ATP8A2

Protein identityUniProt · HPA

UniProt accession

Q9NTI2

Gene

ATP8A2

Ensembl

ENSG00000132932

Chromosome

13

Canonical length

1188 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted membrane proteins

Subcellular location

Nucleoplasm,Plasma membrane,Acrosome,Mid piece,Annulus

OverviewNCBI Gene

The protein encoded by this gene is a member of the P4 ATPase family of proteins, which are thought to be involved in a process called lipid flipping, whereby phospholipids are translocated inwards from the exoplasmic leaflet to the cytosolic leaflet of the cell membrane, which aids in generating and maintaining asymmetry in membrane lipids. This protein is predicted to contain an E1 E2 ATPase, a haloacid dehalogenase-like hydrolase (HAD) domain, and multiple transmembrane domains. Associations between this protein and cell cycle control protein 50A are important for translocation of phosphatidylserine across membranes. Mutations in this gene have been associated with a syndrome (CAMRQ4) characterized by cerebellar ataxia and cognitive disabilities. In addition, a translocation breakpoint within this gene was observed in an individual with neurological dysfunction. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2017]

Canonical amino-acid sequenceUniProt

1188 residues, UniProt reviewed canonical sequence.

>Q9NTI2|ATP8A2
     1  MLNGAGLDKA LKMSLPRRSR IRSSVGPVRS SLGYKKAEDE MSRATSVGDQ LEAPARTIYL
    61  NQPHLNKFRD NQISTAKYSV LTFLPRFLYE QIRRAANAFF LFIALLQQIP DVSPTGRYTT
   121  LVPLIIILTI AGIKEIVEDF KRHKADNAVN KKKTIVLRNG MWHTIMWKEV AVGDIVKVVN
   181  GQYLPADVVL LSSSEPQAMC YVETANLDGE TNLKIRQGLS HTADMQTREV LMKLSGTIEC
   241  EGPNRHLYDF TGNLNLDGKS LVALGPDQIL LRGTQLRNTQ WVFGIVVYTG HDTKLMQNST
   301  KAPLKRSNVE KVTNVQILVL FGILLVMALV SSAGALYWNR SHGEKNWYIK KMDTTSDNFG
   361  YNLLTFIILY NNLIPISLLV TLEVVKYTQA LFINWDTDMY YIGNDTPAMA RTSNLNEELG
   421  QVKYLFSDKT GTLTCNIMNF KKCSIAGVTY GHFPELAREP SSDDFCRMPP PCSDSCDFDD
   481  PRLLKNIEDR HPTAPCIQEF LTLLAVCHTV VPEKDGDNII YQASSPDEAA LVKGAKKLGF
   541  VFTARTPFSV IIEAMGQEQT FGILNVLEFS SDRKRMSVIV RTPSGRLRLY CKGADNVIFE
   601  RLSKDSKYME ETLCHLEYFA TEGLRTLCVA YADLSENEYE EWLKVYQEAS TILKDRAQRL
   661  EECYEIIEKN LLLLGATAIE DRLQAGVPET IATLLKAEIK IWVLTGDKQE TAINIGYSCR
   721  LVSQNMALIL LKEDSLDATR AAITQHCTDL GNLLGKENDV ALIIDGHTLK YALSFEVRRS
   781  FLDLALSCKA VICCRVSPLQ KSEIVDVVKK RVKAITLAIG DGANDVGMIQ TAHVGVGISG
   841  NEGMQATNNS DYAIAQFSYL EKLLLVHGAW SYNRVTKCIL YCFYKNVVLY IIELWFAFVN
   901  GFSGQILFER WCIGLYNVIF TALPPFTLGI FERSCTQESM LRFPQLYKIT QNGEGFNTKV
   961  FWGHCINALV HSLILFWFPM KALEHDTVLT SGHATDYLFV GNIVYTYVVV TVCLKAGLET
  1021  TAWTKFSHLA VWGSMLTWLV FFGIYSTIWP TIPIAPDMRG QATMVLSSAH FWLGLFLVPT
  1081  ACLIEDVAWR AAKHTCKKTL LEEVQELETK SRVLGKAVLR DSNGKRLNER DRLIKRLGRK
  1141  TPPTLFRGSS LQQGVPHGYA FSQEEHGAVS QEEVIRAYDT TKKKSRKK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ATP8A2 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)

0.27

Highest tissue expression

18 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ATP8A2.

Disease | AllUniProt

Conditions ATP8A2 is implicated in, by any mechanism.

• Cerebellar ataxia, impaired intellectual development, and dysequilibrium syndrome 4 (CAMRQ4) MIM:615268

Disease | GeneticClinVar

52 pathogenic / likely-pathogenic of 570 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 4
• Inborn genetic diseases
• ATP8A2-related disorder
• Dysequilibrium syndrome

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)

0.6

gnomAD pLI

0

gnomAD missense Z

2.3

DepMap mean gene effect

-0.04

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

• aminophospholipid translocation
• axonogenesis
• detection of light stimulus involved in visual perception
• determination of adult lifespan
• eating behavior
• inner ear morphogenesis
• negative regulation of cell population proliferation
• neurofilament cytoskeleton organization
• neuromuscular process controlling posture
• neuron development
• phospholipid translocation
• positive regulation of multicellular organism growth
• positive regulation of neuron projection development
• positive regulation of phospholipid translocation
• response to auditory stimulus
• retina layer formation
• skin development
• involuntary skeletal muscle contraction

Molecular functions

• ATP binding
• ATP hydrolysis activity
• ATPase-coupled intramembrane lipid transporter activity
• magnesium ion binding
• phosphatidylethanolamine flippase activity
• phosphatidylserine flippase activity
• phosphatidylserine floppase activity

Cellular components

• acrosomal vesicle
• endosome membrane
• Golgi apparatus
• Golgi membrane
• nucleoplasm
• phospholipid-translocating ATPase complex
• plasma membrane
• sperm annulus
• sperm midpiece
• trans-Golgi network

Protein domainsUniProt · Pfam · InterPro

• P-type ATPase
• P-type ATPase, subfamily IV
• 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
• P-type ATPase, C-terminal
• P-type ATPase, N-terminal
• HAD-like superfamily
• P-type ATPase, haloacid dehalogenase domain
• P-type ATPase, A domain
• P-type ATPase actuator domain
• P-type ATPase, cytoplasmic domain N
• Phospholipid-translocating ATPase N-terminal
• Phospholipid-translocating P-type ATPase C-terminal

KeywordsUniProt

• ATP-binding
• Cell membrane
• Cell projection
• Chromosomal rearrangement
• Endosome
• Golgi apparatus
• Intellectual disability
• Lipid transport
• Magnesium
• Membrane
• Metal-binding
• Nucleotide-binding
• Phosphoprotein
• Translocase
• Transmembrane
• Transmembrane helix
• Transport

InteractionsUniProt · HPA

Protein binding partners of ATP8A2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• TMEM30A