Wikipedia

TNNT2

Srčanomišićni troponin T (cTnT) jest protein koji je kod ljudi kodiran genom TNNT2 sa hromosoma 1.[5][6] Srčani TnT je tropomiozin-vezujuća podjedinica troponinskog kompleksa, koja se nalazi na tankom filamentu poprečnoprugastih mišića i reguliše mišićnu kontrakciju kao odgovor na promjene u koncentraciji unutarćelijskih iona kalcija.

TNNT2
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

1J1D, 1J1E, 4Y99

Identifikatori
AliasiTNNT2
Vanjski ID-jeviOMIM: 191045 MGI: 104597 HomoloGene: 68050 GeneCards: TNNT2
Lokacija gena (čovjek)
Hromosom 1 (čovjek)
Hrom.Hromosom 1 (čovjek)[1]
Hromosom 1 (čovjek)
Genomska lokacija za TNNT2
Genomska lokacija za TNNT2
Bend1q32.1Početak201,359,008 bp[1]
Kraj201,377,764 bp[1]
Lokacija gena (miš)
Hromosom 1 (miš)
Hrom.Hromosom 1 (miš)[2]
Hromosom 1 (miš)
Genomska lokacija za TNNT2
Genomska lokacija za TNNT2
Bend1 E4|1 59.32 cMPočetak135,764,092 bp[2]
Kraj135,779,998 bp[2]
Obrazac RNK ekspresije
Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija• protein-macromolecule adaptor activity
• ATPase activity
• GO:0001948, GO:0016582 vezivanje za proteine
• actin binding
• tropomyosin binding
• troponin C binding
• troponin I binding
• calcium ion binding
• calcium-dependent ATPase activity
Ćelijska komponenta• citosol
• troponin complex
• Sarkomera
• striated muscle thin filament
• Miofibril
• cardiac myofibril
• cardiac Troponin complex
Biološki proces• regulation of muscle contraction
• Mišićna kontrakcija
• regulation of heart contraction
• positive regulation of ATP-dependent activity
• negative regulation of ATP-dependent activity
• response to calcium ion
• ventricular cardiac muscle tissue morphogenesis
• actin crosslink formation
• muscle filament sliding
• regulation of muscle filament sliding speed
• cardiac muscle contraction
• protein heterooligomerization
• skeletal muscle contraction
• sarcomere organization
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez

7139

21956

Ensembl

ENSG00000118194

ENSMUSG00000026414

UniProt

P45379

P50752

RefSeq (mRNK)
NM_000364
NM_001001430
NM_001001431
NM_001001432
NM_001276345

NM_001276346
NM_001276347

NM_001130174
NM_001130175
NM_001130176
NM_001130177
NM_001130178

NM_001130179
NM_001130180
NM_001130181
NM_011619

RefSeq (bjelančevina)
NP_000355
NP_001001430
NP_001001431
NP_001001432
NP_001263274

NP_001263275
NP_001263276

NP_001123646
NP_001123647
NP_001123648
NP_001123649
NP_001123650

NP_001123651
NP_001123652
NP_001123653
NP_035749

Lokacija (UCSC)Chr 1: 201.36 – 201.38 MbChr 1: 135.76 – 135.78 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

U ljudskom hromosomskom genomu, TNNT2 gen nalazi se na pozicijki 1q32, koja kodira izoformu srčanog mišića troponina T (cTnT). Ljudski cTnT je protein od ~36 kDa koji se sastoji od 297 aminokiselina uključujući prvi metionin sa izoelektričnom tačkom (pI) od 4,88. To je tropomiozin-vezujuća i tanka filamentna podjedinica troponinskog kompleksa u ćelijama srčanog mišića.[7][8][9] TNNT2 gen eksprimira se u srčanom mišiću kičmenjaka i skeletnim mišićima embriona.[8][9][10]

Aminokiselinska sekvenca

uredi

Dužina polipeptidnog lanca je 298 aminokiselina, a molekulska težina 35.924 Da.[11]

1020304050
MSDIEEVVEEYEEEEQEEAAVEEEEDWREDEDEQEEAAEEDAEAEAETEE
TRAEEDEEEEEAKEAEDGPMEESKPKPRSFMPNLVPPKIPDGERVDFDDI
HRKRMEKDLNELQALIEAHFENRKKEEEELVSLKDRIERRRAERAEQQRI
RNEREKERQNRLAEERARREEEENRRKAEDEARKKKALSNMMHFGGYIQK
QAQTERKSGKRQTEREKKKKILAERRKVLAIDHLNEDQLREKAKELWQSI
YNLEAEKFDLQEKFKQQKYEINVLRNRINDNQKVSKTRGKAKVTGRWK

Struktura

uredi

Srčani TnT je protein od 35,9 kDa koji se sastoji od 298 aminokiselina.[12][13] Najveća je od tri troponinske podjedinice (cTnT, troponin I (TnI), troponin C (TnC)) na aktinskom tankom filamentu srčanog mišića. Struktura TnT je asimetrična; globulski C-terminalni domen je u interakciji sa tropomiozinom (Tm), TnI i TnC, sa N-terminalnim vezom koja snažno vezuje Tm. N-terminalni region TnT je alternativno prerađen, što uzrokuje pojavu više izoformi uočenih u srčanom mišiću.[14]

