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

Summary

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: mouse all
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Genomic context

Location:: 12q24.11

Exon count:: 21

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (110280616..110351093)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (110258258..110328744)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (110718421..110788898)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Persistent Cutaneous Lesions of Darier Disease and Second-Hit Somatic Variants in ATP2A2 Gene.
Title: Persistent Cutaneous Lesions of Darier Disease and Second-Hit Somatic Variants in ATP2A2 Gene.
IL-37 Modulates Myocardial Calcium Handling via the p-STAT3/SERCA2a Axis in HF-Related Engineered Human Heart Tissue.
Title: IL-37 Modulates Myocardial Calcium Handling via the p-STAT3/SERCA2a Axis in HF-Related Engineered Human Heart Tissue.
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.
SERCA2 phosphorylation at the heart of the disease.
Title: SERCA2 phosphorylation at the heart of the disease.
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.
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.
Association of Somatic ATP2A2 Damaging Variants With Grover Disease.
Title: Association of Somatic ATP2A2 Damaging Variants With Grover Disease.
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.
Identification and Characterization of p300-Mediated Lysine Residues in Cardiac SERCA2a.
Title: Identification and Characterization of p300-Mediated Lysine Residues in Cardiac SERCA2a.
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.

Submit: New GeneRIF Correction See all GeneRIFs (175)

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 EBI GWAS CatalogPubMed
Biological insights from 108 schizophrenia-associated genetic loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization. EBI GWAS Catalog EBI GWAS CatalogPubMed

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
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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

MARC_24304-24305:1030108971:1 (e-PCR)
- UniSTS:268880

G15902 (e-PCR)
- UniSTS:4216

D12S1133E (e-PCR)
- UniSTS:151421

ATP2A2 (e-PCR)
- UniSTS:504208

D12S1188E (e-PCR)
- UniSTS:151458

ATP2A2__4219 (e-PCR)
- UniSTS:462756

G32862 (e-PCR)
- UniSTS:117441

D12S1965 (e-PCR)
- UniSTS:79568

WI-18984 (e-PCR)
- UniSTS:21223

D12S2026 (e-PCR)
- UniSTS:21224

RH67554 (e-PCR)
- UniSTS:83950

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	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables P-type calcium transporter activity	TAS Traceable Author Statement more info	PubMed
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 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	IDA Inferred from Direct Assay more info	PubMed
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 cardiac muscle contraction by calcium ion signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of the force of heart contraction	IEA Inferred from Electronic Annotation more info
involved_in relaxation of cardiac muscle	IDA Inferred from Direct Assay more info	PubMed
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
part_of calcium ion-transporting ATPase complex	IDA Inferred from Direct Assay more info	PubMed
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
colocalizes_with intercalated disc	IDA Inferred from Direct Assay more info	PubMed
located_in longitudinal sarcoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
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	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

EC 7.2.2.10

NP_001399943.1

EC 7.2.2.10

NP_001399944.1

EC 7.2.2.10

NP_001672.1

EC 7.2.2.10

NP_733765.1

EC 7.2.2.10

XP_011536704.1

EC 7.2.2.10

XP_054228098.1

EC 7.2.2.10

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

NG_007097.2 RefSeqGene

Range

4621..74467

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

Status: REVIEWED

Source sequence(s)

AC006088
NM_001413014.1 → NP_001399943.1 sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform d

Status: REVIEWED

Source sequence(s)

AC006088
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
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
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_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000012.12 Reference GRCh38.p14 Primary Assembly

Range

110280616..110351093

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

NC_060936.1 Alternate T2T-CHM13v2.0

Range

110258258..110328744

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

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.