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FLASH GENE

Symbol

ATP1A1

contributors: mct - updated : 21-02-2018

HGNC name	ATPase, Na+/K+ transporting, alpha 1 polypeptide
HGNC id	799

DNA

TYPE	functioning gene
STRUCTURE	31.56 kb 23 Exon(s)

Genomic sequence alignment details

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

linked

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification	nb exons	type	bp	product
identification	nb exons	type	bp	Protein	kDa	AA	specific expression	Year	Pubmed
	23	-	3754		112	1023	-	Chehab (1987)
	isoform a preproprotein
	23	-	3778		-	1023	-	-
	isoform c
	23	-	3587		-	992	-	-
	isoform d

EXPRESSION

Type

widely

expressed in

(based on citations)

organ(s)

System	Organ level 1	Organ level 2	Organ level 3	Organ level 4	Level	Pubmed	Species	Stage	Rna symbol
Nervous	brain
	spinal cord	anterior horn					Homo sapiens
Urinary	kidney

tissue

System	Tissue	Tissue level 1	Tissue level 2	Level	Pubmed	Species	Stage	Rna symbol
Connective	adipose
Muscular	striatum	skeletal

cells

System	Cell	Pubmed	Species	Stage	Rna symbol
Nervous	neuron		Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

conjugated

PhosphoP

HOMOLOGY

interspecies	homolog to murine Atp1a1 (96.9pc)
	homolog to rattus Atp1a1 (96.8pc)

Homologene

FAMILY	cation transport ATPase (P-type) family
	type IIC subfamily

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,organelle,endosome

basic FUNCTION	catalyzes the hydrolysis of ATP coupled with exchange of Na+/K+ ions across the plasma membrane, thus creating the electrochemical gradient of Ca2+ and K+ ions, providing the energy for active transport of various nutrients
	roles for the Na,K-ATPase subunits, ATP1A1 and FXYD1, during brain ventricle development
	osmotic balance and cell volume stability
	might interact with and regulate SRC activity in a conformation-dependent manner
	new role for ATP1A1 as a regulator of RAB27A targeting and activation
	has an important role in synaptic transmission and memory formation
	important role of ATP1A1 in oxidative stress and oxidative stress-related disease
	is the catalytic alpha subunit of a P-type Na+,K+-ATPase ion pump that establishes Na+ and K+ gradients across cell membranes
	generates the electrochemical driving force that powers essential functions, such as neuronal firing, muscle contraction, and transepithelial ion transport (pMID: 30388404)

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

active transport

text

Na+, K+ pump

PATHWAY

metabolism

signaling

signal transduction

a component	catalytic component of the active enzyme (composed of an alpha and a beta subunit)
	complexing with ATP1B1 and maybe others

INTERACTION

DNA

RNA

small molecule	metal binding, nucleotide,
	ATP binding
	Mg2+, K+, Na+

protein	ATP1B1
	binding the HLA class II histocompatibility antigen DR1
	binds to the N-ter of the inositol 1,4,5-trisphosphate receptor and can trigger an antiapoptotic calcium signal (Zhang 2006)
	FXYD1 has recently been recognized as a critical regulator of ATP1A1 in the heart
	ZNRF1 and ZNRF2 can ubiquitylate the cytoplasmic loop encompassing the nucleotide-binding and phosphorylation regions of the ATP1A1 subunit
	may be a key player in dynamic regulation of cellular SRC activity and the capability of normal conformation transition is essential for both pumping and signaling functions of ATP1A1
	role for MAPK14 in mediating cross-talk between apical Na(+) entry via SCNN1G and its basolateral exit via ATP1A1, which may allow principal cells to maintain intracellular Na(+) concentrations within narrow limits in collecting duct principal cells
	ATP1A1 plays an essential role in RAB27A-dependent melanosome transport
	ATP1A1 is a recruitment factor for FGF2 at the inner leaflet of plasma membranes that may control phosphatidylinositol 4,5-bisphosphate-dependent membrane translocation as part of the unconventional secretory pathway of FGF2
	role of beta-amyloid as a novel physiological regulator of ATP1A1
	ouabain stimulates ATP1A1 in renal proximal tubule cells through an angiotensin/AGTR1-dependent mechanism and that this pathway contributes to cardiac glycoside associated hypertension
	increase of ATP1A1 activity is dependent on activation of the SRC pathway
	GPNMB promotes glioma growth via ATP1A1, ATP1A2, ATP1A3, ATP1A4

cell & other

REGULATION

Other	phosphorylation on tyr10 modulates pumping activity
	phosphorylation of AP-2 mu2 subunit is essential for Na+/K+-ATPase endocytosis in response to a variety of signals, such as dopamine or ROS (Chen 2006)

ASSOCIATED DISORDERS

corresponding disease(s)

DICMT2 , HOMGSMR2

Other morbid association(s)

Type	Gene Modification	Protein expression
tumoral	somatic mutation
in aldosterone-producing adenomas (APAs)
tumoral		--over
is strongly associated with the presence and severity of ESCC (esophageal squamous cell carcinoma)
constitutional	somatic mutation
in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension

Susceptibility

Variant & Polymorphism SNP	genetic variations are associated with bipolar disorders suggesting a role of the enzyme in the etiology of the disease (Goldstein 2009)

Candidate gene

for interacting hypertension susceptibility locus

Marker

Therapy target

System	Type	Disorder	Pubmed
cancer	digestive	liver
targeting ATP1A1 is a novel approach to the treatment of hepatocellular carcinoma

ANIMAL & CELL MODELS

	Dahl salt-sensitive (S) rats bearing Dahl salt-resistant wildtype ATP1A1 cDNA exhibited less rat salt-sensitive hypertension, less hypersensitive renal disease, and longer life span compared with Dahl S controls
	hearts from heterozygous ATP1A1 mice (with a targeted disruption in the gene) are hyponcontractile