Funkcija

uredi

Kao dio troponinskog kompleksa, funkcija cTnT je da regulira kontrakciju mišića. N-terminalni region TnT koji snažno vezuje aktin najverovatnije se pomjera sa Tm i aktinom tokom jakog miozinskog poprečnog vezivanja i stvaranja sile . Ovaj region je vjerovatno uključen u transdukciju kooperativnosti niz tanki filament.[15] C-terminalni region TnT čini dio domena globulastog troponinskog kompleksa i učestvuje u korištenju osetljivost na kalcij jakog miozinskog poprečnog mosta koji se vezuje za tanki filament.[16]

Alternativna prerada

uredi

TNNT2 gen sisara sadrži 14 konstitutivnih egzona i tri alternativno preražena egzona.[17] Egzoni 4 i 5 koji kodiraju N-terminalni varijabilni region i egzon 13 između srednjeg i C-terminalnog regiona su alternativno prerađeni.[18] Egzon 5 kodira segment od 9 ili 10 aminokiselina koji je visoko kiseo i negativno nabijen pri fiziološkom pH.[8] Ekgzon 5 eksprimira se u srcu embriona, a reguliše naniže i prestaje ekspresiju tokom postnatalnog razvoja.[19]

Embrionalni cTnT s više negativnog naboja na N-terminalnom području pokazuje veću osjetljivost na kalcij, aktivnost aktomiozinske ATPaze i proizvodnju sile miofilamenta, u poređenju sa srčanim TnT odraslih osoba, kao i veću toleranciju na acidozu.[20] TNNT2 gen je prolazno eksprimiran u embrionalnim i neonatalnim skeletnim mišićima i kod ptičjih i kod sisara.[21][22][23] Kada se TNNT2 eksprimira u neonatusnog skeletnog mišića, alternativna prerada egzona 5 pokazuje sinhronizovanu regulaciju sa onom u srcu na način specifičan za vrstu.[21] Ovaj fenomen ukazuje da je alternativna perada pre-iRNK TNNT2 pod kontrolom genetički ugrađenog sistemskog biološkog sata.

Posttranslacijske modifikacije

uredi

Fosforilacija

uredi

Ser2 cTnT na N-terminalu fosforiliran je konstitutivno nepoznatim mehanizmima.[7] Pronađeno je da je cTnT fosforiliran putem PKC na Thr197, Ser201, Thr206, Ser208 i Thr287 u C-terminalnoj regiji. Samo fosforilacija Thr206 bila je dovoljna da smanji osjetljivost miofilamenta na kalcij i proizvodnju sile. cTnT je također fosforiliran na Thr194 i Ser198 u uslovima stresa,[24] što dovodi do oslabljene kontraktilnosti kardiomiocita. Pokazalo se da fosforilacija cTnT na Ser278 i Thr287 pomoću ROCK-II smanjuje aktivnost miozinske ATPaze i razvoj sile miofilamenta u prekrivenom srčanom mišiću.[25] Tabela 1 sumira modifikacije fosforilacije cTnT i moguće funkcije.

O-vezana GlcNAcilacija

uredi

cTnT se sve više modificira na Ser190 O-GlcNAcilacijom tokom razvoja srčane insuficijencije kod pacova, praćeno smanjenom fosforilacijom Ser208.[26]

Proteolitska modifikacija

uredi

U apoptotskim kardiomiocitima, cTnT je razdvojen kaspazom 3, da bi se stvorio skraćeni fragment od 25 kDa na N-terminalnom dijelu.[27] Ova destruktivna fragmentacija uklanja dio srednjeg područja vezivanja tropomiozina 1,[28] dovodeći do slabljenja proizvodnje sile miofilamenta, smanjenjem aktivnosti miozinske ATPaze.

U srčanom mišiću u uslovima stresa, srčani TnT se cijepa kalpainom I, restriktivno uklanjajući čitavu varijabilnu regiju N-terminala.[29][30] Ova proteolitska modifikacija cTnT se javlja u srčanom mišiću u akutnoj ishemiji-reperfuziji ili preopterećenju pritiskom.[31]

Restriktivno skraćeni cTnT na N-terminalnom dijelu ostaje funkcionalan u miofilamentima i dovodi do smanjene kontraktilne brzine ventrikularnog mišića, što produžava fazu brzog izbacivanja i rezultira povećanjem udarnog volumena, posebno pod povećanim naknadnim opterećenjem.[31] In vitro studije pokazale su da je N-terminalni skraćeni cTnT očuvao ukupnu osjetljivost srčanog miofilamenta na kalcij i kooperativnost, ali je promijenio afinitete vezivanja TnT-a za tropomiozin, TnI i TnC proteine,[32] i dovode do blago smanjene maksimalne aktivnosti miozinske ATPaze i proizvodnje sile miofilamenta, što čini osnovu selektivnog smanjenja kontraktilne brzine srčanokomornog mišića, kako bi se povećao udarni volumen, bez značajnog povećanja potrošnje energije.[31]

Sa relativno kratkim poluživotom cTnT u kardiomiocitima (3-4 dana),[33] N-terminalni skraćeni cTnT bi bio zamijenjen novosintetiziranim netaknutim cTnT za nekoliko dana. Stoga ovaj mehanizam obezbjeđuje reverzibilnu posttranslacionu regulaciju za modulaciju srčane funkcije u prilagođavanju na stresne uslove.

