ATP1A2 (ATPase Na+/K+ transporting subunit alpha 2)

Gene

• Entrez ID: 477
• Gene name: ATPase Na+/K+ transporting subunit alpha 2
• Gene symbol: ATP1A2
• Synonyms: FHM2, MHP2
• Chromosome: 1
• Chromosome location: 1q23.2
• Summary: 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]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs28933398	T>C	Pathogenic	Coding sequence variant, missense variant
rs28933399	T>C	Pathogenic	Coding sequence variant, missense variant
rs28933400	T>C	Pathogenic	Coding sequence variant, missense variant
rs28933401	G>A	Pathogenic, likely-pathogenic	Coding sequence variant, missense variant
rs28934002	C>A,T	Pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs55741021	G>A,C	Benign, uncertain-significance, conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant
rs121918612	G>A	Pathogenic	Missense variant, coding sequence variant
rs121918613	A>G	Pathogenic	Missense variant, coding sequence variant
rs121918614	G>A	Pathogenic	Missense variant, coding sequence variant
rs121918615	C>T	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs121918616	G>A	Pathogenic	Missense variant, coding sequence variant
rs121918617	T>C	Pathogenic	Missense variant, coding sequence variant
rs121918618	C>T	Pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs121918619	C>A,T	Pathogenic, uncertain-significance	Synonymous variant, coding sequence variant, missense variant
rs121918620	C>G,T	Pathogenic	Missense variant, coding sequence variant
rs142348542	G>A	Uncertain-significance, conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, missense variant
rs143969080	C>T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant
rs144106169	G>A,T	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Coding sequence variant, missense variant
rs146839867	G>A	Uncertain-significance, conflicting-interpretations-of-pathogenicity, benign	Synonymous variant, coding sequence variant
rs147183887	G>C	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs148929192	C>T	Uncertain-significance, benign, conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs149144720	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs149286529	C>T	Conflicting-interpretations-of-pathogenicity, likely-benign	Synonymous variant, coding sequence variant
rs187733403	G>A,T	Conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, missense variant
rs370023134	C>A,T	Conflicting-interpretations-of-pathogenicity, likely-benign	Intron variant
rs373178892	G>A	Conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, missense variant
rs529607288	A>G	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs574788908	C>A	Conflicting-interpretations-of-pathogenicity, benign	Intron variant
rs751808345	T>C	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant
rs755310507	C>A,T	Pathogenic	Synonymous variant, coding sequence variant, stop gained
rs757310141	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs765909830	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs777400961	C>A,T	Pathogenic	Coding sequence variant, missense variant
rs796052277	T>A	Likely-pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs869025341	G>A	Pathogenic	Missense variant, coding sequence variant
rs886039530	C>T	Pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs1057521630	G>T	Likely-pathogenic	Missense variant, coding sequence variant
rs1064794725	G>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1064796771	AGGGGTCGCTGTATTC>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1085307953	G>A	Likely-pathogenic	Intron variant
rs1165052640	C>T	Pathogenic, likely-pathogenic	Stop gained, coding sequence variant
