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ATP2A2 ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 [ Homo sapiens (human) ]

Gene ID: 488, updated on 13-Apr-2024

Summary

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Official Symbol
ATP2A2provided by HGNC
Official Full Name
ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2provided by HGNC
Primary source
HGNC:HGNC:812
See related
Ensembl:ENSG00000174437 MIM:108740; AllianceGenome:HGNC:812
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
DD; DAR; ATP2B; SERCA2
Summary
This gene encodes one of the SERCA Ca(2+)-ATPases, which are intracellular pumps located in the sarcoplasmic or endoplasmic reticula of the skeletal muscle. This enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol into the sarcoplasmic reticulum lumen, and is involved in regulation of the contraction/relaxation cycle. Mutations in this gene cause Darier-White disease, also known as keratosis follicularis, an autosomal dominant skin disorder characterized by loss of adhesion between epidermal cells and abnormal keratinization. Other types of mutations in this gene have been associated with various forms of muscular dystrophies. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2019]
Expression
Broad expression in heart (RPKM 220.5), esophagus (RPKM 62.0) and 24 other tissues See more
Orthologs
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Genomic context

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Location:
12q24.11
Exon count:
21
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (110280616..110351093)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (110258258..110328744)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (110719052..110788898)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105369976 Neighboring gene Sharpr-MPRA regulatory region 13461 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:110546777-110547368 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:110547369-110547960 Neighboring gene CRISPRi-validated cis-regulatory element chr12.3595 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4853 Neighboring gene intraflagellar transport 81 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:110610112-110610892 Neighboring gene MPRA-validated peak1945 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:110661551-110662051 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:110695091-110695683 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:110706905-110707507 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6998 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4854 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:110719747-110720501 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6999 Neighboring gene Sharpr-MPRA regulatory region 3729 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7000 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr12:110778306-110779505 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr12:110782389-110783588 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:110786998-110787545 Neighboring gene MPRA-validated peak1946 silencer Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:110803582-110804450 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:110804451-110805318 Neighboring gene uncharacterized LOC124903014 Neighboring gene RNA, 7SL, cytoplasmic 769, pseudogene

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. SERCA2 phosphorylation at serine 663 is a key regulator of Ca(2+) homeostasis in heart diseases. Gonnot F, et al. Nat Commun, 2023 Jun 8. PMID 37291092, Free PMC Article
  2. Reduced sarcoplasmic reticulum Ca(2+) ATPase activity underlies skeletal muscle wasting in asthma. Qaisar R, et al. Life Sci, 2021 May 15. PMID 33675897
  3. Clioquinol inhibits cell growth in a SERCA2-dependent manner. Lv X, et al. J Biochem Mol Toxicol, 2021 May. PMID 33511738
  4. Involvement of sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) in mPRα (PAQR7)-mediated progesterone induction of vascular smooth muscle relaxation. Pang Y, et al. Am J Physiol Endocrinol Metab, 2021 Mar 1. PMID 33427050
  5. Dimerization of SERCA2a Enhances Transport Rate and Improves Energetic Efficiency in Living Cells. Bovo E, et al. Biophys J, 2020 Oct 6. PMID 32946770, Free PMC Article

See all (380) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Familial comedonal Darier's disease: a new ATP2A2 mutation with intra-family clinical heterogeneity.
    Title: Familial comedonal Darier's disease: a new ATP2A2 mutation with intra-family clinical heterogeneity.
  2. SERCA2 phosphorylation at the heart of the disease.
    Title: SERCA2 phosphorylation at the heart of the disease.
  3. Mitochondria-ER contact mediated by MFN2-SERCA2 interaction supports CD8[+] T cell metabolic fitness and function in tumors.
    Title: Mitochondria-ER contact mediated by MFN2-SERCA2 interaction supports CD8(+) T cell metabolic fitness and function in tumors.
  4. Disruption of Phosphodiesterase 3A Binding to SERCA2 Increases SERCA2 Activity and Reduces Mortality in Mice With Chronic Heart Failure.
    Title: Disruption of Phosphodiesterase 3A Binding to SERCA2 Increases SERCA2 Activity and Reduces Mortality in Mice With Chronic Heart Failure.
  5. Association of Somatic ATP2A2 Damaging Variants With Grover Disease.
    Title: Association of Somatic ATP2A2 Damaging Variants With Grover Disease.
  6. SERCA2 phosphorylation at serine 663 is a key regulator of Ca[2+] homeostasis in heart diseases.
    Title: SERCA2 phosphorylation at serine 663 is a key regulator of Ca(2+) homeostasis in heart diseases.
  7. Identification and Characterization of p300-Mediated Lysine Residues in Cardiac SERCA2a.
    Title: Identification and Characterization of p300-Mediated Lysine Residues in Cardiac SERCA2a.
  8. A motor neuron disease-associated mutation produces non-glycosylated Seipin that induces ER stress and apoptosis by inactivating SERCA2b.
    Title: A motor neuron disease-associated mutation produces non-glycosylated Seipin that induces ER stress and apoptosis by inactivating SERCA2b.
  9. MicroRNA-200c-3p Negatively Regulates ATP2A2 and Promotes the Progression of Papillary Thyroid Carcinoma.
    Title: MicroRNA-200c-3p Negatively Regulates ATP2A2 and Promotes the Progression of Papillary Thyroid Carcinoma.
  10. Expression of TSP50, SERCA2 and IL-8 in Colorectal Adenoma and Carcinoma: Correlation to Clinicopathological Factors.
    Title: Expression of TSP50, SERCA2 and IL-8 in Colorectal Adenoma and Carcinoma: Correlation to Clinicopathological Factors.
Submit: New GeneRIF Correction See all GeneRIFs (173)

