TNNT2

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Troponin T type 2 (cardiac)
Protein TNNT2 PDB 1j1d.png
PDB rendering based on 1j1d.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols TNNT2 ; CMD1D; CMH2; CMPD2; LVNC6; RCM3; TnTC; cTnT
External IDs OMIM191045 MGI104597 HomoloGene68050 ChEMBL: 1741182 GeneCards: TNNT2 Gene
RNA expression pattern
PBB GE TNNT2 215389 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 7139 21956
Ensembl ENSG00000118194 ENSMUSG00000026414
UniProt P45379 P50752
RefSeq (mRNA) NM_000364 NM_001130174
RefSeq (protein) NP_000355 NP_001123646
Location (UCSC) Chr 1:
201.33 – 201.35 Mb
Chr 1:
135.84 – 135.85 Mb
PubMed search [1] [2]

Cardiac Troponin T (TnT), is a protein which in humans is encoded by the TNNT2 gene.[1][2] Cardiac TnT is the tropomyosin-binding subunit of the troponin complex, which is located on the thin filament of striated muscles and regulates muscle contraction in response to alterations in intracellular calcium ion concentration.

Structure[edit]

Cardiac TnT is a 35.9 kDa protein composed of 298 amino acids.[3][4] Cardiac TnT is the largest of the three troponin subunits (cTnT, troponin I (TnI), troponin C (TnC)) on the actin thin filament of cardiac muscle. The structure of TnT is asymmetric; the globular C-terminal domain interacts with tropomyosin (Tm), TnI and TnC, and the N-terminal tether which strongly binds Tm. The N-terminal region of TnT is alternatively spliced, accounting for multiple isoforms observed in cardiac muscle.[5]

Function[edit]

As part of the Troponin complex, the function of cTnT is to regulate muscle contraction. The N-terminal region of TnT that strongly binds actin most likely moves with Tm and actin during strong myosin crossbridge binding and force generation. This region is likely involved in the transduction of cooperativity down the thin filament.[6] The C-terminal region of TnT constitutes part of the globular troponin complex domain, and participates in employing the calcium sensitivity of strong myosin crossbridge binding to the thin filament.[7]

Clinical significance[edit]

Mutations in this gene have been associated with familial hypertrophic cardiomyopathy as well as with restrictive[8] and dilated cardiomyopathy. Transcripts for this gene undergo alternative splicing that results in many tissue-specific isoforms, however, the full-length nature of some of these variants has not yet been determined.[9] Mutations of this gene may be associated with mild or absent hypertrophy and predominant restrictive disease, with a high risk of sudden cardiac death.[8] Advancement to dilated cardiomyopathy may be more rapid in patients with TNNT2 mutations than in those with myosin heavy chain mutations.[10][11]

See also[edit]

References[edit]

  1. ^ Townsend PJ, Farza H, MacGeoch C, Spurr NK, Wade R, Gahlmann R et al. (May 1994). "Human cardiac troponin T: identification of fetal isoforms and assignment of the TNNT2 locus to chromosome 1q". Genomics 21 (2): 311–6. doi:10.1006/geno.1994.1271. PMID 8088824. 
  2. ^ Gerull B, Osterziel KJ, Witt C, Dietz R, Thierfelder L (1998). "A rapid protocol for cardiac troponin T gene mutation detection in familial hypertrophic cardiomyopathy". Human Mutation 11 (2): 179–82. doi:10.1002/(SICI)1098-1004(1998)11:2<179::AID-HUMU12>3.0.CO;2-W. PMID 9482583. 
  3. ^ http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=P45379.  Missing or empty |title= (help)
  4. ^ Zong, N. C.; Li, H; Li, H; Lam, M. P.; Jimenez, R. C.; Kim, C. S.; Deng, N; Kim, A. K.; Choi, J. H.; Zelaya, I; Liem, D; Meyer, D; Odeberg, J; Fang, C; Lu, H. J.; Xu, T; Weiss, J; Duan, H; Uhlen, M; Yates Jr, 3rd; Apweiler, R; Ge, J; Hermjakob, H; Ping, P (2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.  edit
  5. ^ Anderson PA, Malouf NN, Oakeley AE, Pagani ED, Allen PD (Nov 1991). "Troponin T isoform expression in humans. A comparison among normal and failing adult heart, fetal heart, and adult and fetal skeletal muscle". Circulation Research 69 (5). PMID 1934353. 
  6. ^ Kobayashi T, Solaro RJ. "Calcium, thin filaments, and the integrative biology of cardiac contractility". Annual Review of Physiology 67. doi:10.1146/annurev.physiol.67.040403.114025. PMID 15709952. 
  7. ^ Kobayashi T, Jin L, de Tombe PP (Oct 2008). "Cardiac thin filament regulation". Pflügers Archiv 457 (1). doi:10.1007/s00424-008-0511-8. PMID 18421471. 
  8. ^ a b Revera M, Van der Merwe L, Heradien M, Goosen A, Corfield VA, Brink PA et al. (2007). "Long-term follow-up of R403WMYH7 and R92WTNNT2 HCM families: mutations determine left ventricular dimensions but not wall thickness during disease progression" (PDF). Cardiovascular Journal of Africa 18 (3): 146–53. PMID 17612745. 
  9. ^ "Entrez Gene: TNNT2 troponin T type 2 (cardiac)". 
  10. ^ Fujino N, Shimizu M, Ino H, Okeie K, Yamaguchi M, Yasuda T et al. (May 2001). "Cardiac troponin T Arg92Trp mutation and progression from hypertrophic to dilated cardiomyopathy". Clinical Cardiology 24 (5): 397–402. doi:10.1002/clc.4960240510. PMID 11346248. 
  11. ^ Fujino N, Shimizu M, Ino H, Yamaguchi M, Yasuda T, Nagata M et al. (Jan 2002). "A novel mutation Lys273Glu in the cardiac troponin T gene shows high degree of penetrance and transition from hypertrophic to dilated cardiomyopathy". The American Journal of Cardiology 89 (1): 29–33. doi:10.1016/S0002-9149(01)02158-0. PMID 11779518. 

Further reading[edit]

  • Gomes AV, Barnes JA, Harada K, Potter JD (Aug 2004). "Role of troponin T in disease". Molecular and Cellular Biochemistry 263 (1-2): 115–29. doi:10.1023/B:MCBI.0000041853.20588.a0. PMID 15524172. 
  • Noland TA, Raynor RL, Kuo JF (Dec 1989). "Identification of sites phosphorylated in bovine cardiac troponin I and troponin T by protein kinase C and comparative substrate activity of synthetic peptides containing the phosphorylation sites". The Journal of Biological Chemistry 264 (34): 20778–85. PMID 2584239. 
  • Breitbart RE, Nadal-Ginard B (Jun 1987). "Developmentally induced, muscle-specific trans factors control the differential splicing of alternative and constitutive troponin T exons". Cell 49 (6): 793–803. doi:10.1016/0092-8674(87)90617-9. PMID 3581171. 
  • Medford RM, Nguyen HT, Destree AT, Summers E, Nadal-Ginard B (Sep 1984). "A novel mechanism of alternative RNA splicing for the developmentally regulated generation of troponin T isoforms from a single gene". Cell 38 (2): 409–21. doi:10.1016/0092-8674(84)90496-3. PMID 6205765. 
  • Tanokura M, Ohtsuki I (May 1984). "Interactions among chymotryptic troponin T subfragments, tropomyosin, troponin I and troponin C". Journal of Biochemistry 95 (5): 1417–21. PMID 6746613. 
  • Pearlstone JR, Smillie LB (Feb 1983). "Effects of troponin-I plus-C on the binding of troponin-T and its fragments to alpha-tropomyosin. Ca2+ sensitivity and cooperativity". The Journal of Biological Chemistry 258 (4): 2534–42. PMID 6822572. 
  • Kovalyov LI, Shishkin SS, Efimochkin AS, Kovalyova MA, Ershova ES, Egorov TA et al. (Jul 1995). "The major protein expression profile and two-dimensional protein database of human heart". Electrophoresis 16 (7): 1160–9. doi:10.1002/elps.11501601192. PMID 7498159. 
  • Anderson PA, Greig A, Mark TM, Malouf NN, Oakeley AE, Ungerleider RM et al. (Apr 1995). "Molecular basis of human cardiac troponin T isoforms expressed in the developing, adult, and failing heart". Circulation Research 76 (4): 681–6. doi:10.1161/01.res.76.4.681. PMID 7534662. 
  • Mesnard L, Logeart D, Taviaux S, Diriong S, Mercadier JJ, Samson F (Apr 1995). "Human cardiac troponin T: cloning and expression of new isoforms in the normal and failing heart". Circulation Research 76 (4): 687–92. doi:10.1161/01.res.76.4.687. PMID 7895342. 
  • Watkins H, McKenna WJ, Thierfelder L, Suk HJ, Anan R, O'Donoghue A et al. (Apr 1995). "Mutations in the genes for cardiac troponin T and alpha-tropomyosin in hypertrophic cardiomyopathy". The New England Journal of Medicine 332 (16): 1058–64. doi:10.1056/NEJM199504203321603. PMID 7898523. 
  • Watkins H, MacRae C, Thierfelder L, Chou YH, Frenneaux M, McKenna W et al. (Apr 1993). "A disease locus for familial hypertrophic cardiomyopathy maps to chromosome 1q3". Nature Genetics 3 (4): 333–7. doi:10.1038/ng0493-333. PMID 7981753. 
  • Townsend PJ, Farza H, MacGeoch C, Spurr NK, Wade R, Gahlmann R et al. (May 1994). "Human cardiac troponin T: identification of fetal isoforms and assignment of the TNNT2 locus to chromosome 1q". Genomics 21 (2): 311–6. doi:10.1006/geno.1994.1271. PMID 8088824. 
  • Thierfelder L, Watkins H, MacRae C, Lamas R, McKenna W, Vosberg HP et al. (Jun 1994). "Alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere". Cell 77 (5): 701–12. doi:10.1016/0092-8674(94)90054-X. PMID 8205619. 
  • Mesnard L, Samson F, Espinasse I, Durand J, Neveux JY, Mercadier JJ (Aug 1993). "Molecular cloning and developmental expression of human cardiac troponin T". FEBS Letters 328 (1-2): 139–44. doi:10.1016/0014-5793(93)80981-Y. PMID 8344420. 
  • Durand JB, Bachinski LL, Bieling LC, Czernuszewicz GZ, Abchee AB, Yu QT et al. (Dec 1995). "Localization of a gene responsible for familial dilated cardiomyopathy to chromosome 1q32". Circulation 92 (12): 3387–9. doi:10.1161/01.cir.92.12.3387. PMID 8521556. 
  • Townsend PJ, Barton PJ, Yacoub MH, Farza H (Oct 1995). "Molecular cloning of human cardiac troponin T isoforms: expression in developing and failing heart". Journal of Molecular and Cellular Cardiology 27 (10): 2223–36. doi:10.1016/S0022-2828(95)91587-7. PMID 8576938. 
  • Jideama NM, Noland TA, Raynor RL, Blobe GC, Fabbro D, Kazanietz MG et al. (Sep 1996). "Phosphorylation specificities of protein kinase C isozymes for bovine cardiac troponin I and troponin T and sites within these proteins and regulation of myofilament properties". The Journal of Biological Chemistry 271 (38): 23277–83. doi:10.1074/jbc.271.38.23277. PMID 8798526. 
  • Forissier JF, Carrier L, Farza H, Bonne G, Bercovici J, Richard P et al. (Dec 1996). "Codon 102 of the cardiac troponin T gene is a putative hot spot for mutations in familial hypertrophic cardiomyopathy". Circulation 94 (12): 3069–73. doi:10.1161/01.cir.94.12.3069. PMID 8989109. 
  • Moolman JC, Corfield VA, Posen B, Ngumbela K, Seidman C, Brink PA et al. (Mar 1997). "Sudden death due to troponin T mutations". Journal of the American College of Cardiology 29 (3): 549–55. doi:10.1016/S0735-1097(96)00530-X. PMID 9060892. 
  • Nakajima-Taniguchi C, Matsui H, Fujio Y, Nagata S, Kishimoto T, Yamauchi-Takihara K (Feb 1997). "Novel missense mutation in cardiac troponin T gene found in Japanese patient with hypertrophic cardiomyopathy". Journal of Molecular and Cellular Cardiology 29 (2): 839–43. doi:10.1006/jmcc.1996.0322. PMID 9140840. 

External links[edit]