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Q08043 (ACTN3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Alpha-actinin-3
Alternative name(s):
Alpha-actinin skeletal muscle isoform 3
F-actin cross-linking protein
Gene names
Name:ACTN3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length901 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein.

Subunit structure

Homodimer; antiparallel. Also forms heterodimers with ACTN2. Interacts with MYOZ1. Ref.5

Tissue specificity

Expressed only in a subset of type 2 skeletal muscle fibers. Ref.4

Polymorphism

About 18% of the world population lack a functional ACTN3 due to a stop codon polymorphism at position 577. The absence of a functional ACTN3 expression is not correlated with a disease state [MIM:102574].

Sequence similarities

Belongs to the alpha-actinin family.

Contains 1 actin-binding domain.

Contains 2 CH (calponin-homology) domains.

Contains 2 EF-hand domains.

Contains 4 spectrin repeats.

Sequence caution

The sequence AP002748 differs from that shown. Reason: According to the human genome assembly there is a stop codon in position 577 which is only found in 18% of the world population.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 901901Alpha-actinin-3
PRO_0000073438

Regions

Domain1 – 261261Actin-binding
Domain45 – 149105CH 1
Domain158 – 261104CH 2
Repeat288 – 398111Spectrin 1
Repeat408 – 513106Spectrin 2
Repeat523 – 634112Spectrin 3
Repeat644 – 747104Spectrin 4
Domain760 – 79536EF-hand 1
Domain796 – 83136EF-hand 2
Calcium binding773 – 784121; possibly ancestral
Calcium binding809 – 820122; possibly ancestral

Amino acid modifications

Modified residue11N-acetylmethionine Ref.6

Natural variations

Natural variant5231R → Q. Ref.1 Ref.3 Ref.8
Corresponds to variant rs1671064 [ dbSNP | Ensembl ].
VAR_012705
Natural variant6281C → R. Ref.1 Ref.3
Corresponds to variant rs618838 [ dbSNP | Ensembl ].
VAR_047528
Natural variant6351E → A.
Corresponds to variant rs2229456 [ dbSNP | Ensembl ].
VAR_033488
Natural variant7761Q → R. Ref.1 Ref.3
Corresponds to variant rs540874 [ dbSNP | Ensembl ].
VAR_047529

Secondary structure

.................................. 901
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q08043 [UniParc].

Last modified November 25, 2008. Version 2.
Checksum: C49B7885E7E1EDA7

FASTA901103,241
        10         20         30         40         50         60 
MMMVMQPEGL GAGEGRFAGG GGGGEYMEQE EDWDRDLLLD PAWEKQQRKT FTAWCNSHLR 

        70         80         90        100        110        120 
KAGTQIENIE EDFRNGLKLM LLLEVISGER LPRPDKGKMR FHKIANVNKA LDFIASKGVK 

       130        140        150        160        170        180 
LVSIGAEEIV DGNLKMTLGM IWTIILRFAI QDISVEETSA KEGLLLWCQR KTAPYRNVNV 

       190        200        210        220        230        240 
QNFHTSWKDG LALCALIHRH RPDLIDYAKL RKDDPIGNLN TAFEVAEKYL DIPKMLDAED 

       250        260        270        280        290        300 
IVNTPKPDEK AIMTYVSCFY HAFAGAEQAE TAANRICKVL AVNQENEKLM EEYEKLASEL 

       310        320        330        340        350        360 
LEWIRRTVPW LENRVGEPSM SAMQRKLEDF RDYRRLHKPP RIQEKCQLEI NFNTLQTKLR 

       370        380        390        400        410        420 
LSHRPAFMPS EGKLVSDIAN AWRGLEQVEK GYEDWLLSEI RRLQRLQHLA EKFRQKASLH 

       430        440        450        460        470        480 
EAWTRGKEEM LSQRDYDSAL LQEVRALLRR HEAFESDLAA HQDRVEHIAA LAQELNELDY 

       490        500        510        520        530        540 
HEAASVNSRC QAICDQWDNL GTLTQKRRDA LERMEKLLET IDRLQLEFAR RAAPFNNWLD 

       550        560        570        580        590        600 
GAVEDLQDVW LVHSVEETQS LLTAHDQFKA TLPEADRERG AIMGIQGEIQ KICQTYGLRP 

       610        620        630        640        650        660 
CSTNPYITLS PQDINTKWDM VRKLVPSCDQ TLQEELARQQ VNERLRRQFA AQANAIGPWI 

       670        680        690        700        710        720 
QAKVEEVGRL AAGLAGSLEE QMAGLRQQEQ NIINYKTNID RLEGDHQLLQ ESLVFDNKHT 

       730        740        750        760        770        780 
VYSMEHIRVG WEQLLTSIAR TINEVENQVL TRDAKGLSQE QLNEFRASFN HFDRKQNGMM 

