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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 763551989  90 YSVQVGHDLKIEVPISGRPKPTITWTKDGHPLKQTTRINVTDSPNLTVLSIKETHKDDGGHYEITVANVVGQKTASIEI 168
Cdd:cd05748    2 IVVRAGESLRLDIPIKGRPTPTVTWSKDGQPLKETGRVQIETTASSTSLVIKNAKRSDSGKYTLTLKNSAGEKSATINV 80

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 763551989   1 SWTKPEHDGGsKIIQYIVEMQAKQSEKWSEC--ARVKSLEAVIANLTQGEEYLFRVIAVNEKGRSDP 65
Cdd:cd00063   20 SWTPPEDDGG-PITGYVVEYREKGSGDWKEVevTPGSETSYTLTGLKPGTEYEFRVRAVNGGGESPP 85

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 763551989  90 YSVQVGHDLKIEVPISGRPKPTITWTKDGHPLKQTTRINVTDSPNLTVLSIKETHKDDGGHYEITVANVVGQKTASIEI 168
Cdd:cd05748    2 IVVRAGESLRLDIPIKGRPTPTVTWSKDGQPLKETGRVQIETTASSTSLVIKNAKRSDSGKYTLTLKNSAGEKSATINV 80

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763551989   174 PDPPKGpVKFDEVSAESITLSWNPPLYTGG-CQITNYIVQKRDTTTTiWEVVSATVARTTLKVTKLKTGTEYQFRIFAEN 252
Cdd:smart00060   1 PSPPSN-LRVTDVTSTSVTLSWEPPPDDGItGYIVGYRVEYREEGSE-WKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVN 78

                   ....*
gi 763551989   253 RYGQS 257
Cdd:smart00060  79 GAGEG 83

Fibronectin type III domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763551989  175 DPPKGpVKFDEVSAESITLSWNPPLYTGGcQITNYIVQKRDTTTT---IWEVVSATvaRTTLKVTKLKTGTEYQFRIFAE 251
Cdd:pfam00041   1 SAPSN-LTVTDVTSTSLTVSWTPPPDGNG-PITGYEVEYRPKNSGepwNEITVPGT--TTSVTLTGLKPGTEYEVRVQAV 76

                  ....*.
gi 763551989  252 NRYGQS 257
Cdd:pfam00041  77 NGGGEG 82

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 763551989   1 SWTKPEHDGGsKIIQYIVEMQAKQSEKWSEC--ARVKSLEAVIANLTQGEEYLFRVIAVNEKGRSDP 65
Cdd:cd00063   20 SWTPPEDDGG-PITGYVVEYREKGSGDWKEVevTPGSETSYTLTGLKPGTEYEFRVRAVNGGGESPP 85

Fibronectin type 3 domain [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763551989 134 NLTVLSIKETHKDDGGHYEITV-----ANVVGQKTASIEITT-LDKPDPPKGpVKFDEVSAESITLSWNPPLYTGgcqIT 207
Cdd:COG3401  281 TVTTTSYTDTGLTNGTTYYYRVtavdaAGNESAPSNVVSVTTdLTPPAAPSG-LTATAVGSSSITLSWTASSDAD---VT 356

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 763551989 208 NYIVQKRDTTTTIWEVVSATVARTTLKVTKLKTGTEYQFRIFAENRYGqsfaLESDP 264
Cdd:COG3401  357 GYNVYRSTSGGGTYTKIAETVTTTSYTDTGLTPGTTYYYKVTAVDAAG----NESAP 409

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 763551989  90 YSVQVGHDLKIEVPISGRPKPTITWTKDGHPLKQTTRINVTDSPNLTVLSIKETHKDDGGHYEITVANVVGQKTASIEI 168
Cdd:cd05748    2 IVVRAGESLRLDIPIKGRPTPTVTWSKDGQPLKETGRVQIETTASSTSLVIKNAKRSDSGKYTLTLKNSAGEKSATINV 80

