UniProtKB - Q08043 (ACTN3_HUMAN)
Protein
Alpha-actinin-3
Gene
ACTN3
Organism
Homo sapiens (Human)
Status
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Calcium bindingi | 773 – 784 | 1; possibly ancestralAdd BLAST | 12 | |
Calcium bindingi | 809 – 820 | 2; possibly ancestralAdd BLAST | 12 |
GO - Molecular functioni
- actin binding Source: UniProtKB-KW
- calcium ion binding Source: InterPro
- identical protein binding Source: IntAct
- integrin binding Source: UniProtKB
- ion channel binding Source: UniProtKB
- structural constituent of muscle Source: ProtInc
GO - Biological processi
- focal adhesion assembly Source: UniProtKB
- muscle filament sliding Source: Reactome
- negative regulation of calcineurin-NFAT signaling cascade Source: UniProtKB
- negative regulation of cold-induced thermogenesis Source: YuBioLab
- negative regulation of glycolytic process Source: UniProtKB
- negative regulation of oxidative phosphorylation Source: UniProtKB
- positive regulation of glucose catabolic process to lactate via pyruvate Source: UniProtKB
- positive regulation of skeletal muscle tissue growth Source: UniProtKB
- regulation of aerobic respiration Source: UniProtKB
- regulation of apoptotic process Source: UniProtKB
- regulation of the force of skeletal muscle contraction Source: UniProtKB
- response to denervation involved in regulation of muscle adaptation Source: UniProtKB
- skeletal muscle atrophy Source: UniProtKB
- transition between fast and slow fiber Source: UniProtKB
Keywordsi
Molecular function | Actin-binding |
Ligand | Calcium, Metal-binding |
Enzyme and pathway databases
PathwayCommonsi | Q08043 |
Reactomei | R-HSA-373753, Nephrin family interactions R-HSA-390522, Striated Muscle Contraction |
Names & Taxonomyi
Protein namesi | Recommended name: Alpha-actinin-3Alternative name(s): Alpha-actinin skeletal muscle isoform 3 F-actin cross-linking protein |
Gene namesi | Name:ACTN3 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000248746.5 |
HGNCi | HGNC:165, ACTN3 |
neXtProti | NX_Q08043 |
Subcellular locationi
Cytoskeleton
- actin filament Source: ProtInc
Cytosol
- cytosol Source: Reactome
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
Other locations
- focal adhesion Source: UniProtKB
- pseudopodium Source: UniProtKB
Pathology & Biotechi
Organism-specific databases
DisGeNETi | 89 |
MalaCardsi | ACTN3 |
MIMi | 102574, phenotype 617749, phenotype |
OpenTargetsi | ENSG00000248746 |
PharmGKBi | PA24485 |
Miscellaneous databases
Pharosi | Q08043, Tbio |
Polymorphism and mutation databases
BioMutai | ACTN3 |
DMDMi | 215273967 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000073438 | 1 – 901 | Alpha-actinin-3Add BLAST | 901 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1 | N-acetylmethionineCombined sources | 1 |
Keywords - PTMi
AcetylationProteomic databases
EPDi | Q08043 |
jPOSTi | Q08043 |
MassIVEi | Q08043 |
MaxQBi | Q08043 |
PeptideAtlasi | Q08043 |
PRIDEi | Q08043 |
ProteomicsDBi | 58566 |
PTM databases
iPTMneti | Q08043 |
PhosphoSitePlusi | Q08043 |
SwissPalmi | Q08043 |
Expressioni
Tissue specificityi
Expressed only in a subset of type 2 skeletal muscle fibers.1 Publication
Gene expression databases
Bgeei | ENSG00000248746, Expressed in skeletal muscle tissue of rectus abdominis and 100 other tissues |
ExpressionAtlasi | Q08043, baseline and differential |
Genevisiblei | Q08043, HS |
Organism-specific databases
HPAi | ENSG00000248746, Tissue enriched (skeletal) |
Interactioni
Subunit structurei
Homodimer; antiparallel. Also forms heterodimers with ACTN2.
Interacts with MYOZ1.
