TPM2: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
m (Robot: Automated text replacement (-{{reflist}} +{{reflist|2}}, -<references /> +{{reflist|2}}, -{{WikiDoc Cardiology Network Infobox}} +))
 
m (1 revision imported)
 
(2 intermediate revisions by 2 users not shown)
Line 1: Line 1:
<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{for|the computer standard TPM 2.0|Trusted Platform Module}}
{{PBB_Controls
{{Infobox_gene}}
| update_page = yes
'''β-Tropomyosin''', also known as '''tropomyosin beta chain''' is a [[protein]] that in humans is encoded by the ''TPM2'' [[gene]].<ref name="pmid7606936">{{cite journal | vauthors = Hunt CC, Eyre HJ, Akkari PA, Meredith C, Dorosz SM, Wilton SD, Callen DF, Laing NG, Baker E | title = Assignment of the human beta tropomyosin gene (TPM2) to band 9p13 by fluorescence in situ hybridisation | journal = Cytogenetics and Cell Genetics | volume = 71 | issue = 1 | pages = 94–5 | date = Aug 1995 | pmid = 7606936 | pmc = | doi = 10.1159/000134070 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: TPM2 tropomyosin 2 (beta)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7169| accessdate = }}</ref> β-tropomyosin is striated muscle-specific [[coiled coil]] dimer that functions to stabilize [[ACTC1|actin]] filaments and regulate [[muscle contraction]].
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
== Structure ==
{{GNF_Protein_box
β-tropomyosin is roughly 32 kDa in molecular weight (284 amino acids), but multiple splice variants exist.<ref>{{cite journal | vauthors = Perry SV | title = Vertebrate tropomyosin: distribution, properties and function | journal = Journal of Muscle Research and Cell Motility | volume = 22 | issue = 1 | pages = 5–49 | date = 2001 | pmid = 11563548 | doi=10.1023/A:1010303732441}}</ref><ref>{{cite web|title=Protein sequence of human TPM2 (Uniprot ID: P07951)|url=http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=P07951|website=Cardiac Organellar Protein Atlas Knowledgebase (COPaKB)|accessdate=1 July 2015}}</ref><ref>{{cite web|title=Protein sequence of human TPM2 (Uniprot ID: P07951-2)|url=http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=P07951-2|website=Cardiac Organellar Protein Atlas Knowledgebase (COPaKB)|accessdate=1 July 2015}}</ref><ref>{{cite web|title=Protein sequence of human TPM2 (Uniprot ID: P07951-3)|url=http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=P07951-3|website=Cardiac Organellar Protein Atlas Knowledgebase (COPaKB)|accessdate=1 July 2015}}</ref> Tropomysin is a flexible protein homodimer or heterodimer composed of two [[alpha helix|alpha-helical]] chains, which adopt a bent [[coiled coil]] conformation to wrap around the seven [[ACTC1|actin]] molecules in a functional unit of muscle. It is polymerized end to end along the two grooves of [[ACTC1|actin]] filaments and provides stability to the filaments.<ref>{{cite journal | vauthors = Brown JH, Kim KH, Jun G, Greenfield NJ, Dominguez R, Volkmann N, Hitchcock-DeGregori SE, Cohen C | title = Deciphering the design of the tropomyosin molecule | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 15 | pages = 8496–501 | date = Jul 2001 | pmid = 11438684 | doi = 10.1073/pnas.131219198 | pmc=37464}}</ref> Tropomyosin dimers are composed of varying combinations of tropomyosin isoforms; human [[striated muscle]]s express protein from the ''TPM1'' (α-tropoomyosin), ''TPM2'' (β-tropomyosin) and ''TPM3'' (γ-tropomyosin) genes, with [[TPM1|α-tropomyosin]] being the predominant isoform in striated muscle. Fast [[skeletal muscle]] and [[cardiac muscle]] contain more αα-homodimers, and slow [[skeletal muscle]] contains more ββ-homodimers.<ref name = "Muthuchamy_1995">{{cite journal | vauthors = Muthuchamy M, Grupp IL, Grupp G, O'Toole BA, Kier AB, Boivin GP, Neumann J, Wieczorek DF | title = Molecular and physiological effects of overexpressing striated muscle beta-tropomyosin in the adult murine heart | journal = The Journal of Biological Chemistry | volume = 270 | issue = 51 | pages = 30593–603 | date = Dec 1995 | pmid = 8530495 | doi=10.1074/jbc.270.51.30593}}</ref> In human [[cardiac muscle]] the ratio of [[TPM1|α-tropomyosin]] to β-tropomyosin is roughly 5:1.<ref>{{cite journal | vauthors = Dube DK, McLean MD, Dube S, Poiesz BJ | title = Translational control of tropomyosin expression in vertebrate hearts | journal = Anatomical Record | volume = 297 | issue = 9 | pages = 1585–95 | date = Sep 2014 | pmid = 25125172 | doi = 10.1002/ar.22978 }}</ref><ref>{{cite journal | vauthors = Yin Z, Ren J, Guo W | title = Sarcomeric protein isoform transitions in cardiac muscle: a journey to heart failure | journal = Biochimica et Biophysica Acta | volume = 1852 | issue = 1 | pages = 47–52 | date = Jan 2015 | pmid = 25446994 | doi = 10.1016/j.bbadis.2014.11.003 | pmc=4268308}}</ref> It has been shown that different combinations of tropomyosin isoforms bind [[TNNT2|troponin T]] with differing affinities, demonstrating that isoform combinations are used to impart a specific functional impact.<ref name = "Muthuchamy_1995"/>
| image =
| image_source =
| PDB =  
| Name = Tropomyosin 2 (beta)
| HGNCid = 12011
| Symbol = TPM2
| AltSymbols =; AMCD1; DA1; TMSB
| OMIM = 190990
| ECnumber =
| Homologene = 55509
| MGIid = 98810
| GeneAtlas_image1 = PBB_GE_TPM2_204083_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_TPM2_212654_at_tn.png
| Function = {{GNF_GO|id=GO:0003779 |text = actin binding}} {{GNF_GO|id=GO:0008307 |text = structural constituent of muscle}}
| Component = {{GNF_GO|id=GO:0005856 |text = cytoskeleton}} {{GNF_GO|id=GO:0005862 |text = muscle thin filament tropomyosin}}
| Process =  
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 7169
    | Hs_Ensembl = ENSG00000198467
    | Hs_RefseqProtein = NP_003280
    | Hs_RefseqmRNA = NM_003289
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 9
    | Hs_GenLoc_start = 35671989
    | Hs_GenLoc_end = 35681017
    | Hs_Uniprot = P07951
    | Mm_EntrezGene = 22004
    | Mm_Ensembl = ENSMUSG00000028464
    | Mm_RefseqmRNA = NM_009416
    | Mm_RefseqProtein = NP_033442
    | Mm_GenLoc_db =
    | Mm_GenLoc_chr = 4
    | Mm_GenLoc_start = 43535812
    | Mm_GenLoc_end = 43544538
    | Mm_Uniprot = Q61344
  }}
}}
'''Tropomyosin 2 (beta)''', also known as '''TPM2''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: TPM2 tropomyosin 2 (beta)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7169| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
== Function ==
{{PBB_Summary
β-tropomyosin functions in association with [[TPM1|α-tropomyosin]] and the [[troponin]] complex—composed of [[TNNI3|troponin I]], [[TNNC1|troponin C]] and [[TNNT2|troponin T]]—to modulated the [[ACTC1|actin]] and [[MYH7|myosin]] interaction. In [[diastole]], the tropomyosin-[[troponin]] complex inhibits this interaction, and during [[systole]] the rise in intracellular [[calcium]] from [[sarcoplasmic reticulum]] binds to [[TNNC1|troponin C]] and induces a conformational change in the [[troponin]]-tropomyosin complex that disinhibits the actomyosin ATPase and permits [[Muscle contraction|contraction]].<ref name = "Muthuchamy_1995"/>
| section_title =  
| summary_text =
}}