Mesta fosforilacije u cTnT u poređenju sa ssTnT i fsTnT
Mjesto fosforilacije Kinaza Funkcija Reference
cTnT ssTnT fsTnT
Ser2 c c PKC Nepoznata [34][35][36]
Thr197 n N PKC Bez utijaja na funkciju [37][38]
Ser201 n n PKC Bez utijaja na funkciju [37][38]
Thr204 n n PKC Smanjuje aktivnost miozinske ATPaze, proizvodi sile miofilamenta i osjetljivost Ca2+ [38][39][40]
Thr204 n n CaMK II Nepotnata [41]
Thr204 n n ASK I Smanjuje kontraktilnost kardiomiocita [24]
Thr206 PKC Smanjuje Ca2+ osjetljivost, aktivnost aktomiozin ATPaze i razvoj napetosti [37]
Ser208 n n PKC Smanjuje aktivnost miozin ATPaze, mijenja osjetljivost miofilamenta Ca2+ [38][40][42]
Ser208 n n ASK I Smanjuje kontraktilnost kardiomiocita [24]
Thr213 c c PKC Smanjuje aktivnost miozin ATPaze, proizvodnju sile miofilamenta i Ca2+ osjetljivost [43]
Thr213 c c Raf-1 Nepoznata [44]
Ser285 n c PKC Smanjuje aktivnost miozin ATPaze, proizvodnju sile miofilamenta i Ca2+ osjetljivost [42]
Ser285 n c ROCK-II Smanjuja razvoj sile miofilamenta, aktivnost miozin ATPaze i Ca2+ osjetljivost [25]
Thr294 n n PKC Smanjuje aktivnost miozin ATPaze, proizvodnju sile miofilamenta i Ca2+ osjetljivost [38][39][40][42]
Thr294 n n ROCK-II Smanjuje razvoj sile miofilamenta, aktivnost miozin ATPaze i osjetljivost na Ca2+ [25]

Sumirani su rezidui u srčanom TnT sa regulacijom fosforilacije. Broj ostataka za fosforilacijski serin i treonin je onaj u ljudskom srčanom TnT sa uključenim prvim metioninom. Fosforilacija srčanog TnT na ovim ostacima upoređena je sa parnjacima u brzom TnT i sporom TnT. C, konzerciran; N je nekonzerviran. Također navedene su i kinaze odgovorne za svaku fosforilaciju, funkcionalne efekte.

Mutacije u kardiomiopatijama

uredi

Tačkaste mutacije u genu TNNT2 uzrokuju različite tipove kardiomiopatija, uključujući hipertrofnu kardiomiopatiju (HCM), proširenu kardiomiopatiju (DCM) i restriktivnu kardiomiopatiju (RCM). Tabela u nastavku rezimira reprezentativne TNNT2 mutacije i abnormalne spojeve pronađene kod ljudskih i životinjskih kardiomiopatija.

Reprezentativne TNNT2 mutacije i abnormalne prerade koje uzrokuju kardiomiopatiju
Mutacija Dijagnoza Referenca
Ile79Asn HCM [45][46][47]
Arg92Gln HCM [45][48]
Intron 16G1→A (D14 and D28+7) HCM [45]
Arg92Leu HCM [47][49]
Arg92Trp HCM [50][51][52]
Arg94Leu HCM [47][53]
Arg94Cys HCM [54]
ΔE96 RCM [55][56]
Ala104Val HCM [57]
Phe110Ile DCM [58][59]
Arg130Cys HCM [60]
Arg131Trp DCM [61][62]
E136K RCM [63]
Arg141Trp DCM [64][65]
DGlu160 HCM [66]
Glu163Arg HCM [60]
Glu163Lys HCM [58]
Ser179Phe HCM [67]
Arg205Leu DCM [61]
DLys210 DCM [68][69][70]
Glu244Asp HCM [58]
Asp270Asn DCM [68]
Lys273Glu DCM [71]
Arg278Cys HCM [58][72]

Aminokiselinski ostaci mutacija su numerisani kao u ljudskom srčanom TnT, sa uključenim prvim metioninom. Mutacije srčanog TnT koje su uzrokovale kardiomiopatije uglavnom su nađene u komnzerviranim srednjim i C-terminalnim regijama.

