Immunoglobulin Domain C1 of human cardiac Myosin Binding Protein C and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain C1 of human cardiac Myosin Binding Protein C (MyBP-C). MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. 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 C1 domain of the MyBP-C 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 1331920387  156 LFVMRPQDGEVTVGGSITFSARVAGASLLKPPVVKWFKGKWVDLSSKVGQHLQLHDSYDRASKVYLFELHITDAQPAFTG 235
Cdd:cd20962      1 LFVMRPQDGEVTVGGSITFSARVAGASLLKPPVVKWFKGKWVDLSSKVGQHLQLHDSYDRASKVYLFELHITDAQPAFAG 80

                           90       100
                   ....*....|....*....|.
gi 1331920387  236 GYRCEVSTKDKFDCSNFNLTV 256
Cdd:cd20962     81 GYRCEVSTKDKFDCSNFNLTV 101

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. 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 structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. 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 1331920387  367 KKLEPAYQVSKGHKIRLTVELADHDAEVKWFKNGQEIQMSgSRYIFESIGAKRTLTISQCSLADDAAYQCMVGGEKCSTE 446
Cdd:cd20967      1 KKAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSS-SKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFE 79

                   ...
gi 1331920387  447 LFV 449
Cdd:cd20967     80 LFV 82

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 1331920387  982 TIQKKVREPVNLLIPFQGKPRPQVTWTKEGQPLAG-EEVSVRNSPTDTILFIRAARRVHSGTYQVTVRIENMEDKATLVL 1060
Cdd:cd05748      1 TIVVRAGESLRLDIPIKGRPTPTVTWSKDGQPLKEtGRVQIETTASSTSLVIKNAKRSDSGKYTLTLKNSAGEKSATINV 80

                   ..
gi 1331920387 1061 QV 1062
Cdd:cd05748     81 KV 82

Fibronectin type 3 domain [General function prediction only];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331920387  749 YTVTVKNPVGEDQVNLTVKVIDVPDAPAAP---KISNVGEDSCTVQWEPPAYDGgqpILGYILERKKKKSYRWMRLNFdl 825
Cdd:COG3401    207 YRVAATDTGGESAPSNEVSVTTPTTPPSAPtglTATADTPGSVTLSWDPVTESD---ATGYRVYRSNSGDGPFTKVAT-- 281

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331920387  826 IQELSHEARRMIEGVVYEMRVYAVNAIG-MSRPSPASQPFMPIGPPSEPTHLAVEDVSDTTVSLKWRPperVGAGGLDGY 904
Cdd:COG3401    282 VTTTSYTDTGLTNGTTYYYRVTAVDAAGnESAPSNVVSVTTDLTPPAAPSGLTATAVGSSSITLSWTA---SSDADVTGY 358

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1331920387  905 SVEYCPEGCSEWVAALQGLTEhTSILVKDLPTGARLLFRVRAHNMAG----PGAPVT-TTEPVTVQEILQRP 971
Cdd:COG3401    359 NVYRSTSGGGTYTKIAETVTT-TSYTDTGLTPGTTYYYKVTAVDAAGnesaPSEEVSaTTASAASGESLTAS 429

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 1331920387  456 ITRPLEDQLVMVGQRVEFECEVSEEGA-QVKWLKDGVELTreETFKYRFKKDGRRHHLIINEATLEDAGHYALRT--SGG 532
Cdd:pfam07679    3 FTQKPKDVEVQEGESARFTCTVTGTPDpEVSWFKDGQPLR--SSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnSAG 80

                   ....*....
gi 1331920387  533 QALAELIVQ 541
Cdd:pfam07679   81 EAEASAELT 89

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        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331920387 1066 PSPPQDLRVTDAWGLNVALEWKPPQDvGNTELWGYTVQKADKKTMEWFTVLEHY-RRTHCVVPELIIGNGYYFRVFSQNM 1144
Cdd:cd00063      1 PSPPTNLRVTDVTSTSVTLSWTPPED-DGGPITGYVVEYREKGSGDWKEVEVTPgSETSYTLTGLKPGTEYEFRVRAVNG 79

                           90
                   ....*....|
gi 1331920387 1145 VGSSDRAATT 1154
Cdd:cd00063     80 GGESPPSESV 89