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763551989   174 PDPPKGpVKFDEVSAESITLSWNPPLYTGG-CQITNYIVQKRDTTTTiWEVVSATVARTTLKVTKLKTGTEYQFRIFAEN 252
Cdd:smart00060   1 PSPPSN-LRVTDVTSTSVTLSWEPPPDDGItGYIVGYRVEYREEGSE-WKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVN 78

                   ....*
gi 763551989   253 RYGQS 257
Cdd:smart00060  79 GAGEG 83

C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C); The members here are composed of the C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C). MyBP-C consists of repeated domains, Ig and fibronectin type 3, and various linkers. Three isoforms of MYBP-C exist: slow-skeletal (ssMyBP-C), fast-skeletal (fsMyBP-C), and cardiac (cMyBP-C). cMYBP-C has insertions between and inside domains and an additional cardiac-specific Ig domain at the N-terminus. For cMYBP_C an interaction has been demonstrated between this C5 domain and the Ig C8 domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763551989  88 NSYSVQVGHDLKIEVPISGRPKPTITWTKDGHPLKQTT-RINVTDSPNLTVLSIKETHKDDGGHYEITVANVVGQKTASI 166
Cdd:cd05894    3 NTIVVVAGNKLRLDVPISGEPAPTVTWSRGDKAFTATEgRVRVESYKDLSSFVIEGAEREDEGVYTITVTNPVGEDHASL 82

                 ..
gi 763551989 167 EI 168
Cdd:cd05894   83 FV 84

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763551989    89 SYSVQVGHDLKIEVPISGRPKPTITWTKDGH-PLKQTTRINVTDSPNLTVLSIKETHKDDGGHYEITVANVVGQKTASIE 167
Cdd:smart00410   3 SVTVKEGESVTLSCEASGSPPPEVTWYKQGGkLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTT 82

                   ..
gi 763551989   168 IT 169
Cdd:smart00410  83 LT 84

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 763551989 105 SGRPKPTITWTKDGHPLKQTTRINVTD--SPNLTVLS---IKETHKDDGGHYEITVANVVGQ 161
Cdd:cd20956   26 SGNPLPQITWTLDGFPIPESPRFRVGDyvTSDGDVVSyvnISSVRVEDGGEYTCTATNDVGS 87

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 763551989  98 LKIEVPISGRPKPTITWTKDGHPLKQTTRINVTDSPNLTVLSIKETHKDDGGHYEITVANVVGQKTASI 166
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASAS 69

Eighth immunoglobulin (Ig)-like domain of human myosin light-chain kinase (MLCK) and similar protein; member of the I-set of IgSF domains; The members here are composed of the eighth immunoglobulin (Ig)-like domain of human myosin light-chain kinase (MLCK) and similar proteins. Myosin light-chain kinase (MLCK) is a key regulator of different forms of cell motility involving actin and myosin II. Agonist stimulation of smooth muscle cells increases cytosolic Ca2+ which binds calmodulin. This Ca2+-calmodulin complex in turn binds to and activates MLCK. Activated MLCK leads to the phosphorylation of the 20 kDa myosin regulatory light chain (RLC) of myosin II and the stimulation of actin-activated myosin MgATPase activity. MLCK is widely present in vertebrate tissues; it phosphorylates the 20 kDa RLC of both smooth and nonmuscle myosin II. Phosphorylation leads to the activation of the myosin motor domain and altered structural properties of myosin II. In smooth muscle MLCK it is involved in initiating contraction. In nonmuscle cells, MLCK may participate in cell division and cell motility; it has been suggested MLCK plays a role in cardiomyocyte differentiation and contraction through regulation of nonmuscle myosin II.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763551989  92 VQVGHDLKIEVPISGRPKPTITWTKDGHPLKQTTRINVTDSPNLTVLSIKETHKDDGGHYEITVANVVGQKTASIEITTL 171
Cdd:cd05762   13 VRAGESVELFCKVTGTQPITCTWMKFRKQIQEGEGIKIENTENSSKLTITEGQQEHCGCYTLEVENKLGSRQAQVNLTVV 92