rs1226796744	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs1414742926	G>A	Pathogenic	Missense variant, coding sequence variant
rs1553244022	G>A	Likely-pathogenic	Splice donor variant
rs1553244746	C>G	Pathogenic	Coding sequence variant, missense variant
rs1553244883	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs1553245178	G>A,T	Uncertain-significance, pathogenic	Coding sequence variant, missense variant
rs1553245183	C>A	Likely-pathogenic	Coding sequence variant, missense variant
rs1553245659	G>A	Pathogenic	Coding sequence variant, missense variant
rs1553245771	G>A	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs1553245857	G>A	Pathogenic	Coding sequence variant, missense variant
rs1553245908	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs1553245943	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs1558003446	->TC	Pathogenic	Coding sequence variant, frameshift variant
rs1558005340	C>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1558008455	GT>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1558008759	G>C	Likely-pathogenic	Coding sequence variant, missense variant
rs1558010146	G>T	Pathogenic	Stop gained, coding sequence variant
rs1570988755	C>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1570990484	C>A	Pathogenic	Coding sequence variant, stop gained
rs1570998206	T>A	Likely-pathogenic	Coding sequence variant, stop gained

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT003095	hsa-miR-122-5p	Luciferase reporter assay, qRT-PCR	19296470
MIRT047687	hsa-miR-10a-5p	CLASH	23622248
MIRT048595	hsa-miR-100-5p	CLASH	23622248
MIRT660444	hsa-miR-6875-3p	HITS-CLIP	23824327
MIRT660445	hsa-miR-6826-3p	HITS-CLIP	23824327
MIRT660446	hsa-miR-3160-5p	HITS-CLIP	23824327
MIRT660447	hsa-miR-4778-3p	HITS-CLIP	23824327
MIRT660448	hsa-miR-6795-3p	HITS-CLIP	23824327
MIRT660449	hsa-miR-4714-3p	HITS-CLIP	23824327
MIRT663251	hsa-miR-5096	HITS-CLIP	23824327
MIRT663252	hsa-miR-3187-3p	HITS-CLIP	23824327
MIRT663253	hsa-miR-4435	HITS-CLIP	23824327
MIRT663254	hsa-miR-588	HITS-CLIP	23824327
MIRT663255	hsa-miR-4701-5p	HITS-CLIP	23824327
MIRT663256	hsa-miR-548s	HITS-CLIP	23824327
MIRT663257	hsa-miR-197-3p	HITS-CLIP	23824327
MIRT663258	hsa-miR-411-5p	HITS-CLIP	23824327
MIRT663259	hsa-miR-6832-5p	HITS-CLIP	23824327
MIRT663260	hsa-miR-4755-3p	HITS-CLIP	23824327
MIRT663261	hsa-miR-4524a-3p	HITS-CLIP	23824327
MIRT663262	hsa-miR-1281	HITS-CLIP	23824327
MIRT663263	hsa-miR-4716-5p	HITS-CLIP	23824327
MIRT663264	hsa-miR-6823-5p	HITS-CLIP	23824327
MIRT663265	hsa-miR-484	HITS-CLIP	23824327
MIRT663266	hsa-miR-3155b	HITS-CLIP	23824327
MIRT663267	hsa-miR-3155a	HITS-CLIP	23824327
MIRT663268	hsa-miR-4781-3p	HITS-CLIP	23824327
MIRT663269	hsa-miR-4524b-3p	HITS-CLIP	23824327

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001504	Process	Neurotransmitter uptake	ISS
GO:0001662	Process	Behavioral fear response	ISS
GO:0002026	Process	Regulation of the force of heart contraction	ISS
GO:0002087	Process	Regulation of respiratory gaseous exchange by nervous system process	ISS
GO:0005391	Function	P-type sodium:potassium-exchanging ATPase activity	IBA	21873635
GO:0005391	Function	P-type sodium:potassium-exchanging ATPase activity	IDA	10636900
GO:0005391	Function	P-type sodium:potassium-exchanging ATPase activity	IGI	18052210, 18728015, 20100892
GO:0005391	Function	P-type sodium:potassium-exchanging ATPase activity	IMP	12539047, 23954377
GO:0005391	Function	P-type sodium:potassium-exchanging ATPase activity	ISS
GO:0005496	Function	Steroid binding	IPI	23954377
GO:0005515	Function	Protein binding	IPI	23954377
