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 568938953 334 FISVKHRKQPVQETTAGRRSYRLSMKVKAFPSPEIVWLKDGSPATLKSARYLVHGYSLIIKDVTTEDAGDYTILLGIKQS 413
Cdd:cd07702    1 FITVKHRKQQVLETFAGQKSYRLSMKVKAFPSPEVIWLKDGLPATEKCARYLTRGYSLIIKDVTEEDAGNYTILLSIKQS 80

                         90
                 ....*....|..
gi 568938953 414 RLFKNLTATLIV 425
Cdd:cd07702   81 NLFKNLTATLIV 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568938953 447 LGSRQVLTCTVYGIPRPTITWLwhpchHNhskerydfcteneesfildpssnlGNRIESISQRMTVIEGTnKTVSTLVVA 526
Cdd:cd20978   15 GGQDVTLPCQVTGVPQPKITWL-----HN------------------------GKPLQGPMERATVEDGT-LTIINVQPE 64

                         90       100
                 ....*....|....*....|....*..
gi 568938953 527 DSqtpGIYSCRAFNKIGTVERNIKFYV 553
Cdd:cd20978   65 DT---GYYGCVATNEIGDIYTETLLHV 88

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
                  ....*....|....*....|....*....|....*....|....*
gi 568938953  662 PHLLQNLSDYEVSISGSTTLDCQARGVPAPQITWFKNNHKIQQEP 706
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSD 45

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568938953   32 PELSLKGTQHVMQAGQTLFLKCRgeaAHSWSLPTTVSQEDKRLSITPPSACGRDNRQFcSTLTLDTAQANHTGLYTCR 109
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCE---ATGSPPPTITWYKNGEPISSGSTRSRSLSGSN-STLTISNVTRSDAGTYTCV 75

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 1 (VEGFR-1); 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 1 (VEGFR-1). 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-1 binds VEGF-A strongly; 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-1 may play an inhibitory role in the function of VEGFR-2 by binding VEGF-A and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis and 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 568938953 334 FISVKHRKQPVQETTAGRRSYRLSMKVKAFPSPEIVWLKDGSPATLKSARYLVHGYSLIIKDVTTEDAGDYTILLGIKQS 413
Cdd:cd07702    1 FITVKHRKQQVLETFAGQKSYRLSMKVKAFPSPEVIWLKDGLPATEKCARYLTRGYSLIIKDVTEEDAGNYTILLSIKQS 80

                         90
                 ....*....|..
gi 568938953 414 RLFKNLTATLIV 425
Cdd:cd07702   81 NLFKNLTATLIV 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 568938953   238 PSPVRLLHGQTLVLNCTATTelNTRVQMSWNYPGKatKRASIRQRIDRSHSHNNvfhSVLKINNVESRDKGLYTCRVKSG 317
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASG--SPPPEVTWYKQGG--KLLAESGRFSVSRSGST---STLTISNVTPEDSGTYTCAATNS 73

                           90
                   ....*....|..
gi 568938953   318 SSFQSFNTSVHV 329
Cdd:smart00410  74 SGSASSGTTLTV 85

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568938953 447 LGSRQVLTCTVYGIPRPTITWLwhpchHNhskerydfcteneesfildpssnlGNRIESISQRMTVIEGTnKTVSTLVVA 526
Cdd:cd20978   15 GGQDVTLPCQVTGVPQPKITWL-----HN------------------------GKPLQGPMERATVEDGT-LTIINVQPE 64

                         90       100
                 ....*....|....*....|....*..
gi 568938953 527 DSqtpGIYSCRAFNKIGTVERNIKFYV 553
Cdd:cd20978   65 DT---GYYGCVATNEIGDIYTETLLHV 88

Immunoglobulin I-set domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 568938953  662 PHLLQNLSDYEVSISGSTTLDCQARGVPAPQITWFKNNHKIQQEP 706
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSD 45

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568938953  570 EGEDLKLSCVVNKFLYRDITWillrTVNNRTMHHsiskQKMATTQDYSITLNLVIKNVSLEDSGTYACRARN 641
Cdd:pfam13927  15 EGETVTLTCEATGSPPPTITW----YKNGEPISS----GSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 568938953   355 RLSMKVKAFPSPEIVWLKDGSPATLKSARYLVHG----YSLIIKDVTTEDAGDYT 405
Cdd:smart00410  13 TLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRsgstSTLTISNVTPEDSGTYT 67

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568938953  428 KPQIyeksvSSLPSPPLYPLGSRQVLTCTVYGIPRPTITWLWHpchhnhskerydfcteneesfildpssnlGNRIESIS 507
Cdd:pfam13927   1 KPVI-----TVSPSSVTVREGETVTLTCEATGSPPPTITWYKN-----------------------------GEPISSGS 46

                          90       100       110
                  ....*....|....*....|....*....|...
gi 568938953  508 QRMTVIEGTNKTVSTLVVADSQTpGIYSCRAFN 540
Cdd:pfam13927  47 TRSRSLSGSNSTLTISNVTRSDA-GTYTCVASN 78

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568938953   144 PKLVHMTEGRQLIIPCRVTS-PNVTVTLKKFPFDTLTPDGqRITWDSRRG---FIIANATYKEIGLLNCEATVNGHLYQT 219
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGsPPPEVTWYKQGGKLLAESG-RFSVSRSGStstLTISNVTPEDSGTYTCAATNSSGSASS 79

                   .
gi 568938953   220 N 220
Cdd:smart00410  80 G 80

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568938953   32 PELSLKGTQHVMQAGQTLFLKCRgeaAHSWSLPTTVSQEDKRLSITPPSACGRDNRQFcSTLTLDTAQANHTGLYTCR 109
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCE---ATGSPPPTITWYKNGEPISSGSTRSRSLSGSN-STLTISNVTRSDAGTYTCV 75

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 1 (VEGFR-1); 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 1 (VEGFR-1). 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-1 binds VEGF-A strongly; 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-1 may play an inhibitory role in the function of VEGFR-2 by binding VEGF-A and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis and 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 568938953 334 FISVKHRKQPVQETTAGRRSYRLSMKVKAFPSPEIVWLKDGSPATLKSARYLVHGYSLIIKDVTTEDAGDYTILLGIKQS 413
Cdd:cd07702    1 FITVKHRKQQVLETFAGQKSYRLSMKVKAFPSPEVIWLKDGLPATEKCARYLTRGYSLIIKDVTEEDAGNYTILLSIKQS 80

                         90
                 ....*....|..
gi 568938953 414 RLFKNLTATLIV 425
Cdd:cd07702   81 NLFKNLTATLIV 92

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 568938953 334 FISVKHRKQPVQETTAGRRSYRLSMKVKAFPSPEIVWLKDGSPATLKsARYLVhGYSLIIKDVTTEDAGDYTILLGIKQS 413
Cdd:cd04976    1 FITVKHRKQQVLEATAGKRSVRLPMKVKAYPPPEVVWYKDGLPLTEK-ARYLT-RHSLIIKEVTEEDTGNYTILLSNKQS 78

                         90
                 ....*....|..
gi 568938953 414 RLFKNLTATLIV 425
Cdd:cd04976   79 NVFKNLTATLVV 90

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 3 (VEGFR-3); 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 3 (VEGFR-3). 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-3 (Flt-4) binds two members of the VEGF family (VEGF-C and VEGF-D) and is 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 568938953 334 FISVKHRKQPVQETTAGRRSYRLSMKVKAFPSPEIVWLKDGSpatLKSARYLVHgySLIIKDVTTEDAGDYTILLGIKQS 413
Cdd:cd05863    2 FISVEWRKGPVIEATAGDELVKLPVKVAAYPPPEFQWYKDGK---LISGKHSPH--SLQIKDVTEASAGTYTLVLWNSAA 76

                         90
                 ....*....|..
gi 568938953 414 RLFKNLTATLIV 425
Cdd:cd05863   77 GLEKRISLELIV 88

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 568938953 334 FISVKHRKQPVQETTAGRRSyRLSMKVKAFPSPEIVWLKDGSPatLKSARYLVHGYSLIIKDVTTEDAGDYTILLGIKQS 413
Cdd:cd05864    1 FIALGSGMESLVEAKVGERV-RIPVKYLGYPPPEIKWYKNGIP--IESNHTIKAGHVLTIMEVTEKDAGNYTVVLTNPIS 77

                         90
                 ....*....|..
gi 568938953 414 RLFKNLTATLIV 425
Cdd:cd05864   78 KEKQRHTFSLVV 89

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568938953 340 RKQPVQETTAGRrSYRLSMKVKAFPSPEIVWLKDGSPATLKSA--RYLVHG--YSLIIKDVTTEDAGDYTIL 407
Cdd:cd05744    5 QAPGDLEVQEGR-LCRFDCKVSGLPTPDLFWQLNGKPVRPDSAhkMLVRENgrHSLIIEPVTKRDAGIYTCI 75

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568938953   570 EGEDLKLSCVVNKFLYRDITWIllrtvnnRTMHHSISKQKMATTQDYSITLNLVIKNVSLEDSGTYACRARN 641
Cdd:smart00410   8 EGESVTLSCEASGSPPPEVTWY-------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 568938953 349 AGRrSYRLSMKVKAFPSPEIVWLKDGSPATLkSARYLVHGY----SLIIKDVTTEDAGDYTILLgikqsrlfKNL--TAT 422
Cdd:cd05748    6 AGE-SLRLDIPIKGRPTPTVTWSKDGQPLKE-TGRVQIETTasstSLVIKNAKRSDSGKYTLTL--------KNSagEKS 75

                 ....*.
gi 568938953 423 LIVNVK 428
Cdd:cd05748   76 ATINVK 81

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568938953  237 PPSPVRLLHGQTLVLNCTATTelNTRVQMSWNYPGKATKRASIRQRidrshsHNNVFHSVLKINNVESRDKGLYTCRVK 315
Cdd:pfam13927   7 SPSSVTVREGETVTLTCEATG--SPPPTITWYKNGEPISSGSTRSR------SLSGSNSTLTISNVTRSDAGTYTCVAS 77

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568938953  570 EGEDLKLSCVVNKFLYRDITWillrTVNNRTMHHsiskQKMATTQDYSITLNLVIKNVSLEDSGTYACRARN 641
Cdd:pfam13927  15 EGETVTLTCEATGSPPPTITW----YKNGEPISS----GSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568938953  235 IRPPSPVRLLHGQTLVLNCTATTELNTRVqmSWNYPGKATkRASIRQRIDRSHSHnnvfhSVLKINNVESRDKGLYTCRV 314
Cdd:pfam07679   4 TQKPKDVEVQEGESARFTCTVTGTPDPEV--SWFKDGQPL-RSSDRFKVTYEGGT-----YTLTISNVQPDDSGKYTCVA 75

                          90
                  ....*....|....*
gi 568938953  315 KSGSSFQSFNTSVHV 329
Cdd:pfam07679  76 TNSAGEAEASAELTV 90

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 568938953   355 RLSMKVKAFPSPEIVWLKDGSPATLKSARYLVHG----YSLIIKDVTTEDAGDYT 405
Cdd:smart00410  13 TLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRsgstSTLTISNVTPEDSGTYT 67

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 568938953 662 PHLLQNLSDYEVSISGSTTLDCQARGVPAPQITWFKNNHKIQ 703
Cdd:cd05744    1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVR 42

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 568938953  662 PHLLQNLSDYEVSISGSTTLDCQARGVPAPQITWFKNNHKIQQEPD 707
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGST 47

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 568938953 355 RLSMKVKAFPSPEIVWLKDGSPATlKSARYLV-----HGYSLIIKDVTTEDAGDYT 405
Cdd:cd20973   16 RFDCKVEGYPDPEVKWMKDDNPIV-ESRRFQIdqdedGLCSLIISDVCGDDSGKYT 70

Fourth immunoglobulin (Ig)-like domain of platelet-derived growth factor receptor (PDGFR); The members here are composed of the fourth immunoglobulin (Ig)-like domain of platelet-derived growth factor receptor (PDGFR; also known as cluster of differentiation (CD) 140a) alpha and beta. PDGF is a potent mitogen for connective tissue cells. PDGF-stimulated processes are mediated by three different PDGFs (PDGF-A,PDGF-B, and PDGF-C). PDGFR alpha binds to all three PDGFs, whereas the PDGFR beta binds only to PDGF-B. PDGF alpha is organized as an extracellular component having five Ig-like domains, a transmembrane segment, and a cytoplasmic portion having protein tyrosine kinase activity. In mice, PDGFR alpha and PDGFR beta are essential for normal development.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568938953 333 GFISVKHRKQPVqETTAGRRSYRLSMKVKAFPSPEIVWLKDGSP------------ATLKSARYlVHGYSLIikDVTTED 400
Cdd:cd05859    1 GFIALKPTFGQL-EFANLHEVKEFVVEVEAYPPPQIRWLKDNRTlienlteittstRNVQETRY-VSKLKLI--RAKEED 76

                         90       100
                 ....*....|....*....|....*..
gi 568938953 401 AGDYTILlgIKQSRLFKNLTATLIVNV 427
Cdd:cd05859   77 SGLYTAL--AQNEDAVKSYTFALQIQV 101