                 ....*.
gi 763551989 172 DKPDPP 177
Cdd:cd05762   93 DKPDPP 98

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 763551989     1 SWTKPEHDGG-SKIIQYIVEMQAKQSEKWSECARVKSLEAVIANLTQGEEYLFRVIAVNEKGRS 63
Cdd:smart00060  20 SWEPPPDDGItGYIVGYRVEYREEGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNGAGEG 83

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. 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. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 763551989  91 SVQVGHDLKIEVPISGRPKPTITWTKDGHPLKQTTRINVTDSPnltVLSIKETHKDDGGHYEITVANVVGQKTASIEI 168
Cdd:cd20957   12 TVDFGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSED---VLVIPSVKREDKGMYQCFVRNDGDSAQATAEL 86

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 763551989  95 GHDLKIEVPISGRPKPTITWTKDGHPLkQTTRINVTDSPNLTVLSIKETHKDDGGHYEITVANVVGQKTASIEIT 169
Cdd:cd20976   16 GQDFVAQCSARGKPVPRITWIRNAQPL-QYAADRSTCEAGVGELHIQDVLPEDHGTYTCLAKNAAGQVSCSAWVT 89

Fibronectin type 3 domain [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763551989 134 NLTVLSIKETHKDDGGHYEITV-----ANVVGQKTASIEITT-LDKPDPPKGpVKFDEVSAESITLSWNPPLYTGgcqIT 207
Cdd:COG3401  281 TVTTTSYTDTGLTNGTTYYYRVtavdaAGNESAPSNVVSVTTdLTPPAAPSG-LTATAVGSSSITLSWTASSDAD---VT 356

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 763551989 208 NYIVQKRDTTTTIWEVVSATVARTTLKVTKLKTGTEYQFRIFAENRYGqsfaLESDP 264
Cdd:COG3401  357 GYNVYRSTSGGGTYTKIAETVTTTSYTDTGLTPGTTYYYKVTAVDAAG----NESAP 409

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        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 763551989  95 GHDLKIEVPISGRPKPTITWTKDGHPLKQTTRIN-VTDSPNLTVLSIKETHKDDGGHYEITVANVVGQKTASIEIT 169
Cdd:cd20973   12 GSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQiDQDEDGLCSLIISDVCGDDSGKYTCKAVNSLGEATCSAELT 87

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup 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. 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. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin 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. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763551989  91 SVQVGHDLKIEVPISGRPKPTITWTKDG---HPLKQTTRINVTdsPNLTVLSIKETHKDDGGHYEITVANVVGQKTASIE 167
Cdd:cd05763   10 TIRAGSTARLECAATGHPTPQIAWQKDGgtdFPAARERRMHVM--PEDDVFFIVDVKIEDTGVYSCTAQNSAGSISANAT 87

                 ....
gi 763551989 168 ITTL 171
Cdd:cd05763   88 LTVL 91

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763551989  86 AFNSYSVQVGHDLKIEVPISGRPKPTITWTKDGHPLKQTTRIN-VTDSPNLTVLSIKETHKDDGGHYEITVANVVGQKTA 164
Cdd:cd05744    6 APGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKmLVRENGRHSLIIEPVTKRDAGIYTCIARNRAGENSF 85

                 ....
gi 763551989 165 SIEI 168
Cdd:cd05744   86 NAEL 89

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. 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, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -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, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -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 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. The fifth Ig-like domain of Robo 1 and 2 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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763551989  90 YSVQVGHDLKIEVPISGRPKPTITWTKDGHPLK-QTTRINVTdspNLTVLSIKETHKDDGGHYEITVANVVGQKTASIEI 168
Cdd:cd20952    9 QTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLgKDERITTL---ENGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVL 85

                 .
gi 763551989 169 T 169
Cdd:cd20952   86 D 86

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. 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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763551989  84 RPAFNsysVQVGHDLKIEVPIS--GRPKPTITWTKDGHPLKQTTRINVTDSPNLTVLSIKethKDDGGHYEITVANVVG- 160
Cdd:cd20968    4 RPPTN---VTIIEGLKAVLPCTtmGNPKPSVSWIKGDDLIKENNRIAVLESGSLRIHNVQ---KEDAGQYRCVAKNSLGi 77

                         90
                 ....*....|
gi 763551989 161 --QKTASIEI 168
Cdd:cd20968   78 aySKPVTIEV 87

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 763551989  91 SVQVGHDLKIEVPISGRPKPTITWTKDGHPLKQTTRINVTDSPNLTVLSIKETHKDDGGHYEITVANVVGQKTASIEIT 169
Cdd:cd20949   10 TVKEGQSATILCEVKGEPQPNVTWHFNGQPISASVADMSKYRILADGLLINKVTQDDTGEYTCRAYQVNSIASDMQERT 88

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 763551989  94 VGHDLKIEVPISGRPKPTITWTKDGHPLKQTTrINVTDSPNLTvLSIKETHKDDGGHYEITVANVVGQKTASIEI 168
Cdd:cd05856   18 VGSSVRLKCVASGNPRPDITWLKDNKPLTPPE-IGENKKKKWT-LSLKNLKPEDSGKYTCHVSNRAGEINATYKV 90

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763551989  81 PDVRPAFNSYSVQVGHDLKIEVPISGRPKPTITWTKDGHPlkqttrINVTDSP---------NLTVLSIKETHKDDGGHY 151
Cdd:cd20951    1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVP------IDPSSIPgkykieseyGVHVLHIRRVTVEDSAVY 74

                         90
                 ....*....|....
gi 763551989 152 EITVANVVGQKTAS 165
Cdd:cd20951   75 SAVAKNIHGEASSS 88

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 763551989  95 GHDLKIEVPISGRPKPTITWTKDGHPLKQTT-RINV-TDSPNLTVLSIKETHKDDGGHYEITVANVVG 160
Cdd:cd05892   15 GDPVRLECQISAIPPPQIFWKKNNEMLQYNTdRISLyQDNCGRICLLIQNANKKDAGWYTVSAVNEAG 82

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 763551989  97 DLKIEVPISGRPKPTITWTKDGHPLKQTTRINVTDSPNLTVLSIKethKDDGGHYEITVANVVGQKTASIEI 168
Cdd:cd05723   14 DIVFECEVTGKPTPTVKWVKNGDVVIPSDYFKIVKEHNLQVLGLV---KSDEGFYQCIAENDVGNAQASAQL 82

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763551989   92 VQVGHDLKIEVPISGRPKPTITWTKDGHPLKQttrinvtdSPNLTVLSIketHKDDGGHYEITVAN-VVGQKTASIEITT 170
Cdd:pfam13895  11 VTEGEPVTLTCSAPGNPPPSYTWYKDGSAISS--------SPNFFTLSV---SAEDSGTYTCVARNgRGGKVSNPVELTV 79

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; 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. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 763551989  90 YSVQVGHDLKIEVPISGRPKPTITWTKDGHPLKQTTRI 127
Cdd:cd05857   14 HAVPAANTVKFRCPAAGNPTPTMRWLKNGKEFKQEHRI 51

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 763551989 105 SGRPKPTITWTKDGHPLKQTT---RINVTDSpnlTVLSIKETHKDDGGHYEITVANVVGQK 162
Cdd:cd05738   24 SGNPDPEISWFKDFLPVDTATsngRIKQLRS---GALQIENSEESDQGKYECVATNSAGTR 81

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 763551989  91 SVQVGHDLKIEVPISGRPKPTITWTK-------DGHPLKQTTRINVTdsPNLTvLSIKETHKDDGGHYEITVANVVG 160
Cdd:cd20954   12 NVAAGQDVMLHCQADGFPTPTVTWKKatgstpgEYKDLLYDPNVRIL--PNGT-LVFGHVQKENEGHYLCEAKNGIG 85

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 763551989  95 GHDLKIEVPISGRPKPTITWTKDGHPLKQTTRINVT-DSPNLTVLSIKETHKDDGGHYEITVANVVGQKTASIEIT 169
Cdd:cd05891   16 GKTLNLTCTVFGNPDPEVIWFKNDQDIELSEHYSVKlEQGKYASLTIKGVTSEDSGKYSINVKNKYGGETVDVTVS 91