ID TNNC2_HUMAN Reviewed; 160 AA. AC P02585; Q6FH92; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 27-MAR-2024, entry version 200. DE RecName: Full=Troponin C, skeletal muscle; GN Name=TNNC2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=3166492; DOI=10.1016/0022-2836(88)90145-3; RA Gahlmann R., Wade R., Gunning R., Kedes L.; RT "Differential expression of slow and fast skeletal muscle troponin C. Slow RT skeletal muscle troponin C is expressed in human fibroblasts."; RL J. Mol. Biol. 201:379-391(1988). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2373703; DOI=10.1016/s0021-9258(19)38376-0; RA Gahlmann R., Kedes L.; RT "Cloning, structural analysis, and expression of the human fast twitch RT skeletal muscle troponin C gene."; RL J. Biol. Chem. 265:12520-12528(1990). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Muscle; RA Wu Q.L.; RL Submitted (MAR-1996) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Tongue; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=11780052; DOI=10.1038/414865a; RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Liver; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP PROTEIN SEQUENCE OF 2-160, AND ACETYLATION AT THR-2. RC TISSUE=Skeletal muscle; RX PubMed=978749; DOI=10.1007/bf01730999; RA Romero-Herrera A.E., Castillo O., Lehmann H.; RT "Human skeletal muscle proteins. The primary structure of troponin C."; RL J. Mol. Evol. 8:251-270(1976). RN [10] RP INVOLVEMENT IN CMYP15, VARIANTS CMYP15 TYR-34 AND ILE-79, CHARACTERIZATION RP OF VARIANTS CMYP15 TYR-34 AND ILE-79, AND FUNCTION. RX PubMed=33755597; DOI=10.1172/jci145700; RA van de Locht M., Donkervoort S., de Winter J.M., Conijn S., Begthel L., RA Kusters B., Mohassel P., Hu Y., Medne L., Quinn C., Moore S.A., Foley A.R., RA Seo G., Hwee D.T., Malik F.I., Irving T., Ma W., Granzier H.L., RA Kamsteeg E.J., Immadisetty K., Kekenes-Huskey P., Pinto J.R., Voermans N., RA Boennemann C.G., Ottenheijm C.A.; RT "Pathogenic variants in TNNC2 cause congenital myopathy due to an impaired RT force response to calcium."; RL J. Clin. Invest. 131:0-0(2021). CC -!- FUNCTION: Troponin is the central regulatory protein of striated muscle CC contraction. Tn consists of three components: Tn-I which is the CC inhibitor of actomyosin ATPase, Tn-T which contains the binding site CC for tropomyosin and Tn-C. The binding of calcium to Tn-C abolishes the CC inhibitory action of Tn on actin filaments. CC {ECO:0000269|PubMed:33755597}. CC -!- INTERACTION: CC P02585; Q86TI0: TBC1D1; NbExp=3; IntAct=EBI-10249681, EBI-1644036; CC P02585; P19429: TNNI3; NbExp=3; IntAct=EBI-10249681, EBI-704146; CC P02585; Q6FGX2: TNNI3; NbExp=3; IntAct=EBI-10249681, EBI-10249686; CC -!- DISEASE: Congenital myopathy 15 (CMYP15) [MIM:620161]: An autosomal CC dominant myopathy characterized by neonatal onset of hypotonia, muscle CC weakness, and respiratory muscle involvement resulting in severe CC respiratory insufficiency. The disorder improves over time, although CC forced vital capacity remains decreased. Other features include facial CC weakness, often with ptosis or external ophthalmoplegia, jaw or distal CC joint contractures, scoliosis, and osteopenia. CC {ECO:0000269|PubMed:33755597}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: Skeletal muscle troponin C binds four calcium ions. CC -!- SIMILARITY: Belongs to the troponin C family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X07898; CAA30737.1; -; mRNA. DR EMBL; M33772; AAA61197.1; -; Genomic_DNA. DR EMBL; M33771; AAA61197.1; JOINED; Genomic_DNA. DR EMBL; M22307; AAA91854.1; -; mRNA. DR EMBL; AK291323; BAF84012.1; -; mRNA. DR EMBL; CR541864; CAG46662.1; -; mRNA. DR EMBL; CR541884; CAG46682.1; -; mRNA. DR EMBL; CH471077; EAW75803.1; -; Genomic_DNA. DR EMBL; AL050348; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC005323; AAH05323.1; -; mRNA. DR CCDS; CCDS13375.1; -. DR PIR; A36574; TPHUCS. DR RefSeq; NP_003270.1; NM_003279.2. DR PDB; 7KAA; NMR; -; A=1-88. DR PDBsum; 7KAA; -. DR AlphaFoldDB; P02585; -. DR BMRB; P02585; -. DR SMR; P02585; -. DR BioGRID; 112980; 66. DR IntAct; P02585; 7. DR STRING; 9606.ENSP00000361636; -. DR ChEMBL; CHEMBL3831282; -. DR DrugBank; DB01373; Calcium. DR DrugBank; DB01023; Felodipine. DR DrugBank; DB04682; Octylphenoxy polyethoxyethanol. DR iPTMnet; P02585; -. DR PhosphoSitePlus; P02585; -. DR BioMuta; TNNC2; -. DR DMDM; 136043; -. DR MassIVE; P02585; -. DR PaxDb; 9606-ENSP00000361636; -. DR PeptideAtlas; P02585; -. DR ProteomicsDB; 51535; -. DR Pumba; P02585; -. DR Antibodypedia; 27766; 188 antibodies from 25 providers. DR DNASU; 7125; -. DR Ensembl; ENST00000372555.8; ENSP00000361636.3; ENSG00000101470.10. DR GeneID; 7125; -. DR KEGG; hsa:7125; -. DR MANE-Select; ENST00000372555.8; ENSP00000361636.3; NM_003279.3; NP_003270.1. DR