==References==
Specific functional insights into the function of the β-tropomyosin [[isoform]] have come from studies employing transgenesis. A study overexpressing β-tropomyosin in adult [[cardiac muscle]] evoked a 34-fold increase in expression of β-tropomyosin, resulting in preferential formation of the αβ-tropomyosin heterodimer. Transgenic hearts showed a significant delay in [[cardiac cycle#diastole|relaxation time]] as well as a decrease in the maximum rate of left [[ventricle (heart)|ventricular]] [[cardiac cycle#diastole|relaxation]].<ref name = "Muthuchamy_1995"/> A more aggressive overexpression of β-tropomyosin (to over 75% of total tropomyosin) in the heart causes death of mice 10–14 days old, along with cardiac abnormalities, suggesting that the normal distribution of tropomyosin isoforms is critical to normal cardiac function.<ref>{{cite journal | vauthors = Muthuchamy M, Boivin GP, Grupp IL, Wieczorek DF | title = Beta-tropomyosin overexpression induces severe cardiac abnormalities | journal = Journal of Molecular and Cellular Cardiology | volume = 30 | issue = 8 | pages = 1545–57 | date = Aug 1998 | pmid = 9737941 | doi = 10.1006/jmcc.1998.0720 }}</ref>
{{reflist|2}}
 
==Further reading==
In a disease model of [[cardiac hypertrophy]], β-tropomyosin was shown to be reexpressed within two days following induction of pressure overload.<ref>{{cite journal | vauthors = Izumo S, Nadal-Ginard B, Mahdavi V | title = Protooncogene induction and reprogramming of cardiac gene expression produced by pressure overload | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 85 | issue = 2 | pages = 339–43 | date = Jan 1988 | pmid = 2963328 | doi=10.1073/pnas.85.2.339 | pmc=279543}}</ref>
{{refbegin | 2}}
 
{{PBB_Further_reading
Studies from mice, which express 98% [[TPM1|α-tropomyosin]], have shown that α-tropomyosin can be [[phosphorylation|phosphorylated]] at [[Serine]]-283, which is one [[amino acid]] away from the [[C-terminus]]. β-tropomyosin also has a [[Serine]] residue at position 283,<ref>{{cite web|title=Protein sequence alignment of human TPM1 and TPM2|url=https://www.uniprot.org/align/A2015070214JCWXFD4L|website=Uniprot Knowledgebase|accessdate=2 July 2015}}</ref> thus, it is likely that β-tropomyosin is also [[phosphorylation|phosphorylated]]. Mouse transgenic studies in which the [[phosphorylation]] site in [[TPM1|α-tropomyosin]] is mutated to [[Alanine]] have shown that [[phosphorylation]] may function to modulate tropomyosin polymerization, head-to-tail interactions between adjacent tropomyosin molecules, cooperativity, [[myosin]] [[ATPase]] activity, and the cardiac response to stress.<ref>{{cite journal|last1=Schulz|first1=EM|last2=Wieczorek|first2=DF|title=Tropomyosin de-phosphorylation in the heart: what are the consequences?|journal=Journal of muscle research and cell motility|date=August 2013|volume=34|issue=3–4|pages=239–46|pmid=23793376|doi=10.1007/s10974-013-9348-7}}</ref>
| citations =
 
*{{cite journal  | author=Gunning P, Weinberger R, Jeffrey P |title=Actin and tropomyosin isoforms in morphogenesis. |journal=Anat. Embryol. |volume=195 |issue= 4 |pages= 311-5 |year= 1997 |pmid= 9108196 |doi= }}
== Clinical significance ==
*{{cite journal | author=Holtzer ME, Kidd SG, Crimmins DL, Holtzer A |title=Beta beta homodimers exist in native rabbit skeletal muscle tropomyosin and increase after denaturation-renaturation. |journal=Protein Sci. |volume=1 |issue= 3 |pages= 335-41 |year= 1993 |pmid= 1304342 |doi= }}
A decrease in β-tropomyosin in patients with [[heart failure]] was demonstrated, as failing [[ventricle (heart)|ventricle]]s expressed solely [[TPM1|α-tropomyosin]].<ref>{{cite journal | vauthors = Purcell IF, Bing W, Marston SB | title = Functional analysis of human cardiac troponin by the in vitro motility assay: comparison of adult, foetal and failing hearts | journal = Cardiovascular Research | volume = 43 | issue = 4 | pages = 884–91 | date = Sep 1999 | pmid = 10615415 | doi=10.1016/s0008-6363(99)00123-6}}</ref>
*{{cite journal  | author=Höner B, Shoeman RL, Traub P |title=Degradation of cytoskeletal proteins by the human immunodeficiency virus type 1 protease. |journal=Cell Biol. Int. Rep. |volume=16 |issue= 7 |pages= 603-12 |year= 1992 |pmid= 1516138 |doi= }}
 
