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Protein

Actin, aortic smooth muscle

Gene

ACTA2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.

Miscellaneous

In vertebrates 3 main groups of actin isoforms, alpha, beta and gamma have been identified. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins coexist in most cell types as components of the cytoskeleton and as mediators of internal cell motility.

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionMuscle protein
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-445355. Smooth Muscle Contraction.
SignaLinkiP62736.
SIGNORiP62736.

Names & Taxonomyi

Protein namesi
Recommended name:
Actin, aortic smooth muscle
Alternative name(s):
Alpha-actin-2
Cell growth-inhibiting gene 46 protein
Gene namesi
Name:ACTA2
Synonyms:ACTSA, ACTVS
ORF Names:GIG46
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000107796.12.
HGNCiHGNC:130. ACTA2.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton

Pathology & Biotechi

Involvement in diseasei

ACTA2 mutations predispose patients to a variety of diffuse and diverse vascular diseases, premature onset coronary artery disease (CAD), premature ischemic strokes and Moyamoya disease.1 Publication
Aortic aneurysm, familial thoracic 6 (AAT6)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by permanent dilation of the thoracic aorta usually due to degenerative changes in the aortic wall. It is primarily associated with a characteristic histologic appearance known as 'medial necrosis' or 'Erdheim cystic medial necrosis' in which there is degeneration and fragmentation of elastic fibers, loss of smooth muscle cells, and an accumulation of basophilic ground substance.
See also OMIM:611788
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06257739R → H in AAT6. 1 PublicationCorresponds to variant dbSNP:rs794728021Ensembl.1
Natural variantiVAR_045915117N → T in AAT6. 2 Publications1
Natural variantiVAR_045916118R → Q in AAT6. 2 PublicationsCorresponds to variant dbSNP:rs112602953Ensembl.1
Natural variantiVAR_045917135Y → H in AAT6. 1 PublicationCorresponds to variant dbSNP:rs751300489Ensembl.1
Natural variantiVAR_062578145Y → C in AAT6. 1 Publication1
Natural variantiVAR_045918149R → C in AAT6. 3 PublicationsCorresponds to variant dbSNP:rs121434526Ensembl.1
Natural variantiVAR_045919154V → A in AAT6. 2 Publications1
Natural variantiVAR_062579185R → Q in AAT6. 1 Publication1
Natural variantiVAR_062580212R → Q in AAT6. 2 PublicationsCorresponds to variant dbSNP:rs397516685Ensembl.1
Natural variantiVAR_045920258R → C in AAT6. 2 PublicationsCorresponds to variant dbSNP:rs121434528Ensembl.1
Natural variantiVAR_045921258R → H in AAT6. 2 PublicationsCorresponds to variant dbSNP:rs121434527Ensembl.1
Natural variantiVAR_045922292R → G in AAT6. 1 Publication1
Natural variantiVAR_062581326T → N in AAT6. 1 PublicationCorresponds to variant dbSNP:rs777832794Ensembl.1
Natural variantiVAR_045923353T → N in AAT6. 2 Publications1
Moyamoya disease 5 (MYMY5)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA progressive cerebral angiopathy characterized by bilateral intracranial carotid artery stenosis and telangiectatic vessels in the region of the basal ganglia. The abnormal vessels resemble a 'puff of smoke' (moyamoya) on cerebral angiogram. Affected individuals can develop transient ischemic attacks and/or cerebral infarction, and rupture of the collateral vessels can cause intracranial hemorrhage. Hemiplegia of sudden onset and epileptic seizures constitute the prevailing presentation in childhood, while subarachnoid bleeding occurs more frequently in adults.
See also OMIM:614042
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_064516179R → H in MYMY5 and MSMDYS; disease phenotype include smooth muscle cells dysfunction in organs throughout the body with decreased contractile function in the iris, bladder and gastrointestinal tract. 2 PublicationsCorresponds to variant dbSNP:rs387906592Ensembl.1
Multisystemic smooth muscle dysfunction syndrome (MSMDYS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA syndrome characterized by dysfunction of smooth muscle cells throughout the body, leading to aortic and cerebrovascular disease, fixed dilated pupils, hypotonic bladder, malrotation, and hypoperistalsis of the gut and pulmonary hypertension.
See also OMIM:613834
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_064516179R → H in MYMY5 and MSMDYS; disease phenotype include smooth muscle cells dysfunction in organs throughout the body with decreased contractile function in the iris, bladder and gastrointestinal tract. 2 PublicationsCorresponds to variant dbSNP:rs387906592Ensembl.1

Keywords - Diseasei

Aortic aneurysm, Disease mutation

Organism-specific databases

DisGeNETi59.
GeneReviewsiACTA2.
MalaCardsiACTA2.
MIMi611788. phenotype.
613834. phenotype.
614042. phenotype.
OpenTargetsiENSG00000107796.
Orphaneti91387. Familial thoracic aortic aneurysm and aortic dissection.
2573. Moyamoya disease.
404463. Multisystemic smooth muscle dysfunction syndrome.
PharmGKBiPA24456.