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
Acrokeratosis verruciformis of Hopf
MedGen: C0265971 OMIM: 101900 GeneReviews: Not available
Compare labs
Keratosis follicularis
MedGen: C0022595 OMIM: 124200 GeneReviews: Not available
Compare labs

EBI GWAS Catalog

Description
A genome-wide association study identifies protein quantitative trait loci (pQTLs).
EBI GWAS Catalog
Biological insights from 108 schizophrenia-associated genetic loci.
EBI GWAS Catalog
Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.
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)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp160, precursor env HIV-1 Env is identified to have a physical interaction with ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 (ATP2A2) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed
Rev rev HIV-1 Rev interacting protein, Ca++ dependent-ATPase 2 (ATP2A2), is identified by the in-vitro binding experiments involving cytosolic or nuclear extracts from HeLa. The interaction of Rev with ATP2A2 is increased by RRE 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

  • FLJ20293, FLJ38063, MGC45367, DKFZp686P0211

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables ATP hydrolysis activity IEA
Inferred from Electronic Annotation
more info
  
enables P-type calcium transporter activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables P-type calcium transporter activity TAS
Traceable Author Statement
more info
  
enables P-type calcium transporter activity involved in regulation of cardiac muscle cell membrane potential IBA
Inferred from Biological aspect of Ancestor
more info
  
enables P-type calcium transporter activity involved in regulation of cardiac muscle cell membrane potential IDA
Inferred from Direct Assay
more info
 PubMed 
enables P-type calcium transporter activity involved in regulation of cardiac muscle cell membrane potential ISS
Inferred from Sequence or Structural Similarity
more info
  
enables P-type calcium transporter activity involved in regulation of cardiac muscle cell membrane potential TAS
Traceable Author Statement
more info
 PubMed 
enables S100 protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables calcium ion binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables enzyme binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables lncRNA binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables transmembrane transporter binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in ER-nucleus signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in T-tubule organization IEA
Inferred from Electronic Annotation
more info
  
involved_in autophagosome assembly IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in autophagosome assembly IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in autophagosome membrane docking IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in calcium ion import into sarcoplasmic reticulum IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in calcium ion import into sarcoplasmic reticulum ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in calcium ion transmembrane transport IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in calcium ion transmembrane transport IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in calcium ion transport from cytosol to endoplasmic reticulum IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cardiac muscle hypertrophy in response to stress IEA
Inferred from Electronic Annotation
more info
  
involved_in cell adhesion TAS
Traceable Author Statement
more info
 PubMed 
involved_in cellular response to oxidative stress IEA
Inferred from Electronic Annotation
more info
  
involved_in endoplasmic reticulum calcium ion homeostasis IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in epidermis development TAS
Traceable Author Statement
more info
 PubMed 
involved_in intracellular calcium ion homeostasis IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in intracellular calcium ion homeostasis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in mitochondrion-endoplasmic reticulum membrane tethering IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in monoatomic ion transmembrane transport TAS
Traceable Author Statement
more info
  
involved_in negative regulation of heart contraction IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of receptor binding IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in neuron cellular homeostasis IEA
Inferred from Electronic Annotation
more info
  
involved_in organelle localization by membrane tethering IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of cardiac muscle cell apoptotic process IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of endoplasmic reticulum calcium ion concentration IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of heart rate TAS
Traceable Author Statement
more info
 PubMed 
involved_in regulation of calcium ion-dependent exocytosis of neurotransmitter IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of cardiac conduction TAS
Traceable Author Statement
more info
  
involved_in regulation of cardiac muscle cell action potential involved in regulation of contraction ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of cardiac muscle cell membrane potential IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of cardiac muscle cell membrane potential ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of cardiac muscle cell membrane potential TAS
Traceable Author Statement
more info
 PubMed 
involved_in regulation of cardiac muscle contraction by calcium ion signaling IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in regulation of the force of heart contraction IEA
Inferred from Electronic Annotation
more info
  
