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{{Infobox_gene}}
{{PBB_Controls
'''Troponin I, slow skeletal muscle''' is a [[protein]] that in humans is encoded by the ''TNNI1'' [[gene]].<ref name="pmid2365354">{{cite journal | vauthors = Wade R, Eddy R, Shows TB, Kedes L | title = cDNA sequence, tissue-specific expression, and chromosomal mapping of the human slow-twitch skeletal muscle isoform of troponin I | journal = Genomics | volume = 7 | issue = 3 | pages = 346–57 | date = Jul 1990 | pmid = 2365354 | pmc =  | doi = 10.1016/0888-7543(90)90168-T }}</ref><ref name="pmid8144655">{{cite journal | vauthors = Corin SJ, Juhasz O, Zhu L, Conley P, Kedes L, Wade R | title = Structure and expression of the human slow twitch skeletal muscle troponin I gene | journal = The Journal of Biological Chemistry | volume = 269 | issue = 14 | pages = 10651–9 | date = Apr 1994 | pmid = 8144655 | pmc = | doi = }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: TNNI1 troponin I type 1 (skeletal, slow)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7135| accessdate = }}</ref> It is a tissue-specific subtype of [[troponin I]], which in turn is a part of the [[troponin complex]].
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
Gene ''TNNI1'', troponin I type 1 (skeletal muscle, slow), also known as ''TNN1'' and ''SSTNI'', is located at 1q31.3 in the human chromosomal genome, encoding the slow twitch skeletal muscle isoform of troponin I (ssTnI), the inhibitory subunit of the troponin complex in striated muscle myofilaments.<ref name = "Perry_1999">{{cite journal | vauthors = Perry SV | title = Troponin I: inhibitor or facilitator | journal = Molecular and Cellular Biochemistry | volume = 190 | issue = 1-2 | pages = 9–32 | date = Jan 1999 | pmid = 10098965 | doi = 10.1023/A:1006939307715 }}</ref><ref>{{cite journal | vauthors = Jin JP, Zhang Z, Bautista JA | title = Isoform diversity, regulation, and functional adaptation of troponin and calponin | journal = Critical Reviews in Eukaryotic Gene Expression | volume = 18 | issue = 2 | pages = 93–124 | pmid = 18304026 | doi =  10.1615/critreveukargeneexpr.v18.i2.10 | year=2008}}</ref> Human ''TNNI1'' spans 12.5 kilobases in the genomic DNA and contains 9 exons and 8 introns.<ref>{{cite journal | vauthors = Corin SJ, Juhasz O, Zhu L, Conley P, Kedes L, Wade R | title = Structure and expression of the human slow twitch skeletal muscle troponin I gene | journal = The Journal of Biological Chemistry | volume = 269 | issue = 14 | pages = 10651–9 | date = Apr 1994 | pmid = 8144655 | doi = }}</ref> Exon 2 to exon 8 contain the coding sequences, encoding a protein of 21.7 kDa consisting of 187 amino acids including the first methionine with an isoelectric point (pI) of 9.59.
{{GNF_Protein_box
| image = 
| image_source = 
| PDB =
| Name = Troponin I type 1 (skeletal, slow)
| HGNCid = 11945
| Symbol = TNNI1
| AltSymbols =; DKFZp451O223; TNN1
| OMIM = 191042
| ECnumber = 
| Homologene = 2462
| MGIid = 105073
| GeneAtlas_image1 = PBB_GE_TNNI1_205177_at_tn.png
| Function = {{GNF_GO|id=GO:0003779 |text = actin binding}} {{GNF_GO|id=GO:0005523 |text = tropomyosin binding}}
| Component = {{GNF_GO|id=GO:0005861 |text = troponin complex}}
| Process = {{GNF_GO|id=GO:0006942 |text = regulation of striated muscle contraction}}  
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 7135
    | Hs_Ensembl = ENSG00000159173
    | Hs_RefseqProtein = NP_003272
    | Hs_RefseqmRNA = NM_003281
    | Hs_GenLoc_db =
    | Hs_GenLoc_chr = 1
    | Hs_GenLoc_start = 199639519
    | Hs_GenLoc_end = 199665617
    | Hs_Uniprot = P19237
    | Mm_EntrezGene = 21952
    | Mm_Ensembl = ENSMUSG00000026418
    | Mm_RefseqmRNA = NM_021467
    | Mm_RefseqProtein = NP_067442
    | Mm_GenLoc_db =   
    | Mm_GenLoc_chr = 1
    | Mm_GenLoc_start = 137615850
    | Mm_GenLoc_end = 137627398
    | Mm_Uniprot = Q9WUZ5
  }}
}}
'''Troponin I type 1 (skeletal, slow)''', also known as '''TNNI1''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: TNNI1 troponin I type 1 (skeletal, slow)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7135| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Gene evolution ==
{{PBB_Summary
| section_title =  
| summary_text =  
}}


==References==
[[File:SsTnI align.jpg|thumb|left|Figure 1: Evolutionary lineage of vertebrate TNNI1 deduced from alignment of ssTnI amino acid sequences.]]
{{reflist|2}}
 
==Further reading==
Three homologous genes have evolved in vertebrates, encoding three muscle type-specific isoforms of TnI.<ref name="Perry_1999" /><ref>{{cite journal | vauthors = Hastings KE | title = Molecular evolution of the vertebrate troponin I gene family | journal = Cell Structure and Function | volume = 22 | issue = 1 | pages = 205–11 | date = Feb 1997 | pmid = 9113408 | doi = 10.1247/csf.22.205 }}</ref><ref>{{cite journal | vauthors = Chong SM, Jin JP | title = To investigate protein evolution by detecting suppressed epitope structures | journal = Journal of Molecular Evolution | volume = 68 | issue = 5 | pages = 448–60 | date = May 2009 | pmid = 19365646 | doi = 10.1007/s00239-009-9202-0 | pmc=2752406}}</ref> In mammals, the amino acid sequence of ssTnI is highly conserved. Mouse and bovine ssTnI each differs from human ssTnI in only four amino acids, and rhesus monkey ssTnI is identical to human in the amino acid sequences. In lower vertebrates, the divergence of ssTnI between species is larger than that in the higher vertebrates (Fig1).
{{refbegin | 2}}
 
{{PBB_Further_reading
== Tissue distribution ==
| citations =  
 
*{{cite journal | author=Hunkeler NM, Kullman J, Murphy AM |title=Troponin I isoform expression in human heart. |journal=Circ. Res. |volume=69 |issue= 5 |pages= 1409-14 |year= 1991 |pmid= 1934363 |doi= }}
Comparing with the fast twitch skeletal muscle and cardiac TnI isoform genes (''TNNT2'' and ''TNNT3''), ''TNNI1'' has a broader range of expression in avian and mammalian striated muscles. It is the predominant TnI isoform expressed in both slow skeletal muscle and cardiac muscle in early embryonic stage.<ref name="Sasse_1993">{{cite journal | vauthors = Sasse S, Brand NJ, Kyprianou P, Dhoot GK, Wade R, Arai M, Periasamy M, Yacoub MH, Barton PJ | title = Troponin I gene expression during human cardiac development and in end-stage heart failure | journal = Circulation Research | volume = 72 | issue = 5 | pages = 932–8 | date = May 1993 | pmid = 8477526 | doi = 10.1161/01.res.72.5.932}}</ref> An isoform switch from ssTnI to cTnI occurs during perinatal heart development.<ref name="Sasse_1993" /><ref>{{cite journal | vauthors = Saggin L, Gorza L, Ausoni S, Schiaffino S | title = Troponin I switching in the developing heart | journal = The Journal of Biological Chemistry | volume = 264 | issue = 27 | pages = 16299–302 | date = Sep 1989 | pmid = 2777792 | doi =  }}</ref><ref>{{cite journal | vauthors = Jin JP | title = Alternative RNA splicing-generated cardiac troponin T isoform switching: a non-heart-restricted genetic programming synchronized in developing cardiac and skeletal muscles | journal = Biochemical and Biophysical Research Communications | volume = 225 | issue = 3 | pages = 883–9 | date = Aug 1996 | pmid = 8780706 | doi = 10.1006/bbrc.1996.1267 }}</ref> ssTnI is not expressed in the embryonic hearts of ''Xenopus'' and zebrafish, while it is expressed in the somites and skeletal muscles.<ref>{{cite journal | vauthors = Warkman AS, Atkinson BG | title = The slow isoform of Xenopus troponin I is expressed in developing skeletal muscle but not in the heart | journal = Mechanisms of Development | volume = 115 | issue = 1-2 | pages = 143–6 | date = Jul 2002 | pmid = 12049779 | doi=10.1016/s0925-4773(02)00096-5}}</ref><ref>{{cite journal | vauthors = Fu CY, Lee HC, Tsai HJ | title = The molecular structures and expression patterns of zebrafish troponin I genes | journal = Gene Expression Patterns | volume = 9 | issue = 5 | pages = 348–56 | date = Jun 2009 | pmid = 19602390 | doi = 10.1016/j.gep.2009.02.001 }}</ref>
*{{cite journal  | author=Bhavsar PK, Dhoot GK, Cumming DV, ''et al.'' |title=Developmental expression of troponin I isoforms in fetal human heart. |journal=FEBS Lett. |volume=292 |issue= 1-2 |pages= 5-8 |year= 1992 |pmid= 1959627 |doi=  }}
 
*{{cite journal  | author=Suzuki H, Kawarabayasi Y, Kondo J, ''et al.'' |title=Structure and regulation of rat long-chain acyl-CoA synthetase. |journal=J. Biol. Chem. |volume=265 |issue= 15 |pages= 8681-5 |year= 1990 |pmid= 2341402 |doi= }}
== Structure-function relationships ==
*{{cite journal  | author=Wade R, Eddy R, Shows TB, Kedes L |title=cDNA sequence, tissue-specific expression, and chromosomal mapping of the human slow-twitch skeletal muscle isoform of troponin I. |journal=Genomics |volume=7 |issue= 3 |pages= 346-57 |year= 1990 |pmid= 2365354 |doi=  }}
 
*{{cite journal | author=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1-2 |pages= 171-4 |year= 1994 |pmid= 8125298 |doi= }}
The function of TnI is to control striated muscle contraction and relaxation. Troponin I interacts with all major regulatory proteins in the sarcomeric thin filaments of cardiac and skeletal muscles: troponin C, troponin T, tropomyosin and actin. When cytosolic Ca<sup>2+</sup> is low, TnI binds the thin filament to block the myosin binding sites on actin. The rise of cytosolic Ca<sup>2+</sup> results in binding to the N-terminal domain of troponin C and induces conformational changes in troponin C and the troponin complex, which releases the inhibition of myosin-actin interaction and activates myosin ATPase and cross bridge cycling to generate myosin power strokes and muscle contraction.
*{{cite journal | author=Corin SJ, Juhasz O, Zhu L, ''et al.'' |title=Structure and expression of the human slow twitch skeletal muscle troponin I gene. |journal=J. Biol. Chem. |volume=269 |issue= 14 |pages= 10651-9 |year= 1994 |pmid= 8144655 |doi= }}
 
*{{cite journal | author=Jha PK, Leavis PC, Sarkar S |title=Interaction of deletion mutants of troponins I and T: COOH-terminal truncation of troponin T abolishes troponin I binding and reduces Ca2+ sensitivity of the reconstituted regulatory system. |journal=Biochemistry |volume=35 |issue= 51 |pages= 16573-80 |year= 1997 |pmid= 8987992 |doi= 10.1021/bi9622433 }}
To date, no high resolution structure of ssTnI has been solved. As homologous proteins, ssTnI, fast skeletal muscle TnI and cardiac TnI have highly conserved structures and crystallographic high resolution structure of partial cardiac and fast skeletal troponin complex are both available. Therefore, the structure-function relationship of ssTnI would rely on the information from studies performed on fast skeletal muscle and cardiac TnI.
*{{cite journal  | author=Tiso N, Rampoldi L, Pallavicini A, ''et al.'' |title=Fine mapping of five human skeletal muscle genes: alpha-tropomyosin, beta-tropomyosin, troponin-I slow-twitch, troponin-I fast-twitch, and troponin-C fast. |journal=Biochem. Biophys. Res. Commun. |volume=230 |issue= 2 |pages= 347-50 |year= 1997 |pmid= 9016781 |doi= 10.1006/bbrc.1996.5958 }}
 
*{{cite journal  | author=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, ''et al.'' |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1-2 |pages= 149-56 |year= 1997 |pmid= 9373149 |doi= }}
== Posttranslational modifications ==
*{{cite journal | author=Jha PK, Sarkar S |title=A recombinant monocysteine mutant (Ser to Cys-155) of fast skeletal troponin T: identification by cross-linking of a domain involved in a physiologically relevant interaction with troponins C and I. |journal=Biochemistry |volume=37 |issue= 35 |pages= 12253-60 |year= 1998 |pmid= 9724539 |doi= 10.1021/bi980025z }}
 
*{{cite journal | author=Hartley JL, Temple GF, Brasch MA |title=DNA cloning using in vitro site-specific recombination. |journal=Genome Res. |volume=10 |issue= 11 |pages= 1788-95 |year= 2001 |pmid= 11076863 |doi= }}
To date, no posttranslational modification of ssTnI has been identified.
*{{cite journal | author=Wiemann S, Weil B, Wellenreuther R, ''et al.'' |title=Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. |journal=Genome Res. |volume=11 |issue= 3 |pages= 422-35 |year= 2001 |pmid= 11230166 |doi= 10.1101/gr.154701 }}
 
*{{cite journal | author=Lindhout DA, Li MX, Schieve D, Sykes BD |title=Effects of T142 phosphorylation and mutation R145G on the interaction of the inhibitory region of human cardiac troponin I with the C-domain of human cardiac troponin C. |journal=Biochemistry |volume=41 |issue= 23 |pages= 7267-74 |year= 2002 |pmid= 12044157 |doi= }}
== Mutations ==
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
 
*{{cite journal | author=Westfall MV, Borton AR |title=Role of troponin I phosphorylation in protein kinase C-mediated enhanced contractile performance of rat myocytes. |journal=J. Biol. Chem. |volume=278 |issue= 36 |pages= 33694-700 |year= 2003 |pmid= 12815045 |doi= 10.1074/jbc.M305404200 }}
To date, no human disease has been reported with mutations in ''TNNI1''.
*{{cite journal | author=Polly P, Haddadi LM, Issa LL, ''et al.'' |title=hMusTRD1alpha1 represses MEF2 activation of the troponin I slow enhancer. |journal=J. Biol. Chem. |volume=278 |issue= 38 |pages= 36603-10 |year= 2003 |pmid= 12857748 |doi= 10.1074/jbc.M212814200 }}
 
*{{cite journal | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40-5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
== Clinical significance ==
*{{cite journal | author=Thijssen VL, Ausma J, Gorza L, ''et al.'' |title=Troponin I isoform expression in human and experimental atrial fibrillation. |journal=Circulation |volume=110 |issue= 7 |pages= 770-5 |year= 2005 |pmid= 15289369 |doi= 10.1161/01.CIR.0000138849.03311.C6 }}
 
*{{cite journal | author=Brobbey A, Ravakhah K |title=Elevated serum cardiac troponin I level in a patient after a grand mal seizure and with no evidence of cardiac disease. |journal=Am. J. Med. Sci. |volume=328 |issue= 3 |pages= 189-91 |year= 2004 |pmid= 15367881 |doi= }}
Slow to fast skeletal TnI isoform switch occurs as an indicator for slow to fast fiber type transition in muscle adaptations.<ref>{{cite journal | vauthors = Stevens L, Bastide B, Kischel P, Pette D, Mounier Y | title = Time-dependent changes in expression of troponin subunit isoforms in unloaded rat soleus muscle | journal = American Journal of Physiology. Cell Physiology | volume = 282 | issue = 5 | pages = C1025-30 | date = May 2002 | pmid = 11940518 | doi = 10.1152/ajpcell.00252.2001 }}</ref> Slow skeletal TnI has been proposed as a sensitive and muscle fiber type-specific marker for skeletal muscle injuries.<ref>{{cite journal | vauthors = Simpson JA, Labugger R, Collier C, Brison RJ, Iscoe S, Van Eyk JE | title = Fast and slow skeletal troponin I in serum from patients with various skeletal muscle disorders: a pilot study | journal = Clinical Chemistry | volume = 51 | issue = 6 | pages = 966–72 | date = Jun 2005 | pmid = 15833785 | doi = 10.1373/clinchem.2004.042671 }}</ref><ref>{{cite journal | vauthors = Chapman DW, Simpson JA, Iscoe S, Robins T, Nosaka K | title = Changes in serum fast and slow skeletal troponin I concentration following maximal eccentric contractions | journal = Journal of Science and Medicine in Sport / Sports Medicine Australia | volume = 16 | issue = 1 | pages = 82–5 | date = Jan 2013 | pmid = 22795680 | doi = 10.1016/j.jsams.2012.05.006 }}</ref> In patients with skeletal muscle disorders, intact ssTnI or its degraded products may be detected in peripheral blood as a diagnostic indicator for slow fiber damages.
*{{cite journal | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
 
}}
== References ==
{{reflist|33em}}
 
== Further reading ==
{{refbegin|33em}}
* {{cite journal | vauthors = Hunkeler NM, Kullman J, Murphy AM | title = Troponin I isoform expression in human heart | journal = Circulation Research | volume = 69 | issue = 5 | pages = 1409–14 | date = Nov 1991 | pmid = 1934363 | doi = 10.1161/01.res.69.5.1409 }}
* {{cite journal | vauthors = Bhavsar PK, Dhoot GK, Cumming DV, Butler-Browne GS, Yacoub MH, Barton PJ | title = Developmental expression of troponin I isoforms in fetal human heart | journal = FEBS Letters | volume = 292 | issue = 1-2 | pages = 5–8 | date = Nov 1991 | pmid = 1959627 | doi = 10.1016/0014-5793(91)80820-S }}
* {{cite journal | vauthors = Suzuki H, Kawarabayasi Y, Kondo J, Abe T, Nishikawa K, Kimura S, Hashimoto T, Yamamoto T | title = Structure and regulation of rat long-chain acyl-CoA synthetase | journal = The Journal of Biological Chemistry | volume = 265 | issue = 15 | pages = 8681–5 | date = May 1990 | pmid = 2341402 | doi = }}
* {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1-2 | pages = 171–4 | date = Jan 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
* {{cite journal | vauthors = Jha PK, Leavis PC, Sarkar S | title = Interaction of deletion mutants of troponins I and T: COOH-terminal truncation of troponin T abolishes troponin I binding and reduces Ca2+ sensitivity of the reconstituted regulatory system | journal = Biochemistry | volume = 35 | issue = 51 | pages = 16573–80 | date = Dec 1996 | pmid = 8987992 | doi = 10.1021/bi9622433 }}
* {{cite journal | vauthors = Tiso N, Rampoldi L, Pallavicini A, Zimbello R, Pandolfo D, Valle G, Lanfranchi G, Danieli GA | title = Fine mapping of five human skeletal muscle genes: alpha-tropomyosin, beta-tropomyosin, troponin-I slow-twitch, troponin-I fast-twitch, and troponin-C fast | journal = Biochemical and Biophysical Research Communications | volume = 230 | issue = 2 | pages = 347–50 | date = Jan 1997 | pmid = 9016781 | doi = 10.1006/bbrc.1996.5958 }}
* {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1-2 | pages = 149–56 | date = Oct 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
* {{cite journal | vauthors = Jha PK, Sarkar S | title = A recombinant monocysteine mutant (Ser to Cys-155) of fast skeletal troponin T: identification by cross-linking of a domain involved in a physiologically relevant interaction with troponins C and I | journal = Biochemistry | volume = 37 | issue = 35 | pages = 12253–60 | date = Sep 1998 | pmid = 9724539 | doi = 10.1021/bi980025z }}
* {{cite journal | vauthors = Hartley JL, Temple GF, Brasch MA | title = DNA cloning using in vitro site-specific recombination | journal = Genome Research | volume = 10 | issue = 11 | pages = 1788–95 | date = Nov 2000 | pmid = 11076863 | pmc = 310948 | doi = 10.1101/gr.143000 }}
* {{cite journal | vauthors = Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A | title = Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs | journal = Genome Research | volume = 11 | issue = 3 | pages = 422–35 | date = Mar 2001 | pmid = 11230166 | pmc = 311072 | doi = 10.1101/gr.GR1547R }}
* {{cite journal | vauthors = Lindhout DA, Li MX, Schieve D, Sykes BD | title = Effects of T142 phosphorylation and mutation R145G on the interaction of the inhibitory region of human cardiac troponin I with the C-domain of human cardiac troponin C | journal = Biochemistry | volume = 41 | issue = 23 | pages = 7267–74 | date = Jun 2002 | pmid = 12044157 | doi = 10.1021/bi020100c }}
* {{cite journal | vauthors = Westfall MV, Borton AR | title = Role of troponin I phosphorylation in protein kinase C-mediated enhanced contractile performance of rat myocytes | journal = The Journal of Biological Chemistry | volume = 278 | issue = 36 | pages = 33694–700 | date = Sep 2003 | pmid = 12815045 | doi = 10.1074/jbc.M305404200 }}
* {{cite journal | vauthors = Polly P, Haddadi LM, Issa LL, Subramaniam N, Palmer SJ, Tay ES, Hardeman EC | title = hMusTRD1alpha1 represses MEF2 activation of the troponin I slow enhancer | journal = The Journal of Biological Chemistry | volume = 278 | issue = 38 | pages = 36603–10 | date = Sep 2003 | pmid = 12857748 | doi = 10.1074/jbc.M212814200 }}
* {{cite journal | vauthors = Thijssen VL, Ausma J, Gorza L, van der Velden HM, Allessie MA, Van Gelder IC, Borgers M, van Eys GJ | title = Troponin I isoform expression in human and experimental atrial fibrillation | journal = Circulation | volume = 110 | issue = 7 | pages = 770–5 | date = Aug 2004 | pmid = 15289369 | doi = 10.1161/01.CIR.0000138849.03311.C6 }}
* {{cite journal | vauthors = Brobbey A, Ravakhah K | title = Elevated serum cardiac troponin I level in a patient after a grand mal seizure and with no evidence of cardiac disease | journal = The American Journal of the Medical Sciences | volume = 328 | issue = 3 | pages = 189–91 | date = Sep 2004 | pmid = 15367881 | doi = 10.1097/00000441-200409000-00012 }}
{{refend}}
{{refend}}


{{protein-stub}}
{{Cytoskeletal Proteins}}
{{WikiDoc Sources}}

Revision as of 06:10, 3 December 2017

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Troponin I, slow skeletal muscle is a protein that in humans is encoded by the TNNI1 gene.[1][2][3] It is a tissue-specific subtype of troponin I, which in turn is a part of the troponin complex.

Gene TNNI1, troponin I type 1 (skeletal muscle, slow), also known as TNN1 and SSTNI, is located at 1q31.3 in the human chromosomal genome, encoding the slow twitch skeletal muscle isoform of troponin I (ssTnI), the inhibitory subunit of the troponin complex in striated muscle myofilaments.[4][5] Human TNNI1 spans 12.5 kilobases in the genomic DNA and contains 9 exons and 8 introns.[6] Exon 2 to exon 8 contain the coding sequences, encoding a protein of 21.7 kDa consisting of 187 amino acids including the first methionine with an isoelectric point (pI) of 9.59.

Gene evolution

File:SsTnI align.jpg
Figure 1: Evolutionary lineage of vertebrate TNNI1 deduced from alignment of ssTnI amino acid sequences.

Three homologous genes have evolved in vertebrates, encoding three muscle type-specific isoforms of TnI.[4][7][8] In mammals, the amino acid sequence of ssTnI is highly conserved. Mouse and bovine ssTnI each differs from human ssTnI in only four amino acids, and rhesus monkey ssTnI is identical to human in the amino acid sequences. In lower vertebrates, the divergence of ssTnI between species is larger than that in the higher vertebrates (Fig1).

Tissue distribution

Comparing with the fast twitch skeletal muscle and cardiac TnI isoform genes (TNNT2 and TNNT3), TNNI1 has a broader range of expression in avian and mammalian striated muscles. It is the predominant TnI isoform expressed in both slow skeletal muscle and cardiac muscle in early embryonic stage.[9] An isoform switch from ssTnI to cTnI occurs during perinatal heart development.[9][10][11] ssTnI is not expressed in the embryonic hearts of Xenopus and zebrafish, while it is expressed in the somites and skeletal muscles.[12][13]

Structure-function relationships

The function of TnI is to control striated muscle contraction and relaxation. Troponin I interacts with all major regulatory proteins in the sarcomeric thin filaments of cardiac and skeletal muscles: troponin C, troponin T, tropomyosin and actin. When cytosolic Ca2+ is low, TnI binds the thin filament to block the myosin binding sites on actin. The rise of cytosolic Ca2+ results in binding to the N-terminal domain of troponin C and induces conformational changes in troponin C and the troponin complex, which releases the inhibition of myosin-actin interaction and activates myosin ATPase and cross bridge cycling to generate myosin power strokes and muscle contraction.

To date, no high resolution structure of ssTnI has been solved. As homologous proteins, ssTnI, fast skeletal muscle TnI and cardiac TnI have highly conserved structures and crystallographic high resolution structure of partial cardiac and fast skeletal troponin complex are both available. Therefore, the structure-function relationship of ssTnI would rely on the information from studies performed on fast skeletal muscle and cardiac TnI.

Posttranslational modifications

To date, no posttranslational modification of ssTnI has been identified.

Mutations

To date, no human disease has been reported with mutations in TNNI1.

Clinical significance

Slow to fast skeletal TnI isoform switch occurs as an indicator for slow to fast fiber type transition in muscle adaptations.[14] Slow skeletal TnI has been proposed as a sensitive and muscle fiber type-specific marker for skeletal muscle injuries.[15][16] In patients with skeletal muscle disorders, intact ssTnI or its degraded products may be detected in peripheral blood as a diagnostic indicator for slow fiber damages.

References

  1. ↑ Wade R, Eddy R, Shows TB, Kedes L (Jul 1990). "cDNA sequence, tissue-specific expression, and chromosomal mapping of the human slow-twitch skeletal muscle isoform of troponin I". Genomics. 7 (3): 346–57. doi:10.1016/0888-7543(90)90168-T. PMID 2365354.
  2. ↑ Corin SJ, Juhasz O, Zhu L, Conley P, Kedes L, Wade R (Apr 1994). "Structure and expression of the human slow twitch skeletal muscle troponin I gene". The Journal of Biological Chemistry. 269 (14): 10651–9. PMID 8144655.
  3. ↑ "Entrez Gene: TNNI1 troponin I type 1 (skeletal, slow)".
  4. ↑ 4.0 4.1 Perry SV (Jan 1999). "Troponin I: inhibitor or facilitator". Molecular and Cellular Biochemistry. 190 (1–2): 9–32. doi:10.1023/A:1006939307715. PMID 10098965.
  5. ↑ 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.
  6. ↑ Corin SJ, Juhasz O, Zhu L, Conley P, Kedes L, Wade R (Apr 1994). "Structure and expression of the human slow twitch skeletal muscle troponin I gene". The Journal of Biological Chemistry. 269 (14): 10651–9. PMID 8144655.
  7. ↑ Hastings KE (Feb 1997). "Molecular evolution of the vertebrate troponin I gene family". Cell Structure and Function. 22 (1): 205–11. doi:10.1247/csf.22.205. PMID 9113408.
  8. ↑ Chong SM, Jin JP (May 2009). "To investigate protein evolution by detecting suppressed epitope structures". Journal of Molecular Evolution. 68 (5): 448–60. doi:10.1007/s00239-009-9202-0. PMC 2752406. PMID 19365646.
  9. ↑ 9.0 9.1 Sasse S, Brand NJ, Kyprianou P, Dhoot GK, Wade R, Arai M, Periasamy M, Yacoub MH, Barton PJ (May 1993). "Troponin I gene expression during human cardiac development and in end-stage heart failure". Circulation Research. 72 (5): 932–8. doi:10.1161/01.res.72.5.932. PMID 8477526.
  10. ↑ Saggin L, Gorza L, Ausoni S, Schiaffino S (Sep 1989). "Troponin I switching in the developing heart". The Journal of Biological Chemistry. 264 (27): 16299–302. PMID 2777792.
  11. ↑ 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.
  12. ↑ Warkman AS, Atkinson BG (Jul 2002). "The slow isoform of Xenopus troponin I is expressed in developing skeletal muscle but not in the heart". Mechanisms of Development. 115 (1–2): 143–6. doi:10.1016/s0925-4773(02)00096-5. PMID 12049779.
  13. ↑ Fu CY, Lee HC, Tsai HJ (Jun 2009). "The molecular structures and expression patterns of zebrafish troponin I genes". Gene Expression Patterns. 9 (5): 348–56. doi:10.1016/j.gep.2009.02.001. PMID 19602390.
  14. ↑ Stevens L, Bastide B, Kischel P, Pette D, Mounier Y (May 2002). "Time-dependent changes in expression of troponin subunit isoforms in unloaded rat soleus muscle". American Journal of Physiology. Cell Physiology. 282 (5): C1025–30. doi:10.1152/ajpcell.00252.2001. PMID 11940518.
  15. ↑ Simpson JA, Labugger R, Collier C, Brison RJ, Iscoe S, Van Eyk JE (Jun 2005). "Fast and slow skeletal troponin I in serum from patients with various skeletal muscle disorders: a pilot study". Clinical Chemistry. 51 (6): 966–72. doi:10.1373/clinchem.2004.042671. PMID 15833785.
  16. ↑ Chapman DW, Simpson JA, Iscoe S, Robins T, Nosaka K (Jan 2013). "Changes in serum fast and slow skeletal troponin I concentration following maximal eccentric contractions". Journal of Science and Medicine in Sport / Sports Medicine Australia. 16 (1): 82–5. doi:10.1016/j.jsams.2012.05.006. PMID 22795680.

Further reading

  • Hunkeler NM, Kullman J, Murphy AM (Nov 1991). "Troponin I isoform expression in human heart". Circulation Research. 69 (5): 1409–14. doi:10.1161/01.res.69.5.1409. PMID 1934363.
  • Bhavsar PK, Dhoot GK, Cumming DV, Butler-Browne GS, Yacoub MH, Barton PJ (Nov 1991). "Developmental expression of troponin I isoforms in fetal human heart". FEBS Letters. 292 (1–2): 5–8. doi:10.1016/0014-5793(91)80820-S. PMID 1959627.
  • Suzuki H, Kawarabayasi Y, Kondo J, Abe T, Nishikawa K, Kimura S, Hashimoto T, Yamamoto T (May 1990). "Structure and regulation of rat long-chain acyl-CoA synthetase". The Journal of Biological Chemistry. 265 (15): 8681–5. PMID 2341402.
  • Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
  • Jha PK, Leavis PC, Sarkar S (Dec 1996). "Interaction of deletion mutants of troponins I and T: COOH-terminal truncation of troponin T abolishes troponin I binding and reduces Ca2+ sensitivity of the reconstituted regulatory system". Biochemistry. 35 (51): 16573–80. doi:10.1021/bi9622433. PMID 8987992.
  • Tiso N, Rampoldi L, Pallavicini A, Zimbello R, Pandolfo D, Valle G, Lanfranchi G, Danieli GA (Jan 1997). "Fine mapping of five human skeletal muscle genes: alpha-tropomyosin, beta-tropomyosin, troponin-I slow-twitch, troponin-I fast-twitch, and troponin-C fast". Biochemical and Biophysical Research Communications. 230 (2): 347–50. doi:10.1006/bbrc.1996.5958. PMID 9016781.
  • Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
  • Jha PK, Sarkar S (Sep 1998). "A recombinant monocysteine mutant (Ser to Cys-155) of fast skeletal troponin T: identification by cross-linking of a domain involved in a physiologically relevant interaction with troponins C and I". Biochemistry. 37 (35): 12253–60. doi:10.1021/bi980025z. PMID 9724539.
  • Hartley JL, Temple GF, Brasch MA (Nov 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
  • Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A (Mar 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Research. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
  • Lindhout DA, Li MX, Schieve D, Sykes BD (Jun 2002). "Effects of T142 phosphorylation and mutation R145G on the interaction of the inhibitory region of human cardiac troponin I with the C-domain of human cardiac troponin C". Biochemistry. 41 (23): 7267–74. doi:10.1021/bi020100c. PMID 12044157.
  • Westfall MV, Borton AR (Sep 2003). "Role of troponin I phosphorylation in protein kinase C-mediated enhanced contractile performance of rat myocytes". The Journal of Biological Chemistry. 278 (36): 33694–700. doi:10.1074/jbc.M305404200. PMID 12815045.
  • Polly P, Haddadi LM, Issa LL, Subramaniam N, Palmer SJ, Tay ES, Hardeman EC (Sep 2003). "hMusTRD1alpha1 represses MEF2 activation of the troponin I slow enhancer". The Journal of Biological Chemistry. 278 (38): 36603–10. doi:10.1074/jbc.M212814200. PMID 12857748.
  • Thijssen VL, Ausma J, Gorza L, van der Velden HM, Allessie MA, Van Gelder IC, Borgers M, van Eys GJ (Aug 2004). "Troponin I isoform expression in human and experimental atrial fibrillation". Circulation. 110 (7): 770–5. doi:10.1161/01.CIR.0000138849.03311.C6. PMID 15289369.
  • Brobbey A, Ravakhah K (Sep 2004). "Elevated serum cardiac troponin I level in a patient after a grand mal seizure and with no evidence of cardiac disease". The American Journal of the Medical Sciences. 328 (3): 189–91. doi:10.1097/00000441-200409000-00012. PMID 15367881.
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