Polymorphism and mutation databases

BioMutaiACTA2.
DMDMi51316972.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PropeptideiPRO_00000007381 – 2Removed in mature formCombined sources2
ChainiPRO_00000007393 – 377Actin, aortic smooth muscleAdd BLAST375

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei3N-acetylglutamateCombined sources1
Modified residuei46Methionine (R)-sulfoxideBy similarity1
Modified residuei49Methionine (R)-sulfoxideBy similarity1
Cross-linki52Isoglutamyl lysine isopeptide (Lys-Glu) (interchain with E-272); by Vibrio toxins RtxA and VgrG1By similarity
Modified residuei75Tele-methylhistidineBy similarity1
Modified residuei86N6-methyllysineBy similarity1
Cross-linki272Isoglutamyl lysine isopeptide (Glu-Lys) (interchain with K-52); by Vibrio toxins RtxA and VgrG1By similarity

Post-translational modificationi

Oxidation of Met-46 and Met-49 by MICALs (MICAL1, MICAL2 or MICAL3) to form methionine sulfoxide promotes actin filament depolymerization. MICAL1 and MICAL2 produce the (R)-S-oxide form. The (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promote actin repolymerization (By similarity).By similarity
Monomethylation at Lys-86 (K84me1) regulates actin-myosin interaction and actomyosin-dependent processes. Demethylation by ALKBH4 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration.By similarity
(Microbial infection) Monomeric actin is cross-linked by V.cholerae toxins RtxA and VgrG1 in case of infection: bacterial toxins mediate the cross-link between Lys-52 of one monomer and Glu-272 of another actin monomer, resulting in formation of highly toxic actin oligomers that cause cell rounding (PubMed:19015515). The toxin can be highly efficient at very low concentrations by acting on formin homology family proteins: toxic actin oligomers bind with high affinity to formins and adversely affect both nucleation and elongation abilities of formins, causing their potent inhibition in both profilin-dependent and independent manners (PubMed:26228148).2 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Oxidation

Proteomic databases

EPDiP62736.
MaxQBiP62736.
PaxDbiP62736.
PeptideAtlasiP62736.
PRIDEiP62736.
TopDownProteomicsiP62736.

2D gel databases

REPRODUCTION-2DPAGEiIPI00008603.
UCD-2DPAGEiP62736.

PTM databases

iPTMnetiP62736.
PhosphoSitePlusiP62736.
SwissPalmiP62736.

Miscellaneous databases

PMAP-CutDBiP62736.

Expressioni

Inductioni

Up-regulated in response to enterovirus 71 (EV71) infection.1 Publication

Gene expression databases

BgeeiENSG00000107796.
CleanExiHS_ACTA2.
ExpressionAtlasiP62736. baseline and differential.
GenevisibleiP62736. HS.

Organism-specific databases

HPAiCAB000002.
CAB013531.
HPA041264.
HPA041271.

Interactioni

Subunit structurei

Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix. Each actin can bind to 4 others.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi106574. 166 interactors.
CORUMiP62736.
ELMiP62736.
IntActiP62736. 25 interactors.
STRINGi9606.ENSP00000224784.

Structurei

3D structure databases

ProteinModelPortaliP62736.
SMRiP62736.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the actin family.Curated

Phylogenomic databases

eggNOGiKOG0676. Eukaryota.
COG5277. LUCA.
GeneTreeiENSGT00760000118957.
HOGENOMiHOG000233340.
HOVERGENiHBG003771.
InParanoidiP62736.
KOiK12313.
OMAiAMCEEED.
OrthoDBiEOG091G08LD.
PhylomeDBiP62736.
TreeFamiTF354237.

