ATP4A

Protein identityUniProt · HPA

UniProt accession

P20648

Gene

ATP4A

Ensembl

ENSG00000105675

Chromosome

19

Canonical length

1035 aa

Protein class

Enzymes, FDA approved drug targets, Metabolic proteins, Plasma proteins, Predicted membrane proteins, Transporters

OverviewNCBI Gene

The protein encoded by this gene belongs to a family of P-type cation-transporting ATPases. The gastric H+, K+-ATPase is a heterodimer consisting of a high molecular weight catalytic alpha subunit and a smaller but heavily glycosylated beta subunit. This enzyme is a proton pump that catalyzes the hydrolysis of ATP coupled with the exchange of H(+) and K(+) ions across the plasma membrane. It is also responsible for gastric acid secretion. This gene encodes a catalytic alpha subunit of the gastric H+, K+-ATPase. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

1035 residues, UniProt reviewed canonical sequence.

>P20648|ATP4A
     1  MGKAENYELY SVELGPGPGG DMAAKMSKKK KAGGGGGKRK EKLENMKKEM EINDHQLSVA
    61  ELEQKYQTSA TKGLSASLAA ELLLRDGPNA LRPPRGTPEY VKFARQLAGG LQCLMWVAAA
   121  ICLIAFAIQA SEGDLTTDDN LYLAIALIAV VVVTGCFGYY QEFKSTNIIA SFKNLVPQQA
   181  TVIRDGDKFQ INADQLVVGD LVEMKGGDRV PADIRILAAQ GCKVDNSSLT GESEPQTRSP
   241  ECTHESPLET RNIAFFSTMC LEGTVQGLVV NTGDRTIIGR IASLASGVEN EKTPIAIEIE
   301  HFVDIIAGLA ILFGATFFIV AMCIGYTFLR AMVFFMAIVV AYVPEGLLAT VTVCLSLTAK
   361  RLASKNCVVK NLEAVETLGS TSVICSDKTG TLTQNRMTVS HLWFDNHIHT ADTTEDQSGQ
   421  TFDQSSETWR ALCRVLTLCN RAAFKSGQDA VPVPKRIVIG DASETALLKF SELTLGNAMG
   481  YRDRFPKVCE IPFNSTNKFQ LSIHTLEDPR DPRHLLVMKG APERVLERCS SILIKGQELP
   541  LDEQWREAFQ TAYLSLGGLG ERVLGFCQLY LNEKDYPPGY AFDVEAMNFP SSGLCFAGLV
   601  SMIDPPRATV PDAVLKCRTA GIRVIMVTGD HPITAKAIAA SVGIISEGSE TVEDIAARLR
   661  VPVDQVNRKD ARACVINGMQ LKDMDPSELV EALRTHPEMV FARTSPQQKL VIVESCQRLG
   721  AIVAVTGDGV NDSPALKKAD IGVAMGIAGS DAAKNAADMI LLDDNFASIV TGVEQGRLIF
   781  DNLKKSIAYT LTKNIPELTP YLIYITVSVP LPLGCITILF IELCTDIFPS VSLAYEKAES
   841  DIMHLRPRNP KRDRLVNEPL AAYSYFQIGA IQSFAGFTDY FTAMAQEGWF PLLCVGLRAQ
   901  WEDHHLQDLQ DSYGQEWTFG QRLYQQYTCY TVFFISIEVC QIADVLIRKT RRLSAFQQGF
   961  FRNKILVIAI VFQVCIGCFL CYCPGMPNIF NFMPIRFQWW LVPLPYGILI FVYDEIRKLG
  1021  VRCCPGSWWD QELYY

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ATP4A 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

Cell surface

Secreted

No

Transmembrane segments

10

Mean surface accessibility (rSASA)

0.24

Highest tissue expression

780 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ATP4A.

Disease | AutoantibodyPubMed

Conditions in which antibodies against ATP4A are reported. Each links to that disease's full target list.

• Diabetes Mellitus, Type 1 4

ReferencesPubMed · IEDB

Publications for ATP4A from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

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)

0.75

gnomAD pLI

0

gnomAD missense Z

2.87

DepMap mean gene effect

0.02

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• intracellular potassium ion homeostasis
• intracellular sodium ion homeostasis
• monoatomic ion transmembrane transport
• pH reduction
• potassium ion import across plasma membrane
• potassium ion transmembrane transport
• proton transmembrane transport
• regulation of proton transport
• response to xenobiotic stimulus
• sodium ion export across plasma membrane

Molecular functions

• ATP binding
• ATP hydrolysis activity
• magnesium ion binding
• P-type potassium:proton transporter activity
• P-type sodium:potassium-exchanging transporter activity
• potassium ion binding

Cellular components

• apical plasma membrane
• extracellular space
• plasma membrane
• potassium:proton exchanging ATPase complex

Protein domainsUniProt · Pfam · InterPro

• P-type ATPase
• Cation-transporting P-type ATPase, N-terminal
• P-type ATPase subfamily IIC, subunit alpha
• Cation-transporting P-type ATPase, C-terminal
• P-type ATPase, A domain superfamily
• P-type ATPase, phosphorylation site
• HAD superfamily
• P-type ATPase, transmembrane domain superfamily
• P-type ATPase, cytoplasmic domain N
• HAD-like superfamily
• P-type ATPase, haloacid dehalogenase domain
• Cation transport ATPase (P-type)
• P-type ATPase, A domain
• P-type ATPase actuator domain
• Cation transporting ATPase, C-terminus
• Cation transporter/ATPase, N-terminus
• haloacid dehalogenase-like hydrolase
• P-type ATPase, cytoplasmic domain N
• Gastric H+/K+-transporter P-type ATPase, N-terminal
• Gastric H+/K+-ATPase, N terminal domain

KeywordsUniProt

• ATP-binding
• Cell membrane
• Hydrogen ion transport
• Ion transport
• Magnesium
• Membrane
• Metal-binding
• Nucleotide-binding
• Phosphoprotein
• Potassium
• Potassium transport
• Translocase
• Transmembrane
• Transmembrane helix
• Transport