Immunoglobulin Domain C1 of human cardiac Myosin Binding Protein C and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain C1 of human cardiac Myosin Binding Protein C (MyBP-C). MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. 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 C1 domain of the MyBP-C 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 1331920387  156 LFVMRPQDGEVTVGGSITFSARVAGASLLKPPVVKWFKGKWVDLSSKVGQHLQLHDSYDRASKVYLFELHITDAQPAFTG 235
Cdd:cd20962      1 LFVMRPQDGEVTVGGSITFSARVAGASLLKPPVVKWFKGKWVDLSSKVGQHLQLHDSYDRASKVYLFELHITDAQPAFAG 80

                           90       100
                   ....*....|....*....|.
gi 1331920387  236 GYRCEVSTKDKFDCSNFNLTV 256
Cdd:cd20962     81 GYRCEVSTKDKFDCSNFNLTV 101

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. 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 structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. 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 1331920387  367 KKLEPAYQVSKGHKIRLTVELADHDAEVKWFKNGQEIQMSgSRYIFESIGAKRTLTISQCSLADDAAYQCMVGGEKCSTE 446
Cdd:cd20967      1 KKAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSS-SKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFE 79

                   ...
gi 1331920387  447 LFV 449
Cdd:cd20967     80 LFV 82

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 1331920387  982 TIQKKVREPVNLLIPFQGKPRPQVTWTKEGQPLAG-EEVSVRNSPTDTILFIRAARRVHSGTYQVTVRIENMEDKATLVL 1060
Cdd:cd05748      1 TIVVRAGESLRLDIPIKGRPTPTVTWSKDGQPLKEtGRVQIETTASSTSLVIKNAKRSDSGKYTLTLKNSAGEKSATINV 80

                   ..
gi 1331920387 1061 QV 1062
Cdd:cd05748     81 KV 82

Fibronectin type 3 domain [General function prediction only];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331920387  749 YTVTVKNPVGEDQVNLTVKVIDVPDAPAAP---KISNVGEDSCTVQWEPPAYDGgqpILGYILERKKKKSYRWMRLNFdl 825
Cdd:COG3401    207 YRVAATDTGGESAPSNEVSVTTPTTPPSAPtglTATADTPGSVTLSWDPVTESD---ATGYRVYRSNSGDGPFTKVAT-- 281

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331920387  826 IQELSHEARRMIEGVVYEMRVYAVNAIG-MSRPSPASQPFMPIGPPSEPTHLAVEDVSDTTVSLKWRPperVGAGGLDGY 904
Cdd:COG3401    282 VTTTSYTDTGLTNGTTYYYRVTAVDAAGnESAPSNVVSVTTDLTPPAAPSGLTATAVGSSSITLSWTA---SSDADVTGY 358

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1331920387  905 SVEYCPEGCSEWVAALQGLTEhTSILVKDLPTGARLLFRVRAHNMAG----PGAPVT-TTEPVTVQEILQRP 971
Cdd:COG3401    359 NVYRSTSGGGTYTKIAETVTT-TSYTDTGLTPGTTYYYKVTAVDAAGnesaPSEEVSaTTASAASGESLTAS 429

Tri-helix bundle domain; This domain can be found in the myosin-binding motif (m-domain) region present in myosin-binding protein C (MyBP-C). MyBP-C is a sarcomeric assembly protein necessary for the regulation of sarcomere structure and function. The MyBP-C family of proteins consists mainly of modules with immunoglobulin (Ig) or fibronectin folds. This domain exhibits a three-helix bundle fold and there is a known actin-binding motif, LK(R/K)XK positioned in the third helix (alpha3), similar to that found in villin and related proteins.

                           10        20        30
                   ....*....|....*....|....*....|....
gi 1331920387  320 DVWEILRQAPPSEYERIAFQYGVTDLRGMLKRLK 353
Cdd:pfam18362    1 DVWEILSNAPPKDYEKIAFQYGITDLRGMLKKLK 34

Immunoglobulin I-set domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331920387  456 ITRPLEDQLVMVGQRVEFECEVSEEGA-QVKWLKDGVELTreETFKYRFKKDGRRHHLIINEATLEDAGHYALRT--SGG 532
Cdd:pfam07679    3 FTQKPKDVEVQEGESARFTCTVTGTPDpEVSWFKDGQPLR--SSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnSAG 80

                   ....*....
gi 1331920387  533 QALAELIVQ 541
Cdd:pfam07679   81 EAEASAELT 89

Immunoglobulin I-set domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331920387  654 RIPDTIVVVAGNKLRLDVPISGDPAPTVIWQKAitqgnkaparpapdapedtgdsdewvfDKKLlcETEGRVRVETTKDR 733
Cdd:pfam07679    5 QKPKDVEVQEGESARFTCTVTGTPDPEVSWFKD---------------------------GQPL--RSSDRFKVTYEGGT 55

