ATP1A2

Protein identityUniProt · HPA

UniProt accession

P50993

Gene

ATP1A2

Ensembl

ENSG00000018625

Chromosome

1

Canonical length

1020 aa

Protein class

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

OverviewNCBI Gene

The protein encoded by this gene belongs to the family of P-type cation transport ATPases, and to the subfamily of Na+/K+ -ATPases. Na+/K+ -ATPase is an integral membrane protein responsible for establishing and maintaining the electrochemical gradients of Na and K ions across the plasma membrane. These gradients are essential for osmoregulation, for sodium-coupled transport of a variety of organic and inorganic molecules, and for electrical excitability of nerve and muscle. This enzyme is composed of two subunits, a large catalytic subunit (alpha) and a smaller glycoprotein subunit (beta). The catalytic subunit of Na+/K+ -ATPase is encoded by multiple genes. This gene encodes an alpha 2 subunit. Mutations in this gene result in familial basilar or hemiplegic migraines, and in a rare syndrome known as alternating hemiplegia of childhood. [provided by RefSeq, Oct 2008]

Canonical amino-acid sequenceUniProt

1020 residues, UniProt reviewed canonical sequence.

>P50993|ATP1A2
     1  MGRGAGREYS PAATTAENGG GKKKQKEKEL DELKKEVAMD DHKLSLDELG RKYQVDLSKG
    61  LTNQRAQDVL ARDGPNALTP PPTTPEWVKF CRQLFGGFSI LLWIGAILCF LAYGIQAAME
   121  DEPSNDNLYL GVVLAAVVIV TGCFSYYQEA KSSKIMDSFK NMVPQQALVI REGEKMQINA
   181  EEVVVGDLVE VKGGDRVPAD LRIISSHGCK VDNSSLTGES EPQTRSPEFT HENPLETRNI
   241  CFFSTNCVEG TARGIVIATG DRTVMGRIAT LASGLEVGRT PIAMEIEHFI QLITGVAVFL
   301  GVSFFVLSLI LGYSWLEAVI FLIGIIVANV PEGLLATVTV CLTLTAKRMA RKNCLVKNLE
   361  AVETLGSTST ICSDKTGTLT QNRMTVAHMW FDNQIHEADT TEDQSGATFD KRSPTWTALS
   421  RIAGLCNRAV FKAGQENISV SKRDTAGDAS ESALLKCIEL SCGSVRKMRD RNPKVAEIPF
   481  NSTNKYQLSI HEREDSPQSH VLVMKGAPER ILDRCSTILV QGKEIPLDKE MQDAFQNAYM
   541  ELGGLGERVL GFCQLNLPSG KFPRGFKFDT DELNFPTEKL CFVGLMSMID PPRAAVPDAV
   601  GKCRSAGIKV IMVTGDHPIT AKAIAKGVGI ISEGNETVED IAARLNIPMS QVNPREAKAC
   661  VVHGSDLKDM TSEQLDEILK NHTEIVFART SPQQKLIIVE GCQRQGAIVA VTGDGVNDSP
   721  ALKKADIGIA MGISGSDVSK QAADMILLDD NFASIVTGVE EGRLIFDNLK KSIAYTLTSN
   781  IPEITPFLLF IIANIPLPLG TVTILCIDLG TDMVPAISLA YEAAESDIMK RQPRNSQTDK
   841  LVNERLISMA YGQIGMIQAL GGFFTYFVIL AENGFLPSRL LGIRLDWDDR TMNDLEDSYG
   901  QEWTYEQRKV VEFTCHTAFF ASIVVVQWAD LIICKTRRNS VFQQGMKNKI LIFGLLEETA
   961  LAAFLSYCPG MGVALRMYPL KVTWWFCAFP YSLLIFIYDE VRKLILRRYP GGWVEKETYY

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ATP1A2 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

826 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ATP1A2.

Disease | AllUniProt

Conditions ATP1A2 is implicated in, by any mechanism.

• Migraine, familial hemiplegic, 2 (FHM2) MIM:602481
• Alternating hemiplegia of childhood 1 (AHC1) MIM:104290
• Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies (FARIMPD) MIM:619602
• Developmental and epileptic encephalopathy 98 (DEE98) MIM:619605

Disease | GeneticClinVar

136 pathogenic / likely-pathogenic of 1,558 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Familial hemiplegic migraine
• Migraine, familial hemiplegic, 2
• Developmental and epileptic encephalopathy 98
• Alternating hemiplegia of childhood 1
• Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies

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)

0.5

gnomAD pLI

0

gnomAD missense Z

4.77

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

• adult locomotory behavior
• amygdala development
• ATP metabolic process
• behavioral fear response
• cardiac muscle contraction
• cell communication by electrical coupling involved in cardiac conduction
• cellular response to mechanical stimulus
• cellular response to steroid hormone stimulus
• intracellular potassium ion homeostasis
• intracellular sodium ion homeostasis
• L-ascorbic acid metabolic process
• locomotion
• locomotory exploration behavior
• membrane depolarization during cardiac muscle cell action potential
• membrane repolarization
• monoatomic cation transmembrane transport
• negative regulation of calcium ion transmembrane transport
• negative regulation of cytosolic calcium ion concentration
• negative regulation of heart contraction
• negative regulation of striated muscle contraction
• neuronal action potential propagation
• neurotransmitter uptake
• positive regulation of heart contraction
• potassium ion import across plasma membrane
• potassium ion transmembrane transport
• potassium ion transport
• proton transmembrane transport
• regulation of blood pressure
• regulation of cardiac muscle cell contraction
• regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion
• regulation of glutamate uptake involved in transmission of nerve impulse
• regulation of muscle contraction
• regulation of respiratory gaseous exchange by nervous system process
• regulation of smooth muscle contraction
• regulation of striated muscle contraction
• regulation of synaptic transmission, glutamatergic
• regulation of the force of heart contraction
• regulation of vasoconstriction
• relaxation of cardiac muscle
• response to auditory stimulus
• response to glycoside
• response to nicotine
• response to potassium ion
• sodium ion export across plasma membrane
• sodium ion transmembrane transport
• sodium ion transport
• transport across blood-brain barrier
• visual learning
• olfactory cortex development

Molecular functions

• ATP binding
• ATP hydrolysis activity
• ATPase-coupled monoatomic cation transmembrane transporter activity
• P-type sodium:potassium-exchanging transporter activity
• phosphatase activity
• potassium ion binding
• protein heterodimerization activity
• protein-folding chaperone binding
• sodium ion binding
• steroid binding
• steroid hormone binding

Cellular components

• caveola
• cell projection
• cell surface
• cytoplasm
• dendritic spine
• endoplasmic reticulum
• endosome
• extracellular vesicle
• intercalated disc
• membrane
• neuronal cell body
• organelle membrane
• plasma membrane
• sodium:potassium-exchanging ATPase complex
• T-tubule

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
• P-type ATPase, cytoplasmic domain N

KeywordsUniProt

• ATP-binding
• Cell membrane
• Epilepsy
• Intellectual disability
• Ion transport
• Magnesium
• Membrane
• Metal-binding
• Nucleotide-binding
• Phosphoprotein
• Potassium
• Potassium transport
• Sodium
• Sodium transport
• Sodium/potassium transport
• Translocase
• Transmembrane
• Transmembrane helix
• Transport

InteractionsUniProt · HPA

Protein binding partners of ATP1A2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ATP1A3