*{{cite journal  | author=Chevray PM, Nathans D |title=Protein interaction cloning in yeast: identification of mammalian proteins that react with the leucine zipper of Jun. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=89 |issue= 13 |pages= 5789-93 |year= 1992 |pmid= 1631061 |doi= }}
Heterozygous mutations in ''TPM2'' have been identified in patients with congenital cap myopathy, a rare disorder defined by cap-like structures in muscle fiber periphery.<ref>{{cite journal | vauthors = Ohlsson M, Quijano-Roy S, Darin N, Brochier G, Lacène E, Avila-Smirnow D, Fardeau M, Oldfors A, Tajsharghi H | title = New morphologic and genetic findings in cap disease associated with beta-tropomyosin (TPM2) mutations | journal = Neurology | volume = 71 | issue = 23 | pages = 1896–901 | date = Dec 2008 | pmid = 19047562 | doi = 10.1212/01.wnl.0000336654.44814.b8 }}</ref><ref>{{cite journal | vauthors = Tajsharghi H, Ohlsson M, Lindberg C, Oldfors A | title = Congenital myopathy with nemaline rods and cap structures caused by a mutation in the beta-tropomyosin gene (TPM2) | journal = Archives of Neurology | volume = 64 | issue = 9 | pages = 1334–8 | date = Sep 2007 | pmid = 17846275 | doi = 10.1001/archneur.64.9.1334 }}</ref><ref>{{cite journal | vauthors = Lehtokari VL, Ceuterick-de Groote C, de Jonghe P, Marttila M, Laing NG, Pelin K, Wallgren-Pettersson C | title = Cap disease caused by heterozygous deletion of the beta-tropomyosin gene TPM2 | journal = Neuromuscular Disorders | volume = 17 | issue = 6 | pages = 433–42 | date = Jun 2007 | pmid = 17434307 | doi = 10.1016/j.nmd.2007.02.015 }}</ref><ref>{{cite journal | vauthors = Clarke NF, Domazetovska A, Waddell L, Kornberg A, McLean C, North KN | title = Cap disease due to mutation of the beta-tropomyosin gene (TPM2) | journal = Neuromuscular Disorders | volume = 19 | issue = 5 | pages = 348–51 | date = May 2009 | pmid = 19345583 | doi = 10.1016/j.nmd.2009.03.003 }}</ref>
*{{cite journal | author=Prasad GL, Meissner S, Sheer DG, Cooper HL |title=A cDNA encoding a muscle-type tropomyosin cloned from a human epithelial cell line: identity with human fibroblast tropomyosin TM1. |journal=Biochem. Biophys. Res. Commun. |volume=177 |issue= 3 |pages= 1068-75 |year= 1991 |pmid= 2059197 |doi= }}
 
*{{cite journal | author=Libri D, Mouly V, Lemonnier M, Fiszman MY |title=A nonmuscle tropomyosin is encoded by the smooth/skeletal beta-tropomyosin gene and its RNA is transcribed from an internal promoter. |journal=J. Biol. Chem. |volume=265 |issue= 6 |pages= 3471-3 |year= 1990 |pmid= 2303454 |doi= }}
Mutations in ''TPM2'' have also been associated with [[nemaline myopathy]], a rare disorder characterized by muscle weakness and nemaline bodies,<ref>{{cite journal | vauthors = Mokbel N, Ilkovski B, Kreissl M, Memo M, Jeffries CM, Marttila M, Lehtokari VL, Lemola E, Grönholm M, Yang N, Menard D, Marcorelles P, Echaniz-Laguna A, Reimann J, Vainzof M, Monnier N, Ravenscroft G, McNamara E, Nowak KJ, Laing NG, Wallgren-Pettersson C, Trewhella J, Marston S, Ottenheijm C, North KN, Clarke NF | title = K7del is a common TPM2 gene mutation associated with nemaline myopathy and raised myofibre calcium sensitivity | journal = Brain | volume = 136 | issue = Pt 2 | pages = 494–507 | date = Feb 2013 | pmid = 23378224 | doi = 10.1093/brain/aws348 }}</ref><ref>{{cite journal | vauthors = Monnier N, Lunardi J, Marty I, Mezin P, Labarre-Vila A, Dieterich K, Jouk PS | title = Absence of beta-tropomyosin is a new cause of Escobar syndrome associated with nemaline myopathy | journal = Neuromuscular Disorders | volume = 19 | issue = 2 | pages = 118–23 | date = Feb 2009 | pmid = 19155175 | doi = 10.1016/j.nmd.2008.11.009 | url = http://www.hal.inserm.fr/inserm-00410304 }}</ref><ref>{{cite journal | vauthors = Donner K, Ollikainen M, Ridanpää M, Christen HJ, Goebel HH, de Visser M, Pelin K, Wallgren-Pettersson C | title = Mutations in the beta-tropomyosin (TPM2) gene--a rare cause of nemaline myopathy | journal = Neuromuscular Disorders | volume = 12 | issue = 2 | pages = 151–8 | date = Feb 2002 | pmid = 11738357 | doi=10.1016/s0960-8966(01)00252-8}}</ref>
*{{cite journal | author=Widada JS, Ferraz C, Capony JP, Liautard JP |title=Complete nucleotide sequence of the adult skeletal isoform of human skeletal muscle beta-tropomyosin. |journal=Nucleic Acids Res. |volume=16 |issue= 7 |pages= 3109 |year= 1988 |pmid= 3368322 |doi= }}
 
