Human Gene ACTN2 (ENST00000366578.6_11) from GENCODE V47lift37
  Description: actinin alpha 2, transcript variant 1 (from RefSeq NM_001103.4)
Gencode Transcript: ENST00000366578.6_11
Gencode Gene: ENSG00000077522.15_15
Transcript (Including UTRs)
   Position: hg19 chr1:236,849,799-236,927,931 Size: 78,133 Total Exon Count: 21 Strand: +
Coding Region
   Position: hg19 chr1:236,849,974-236,925,919 Size: 75,946 Coding Exon Count: 21 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviewsModel Information
Methods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr1:236,849,799-236,927,931)mRNA (may differ from genome)Protein (894 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
HGNCMalacardsMGIOMIMPubMedReactome
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: ACTN2_HUMAN
DESCRIPTION: RecName: Full=Alpha-actinin-2; AltName: Full=Alpha-actinin skeletal muscle isoform 2; AltName: Full=F-actin cross-linking protein;
FUNCTION: F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein.
SUBUNIT: 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).
INTERACTION: Self; NbExp=2; IntAct=EBI-77797, EBI-77797; Q61824:Adam12 (xeno); NbExp=3; IntAct=EBI-77797, EBI-77785; P03950:ANG; NbExp=4; IntAct=EBI-77797, EBI-525291; Q9UKG1:APPL1; NbExp=2; IntAct=EBI-77797, EBI-741243; Q9NRI5:DISC1; NbExp=3; IntAct=EBI-77797, EBI-529989; O75923:DYSF; NbExp=2; IntAct=EBI-77797, EBI-2799016; P54296:MYOM2; NbExp=2; IntAct=EBI-77797, EBI-5357134; Q8WZ42:TTN; NbExp=7; IntAct=EBI-77797, EBI-681210;
SUBCELLULAR LOCATION: Cytoplasm, myofibril, sarcomere, Z line. Note=Colocalizes with MYOZ1 and FLNC at the Z-lines of skeletal muscle.
TISSUE SPECIFICITY: Expressed in both skeletal and cardiac muscle.
DISEASE: Defects in ACTN2 are the cause of cardiomyopathy dilated type 1AA (CMD1AA) [MIM:612158]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
SIMILARITY: Belongs to the alpha-actinin family.
SIMILARITY: Contains 1 actin-binding domain.
SIMILARITY: Contains 2 CH (calponin-homology) domains.
SIMILARITY: Contains 2 EF-hand domains.
SIMILARITY: Contains 4 spectrin repeats.
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ACTN2";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: ACTN2
Diseases sorted by gene-association score: cardiomyopathy, dilated, 1aa, with or without lvnc* (1200), actn2-related dilated cardiomyopathy* (500), dilated cardiomyopathy 1aa* (400), cardiomyopathy* (196), atrial standstill, digenic* (141), actn2-related familial hypertrophic cardiomyopathy* (100), familial isolated dilated cardiomyopathy* (66), endocardial fibroelastosis (13), myopathy, myofibrillar, 4 (9), arrhythmogenic right ventricular cardiomyopathy (8), cardiomyopathy, familial hypertrophic (8), left ventricular noncompaction (6), mitochondrial dna depletion syndrome 7 (5), dilated cardiomyopathy (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 615.98 RPKM in Muscle - Skeletal
Total median expression: 1513.39 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -60.90175-0.348 Picture PostScript Text
3' UTR -485.202012-0.241 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001589 - Actinin_actin-bd_CS
IPR001715 - CH-domain
IPR011992 - EF-hand-like_dom
IPR014837 - EF-hand_Ca_insen
IPR018249 - EF_HAND_2
IPR002048 - EF_hand_Ca-bd
IPR018159 - Spectrin/alpha-actinin
IPR002017 - Spectrin_repeat

Pfam Domains:
PF00307 - Calponin homology (CH) domain
PF00435 - Spectrin repeat
PF08726 - Ca2+ insensitive EF hand
PF11971 - CAMSAP CH domain
PF13833 - EF-hand domain pair

SCOP Domains:
47473 - EF-hand
47576 - Calponin-homology domain, CH-domain
46966 - Spectrin repeat

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1H8B - NMR MuPIT 1HCI - X-ray MuPIT 1QUU - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P35609
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGDEnsembl   
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003779 actin binding
GO:0005088 Ras guanyl-nucleotide exchange factor activity
GO:0005178 integrin binding
GO:0005509 calcium ion binding
GO:0005515 protein binding
GO:0005546 phosphatidylinositol-4,5-bisphosphate binding
GO:0008092 cytoskeletal protein binding
GO:0008307 structural constituent of muscle
GO:0019904 protein domain specific binding
GO:0030274 LIM domain binding
GO:0030374 ligand-dependent nuclear receptor transcription coactivator activity
GO:0030375 thyroid hormone receptor coactivator activity
GO:0031432 titin binding
GO:0042802 identical protein binding
GO:0042803 protein homodimerization activity
GO:0044325 ion channel binding
GO:0046872 metal ion binding
GO:0046983 protein dimerization activity
GO:0051015 actin filament binding
GO:0051373 FATZ binding
GO:0070080 titin Z domain binding

Biological Process:
GO:0000165 MAPK cascade
GO:0002576 platelet degranulation
GO:0006936 muscle contraction
GO:0007155 cell adhesion
GO:0030035 microspike assembly
GO:0030049 muscle filament sliding
GO:0042391 regulation of membrane potential
GO:0042981 regulation of apoptotic process
GO:0043267 negative regulation of potassium ion transport
GO:0043268 positive regulation of potassium ion transport
GO:0045214 sarcomere organization
GO:0048041 focal adhesion assembly
GO:0051289 protein homotetramerization
GO:0051695 actin filament uncapping
GO:0055013 cardiac muscle cell development
GO:0072659 protein localization to plasma membrane
GO:0086097 phospholipase C-activating angiotensin-activated signaling pathway
GO:1901017 negative regulation of potassium ion transmembrane transporter activity
GO:1901018 positive regulation of potassium ion transmembrane transporter activity
GO:2000009 negative regulation of protein localization to cell surface
GO:2001137 positive regulation of endocytic recycling
GO:2001259 positive regulation of cation channel activity

Cellular Component:
GO:0005576 extracellular region
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005856 cytoskeleton
GO:0005884 actin filament
GO:0005925 focal adhesion
GO:0030017 sarcomere
GO:0030018 Z disc
GO:0030175 filopodium
GO:0030864 cortical actin cytoskeleton
GO:0031093 platelet alpha granule lumen
GO:0031143 pseudopodium
GO:0043197 dendritic spine
GO:0070062 extracellular exosome
GO:0005886 plasma membrane


-  Descriptions from all associated GenBank mRNAs
  AK315250 - Homo sapiens cDNA, FLJ96254, highly similar to Homo sapiens actinin, alpha 2 (ACTN2), mRNA.
AK297886 - Homo sapiens cDNA FLJ55401 complete cds, highly similar to Alpha-actinin-2.
M86406 - Homo sapiens skeletal muscle alpha 2 actinin (ACTN20 mRNA, complete cds.
BC051770 - Homo sapiens actinin, alpha 2, mRNA (cDNA clone MGC:54270 IMAGE:6198688), complete cds.
AB209521 - Homo sapiens mRNA for actinin, alpha 2 variant protein.
JD191803 - Sequence 172827 from Patent EP1572962.
BC047901 - Homo sapiens actinin, alpha 2, mRNA (cDNA clone MGC:57723 IMAGE:6199155), complete cds.
JD065583 - Sequence 46607 from Patent EP1572962.
JD458351 - Sequence 439375 from Patent EP1572962.
AB590561 - Synthetic construct DNA, clone: pFN21AE2106, Homo sapiens ACTN2 gene for actinin, alpha 2, without stop codon, in Flexi system.
CU690840 - Synthetic construct Homo sapiens gateway clone IMAGE:100021550 5' read ACTN2 mRNA.
KJ890623 - Synthetic construct Homo sapiens clone ccsbBroadEn_00017 ACTN2 gene, encodes complete protein.
KR711058 - Synthetic construct Homo sapiens clone CCSBHm_00019478 ACTN2 (ACTN2) mRNA, encodes complete protein.
KR712245 - Synthetic construct Homo sapiens clone CCSBHm_00900205 ACTN2 (ACTN2) mRNA, encodes complete protein.
KR712248 - Synthetic construct Homo sapiens clone CCSBHm_00900208 ACTN2 (ACTN2) mRNA, encodes complete protein.
AK294906 - Homo sapiens cDNA FLJ51840 complete cds, highly similar to Alpha-actinin-2.
AK297628 - Homo sapiens cDNA FLJ54277 complete cds, highly similar to Alpha-actinin-2.
AK297469 - Homo sapiens cDNA FLJ50104 complete cds, highly similar to Alpha-actinin-2.
AK297618 - Homo sapiens cDNA FLJ55142 complete cds, highly similar to Alpha-actinin-2.
JD082002 - Sequence 63026 from Patent EP1572962.
JD566455 - Sequence 547479 from Patent EP1572962.
JD474192 - Sequence 455216 from Patent EP1572962.
JD235388 - Sequence 216412 from Patent EP1572962.
JD528512 - Sequence 509536 from Patent EP1572962.
JD170865 - Sequence 151889 from Patent EP1572962.
JD247265 - Sequence 228289 from Patent EP1572962.
JD291132 - Sequence 272156 from Patent EP1572962.
JD040997 - Sequence 22021 from Patent EP1572962.
JD499818 - Sequence 480842 from Patent EP1572962.
JD092604 - Sequence 73628 from Patent EP1572962.
JD539721 - Sequence 520745 from Patent EP1572962.
JD283766 - Sequence 264790 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  BioCarta from NCI Cancer Genome Anatomy Project
h_ucalpainPathway - uCalpain and friends in Cell spread
h_cell2cellPathway - Cell to Cell Adhesion Signaling
h_integrinPathway - Integrin Signaling Pathway

Reactome (by CSHL, EBI, and GO)

Protein P35609 (Reactome details) participates in the following event(s):

R-HSA-481007 Exocytosis of platelet alpha granule contents
R-HSA-432172 Activation of NMDA receptor
R-HSA-432162 Unblocking of NMDA receptor
R-HSA-451403 Interaction of nephrin with adherens junction-associated proteins
R-HSA-442760 Activation of RasGRF
R-HSA-390595 Calcium Binds Troponin-C
R-HSA-390597 Release Of ADP From Myosin
R-HSA-390593 ATP Hydrolysis By Myosin
R-HSA-390598 Myosin Binds ATP
R-HSA-432164 Ca2+ influx into the post-synaptic cell
R-HSA-445367 CaMKII enters cytoplasm
R-HSA-442732 Ras activation
R-HSA-5672965 RAS GEFs promote RAS nucleotide exchange
R-HSA-114608 Platelet degranulation
R-HSA-438066 Unblocking of NMDA receptor, glutamate binding and activation
R-HSA-373753 Nephrin family interactions
R-HSA-76005 Response to elevated platelet cytosolic Ca2+
R-HSA-442982 Ras activation upon Ca2+ influx through NMDA receptor
R-HSA-442755 Activation of NMDA receptor and postsynaptic events
R-HSA-390522 Striated Muscle Contraction
R-HSA-1500931 Cell-Cell communication
R-HSA-76002 Platelet activation, signaling and aggregation
R-HSA-442742 CREB phosphorylation through the activation of Ras
R-HSA-442729 CREB phosphorylation through the activation of CaMKII
R-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-397014 Muscle contraction
R-HSA-109582 Hemostasis
R-HSA-438064 Post NMDA receptor activation events
R-HSA-112315 Transmission across Chemical Synapses
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-112316 Neuronal System
R-HSA-5684996 MAPK1/MAPK3 signaling
R-HSA-5683057 MAPK family signaling cascades
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: ACTN2_HUMAN, B1ANE4, B2RCS5, ENST00000366578.1, ENST00000366578.2, ENST00000366578.3, ENST00000366578.4, ENST00000366578.5, NM_001103, P35609, Q86TF4, Q86TI8, uc318fex.1, uc318fex.2
UCSC ID: ENST00000366578.6_11
RefSeq Accession: NM_001103.4
Protein: P35609 (aka ACTN2_HUMAN or AAC2_HUMAN)

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene ACTN2:
dcm-ov (Dilated Cardiomyopathy Overview)
hyper-card (Hypertrophic Cardiomyopathy Overview)

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.