Family and domain databases

InterProiView protein in InterPro
IPR004000. Actin.
IPR020902. Actin/actin-like_CS.
IPR004001. Actin_CS.
PANTHERiPTHR11937. PTHR11937. 1 hit.
PfamiView protein in Pfam
PF00022. Actin. 1 hit.
PRINTSiPR00190. ACTIN.
SMARTiView protein in SMART
SM00268. ACTIN. 1 hit.
PROSITEiView protein in PROSITE
PS00406. ACTINS_1. 1 hit.
PS00432. ACTINS_2. 1 hit.
PS01132. ACTINS_ACT_LIKE. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P62736-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MCEEEDSTAL VCDNGSGLCK AGFAGDDAPR AVFPSIVGRP RHQGVMVGMG
60 70 80 90 100
QKDSYVGDEA QSKRGILTLK YPIEHGIITN WDDMEKIWHH SFYNELRVAP
110 120 130 140 150
EEHPTLLTEA PLNPKANREK MTQIMFETFN VPAMYVAIQA VLSLYASGRT
160 170 180 190 200
TGIVLDSGDG VTHNVPIYEG YALPHAIMRL DLAGRDLTDY LMKILTERGY
210 220 230 240 250
SFVTTAEREI VRDIKEKLCY VALDFENEMA TAASSSSLEK SYELPDGQVI
260 270 280 290 300
TIGNERFRCP ETLFQPSFIG MESAGIHETT YNSIMKCDID IRKDLYANNV
310 320 330 340 350
LSGGTTMYPG IADRMQKEIT ALAPSTMKIK IIAPPERKYS VWIGGSILAS
360 370
LSTFQQMWIS KQEYDEAGPS IVHRKCF
Length:377
Mass (Da):42,009
Last modified:August 16, 2004 - v1
Checksum:i2D0543262DB35CA5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti234S → W in AAA51577 (PubMed:2295650).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06257739R → H in AAT6. 1 PublicationCorresponds to variant dbSNP:rs794728021Ensembl.1
Natural variantiVAR_045915117N → T in AAT6. 2 Publications1
Natural variantiVAR_045916118R → Q in AAT6. 2 PublicationsCorresponds to variant dbSNP:rs112602953Ensembl.1
Natural variantiVAR_045917135Y → H in AAT6. 1 PublicationCorresponds to variant dbSNP:rs751300489Ensembl.1
Natural variantiVAR_062578145Y → C in AAT6. 1 Publication1
Natural variantiVAR_045918149R → C in AAT6. 3 PublicationsCorresponds to variant dbSNP:rs121434526Ensembl.1
Natural variantiVAR_045919154V → A in AAT6. 2 Publications1
Natural variantiVAR_064516179R → H in MYMY5 and MSMDYS; disease phenotype include smooth muscle cells dysfunction in organs throughout the body with decreased contractile function in the iris, bladder and gastrointestinal tract. 2 PublicationsCorresponds to variant dbSNP:rs387906592Ensembl.1
Natural variantiVAR_062579185R → Q in AAT6. 1 Publication1
Natural variantiVAR_011944196T → S. Corresponds to variant dbSNP:rs1803028Ensembl.1
Natural variantiVAR_062580212R → Q in AAT6. 2 PublicationsCorresponds to variant dbSNP:rs397516685Ensembl.1
Natural variantiVAR_045920258R → C in AAT6. 2 PublicationsCorresponds to variant dbSNP:rs121434528Ensembl.1
Natural variantiVAR_045921258R → H in AAT6. 2 PublicationsCorresponds to variant dbSNP:rs121434527Ensembl.1
Natural variantiVAR_045922292R → G in AAT6. 1 Publication1
Natural variantiVAR_011945320T → A. Corresponds to variant dbSNP:rs1803027Ensembl.1
Natural variantiVAR_062581326T → N in AAT6. 1 PublicationCorresponds to variant dbSNP:rs777832794Ensembl.1
Natural variantiVAR_045923353T → N in AAT6. 2 Publications1
Natural variantiVAR_011946373H → P. Corresponds to variant dbSNP:rs1062398Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X13839 mRNA. Translation: CAA32064.1.
J05192 mRNA. Translation: AAA51577.1.
AY692464 mRNA. Translation: AAW29811.1.
CR536518 mRNA. Translation: CAG38756.1.
AK313294 mRNA. Translation: BAG36101.1.
AL157394 Genomic DNA. No translation available.
CH471066 Genomic DNA. Translation: EAW50153.1.
BC017554 mRNA. Translation: AAH17554.1.
BC093052 mRNA. Translation: AAH93052.1.
K01741 Genomic DNA. No translation available.
K01742 Genomic DNA. No translation available.
K01743 Genomic DNA. No translation available.
M33216 Genomic DNA. Translation: AAA60560.1.
CCDSiCCDS7392.1.
PIRiA35020. ATHUSM.
RefSeqiNP_001135417.1. NM_001141945.2.
NP_001307784.1. NM_001320855.1.
NP_001604.1. NM_001613.2.
UniGeneiHs.500483.

Genome annotation databases

EnsembliENST00000224784; ENSP00000224784; ENSG00000107796.
GeneIDi59.
KEGGihsa:59.
UCSCiuc001kfp.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiACTA_HUMAN
AccessioniPrimary (citable) accession number: P62736
Secondary accession number(s): B2R8A4
, P03996, P04108, Q6FI19
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 23, 1986
Last sequence update: August 16, 2004
Last modified: September 27, 2017
This is version 142 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families