       790        800        810        820        830        840 
EPDDFRACLI SMGYDLGEVE FARIMTMVDP NAAGVVTFQA FIDFMTRETA ETDTTEQVVA 

       850        860        870        880        890        900 
SFKILAGDKN YITPEELRRE LPAKQAEYCI RRMVPYKGSG APAGALDYVA FSSALYGESD 


L 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and characterization of two human skeletal muscle alpha-actinin genes located on chromosomes 1 and 11."
Beggs A.H., Byers T.J., Knoll J.H.M., Boyce F.M., Bruns G.A.P., Kunkel L.M.
J. Biol. Chem. 267:9281-9288(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS GLN-523; ARG-628 AND ARG-776.
Tissue: Skeletal muscle.
[2]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS GLN-523; ARG-628 AND ARG-776.
[4]"Differential expression of the actin-binding proteins, alpha-actinin-2 and -3, in different species: implications for the evolution of functional redundancy."
Mills M., Yang N., Weinberger R., Vander Woude D.L., Beggs A.H., Easteal S., North K.N.
Hum. Mol. Genet. 10:1335-1346(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, POLYMORPHISM.
[5]"Myozenin: an alpha-actinin- and gamma-filamin-binding protein of skeletal muscle Z lines."
Takada F., Vander Woude D.L., Tong H.-Q., Thompson T.G., Watkins S.C., Kunkel L.M., Beggs A.H.
Proc. Natl. Acad. Sci. U.S.A. 98:1595-1600(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MYOZ1.
[6]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]"The crystal structure of the actin binding domain from alpha-actinin in its closed conformation: structural insight into phospholipid regulation of alpha-actinin."
Franzot G., Sjoblom B., Gautel M., Djinovic Carugo K.
J. Mol. Biol. 348:151-165(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 26-273.
[8]"A common nonsense mutation results in alpha-actinin-3 deficiency in the general population."
North K.N., Yang N., Wattanasirichaigoon D., Mills M., Easteal S., Beggs A.H.
Nat. Genet. 21:353-354(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLN-523, POLYMORPHISM.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M86407 mRNA. Translation: AAA51585.1.
AP002748 Genomic DNA. No translation available.
BC099647 mRNA. Translation: AAH99647.1.
BC099649 mRNA. Translation: AAH99649.1.
PIRFAHUA3. B40199.
RefSeqNP_001095.2. NM_001104.3.
UniGeneHs.654432.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1TJTX-ray2.19A26-273[»]
1WKUX-ray1.60A/B26-273[»]
3LUEelectron microscopy-K/L/M/N/O/P/Q/R/S/T42-150[»]
ProteinModelPortalQ08043.
SMRQ08043. Positions 42-268, 281-901.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106604. 3 interactions.
IntActQ08043. 4 interactions.
MINTMINT-269455.

PTM databases

PhosphoSiteQ08043.

Polymorphism databases

DMDM215273967.

Proteomic databases

PRIDEQ08043.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID89.
KEGGhsa:89.

Organism-specific databases

CTD89.
GeneCardsGC11P066314.
HGNCHGNC:165. ACTN3.
MIM102574. gene+phenotype.
neXtProtNX_Q08043.
PharmGKBPA24485.
GenAtlasSearch...

Phylogenomic databases

HOVERGENHBG050453.
KOK05699.
PhylomeDBQ08043.

Enzyme and pathway databases

ReactomeREACT_111155. Cell-Cell communication.
REACT_17044. Muscle contraction.

Gene expression databases

CleanExHS_ACTN3.
GenevestigatorQ08043.

Family and domain databases

Gene3D1.10.238.10. 2 hits.
1.10.418.10. 2 hits.
InterProIPR001589. Actinin_actin-bd_CS.
IPR001715. CH-domain.
IPR011992. EF-hand-dom_pair.
IPR014837. EF-hand_Ca_insen.
IPR002048. EF_hand_dom.
IPR018159. Spectrin/alpha-actinin.
IPR002017. Spectrin_repeat.
[Graphical view]
PfamPF00307. CH. 2 hits.
PF08726. EFhand_Ca_insen. 1 hit.
PF00435. Spectrin. 4 hits.
[Graphical view]
SMARTSM00033. CH. 2 hits.
SM00054. EFh. 2 hits.
SM00150. SPEC. 2 hits.
[Graphical view]
SUPFAMSSF47576. SSF47576. 1 hit.
PROSITEPS00019. ACTININ_1. 1 hit.
PS00020. ACTININ_2. 1 hit.
PS50021. CH. 2 hits.
PS50222. EF_HAND_2. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ08043.
GeneWikiACTN3.
GenomeRNAi89.
NextBio331.
PROQ08043.
SOURCESearch...

Entry information

Entry nameACTN3_HUMAN
AccessionPrimary (citable) accession number: Q08043
Secondary accession number(s): A6NP77, Q4KKV2
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: November 25, 2008
Last modified: April 16, 2014
This is version 133 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM