ATP1A1

Protein identityUniProt · HPA

UniProt accession

P05023

Gene

ATP1A1

Ensembl

ENSG00000163399

Chromosome

1

Canonical length

1023 aa

Protein class

Cancer-related genes, Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted membrane proteins, Transporters

Subcellular location

Vesicles,Plasma membrane

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 1 subunit. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

Canonical amino-acid sequenceUniProt

1023 residues, UniProt reviewed canonical sequence.

>P05023|ATP1A1
     1  MGKGVGRDKY EPAAVSEQGD KKGKKGKKDR DMDELKKEVS MDDHKLSLDE LHRKYGTDLS
    61  RGLTSARAAE ILARDGPNAL TPPPTTPEWI KFCRQLFGGF SMLLWIGAIL CFLAYSIQAA
   121  TEEEPQNDNL YLGVVLSAVV IITGCFSYYQ EAKSSKIMES FKNMVPQQAL VIRNGEKMSI
   181  NAEEVVVGDL VEVKGGDRIP ADLRIISANG CKVDNSSLTG ESEPQTRSPD FTNENPLETR
   241  NIAFFSTNCV EGTARGIVVY TGDRTVMGRI ATLASGLEGG QTPIAAEIEH FIHIITGVAV
   301  FLGVSFFILS LILEYTWLEA VIFLIGIIVA NVPEGLLATV TVCLTLTAKR MARKNCLVKN
   361  LEAVETLGST STICSDKTGT LTQNRMTVAH MWFDNQIHEA DTTENQSGVS FDKTSATWLA
   421  LSRIAGLCNR AVFQANQENL PILKRAVAGD ASESALLKCI ELCCGSVKEM RERYAKIVEI
   481  PFNSTNKYQL SIHKNPNTSE PQHLLVMKGA PERILDRCSS ILLHGKEQPL DEELKDAFQN
   541  AYLELGGLGE RVLGFCHLFL PDEQFPEGFQ FDTDDVNFPI DNLCFVGLIS MIDPPRAAVP
   601  DAVGKCRSAG IKVIMVTGDH PITAKAIAKG VGIISEGNET VEDIAARLNI PVSQVNPRDA
   661  KACVVHGSDL KDMTSEQLDD ILKYHTEIVF ARTSPQQKLI IVEGCQRQGA IVAVTGDGVN
   721  DSPALKKADI GVAMGIAGSD VSKQAADMIL LDDNFASIVT GVEEGRLIFD NLKKSIAYTL
   781  TSNIPEITPF LIFIIANIPL PLGTVTILCI DLGTDMVPAI SLAYEQAESD IMKRQPRNPK
   841  TDKLVNERLI SMAYGQIGMI QALGGFFTYF VILAENGFLP IHLLGLRVDW DDRWINDVED
   901  SYGQQWTYEQ RKIVEFTCHT AFFVSIVVVQ WADLVICKTR RNSVFQQGMK NKILIFGLFE
   961  ETALAAFLSY CPGMGVALRM YPLKPTWWFC AFPYSLLIFV YDEVRKLIIR RRPGGWVEKE
  1021  TYY

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ATP1A1 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

1,394 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ATP1A1.

Disease | AllUniProt

Conditions ATP1A1 is implicated in, by any mechanism.

• Charcot-Marie-Tooth disease, axonal, type 2DD (CMT2DD) MIM:618036
• Hypomagnesemia, seizures, and impaired intellectual development 2 (HOMGSMR2) MIM:618314

Disease | GeneticClinVar

27 pathogenic / likely-pathogenic of 956 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Charcot-Marie-tooth disease, axonal, type 2DD
• Hypomagnesemia, seizures, and intellectual disability 2
• Charcot-Marie-Tooth disease type 2A2
• Aldosterone-producing adrenal cortex adenoma
• Inborn genetic diseases

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)

0.12

gnomAD pLI

1

gnomAD missense Z

6.22

DepMap mean gene effect

-1.03

DepMap dependency class

common

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cardiac muscle cell action potential involved in contraction
• cell communication by electrical coupling involved in cardiac conduction
• cellular response to steroid hormone stimulus
• establishment or maintenance of transmembrane electrochemical gradient
• intracellular potassium ion homeostasis
• intracellular sodium ion homeostasis
• membrane repolarization
• membrane repolarization during cardiac muscle cell action potential
• negative regulation of heart contraction
• osmosensory signaling pathway
• positive regulation of heart contraction
• positive regulation of striated muscle contraction
• potassium ion import across plasma membrane
• potassium ion transmembrane transport
• proton transmembrane transport
• regulation of blood pressure
• regulation of sodium ion transport
• regulation of the force of heart contraction
• relaxation of cardiac muscle
• response to glycoside
• response to xenobiotic stimulus
• sodium ion export across plasma membrane
• sodium ion transmembrane transport
• negative regulation of glucocorticoid biosynthetic process

Molecular functions

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

Cellular components

• apical plasma membrane
• axon
• basolateral plasma membrane
• endoplasmic reticulum
• extracellular exosome
• extracellular vesicle
• Golgi apparatus
• lateral plasma membrane
• melanosome
• membrane
• membrane raft
• organelle membrane
• photoreceptor inner segment membrane
• plasma membrane
• postsynaptic density
• protein-containing complex
• sarcolemma
• sodium:potassium-exchanging ATPase complex
• sperm flagellum
• 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

• Acetylation
• ATP-binding
• Cell membrane
• Cell projection
• Charcot-Marie-Tooth disease
• Epilepsy
• Intellectual disability
• Ion transport
• Magnesium
• Membrane
• Metal-binding
• Neurodegeneration
• Neuropathy
• Nucleotide-binding
• Phosphoprotein
• Potassium
• Potassium transport
• Primary hypomagnesemia
• Sodium
• Sodium transport
• Sodium/potassium transport
• Translocase
• Transmembrane
• Transmembrane helix
• Transport

InteractionsUniProt · HPA

Protein binding partners of ATP1A1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CLN3
• SCN7A
• SIK1
• SLC35G1
• STIM1
• ATP1A3
• ATP1B1
• ATP1B3
• NDRG1
• SLC3A2