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 827835089 231 DVQISPPSPVRFLRGQTLVLNCTVTTDLNTRVQMSWNYPG-KATKRASIRQRIDQSNPHSNVFHSVLKINNVESRDKGLY 309
Cdd:cd05862    2 DVQLSPPKPVELLVGEKLVLNCTARTELNVGVDFQWDYPGkKEQRRASVRRRRKQQSSEATEFSSTLTIDNVTLSDKGLY 81

                         90       100
                 ....*....|....*....|.
gi 827835089 310 TCRVKSGSSFRTFNTSVHVYE 330
Cdd:cd05862   82 TCAASSGPMFKKNSTSVIVHE 102

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 827835089 447 GSRQVLTCTVYGIPQPTIKWLwhpchynhskeRNdfcfgseesfildsssniGNRIEGITQRMMVIE-GTNKTVSTLVVA 525
Cdd:cd20970   17 GENATFMCRAEGSPEPEISWT-----------RN------------------GNLIIEFNTRYIVREnGTTLTIRNIRRS 67

                         90       100
                 ....*....|....*....|....*...
gi 827835089 526 DSrtpGIYSCKAFNKI-GTVERDIRFYV 552
Cdd:cd20970   68 DM---GIYLCIASNGVpGSVEKRITLQV 92

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 827835089 231 DVQISPPSPVRFLRGQTLVLNCTVTTDLNTRVQMSWNYPG-KATKRASIRQRIDQSNPHSNVFHSVLKINNVESRDKGLY 309
Cdd:cd05862    2 DVQLSPPKPVELLVGEKLVLNCTARTELNVGVDFQWDYPGkKEQRRASVRRRRKQQSSEATEFSSTLTIDNVTLSDKGLY 81

                         90       100
                 ....*....|....*....|.
gi 827835089 310 TCRVKSGSSFRTFNTSVHVYE 330
Cdd:cd05862   82 TCAASSGPMFKKNSTSVIVHE 102

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 827835089   237 PSPVRFLRGQTLVLNCTVTTDLNtrVQMSWNYPGKatKRASIRQRIDQSNPHSNvfhSVLKINNVESRDKGLYTCRVKSG 316
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPP--PEVTWYKQGG--KLLAESGRFSVSRSGST---STLTISNVTPEDSGTYTCAATNS 73

                           90
                   ....*....|..
gi 827835089   317 SSFRTFNTSVHV 328
Cdd:smart00410  74 SGSASSGTTLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 827835089  234 ISPPSPVRFLRGQTLVLNCTVTTdlNTRVQMSWNYPGKATKRASIRQRIDQSNphsnvfHSVLKINNVESRDKGLYTCRV 313
Cdd:pfam13927   5 TVSPSSVTVREGETVTLTCEATG--SPPPTITWYKNGEPISSGSTRSRSLSGS------NSTLTISNVTRSDAGTYTCVA 76

                  .
gi 827835089  314 K 314
Cdd:pfam13927  77 S 77

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 827835089 573 LKLSCVVSKFLYRDITWillrTVNNRtmhhSISKQKMATTQDYSITLNLVIKNVSLEDSGTYACRARNIYTGEE 646
Cdd:cd00096    1 VTLTCSASGNPPPTITW----YKNGK----PLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSA 66

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. 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 the MuSK lacks this strand and thus it 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 827835089 447 GSRQVLTCTVYGIPQPTIKWLwhpchynhskeRNdfcfgseesfildsssniGNRIEGITQRMMVIE-GTNKTVSTLVVA 525
Cdd:cd20970   17 GENATFMCRAEGSPEPEISWT-----------RN------------------GNLIIEFNTRYIVREnGTTLTIRNIRRS 67

                         90       100
                 ....*....|....*....|....*...
gi 827835089 526 DSrtpGIYSCKAFNKI-GTVERDIRFYV 552
Cdd:cd20970   68 DM---GIYLCIASNGVpGSVEKRITLQV 92

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 827835089   143 PKLVHMTEGRELIIPCRVTS-PNITVTLKKFPFDALTPDGqRIAWDSRRG---FIIANATYKEIGLLTCEATVNGHLYQT 218
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGsPPPEVTWYKQGGKLLAESG-RFSVSRSGStstLTISNVTPEDSGTYTCAATNSSGSASS 79

                   .
gi 827835089   219 S 219
Cdd:smart00410  80 G 80

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 827835089 231 DVQISPPSPVRFLRGQTLVLNCTVTTDLNTRVQMSWNYPG-KATKRASIRQRIDQSNPHSNVFHSVLKINNVESRDKGLY 309
Cdd:cd05862    2 DVQLSPPKPVELLVGEKLVLNCTARTELNVGVDFQWDYPGkKEQRRASVRRRRKQQSSEATEFSSTLTIDNVTLSDKGLY 81

                         90       100
                 ....*....|....*....|.
gi 827835089 310 TCRVKSGSSFRTFNTSVHVYE 330
Cdd:cd05862   82 TCAASSGPMFKKNSTSVIVHE 102

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 827835089 231 DVQISPPS-PVRFLRGQTLVLNCTVTTDLNTRVQMSWNYPG-KATKRASIRQRIDQSNPHSNVFHSVLKINNVESRDKGL 308
Cdd:cd05742    2 DLELSPNAePTVLPQGETLVLNCTANVNLNEVVDFQWTYPSeKEGKLALLKPDIKVDWSEPGEFVSTLTIPEATLKDSGT 81

                         90       100
                 ....*....|....*....|.
gi 827835089 309 YTCRVKSGSSFRTFNTSVHVY 329
Cdd:cd05742   82 YTCAARSGVMKKEKQTSVSVH 102

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 827835089 333 FISVKHRKQQVQETIAGKRShRLSMKVKAFPSPEVVWLKDGVPAtekSARYSVH-GYSLIIKDVTAEDAGDYTILLGIKQ 411
Cdd:cd05864    1 FIALGSGMESLVEAKVGERV-RIPVKYLGYPPPEIKWYKNGIPI---ESNHTIKaGHVLTIMEVTEKDAGNYTVVLTNPI 76

                         90
                 ....*....|...
gi 827835089 412 SKLFRNLTATLIV 424
Cdd:cd05864   77 SKEKQRHTFSLVV 89

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 827835089   237 PSPVRFLRGQTLVLNCTVTTDLNtrVQMSWNYPGKatKRASIRQRIDQSNPHSNvfhSVLKINNVESRDKGLYTCRVKSG 316
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPP--PEVTWYKQGG--KLLAESGRFSVSRSGST---STLTISNVTPEDSGTYTCAATNS 73

                           90
                   ....*....|..
gi 827835089   317 SSFRTFNTSVHV 328
Cdd:smart00410  74 SGSASSGTTLTV 85

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 827835089   568 TEGEDLKLSCVVSKFLYRDITWIllrtvnnRTMHHSISKQKMATTQDYSITLNLVIKNVSLEDSGTYACRARN 640
Cdd:smart00410   7 KEGESVTLSCEASGSPPPEVTWY-------KQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATN 72

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 827835089 348 AGkRSHRLSMKVKAFPSPEVVWLKDGVPATEkSARYSVHGY----SLIIKDVTAEDAGDYTILLgikqsklfRNL--TAT 421
Cdd:cd05748    6 AG-ESLRLDIPIKGRPTPTVTWSKDGQPLKE-TGRVQIETTasstSLVIKNAKRSDSGKYTLTL--------KNSagEKS 75

                 ....*.
gi 827835089 422 LIVNVK 427
Cdd:cd05748   76 ATINVK 81

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 827835089  568 TEGEDLKLSCVVSKFLYRDITWillrTVNNRTMHHsiskQKMATTQDYSITLNLVIKNVSLEDSGTYACRARN 640
Cdd:pfam13927  14 REGETVTLTCEATGSPPPTITW----YKNGEPISS----GSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. 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 the telokin Ig domain lacks this strand and thus it 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
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 827835089 354 RLSMKVKAFPSPEVVWLKDGVPATEkSARYSV-----HGYSLIIKDVTAEDAGDYT 404
Cdd:cd20973   16 RFDCKVEGYPDPEVKWMKDDNPIVE-SRRFQIdqdedGLCSLIISDVCGDDSGKYT 70