Klinički značaj

uredi

Mutacije ovog gena povezane su sa porodičnom hipertrofnom kardiomiopatijom, kao i sa restriktivnom[73] i dilatacijskom kardiomiopatijom. Transkripti za ovaj gen prolaze kroz alterasnivnu preradu, što rezultira mnogim tkivno specifičnim izoformama; međutim, priroda pune dužine nekih od ovih varijanti još nije utvrđena. Mutacije ovog gena mogu biti povezane sa blagom ili odsutnom hipertrofijom i dominantnom restriktivnom bolešću, sa visokim rizikom od iznenadne srčane smrti.[73] Može doći do bržeg napredovanja dilatacijske kardiomiopatije kod pacijenata sa TNNT2 mutacijama, nego kod onih sa mutacijama teškog lanca miozina.[50][71]

Evolucija

uredi
 
Par grna TnT i TnI

Kod kičmenjaka, evoluirala su tri homologna gena, koji kodiraju tri izoforme TnT specifične za tip mišića.[9] Svaki od gena izoformi TnT vezan je u hromosomskoj DNK sa genom izoforme troponina I (TnI), koji kodira inhibitornu podjedinicu troponinskog kompleksa i formira tri para gena: brzi skeletni mišić TnI (fsTnI)-fsTnT, spori skeletni mišić TnI ( ssTnI)-cTnT i cTnI-ssTnT parovi. Studije o konzerviranosti sekvenci i epitopa sugeriraju da geni koji kodiraju izoforme TnT i TnI specifične za tip mišića potiču iz predačkog gena sličnog TnI i dupliciraju se i diverzificiraju iz para gena sličnog fsTnI-u i fsTnT.[28]

 
Filogenetsko stablo gena TNNT2

Očigledno isprepletena veza između ssTnI-cTnT i cTnI-ssTnT gena zapravo odražava originalne funkcionalne veze jer je gen TNNT2 eksprimiran zajedno sa ssTnI genom u embrionskom srčanom mišiću.[21] Poravnavanje proteinske sekvence gena pokazalo je da je TNNT2 gen pkouzzerviran kod vrsta kičmenjaka (slika 2) u srednjem i C-terminalnom području, dok se tri izoforme mišićnog tipa značajno razlikuju.[8][9]

Klinički značaj

uredi

Mutacije ovog gena povezane su sa porodičnom hipertrofnom kardiomiopatijom, kao i sa restriktivnom[73] i dilatacijskom kardiomiopatijom. Transkripti za ovaj gen prolaze kroz alternativnu preradu, što rezultira mnogim tkivno specifičnim izoformama, ali priroda pune dužine nekih od ovih varijanti još nije utvrđena.[74] Mutacije ovog gena mogu biti povezane sa blagom ili odsutnom hipertrofijom i dominantnom restriktivnom bolešću, sa visokim rizikom od iznenadne srčane smrti.[73]

Reference

uredi
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000118194 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026414 - Ensembl, maj 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Townsend PJ, Farza H, MacGeoch C, Spurr NK, Wade R, Gahlmann R, Yacoub MH, Barton PJ (maj 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.
  6. ^ 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.
  7. ^ a b Perry SV (Aug 1998). "Troponin T: genetics, properties and function". Journal of Muscle Research and Cell Motility. 19 (6): 575–602. doi:10.1023/a:1005397501968. PMID 9742444. S2CID 1882224.
  8. ^ a b c d Jin JP, Zhang Z, Bautista JA (2008). "Isoform diversity, regulation, and functional adaptation of troponin and calponin". Critical Reviews in Eukaryotic Gene Expression. 18 (2): 93–124. doi:10.1615/critreveukargeneexpr.v18.i2.10. PMID 18304026.
  9. ^ a b c d Wei B, Jin JP (Jan 2011). "Troponin T isoforms and posttranscriptional modifications: Evolution, regulation and function". Archives of Biochemistry and Biophysics. 505 (2): 144–54. doi:10.1016/j.abb.2010.10.013. PMC 3018564. PMID 20965144.
  10. ^ Sheng JJ, Jin JP (2014). "Gene regulation, alternative splicing, and posttranslational modification of troponin subunits in cardiac development and adaptation: a focused review". Frontiers in Physiology. 5: 165. doi:10.3389/fphys.2014.00165. PMC 4012202. PMID 24817852.
  11. ^ "UniProt, P45379" (jezik: engleski). Pristupljeno 17. 12. 2021.
  12. ^ "Troponin T, cardiac muscle". Cardiac Organellar Protein Atlas Database. Arhivirano s originala, 5. 3. 2016. Pristupljeno 17. 12. 2021. Greška kod citiranja: Neispravna oznaka <ref>; naziv "COPa_Knowledgebase" definiran je nekoliko puta s različitim sadržajem
  13. ^ Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P (Oct 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.
  14. ^ 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): 1226–33. doi:10.1161/01.res.69.5.1226. PMID 1934353.
  15. ^ Kobayashi T, Solaro RJ (2005). "Calcium, thin filaments, and the integrative biology of cardiac contractility". Annual Review of Physiology. 67: 39–67. doi:10.1146/annurev.physiol.67.040403.114025. PMID 15709952.
  16. ^ Kobayashi T, Jin L, de Tombe PP (Oct 2008). "Cardiac thin filament regulation". Pflügers Archiv. 457 (1): 37–46. doi:10.1007/s00424-008-0511-8. PMC 2898130. PMID 18421471.
  17. ^ Jin JP, Huang QQ, Yeh HI, Lin JJ (Oct 1992). "Complete nucleotide sequence and structural organization of rat cardiac troponin T gene. A single gene generates embryonic and adult isoforms via developmentally regulated alternative splicing". Journal of Molecular Biology. 227 (4): 1269–76. doi:10.1016/0022-2836(92)90540-Z. PMID 1433301.
  18. ^ Farza H, Townsend PJ, Carrier L, Barton PJ, Mesnard L, Bährend E, Forissier JF, Fiszman M, Yacoub MH, Schwartz K (Jun 1998). "Genomic organisation, alternative splicing and polymorphisms of the human cardiac troponin T gene". Journal of Molecular and Cellular Cardiology. 30 (6): 1247–53. doi:10.1006/jmcc.1998.0698. PMID 9689598.
  19. ^ Jin JP, Lin JJ (Aug 1989). "Isolation and characterization of cDNA clones encoding embryonic and adult isoforms of rat cardiac troponin T". The Journal of Biological Chemistry. 264 (24): 14471–7. doi:10.1016/S0021-9258(18)71702-X. PMID 2760070.
  20. ^ Solaro RJ, Lee JA, Kentish JC, Allen DG (Oct 1988). "Effects of acidosis on ventricular muscle from adult and neonatal rats". Circulation Research. 63 (4): 779–87. doi:10.1161/01.RES.63.4.779. PMID 3168178.
  21. ^ a b c Jin JP (Aug 1996). "Alternative RNA splicing-generated cardiac troponin T isoform switching: a non-heart-restricted genetic programming synchronized in developing cardiac and skeletal muscles". Biochemical and Biophysical Research Communications. 225 (3): 883–9. doi:10.1006/bbrc.1996.1267. PMID 8780706.
  22. ^ Toyota N, Shimada Y (maj 1983). "Isoform variants of troponin in skeletal and cardiac muscle cells cultured with and without nerves". Cell. 33 (1): 297–304. doi:10.1016/0092-8674(83)90358-6. PMID 6380757. S2CID 10037331.
  23. ^ Cooper TA, Ordahl CP (Sep 1985). "A single cardiac troponin T gene generates embryonic and adult isoforms via developmentally regulated alternate splicing". The Journal of Biological Chemistry. 260 (20): 11140–8. doi:10.1016/S0021-9258(17)39158-5. PMID 2993302.
  24. ^ a b c He X, Liu Y, Sharma V, Dirksen RT, Waugh R, Sheu SS, Min W (Jul 2003). "ASK1 associates with troponin T and induces troponin T phosphorylation and contractile dysfunction in cardiomyocytes". The American Journal of Pathology. 163 (1): 243–51. doi:10.1016/S0002-9440(10)63647-4. PMC 1868161. PMID 12819028.