*{{cite journal | author=Brown HR, Schachat FH |title=Renaturation of skeletal muscle tropomyosin: implications for in vivo assembly. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=82 |issue= 8 |pages= 2359-63 |year= 1985 |pmid= 3857586 |doi= }}
as well as distal [[arthrogryposis]].<ref>{{cite journal | vauthors = Tajsharghi H, Kimber E, Holmgren D, Tulinius M, Oldfors A | title = Distal arthrogryposis and muscle weakness associated with a beta-tropomyosin mutation | journal = Neurology | volume = 68 | issue = 10 | pages = 772–5 | date = Mar 2007 | pmid = 17339586 | doi = 10.1212/01.wnl.0000256339.40667.fb }}</ref><ref>{{cite journal | vauthors = Sung SS, Brassington AM, Grannatt K, Rutherford A, Whitby FG, Krakowiak PA, Jorde LB, Carey JC, Bamshad M | title = Mutations in genes encoding fast-twitch contractile proteins cause distal arthrogryposis syndromes | journal = American Journal of Human Genetics | volume = 72 | issue = 3 | pages = 681–90 | date = Mar 2003 | pmid = 12592607 | doi = 10.1086/368294 | pmc=1180243}}</ref>
*{{cite journal | author=MacLeod AR, Houlker C, Reinach FC, ''et al.'' |title=A muscle-type tropomyosin in human fibroblasts: evidence for expression by an alternative RNA splicing mechanism. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=82 |issue= 23 |pages= 7835-9 |year= 1986 |pmid= 3865200 |doi= }}
 
*{{cite journal | author=Gimona M, Watakabe A, Helfman DM |title=Specificity of dimer formation in tropomyosins: influence of alternatively spliced exons on homodimer and heterodimer assembly. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=92 |issue= 21 |pages= 9776-80 |year= 1995 |pmid= 7568216 |doi= }}
The muscle weakness observed in these patients may be due to a change in mutated ''TPM2'' affinity for [[ACTC1|actin]] or decreased [[calcium]]-induced activation of [[contractility]].<ref>{{cite journal | vauthors = Marttila M, Lehtokari VL, Marston S, Nyman TA, Barnerias C, Beggs AH, Bertini E, Ceyhan-Birsoy O, Cintas P, Gerard M, Gilbert-Dussardier B, Hogue JS, Longman C, Eymard B, Frydman M, Kang PB, Klinge L, Kolski H, Lochmüller H, Magy L, Manel V, Mayer M, Mercuri E, North KN, Peudenier-Robert S, Pihko H, Probst FJ, Reisin R, Stewart W, Taratuto AL, de Visser M, Wilichowski E, Winer J, Nowak K, Laing NG, Winder TL, Monnier N, Clarke NF, Pelin K, Grönholm M, Wallgren-Pettersson C | title = Mutation update and genotype-phenotype correlations of novel and previously described mutations in TPM2 and TPM3 causing congenital myopathies | journal = Human Mutation | volume = 35 | issue = 7 | pages = 779–90 | date = Jul 2014 | pmid = 24692096 | doi = 10.1002/humu.22554 | pmc=4200603}}</ref><ref name = "Robinson_2007">{{cite journal | vauthors = Robinson P, Lipscomb S, Preston LC, Altin E, Watkins H, Ashley CC, Redwood CS | title = Mutations in fast skeletal troponin I, troponin T, and beta-tropomyosin that cause distal arthrogryposis all increase contractile function | journal = FASEB Journal | volume = 21 | issue = 3 | pages = 896–905 | date = Mar 2007 | pmid = 17194691 | doi = 10.1096/fj.06-6899com }}</ref><ref>{{cite journal | vauthors = Marttila M, Lemola E, Wallefeld W, Memo M, Donner K, Laing NG, Marston S, Grönholm M, Wallgren-Pettersson C | title = Abnormal actin binding of aberrant β-tropomyosins is a molecular cause of muscle weakness in TPM2-related nemaline and cap myopathy | journal = The Biochemical Journal | volume = 442 | issue = 1 | pages = 231–9 | date = Feb 2012 | pmid = 22084935 | doi = 10.1042/BJ20111030 }}</ref> Moreover, studies unveiled alterations in cross-bridge attachment and detachment rates,<ref>{{cite journal | vauthors = Ochala J, Li M, Tajsharghi H, Kimber E, Tulinius M, Oldfors A, Larsson L | title = Effects of a R133W beta-tropomyosin mutation on regulation of muscle contraction in single human muscle fibres | journal = The Journal of Physiology | volume = 581 | issue = Pt 3 | pages = 1283–92 | date = Jun 2007 | pmid = 17430991 | doi = 10.1113/jphysiol.2007.129759 | pmc=2170843}}</ref> as well as changes in ATPase rates.<ref name = "Robinson_2007"/><ref>{{cite journal | vauthors = Marston S, Memo M, Messer A, Papadaki M, Nowak K, McNamara E, Ong R, El-Mezgueldi M, Li X, Lehman W | title = Mutations in repeating structural motifs of tropomyosin cause gain of function in skeletal muscle myopathy patients | journal = Human Molecular Genetics | volume = 22 | issue = 24 | pages = 4978–87 | date = Dec 2013 | pmid = 23886664 | doi = 10.1093/hmg/ddt345 | pmc=3836477}}</ref>
*{{cite journal | author=Hunt CC, Eyre HJ, Akkari PA, ''et al.'' |title=Assignment of the human beta tropomyosin gene (TPM2) to band 9p13 by fluorescence in situ hybridisation. |journal=Cytogenet. Cell Genet. |volume=71 |issue= 1 |pages= 94-5 |year= 1995 |pmid= 7606936 |doi= }}
 
