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Protein

Alpha-actinin-3

Gene

ACTN3

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

Functioni

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

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi773 – 7841; possibly ancestralAdd BLAST12
Calcium bindingi809 – 8202; possibly ancestralAdd BLAST12

GO - Molecular functioni

  • calcium ion binding Source: InterPro
  • integrin binding Source: UniProtKB
  • ion channel binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • structural constituent of muscle Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Ligandi

Actin-binding, Calcium, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-373753. Nephrin interactions.
R-HSA-390522. Striated Muscle Contraction.

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-actinin-3
Alternative name(s):
Alpha-actinin skeletal muscle isoform 3
F-actin cross-linking protein
Gene namesi
Name:ACTN3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:165. ACTN3.

Subcellular locationi

GO - Cellular componenti

  • actin filament Source: ProtInc
  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • focal adhesion Source: UniProtKB
  • intracellular Source: UniProtKB
  • pseudopodium Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

DisGeNETi89.
MIMi102574. gene+phenotype.
OpenTargetsiENSG00000248746.
PharmGKBiPA24485.

Polymorphism and mutation databases

DMDMi215273967.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000734381 – 901Alpha-actinin-3Add BLAST901

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ08043.
MaxQBiQ08043.
PeptideAtlasiQ08043.
PRIDEiQ08043.

PTM databases

iPTMnetiQ08043.
PhosphoSitePlusiQ08043.
SwissPalmiQ08043.

Expressioni

Tissue specificityi

Expressed only in a subset of type 2 skeletal muscle fibers.1 Publication

Gene expression databases

CleanExiHS_ACTN3.
ExpressionAtlasiQ08043. baseline and differential.
GenevisibleiQ08043. HS.

Organism-specific databases

HPAiHPA006035.

Interactioni

Subunit structurei

Homodimer; antiparallel. Also forms heterodimers with ACTN2. Interacts with MYOZ1.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
ACTN1P128144EBI-2880652,EBI-351710

GO - Molecular functioni

  • integrin binding Source: UniProtKB
  • ion channel binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi106604. 22 interactors.
IntActiQ08043. 32 interactors.
MINTiMINT-269455.

Structurei

Secondary structure

1901
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi43 – 59Combined sources17
Helixi60 – 62Combined sources3
Turni69 – 75Combined sources7
Helixi77 – 87Combined sources11
Helixi100 – 115Combined sources16
Turni116 – 118Combined sources3
Helixi126 – 131Combined sources6
Helixi134 – 149Combined sources16
Turni150 – 152Combined sources3
Helixi160 – 172Combined sources13
Beta strandi182 – 184Combined sources3
Helixi185 – 187Combined sources3
Helixi191 – 200Combined sources10
Turni202 – 204Combined sources3
Helixi207 – 209Combined sources3
Helixi215 – 229Combined sources15
Helixi238 – 243Combined sources6
Beta strandi244 – 246Combined sources3
Helixi249 – 265Combined sources17

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
ProteinModelPortaliQ08043.
SMRiQ08043.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ08043.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 261Actin-bindingAdd BLAST261
Domaini45 – 149CH 1PROSITE-ProRule annotationAdd BLAST105
Domaini158 – 261CH 2PROSITE-ProRule annotationAdd BLAST104
Repeati288 – 398Spectrin 1Add BLAST111
Repeati408 – 513Spectrin 2Add BLAST106
Repeati523 – 634Spectrin 3Add BLAST112
Repeati644 – 747Spectrin 4Add BLAST104
Domaini760 – 795EF-hand 1PROSITE-ProRule annotationAdd BLAST36
Domaini796 – 831EF-hand 2PROSITE-ProRule annotationAdd BLAST36

Sequence similaritiesi

Belongs to the alpha-actinin family.Curated
Contains 1 actin-binding domain.Curated
Contains 2 CH (calponin-homology) domains.PROSITE-ProRule annotation
Contains 2 EF-hand domains.PROSITE-ProRule annotation
Contains 4 spectrin repeats.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

GeneTreeiENSGT00760000118813.
HOVERGENiHBG050453.
InParanoidiQ08043.
KOiK05699.
PhylomeDBiQ08043.

Family and domain databases

CDDicd00014. CH. 2 hits.
cd00051. EFh. 1 hit.
Gene3Di1.10.238.10. 2 hits.
1.10.418.10. 2 hits.
InterProiIPR001589. 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]
PfamiPF00307. CH. 2 hits.
PF08726. EFhand_Ca_insen. 1 hit.
PF00435. Spectrin. 4 hits.
[Graphical view]
SMARTiSM00033. CH. 2 hits.
SM00054. EFh. 2 hits.
SM00150. SPEC. 2 hits.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
SSF47576. SSF47576. 1 hit.
PROSITEiPS00019. ACTININ_1. 1 hit.
PS00020. ACTININ_2. 1 hit.
PS50021. CH. 2 hits.
PS50222. EF_HAND_2. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q08043-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MMMVMQPEGL GAGEGRFAGG GGGGEYMEQE EDWDRDLLLD PAWEKQQRKT
60 70 80 90 100
FTAWCNSHLR KAGTQIENIE EDFRNGLKLM LLLEVISGER LPRPDKGKMR
110 120 130 140 150
FHKIANVNKA LDFIASKGVK LVSIGAEEIV DGNLKMTLGM IWTIILRFAI
160 170 180 190 200
QDISVEETSA KEGLLLWCQR KTAPYRNVNV QNFHTSWKDG LALCALIHRH
210 220 230 240 250
RPDLIDYAKL RKDDPIGNLN TAFEVAEKYL DIPKMLDAED IVNTPKPDEK
260 270 280 290 300
AIMTYVSCFY HAFAGAEQAE TAANRICKVL AVNQENEKLM EEYEKLASEL
310 320 330 340 350
LEWIRRTVPW LENRVGEPSM SAMQRKLEDF RDYRRLHKPP RIQEKCQLEI
360 370 380 390 400
NFNTLQTKLR LSHRPAFMPS EGKLVSDIAN AWRGLEQVEK GYEDWLLSEI
410 420 430 440 450
RRLQRLQHLA EKFRQKASLH EAWTRGKEEM LSQRDYDSAL LQEVRALLRR
460 470 480 490 500
HEAFESDLAA HQDRVEHIAA LAQELNELDY HEAASVNSRC QAICDQWDNL
510 520 530 540 550
GTLTQKRRDA LERMEKLLET IDRLQLEFAR RAAPFNNWLD GAVEDLQDVW
560 570 580 590 600
LVHSVEETQS LLTAHDQFKA TLPEADRERG AIMGIQGEIQ KICQTYGLRP
610 620 630 640 650
CSTNPYITLS PQDINTKWDM VRKLVPSCDQ TLQEELARQQ VNERLRRQFA
660 670 680 690 700
AQANAIGPWI QAKVEEVGRL AAGLAGSLEE QMAGLRQQEQ NIINYKTNID
710 720 730 740 750
RLEGDHQLLQ ESLVFDNKHT VYSMEHIRVG WEQLLTSIAR TINEVENQVL
760 770 780 790 800
TRDAKGLSQE QLNEFRASFN HFDRKQNGMM EPDDFRACLI SMGYDLGEVE
810 820 830 840 850
FARIMTMVDP NAAGVVTFQA FIDFMTRETA ETDTTEQVVA SFKILAGDKN
860 870 880 890 900
YITPEELRRE LPAKQAEYCI RRMVPYKGSG APAGALDYVA FSSALYGESD

L
Length:901
Mass (Da):103,241
Last modified:November 25, 2008 - v2
Checksum:iC49B7885E7E1EDA7
GO

Sequence cautioni

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

Polymorphismi

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 [MIMi:102574].

