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Reviewed, UniProtKB/Swiss-Prot P06753 (TPM3_HUMAN)

Last modified June 16, 2009. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Tropomyosin alpha-3 chain
Alternative name(s):
    Tropomyosin-3
    Gamma-tropomyosin
    Tropomyosin-5
      Short name=hTM5
Gene names
Name: TPM3
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length284 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (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 structure

Heterodimer of an alpha and a beta chain. Binds to TMOD1. Ref.12

Subcellular location

Cytoplasmcytoskeleton.

Domain

The molecule is in a coiled coil structure that is formed by 2 polypeptide chains. The sequence exhibits a prominent seven-residues periodicity.

Involvement in 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. Ref.18 Ref.20

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.

Sequence similarities

Belongs to the tropomyosin family.

Ontologies

Keywords
   Cellular componentCytoplasm
Cytoskeleton
   Coding sequence diversityAlternative splicing
Chromosomal rearrangement
   DiseaseDisease mutation
Proto-oncogene
   DomainCoiled coil
   LigandActin-binding
   Molecular functionMuscle protein
   PTMAcetylation
Phosphoprotein
   Technical termDirect protein sequencing
Gene Ontology (GO)
   Biological processcell motion

Traceable author statement. Source: UniProtKB

regulation of muscle contraction

Non-traceable author statement. Source: UniProtKB

   Cellular componentmuscle thin filament tropomyosin Ref.1

Traceable author statement. Source: UniProtKB

   Molecular functionactin binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

EIF4A2Q142401EBI-355607,EBI-73473
MCCP235081EBI-355607,EBI-307531

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: P06753-1)

Also known as: Skeletal muscle;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P06753-2)

Also known as: Cytoskeletal; TM30nm;

The sequence of this isoform differs from the canonical sequence as follows:
     1-80: MEAIKKKMQM...LELAEKKAAD → MAGITTIEAV...VEGERRAREQ
     189-211: KCSELEEELKNVTNNLKSLEAQA → RCREMDEQIRLMDQNLKCLSAAE
     259-284: ELYAQKLKYKAISEELDHALNDMTSI → KLKCTKEEHLCTQRMLDQTLLDLNEM
Note: Peptides 2-27, 41-55, 132-153, 163-169, 216-225 and 237-248 identified and sequenced in Ref.8. Peptides 2-12 and 43-55 identified and sequenced in Ref.9. Initiator Met-1 is removed. Acetylated on Ala-2 and Lys-228. Note=Ref.7 (ABC40673) sequence is in conflict in positions: 33:R->Q, 43:E -> K, 66:A -> P, 85:D -> G, 110:I -> L, 135:I -> T, 150:A -> T, 192:L -> F, 196:L -> P, 202:R -> C. Ref.7 (ABC40673) sequence corresponds to a TPM3 retrocopy (rcTPM3) on chromosome 16 that is generated by retroposition of reversed transcribed mRNA back to the genome. rcTPM3 functionality is uncertain. It has been detected by MS in primary breast cancer tissues (Ref.17).
Isoform 3 (identifier: P06753-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-80: MEAIKKKMQM...LELAEKKAAD → MAGITTIEAV...VEGERRAREQ
     189-211: KCSELEEELKNVTNNLKSLEAQA → RCREMDEQIRLMDQNLKCLSAAE
     258-284: DELYAQKLKYKAISEELDHALNDMTSI → ERLYSQLERNRLLSNELKLTLHDLCD
Note: Peptides 2-27, 41-55, 132-153 and 163-169 identified and sequenced in Ref.8. Peptides 2-12 and 43-55 identified and sequenced in Ref.9. Initiator Met-1 is removed. Acetylated on Ala-2.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 284284Tropomyosin alpha-3 chain
PRO_0000205632

Regions

Coiled coil1 – 284284 By similarity

Amino acid modifications

Modified residue1621Phosphotyrosine Ref.16
Modified residue2521Phosphothreonine Ref.13 Ref.14
Modified residue2831Phosphoserine By similarity

Natural variations

Alternative sequence1 – 8080MEAIK…KKAAD → MAGITTIEAVKRKIQVLQQQ ADDAEERAERLQREVEGERR AREQ in isoform 2 and isoform 3.
VSP_006604
Alternative sequence189 – 21123KCSEL…LEAQA → RCREMDEQIRLMDQNLKCLS AAE in isoform 2 and isoform 3.
VSP_006605
Alternative sequence258 – 28427DELYA…DMTSI → ERLYSQLERNRLLSNELKLT LHDLCD in isoform 3.
VSP_006607
Alternative sequence259 – 28426ELYAQ…DMTSI → KLKCTKEEHLCTQRMLDQTL LDLNEM in isoform 2.
VSP_006606
Natural variant81M → R in NEM1; decrease in the sensitivity of contraction to activating calcium. Ref.18 Ref.20
VAR_013460

Experimental info

Sequence conflict1491K → E in CAA27243. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Skeletal muscle) [UniParc].

Last modified January 1, 1988. Version 1.
Checksum: A3BCE715565DABBD

FASTA28432,819
        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 

« Hide

Isoform 2 (Cytoskeletal) (TM30nm).

Checksum: 5C049312A337BC19
Show »

FASTA24829,033
Isoform 3.

Checksum: 4929E6D4591374D3
Show »

FASTA24728,955

References

« Hide 'large scale' references
[1]"Tissue-specific expression of the human tropomyosin gene involved in the generation of the trk oncogene."
Reinach F.C., McLeod A.R.
Nature 322:648-650(1986) [PubMed: 3018581] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"The mRNA and RNA-copy pseudogenes encoding TM30nm, a human cytoskeletal tropomyosin."
McLeod A.R., Houlker C., Talbot K.
Nucleic Acids Res. 14:8413-8426(1986) [PubMed: 3024106] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]"Organization of the hTMnm gene. Implications for the evolution of muscle and non-muscle tropomyosins."
Clayton L., Reinach F.C., Chumbley G.M., MacLeod A.R.
J. Mol. Biol. 201:507-515(1988) [PubMed: 3418707] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE (ISOFORMS 1 AND 2).
[4]"Identification and characterization of a novel tropomyosin isoform from a colon cancer cell line T84."
Lin J.J.-C., Lin J.L.-C., Geng X., Das K.M.
Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 3).
Tissue: Colon cancer.
[5]"The DNA sequence and biological annotation of human chromosome 1."
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. expand/collapse author list , 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.
Nature 441:315-321(2006) [PubMed: 16710414] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Bone, Kidney, Skeletal muscle and Uterus.
[7]"Emergence of young human genes after a burst of retroposition in primates."
Marques A.C., Dupanloup I., Vinckenbosch N., Reymond A., Kaessmann H.
PLoS Biol. 3:1970-1979(2005) [PubMed: 16201836] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 2-248 (ISOFORM 2), IDENTIFICATION OF RCTPM3.
[8]Bienvenut W.V., Claeys D.
Submitted (DEC-2005) to UniProtKB
Cited for: 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), MASS SPECTROMETRY.
Tissue: B-cell lymphoma and Platelet.
[9]Bienvenut W.V., Glen H., Brunton V.G., Frame M.C.
Submitted (JUL-2007) to UniProtKB
Cited for: 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), MASS SPECTROMETRY.
Tissue: Osteosarcoma.
[10]"A human oncogene formed by the fusion of truncated tropomyosin and protein tyrosine kinase sequences."
Martin-Zanca D., Hughes S.H., Barbacid M.
Nature 319:743-748(1986) [PubMed: 2869410] [Abstract]
Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), CHROMOSOMAL TRANSLOCATION WITH NTRK1.
[11]"Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes."
Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E., Vandekerckhove J.
Electrophoresis 13:960-969(1992) [PubMed: 1286667] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE.
Tissue: Keratinocyte.
[12]"Erythrocyte tropomodulin binds to the N-terminus of hTM5, a tropomyosin isoform encoded by the gamma-tropomyosin gene."
Sung L.A., Lin J.J.-C.
Biochem. Biophys. Res. Commun. 201:627-634(1994) [PubMed: 8002995] [Abstract]
Cited for: INTERACTION WITH TMOD1.
[13]"Large-scale characterization of HeLa cell nuclear phosphoproteins."
Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-252, MASS SPECTROMETRY.
Tissue: Epithelium.
[14]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed: 17081983] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-252, MASS SPECTROMETRY.
Tissue: Epithelium.
[15]"Substrate and functional diversity of lysine acetylation revealed by a proteomics survey."
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.
Mol. Cell 23:607-618(2006) [PubMed: 16916647] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-228 (ISOFORM 2), MASS SPECTROMETRY.
Tissue: Epithelium.
[16]"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer."
Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. expand/collapse author list , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.
Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-162, MASS SPECTROMETRY.
Tissue: Lung.
[17]"Abnormal proteins in primary breast cancer tissues from 25 Sudanese patients."
Ahamed M.E., Ahmed M.E., Eltoum A.M., Altahir G.O., Ahmed K.M., Harbi S.O., Stansalas J., Mohamed A.O.
Eur. J. Inflamm. 6:0-0(2008)
Cited for: IDENTIFICATION OF RCTPM3 BY MASS SPECTROMETRY.
Tissue: Mammary cancer.
[18]"A mutation in the alpha tropomyosin gene TPM3 associated with autosomal dominant nemaline myopathy."
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. 9:75-79(1995) [PubMed: 7704029] [Abstract]
Cited for: VARIANT NEM1 ARG-8.
[19]Erratum
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) [PubMed: 7663526] [Abstract]
[20]"A nemaline myopathy mutation in alpha-tropomyosin causes defective regulation of striated muscle force production."
Michele D.E., Albayya F.P., Metzger J.M.
J. Clin. Invest. 104:1575-1581(1999) [PubMed: 10587521] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT NEM1 ARG-8.
+Additional computationally mapped references.