*{{cite journal | author=Bamshad M, Watkins WS, Zenger RK, ''et al.'' |title=A gene for distal arthrogryposis type I maps to the pericentromeric region of chromosome 9. |journal=Am. J. Hum. Genet. |volume=55 |issue= 6 |pages= 1153-8 |year= 1994 |pmid= 7977374 |doi= }}
== Interactions ==
*{{cite journal | author=Takenaga K, Nakamura Y, Sakiyama S, ''et al.'' |title=Binding of pEL98 protein, an S100-related calcium-binding protein, to nonmuscle tropomyosin. |journal=J. Cell Biol. |volume=124 |issue= 5 |pages= 757-68 |year= 1994 |pmid= 8120097 |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= }}
TPM2 has been shown to [[Protein-protein interaction|interact]] with:
*{{cite journal | author=Shoeman RL, Sachse C, Höner B, ''et al.'' |title=Cleavage of human and mouse cytoskeletal and sarcomeric proteins by human immunodeficiency virus type 1 protease. Actin, desmin, myosin, and tropomyosin. |journal=Am. J. Pathol. |volume=142 |issue= 1 |pages= 221-30 |year= 1993 |pmid= 8424456 |doi=  }}
*[[RRAD]],<ref name=pmid8557685>{{cite journal | vauthors = Zhu J, Bilan PJ, Moyers JS, Antonetti DA, Kahn CR | title = Rad, a novel Ras-related GTPase, interacts with skeletal muscle beta-tropomyosin | journal = The Journal of Biological Chemistry | volume = 271 | issue = 2 | pages = 768–73 | date = Jan 1996 | pmid = 8557685 | doi = 10.1074/jbc.271.2.768 }}</ref>
*{{cite journal  | author=Zhu J, Bilan PJ, Moyers JS, ''et al.'' |title=Rad, a novel Ras-related GTPase, interacts with skeletal muscle beta-tropomyosin. |journal=J. Biol. Chem. |volume=271 |issue= 2 |pages= 768-73 |year= 1996 |pmid= 8557685 |doi= }}
*[[PDLIM7]],<ref name=pmid10359609>{{cite journal | vauthors = Guy PM, Kenny DA, Gill GN | title = The PDZ domain of the LIM protein enigma binds to beta-tropomyosin | journal = Molecular Biology of the Cell | volume = 10 | issue = 6 | pages = 1973–84 | date = Jun 1999 | pmid = 10359609 | pmc = 25398 | doi = 10.1091/mbc.10.6.1973 }}</ref>
*{{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 }}
* [[TNNT3]], and
*{{cite journal | author=Gimona M, Lando Z, Dolginov Y, ''et al.'' |title=Ca2+-dependent interaction of S100A2 with muscle and nonmuscle tropomyosins. |journal=J. Cell. Sci. |volume=110 ( Pt 5) |issue= |pages= 611-21 |year= 1997 |pmid= 9092943 |doi= }}
* [[TPM1]].<ref name=pmid3857586>{{cite journal | vauthors = Brown HR, Schachat FH | title = Renaturation of skeletal muscle tropomyosin: implications for in vivo assembly | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 82 | issue = 8 | pages = 2359–63 | date = Apr 1985 | pmid = 3857586 | pmc = 397557 | doi = 10.1073/pnas.82.8.2359 }}</ref>
*{{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= }}
 
}}
== References ==
{{reflist|33em}}
 
== Further reading ==
{{refbegin|33em}}
* {{cite journal | vauthors = Gunning P, Weinberger R, Jeffrey P | title = Actin and tropomyosin isoforms in morphogenesis | journal = Anatomy and Embryology | volume = 195 | issue = 4 | pages = 311–5 | date = Apr 1997 | pmid = 9108196 | doi = 10.1007/s004290050050 }}
* {{cite journal | vauthors = Holtzer ME, Kidd SG, Crimmins DL, Holtzer A | title = Beta beta homodimers exist in native rabbit skeletal muscle tropomyosin and increase after denaturation-renaturation | journal = Protein Science | volume = 1 | issue = 3 | pages = 335–41 | date = Mar 1992 | pmid = 1304342 | pmc = 2142203 | doi = 10.1002/pro.5560010305 }}
* {{cite journal | vauthors = Höner B, Shoeman RL, Traub P | title = Degradation of cytoskeletal proteins by the human immunodeficiency virus type 1 protease | journal = Cell Biology International Reports | volume = 16 | issue = 7 | pages = 603–12 | date = Jul 1992 | pmid = 1516138 | doi = 10.1016/S0309-1651(06)80002-0 }}
* {{cite journal | vauthors = Chevray PM, Nathans D | title = Protein interaction cloning in yeast: identification of mammalian proteins that react with the leucine zipper of Jun | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 89 | issue = 13 | pages = 5789–93 | date = Jul 1992 | pmid = 1631061 | pmc = 402103 | doi = 10.1073/pnas.89.13.5789 }}
* {{cite journal | vauthors = Prasad GL, Meissner S, Sheer DG, Cooper HL | title = A cDNA encoding a muscle-type tropomyosin cloned from a human epithelial cell line: identity with human fibroblast tropomyosin TM1 | journal = Biochemical and Biophysical Research Communications | volume = 177 | issue = 3 | pages = 1068–75 | date = Jun 1991 | pmid = 2059197 | doi = 10.1016/0006-291X(91)90647-P }}
* {{cite journal | vauthors = Libri D, Mouly V, Lemonnier M, Fiszman MY | title = A nonmuscle tropomyosin is encoded by the smooth/skeletal beta-tropomyosin gene and its RNA is transcribed from an internal promoter | journal = The Journal of Biological Chemistry | volume = 265 | issue = 6 | pages = 3471–3 | date = Feb 1990 | pmid = 2303454 | doi =  }}
* {{cite journal | vauthors = Widada JS, Ferraz C, Capony JP, Liautard JP | title = Complete nucleotide sequence of the adult skeletal isoform of human skeletal muscle beta-tropomyosin | journal = Nucleic Acids Research | volume = 16 | issue = 7 | pages = 3109 | date = Apr 1988 | pmid = 3368322 | pmc = 336462 | doi = 10.1093/nar/16.7.3109 }}
* {{cite journal | vauthors = MacLeod AR, Houlker C, Reinach FC, Smillie LB, Talbot K, Modi G, Walsh FS | title = A muscle-type tropomyosin in human fibroblasts: evidence for expression by an alternative RNA splicing mechanism | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 82 | issue = 23 | pages = 7835–9 | date = Dec 1985 | pmid = 3865200 | pmc = 390864 | doi = 10.1073/pnas.82.23.7835 }}
* {{cite journal | vauthors = Gimona M, Watakabe A, Helfman DM | title = Specificity of dimer formation in tropomyosins: influence of alternatively spliced exons on homodimer and heterodimer assembly | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 92 | issue = 21 | pages = 9776–80 | date = Oct 1995 | pmid = 7568216 | pmc = 40885 | doi = 10.1073/pnas.92.21.9776 }}
* {{cite journal | vauthors = Bamshad M, Watkins WS, Zenger RK, Bohnsack JF, Carey JC, Otterud B, Krakowiak PA, Robertson M, Jorde LB | title = A gene for distal arthrogryposis type I maps to the pericentromeric region of chromosome 9 | journal = American Journal of Human Genetics | volume = 55 | issue = 6 | pages = 1153–8 | date = Dec 1994 | pmid = 7977374 | pmc = 1918435 | doi =  }}
* {{cite journal | vauthors = Takenaga K, Nakamura Y, Sakiyama S, Hasegawa Y, Sato K, Endo H | title = Binding of pEL98 protein, an S100-related calcium-binding protein, to nonmuscle tropomyosin | journal = The Journal of Cell Biology | volume = 124 | issue = 5 | pages = 757–68 | date = Mar 1994 | pmid = 8120097 | pmc = 2119958 | doi = 10.1083/jcb.124.5.757 }}
* {{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 = Shoeman RL, Sachse C, Höner B, Mothes E, Kaufmann M, Traub P | title = Cleavage of human and mouse cytoskeletal and sarcomeric proteins by human immunodeficiency virus type 1 protease. Actin, desmin, myosin, and tropomyosin | journal = The American Journal of Pathology | volume = 142 | issue = 1 | pages = 221–30 | date = Jan 1993 | pmid = 8424456 | pmc = 1886840 | doi =  }}
* {{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 = Gimona M, Lando Z, Dolginov Y, Vandekerckhove J, Kobayashi R, Sobieszek A, Helfman DM | title = Ca2+-dependent interaction of S100A2 with muscle and nonmuscle tropomyosins | journal = Journal of Cell Science | volume = 110 | issue = 5 | pages = 611–21 | date = Mar 1997 | pmid = 9092943 | doi =  }}
* {{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 }}
{{refend}}
{{refend}}


{{protein-stub}}
== External links ==
{{WikiDoc Sources}}
* [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=nem  GeneReviews/NCBI/NIH/UW entry on Nemaline Myopathy]
 
{{Cytoskeletal Proteins}}

Latest revision as of 07:33, 10 January 2019

For the computer standard TPM 2.0, see Trusted Platform Module.
VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

n/a

n/a

Ensembl

n/a

n/a

UniProt

n/a

n/a

RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

β-Tropomyosin, also known as tropomyosin beta chain is a protein that in humans is encoded by the TPM2 gene.[1][2] β-tropomyosin is striated muscle-specific coiled coil dimer that functions to stabilize actin filaments and regulate muscle contraction.

Structure

β-tropomyosin is roughly 32 kDa in molecular weight (284 amino acids), but multiple splice variants exist.[3][4][5][6] Tropomysin is a flexible protein homodimer or heterodimer composed of two alpha-helical chains, which adopt a bent coiled coil conformation to wrap around the seven actin molecules in a functional unit of muscle. It is polymerized end to end along the two grooves of actin filaments and provides stability to the filaments.[7] Tropomyosin dimers are composed of varying combinations of tropomyosin isoforms; human striated muscles express protein from the TPM1 (α-tropoomyosin), TPM2 (β-tropomyosin) and TPM3 (γ-tropomyosin) genes, with α-tropomyosin being the predominant isoform in striated muscle. Fast skeletal muscle and cardiac muscle contain more αα-homodimers, and slow skeletal muscle contains more ββ-homodimers.[8] In human cardiac muscle the ratio of α-tropomyosin to β-tropomyosin is roughly 5:1.[9][10] It has been shown that different combinations of tropomyosin isoforms bind troponin T with differing affinities, demonstrating that isoform combinations are used to impart a specific functional impact.[8]

Function

β-tropomyosin functions in association with α-tropomyosin and the troponin complex—composed of troponin I, troponin C and troponin T—to modulated the actin and myosin interaction. In diastole, the tropomyosin-troponin complex inhibits this interaction, and during systole the rise in intracellular calcium from sarcoplasmic reticulum binds to troponin C and induces a conformational change in the troponin-tropomyosin complex that disinhibits the actomyosin ATPase and permits contraction.[8]

Specific functional insights into the function of the β-tropomyosin isoform have come from studies employing transgenesis. A study overexpressing β-tropomyosin in adult cardiac muscle evoked a 34-fold increase in expression of β-tropomyosin, resulting in preferential formation of the αβ-tropomyosin heterodimer. Transgenic hearts showed a significant delay in relaxation time as well as a decrease in the maximum rate of left ventricular relaxation.[8] A more aggressive overexpression of β-tropomyosin (to over 75% of total tropomyosin) in the heart causes death of mice 10–14 days old, along with cardiac abnormalities, suggesting that the normal distribution of tropomyosin isoforms is critical to normal cardiac function.[11]

In a disease model of cardiac hypertrophy, β-tropomyosin was shown to be reexpressed within two days following induction of pressure overload.[12]

Studies from mice, which express 98% α-tropomyosin, have shown that α-tropomyosin can be phosphorylated at Serine-283, which is one amino acid away from the C-terminus. β-tropomyosin also has a Serine residue at position 283,[13] thus, it is likely that β-tropomyosin is also phosphorylated. Mouse transgenic studies in which the phosphorylation site in α-tropomyosin is mutated to Alanine have shown that phosphorylation may function to modulate tropomyosin polymerization, head-to-tail interactions between adjacent tropomyosin molecules, cooperativity, myosin ATPase activity, and the cardiac response to stress.[14]

Clinical significance

A decrease in β-tropomyosin in patients with heart failure was demonstrated, as failing ventricles expressed solely α-tropomyosin.[15]

Heterozygous mutations in TPM2 have been identified in patients with congenital cap myopathy, a rare disorder defined by cap-like structures in muscle fiber periphery.[16][17][18][19]

Mutations in TPM2 have also been associated with nemaline myopathy, a rare disorder characterized by muscle weakness and nemaline bodies,[20][21][22]

as well as distal arthrogryposis.[23][24]

The muscle weakness observed in these patients may be due to a change in mutated TPM2 affinity for actin or decreased calcium-induced activation of contractility.[25][26][27] Moreover, studies unveiled alterations in cross-bridge attachment and detachment rates,[28] as well as changes in ATPase rates.[26][29]

Interactions

TPM2 has been shown to interact with:

References

  1. ↑ Hunt CC, Eyre HJ, Akkari PA, Meredith C, Dorosz SM, Wilton SD, Callen DF, Laing NG, Baker E (Aug 1995). "Assignment of the human beta tropomyosin gene (TPM2) to band 9p13 by fluorescence in situ hybridisation". Cytogenetics and Cell Genetics. 71 (1): 94–5. doi:10.1159/000134070. PMID 7606936.
  2. ↑ "Entrez Gene: TPM2 tropomyosin 2 (beta)".
  3. ↑ Perry SV (2001). "Vertebrate tropomyosin: distribution, properties and function". Journal of Muscle Research and Cell Motility. 22 (1): 5–49. doi:10.1023/A:1010303732441. PMID 11563548.
  4. ↑ "Protein sequence of human TPM2 (Uniprot ID: P07951)". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Retrieved 1 July 2015.
  5. ↑ "Protein sequence of human TPM2 (Uniprot ID: P07951-2)". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Retrieved 1 July 2015.
  6. ↑ "Protein sequence of human TPM2 (Uniprot ID: P07951-3)". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Retrieved 1 July 2015.
  7. ↑ Brown JH, Kim KH, Jun G, Greenfield NJ, Dominguez R, Volkmann N, Hitchcock-DeGregori SE, Cohen C (Jul 2001). "Deciphering the design of the tropomyosin molecule". Proceedings of the National Academy of Sciences of the United States of America. 98 (15): 8496–501. doi:10.1073/pnas.131219198. PMC 37464. PMID 11438684.
  8. ↑ 8.0 8.1 8.2 8.3 Muthuchamy M, Grupp IL, Grupp G, O'Toole BA, Kier AB, Boivin GP, Neumann J, Wieczorek DF (Dec 1995). "Molecular and physiological effects of overexpressing striated muscle beta-tropomyosin in the adult murine heart". The Journal of Biological Chemistry. 270 (51): 30593–603. doi:10.1074/jbc.270.51.30593. PMID 8530495.
  9. ↑ Dube DK, McLean MD, Dube S, Poiesz BJ (Sep 2014). "Translational control of tropomyosin expression in vertebrate hearts". Anatomical Record. 297 (9): 1585–95. doi:10.1002/ar.22978. PMID 25125172.
  10. ↑ Yin Z, Ren J, Guo W (Jan 2015). "Sarcomeric protein isoform transitions in cardiac muscle: a journey to heart failure". Biochimica et Biophysica Acta. 1852 (1): 47–52. doi:10.1016/j.bbadis.2014.11.003. PMC 4268308. PMID 25446994.
  11. ↑ Muthuchamy M, Boivin GP, Grupp IL, Wieczorek DF (Aug 1998). "Beta-tropomyosin overexpression induces severe cardiac abnormalities". Journal of Molecular and Cellular Cardiology. 30 (8): 1545–57. doi:10.1006/jmcc.1998.0720. PMID 9737941.
  12. ↑ Izumo S, Nadal-Ginard B, Mahdavi V (Jan 1988). "Protooncogene induction and reprogramming of cardiac gene expression produced by pressure overload". Proceedings of the National Academy of Sciences of the United States of America. 85 (2): 339–43. doi:10.1073/pnas.85.2.339. PMC 279543. PMID 2963328.
  13. ↑ "Protein sequence alignment of human TPM1 and TPM2". Uniprot Knowledgebase. Retrieved 2 July 2015.
  14. ↑ Schulz, EM; Wieczorek, DF (August 2013). "Tropomyosin de-phosphorylation in the heart: what are the consequences?". Journal of muscle research and cell motility. 34 (3–4): 239–46. doi:10.1007/s10974-013-9348-7. PMID 23793376.
  15. ↑ Purcell IF, Bing W, Marston SB (Sep 1999). "Functional analysis of human cardiac troponin by the in vitro motility assay: comparison of adult, foetal and failing hearts". Cardiovascular Research. 43 (4): 884–91. doi:10.1016/s0008-6363(99)00123-6. PMID 10615415.
  16. ↑ Ohlsson M, Quijano-Roy S, Darin N, Brochier G, Lacène E, Avila-Smirnow D, Fardeau M, Oldfors A, Tajsharghi H (Dec 2008). "New morphologic and genetic findings in cap disease associated with beta-tropomyosin (TPM2) mutations". Neurology. 71 (23): 1896–901. doi:10.1212/01.wnl.0000336654.44814.b8. PMID 19047562.
  17. ↑ Tajsharghi H, Ohlsson M, Lindberg C, Oldfors A (Sep 2007). "Congenital myopathy with nemaline rods and cap structures caused by a mutation in the beta-tropomyosin gene (TPM2)". Archives of Neurology. 64 (9): 1334–8. doi:10.1001/archneur.64.9.1334. PMID 17846275.
  18. ↑ Lehtokari VL, Ceuterick-de Groote C, de Jonghe P, Marttila M, Laing NG, Pelin K, Wallgren-Pettersson C (Jun 2007). "Cap disease caused by heterozygous deletion of the beta-tropomyosin gene TPM2". Neuromuscular Disorders. 17 (6): 433–42. doi:10.1016/j.nmd.2007.02.015. PMID 17434307.