  25. ^ a b c Vahebi S, Kobayashi T, Warren CM, de Tombe PP, Solaro RJ (Apr 2005). "Functional effects of rho-kinase-dependent phosphorylation of specific sites on cardiac troponin". Circulation Research. 96 (7): 740–7. doi:10.1161/01.RES.0000162457.56568.7d. PMID 15774859.
  26. ^ Dubois-Deruy E, Belliard A, Mulder P, Bouvet M, Smet-Nocca C, Janel S, Lafont F, Beseme O, Amouyel P, Richard V, Pinet F (Jul 2015). "Interplay between troponin T phosphorylation and O-N-acetylglucosaminylation in ischaemic heart failure". Cardiovascular Research. 107 (1): 56–65. doi:10.1093/cvr/cvv136. PMID 25916824.
  27. ^ Communal C, Sumandea M, de Tombe P, Narula J, Solaro RJ, Hajjar RJ (Apr 2002). "Functional consequences of caspase activation in cardiac myocytes". Proceedings of the National Academy of Sciences of the United States of America. 99 (9): 6252–6. Bibcode:2002PNAS...99.6252C. doi:10.1073/pnas.092022999. PMC 122935. PMID 11972044.
  28. ^ a b Chong SM, Jin JP (maj 2009). "To investigate protein evolution by detecting suppressed epitope structures". Journal of Molecular Evolution. 68 (5): 448–60. Bibcode:2009JMolE..68..448C. doi:10.1007/s00239-009-9202-0. PMC 2752406. PMID 19365646.
  29. ^ Geesink GH, Kuchay S, Chishti AH, Koohmaraie M (Oct 2006). "Micro-calpain is essential for postmortem proteolysis of muscle proteins". Journal of Animal Science. 84 (10): 2834–40. doi:10.2527/jas.2006-122. PMID 16971586.[mrtav link]
  30. ^ Zhang Z, Biesiadecki BJ, Jin JP (Sep 2006). "Selective deletion of the NH2-terminal variable region of cardiac troponin T in ischemia reperfusion by myofibril-associated mu-calpain cleavage". Biochemistry. 45 (38): 11681–94. doi:10.1021/bi060273s. PMC 1762003. PMID 16981728.
  31. ^ a b c Feng HZ, Biesiadecki BJ, Yu ZB, Hossain MM, Jin JP (Jul 2008). "Restricted N-terminal truncation of cardiac troponin T: a novel mechanism for functional adaptation to energetic crisis". The Journal of Physiology. 586 (14): 3537–50. doi:10.1113/jphysiol.2008.153577. PMC 2538805. PMID 18556368.
  32. ^ Pan BS, Gordon AM, Potter JD (Jul 1991). "Deletion of the first 45 NH2-terminal residues of rabbit skeletal troponin T strengthens binding of troponin to immobilized tropomyosin". The Journal of Biological Chemistry. 266 (19): 12432–8. doi:10.1016/S0021-9258(18)98916-7. PMID 1829457.
  33. ^ Martin AF (Jan 1981). "Turnover of cardiac troponin subunits. Kinetic evidence for a precursor pool of troponin-I". The Journal of Biological Chemistry. 256 (2): 964–8. doi:10.1016/S0021-9258(19)70073-8. PMID 7451483.
  34. ^ Villar-Palasi C, Kumon A (Jul 1981). "Purification and properties of dog cardiac troponin T kinase". The Journal of Biological Chemistry. 256 (14): 7409–15. doi:10.1016/S0021-9258(19)68978-7. PMID 7251602.
  35. ^ Gusev NB, Barskaya NV, Verin AD, Duzhenkova IV, Khuchua ZA, Zheltova AO (Jul 1983). "Some properties of cardiac troponin T structure". The Biochemical Journal. 213 (1): 123–9. doi:10.1042/bj2130123. PMC 1152098. PMID 6615417.
  36. ^ Zhang J, Zhang H, Ayaz-Guner S, Chen YC, Dong X, Xu Q, Ge Y (Jul 2011). "Phosphorylation, but not alternative splicing or proteolytic degradation, is conserved in human and mouse cardiac troponin T". Biochemistry. 50 (27): 6081–92. doi:10.1021/bi2006256. PMC 3312388. PMID 21639091.
  37. ^ a b c Sumandea MP, Pyle WG, Kobayashi T, de Tombe PP, Solaro RJ (Sep 2003). "Identification of a functionally critical protein kinase C phosphorylation residue of cardiac troponin T". The Journal of Biological Chemistry. 278 (37): 35135–44. doi:10.1074/jbc.M306325200. PMID 12832403.
  38. ^ a b c d e Jideama NM, Noland TA, Raynor RL, Blobe GC, Fabbro D, Kazanietz MG, Blumberg PM, Hannun YA, Kuo JF (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.
  39. ^ a b 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. doi:10.1016/S0021-9258(19)47130-5. PMID 2584239.
  40. ^ a b c Montgomery DE, Chandra M, Huang Q, Jin J, Solaro RJ (Mar 2001). "Transgenic incorporation of skeletal TnT into cardiac myofilaments blunts PKC-mediated depression of force". American Journal of Physiology. Heart and Circulatory Physiology. 280 (3): H1011–8. doi:10.1152/ajpheart.2001.280.3.H1011. PMID 11179042. S2CID 22690543.
  41. ^ Jaquet K, Fukunaga K, Miyamoto E, Meyer HE (Apr 1995). "A site phosphorylated in bovine cardiac troponin T by cardiac CaM kinase II". Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology. 1248 (2): 193–5. doi:10.1016/0167-4838(95)00028-s. PMID 7748902.
