Seroatlas · Human Serome Atlas

ATP2A2

Sarcoplasmic/endoplasmic reticulum calcium ATPase 2

Also known as: AT2A2_HUMAN, ATP2B, DAR, SERCA2

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
P16615
Gene
ATP2A2
Ensembl
ENSG00000174437
Chromosome
12
Canonical length
1042 aa
Protein class
Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins, Transporters
Subcellular location
Nucleoplasm,Plasma membrane,Primary cilium,Perinuclear theca,Mid piece,End piece

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

1042 residues, UniProt reviewed canonical sequence.

>P16615|ATP2A2
     1  MENAHTKTVE EVLGHFGVNE STGLSLEQVK KLKERWGSNE LPAEEGKTLL ELVIEQFEDL
    61  LVRILLLAAC ISFVLAWFEE GEETITAFVE PFVILLILVA NAIVGVWQER NAENAIEALK
   121  EYEPEMGKVY RQDRKSVQRI KAKDIVPGDI VEIAVGDKVP ADIRLTSIKS TTLRVDQSIL
   181  TGESVSVIKH TDPVPDPRAV NQDKKNMLFS GTNIAAGKAM GVVVATGVNT EIGKIRDEMV
   241  ATEQERTPLQ QKLDEFGEQL SKVISLICIA VWIINIGHFN DPVHGGSWIR GAIYYFKIAV
   301  ALAVAAIPEG LPAVITTCLA LGTRRMAKKN AIVRSLPSVE TLGCTSVICS DKTGTLTTNQ
   361  MSVCRMFILD RVEGDTCSLN EFTITGSTYA PIGEVHKDDK PVNCHQYDGL VELATICALC
   421  NDSALDYNEA KGVYEKVGEA TETALTCLVE KMNVFDTELK GLSKIERANA CNSVIKQLMK
   481  KEFTLEFSRD RKSMSVYCTP NKPSRTSMSK MFVKGAPEGV IDRCTHIRVG STKVPMTSGV
   541  KQKIMSVIRE WGSGSDTLRC LALATHDNPL RREEMHLEDS ANFIKYETNL TFVGCVGMLD
   601  PPRIEVASSV KLCRQAGIRV IMITGDNKGT AVAICRRIGI FGQDEDVTSK AFTGREFDEL
   661  NPSAQRDACL NARCFARVEP SHKSKIVEFL QSFDEITAMT GDGVNDAPAL KKAEIGIAMG
   721  SGTAVAKTAS EMVLADDNFS TIVAAVEEGR AIYNNMKQFI RYLISSNVGE VVCIFLTAAL
   781  GFPEALIPVQ LLWVNLVTDG LPATALGFNP PDLDIMNKPP RNPKEPLISG WLFFRYLAIG
   841  CYVGAATVGA AAWWFIAADG GPRVSFYQLS HFLQCKEDNP DFEGVDCAIF ESPYPMTMAL
   901  SVLVTIEMCN ALNSLSENQS LLRMPPWENI WLVGSICLSM SLHFLILYVE PLPLIFQITP
   961  LNVTQWLMVL KISLPVILMD ETLKFVARNY LEPGKECVQP ATKSCSFSAC TDGISWPFVL
  1021  LIMPLVIWVY STDTNFSDMF WS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ATP2A2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Other membrane
Secreted
No
Transmembrane segments
10
Mean surface accessibility (rSASA)
0.24
Highest tissue expression
2,676 nTPM

Expression across tissuesHPA

Tissue

  • skeletal muscle: 2,676 nTPM
  • tongue: 2,586 nTPM
  • heart muscle: 942 nTPM
  • esophagus: 171 nTPM
  • prostate: 88 nTPM
  • urinary bladder: 85 nTPM

Single-cell type

  • myonuclei: 3,843 nCPM
  • cardiomyocytes: 1,388 nCPM
  • endometrial ciliated cells: 881 nCPM
  • endometrial glandular cells: 650 nCPM
  • thymic myoid cells: 609 nCPM
  • endometrial luminal cells: 509 nCPM

Immune cell

  • intermediate monocyte: 1.3 nTPM
  • non-classical monocyte: 0.7 nTPM
  • classical monocyte: 0.6 nTPM
  • gdT-cell: 0.5 nTPM
  • myeloid DC: 0.5 nTPM
  • plasmacytoid DC: 0.5 nTPM

Brain region

  • thalamus: 205 nTPM
  • midbrain: 179 nTPM
  • hippocampal formation: 161 nTPM
  • cerebellum: 155 nTPM
  • white matter: 152 nTPM
  • basal ganglia: 150 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ATP2A2.

Disease | AllUniProt

Conditions ATP2A2 is implicated in, by any mechanism.

Disease | GeneticClinVar

93 pathogenic / likely-pathogenic of 413 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

  • Keratosis follicularis
  • ATP2A2-related disorder
  • Acrokeratosis verruciformis of Hopf
  • Darier disease, acral hemorrhagic type
  • Darier disease, segmental

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
0.25
gnomAD pLI
1
gnomAD missense Z
4.88
DepMap mean gene effect
-1.71
DepMap dependency class
pan

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of ATP2A2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads ATP2A2 as an antibody target. Whether an autoantibody or antibody against ATP2A2 could matter depends on whether native ATP2A2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

ATP2A2 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label ATP2A2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/ATP2A2. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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