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Q08043

- ACTN3_HUMAN

UniProt

Q08043 - ACTN3_HUMAN

Protein

Alpha-actinin-3

Gene

ACTN3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 137 (01 Oct 2014)
      Sequence version 2 (25 Nov 2008)
      Previous versions | rss
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    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)LengthDescriptionGraphical viewFeature identifierActions
    Calcium bindingi773 – 784121; possibly ancestralAdd
    BLAST
    Calcium bindingi809 – 820122; possibly ancestralAdd
    BLAST

    GO - Molecular functioni

    1. calcium ion binding Source: InterPro
    2. integrin binding Source: UniProtKB
    3. protein binding Source: UniProtKB
    4. protein homodimerization activity Source: UniProtKB
    5. structural constituent of muscle Source: ProtInc

    GO - Biological processi

    1. focal adhesion assembly Source: UniProtKB
    2. muscle filament sliding Source: Reactome
    3. regulation of apoptotic process Source: UniProtKB

    Keywords - Ligandi

    Actin-binding, Calcium, Metal-binding

    Enzyme and pathway databases

    ReactomeiREACT_16969. Striated Muscle Contraction.
    REACT_23832. Nephrin interactions.

    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
    ProteomesiUP000005640: Unplaced

    Organism-specific databases

    HGNCiHGNC:165. ACTN3.

    Subcellular locationi

    GO - Cellular componenti

    1. actin filament Source: ProtInc
    2. cytosol Source: Reactome
    3. focal adhesion Source: UniProtKB
    4. pseudopodium Source: UniProtKB

    Pathology & Biotechi

    Organism-specific databases

    MIMi102574. gene+phenotype.
    PharmGKBiPA24485.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 901901Alpha-actinin-3PRO_0000073438Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionine1 Publication

    Keywords - PTMi

    Acetylation

    Proteomic databases

    MaxQBiQ08043.
    PRIDEiQ08043.

    PTM databases

    PhosphoSiteiQ08043.

    Expressioni

    Tissue specificityi

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

    Gene expression databases

    CleanExiHS_ACTN3.
    GenevestigatoriQ08043.

    Interactioni

    Subunit structurei

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

    Protein-protein interaction databases

    BioGridi106604. 3 interactions.
    IntActiQ08043. 4 interactions.
    MINTiMINT-269455.

    Structurei

    Secondary structure

    1
    901
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi43 – 5917
    Helixi60 – 623
    Turni69 – 757
    Helixi77 – 8711
    Helixi100 – 11516
    Turni116 – 1183
    Helixi126 – 1316
    Helixi134 – 14916
    Turni150 – 1523
    Helixi160 – 17213
    Beta strandi182 – 1843
    Helixi185 – 1873
    Helixi191 – 20010
    Turni202 – 2043
    Helixi207 – 2093
    Helixi215 – 22915
    Helixi238 – 2436
    Beta strandi244 – 2463
    Helixi249 – 26517

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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. Positions 42-268, 281-901.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ08043.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini1 – 261261Actin-bindingAdd
    BLAST
    Domaini45 – 149105CH 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini158 – 261104CH 2PROSITE-ProRule annotationAdd
    BLAST
    Repeati288 – 398111Spectrin 1Add
    BLAST
    Repeati408 – 513106Spectrin 2Add
    BLAST
    Repeati523 – 634112Spectrin 3Add
    BLAST
    Repeati644 – 747104Spectrin 4Add
    BLAST
    Domaini760 – 79536EF-hand 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini796 – 83136EF-hand 2PROSITE-ProRule annotationAdd
    BLAST

    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

    HOVERGENiHBG050453.
    KOiK05699.
    PhylomeDBiQ08043.

    Family and domain databases

    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]
    SUPFAMiSSF47576. 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

    MMMVMQPEGL GAGEGRFAGG GGGGEYMEQE EDWDRDLLLD PAWEKQQRKT    50
    FTAWCNSHLR KAGTQIENIE EDFRNGLKLM LLLEVISGER LPRPDKGKMR 100
    FHKIANVNKA LDFIASKGVK LVSIGAEEIV DGNLKMTLGM IWTIILRFAI 150
    QDISVEETSA KEGLLLWCQR KTAPYRNVNV QNFHTSWKDG LALCALIHRH 200
    RPDLIDYAKL RKDDPIGNLN TAFEVAEKYL DIPKMLDAED IVNTPKPDEK 250
    AIMTYVSCFY HAFAGAEQAE TAANRICKVL AVNQENEKLM EEYEKLASEL 300
    LEWIRRTVPW LENRVGEPSM SAMQRKLEDF RDYRRLHKPP RIQEKCQLEI 350
    NFNTLQTKLR LSHRPAFMPS EGKLVSDIAN AWRGLEQVEK GYEDWLLSEI 400
    RRLQRLQHLA EKFRQKASLH EAWTRGKEEM LSQRDYDSAL LQEVRALLRR 450
    HEAFESDLAA HQDRVEHIAA LAQELNELDY HEAASVNSRC QAICDQWDNL 500
    GTLTQKRRDA LERMEKLLET IDRLQLEFAR RAAPFNNWLD GAVEDLQDVW 550
    LVHSVEETQS LLTAHDQFKA TLPEADRERG AIMGIQGEIQ KICQTYGLRP 600
    CSTNPYITLS PQDINTKWDM VRKLVPSCDQ TLQEELARQQ VNERLRRQFA 650
    AQANAIGPWI QAKVEEVGRL AAGLAGSLEE QMAGLRQQEQ NIINYKTNID 700
    RLEGDHQLLQ ESLVFDNKHT VYSMEHIRVG WEQLLTSIAR TINEVENQVL 750
    TRDAKGLSQE QLNEFRASFN HFDRKQNGMM EPDDFRACLI SMGYDLGEVE 800
    FARIMTMVDP NAAGVVTFQA FIDFMTRETA ETDTTEQVVA SFKILAGDKN 850
    YITPEELRRE LPAKQAEYCI RRMVPYKGSG APAGALDYVA FSSALYGESD 900
    L 901
    Length:901
    Mass (Da):103,241
    Last modified:November 25, 2008 - v2
    Checksum:iC49B7885E7E1EDA7
    GO

    Sequence cautioni

    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.

    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)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti523 – 5231R → Q.3 Publications
    Corresponds to variant rs1671064 [ dbSNP | Ensembl ].
    VAR_012705
    Natural varianti628 – 6281C → R.2 Publications
    Corresponds to variant rs618838 [ dbSNP | Ensembl ].
    VAR_047528
    Natural varianti635 – 6351E → A.
    Corresponds to variant rs2229456 [ dbSNP | Ensembl ].
    VAR_033488
    Natural varianti776 – 7761Q → R.2 Publications
    Corresponds to variant rs540874 [ dbSNP | Ensembl ].
    VAR_047529

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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.

    Genome annotation databases

    GeneIDi89.
    KEGGihsa:89.

    Polymorphism databases

    DMDMi215273967.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M86407 mRNA. Translation: AAA51585.1 .
    AP002748 Genomic DNA. No translation available.
    BC099647 mRNA. Translation: AAH99647.1 .
    BC099649 mRNA. Translation: AAH99649.1 .
    PIRi B40199. FAHUA3.
    RefSeqi NP_001095.2. NM_001104.3.
    NP_001245300.2. NM_001258371.2.
    UniGenei Hs.654432.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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 [» ]
    ProteinModelPortali Q08043.
    SMRi Q08043. Positions 42-268, 281-901.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 106604. 3 interactions.
    IntActi Q08043. 4 interactions.
    MINTi MINT-269455.

    PTM databases

    PhosphoSitei Q08043.

    Polymorphism databases

    DMDMi 215273967.

    Proteomic databases

    MaxQBi Q08043.
    PRIDEi Q08043.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 89.
    KEGGi hsa:89.

    Organism-specific databases

    CTDi 89.
    GeneCardsi GC11P066314.
    HGNCi HGNC:165. ACTN3.
    MIMi 102574. gene+phenotype.
    neXtProti NX_Q08043.
    PharmGKBi PA24485.
    GenAtlasi Search...

    Phylogenomic databases

    HOVERGENi HBG050453.
    KOi K05699.
    PhylomeDBi Q08043.

    Enzyme and pathway databases

    Reactomei REACT_16969. Striated Muscle Contraction.
    REACT_23832. Nephrin interactions.

    Miscellaneous databases

    EvolutionaryTracei Q08043.
    GeneWikii ACTN3.
    GenomeRNAii 89.
    NextBioi 331.
    PROi Q08043.
    SOURCEi Search...

    Gene expression databases

    CleanExi HS_ACTN3.
    Genevestigatori Q08043.

    Family and domain databases

    Gene3Di 1.10.238.10. 2 hits.
    1.10.418.10. 2 hits.
    InterProi IPR001589. 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 ]
    Pfami PF00307. CH. 2 hits.
    PF08726. EFhand_Ca_insen. 1 hit.
    PF00435. Spectrin. 4 hits.
    [Graphical view ]
    SMARTi SM00033. CH. 2 hits.
    SM00054. EFh. 2 hits.
    SM00150. SPEC. 2 hits.
    [Graphical view ]
    SUPFAMi SSF47576. SSF47576. 1 hit.
    PROSITEi PS00019. ACTININ_1. 1 hit.
    PS00020. ACTININ_2. 1 hit.
    PS50021. CH. 2 hits.
    PS50222. EF_HAND_2. 2 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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. 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.

    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: October 1, 2014
    This is version 137 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

    External Data

    Dasty 3