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UniProtKB/Swiss-Prot entry P06753


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name TPM3_HUMAN
Primary accession number P06753
Secondary accession numbers P12324 Q969Q2 Q9NQH8
Integrated into Swiss-Prot on January 1, 1988
Sequence was last modified on January 1, 1988 (Sequence version 1)
Annotations were last modified on    November 4, 2008 (Entry version 112)
Name and origin of the protein
Protein name Tropomyosin alpha-3 chain
Synonyms Tropomyosin-3
Gamma-tropomyosin
Tropomyosin-5
hTM5
Gene name
Name: TPM3
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
DOI=10.1038/322648a0; PubMed=3018581 [NCBI, ExPASy, EBI, Israel, Japan]
Reinach F.C., McLeod A.R.;
"Tissue-specific expression of the human tropomyosin gene involved in the generation of the trk oncogene.";
Nature 322:648-650(1986).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
DOI=10.1093/nar/14.21.8413; PubMed=3024106 [NCBI, ExPASy, EBI, Israel, Japan]
McLeod A.R., Houlker C., Talbot K.;
"The mRNA and RNA-copy pseudogenes encoding TM30nm, a human cytoskeletal tropomyosin.";
Nucleic Acids Res. 14:8413-8426(1986).
[3]
NUCLEOTIDE SEQUENCE (ISOFORMS 1 AND 2).
DOI=10.1016/0022-2836(88)90633-X; PubMed=3418707 [NCBI, ExPASy, EBI, Israel, Japan]
Clayton L., Reinach F.C., Chumbley G.M., MacLeod A.R.;
"Organization of the hTMnm gene. Implications for the evolution of muscle and non-muscle tropomyosins.";
J. Mol. Biol. 201:507-515(1988).
[4]
NUCLEOTIDE SEQUENCE (ISOFORM 3).
TISSUE=Colon cancer;
Lin J.J.-C., Lin J.L.-C., Geng X., Das K.M.;
"Identification and characterization of a novel tropomyosin isoform from a colon cancer cell line T84.";
Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/nature04727; PubMed=16710414 [NCBI, ExPASy, EBI, Israel, Japan]
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
"The DNA sequence and biological annotation of human chromosome 1.";
Nature 441:315-321(2006).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
TISSUE=Bone, Kidney, Skeletal muscle, and Uterus;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[7]
PROTEIN SEQUENCE OF 92-125; 134-149; 153-167 AND 214-244 (ISOFORMS 1/2/3), PARTIAL PROTEIN SEQUENCE (ISOFORMS 2/3), CLEAVAGE OF INITIATOR METHIONINE (ISOFORMS 2/3), ACETYLATION AT ALA-2 (ISOFORMS 2/3), AND MASS SPECTROMETRY.
TISSUE=B-cell lymphoma, and Platelet;
Bienvenut W.V., Claeys D.;
Submitted (DEC-2005) to UniProtKB.
[8]
PROTEIN SEQUENCE OF 92-118 (ISOFORMS 1/2/3), PARTIAL PROTEIN SEQUENCE (ISOFORMS 2/3), CLEAVAGE OF INITIATOR METHIONINE (ISOFORMS 2/3), ACETYLATION AT ALA-2 (ISOFORMS 2/3), AND MASS SPECTROMETRY.
TISSUE=Osteosarcoma;
Bienvenut W.V., Glen H., Brunton V.G., Frame M.C.;
Submitted (JUL-2007) to UniProtKB.
[9]
PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND CHROMOSOMAL TRANSLOCATION WITH NTRK1.
DOI=10.1038/319743a0; PubMed=2869410 [NCBI, ExPASy, EBI, Israel, Japan]
Martin-Zanca D., Hughes S.H., Barbacid M.;
"A human oncogene formed by the fusion of truncated tropomyosin and protein tyrosine kinase sequences.";
Nature 319:743-748(1986).
[10]
PARTIAL PROTEIN SEQUENCE.
TISSUE=Keratinocyte;
DOI=10.1002/elps.11501301199; PubMed=1286667 [NCBI, ExPASy, EBI, Israel, Japan]
Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E., Vandekerckhove J.;
"Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes.";
Electrophoresis 13:960-969(1992).
[11]
INTERACTION WITH TMOD1.
DOI=10.1006/bbrc.1994.1747; PubMed=8002995 [NCBI, ExPASy, EBI, Israel, Japan]
Sung L.A., Lin J.J.-C.;
"Erythrocyte tropomodulin binds to the N-terminus of hTM5, a tropomyosin isoform encoded by the gamma-tropomyosin gene.";
Biochem. Biophys. Res. Commun. 201:627-634(1994).
[12]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-252, AND MASS SPECTROMETRY.
TISSUE=Epithelium;
DOI=10.1073/pnas.0404720101; PubMed=15302935 [NCBI, ExPASy, EBI, Israel, Japan]
Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P.;
"Large-scale characterization of HeLa cell nuclear phosphoproteins.";
Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004).
[13]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-252, AND MASS SPECTROMETRY.
TISSUE=Epithelium;
DOI=10.1016/j.cell.2006.09.026; PubMed=17081983 [NCBI, ExPASy, EBI, Israel, Japan]
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.";
Cell 127:635-648(2006).
[14]
ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-228 (ISOFORM 2), AND MASS SPECTROMETRY.
TISSUE=Epithelium;
DOI=10.1016/j.molcel.2006.06.026; PubMed=16916647 [NCBI, ExPASy, EBI, Israel, Japan]
Kim S.C., Sprung R., Chen Y., Xu Y., Ball H., Pei J., Cheng T., Kho Y., Xiao H., Xiao L., Grishin N.V., White M., Yang X.-J., Zhao Y.;
"Substrate and functional diversity of lysine acetylation revealed by a proteomics survey.";
Mol. Cell 23:607-618(2006).
[15]
VARIANT NEM1 ARG-8.
DOI=10.1038/ng0195-75; PubMed=7704029 [NCBI, ExPASy, EBI, Israel, Japan]
Laing N.G., Wilton S.D., Akkari P.A., Dorosz S., Boundy K., Kneebone C., Blumbergs P., White S., Watkins H., Love D.R., Haan E.;
"A mutation in the alpha tropomyosin gene TPM3 associated with autosomal dominant nemaline myopathy.";
Nat. Genet. 9:75-79(1995).
[16]
ERRATUM.
PubMed=7663526 [NCBI, ExPASy, EBI, Israel, Japan]
Laing N.G., Wilton S.D., Akkari P.A., Dorosz S., Boundy K., Kneebone C., Blumbergs P., White S., Watkins H., Love D.R., Haan E.;
Nat. Genet. 10:249-249(1995).
[17]
CHARACTERIZATION OF VARIANT NEM1 ARG-8.
PubMed=10587521 [NCBI, ExPASy, EBI, Israel, Japan]
Michele D.E., Albayya F.P., Metzger J.M.;
"A nemaline myopathy mutation in alpha-tropomyosin causes defective regulation of striated muscle force production.";
J. Clin. Invest. 104:1575-1581(1999).
Comments
  • FUNCTION: Binds to actin filaments in muscle and non-muscle cells. Plays a central role, in association with the troponin complex, in the calcium dependent regulation of vertebrate striated muscle contraction. Smooth muscle contraction is regulated by interaction with caldesmon. In non-muscle cells is implicated in stabilizing cytoskeleton actin filaments.
  • SUBUNIT: Heterodimer of an alpha and a beta chain. Binds to TMOD1.
  • INTERACTION:
    P23508:MCC; NbExp=1; IntAct=EBI-355607, EBI-307531;
  • SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton.
  • ALTERNATIVE PRODUCTS: 3 named isoforms [FASTA] produced by alternative splicing. Additional isoforms seem to exist.
    Name1
    SynonymsSkeletal muscle
    Isoform IDP06753-1
    This is the isoform sequence displayed in this entry.
    Name2
    SynonymsCytoskeletal, TM30nm
    Isoform IDP06753-2
    Note: Peptides 2-27, 41-55, 132-153, 163-169, 216-225 and 237-248 identified and sequenced in Ref.7. Peptides 2-12 and 43-55 identified and sequenced in Ref.8. Initiator Met-1 is removed. Acetylated on Ala-2 and Lys-228.
    Features which should be applied to build the isoform sequence: VSP_006604, VSP_006605, VSP_006606.
    Name3
    Isoform IDP06753-3
    Note: Peptides 2-27, 41-55, 132-153 and 163-169 identified and sequenced in Ref.7. Peptides 2-12 and 43-55 identified and sequenced in Ref.8. Initiator Met-1 is removed. Acetylated on Ala-2.
    Features which should be applied to build the isoform sequence: VSP_006604, VSP_006605, VSP_006607.
  • DOMAIN: The molecule is in a coiled coil structure that is formed by 2 polypeptide chains. The sequence exhibits a prominent seven-residues periodicity.
  • DISEASE: Defects in TPM3 are a cause of nemaline myopathy type 1 (NEM1) [MIM:609284]. Nemaline myopathy (NEM) is a form of congenital myopathy characterized by abnormal thread- or rod-like structures in muscle fibers on histologic examination. The clinical phenotype is highly variable, with differing age at onset and severity. NEM1 inheritance is autosomal dominant.
  • DISEASE: A chromosomal aberration involving TPM3 is a cause of thyroid papillary carcinoma (PACT) [MIM:188550]. A rearrangement with NTRK1 generates the TRK fusion transcript by fusing the amino end of isoform 2 of TPM3 to the 3'-end of NTRK1.
  • SIMILARITY: Belongs to the tropomyosin family.
  • WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/TPM3ID225.html";.
  • WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=TPM3";.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
X04201; CAA27798.1; ALT_INIT; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AY004867; AAF87083.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X04588; CAB37185.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AL590431; CAH71264.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC000771; AAH00771.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC008407; AAH08407.1; ALT_INIT; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC008425; AAH08425.1; ALT_INIT; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC015403; AAH15403.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC072428; AAH72428.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X03541; CAA27243.1; ALT_TERM; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR A25530; A25530.
S06210; A24199.
RefSeq NP_001036816.1; -.
NP_001036817.1; -.
NP_689476.2; -.
NP_705935.1; -.
UniGene Hs.535581
3D structure databases
HSSP P42639; 1C1G. [HSSP ENTRY / PDB]
SMR P06753; 1-284.
ModBase P06753.
Protein-protein interaction databases
IntAct P06753; -.
PTM databases
PhosphoSite P06753; -.
2D gel databases
SWISS-2DPAGE P06753; -.
Aarhus/Ghent-2DPAGE 9121; IEF.
Cornea-2DPAGE P06753; -.
DOSAC-COBS-2DPAGE P06753; -.
PHCI-2DPAGE P06753; -.
Organism-specific databases
H-InvDB HIX0001100; -.
HGNC HGNC:12012; TPM3.
GenAtlas TPM3.
HPA HPA009066; -.
MIM 164970; gene. [NCBI / EBI]
188550; phenotype. [NCBI / EBI]
191030; gene. [NCBI / EBI]
609284; phenotype. [NCBI / EBI]
Orphanet 607; Nemaline myopathy.
146; Thyroid carcinoma, papillary or follicular.
PharmGKB PA36692; -.
GeneCards P06753.
Gene expression databases
ArrayExpress P06753; -.
CleanEx HS_TPM3; -.
GermOnline ENSG00000143549; Homo sapiens.
Ontologies
GO
GO:0005862; Cellular component: muscle thin filament tropomyosin (traceable author statement from UniProtKB).
GO:0005515; Molecular function: protein binding (inferred from physical interaction from IntAct).
GO:0006928; Biological process: cell motion (traceable author statement from UniProtKB).
GO:0006937; Biological process: regulation of muscle contraction (non-traceable author statement from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR000533; Tropomyosin.
Graphical view of domain structure.
Pfam PF00261; Tropomyosin; 1.
Pfam graphical view of domain structure.
PRINTS PR00194; TROPOMYOSIN.
PROSITE PS00326; TROPOMYOSIN; 1.
BLOCKS P06753.
ProtoNet P06753.
Genome annotation databases
Ensembl ENSG00000143549; Homo sapiens. [Contig view]
GeneID 7170; -.
KEGG hsa:7170; -.
Phylogenomic databases
HOVERGEN P06753; -.
Other
LinkHub P06753; -.
NextBio 28092; -.
SOURCE TPM3; Homo sapiens.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
Acetylation; Actin-binding; Alternative splicing; Chromosomal rearrangement; Coiled coil; Cytoplasm; Cytoskeleton; Direct protein sequencing; Disease mutation; Muscle protein; Phosphoprotein; Proto-oncogene.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
CHAIN   1   284  284     Tropomyosin alpha-3 chain. PRO_0000205632
COILED   1   284  284     By similarity. 
MOD_RES   252   252        Phosphothreonine. 
MOD_RES   283   283        Phosphoserine (By similarity). 
VAR_SEQ   1    80        MEAIKKKMQMLKLDKENALDRAEQAEAEQKQAEERSKQLE DELAAMQKKLKGTEDELDKYSEALKDAQEKLELAEKKAAD -> MAGITTIEAVKRKIQVLQQQADDAEERAERLQREVEGER RAREQ (in isoform 2 and isoform 3). VSP_006604
VAR_SEQ   189   211        KCSELEEELKNVTNNLKSLEAQA -> RCREMDEQIRLMDQNLKCLSAAE (in isoform 2 and isoform 3). VSP_006605
VAR_SEQ   258   284        DELYAQKLKYKAISEELDHALNDMTSI -> ERLYSQLERNRLLSNELKLTLHDLCD (in isoform 3). VSP_006607
VAR_SEQ   259   284        ELYAQKLKYKAISEELDHALNDMTSI -> KLKCTKEEHLCTQRMLDQTLLDLNEM (in isoform 2). VSP_006606
VARIANT   8     8  1     M -> R (in NEM1; decrease in the sensitivity of contraction to activating calcium). VAR_013460 
CONFLICT   149   149        K -> E (in Ref. 3; CAA27243). 
Sequence information
Length: 284 AA [This is the length of the unprocessed precursor] Molecular weight: 32819 Da [This is the MW of the unprocessed precursor] CRC64: A3BCE715565DABBD [This is a checksum on the sequence]
        10         20         30         40         50         60 
MEAIKKKMQM LKLDKENALD RAEQAEAEQK QAEERSKQLE DELAAMQKKL KGTEDELDKY 

        70         80         90        100        110        120 
SEALKDAQEK LELAEKKAAD AEAEVASLNR RIQLVEEELD RAQERLATAL QKLEEAEKAA 

       130        140        150        160        170        180 
DESERGMKVI ENRALKDEEK MELQEIQLKE AKHIAEEADR KYEEVARKLV IIEGDLERTE 

       190        200        210        220        230        240 
ERAELAESKC SELEEELKNV TNNLKSLEAQ AEKYSQKEDK YEEEIKILTD KLKEAETRAE 

       250        260        270        280 
FAERSVAKLE KTIDDLEDEL YAQKLKYKAI SEELDHALND MTSI 

P06753 in FASTA format

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View entry in raw text format (no links)
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