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_012705523R → Q.3 PublicationsCorresponds to variant rs1671064dbSNPEnsembl.1
Natural variantiVAR_047528628C → R.2 PublicationsCorresponds to variant rs618838dbSNPEnsembl.1
Natural variantiVAR_033488635E → A.Corresponds to variant rs2229456dbSNPEnsembl.1
Natural variantiVAR_047529776Q → R.2 PublicationsCorresponds to variant rs540874dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M86407 mRNA. Translation: AAA51585.1.
AP002748 Genomic DNA. No translation available.
BC099647 mRNA. Translation: AAH99647.1.
BC099649 mRNA. Translation: AAH99649.1.
PIRiB40199. FAHUA3.
RefSeqiNP_001095.2. NM_001104.3.
NP_001245300.2. NM_001258371.2.
UniGeneiHs.654432.
Hs.737862.

Genome annotation databases

EnsembliENST00000513398; ENSP00000426797; ENSG00000248746.
GeneIDi89.
KEGGihsa:89.
UCSCiuc021qlz.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M86407 mRNA. Translation: AAA51585.1.
AP002748 Genomic DNA. No translation available.
BC099647 mRNA. Translation: AAH99647.1.
BC099649 mRNA. Translation: AAH99649.1.
PIRiB40199. FAHUA3.
RefSeqiNP_001095.2. NM_001104.3.
NP_001245300.2. NM_001258371.2.
UniGeneiHs.654432.
Hs.737862.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
ProteinModelPortaliQ08043.
SMRiQ08043.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106604. 22 interactors.
IntActiQ08043. 32 interactors.
MINTiMINT-269455.

PTM databases

iPTMnetiQ08043.
PhosphoSitePlusiQ08043.
SwissPalmiQ08043.

Polymorphism and mutation databases

DMDMi215273967.

Proteomic databases

EPDiQ08043.
MaxQBiQ08043.
PeptideAtlasiQ08043.
PRIDEiQ08043.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000513398; ENSP00000426797; ENSG00000248746.
GeneIDi89.
KEGGihsa:89.
UCSCiuc021qlz.4. human.

Organism-specific databases

CTDi89.
DisGeNETi89.
GeneCardsiACTN3.
HGNCiHGNC:165. ACTN3.
HPAiHPA006035.
MIMi102574. gene+phenotype.
neXtProtiNX_Q08043.
OpenTargetsiENSG00000248746.
PharmGKBiPA24485.
GenAtlasiSearch...

Phylogenomic databases

GeneTreeiENSGT00760000118813.
HOVERGENiHBG050453.
InParanoidiQ08043.
KOiK05699.
PhylomeDBiQ08043.

Enzyme and pathway databases

ReactomeiR-HSA-373753. Nephrin interactions.
R-HSA-390522. Striated Muscle Contraction.

Miscellaneous databases

EvolutionaryTraceiQ08043.
GeneWikiiACTN3.
GenomeRNAii89.
PROiQ08043.
SOURCEiSearch...

Gene expression databases

CleanExiHS_ACTN3.
ExpressionAtlasiQ08043. baseline and differential.
GenevisibleiQ08043. HS.

Family and domain databases

CDDicd00014. CH. 2 hits.
cd00051. EFh. 1 hit.
Gene3Di1.10.238.10. 2 hits.
1.10.418.10. 2 hits.
InterProiIPR001589. 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]
PfamiPF00307. CH. 2 hits.
PF08726. EFhand_Ca_insen. 1 hit.
PF00435. Spectrin. 4 hits.
[Graphical view]
SMARTiSM00033. CH. 2 hits.
SM00054. EFh. 2 hits.
SM00150. SPEC. 2 hits.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
SSF47576. SSF47576. 1 hit.
PROSITEiPS00019. ACTININ_1. 1 hit.
PS00020. ACTININ_2. 1 hit.
PS50021. CH. 2 hits.
PS50222. EF_HAND_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiACTN3_HUMAN
AccessioniPrimary (citable) accession number: Q08043
Secondary accession number(s): A6NP77, Q4KKV2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: November 25, 2008
Last modified: November 30, 2016
This is version 157 of the entry and version 2 of the sequence. [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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.