  42. ^ a b c Sumandea MP, Vahebi S, Sumandea CA, Garcia-Cazarin ML, Staidle J, Homsher E (Aug 2009). "Impact of cardiac troponin T N-terminal deletion and phosphorylation on myofilament function". Biochemistry. 48 (32): 7722–31. doi:10.1021/bi900516n. PMID 19586048.
  43. ^ Streng AS, de Boer D, van der Velden J, van Dieijen-Visser MP, Wodzig WK (Oct 2013). "Posttranslational modifications of cardiac troponin T: an overview". Journal of Molecular and Cellular Cardiology. 63: 47–56. doi:10.1016/j.yjmcc.2013.07.004. PMID 23871791.
  44. ^ Pfleiderer P, Sumandea MP, Rybin VO, Wang C, Steinberg SF (2009). "Raf-1: a novel cardiac troponin T kinase". Journal of Muscle Research and Cell Motility. 30 (1–2): 67–72. doi:10.1007/s10974-009-9176-y. PMC 2893395. PMID 19381846.
  45. ^ a b c Thierfelder L, Watkins H, MacRae C, Lamas R, McKenna W, Vosberg HP, Seidman JG, Seidman CE (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. S2CID 205021038.
  46. ^ Lin D, Bobkova A, Homsher E, Tobacman LS (Jun 1996). "Altered cardiac troponin T in vitro function in the presence of a mutation implicated in familial hypertrophic cardiomyopathy". The Journal of Clinical Investigation. 97 (12): 2842–8. doi:10.1172/JCI118740. PMC 507378. PMID 8675696.
  47. ^ a b c Palm T, Graboski S, Hitchcock-DeGregori SE, Greenfield NJ (Nov 2001). "Disease-causing mutations in cardiac troponin T: identification of a critical tropomyosin-binding region". Biophysical Journal. 81 (5): 2827–37. Bibcode:2001BpJ....81.2827P. doi:10.1016/S0006-3495(01)75924-3. PMC 1301748. PMID 11606294.
  48. ^ Marian AJ, Zhao G, Seta Y, Roberts R, Yu QT (Jul 1997). "Expression of a mutant (Arg92Gln) human cardiac troponin T, known to cause hypertrophic cardiomyopathy, impairs adult cardiac myocyte contractility". Circulation Research. 81 (1): 76–85. doi:10.1161/01.res.81.1.76. PMID 9201030.
  49. ^ Forissier JF, Carrier L, Farza H, Bonne G, Bercovici J, Richard P, Hainque B, Townsend PJ, Yacoub MH, Fauré S, Dubourg O, Millaire A, Hagège AA, Desnos M, Komajda M, Schwartz K (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.
  50. ^ a b Fujino N, Shimizu M, Ino H, Okeie K, Yamaguchi M, Yasuda T, Kokado H, Mabuchi H (maj 2001). "Cardiac troponin T Arg92Trp mutation and progression from hypertrophic to dilated cardiomyopathy". Clinical Cardiology. 24 (5): 397–402. doi:10.1002/clc.4960240510. PMC 6654954. PMID 11346248.
  51. ^ Moolman JC, Corfield VA, Posen B, Ngumbela K, Seidman C, Brink PA, Watkins H (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.
  52. ^ Shimizu M, Ino H, Yamaguchi M, Terai H, Uchiyama K, Inoue M, Ikeda M, Kawashima A, Mabuchi H (Nov 2003). "Autopsy findings in siblings with hypertrophic cardiomyopathy caused by Arg92Trp mutation in the cardiac troponin T gene showing dilated cardiomyopathy-like features". Clinical Cardiology. 26 (11): 536–9. doi:10.1002/clc.4960261112. PMC 6654022. PMID 14640471.
  53. ^ Varnava A, Baboonian C, Davison F, de Cruz L, Elliott PM, Davies MJ, McKenna WJ (Nov 1999). "A new mutation of the cardiac troponin T gene causing familial hypertrophic cardiomyopathy without left ventricular hypertrophy". Heart. 82 (5): 621–4. doi:10.1136/hrt.82.5.621. PMC 1760789. PMID 10525521.
  54. ^ D'Cruz LG, Baboonian C, Phillimore HE, Taylor R, Elliott PM, Varnava A, Davison F, McKenna WJ, Carter ND (Sep 2000). "Cytosine methylation confers instability on the cardiac troponin T gene in hypertrophic cardiomyopathy". Journal of Medical Genetics. 37 (9): 18e–18. doi:10.1136/jmg.37.9.e18. PMC 1734704. PMID 10978365.
  55. ^ Peddy SB, Vricella LA, Crosson JE, Oswald GL, Cohn RD, Cameron DE, Valle D, Loeys BL (maj 2006). "Infantile restrictive cardiomyopathy resulting from a mutation in the cardiac troponin T gene". Pediatrics. 117 (5): 1830–3. doi:10.1542/peds.2005-2301. PMID 16651346. S2CID 40700808.
  56. ^ Pinto JR, Parvatiyar MS, Jones MA, Liang J, Potter JD (Jan 2008). "A troponin T mutation that causes infantile restrictive cardiomyopathy increases Ca2+ sensitivity of force development and impairs the inhibitory properties of troponin". The Journal of Biological Chemistry. 283 (4): 2156–66. doi:10.1074/jbc.M707066200. PMID 18032382.
  57. ^ 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.
  58. ^ a b c d Watkins H, McKenna WJ, Thierfelder L, Suk HJ, Anan R, O'Donoghue A, Spirito P, Matsumori A, Moravec CS, Seidman JG (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.
  59. ^ Nakaura H, Yanaga F, Ohtsuki I, Morimoto S (Sep 1999). "Effects of missense mutations Phe110Ile and Glu244Asp in human cardiac troponin T on force generation in skinned cardiac muscle fibers". Journal of Biochemistry. 126 (3): 457–60. doi:10.1093/oxfordjournals.jbchem.a022473. PMID 10467159.