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 827835089   354 RLSMKVKAFPSPEVVWLKDGVPATEKSARYSVHG----YSLIIKDVTAEDAGDYTILLGIKQSKLFRnlTATLIV 424
Cdd:smart00410  13 TLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRsgstSTLTISNVTPEDSGTYTCAATNSSGSASS--GTTLTV 85

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 827835089 358 KVKAFPSPEVVWLKDGVP---ATEKSARYSVHGYSLIIKDVTAEDAGDYT 404
Cdd:cd00096    6 SASGNPPPTITWYKNGKPlppSSRDSRRSELGNGTLTISNVTLEDSGTYT 55

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 827835089 334 ISVKHRKQQVQEtiagKRSHRLSMKVKAFPSPEVVWLKDGVPATEKSA--------RYSVHgySLIIKDVTAEDAGDYTI 405
Cdd:cd20951    3 FIIRLQSHTVWE----KSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIpgkykiesEYGVH--VLHIRRVTVEDSAVYSA 76

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. 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 the MuSK lacks this strand and thus it 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 827835089 447 GSRQVLTCTVYGIPQPTIKWLwhpchynhskeRNdfcfgseesfildsssniGNRIEGITQRMMVIE-GTNKTVSTLVVA 525
Cdd:cd20970   17 GENATFMCRAEGSPEPEISWT-----------RN------------------GNLIIEFNTRYIVREnGTTLTIRNIRRS 67

                         90       100
                 ....*....|....*....|....*...
gi 827835089 526 DSrtpGIYSCKAFNKI-GTVERDIRFYV 552
Cdd:cd20970   68 DM---GIYLCIASNGVpGSVEKRITLQV 92

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. 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
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 827835089 354 RLSMKVKAFPSPEVVWLKDGVPATEKSARYSVH----GY-SLIIKDVTAEDAGDYTI 405
Cdd:cd05892   19 RLECQISAIPPPQIFWKKNNEMLQYNTDRISLYqdncGRiCLLIQNANKKDAGWYTV 75

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 827835089 346 TIAGKRSHRLSMKVKAFPSPEVVWLKDGvPATEKSARYSV-----HGYSLIIKDVTAEDAGDYTI 405
Cdd:cd05891   12 TIMEGKTLNLTCTVFGNPDPEVIWFKND-QDIELSEHYSVkleqgKYASLTIKGVTSEDSGKYSI 75

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 827835089  569 EGEDLKLSCVVSKF-LYRDITWILLRTVNNRTMHHSiskqkmaTTQDYSITLNLVIKNVSLEDSGTYACRARN 640
Cdd:pfam00047  10 EGDSATLTCSASTGsPGPDVTWSKEGGTLIESLKVK-------HDNGRTTQSSLLISNVTKEDAGTYTCVVNN 75

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 827835089 235 SPPSPVRFLRGQTLVLNCTVTTDLNTRVqmSWNYPGKatkrasirqRIDQSNPHSNVFHSVLKINNVESRDKGLYTCRVK 314
Cdd:cd20978    6 KPEKNVVVKGGQDVTLPCQVTGVPQPKI--TWLHNGK---------PLQGPMERATVEDGTLTIINVQPEDTGYYGCVAT 74

                         90
                 ....*....|....
gi 827835089 315 SGSSFRTFNTSVHV 328
Cdd:cd20978   75 NEIGDIYTETLLHV 88

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 827835089 363 PSPEVVWLKDGVPATEkSARYSV--HGYsLIIKDVTAEDAGDY 403
Cdd:cd05746   11 PEPTITWNKDGVQVTE-SGKFHIspEGY-LAIRDVGVADQGRY 51