  19. ↑ Clarke NF, Domazetovska A, Waddell L, Kornberg A, McLean C, North KN (May 2009). "Cap disease due to mutation of the beta-tropomyosin gene (TPM2)". Neuromuscular Disorders. 19 (5): 348–51. doi:10.1016/j.nmd.2009.03.003. PMID 19345583.
  20. ↑ Mokbel N, Ilkovski B, Kreissl M, Memo M, Jeffries CM, Marttila M, Lehtokari VL, Lemola E, Grönholm M, Yang N, Menard D, Marcorelles P, Echaniz-Laguna A, Reimann J, Vainzof M, Monnier N, Ravenscroft G, McNamara E, Nowak KJ, Laing NG, Wallgren-Pettersson C, Trewhella J, Marston S, Ottenheijm C, North KN, Clarke NF (Feb 2013). "K7del is a common TPM2 gene mutation associated with nemaline myopathy and raised myofibre calcium sensitivity". Brain. 136 (Pt 2): 494–507. doi:10.1093/brain/aws348. PMID 23378224.
  21. ↑ Monnier N, Lunardi J, Marty I, Mezin P, Labarre-Vila A, Dieterich K, Jouk PS (Feb 2009). "Absence of beta-tropomyosin is a new cause of Escobar syndrome associated with nemaline myopathy". Neuromuscular Disorders. 19 (2): 118–23. doi:10.1016/j.nmd.2008.11.009. PMID 19155175.
  22. ↑ Donner K, Ollikainen M, Ridanpää M, Christen HJ, Goebel HH, de Visser M, Pelin K, Wallgren-Pettersson C (Feb 2002). "Mutations in the beta-tropomyosin (TPM2) gene--a rare cause of nemaline myopathy". Neuromuscular Disorders. 12 (2): 151–8. doi:10.1016/s0960-8966(01)00252-8. PMID 11738357.
  23. ↑ Tajsharghi H, Kimber E, Holmgren D, Tulinius M, Oldfors A (Mar 2007). "Distal arthrogryposis and muscle weakness associated with a beta-tropomyosin mutation". Neurology. 68 (10): 772–5. doi:10.1212/01.wnl.0000256339.40667.fb. PMID 17339586.
  24. ↑ Sung SS, Brassington AM, Grannatt K, Rutherford A, Whitby FG, Krakowiak PA, Jorde LB, Carey JC, Bamshad M (Mar 2003). "Mutations in genes encoding fast-twitch contractile proteins cause distal arthrogryposis syndromes". American Journal of Human Genetics. 72 (3): 681–90. doi:10.1086/368294. PMC 1180243. PMID 12592607.
  25. ↑ Marttila M, Lehtokari VL, Marston S, Nyman TA, Barnerias C, Beggs AH, Bertini E, Ceyhan-Birsoy O, Cintas P, Gerard M, Gilbert-Dussardier B, Hogue JS, Longman C, Eymard B, Frydman M, Kang PB, Klinge L, Kolski H, Lochmüller H, Magy L, Manel V, Mayer M, Mercuri E, North KN, Peudenier-Robert S, Pihko H, Probst FJ, Reisin R, Stewart W, Taratuto AL, de Visser M, Wilichowski E, Winer J, Nowak K, Laing NG, Winder TL, Monnier N, Clarke NF, Pelin K, Grönholm M, Wallgren-Pettersson C (Jul 2014). "Mutation update and genotype-phenotype correlations of novel and previously described mutations in TPM2 and TPM3 causing congenital myopathies". Human Mutation. 35 (7): 779–90. doi:10.1002/humu.22554. PMC 4200603. PMID 24692096.
  26. ↑ 26.0 26.1 Robinson P, Lipscomb S, Preston LC, Altin E, Watkins H, Ashley CC, Redwood CS (Mar 2007). "Mutations in fast skeletal troponin I, troponin T, and beta-tropomyosin that cause distal arthrogryposis all increase contractile function". FASEB Journal. 21 (3): 896–905. doi:10.1096/fj.06-6899com. PMID 17194691.
  27. ↑ Marttila M, Lemola E, Wallefeld W, Memo M, Donner K, Laing NG, Marston S, Grönholm M, Wallgren-Pettersson C (Feb 2012). "Abnormal actin binding of aberrant β-tropomyosins is a molecular cause of muscle weakness in TPM2-related nemaline and cap myopathy". The Biochemical Journal. 442 (1): 231–9. doi:10.1042/BJ20111030. PMID 22084935.
  28. ↑ Ochala J, Li M, Tajsharghi H, Kimber E, Tulinius M, Oldfors A, Larsson L (Jun 2007). "Effects of a R133W beta-tropomyosin mutation on regulation of muscle contraction in single human muscle fibres". The Journal of Physiology. 581 (Pt 3): 1283–92. doi:10.1113/jphysiol.2007.129759. PMC 2170843. PMID 17430991.
  29. ↑ Marston S, Memo M, Messer A, Papadaki M, Nowak K, McNamara E, Ong R, El-Mezgueldi M, Li X, Lehman W (Dec 2013). "Mutations in repeating structural motifs of tropomyosin cause gain of function in skeletal muscle myopathy patients". Human Molecular Genetics. 22 (24): 4978–87. doi:10.1093/hmg/ddt345. PMC 3836477. PMID 23886664.
  30. ↑ Zhu J, Bilan PJ, Moyers JS, Antonetti DA, Kahn CR (Jan 1996). "Rad, a novel Ras-related GTPase, interacts with skeletal muscle beta-tropomyosin". The Journal of Biological Chemistry. 271 (2): 768–73. doi:10.1074/jbc.271.2.768. PMID 8557685.
  31. ↑ Guy PM, Kenny DA, Gill GN (Jun 1999). "The PDZ domain of the LIM protein enigma binds to beta-tropomyosin". Molecular Biology of the Cell. 10 (6): 1973–84. doi:10.1091/mbc.10.6.1973. PMC 25398. PMID 10359609.
  32. ↑ Brown HR, Schachat FH (Apr 1985). "Renaturation of skeletal muscle tropomyosin: implications for in vivo assembly". Proceedings of the National Academy of Sciences of the United States of America. 82 (8): 2359–63. doi:10.1073/pnas.82.8.2359. PMC 397557. PMID 3857586.

Further reading

External links

Retrieved from "https://www.wikidoc.org/index.php?title=TPM2&oldid=1522777"