Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R); 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). 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 (also known as Flt-1), VEGFR-2 (also known as KDR or Flk-1) and VEGFR-3 (also known as 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-2 and -1 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421860 204 IDVQISTPRPVKLLRGHTLVLNCTATTPLNTRVQMTWSYPDEKN-KRASVRRRIDQSNSHANIFYSVLTIDKMQNKDKGL 282
Cdd:cd05862     1 YDVQLSPPKPVELLVGEKLVLNCTARTELNVGVDFQWDYPGKKEqRRASVRRRRKQQSSEATEFSSTLTIDNVTLSDKGL 80

                          90       100
                  ....*....|....*....|..
gi 1139421860 283 YTCRVRSGPSFKSVNTSVHIYD 304
Cdd:cd05862    81 YTCAASSGPMFKKNSTSVIVHE 102

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421860 401 KPQIyekavSSFPDPALYPLGSRQILTCTAYGIPQPTIKWFWhpcnhnhsearcdfcsnneesfildadsnMGNRIESIT 480
Cdd:pfam13927   1 KPVI-----TVSPSSVTVREGETVTLTCEATGSPPPTITWYK-----------------------------NGEPISSGS 46

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1139421860 481 QRMAIIEGKNkmaSTLVVADSRI--SGIYICIASN 513
Cdd:pfam13927  47 TRSRSLSGSN---STLTISNVTRsdAGTYTCVASN 78

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R); 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). 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 (also known as Flt-1), VEGFR-2 (also known as KDR or Flk-1) and VEGFR-3 (also known as 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-2 and -1 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421860 204 IDVQISTPRPVKLLRGHTLVLNCTATTPLNTRVQMTWSYPDEKN-KRASVRRRIDQSNSHANIFYSVLTIDKMQNKDKGL 282
Cdd:cd05862     1 YDVQLSPPKPVELLVGEKLVLNCTARTELNVGVDFQWDYPGKKEqRRASVRRRRKQQSSEATEFSSTLTIDNVTLSDKGL 80

                          90       100
                  ....*....|....*....|..
gi 1139421860 283 YTCRVRSGPSFKSVNTSVHIYD 304
Cdd:cd05862    81 YTCAASSGPMFKKNSTSVIVHE 102

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1139421860  542 TEGEDLKLSCTVNKFLYRDVTWILlrtvNNRTMHysISKQKMAITKEHSiTLNLTIMNVSLQDSGTYACRARN 614
Cdd:smart00410   7 KEGESVTLSCEASGSPPPEVTWYK----QGGKLL--AESGRFSVSRSGS-TSTLTISNVTPEDSGTYTCAATN 72

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421860 209 STPRPVKLLRGHTLVLNCTATTPlNTRVQMTWSYPDEKNKRASVRRRIDQSNSHanifySVLTIDKMQNKDKGLYTCRVR 288
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSASTG-SPGPDVTWSKEGGTLIESLKVKHDNGRTTQ-----SSLLISNVTKEDAGTYTCVVN 74

                          90
                  ....*....|..
gi 1139421860 289 SGPSFKSVNTSV 300
Cdd:pfam00047  75 NPGGSATLSTSL 86

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1139421860 542 TEGEDLKLSCTVNKFLYRDVTWILLRTVNNRTMHYSISKQkmaitkehSITLNLTIMNVSLQDSGTYACRARN 614
Cdd:pfam13927  14 REGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLS--------GSNSTLTISNVTRSDAGTYTCVASN 78

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421860 401 KPQIyekavSSFPDPALYPLGSRQILTCTAYGIPQPTIKWFWhpcnhnhsearcdfcsnneesfildadsnMGNRIESIT 480
Cdd:pfam13927   1 KPVI-----TVSPSSVTVREGETVTLTCEATGSPPPTITWYK-----------------------------NGEPISSGS 46

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1139421860 481 QRMAIIEGKNkmaSTLVVADSRI--SGIYICIASN 513
Cdd:pfam13927  47 TRSRSLSGSN---STLTISNVTRsdAGTYTCVASN 78

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421860 420 LGSRQILTCTAYGIPQPTIKWFwhpcnHNhsearcdfcsnneesfildadsnmGNRIESITQRMAIIEGknkmasTLVVA 499
Cdd:cd20978    15 GGQDVTLPCQVTGVPQPKITWL-----HN------------------------GKPLQGPMERATVEDG------TLTII 59

                          90       100
                  ....*....|....*....|....*....
gi 1139421860 500 DSRIS--GIYICIASNKVGTVGRNISFYI 526
Cdd:cd20978    60 NVQPEdtGYYGCVATNEIGDIYTETLLHV 88

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R); 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). 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 (also known as Flt-1), VEGFR-2 (also known as KDR or Flk-1) and VEGFR-3 (also known as 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-2 and -1 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421860 204 IDVQISTPRPVKLLRGHTLVLNCTATTPLNTRVQMTWSYPDEKN-KRASVRRRIDQSNSHANIFYSVLTIDKMQNKDKGL 282
Cdd:cd05862     1 YDVQLSPPKPVELLVGEKLVLNCTARTELNVGVDFQWDYPGKKEqRRASVRRRRKQQSSEATEFSSTLTIDNVTLSDKGL 80

                          90       100
                  ....*....|....*....|..
gi 1139421860 283 YTCRVRSGPSFKSVNTSVHIYD 304
Cdd:cd05862    81 YTCAASSGPMFKKNSTSVIVHE 102

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor (VEGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor (VEGFR). 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). VEGFRs bind VEGFs with high affinity at 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 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 1139421860 307 FITVKHRKQQVLETVAGKRSYRLSMKVKAFPSPEVVWLKDGLPATEKsARYLTRgYSLIIKDVTEEDAGNYTILLSIKQS 386
Cdd:cd04976     1 FITVKHRKQQVLEATAGKRSVRLPMKVKAYPPPEVVWYKDGLPLTEK-ARYLTR-HSLIIKEVTEEDTGNYTILLSNKQS 78

                          90
                  ....*....|..
gi 1139421860 387 NVFKNLTATLIV 398
Cdd:cd04976    79 NVFKNLTATLVV 90

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 2 (VEGFR-2); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 2 (VEGFR-2). 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. VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGFR-2 (KDR/Flk-1) is a major mediator of the mitogenic, angiogenic and microvascular permeability-enhancing effects of VEGF-A; 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. VEGF-A also interacts with VEGFR-1, which it binds more strongly than VEGFR-2. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. 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 1139421860 307 FITVKHRKQQVLETVAGKRSyRLSMKVKAFPSPEVVWLKDGLPATEKSARYltRGYSLIIKDVTEEDAGNYTILLSIKQS 386
Cdd:cd05864     1 FIALGSGMESLVEAKVGERV-RIPVKYLGYPPPEIKWYKNGIPIESNHTIK--AGHVLTIMEVTEKDAGNYTVVLTNPIS 77

                          90
                  ....*....|..
gi 1139421860 387 NVFKNLTATLIV 398
Cdd:cd05864    78 KEKQRHTFSLVV 89

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1139421860 328 RLSMKVKAFPSPEVVWLKDGLPATEkSARYLTR----GYSLIIKDVTEEDAGNYTillsIKQSNVFKNLTATLIVNV 400
Cdd:pfam07679  19 RFTCTVTGTPDPEVSWFKDGQPLRS-SDRFKVTyeggTYTLTISNVQPDDSGKYT----CVATNSAGEAEASAELTV 90

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421860  211 PRPVKLLRGHTLVLNCTATTplNTRVQMTWSYPDEKNKRASVRRRIDQSNSHanifySVLTIDKMQNKDKGLYTCRVRSG 290
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASG--SPPPEVTWYKQGGKLLAESGRFSVSRSGST-----STLTISNVTPEDSGTYTCAATNS 73

                           90
                   ....*....|..
gi 1139421860  291 PSFKSVNTSVHI 302
Cdd:smart00410  74 SGSASSGTTLTV 85

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421860 209 STPRPVKLLRGHTLVLNCTATTPlNTRVQMTWSYPDEKNKRASVRRRIDQSNSHanifySVLTIDKMQNKDKGLYTCRVR 288
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSASTG-SPGPDVTWSKEGGTLIESLKVKHDNGRTTQ-----SSLLISNVTKEDAGTYTCVVN 74

                          90
                  ....*....|..
gi 1139421860 289 SGPSFKSVNTSV 300
Cdd:pfam00047  75 NPGGSATLSTSL 86

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
                  ....*....|....*....|....*....|....*....|....*....|
gi 1139421860 332 KVKAFPSPEVVWLKDG---LPATEKSARYLTRGYSLIIKDVTEEDAGNYT 378
Cdd:cd00096     6 SASGNPPPTITWYKNGkplPPSSRDSRRSELGNGTLTISNVTLEDSGTYT 55

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1139421860  328 RLSMKVKAFPSPEVVWLKDGLPATEKSARYL----TRGYSLIIKDVTEEDAGNYTILLSIKQSNVFKnlTATLIV 398
Cdd:smart00410  13 TLSCEASGSPPPEVTWYKQGGKLLAESGRFSvsrsGSTSTLTISNVTPEDSGTYTCAATNSSGSASS--GTTLTV 85

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 1139421860 308 ITVKHRKQQVLEtvagKRSYRLSMKVKAFPSPEVVWLKDGLPATEKSA----RYLTRGY--SLIIKDVTEEDAGNYtill 381
Cdd:cd20951     3 FIIRLQSHTVWE----KSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIpgkyKIESEYGvhVLHIRRVTVEDSAVY---- 74

                          90       100
                  ....*....|....*....|
gi 1139421860 382 SIKQSNVFKNLTATLIVNVK 401
Cdd:cd20951    75 SAVAKNIHGEASSSASVVVE 94

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1139421860 309 TVKHRKQQVLETVAGKRSYRLSMKVKAFPSPEVVWLKDGLPATEKSARYLTR--GYSLIIKDVTEEDAGNYT 378
Cdd:cd05730     3 TIRARQSEVNATANLGQSVTLACDADGFPEPTMTWTKDGEPIESGEEKYSFNedGSEMTILDVDKLDEAEYT 74

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1139421860 542 TEGEDLKLSCTVNKFLYRDVTWILLRTVNNRTMHYSISKQkmaitkehSITLNLTIMNVSLQDSGTYACRARN 614
Cdd:pfam13927  14 REGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLS--------GSNSTLTISNVTRSDAGTYTCVASN 78

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
                  ....*....|....*....|....*....|....*....|....*
gi 1139421860 334 KAFPSPEVVWLKDGLPATEKSARYLTR-GYSLIIKDVTEEDAGNY 377
Cdd:cd05724    23 RGHPEPTVSWRKDGQPLNLDNERVRIVdDGNLLIAEARKSDEGTY 67

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1139421860 320 TVAGKRSYRLSMKVKAFPSPEVVWLKDGLPATEKSA-RYLTRG---YSLIIKDVTEEDAGNYTIL 380
Cdd:cd20990    11 TVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAhKMLVREngvHSLIIEPVTSRDAGIYTCI 75

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421860  117 PEIIHMTEGRELVIPCRVTS-PNITVTLKKFPLDTLIPDGkRIIWDSRKG---FIISNATYKEIGLLTCEATVNGHLYKT 192
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGsPPPEVTWYKQGGKLLAESG-RFSVSRSGStstLTISNVTPEDSGTYTCAATNSSGSASS 79

                   .
gi 1139421860  193 N 193
Cdd:smart00410  80 G 80

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421860 311 KHRKQQVLETVAGkrSYRLSMKVKAFPSPEVVWLKDGLPAT-EKSARYLTRGYSLIIKDVTEEDAGNYTILLsikqSNVF 389
Cdd:cd05856     8 KMRRRVIARPVGS--SVRLKCVASGNPRPDITWLKDNKPLTpPEIGENKKKKWTLSLKNLKPEDSGKYTCHV----SNRA 81

                          90
                  ....*....|.
gi 1139421860 390 KNLTATLIVNV 400
Cdd:cd05856    82 GEINATYKVDV 92

C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421860 320 TVAGKRSYRLSMKVKAFPSPEVVWLKDGlPATEKSARYLT-----RGYSLIIKDVTEEDAGNYTILLsikqSNVFKNLTA 394
Cdd:cd05891    12 TIMEGKTLNLTCTVFGNPDPEVIWFKND-QDIELSEHYSVkleqgKYASLTIKGVTSEDSGKYSINV----KNKYGGETV 86

                  ....*.
gi 1139421860 395 TLIVNV 400
Cdd:cd05891    87 DVTVSV 92

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 1139421860 318 LETVAGKrSYRLSMKVKAFPSPEVVWLKDGLPATEKSARYLTRGYS--LIIKDVTEEDAGNYTILlsikQSNVFKNLTAT 395
Cdd:cd20976    11 LEAVEGQ-DFVAQCSARGKPVPRITWIRNAQPLQYAADRSTCEAGVgeLHIQDVLPEDHGTYTCL----AKNAAGQVSCS 85

                  ....*
gi 1139421860 396 LIVNV 400
Cdd:cd20976    86 AWVTV 90

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421860 313 RKQQVLETVAGKRSYRLSM--KVKAFPSPEVVWLKDGLPATEKSARYLTRGYSLIIKDVTEEDAGNYTILlsikQSNVF- 389
Cdd:cd04969     4 ELNPVKKKILAAKGGDVIIecKPKASPKPTISWSKGTELLTNSSRICILPDGSLKIKNVTKSDEGKYTCF----AVNFFg 79

                          90
                  ....*....|
gi 1139421860 390 -KNLTATLIV 398
Cdd:cd04969    80 kANSTGSLSV 89

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421860 208 ISTPRPVKLLRGHTLVLNCTAT---TPlntrvQMTWSYPDEKnKRASVRRRIDQSNSHanifySVLTIDKMQNKDKGLYT 284
Cdd:pfam07679   4 TQKPKDVEVQEGESARFTCTVTgtpDP-----EVSWFKDGQP-LRSSDRFKVTYEGGT-----YTLTISNVQPDDSGKYT 72

                  ...
gi 1139421860 285 CRV 287
Cdd:pfam07679  73 CVA 75

First immunoglobulin (Ig)-like domain of neural cell adhesion molecule (NCAM-1); 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-1). NCAM-1 plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-nonNCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves the Ig1, Ig2, and Ig3 domains. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. 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 1139421860 540 MPTEGEdlkLSCTVNKFL---------YRDVTWIllrTVNNRTMhySISKQKMAITKEHSITLNLTIMNVSLQDSGTYAC 610
Cdd:cd05865     6 VPSQGE---ISVGESKFFlcqvageakDKDISWF---SPNGEKL--TPNQQRISVVRNDDYSSTLTIYNANIDDAGIYKC 77

                  ....*....
gi 1139421860 611 RARNVYTGE 619
Cdd:cd05865    78 VVSNEDEGE 86

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1139421860 333 VKAFPSPEVVWLKDGLPATEKSARYLT---RGYSLIIKDVTEEDAGNYT 378
Cdd:cd05736    24 AEGIPLPRVQWLKNGMDINPKLSKQLTliaNGSELHISNVRYEDTGAYT 72

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R); 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). 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 (also known as Flt-1), VEGFR-2 (also known as KDR or Flk-1) and VEGFR-3 (also known as 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-2 and -1 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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1139421860 544 GEDLKLSCTVNKFLYR--DVTWILLRTVNNR--TMHYSISKQKMAITKEHSItlnLTIMNVSLQDSGTYACRARN 614
Cdd:cd05862    16 GEKLVLNCTARTELNVgvDFQWDYPGKKEQRraSVRRRRKQQSSEATEFSST---LTIDNVTLSDKGLYTCAASS 87

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 1139421860 532 GFHVNLEKMPTE---GEDLKLSCTV--NKFLYRDVTWILLRTVNNR--TMHYSISKQKMAITKEHSItlnLTIMNVSLQD 604
Cdd:cd05742     2 DLELSPNAEPTVlpqGETLVLNCTAnvNLNEVVDFQWTYPSEKEGKlaLLKPDIKVDWSEPGEFVST---LTIPEATLKD 78

                  ....*....
gi 1139421860 605 SGTYACRAR 613
Cdd:cd05742    79 SGTYTCAAR 87

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1139421860 542 TEGEDLKLSCTVNKFLYRDVTWillrtvnnrtmhysiSKQKMAITKEHsitlNLTIMNVSLQDSGTYACRARNVYTGE 619
Cdd:pfam13895  12 TEGEPVTLTCSAPGNPPPSYTW---------------YKDGSAISSSP----NFFTLSVSAEDSGTYTCVARNGRGGK 70

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 is comprised of an extracellular region having six Ig-like domains and 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, and 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 1139421860 328 RLSMKVKAFPSPEVVWLKDGLP--ATEKSARYLTRGYSLIIKDVTEEDagnyTILLSIKQSNVFKNLTATLIVNV 400
Cdd:cd05867    18 RLDCQVEGIPTPNITWSINGAPieGTDPDPRRHVSSGALILTDVQPSD----TAVYQCEARNRHGNLLANAHVHV 88

C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1139421860 543 EGEDLKLSCTVNKFLYRDVTWILLRTVNNRTMHYSISKqkmaitkEHSITLNLTIMNVSLQDSGTYACRARNVYTGEEI 621
Cdd:cd05891    15 EGKTLNLTCTVFGNPDPEVIWFKNDQDIELSEHYSVKL-------EQGKYASLTIKGVTSEDSGKYSINVKNKYGGETV 86

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and 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. 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" strands in the other.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1139421860 542 TEGEDLKLSCTVNK-FLYRDVTWI----------LLRTVNNRTMHYSISKQKMAITKEHSITLNLTIMNVSLQDSGTYAC 610
Cdd:cd00099    11 QEGESVTLSCEVSSsFSSTYIYWYrqkpgqgpefLIYLSSSKGKTKGGVPGRFSGSRDGTSSFSLTISNLQPEDSGTYYC 90