Cross-references

Sequence databases

X04201 mRNA. Translation: CAA27798.1. Different initiation.
AY004867 mRNA. Translation: AAF87083.1.
X04588 mRNA. Translation: CAB37185.1.
AL590431 Genomic DNA. Translation: CAH71264.1.
AL590431 Genomic DNA. Translation: CAH71269.1.
BC000771 mRNA. Translation: AAH00771.1.
BC008407 mRNA. Translation: AAH08407.1. Different initiation.
BC008425 mRNA. Translation: AAH08425.1. Different initiation.
BC015403 mRNA. Translation: AAH15403.1.
BC072428 mRNA. Translation: AAH72428.1.
DQ120714 Genomic DNA. Translation: ABC40673.1.
X03541 mRNA. Translation: CAA27243.1. Different termination.
IPIIPI00183968.
IPI00218319.
IPI00218320.
PIRA25530.
A24199. S06210.
RefSeqNP_001036816.1.
NP_001036817.1.
NP_689476.2.
NP_705935.1.
UniGeneHs.535581
Hs.644306
Hs.654421

3D structure databases

HSSPHSSP built from PDB template 1C1G based on UniProtKB P42639.
SMRP06753. Positions 1-284.
ModBaseSearch...

Protein-protein interaction databases

IntActP06753. 15 interactions.

PTM databases

PhosphoSiteP06753.

2-D gel databases

SWISS-2DPAGEP06753.
Aarhus/Ghent-2DPAGE9121. IEF.
Cornea-2DPAGEP06753.
DOSAC-COBS-2DPAGEP06753.
PHCI-2DPAGEP06753.

Proteomic databases

PRIDEP06753.

Genome annotation databases

EnsemblENSG00000143549. Homo sapiens. [Contig view]
GeneID7170.
KEGGhsa:7170.

Organism-specific databases

GeneCardsGC01M152395.
H-InvDBHIX0001100.
HGNCHGNC:12012. TPM3.
HPAHPA009066.
MIM164970. gene.
188550. phenotype.
191030. gene.
609284. phenotype.
Orphanet607. Nemaline myopathy.
PharmGKBPA36692.
GenAtlasSearch...

Phylogenomic databases

HOVERGENP06753.

Gene expression databases

ArrayExpressP06753.
BgeeP06753.
CleanExHS_TPM3.
GermOnlineENSG00000143549. Homo sapiens.

Family and domain databases

InterProIPR000533. Tropomyosin.
[Graphical view]
PfamPF00261. Tropomyosin. 1 hit.
[Graphical view]
PRINTSPR00194. TROPOMYOSIN.
PROSITEPS00326. TROPOMYOSIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio28092.
SOURCESearch...

Entry information

Entry nameTPM3_HUMAN
AccessionPrimary (citable) accession number: P06753
Secondary accession number(s): P12324 expand/collapse secondary AC list , Q2QD06, Q5VU71, Q969Q2, Q9NQH8
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: January 1, 1988
Last modified: June 16, 2009
This is version 120 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents