Alpha-actinin-3 - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot Q08043 (ACTN3_HUMAN)

Last modified January 19, 2010. Version 100. History...

Clusters with 100%, 90%, 50% identity |

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    Alpha-actinin-3
Alternative name(s):
    Alpha-actinin skeletal muscle isoform 3
    F-actin cross-linking protein

Gene names

Name:

ACTN3

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	901 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

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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.
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: Miscellaneous discrepancy. According to the human genome assembly there is a stop codon in position 577 which is only found in 18% of the world population.

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Ontologies

Keywords
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	Actin-binding Calcium
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	focal adhesion assembly Inferred from mutant phenotype. Source: UniProtKB regulation of apoptosis Non-traceable author statement. Source: UniProtKB
Cellular component	actin filament Ref.1 Traceable author statement. Source: ProtInc focal adhesion Inferred from mutant phenotype. Source: UniProtKB pseudopodium Traceable author statement. Source: UniProtKB
Molecular function	actin binding Inferred from electronic annotation. Source: UniProtKB-KW calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW integrin binding Traceable author statement. Source: UniProtKB protein homodimerization activity Traceable author statement. Source: UniProtKB structural constituent of muscle Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 901

901

Alpha-actinin-3

PRO_0000073438

Regions

Domain

1 – 261

261

Actin-binding

Domain

45 – 149

105

CH 1

Domain

158 – 261

104

CH 2

Repeat

288 – 398

111

Spectrin 1

Repeat

408 – 513

106

Spectrin 2

Repeat

523 – 634

112

Spectrin 3

Repeat

644 – 747

104

Spectrin 4

Domain

760 – 795

EF-hand 1

Domain

796 – 831

EF-hand 2

Calcium binding

773 – 784

1; possibly ancestral

Calcium binding

809 – 820

2; possibly ancestral

Natural variations

Natural variant

523

R → Q: dbSNP rs1671064. Ref.1 Ref.3 Ref.7

VAR_012705

Natural variant

628

C → R: dbSNP rs618838. Ref.1 Ref.3

VAR_047528

Natural variant

635

E → A: dbSNP rs2229456.

VAR_033488

Natural variant

776

Q → R: dbSNP rs540874. Ref.1 Ref.3

VAR_047529

Secondary structure

901

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

Q08043-1 [UniParc].

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

901

103,241

        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

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References

	« Hide 'large scale' referencesShow '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: 1339456] [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. Sakaki Y. Nature 440:497-500(2006) [PubMed: 16554811] [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: 15489334] [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: 11440986] [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: 11171996] [Abstract] Cited for: INTERACTION WITH MYOZ1.
[6]	"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: 15808860] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 26-273.
[7]	"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: 10192379] [Abstract] Cited for: VARIANT GLN-523, POLYMORPHISM.
+	Additional computationally mapped references.

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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.

IPI

IPI00032137.

PIR

FAHUA3. B40199.

RefSeq

NP_001095.1.

UniGene

Hs.654432

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1TJT	X-ray	2.19	A	26-273	[»]
1WKU	X-ray	1.60	A/B	26-273	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

Q08043.

PTM databases

PhosphoSite

Q08043.

Proteomic databases

PRIDE

Q08043.

Genome annotation databases

GeneID

89.

KEGG

hsa:89.

Organism-specific databases

CTD

89.

GeneCards

GC11P066070.

H-InvDB

HIX0026163.

HGNC

HGNC:165. ACTN3.

MIM

102574. gene.

PharmGKB

PA24485.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG13309.

HOVERGEN

Q08043.

Enzyme and pathway databases

Reactome

REACT_17044. Muscle contraction.

Gene expression databases

CleanEx

HS_ACTN3.

Genevestigator

Q08043.

GermOnline

ENSG00000204633. Homo sapiens.

Family and domain databases

InterPro

IPR001589. Actinin_actin-bd_CS.
IPR001715. Calponin_act_bd.
IPR014837. EF-hand_Ca_insen.
IPR018249. EF_HAND_2.
IPR002048. EF_hand_Ca_bd.
IPR018159. Spectrin/alpha-actinin.
IPR002017. Spectrin_repeat.
[Graphical view]

Pfam

PF00307. CH. 2 hits.
PF08726. efhand_Ca_insen. 1 hit.
PF00435. Spectrin. 4 hits.
[Graphical view]

SMART

SM00033. CH. 2 hits.
SM00054. EFh. 2 hits.
SM00150. SPEC. 2 hits.
[Graphical view]

PROSITE

PS00019. ACTININ_1. 1 hit.
PS00020. ACTININ_2. 1 hit.
PS50021. CH. 2 hits.
PS50222. EF_HAND_2. 2 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

331.

SOURCE

Search...

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Entry information

Entry name

ACTN3_HUMAN

Accession

Primary (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:	January 19, 2010
This is version 100 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.

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