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk 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. 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 titin Z1z2 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
                 ....*....|....*....|....*....|....*....|....*..
gi 568938953 661 APHLLQNLSDYEVSISGSTTLDCQARGVPAPQITWFKNNHKIQQEPD 707
Cdd:cd20972    1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPD 47

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568938953 359 KVKAFPSPEIVWLKDGSPATLKSA---RYLVHGYSLIIKDVTTEDAGDYTI----LLGIKQSRLFKNL 419
Cdd:cd20949   22 EVKGEPQPNVTWHFNGQPISASVAdmsKYRILADGLLINKVTQDDTGEYTCrayqVNSIASDMQERTV 89

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 568938953  570 EGEDLKLSC-VVNKFLYRDITWILLRTVNNRTMHHSiskqkmaTTQDYSITLNLVIKNVSLEDSGTYACRARN 641
Cdd:pfam00047  10 EGDSATLTCsASTGSPGPDVTWSKEGGTLIESLKVK-------HDNGRTTQSSLLISNVTKEDAGTYTCVVNN 75

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of 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 (Slit1, Slit2, Slit3), 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 Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 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 Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 568938953 662 PHLLQNLSDYEVSISGSTTLDCQARGVPAPQITWFKNNHKIQQEPD 707
Cdd:cd07693    1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETDKD 46

Second immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R), and similar domains; The members here are composed of the second immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R; also known as cluster of differentiation (CD) 121). IL-1 alpha and IL-1 beta are cytokines which participate in the regulation of inflammation, immune responses, and hematopoiesis. These cytokines bind to the IL-1 receptor type 1 (IL1R1), which is activated on additional association with interleukin-1 receptor accessory protein (IL1RAP). IL-1 also binds a second receptor designated type II (IL1R2). Mature IL1R1 consists of three IG-like domains, a transmembrane domain, and a large cytoplasmic domain. Mature IL1R2 is organized similarly except that it has a short cytoplasmic domain. The latter does not initiate signal transduction. A naturally occurring cytokine IL-1RA (IL-1 receptor antagonist) is widely expressed and binds to IL-1 receptors, inhibiting the binding of IL-1 alpha and IL-1 beta. This group also contains ILIR-like 1 (IL1R1L) which maps to the same chromosomal location as IL1R1 and IL1R2.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 568938953 365 SPEIVWLKDGSPATLKSaRYLVHGYSLIIKDVTTEDAGDYT 405
Cdd:cd05757   29 LPPIQWYKDCKPLQGDK-RFIPKGSKLLIQNVTEEDAGNYT 68

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568938953 340 RKQPVQETTAGRRSYRLSM--KVKAFPSPEIVWLKDGSPATLKSARYLVHGYSLIIKDVTTEDAGDYT 405
Cdd:cd04969    4 ELNPVKKKILAAKGGDVIIecKPKASPKPTISWSKGTELLTNSSRICILPDGSLKIKNVTKSDEGKYT 71

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
                 ....*....|....*....|....*..
gi 568938953 680 TLDCQARGVPAPQITWFKNNHKIQQEP 706
Cdd:cd00096    2 TLTCSASGNPPPTITWYKNGKPLPPSS 28

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 568938953 249 LVLNCTATTelNTRVQMSWNYPGKATKRASIRQRIDRSHShnnvfhSVLKINNVESRDKGLYTCRVK 315
Cdd:cd00096    1 VTLTCSASG--NPPPTITWYKNGKPLPPSSRDSRRSELGN------GTLTISNVTLEDSGTYTCVAS 59

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568938953 246 GQTLVLNCTATTElNTRVQMSWNYPGKATKRA-SIRQRIdrshsHNNVFHSVLKINNVESRDKGLYTCRVKSGSSFQSFN 324
Cdd:cd05750   14 GSKLVLKCEATSE-NPSPRYRWFKDGKELNRKrPKNIKI-----RNKKKNSELQINKAKLEDSGEYTCVVENILGKDTVT 87

                 ....*
gi 568938953 325 TSVHV 329
Cdd:cd05750   88 GNVTV 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 568938953   144 PKLVHMTEGRQLIIPCRVTS-PNVTVTLKKFPFDTLTPDGqRITWDSRRG---FIIANATYKEIGLLNCEATVNGHLYQT 219
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGsPPPEVTWYKQGGKLLAESG-RFSVSRSGStstLTISNVTPEDSGTYTCAATNSSGSASS 79

                   .
gi 568938953   220 N 220
Cdd:smart00410  80 G 80