Reviewed, UniProtKB/Swiss-Prot P06753 (TPM3_HUMAN)

Names and origin

Protein names

Recommended name:
    Tropomyosin alpha-3 chain
Alternative name(s):
    Tropomyosin-3
    Gamma-tropomyosin
    Tropomyosin-5
      Short name=hTM5

Gene names

Name:

TPM3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	284 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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	Cytoplasm › cytoskeleton.
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 component	Cytoplasm Cytoskeleton
Coding sequence diversity	Alternative splicing Chromosomal rearrangement
Disease	Disease mutation Proto-oncogene
Domain	Coiled coil
Ligand	Actin-binding
Molecular function	Muscle protein
PTM	Acetylation Phosphoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	cell motion Traceable author statement. Source: UniProtKB regulation of muscle contraction Non-traceable author statement. Source: UniProtKB
Cellular component	muscle thin filament tropomyosin Ref.1 Traceable author statement. Source: UniProtKB
Molecular function	actin binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EIF4A2	Q14240	1	EBI-355607,EBI-73473
MCC	P23508	1	EBI-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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 284	284	Tropomyosin alpha-3 chain		PRO_0000205632
Regions
	Coiled coil	1 – 284	284	By similarity
Amino acid modifications
	Modified residue	162	1	Phosphotyrosine Ref.16
	Modified residue	252	1	Phosphothreonine Ref.13 Ref.14
	Modified residue	283	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	1 – 80	80	MEAIK…KKAAD → MAGITTIEAVKRKIQVLQQQ ADDAEERAERLQREVEGERR AREQ in isoform 2 and isoform 3.		VSP_006604
	Alternative sequence	189 – 211	23	KCSEL…LEAQA → RCREMDEQIRLMDQNLKCLS AAE in isoform 2 and isoform 3.		VSP_006605
	Alternative sequence	258 – 284	27	DELYA…DMTSI → ERLYSQLERNRLLSNELKLT LHDLCD in isoform 3.		VSP_006607
	Alternative sequence	259 – 284	26	ELYAQ…DMTSI → KLKCTKEEHLCTQRMLDQTL LDLNEM in isoform 2.		VSP_006606
	Natural variant	8	1	M → R in NEM1; decrease in the sensitivity of contraction to activating calcium. Ref.18 Ref.20		VAR_013460
Experimental info
	Sequence conflict	149	1	K → E in CAA27243. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Skeletal muscle) [UniParc]. Last modified January 1, 1988. Version 1. Checksum: A3BCE715565DABBD	FASTA	284	32,819
	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
	Isoform 2 (Cytoskeletal) (TM30nm). Checksum: 5C049312A337BC19	FASTA	248	29,033
	10 20 30 40 50 60 MAGITTIEAV KRKIQVLQQQ ADDAEERAER LQREVEGERR AREQAEAEVA SLNRRIQLVE 70 80 90 100 110 120 EELDRAQERL ATALQKLEEA EKAADESERG MKVIENRALK DEEKMELQEI QLKEAKHIAE 130 140 150 160 170 180 EADRKYEEVA RKLVIIEGDL ERTEERAELA ESRCREMDEQ IRLMDQNLKC LSAAEEKYSQ 190 200 210 220 230 240 KEDKYEEEIK ILTDKLKEAE TRAEFAERSV AKLEKTIDDL EDKLKCTKEE HLCTQRMLDQ TLLDLNEM
	Isoform 3. Checksum: 4929E6D4591374D3	FASTA	247	28,955
	10 20 30 40 50 60 MAGITTIEAV KRKIQVLQQQ ADDAEERAER LQREVEGERR AREQAEAEVA SLNRRIQLVE 70 80 90 100 110 120 EELDRAQERL ATALQKLEEA EKAADESERG MKVIENRALK DEEKMELQEI QLKEAKHIAE 130 140 150 160 170 180 EADRKYEEVA RKLVIIEGDL ERTEERAELA ESRCREMDEQ IRLMDQNLKC LSAAEEKYSQ 190 200 210 220 230 240 KEDKYEEEIK ILTDKLKEAE TRAEFAERSV AKLEKTIDDL EERLYSQLER NRLLSNELKL TLHDLCD

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
IPI	IPI00183968. IPI00218319. IPI00218320.
PIR	A25530. A24199. S06210.
RefSeq	NP_001036816.1. NP_001036817.1. NP_689476.2. NP_705935.1.
UniGene	Hs.535581 Hs.644306 Hs.654421
3D structure databases
HSSP	HSSP built from PDB template 1C1G based on UniProtKB P42639.
SMR	P06753. Positions 1-284.
ModBase	Search...
Protein-protein interaction databases
IntAct	P06753. 15 interactions.
PTM databases
PhosphoSite	P06753.
2-D gel databases
SWISS-2DPAGE	P06753.
Aarhus/Ghent-2DPAGE	9121. IEF.
Cornea-2DPAGE	P06753.
DOSAC-COBS-2DPAGE	P06753.
PHCI-2DPAGE	P06753.
Proteomic databases
PRIDE	P06753.
Genome annotation databases
Ensembl	ENSG00000143549. Homo sapiens. [Contig view]
GeneID	7170.
KEGG	hsa:7170.
Organism-specific databases
GeneCards	GC01M152395.
H-InvDB	HIX0001100.
HGNC	HGNC:12012. TPM3.
HPA	HPA009066.
MIM	164970. gene. 188550. phenotype. 191030. gene. 609284. phenotype.
Orphanet	607. Nemaline myopathy.
PharmGKB	PA36692.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	P06753.
Gene expression databases
ArrayExpress	P06753.
Bgee	P06753.
CleanEx	HS_TPM3.
GermOnline	ENSG00000143549. Homo sapiens.
Family and domain databases
InterPro	IPR000533. Tropomyosin. [Graphical view]
Pfam	PF00261. Tropomyosin. 1 hit. [Graphical view]
PRINTS	PR00194. TROPOMYOSIN.
PROSITE	PS00326. TROPOMYOSIN. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	28092.
SOURCE	Search...

Entry information

Entry name

TPM3_HUMAN

Accession

Primary (citable) accession number: P06753
Secondary accession number(s): P12324 , 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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)