involved_in response to endoplasmic reticulum stress ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in sarcoplasmic reticulum calcium ion transport TAS
Traceable Author Statement
more info
 PubMed 
involved_in transition between fast and slow fiber IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in endoplasmic reticulum IDA
Inferred from Direct Assay
more info
 PubMed 
located_in endoplasmic reticulum membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in endoplasmic reticulum membrane TAS
Traceable Author Statement
more info
  
is_active_in membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
 PubMed 
located_in platelet dense tubular network membrane TAS
Traceable Author Statement
more info
  
located_in ribbon synapse IEA
Inferred from Electronic Annotation
more info
  
located_in sarcoplasmic reticulum IDA
Inferred from Direct Assay
more info
 PubMed 
located_in sarcoplasmic reticulum membrane TAS
Traceable Author Statement
more info
 PubMed 

General protein information

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Preferred Names
sarcoplasmic/endoplasmic reticulum calcium ATPase 2
Names
ATPase Ca++ transporting cardiac muscle slow twitch 2
ATPase, Ca++ dependent, slow-twitch, cardiac muscle-2
SR Ca(2+)-ATPase 2
calcium pump 2
cardiac Ca2+ ATPase
endoplasmic reticulum class 1/2 Ca(2+) ATPase
NP_001399942.1
NP_001399943.1
NP_001399944.1
NP_001672.1
NP_733765.1
XP_011536704.1
XP_054228098.1

NCBI Reference Sequences (RefSeq)

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NEW Try the new Transcript table

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_007097.2 RefSeqGene

    Range
    4621..74467
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001413013.1 → NP_001399942.1  sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform c

    Status: REVIEWED

    Source sequence(s)
    AC006088

  2. NM_001413014.1 → NP_001399943.1  sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform d

    Status: REVIEWED

    Source sequence(s)
    AC006088

  3. NM_001413015.1 → NP_001399944.1  sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform e

    Status: REVIEWED

    Source sequence(s)
    AC006088
    Related
    ENSP00000449454.2, ENST00000548169.2

  4. NM_001681.4 → NP_001672.1  sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform a

    See identical proteins and their annotated locations for NP_001672.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (a) differs in the 3' coding region and 3' UTR, resulting in an alternate termination codon, compared to variant 1. The encoded isoform (a, also known as SERCA2a, S2a or HK2) has a shorter and distinct C-terminus, compared to isoform b.
    Source sequence(s)
    AK000300, BG773489, BI553880, M23115
    Consensus CDS
    CCDS9143.1
    UniProtKB/TrEMBL
    H7C5W9
    Related
    ENSP00000311186.6, ENST00000308664.10
    Conserved Domains (1) summary
    cd02083
    Location:5 → 988
    P-type_ATPase_SERCA; sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA), similar to mammalian ATP2A1-3/SERCA1-3

  5. NM_170665.4 → NP_733765.1  sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform b

    See identical proteins and their annotated locations for NP_733765.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (b) represents the longest transcript and encodes the longest isoform (b, also known as SERCA2b, S2b or HK1).
    Source sequence(s)
    AK000300, BC035588, BG773489, BI553880, BX648282
    Consensus CDS
    CCDS9144.1
    UniProtKB/Swiss-Prot
    A6NDN7, B4DF05, P16614, P16615, Q86VJ2
    UniProtKB/TrEMBL
    A0A0S2Z3L2, H7C5W9
    Related
    ENSP00000440045.2, ENST00000539276.7
    Conserved Domains (1) summary
    cd02083
    Location:5 → 988
    P-type_ATPase_SERCA; sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA), similar to mammalian ATP2A1-3/SERCA1-3

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

    Range
    110280616..110351093
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011538402.4 → XP_011536704.1  sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform X1

    See identical proteins and their annotated locations for XP_011536704.1

    UniProtKB/TrEMBL
    H7C5W9
    Conserved Domains (6) summary
    TIGR01116
    Location:53 → 988
    ATPase-IIA1_Ca; sarco/endoplasmic reticulum calcium-translocating P-type ATPase
    pfam00122
    Location:93 → 340
    E1-E2_ATPase; E1-E2 ATPase
    pfam00689
    Location:783 → 986
    Cation_ATPase_C; Cation transporting ATPase, C-terminus
    pfam00690
    Location:4 → 72
    Cation_ATPase_N; Cation transporter/ATPase, N-terminus
    pfam12710
    Location:605 → 711
    HAD; haloacid dehalogenase-like hydrolase
    pfam13246
    Location:419 → 527
    Cation_ATPase; Cation transport ATPase (P-type)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060936.1 Alternate T2T-CHM13v2.0

    Range
    110258258..110328744
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054372123.1 → XP_054228098.1  sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform X1

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_001135765.1: Suppressed sequence

    Description
    NM_001135765.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P16615.1 GenPept UniProtKB/Swiss-Prot:P16615

Gene LinkOut

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