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Protein

Alpha-actinin-2

Gene

ACTN2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 bindingi766 – 7771; possibly ancestralAdd BLAST12
Calcium bindingi802 – 8132; possibly ancestralAdd BLAST12

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActin-binding
LigandCalcium, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-114608 Platelet degranulation
R-HSA-373753 Nephrin family interactions
R-HSA-390522 Striated Muscle Contraction
R-HSA-438066 Unblocking of NMDA receptor, glutamate binding and activation
R-HSA-442729 CREB phosphorylation through the activation of CaMKII
R-HSA-442982 Ras activation upon Ca2+ influx through NMDA receptor
R-HSA-5673001 RAF/MAP kinase cascade

Protein family/group databases

TCDBi8.A.66.1.3 the dystrophin (dystrophin) family

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-actinin-2
Alternative name(s):
Alpha-actinin skeletal muscle isoform 2
F-actin cross-linking protein
Gene namesi
Name:ACTN2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000077522.12
HGNCiHGNC:164 ACTN2
MIMi102573 gene
neXtProtiNX_P35609

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Cardiomyopathy, familial hypertrophic 23, with or without left ventricular non-compaction (CMH23)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.
See also OMIM:612158
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_074292228M → T in CMH23. 1 PublicationCorresponds to variant dbSNP:rs786205144EnsemblClinVar.1
Natural variantiVAR_071971495T → M in CMH23. 1 PublicationCorresponds to variant dbSNP:rs200248944EnsemblClinVar.1
Natural variantiVAR_071972583E → A in CMH23. 1 PublicationCorresponds to variant dbSNP:rs200631005Ensembl.1
Natural variantiVAR_071973628E → G in CMH23. 1 PublicationCorresponds to variant dbSNP:rs786204951EnsemblClinVar.1
Cardiomyopathy, dilated 1AA, with or without left ventricular non-compaction (CMD1AA)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
See also OMIM:612158
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0546289Q → R in CMD1AA. 1 PublicationCorresponds to variant dbSNP:rs121434525EnsemblClinVar.1

Keywords - Diseasei

Cardiomyopathy, Disease mutation

Organism-specific databases

DisGeNETi88
GeneReviewsiACTN2
MalaCardsiACTN2
MIMi612158 phenotype
OpenTargetsiENSG00000077522
Orphaneti154 Familial isolated dilated cardiomyopathy
155 NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy
PharmGKBiPA25

Polymorphism and mutation databases

DMDMi543742

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000734351 – 894Alpha-actinin-2Add BLAST894

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei237PhosphothreonineBy similarity1

Post-translational modificationi

Ubiquitinated by FBXL22, leading to proteasomal degradation.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP35609
MaxQBiP35609
PaxDbiP35609
PeptideAtlasiP35609
PRIDEiP35609
ProteomicsDBi55100

PTM databases

iPTMnetiP35609
PhosphoSitePlusiP35609
SwissPalmiP35609

Expressioni

Tissue specificityi

Expressed in both skeletal and cardiac muscle.

Gene expression databases

BgeeiENSG00000077522 Expressed in 169 organ(s), highest expression level in muscle of leg
CleanExiHS_ACTN2
ExpressionAtlasiP35609 baseline and differential
GenevisibleiP35609 HS

Organism-specific databases

HPAiHPA006035
HPA008315

Interactioni

Subunit structurei

Homodimer; antiparallel. Also forms heterodimers with ACTN3. Interacts with ADAM12, MYOZ1, MYOZ2 and MYOZ3. Interacts via its C-terminal region with the LDB3 PDZ domain. Interacts with XIRP2. Interacts with DST isoform 1 (via N-terminus). Interacts with PARVB. Interacts with SYNPO2.8 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi106603, 62 interactors
DIPiDIP-383N
IntActiP35609, 82 interactors
MINTiP35609
STRINGi9606.ENSP00000355537

Structurei

Secondary structure

1894
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP35609
SMRiP35609
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP35609

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini38 – 142Calponin-homology (CH) 1PROSITE-ProRule annotationAdd BLAST105
Domaini151 – 257Calponin-homology (CH) 2PROSITE-ProRule annotationAdd BLAST107
Repeati281 – 391Spectrin 1Add BLAST111
Repeati401 – 506Spectrin 2Add BLAST106
Repeati516 – 627Spectrin 3Add BLAST112
Repeati637 – 740Spectrin 4Add BLAST104
Domaini753 – 788EF-hand 1PROSITE-ProRule annotationAdd BLAST36
Domaini789 – 824EF-hand 2PROSITE-ProRule annotationAdd BLAST36

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 254Actin-bindingAdd BLAST254

Sequence similaritiesi

Belongs to the alpha-actinin family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0035 Eukaryota
COG5069 LUCA
GeneTreeiENSGT00760000118813
HOGENOMiHOG000263418
HOVERGENiHBG050453
InParanoidiP35609
KOiK21073
OMAiAKWDKVK
OrthoDBiEOG091G020R
PhylomeDBiP35609
TreeFamiTF352676

Family and domain databases

CDDicd00014 CH, 2 hits
cd00051 EFh, 1 hit
Gene3Di1.10.418.10, 2 hits
InterProiView 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
PfamiView protein in Pfam
PF00307 CH, 2 hits
PF08726 EFhand_Ca_insen, 1 hit
PF00435 Spectrin, 4 hits
SMARTiView protein in SMART
SM00033 CH, 2 hits
SM00054 EFh, 2 hits
SM00150 SPEC, 3 hits
SUPFAMiSSF47473 SSF47473, 1 hit
SSF47576 SSF47576, 1 hit
PROSITEiView protein in PROSITE
PS00019 ACTININ_1, 1 hit
PS00020 ACTININ_2, 1 hit
PS50021 CH, 2 hits
PS50222 EF_HAND_2, 2 hits

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: P35609-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MNQIEPGVQY NYVYDEDEYM IQEEEWDRDL LLDPAWEKQQ RKTFTAWCNS
60 70 80 90 100
HLRKAGTQIE NIEEDFRNGL KLMLLLEVIS GERLPKPDRG KMRFHKIANV
110 120 130 140 150
NKALDYIASK GVKLVSIGAE EIVDGNVKMT LGMIWTIILR FAIQDISVEE
160 170 180 190 200
TSAKEGLLLW CQRKTAPYRN VNIQNFHTSW KDGLGLCALI HRHRPDLIDY
210 220 230 240 250
SKLNKDDPIG NINLAMEIAE KHLDIPKMLD AEDIVNTPKP DERAIMTYVS
260 270 280 290 300
CFYHAFAGAE QAETAANRIC KVLAVNQENE RLMEEYERLA SELLEWIRRT
310 320 330 340 350
IPWLENRTPE KTMQAMQKKL EDFRDYRRKH KPPKVQEKCQ LEINFNTLQT
360 370 380 390 400
KLRISNRPAF MPSEGKMVSD IAGAWQRLEQ AEKGYEEWLL NEIRRLERLE
410 420 430 440 450
HLAEKFRQKA STHETWAYGK EQILLQKDYE SASLTEVRAL LRKHEAFESD
460 470 480 490 500
LAAHQDRVEQ IAAIAQELNE LDYHDAVNVN DRCQKICDQW DRLGTLTQKR
510 520 530 540 550
REALERMEKL LETIDQLHLE FAKRAAPFNN WMEGAMEDLQ DMFIVHSIEE
560 570 580 590 600
IQSLITAHEQ FKATLPEADG ERQSIMAIQN EVEKVIQSYN IRISSSNPYS
610 620 630 640 650
TVTMDELRTK WDKVKQLVPI RDQSLQEELA RQHANERLRR QFAAQANAIG
660 670 680 690 700
PWIQNKMEEI ARSSIQITGA LEDQMNQLKQ YEHNIINYKN NIDKLEGDHQ
710 720 730 740 750
LIQEALVFDN KHTNYTMEHI RVGWELLLTT IARTINEVET QILTRDAKGI
760 770 780 790 800
TQEQMNEFRA SFNHFDRRKN GLMDHEDFRA CLISMGYDLG EAEFARIMTL
810 820 830 840 850
VDPNGQGTVT FQSFIDFMTR ETADTDTAEQ VIASFRILAS DKPYILAEEL
860 870 880 890
RRELPPDQAQ YCIKRMPAYS GPGSVPGALD YAAFSSALYG ESDL
Length:894
Mass (Da):103,854
Last modified:June 1, 1994 - v1
Checksum:i7F612C1C3B3E2299
GO
Isoform 2 (identifier: P35609-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     234-261: IVNTPKPDERAIMTYVSCFYHAFAGAEQ → LVYTARPDERAIMTYVSCYYHAFAGAQK

Note: No experimental confirmation available.
Show »
Length:894
Mass (Da):103,920
Checksum:iBA180F6305E25A8D
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F6THM6F6THM6_HUMAN
Alpha-actinin-2
ACTN2
686Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0546289Q → R in CMD1AA. 1 PublicationCorresponds to variant dbSNP:rs121434525EnsemblClinVar.1
Natural variantiVAR_071970119A → T in CMH23 and CMD1AA. 2 PublicationsCorresponds to variant dbSNP:rs727502886EnsemblClinVar.1
Natural variantiVAR_074292228M → T in CMH23. 1 PublicationCorresponds to variant dbSNP:rs786205144EnsemblClinVar.1
Natural variantiVAR_071971495T → M in CMH23. 1 PublicationCorresponds to variant dbSNP:rs200248944EnsemblClinVar.1
Natural variantiVAR_071972583E → A in CMH23. 1 PublicationCorresponds to variant dbSNP:rs200631005Ensembl.1
Natural variantiVAR_033487604M → V1 PublicationCorresponds to variant dbSNP:rs35997569EnsemblClinVar.1
Natural variantiVAR_071973628E → G in CMH23. 1 PublicationCorresponds to variant dbSNP:rs786204951EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_054923234 – 261IVNTP…AGAEQ → LVYTARPDERAIMTYVSCYY HAFAGAQK in isoform 2. 1 PublicationAdd BLAST28

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M86406 mRNA Translation: AAA51583.1
M86804 Genomic DNA Translation: AAA51584.1
AJ249756
, AJ249757, AJ249758, AJ249759, AJ249760, AJ249761, AJ249762, AJ249763, AJ249764, AJ249765, AJ249766, AJ249767, AJ249768, AJ249769, AJ249770, AJ249771, AJ249772, AJ249773, AJ249774, AJ249775, AJ249776 Genomic DNA Translation: CAB61269.1
AK315250 mRNA Translation: BAG37672.1
AL359185 Genomic DNA No translation available.
AL359921 Genomic DNA No translation available.
CH471098 Genomic DNA Translation: EAW70064.1
CH471098 Genomic DNA Translation: EAW70065.1
BC047901 mRNA Translation: AAH47901.2
BC051770 mRNA Translation: AAH51770.2
CCDSiCCDS1613.1 [P35609-1]
CCDS60455.1 [P35609-2]
PIRiA40199 FAHUA2
RefSeqiNP_001094.1, NM_001103.3 [P35609-1]
NP_001265272.1, NM_001278343.1 [P35609-2]
NP_001265273.1, NM_001278344.1
UniGeneiHs.498178

Genome annotation databases

EnsembliENST00000366578; ENSP00000355537; ENSG00000077522 [P35609-1]
ENST00000542672; ENSP00000443495; ENSG00000077522 [P35609-2]
GeneIDi88
KEGGihsa:88
UCSCiuc001hyf.4 human [P35609-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M86406 mRNA Translation: AAA51583.1
M86804 Genomic DNA Translation: AAA51584.1
AJ249756
, AJ249757, AJ249758, AJ249759, AJ249760, AJ249761, AJ249762, AJ249763, AJ249764, AJ249765, AJ249766, AJ249767, AJ249768, AJ249769, AJ249770, AJ249771, AJ249772, AJ249773, AJ249774, AJ249775, AJ249776 Genomic DNA Translation: CAB61269.1
AK315250 mRNA Translation: BAG37672.1
AL359185 Genomic DNA No translation available.
AL359921 Genomic DNA No translation available.
CH471098 Genomic DNA Translation: EAW70064.1
CH471098 Genomic DNA Translation: EAW70065.1
BC047901 mRNA Translation: AAH47901.2
BC051770 mRNA Translation: AAH51770.2
CCDSiCCDS1613.1 [P35609-1]
CCDS60455.1 [P35609-2]
PIRiA40199 FAHUA2
RefSeqiNP_001094.1, NM_001103.3 [P35609-1]
NP_001265272.1, NM_001278343.1 [P35609-2]
NP_001265273.1, NM_001278344.1
UniGeneiHs.498178

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1H8BNMR-A822-894[»]
1HCIX-ray2.80A/B274-746[»]
1QUUX-ray2.50A391-637[»]
4D1EX-ray3.50A19-894[»]
5A36X-ray2.00A/B19-266[»]
5A37X-ray1.88A/B19-266[»]
5A38X-ray1.90A/B19-266[»]
5A4BX-ray2.01A/B19-266[»]
ProteinModelPortaliP35609
SMRiP35609
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106603, 62 interactors
DIPiDIP-383N
IntActiP35609, 82 interactors
MINTiP35609
STRINGi9606.ENSP00000355537

Protein family/group databases

TCDBi8.A.66.1.3 the dystrophin (dystrophin) family

PTM databases

iPTMnetiP35609
PhosphoSitePlusiP35609
SwissPalmiP35609

Polymorphism and mutation databases

DMDMi543742

Proteomic databases

EPDiP35609
MaxQBiP35609
PaxDbiP35609
PeptideAtlasiP35609
PRIDEiP35609
ProteomicsDBi55100

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000366578; ENSP00000355537; ENSG00000077522 [P35609-1]
ENST00000542672; ENSP00000443495; ENSG00000077522 [P35609-2]
GeneIDi88
KEGGihsa:88
UCSCiuc001hyf.4 human [P35609-1]

Organism-specific databases

CTDi88
DisGeNETi88
EuPathDBiHostDB:ENSG00000077522.12
GeneCardsiACTN2
GeneReviewsiACTN2
HGNCiHGNC:164 ACTN2
HPAiHPA006035
HPA008315
MalaCardsiACTN2
MIMi102573 gene
612158 phenotype
neXtProtiNX_P35609
OpenTargetsiENSG00000077522
Orphaneti154 Familial isolated dilated cardiomyopathy
155 NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy
PharmGKBiPA25
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0035 Eukaryota
COG5069 LUCA
GeneTreeiENSGT00760000118813
HOGENOMiHOG000263418
HOVERGENiHBG050453
InParanoidiP35609
KOiK21073
OMAiAKWDKVK
OrthoDBiEOG091G020R
PhylomeDBiP35609
TreeFamiTF352676

Enzyme and pathway databases

ReactomeiR-HSA-114608 Platelet degranulation
R-HSA-373753 Nephrin family interactions
R-HSA-390522 Striated Muscle Contraction
R-HSA-438066 Unblocking of NMDA receptor, glutamate binding and activation
R-HSA-442729 CREB phosphorylation through the activation of CaMKII
R-HSA-442982 Ras activation upon Ca2+ influx through NMDA receptor
R-HSA-5673001 RAF/MAP kinase cascade

Miscellaneous databases

ChiTaRSiACTN2 human
EvolutionaryTraceiP35609
GeneWikiiActinin,_alpha_2
GenomeRNAii88
PROiPR:P35609
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000077522 Expressed in 169 organ(s), highest expression level in muscle of leg
CleanExiHS_ACTN2
ExpressionAtlasiP35609 baseline and differential
GenevisibleiP35609 HS

Family and domain databases

CDDicd00014 CH, 2 hits
cd00051 EFh, 1 hit
Gene3Di1.10.418.10, 2 hits
InterProiView 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
PfamiView protein in Pfam
PF00307 CH, 2 hits
PF08726 EFhand_Ca_insen, 1 hit
PF00435 Spectrin, 4 hits
SMARTiView protein in SMART
SM00033 CH, 2 hits
SM00054 EFh, 2 hits
SM00150 SPEC, 3 hits
SUPFAMiSSF47473 SSF47473, 1 hit
SSF47576 SSF47576, 1 hit
PROSITEiView protein in PROSITE
PS00019 ACTININ_1, 1 hit
PS00020 ACTININ_2, 1 hit
PS50021 CH, 2 hits
PS50222 EF_HAND_2, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiACTN2_HUMAN
AccessioniPrimary (citable) accession number: P35609
Secondary accession number(s): B1ANE4
, B2RCS5, Q86TF4, Q86TI8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: November 7, 2018
This is version 207 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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