UCSC; uc002xpr.4; human. DR AGR; HGNC:11944; -. DR CTD; 7125; -. DR DisGeNET; 7125; -. DR GeneCards; TNNC2; -. DR HGNC; HGNC:11944; TNNC2. DR HPA; ENSG00000101470; Group enriched (skeletal muscle, tongue). DR MalaCards; TNNC2; -. DR MIM; 191039; gene. DR MIM; 620161; phenotype. DR neXtProt; NX_P02585; -. DR OpenTargets; ENSG00000101470; -. DR PharmGKB; PA36633; -. DR VEuPathDB; HostDB:ENSG00000101470; -. DR eggNOG; KOG0027; Eukaryota. DR GeneTree; ENSGT00940000153541; -. DR InParanoid; P02585; -. DR OMA; QVEARSY; -. DR OrthoDB; 4239664at2759; -. DR PhylomeDB; P02585; -. DR TreeFam; TF318191; -. DR PathwayCommons; P02585; -. DR Reactome; R-HSA-390522; Striated Muscle Contraction. DR SignaLink; P02585; -. DR SIGNOR; P02585; -. DR BioGRID-ORCS; 7125; 14 hits in 1144 CRISPR screens. DR ChiTaRS; TNNC2; human. DR GeneWiki; TNNC2; -. DR GenomeRNAi; 7125; -. DR Pharos; P02585; Tbio. DR PRO; PR:P02585; -. DR Proteomes; UP000005640; Chromosome 20. DR RNAct; P02585; Protein. DR Bgee; ENSG00000101470; Expressed in skeletal muscle tissue of rectus abdominis and 118 other cell types or tissues. DR ExpressionAtlas; P02585; baseline and differential. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005861; C:troponin complex; IDA:UniProtKB. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0006937; P:regulation of muscle contraction; IMP:UniProtKB. DR GO; GO:0003009; P:skeletal muscle contraction; IDA:UniProtKB. DR CDD; cd00051; EFh; 2. DR Gene3D; 1.10.238.10; EF-hand; 2. DR InterPro; IPR011992; EF-hand-dom_pair. DR InterPro; IPR018247; EF_Hand_1_Ca_BS. DR InterPro; IPR002048; EF_hand_dom. DR PANTHER; PTHR23048; MYOSIN LIGHT CHAIN 1, 3; 1. DR PANTHER; PTHR23048:SF46; TROPONIN C2, FAST SKELETAL TYPE; 1. DR Pfam; PF13499; EF-hand_7; 2. DR SMART; SM00054; EFh; 4. DR SUPFAM; SSF47473; EF-hand; 1. DR PROSITE; PS00018; EF_HAND_1; 4. DR PROSITE; PS50222; EF_HAND_2; 4. DR Genevisible; P02585; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Calcium; Direct protein sequencing; KW Disease variant; Metal-binding; Muscle protein; Reference proteome; Repeat. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:978749" FT CHAIN 2..160 FT /note="Troponin C, skeletal muscle" FT /id="PRO_0000073703" FT DOMAIN 15..50 FT /note="EF-hand 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT DOMAIN 51..86 FT /note="EF-hand 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT DOMAIN 91..126 FT /note="EF-hand 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT DOMAIN 127..160 FT /note="EF-hand 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 28 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 30 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 34 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 39 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 64 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 66 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 68 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 70 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 75 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 104 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 106 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 108 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 110 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 115 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 140 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 142 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 144 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 146 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 151 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT MOD_RES 2 FT /note="N-acetylthreonine" FT /evidence="ECO:0000269|PubMed:978749" FT VARIANT 34 FT /note="D -> Y (in CMYP15; affects regulation of muscle FT contraction)" FT /evidence="ECO:0000269|PubMed:33755597" FT /id="VAR_087978" FT VARIANT 79 FT /note="M -> I (in CMYP15; affects regulation of muscle FT contraction)" FT /evidence="ECO:0000269|PubMed:33755597" FT /id="VAR_087979" FT CONFLICT 2..3 FT /note="TD -> DT (in Ref. 9; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 114 FT /note="E -> G (in Ref. 3; AAA91854)" FT /evidence="ECO:0000305" FT HELIX 4..10 FT /evidence="ECO:0007829|PDB:7KAA" FT HELIX 14..20 FT /evidence="ECO:0007829|PDB:7KAA" FT HELIX 23..27 FT /evidence="ECO:0007829|PDB:7KAA" FT STRAND 29..32 FT /evidence="ECO:0007829|PDB:7KAA" FT HELIX 37..46 FT /evidence="ECO:0007829|PDB:7KAA" FT HELIX 53..61 FT /evidence="ECO:0007829|PDB:7KAA" FT HELIX 73..88 FT /evidence="ECO:0007829|PDB:7KAA" SQ SEQUENCE 160 AA; 18122 MW; EA93729732A0F916 CRC64; MTDQQAEARS YLSEEMIAEF KAAFDMFDAD GGGDISVKEL GTVMRMLGQT PTKEELDAII EEVDEDGSGT IDFEEFLVMM VRQMKEDAKG KSEEELAECF RIFDRNADGY IDPEELAEIF RASGEHVTDE EIESLMKDGD KNNDGRIDFD EFLKMMEGVQ //