  60. ^ a b Koga Y, Toshima H, Kimura A, Harada H, Koyanagi T, Nishi H, Nakata M, Imaizumi T (Dec 1996). "Clinical manifestations of hypertrophic cardiomyopathy with mutations in the cardiac beta-myosin heavy chain gene or cardiac troponin T gene". Journal of Cardiac Failure. 2 (4 Suppl): S97–103. doi:10.1016/s1071-9164(96)80064-9. PMID 8951566.
  61. ^ a b Mogensen J, Murphy RT, Shaw T, Bahl A, Redwood C, Watkins H, Burke M, Elliott PM, McKenna WJ (Nov 2004). "Severe disease expression of cardiac troponin C and T mutations in patients with idiopathic dilated cardiomyopathy". Journal of the American College of Cardiology. 44 (10): 2033–40. doi:10.1016/j.jacc.2004.08.027. PMID 15542288.
  62. ^ Mirza M, Marston S, Willott R, Ashley C, Mogensen J, McKenna W, Robinson P, Redwood C, Watkins H (Aug 2005). "Dilated cardiomyopathy mutations in three thin filament regulatory proteins result in a common functional phenotype". The Journal of Biological Chemistry. 280 (31): 28498–506. doi:10.1074/jbc.M412281200. PMID 15923195.
  63. ^ Kaski JP, Syrris P, Burch M, Tomé-Esteban MT, Fenton M, Christiansen M, Andersen PS, Sebire N, Ashworth M, Deanfield JE, McKenna WJ, Elliott PM (Nov 2008). "Idiopathic restrictive cardiomyopathy in children is caused by mutations in cardiac sarcomere protein genes". Heart. 94 (11): 1478–84. doi:10.1136/hrt.2007.134684. PMID 18467357. S2CID 44257334.
  64. ^ Li D, Czernuszewicz GZ, Gonzalez O, Tapscott T, Karibe A, Durand JB, Brugada R, Hill R, Gregoritch JM, Anderson JL, Quiñones M, Bachinski LL, Roberts R (Oct 2001). "Novel cardiac troponin T mutation as a cause of familial dilated cardiomyopathy". Circulation. 104 (18): 2188–93. doi:10.1161/hc4301.098285. PMID 11684629.
  65. ^ Lu QW, Morimoto S, Harada K, Du CK, Takahashi-Yanaga F, Miwa Y, Sasaguri T, Ohtsuki I (Dec 2003). "Cardiac troponin T mutation R141W found in dilated cardiomyopathy stabilizes the troponin T-tropomyosin interaction and causes a Ca2+ desensitization". Journal of Molecular and Cellular Cardiology. 35 (12): 1421–7. doi:10.1016/j.yjmcc.2003.09.003. PMID 14654368.
  66. ^ Harada K, Takahashi-Yanaga F, Minakami R, Morimoto S, Ohtsuki I (Feb 2000). "Functional consequences of the deletion mutation deltaGlu160 in human cardiac troponin T". Journal of Biochemistry. 127 (2): 263–8. doi:10.1093/oxfordjournals.jbchem.a022603. PMID 10731693.
  67. ^ Van Driest SL, Ackerman MJ, Ommen SR, Shakur R, Will ML, Nishimura RA, Tajik AJ, Gersh BJ (Dec 2002). "Prevalence and severity of "benign" mutations in the beta-myosin heavy chain, cardiac troponin T, and alpha-tropomyosin genes in hypertrophic cardiomyopathy". Circulation. 106 (24): 3085–90. doi:10.1161/01.cir.0000042675.59901.14. PMID 12473556.
  68. ^ a b Kamisago M, Sharma SD, DePalma SR, Solomon S, Sharma P, McDonough B, Smoot L, Mullen MP, Woolf PK, Wigle ED, Seidman JG, Seidman CE (Dec 2000). "Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy". The New England Journal of Medicine. 343 (23): 1688–96. doi:10.1056/NEJM200012073432304. PMID 11106718.
  69. ^ Hanson EL, Jakobs PM, Keegan H, Coates K, Bousman S, Dienel NH, Litt M, Hershberger RE (Feb 2002). "Cardiac troponin T lysine 210 deletion in a family with dilated cardiomyopathy". Journal of Cardiac Failure. 8 (1): 28–32. doi:10.1054/jcaf.2002.31157. PMID 11862580.
  70. ^ Hershberger RE, Pinto JR, Parks SB, Kushner JD, Li D, Ludwigsen S, Cowan J, Morales A, Parvatiyar MS, Potter JD (Aug 2009). "Clinical and functional characterization of TNNT2 mutations identified in patients with dilated cardiomyopathy". Circulation: Cardiovascular Genetics. 2 (4): 306–13. doi:10.1161/CIRCGENETICS.108.846733. PMC 2900844. PMID 20031601.
  71. ^ a b Fujino N, Shimizu M, Ino H, Yamaguchi M, Yasuda T, Nagata M, Konno T, Mabuchi H (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.
  72. ^ Morimoto S, Nakaura H, Yanaga F, Ohtsuki I (Jul 1999). "Functional consequences of a carboxyl terminal missense mutation Arg278Cys in human cardiac troponin T". Biochemical and Biophysical Research Communications. 261 (1): 79–82. doi:10.1006/bbrc.1999.1000. PMID 10405326.
  73. ^ a b c d Revera M, Van der Merwe L, Heradien M, Goosen A, Corfield VA, Brink PA, Moolman-Smook JC (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. PMC 4213759. PMID 17612745.[mrtav link]
  74. ^ "Entrez Gene: TNNT2 troponin T type 2 (cardiac)".

Vanjski linkovi

uredi
Preuzeto iz "https://bs.wikipedia.org/w/index.php?title=TNNT2&oldid=3438876"