70 YTCRAYQVNS 79