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 827835089 335 SVKHRKQQVQETIAGkrSHRLSMKVKAFPSPEVVWLKDGVPAT-EKSARYSVHGYSLIIKDVTAEDAGDYT 404
Cdd:cd05856    6 PAKMRRRVIARPVGS--SVRLKCVASGNPRPDITWLKDNKPLTpPEIGENKKKKWTLSLKNLKPEDSGKYT 74

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 827835089  569 EGEDLKLSCVVSKFLYRD---ITWILLRTVNNRT--MHHSISKQKMATTQD-YSITLN-------LVIKNVSLEDSGTYA 635
Cdd:pfam07686  10 LGGSVTLPCTYSSSMSEAstsVYWYRQPPGKGPTflIAYYSNGSEEGVKKGrFSGRGDpsngdgsLTIQNLTLSDSGTYT 89

                          90       100
                  ....*....|....*....|.
gi 827835089  636 CRARNIYTGEEIlRKTEVLVR 656
Cdd:pfam07686  90 CAVIPSGEGVFG-KGTRLTVL 109

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 827835089  427 KPQIyeksvSSLPSPPLYPLGSRQVLTCTVYGIPQPTIKWLwhpchynhskerndfcfgseesfiLDSSSNIGNRiegIT 506
Cdd:pfam13927   1 KPVI-----TVSPSSVTVREGETVTLTCEATGSPPPTITWY------------------------KNGEPISSGS---TR 48

                          90       100       110
                  ....*....|....*....|....*....|...
gi 827835089  507 QRMMVIEGTNKTVSTLVVADSrtpGIYSCKAFN 539
Cdd:pfam13927  49 SRSLSGSNSTLTISNVTRSDA---GTYTCVASN 78

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 827835089 248 LVLNCTVTTDLNTRVqmSWNYPGKATKRASIRQRIDQSNphsnvfHSVLKINNVESRDKGLYTCRVK 314
Cdd:cd00096    1 VTLTCSASGNPPPTI--TWYKNGKPLPPSSRDSRRSELG------NGTLTISNVTLEDSGTYTCVAS 59

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 827835089 569 EGEDLKLSCVVSKFLYRDITWillrTVNNRTMHHSISKQKMATTQDYSITLNLVIKNvsleDSGTYACRARNIY-TGEEI 647
Cdd:cd20949   13 EGQSATILCEVKGEPQPNVTW----HFNGQPISASVADMSKYRILADGLLINKVTQD----DTGEYTCRAYQVNsIASDM 84

                 ....
gi 827835089 648 LRKT 651
Cdd:cd20949   85 QERT 88

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 827835089 236 PPSPVRFLRGQTLVLNCTVTTDLNTrVQMSW--NYPGKA------------TKRASIRQRIDQSNPHSNVFHsvLKINNV 301
Cdd:cd00099    4 SPRSLSVQEGESVTLSCEVSSSFSS-TYIYWyrQKPGQGpefliylssskgKTKGGVPGRFSGSRDGTSSFS--LTISNL 80

                         90
                 ....*....|....*..
gi 827835089 302 ESRDKGLYTCRVKSGSS 318
Cdd:cd00099   81 QPEDSGTYYCAVSESGG 97

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; 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 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 and human neurofascin.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 827835089 570 GEDLKLSCVVSKFLYRDITWILL--RTVNNRTmhhsiskqkmaTTQDYSITLNlvIKNVSLEDSGTYACRARN 640
Cdd:cd05731   10 GGVLLLECIAEGLPTPDIRWIKLggELPKGRT-----------KFENFNKTLK--IENVSEADSGEYQCTASN 69

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 827835089 558 GFHVSLEKIPTE---GEDLKLSCVVSKFLYR--DITWILLRTVNNR--TMHHSISKQKMATTQDYSItlnLVIKNVSLED 630
Cdd:cd05742    2 DLELSPNAEPTVlpqGETLVLNCTANVNLNEvvDFQWTYPSEKEGKlaLLKPDIKVDWSEPGEFVST---LTIPEATLKD 78

                 ....*....
gi 827835089 631 SGTYACRAR 639
Cdd:cd05742   79 SGTYTCAAR 87