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1331920387  734 SIFTVEGAEKEDEGVYTVTVKNPVGEDQVNLTVKV 768
Cdd:pfam07679   56 YTLTISNVQPDDSGKYTCVATNSAGEAEASAELTV 90

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 1331920387   870 PSEPTHLAVEDVSDTTVSLKWRPPERVGAGG-LDGYSVEYCPEGcSEWVaALQGLTEHTSILVKDLPTGARLLFRVRAHN 948
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGITGyIVGYRVEYREEG-SEWK-EVNVTPSSTSYTLTGLKPGTEYEFRVRAVN 78

                    ....*
gi 1331920387   949 MAGPG 953
Cdd:smart00060   79 GAGEG 83

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        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331920387 1066 PSPPQDLRVTDAWGLNVALEWKPPQDvGNTELWGYTVQKADKKTMEWFTVLEHY-RRTHCVVPELIIGNGYYFRVFSQNM 1144
Cdd:cd00063      1 PSPPTNLRVTDVTSTSVTLSWTPPED-DGGPITGYVVEYREKGSGDWKEVEVTPgSETSYTLTGLKPGTEYEFRVRAVNG 79

                           90
                   ....*....|
gi 1331920387 1145 VGSSDRAATT 1154
Cdd:cd00063     80 GGESPPSESV 89

Fibronectin type III domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331920387  773 DAPAAPKISNVGEDSCTVQWEPPAYDGGqPILGYILERKKKKSYRWMRLNFDLIQELSHEARRMIEGVVYEMRVYAVNAI 852
Cdd:pfam00041    1 SAPSNLTVTDVTSTSLTVSWTPPPDGNG-PITGYEVEYRPKNSGEPWNEITVPGTTTSVTLTGLKPGTEYEVRVQAVNGG 79

                   ....*.
gi 1331920387  853 GMSRPS 858
Cdd:pfam00041   80 GEGPPS 85

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331920387   981 QTIQKKVREPVNLLIPFQGKPRPQVTWTKEGQ--PLAGEEVSVRNSPTDTILFIRAARRVHSGTYQVTVRIENMEDKATL 1058
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGklLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81

                    ....
gi 1331920387  1059 VLQV 1062
Cdd:smart00410   82 TLTV 85

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1331920387  458 RPLEDQLVMVGQRVEFECEVSEEGAQV--KWLKDGVELTREETFKYRFKKDGRRHHLIINEATLEDAGHYALRTS 530
Cdd:cd05750      4 KEMKSQTVQEGSKLVLKCEATSENPSPryRWFKDGKELNRKRPKNIKIRNKKKNSELQINKAKLEDSGEYTCVVE 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 1331920387   161 PQDGEVTVGGSITFSARVAGASllkPPVVKWFKGKWVDLSSKvgQHLQLHDSYDRASkvylfeLHITDAQPAFTGGYRCE 240
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSP---PPEVTWYKQGGKLLAES--GRFSVSRSGSTST------LTISNVTPEDSGTYTCA 69

                            90
                    ....*....|....*.
gi 1331920387   241 VSTKDKFDCSNFNLTV 256
Cdd:smart00410   70 ATNSSGSASSGTTLTV 85

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

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1331920387   553 DLTVGAKDQAVFKCEVS-DENVRGVWLKNGKELV-PNSRIKVSHIGRVHKLTIDDVTPADEADY 614
Cdd:smart00410    3 SVTVKEGESVTLSCEASgSPPPEVTWYKQGGKLLaESGRFSVSRSGSTSTLTISNVTPEDSGTY 66

Immunoglobulin I-set domain;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1331920387  553 DLTVGAKDQAVFKCEVS---DENVrgVWLKNGKELVPNSRIKVSHIGRVHKLTIDDVTPADEADYSFV 617
Cdd:pfam07679    9 DVEVQEGESARFTCTVTgtpDPEV--SWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCV 74

Immunoglobulin I-set domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331920387  976 PRHLRQTIQKKVRE--PVNLLIPFQGKPRPQVTWTKEGQPLA-GEEVSVRNSPTDTILFIRAARRVHSGTYqvTVRIENM 1052
Cdd:pfam07679    1 PKFTQKPKDVEVQEgeSARFTCTVTGTPDPEVSWFKDGQPLRsSDRFKVTYEGGTYTLTISNVQPDDSGKY--TCVATNS 78

                           90
                   ....*....|..
gi 1331920387 1053 --EDKATLVLQV 1062
Cdd:pfam07679   79 agEAEASAELTV 90

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331920387   371 PAYQVSKGHKIRLTVEL-ADHDAEVKWFKNGQEIQMSGSRYIFESIGAKRTLTISQCSLADDAAYQCMV----GGEKCST 445
Cdd:smart00410    2 PSVTVKEGESVTLSCEAsGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGT 81

                    ....
gi 1331920387   446 ELFV 449
Cdd:smart00410   82 TLTV 85

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

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1331920387    16 PRSVEVAAGSPAVFEAETE-RAGVKVRWQR-GGSDISASNKYGLATEGTRHTLTVREVGPADQGSY 79
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASgSPPPEVTWYKqGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTY 66

Immunoglobulin Domain C1 of human cardiac Myosin Binding Protein C and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain C1 of human cardiac Myosin Binding Protein C (MyBP-C). MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. 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 C1 domain of the MyBP-C 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 1331920387  156 LFVMRPQDGEVTVGGSITFSARVAGASLLKPPVVKWFKGKWVDLSSKVGQHLQLHDSYDRASKVYLFELHITDAQPAFTG 235
Cdd:cd20962      1 LFVMRPQDGEVTVGGSITFSARVAGASLLKPPVVKWFKGKWVDLSSKVGQHLQLHDSYDRASKVYLFELHITDAQPAFAG 80

                           90       100
                   ....*....|....*....|.
gi 1331920387  236 GYRCEVSTKDKFDCSNFNLTV 256
Cdd:cd20962     81 GYRCEVSTKDKFDCSNFNLTV 101

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. 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 structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. 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 1331920387  367 KKLEPAYQVSKGHKIRLTVELADHDAEVKWFKNGQEIQMSgSRYIFESIGAKRTLTISQCSLADDAAYQCMVGGEKCSTE 446
Cdd:cd20967      1 KKAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSS-SKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFE 79

                   ...
gi 1331920387  447 LFV 449
Cdd:cd20967     80 LFV 82

Immunoglobulin I-set domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331920387 1181 PSFTQPLVNRSVIAGYTTMLCCAVRGSPKPKISWFKNGLDLREDARFRMFSKQGVLTLEIRKPCPFDRGIYVCRATNLQG 1260
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAG 80

                           90
                   ....*....|
gi 1331920387 1261 EAQCECRLEV 1270
Cdd:pfam07679   81 EAEASAELTV 90

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        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331920387  772 PDAPAAPKISNVGEDSCTVQWEPPAYDGGqPILGYILERKKKKSYRWMRLNFDLIQELSHEARRMIEGVVYEMRVYAVNA 851
Cdd:cd00063      1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGG-PITGYVVEYREKGSGDWKEVEVTPGSETSYTLTGLKPGTEYEFRVRAVNG 79

                           90
                   ....*....|.
gi 1331920387  852 IGMSRPSPASQ 862
Cdd:cd00063     80 GGESPPSESVT 90

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        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331920387  870 PSEPTHLAVEDVSDTTVSLKWRPPERVGaGGLDGYSVEYCPEGCSEWVAALQGLTEHTSILVKDLPTGARLLFRVRAHNM 949
Cdd:cd00063      1 PSPPTNLRVTDVTSTSVTLSWTPPEDDG-GPITGYVVEYREKGSGDWKEVEVTPGSETSYTLTGLKPGTEYEFRVRAVNG 79

                           90
                   ....*....|....
gi 1331920387  950 AGPGAPVTTTEPVT 963
Cdd:cd00063     80 GGESPPSESVTVTT 93

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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331920387 1184 TQPLVNRSVIAGYTTMLCCAVRGSPKPKISWFKNGLDLREDARFRM-FSKQGVLTLEIRKPCPFDRGIYVCRATNLQGEA 1262
Cdd:cd20973      1 IQTLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIdQDEDGLCSLIISDVCGDDSGKYTCKAVNSLGEA 80

                   ....*...
gi 1331920387 1263 QCECRLEV 1270
Cdd:cd20973     81 TCSAELTV 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        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1331920387 1200 LCCAVRGSPKPKISWFKNGLDLREDARFRMFSKQGVLTLEIRKPCPFDRGIYVCRATNLQGEAQ 1263
Cdd:cd00096      3 LTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSA 66

Immunoglobulin I-set domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331920387  456 ITRPLEDQLVMVGQRVEFECEVSEEGA-QVKWLKDGVELTreETFKYRFKKDGRRHHLIINEATLEDAGHYALRT--SGG 532
Cdd:pfam07679    3 FTQKPKDVEVQEGESARFTCTVTGTPDpEVSWFKDGQPLR--SSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnSAG 80