1 PublicationBinary interactionsi
Hide detailsQ08043
GO - Molecular functioni
- actin binding Source: UniProtKB-KW
- identical protein binding Source: IntAct
- integrin binding Source: UniProtKB
- ion channel binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 106604, 69 interactors |
IntActi | Q08043, 56 interactors |
MINTi | Q08043 |
STRINGi | 9606.ENSP00000422007 |
Miscellaneous databases
RNActi | Q08043, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q08043 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q08043 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 45 – 149 | Calponin-homology (CH) 1PROSITE-ProRule annotationAdd BLAST | 105 | |
Domaini | 158 – 264 | Calponin-homology (CH) 2PROSITE-ProRule annotationAdd BLAST | 107 | |
Repeati | 288 – 398 | Spectrin 1Add BLAST | 111 | |
Repeati | 408 – 513 | Spectrin 2Add BLAST | 106 | |
Repeati | 523 – 634 | Spectrin 3Add BLAST | 112 | |
Repeati | 644 – 747 | Spectrin 4Add BLAST | 104 | |
Domaini | 760 – 795 | EF-hand 1PROSITE-ProRule annotationAdd BLAST | 36 | |
Domaini | 796 – 831 | EF-hand 2PROSITE-ProRule annotationAdd BLAST | 36 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 261 | Actin-bindingAdd BLAST | 261 |
Sequence similaritiesi
Belongs to the alpha-actinin family.Curated
Keywords - Domaini
RepeatPhylogenomic databases
eggNOGi | KOG0035, Eukaryota |
GeneTreei | ENSGT00940000153968 |
HOGENOMi | CLU_005217_1_1_1 |
InParanoidi | Q08043 |
OrthoDBi | 543832at2759 |
PhylomeDBi | Q08043 |
Family and domain databases
CDDi | cd00014, CH, 2 hits cd00051, EFh, 1 hit |
Gene3Di | 1.10.418.10, 2 hits |
InterProi | View protein in InterPro IPR001589, Actinin_actin-bd_CS IPR001715, CH-domain IPR036872, CH_dom_sf IPR011992, EF-hand-dom_pair IPR014837, EF-hand_Ca_insen IPR002048, EF_hand_dom IPR018159, Spectrin/alpha-actinin IPR002017, Spectrin_repeat |
Pfami | View protein in Pfam PF00307, CH, 2 hits PF08726, EFhand_Ca_insen, 1 hit PF00435, Spectrin, 4 hits |
SMARTi | View protein in SMART SM00033, CH, 2 hits SM00054, EFh, 2 hits SM00150, SPEC, 2 hits |
SUPFAMi | SSF47473, SSF47473, 1 hit SSF47576, SSF47576, 1 hit |
PROSITEi | View protein in PROSITE PS00019, ACTININ_1, 1 hit PS00020, ACTININ_2, 1 hit PS50021, CH, 2 hits PS50222, EF_HAND_2, 2 hits |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
Q08043-1 [UniParc]FASTAAdd to basket
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
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A087WSZ2 | A0A087WSZ2_HUMAN | Alpha-actinin-3 | ACTN3 | 944 | Annotation score: | ||
D6RH00 | D6RH00_HUMAN | Alpha-actinin-3 | ACTN3 | 72 | Annotation score: |
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:617749].1 Publication
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_012705 | 523 | R → Q3 PublicationsCorresponds to variant dbSNP:rs1671064Ensembl. | 1 | |
Natural variantiVAR_080044 | 577 – 901 | Missing Common polymorphism. 1 PublicationAdd BLAST | 325 | |
Natural variantiVAR_047528 | 628 | C → R2 PublicationsCorresponds to variant dbSNP:rs618838Ensembl. | 1 | |
Natural variantiVAR_033488 | 635 | E → A. Corresponds to variant dbSNP:rs2229456Ensembl. | 1 | |
Natural variantiVAR_047529 | 776 | Q → R2 PublicationsCorresponds to variant dbSNP:rs540874Ensembl. | 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 |
CCDSi | CCDS53663.1 |
PIRi | B40199, FAHUA3 |
RefSeqi | NP_001095.2, NM_001104.3 NP_001245300.2, NM_001258371.2 |
Genome annotation databases
Ensembli | ENST00000513398; ENSP00000426797; ENSG00000248746 |
GeneIDi | 89 |
KEGGi | hsa:89 |
UCSCi | uc021qlz.4, human |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
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 |
CCDSi | CCDS53663.1 |
PIRi | B40199, FAHUA3 |
RefSeqi | NP_001095.2, NM_001104.3 NP_001245300.2, NM_001258371.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1TJT | X-ray | 2.19 | A | 26-273 | [»] | |
1WKU | X-ray | 1.60 | A/B | 26-273 | [»] | |
3LUE | electron microscopy | - | K/L/M/N/O/P/Q/R/S/T | 42-150 | [»] | |
SMRi | Q08043 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 106604, 69 interactors |
IntActi | Q08043, 56 interactors |
MINTi | Q08043 |
STRINGi | 9606.ENSP00000422007 |
PTM databases
iPTMneti | Q08043 |
PhosphoSitePlusi | Q08043 |
SwissPalmi | Q08043 |
Polymorphism and mutation databases
BioMutai | ACTN3 |
DMDMi | 215273967 |
Proteomic databases
EPDi | Q08043 |
jPOSTi | Q08043 |
MassIVEi | Q08043 |
MaxQBi | Q08043 |
PeptideAtlasi | Q08043 |
PRIDEi | Q08043 |
ProteomicsDBi | 58566 |
Protocols and materials databases
Antibodypediai | 73518, 240 antibodies |
Genome annotation databases
Ensembli | ENST00000513398; ENSP00000426797; ENSG00000248746 |
GeneIDi | 89 |
KEGGi | hsa:89 |
UCSCi | uc021qlz.4, human |
Organism-specific databases
CTDi | 89 |
DisGeNETi | 89 |
EuPathDBi | HostDB:ENSG00000248746.5 |
GeneCardsi | ACTN3 |
HGNCi | HGNC:165, ACTN3 |
HPAi | ENSG00000248746, Tissue enriched (skeletal) |
MalaCardsi | ACTN3 |
MIMi | 102574, phenotype 617749, phenotype |
neXtProti | NX_Q08043 |
OpenTargetsi | ENSG00000248746 |
PharmGKBi | PA24485 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0035, Eukaryota |
GeneTreei | ENSGT00940000153968 |
HOGENOMi | CLU_005217_1_1_1 |
InParanoidi | Q08043 |
OrthoDBi | 543832at2759 |
PhylomeDBi | Q08043 |
Enzyme and pathway databases
PathwayCommonsi | Q08043 |
Reactomei | R-HSA-373753, Nephrin family interactions R-HSA-390522, Striated Muscle Contraction |
Miscellaneous databases
BioGRID-ORCSi | 89, 0 hits in 63 CRISPR screens |
ChiTaRSi | ACTN3, human |
EvolutionaryTracei | Q08043 |
GeneWikii | ACTN3 |
GenomeRNAii | 89 |
Pharosi | Q08043, Tbio |
PROi | PR:Q08043 |
RNActi | Q08043, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000248746, Expressed in skeletal muscle tissue of rectus abdominis and 100 other tissues |
ExpressionAtlasi | Q08043, baseline and differential |
Genevisiblei | Q08043, HS |
Family and domain databases
CDDi | cd00014, CH, 2 hits cd00051, EFh, 1 hit |
Gene3Di | 1.10.418.10, 2 hits |
InterProi | View protein in InterPro IPR001589, Actinin_actin-bd_CS IPR001715, CH-domain IPR036872, CH_dom_sf IPR011992, EF-hand-dom_pair IPR014837, EF-hand_Ca_insen IPR002048, EF_hand_dom IPR018159, Spectrin/alpha-actinin IPR002017, Spectrin_repeat |
Pfami | View protein in Pfam PF00307, CH, 2 hits PF08726, EFhand_Ca_insen, 1 hit PF00435, Spectrin, 4 hits |
SMARTi | View protein in SMART SM00033, CH, 2 hits SM00054, EFh, 2 hits SM00150, SPEC, 2 hits |
SUPFAMi | SSF47473, SSF47473, 1 hit SSF47576, SSF47576, 1 hit |
PROSITEi | View protein in PROSITE PS00019, ACTININ_1, 1 hit PS00020, ACTININ_2, 1 hit PS50021, CH, 2 hits PS50222, EF_HAND_2, 2 hits |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | ACTN3_HUMAN | |
Accessioni | Q08043Primary (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: | December 2, 2020 | |
This is version 186 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- 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 - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations