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CAMK2A calcium/calmodulin dependent protein kinase II alpha [ Homo sapiens (human) ]

Gene ID: 815, updated on 27-Nov-2024

Summary

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Official Symbol
CAMK2Aprovided by HGNC
Official Full Name
calcium/calmodulin dependent protein kinase II alphaprovided by HGNC
Primary source
HGNC:HGNC:1460
See related
Ensembl:ENSG00000070808 MIM:114078; AllianceGenome:HGNC:1460
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CAMKA; MRD53; MRT63; CaMKIIalpha; CaMKIINalpha
Summary
The product of this gene belongs to the serine/threonine protein kinases family, and to the Ca(2+)/calmodulin-dependent protein kinases subfamily. Calcium signaling is crucial for several aspects of plasticity at glutamatergic synapses. This calcium calmodulin-dependent protein kinase is composed of four different chains: alpha, beta, gamma, and delta. The alpha chain encoded by this gene is required for hippocampal long-term potentiation (LTP) and spatial learning. In addition to its calcium-calmodulin (CaM)-dependent activity, this protein can undergo autophosphorylation, resulting in CaM-independent activity. Several transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jun 2018]
Expression
Restricted expression toward brain (RPKM 112.2) See more
Orthologs
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Genomic context

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See CAMK2A in Genome Data Viewer
Location:
5q32
Exon count:
20
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (150219491..150290130, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (150756093..150826669, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (149599054..149669693, complement)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr5:149565453-149566393 Neighboring gene caudal type homeobox 1 Neighboring gene solute carrier family 6 member 7 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:149585404-149586030 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr5:149587985-149589184 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:149589159-149589702 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:149590543-149591114 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:149606977-149607538 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:149607539-149608100 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:149637006-149637189 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:149644251-149644786 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16506 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:149672518-149673099 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:149673100-149673680 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:149681719-149682259 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:149682260-149682800 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:149682801-149683340 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:149688475-149689108 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr5:149689109-149689742 Neighboring gene arylsulfatase family member I Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr5:149696468-149697667 Neighboring gene uncharacterized LOC105378225

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Nitric oxide induces Ca2+-independent activity of the Ca2+/calmodulin-dependent protein kinase II (CaMKII). Coultrap SJ, et al. J Biol Chem, 2014 Jul 11. PMID 24855644, Free PMC Article
  2. Decreased prefrontal CaMKII alpha mRNA in bipolar illness. Xing G, et al. Neuroreport, 2002 Mar 25. PMID 11930170
  3. alpha-CaMKII controls the growth of human osteosarcoma by regulating cell cycle progression. Yuan K, et al. Lab Invest, 2007 Sep. PMID 17632540, Free PMC Article
  4. Association of a CAMK2A genetic variant with logical memory performance and hippocampal volume in the elderly. Rhein C, et al. Brain Res Bull, 2020 Aug. PMID 32418901
  5. Effect of endurance exercise training on Ca2+ calmodulin-dependent protein kinase II expression and signalling in skeletal muscle of humans. Rose AJ, et al. J Physiol, 2007 Sep 1. PMID 17627985, Free PMC Article

See all (224) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. circADAMTS6 via stabilizing CAMK2A is involved in smoking-induced emphysema through driving M2 macrophage polarization.
    Title: circADAMTS6 via stabilizing CAMK2A is involved in smoking-induced emphysema through driving M2 macrophage polarization.
  2. Camk2a suppresses denervated muscle atrophy by maintaining the Ca2+ homeostasis in muscle cells.
    Title: Camk2a suppresses denervated muscle atrophy by maintaining the Ca2+ homeostasis in muscle cells.
  3. Association of CaMK2A and MeCP2 signaling pathways with cognitive ability in adolescents.
    Title: Association of CaMK2A and MeCP2 signaling pathways with cognitive ability in adolescents.
  4. Calcium calmodulin kinase II activity is required for cartilage homeostasis in osteoarthritis.
    Title: Calcium calmodulin kinase II activity is required for cartilage homeostasis in osteoarthritis.
  5. [Dysregulation of MAD2L1/CAMK2A/PTTG1 Gene Cluster Maintains the Stemness Characteristics of Uterine Corpus Endometrial Carcinoma].
    Title: [Dysregulation of MAD2L1/CAMK2A/PTTG1 Gene Cluster Maintains the Stemness Characteristics of Uterine Corpus Endometrial Carcinoma].
  6. Association of a CAMK2A genetic variant with logical memory performance and hippocampal volume in the elderly.
    Title: Association of a CAMK2A genetic variant with logical memory performance and hippocampal volume in the elderly.
  7. Nanoscale regulation of L-type calcium channels differentiates between ischemic and dilated cardiomyopathies.
    Title: Nanoscale regulation of L-type calcium channels differentiates between ischemic and dilated cardiomyopathies.
  8. Role of Oxidation-Dependent CaMKII Activation in the Genesis of Abnormal Action Potentials in Atrial Cardiomyocytes: A Simulation Study.
    Title: Role of Oxidation-Dependent CaMKII Activation in the Genesis of Abnormal Action Potentials in Atrial Cardiomyocytes: A Simulation Study.
  9. Flexible linkers in CaMKII control the balance between activating and inhibitory autophosphorylation.
    Title: Flexible linkers in CaMKII control the balance between activating and inhibitory autophosphorylation.
  10. CAMK2A supported tumor initiating cells of lung adenocarcinoma by upregulating SOX2 through EZH2 phosphorylation.
    Title: CAMK2A supported tumor initiating cells of lung adenocarcinoma by upregulating SOX2 through EZH2 phosphorylation.
Submit: New GeneRIF Correction See all GeneRIFs (68)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Intellectual disability, autosomal dominant 53
MedGen: C4540481 OMIM: 617798 GeneReviews: Not available
Compare labs
Intellectual disability, autosomal recessive 63
MedGen: C4748167 OMIM: 618095 GeneReviews: Not available
Compare labs

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated 2023-05-24)

ClinGen Genome Curation Page
Haploinsufficency

Little evidence for dosage pathogenicity (Last evaluated 2023-05-24)

ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Tat tat HIV-1 Tat induces upregulation of HDAC2 expression and downregulation of CREB and CaMKIIa expression in human neuroblastoma SK-N-MC cells PubMed
tat Tat-induced IL-10 expression is regulated by p38 MAPK- and CaMK II-activated CREB-1 as well as Sp-1 transcription factors PubMed
tat HIV-1 Tat inhibits the activation of CAMKII elicited via LFA-1 in NK cells, providing evidence that Tat inhibits NK cell activation which might contribute to the impairment of natural immunity in HIV-1 infection PubMed
tat HIV-1 Tat inhibits the activation of CAMKII elicited via beta (3) integrin PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • KIAA0968

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables calcium/calmodulin-dependent protein kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables calcium/calmodulin-dependent protein kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables calcium/calmodulin-dependent protein kinase activity TAS
Traceable Author Statement
more info
 PubMed 
enables calmodulin binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables calmodulin binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables glutamate receptor binding ISS
Inferred from Sequence or Structural Similarity
more info
  
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein homodimerization activity IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein serine kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein serine/threonine kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein serine/threonine kinase activity ISS
Inferred from Sequence or Structural Similarity
more info
  
Process Evidence Code Pubs
involved_in G1/S transition of mitotic cell cycle ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in angiotensin-activated signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in calcium ion transport ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in cellular response to interferon-beta IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cellular response to type II interferon IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in dendritic spine development IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of hydrolase activity ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in peptidyl-serine phosphorylation ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in peptidyl-threonine autophosphorylation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of NF-kappaB transcription factor activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of calcium ion transport ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of cardiac muscle cell apoptotic process ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of receptor signaling pathway via JAK-STAT IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein autophosphorylation ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in protein phosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of endocannabinoid signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of mitochondrial membrane permeability involved in apoptotic process ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of neuron migration IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of neuronal synaptic plasticity IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in regulation of neuronal synaptic plasticity ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of neurotransmitter secretion ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of protein localization to plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in response to ischemia ISS
Inferred from Sequence or Structural Similarity
more info
  
Component Evidence Code Pubs
part_of calcium- and calmodulin-dependent protein kinase complex IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in dendritic spine IDA
Inferred from Direct Assay
more info
 PubMed 
located_in endocytic vesicle membrane TAS
Traceable Author Statement
more info
  
located_in mitochondrion ISS
Inferred from Sequence or Structural Similarity
more info
  
is_active_in neuron projection IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in nucleoplasm TAS
Traceable Author Statement
more info
  
located_in nucleus HDA PubMed 
is_active_in postsynaptic density IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
calcium/calmodulin-dependent protein kinase type II subunit alpha
Names
CaM kinase II alpha subunit
CaM-kinase II alpha chain
CaMK-II alpha subunit
caM kinase II subunit alpha
caMK-II subunit alpha
calcium/calmodulin-dependent protein kinase (CaM kinase) II alpha
calcium/calmodulin-dependent protein kinase II alpha-B subunit
calcium/calmodulin-dependent protein kinase type II alpha chain
NP_001350918.1
NP_001350919.1
NP_001355954.1
NP_057065.2
NP_741960.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_047040.1 RefSeqGene

    Range
    5068..75350
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001363989.1 → NP_001350918.1  calcium/calmodulin-dependent protein kinase type II subunit alpha isoform 1

    Status: REVIEWED

    Source sequence(s)
    AC011372
    Consensus CDS
    CCDS43387.1
    UniProtKB/TrEMBL
    A8K161, Q8IWE0
    Related
    ENSP00000507199.1, ENST00000682786.1
    Conserved Domains (2) summary
    cd14086
    Location:11 → 302
    STKc_CaMKII; Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type II
    pfam08332
    Location:357 → 484
    CaMKII_AD; Calcium/calmodulin dependent protein kinase II association domain

  2. NM_001363990.1 → NP_001350919.1  calcium/calmodulin-dependent protein kinase type II subunit alpha isoform 2

    Status: REVIEWED

    Source sequence(s)
    AC011372
    Consensus CDS
    CCDS43386.1
    UniProtKB/Swiss-Prot
    Q9UL21, Q9UQM7, Q9Y2H4, Q9Y352
    UniProtKB/TrEMBL
    Q7LDD5, Q8IWE0
    Related
    ENSP00000500642.1, ENST00000672479.1
    Conserved Domains (2) summary
    cd14086
    Location:11 → 302
    STKc_CaMKII; Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type II
    pfam08332
    Location:346 → 473
    CaMKII_AD; Calcium/calmodulin dependent protein kinase II association domain

  3. NM_001369025.2 → NP_001355954.1  calcium/calmodulin-dependent protein kinase type II subunit alpha isoform 3

    Status: REVIEWED

    Source sequence(s)
    AC011372
    Consensus CDS
    CCDS93803.1
    UniProtKB/TrEMBL
    A0A5F9ZH21, Q8IWE0
    Related
    ENSP00000499939.1, ENST00000672752.1
    Conserved Domains (2) summary
    cd14086
    Location:11 → 302
    STKc_CaMKII; Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type II
    pfam08332
    Location:346 → 473
    CaMKII_AD; Calcium/calmodulin dependent protein kinase II association domain

  4. NM_015981.4 → NP_057065.2  calcium/calmodulin-dependent protein kinase type II subunit alpha isoform 1

    See identical proteins and their annotated locations for NP_057065.2

    Status: REVIEWED

    Source sequence(s)
    AC011372, AK289776, BC040457, BF951952
    Consensus CDS
    CCDS43387.1
    UniProtKB/TrEMBL
    A8K161, Q8IWE0
    Related
    ENSP00000500386.1, ENST00000671881.1
    Conserved Domains (2) summary
    cd14086
    Location:11 → 302
    STKc_CaMKII; Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type II
    pfam08332
    Location:357 → 484
    CaMKII_AD; Calcium/calmodulin dependent protein kinase II association domain

  5. NM_171825.3 → NP_741960.1  calcium/calmodulin-dependent protein kinase type II subunit alpha isoform 2

    See identical proteins and their annotated locations for NP_741960.1

    Status: REVIEWED

    Source sequence(s)
    AB023185, AC011372, BC040457, BF951952
    Consensus CDS
    CCDS43386.1
    UniProtKB/Swiss-Prot
    Q9UL21, Q9UQM7, Q9Y2H4, Q9Y352
    UniProtKB/TrEMBL
    Q7LDD5, Q8IWE0
    Related
    ENSP00000261793.8, ENST00000348628.11
    Conserved Domains (2) summary
    cd14086
    Location:11 → 302
    STKc_CaMKII; Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type II
    pfam08332
    Location:346 → 473
    CaMKII_AD; Calcium/calmodulin dependent protein kinase II association domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

    Range
    150219491..150290130 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060929.1 Alternate T2T-CHM13v2.0

    Range
    150756093..150826669 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9UQM7.2 GenPept UniProtKB/Swiss-Prot:Q9UQM7

Gene LinkOut

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