Troponin I, cardiac muscle

Details

Name
Troponin I, cardiac muscle
Synonyms
  • Cardiac troponin I
  • TNNC1
Gene Name
TNNI3
Organism
Humans
Amino acid sequence
>lcl|BSEQ0020473|Troponin I, cardiac muscle
MADGSSDAAREPRPAPAPIRRRSSNYRAYATEPHAKKKSKISASRKLQLKTLLLQIAKQE
LEREAEERRGEKGRALSTRCQPLELAGLGFAELQDLCRQLHARVDKVDEERYDIEAKVTK
NITEIADLTQKIFDLRGKFKRPTLRRVRISADAMMQALLGARAKESLDLRAHLKQVKKED
TEKENREVGDWRKNIDALSGMEGRKKKFES
Number of residues
210
Molecular Weight
24007.255
Theoretical pI
10.57
GO Classification
Functions
actin binding / calcium channel inhibitor activity / calcium-dependent protein binding / metal ion binding / protein domain specific binding / protein kinase binding / troponin C binding / troponin T binding
Processes
cardiac muscle contraction / cellular calcium ion homeostasis / heart contraction / heart development / muscle filament sliding / negative regulation of ATPase activity / regulation of smooth muscle contraction / regulation of systemic arterial blood pressure by ischemic conditions / skeletal muscle contraction / vasculogenesis / ventricular cardiac muscle tissue morphogenesis
Components
cytosol / sarcomere / troponin complex
General Function
Troponin t binding
Specific Function
Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Not Available
Gene sequence
>lcl|BSEQ0020474|Troponin I, cardiac muscle (TNNI3)
ATGGCGGATGGGAGCAGCGATGCGGCTAGGGAACCTCGCCCTGCACCAGCCCCAATCAGA
CGCCGCTCCTCCAACTACCGCGCTTATGCCACGGAGCCGCACGCCAAGAAAAAATCTAAG
ATCTCCGCCTCGAGAAAATTGCAGCTGAAGACTCTGCTGCTGCAGATTGCAAAGCAAGAG
CTGGAGCGAGAGGCGGAGGAGCGGCGCGGAGAGAAGGGGCGCGCTCTGAGCACCCGCTGC
CAGCCGCTGGAGTTGGCCGGGCTGGGCTTCGCGGAGCTGCAGGACTTGTGCCGACAGCTC
CACGCCCGTGTGGACAAGGTGGATGAAGAGAGATACGACATAGAGGCAAAAGTCACCAAG
AACATCACGGAGATTGCAGATCTGACTCAGAAGATCTTTGACCTTCGAGGCAAGTTTAAG
CGGCCCACCCTGCGGAGAGTGAGGATCTCTGCAGATGCCATGATGCAGGCGCTGCTGGGG
GCCCGGGCTAAGGAGTCCCTGGACCTGCGGGCCCACCTCAAGCAGGTGAAGAAGGAGGAC
ACCGAGAAGGAAAACCGGGAGGTGGGAGACTGGCGCAAGAACATCGATGCACTGAGTGGA
ATGGAGGGCCGCAAGAAAAAGTTTGAGAGCTGA
Chromosome Location
19
Locus
19q13.4
External Identifiers
ResourceLink
UniProtKB IDP19429
UniProtKB Entry NameTNNI3_HUMAN
GenBank Protein ID37428
GenBank Gene IDX54163
GenAtlas IDTNNI3
HGNC IDHGNC:11947
General References
  1. Vallins WJ, Brand NJ, Dabhade N, Butler-Browne G, Yacoub MH, Barton PJ: Molecular cloning of human cardiac troponin I using polymerase chain reaction. FEBS Lett. 1990 Sep 17;270(1-2):57-61. [PubMed:2226790]
  2. Armour KL, Harris WJ, Tempest PR: Cloning and expression in Escherichia coli of the cDNA encoding human cardiac troponin I. Gene. 1993 Sep 15;131(2):287-92. [PubMed:8406024]
  3. Hunkeler NM, Kullman J, Murphy AM: Troponin I isoform expression in human heart. Circ Res. 1991 Nov;69(5):1409-14. [PubMed:1934363]
  4. Bhavsar PK, Brand NJ, Yacoub MH, Barton PJ: Isolation and characterization of the human cardiac troponin I gene (TNNI3). Genomics. 1996 Jul 1;35(1):11-23. [PubMed:8661099]
  5. Mittmann K, Jaquet K, Heilmeyer LM Jr: A common motif of two adjacent phosphoserines in bovine, rabbit and human cardiac troponin I. FEBS Lett. 1990 Oct 29;273(1-2):41-5. [PubMed:2226863]
  6. Keane NE, Quirk PG, Gao Y, Patchell VB, Perry SV, Levine BA: The ordered phosphorylation of cardiac troponin I by the cAMP-dependent protein kinase--structural consequences and functional implications. Eur J Biochem. 1997 Sep 1;248(2):329-37. [PubMed:9346285]
  7. Buscemi N, Foster DB, Neverova I, Van Eyk JE: p21-activated kinase increases the calcium sensitivity of rat triton-skinned cardiac muscle fiber bundles via a mechanism potentially involving novel phosphorylation of troponin I. Circ Res. 2002 Sep 20;91(6):509-16. [PubMed:12242269]
  8. Haworth RS, Cuello F, Herron TJ, Franzen G, Kentish JC, Gautel M, Avkiran M: Protein kinase D is a novel mediator of cardiac troponin I phosphorylation and regulates myofilament function. Circ Res. 2004 Nov 26;95(11):1091-9. Epub 2004 Oct 28. [PubMed:15514163]
  9. Kedar V, McDonough H, Arya R, Li HH, Rockman HA, Patterson C: Muscle-specific RING finger 1 is a bona fide ubiquitin ligase that degrades cardiac troponin I. Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):18135-40. Epub 2004 Dec 15. [PubMed:15601779]
  10. You B, Yan G, Zhang Z, Yan L, Li J, Ge Q, Jin JP, Sun J: Phosphorylation of cardiac troponin I by mammalian sterile 20-like kinase 1. Biochem J. 2009 Feb 15;418(1):93-101. doi: 10.1042/BJ20081340. [PubMed:18986304]
  11. Zhang P, Kirk JA, Ji W, dos Remedios CG, Kass DA, Van Eyk JE, Murphy AM: Multiple reaction monitoring to identify site-specific troponin I phosphorylated residues in the failing human heart. Circulation. 2012 Oct 9;126(15):1828-37. doi: 10.1161/CIRCULATIONAHA.112.096388. Epub 2012 Sep 12. [PubMed:22972900]
  12. Li MX, Spyracopoulos L, Sykes BD: Binding of cardiac troponin-I147-163 induces a structural opening in human cardiac troponin-C. Biochemistry. 1999 Jun 29;38(26):8289-98. [PubMed:10387074]
  13. Wang X, Li MX, Sykes BD: Structure of the regulatory N-domain of human cardiac troponin C in complex with human cardiac troponin I147-163 and bepridil. J Biol Chem. 2002 Aug 23;277(34):31124-33. Epub 2002 Jun 11. [PubMed:12060657]
  14. Kimura A, Harada H, Park JE, Nishi H, Satoh M, Takahashi M, Hiroi S, Sasaoka T, Ohbuchi N, Nakamura T, Koyanagi T, Hwang TH, Choo JA, Chung KS, Hasegawa A, Nagai R, Okazaki O, Nakamura H, Matsuzaki M, Sakamoto T, Toshima H, Koga Y, Imaizumi T, Sasazuki T: Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy. Nat Genet. 1997 Aug;16(4):379-82. [PubMed:9241277]
  15. Niimura H, Patton KK, McKenna WJ, Soults J, Maron BJ, Seidman JG, Seidman CE: Sarcomere protein gene mutations in hypertrophic cardiomyopathy of the elderly. Circulation. 2002 Jan 29;105(4):446-51. [PubMed:11815426]
  16. Mogensen J, Kubo T, Duque M, Uribe W, Shaw A, Murphy R, Gimeno JR, Elliott P, McKenna WJ: Idiopathic restrictive cardiomyopathy is part of the clinical expression of cardiac troponin I mutations. J Clin Invest. 2003 Jan;111(2):209-16. [PubMed:12531876]
  17. Richard P, Charron P, Carrier L, Ledeuil C, Cheav T, Pichereau C, Benaiche A, Isnard R, Dubourg O, Burban M, Gueffet JP, Millaire A, Desnos M, Schwartz K, Hainque B, Komajda M: Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy. Circulation. 2003 May 6;107(17):2227-32. Epub 2003 Apr 21. [PubMed:12707239]
  18. Erdmann J, Daehmlow S, Wischke S, Senyuva M, Werner U, Raible J, Tanis N, Dyachenko S, Hummel M, Hetzer R, Regitz-Zagrosek V: Mutation spectrum in a large cohort of unrelated consecutive patients with hypertrophic cardiomyopathy. Clin Genet. 2003 Oct;64(4):339-49. [PubMed:12974739]
  19. Murphy RT, Mogensen J, Shaw A, Kubo T, Hughes S, McKenna WJ: Novel mutation in cardiac troponin I in recessive idiopathic dilated cardiomyopathy. Lancet. 2004 Jan 31;363(9406):371-2. [PubMed:15070570]
  20. Ingles J, Doolan A, Chiu C, Seidman J, Seidman C, Semsarian C: Compound and double mutations in patients with hypertrophic cardiomyopathy: implications for genetic testing and counselling. J Med Genet. 2005 Oct;42(10):e59. [PubMed:16199542]
  21. Carballo S, Robinson P, Otway R, Fatkin D, Jongbloed JD, de Jonge N, Blair E, van Tintelen JP, Redwood C, Watkins H: Identification and functional characterization of cardiac troponin I as a novel disease gene in autosomal dominant dilated cardiomyopathy. Circ Res. 2009 Aug 14;105(4):375-82. doi: 10.1161/CIRCRESAHA.109.196055. Epub 2009 Jul 9. [PubMed:19590045]
  22. Millat G, Bouvagnet P, Chevalier P, Sebbag L, Dulac A, Dauphin C, Jouk PS, Delrue MA, Thambo JB, Le Metayer P, Seronde MF, Faivre L, Eicher JC, Rousson R: Clinical and mutational spectrum in a cohort of 105 unrelated patients with dilated cardiomyopathy. Eur J Med Genet. 2011 Nov-Dec;54(6):e570-5. doi: 10.1016/j.ejmg.2011.07.005. Epub 2011 Aug 4. [PubMed:21846512]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB04513N-(6-Aminohexyl)-5-Chloro-1-NaphthalenesulfonamideexperimentalunknownDetails