GO:0005524	Function	ATP binding	IMP	23954377
GO:0005737	Component	Cytoplasm	IDA	12539047
GO:0005768	Component	Endosome	IEA
GO:0005886	Component	Plasma membrane	IDA	12539047
GO:0005886	Component	Plasma membrane	IGI	19372756, 19751721
GO:0005886	Component	Plasma membrane	TAS
GO:0005890	Component	Sodium:potassium-exchanging ATPase complex	IC	12539047
GO:0005890	Component	Sodium:potassium-exchanging ATPase complex	IDA	10636900, 23954377
GO:0005890	Component	Sodium:potassium-exchanging ATPase complex	IGI	18052210, 18728015
GO:0005890	Component	Sodium:potassium-exchanging ATPase complex	ISS
GO:0005901	Component	Caveola	IEA
GO:0006813	Process	Potassium ion transport	NAS	10642400
GO:0006814	Process	Sodium ion transport	NAS	10642400
GO:0006883	Process	Cellular sodium ion homeostasis	IBA	21873635
GO:0006883	Process	Cellular sodium ion homeostasis	IDA	10636900
GO:0006937	Process	Regulation of muscle contraction	ISS
GO:0006940	Process	Regulation of smooth muscle contraction	IEA
GO:0006942	Process	Regulation of striated muscle contraction	NAS	10642400
GO:0008217	Process	Regulation of blood pressure	IEA
GO:0008344	Process	Adult locomotory behavior	IEA
GO:0008542	Process	Visual learning	IEA
GO:0010248	Process	Establishment or maintenance of transmembrane electrochemical gradient	IEA
GO:0010881	Process	Regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion	TAS	23608603
GO:0010996	Process	Response to auditory stimulus	ISS
GO:0014704	Component	Intercalated disc	IEA
GO:0016020	Component	Membrane	IDA	23954377
GO:0016020	Component	Membrane	ISS
GO:0016311	Process	Dephosphorylation	IEA
GO:0016791	Function	Phosphatase activity	ISS
GO:0016887	Function	ATPase activity	IMP	23954377
GO:0019229	Process	Regulation of vasoconstriction	IEA
GO:0019829	Function	ATPase-coupled cation transmembrane transporter activity	IDA	19372756
GO:0019829	Function	ATPase-coupled cation transmembrane transporter activity	IGI	20100892
GO:0021764	Process	Amygdala development	ISS
GO:0021989	Process	Olfactory cortex development	ISS
GO:0030007	Process	Cellular potassium ion homeostasis	IBA	21873635
GO:0030007	Process	Cellular potassium ion homeostasis	IC	23954377
GO:0030007	Process	Cellular potassium ion homeostasis	IDA	10636900
GO:0030315	Component	T-tubule	IGI	19751721
GO:0030955	Function	Potassium ion binding	IMP	23954377
GO:0031090	Component	Organelle membrane	IGI	19751721
GO:0031402	Function	Sodium ion binding	IMP	23954377
GO:0034220	Process	Ion transmembrane transport	TAS
GO:0035094	Process	Response to nicotine	IEA
GO:0035641	Process	Locomotory exploration behavior	ISS
GO:0035725	Process	Sodium ion transmembrane transport	IGI	18728015
GO:0036376	Process	Sodium ion export across plasma membrane	IBA	21873635
GO:0036376	Process	Sodium ion export across plasma membrane	IDA	10636900
GO:0040011	Process	Locomotion	ISS
GO:0042995	Component	Cell projection	ISS
GO:0043025	Component	Neuronal cell body	ISS
GO:0043197	Component	Dendritic spine	IEA
GO:0045822	Process	Negative regulation of heart contraction	ISS
GO:0045823	Process	Positive regulation of heart contraction	ISS
GO:0045988	Process	Negative regulation of striated muscle contraction	IEA
GO:0046034	Process	ATP metabolic process	IMP	23954377
GO:0046982	Function	Protein heterodimerization activity	ISS
GO:0051087	Function	Chaperone binding	IPI	10636900
GO:0051481	Process	Negative regulation of cytosolic calcium ion concentration	ISS
GO:0051946	Process	Regulation of glutamate uptake involved in transmission of nerve impulse	NAS	23954377
GO:0051966	Process	Regulation of synaptic transmission, glutamatergic	NAS	23954377
GO:0055119	Process	Relaxation of cardiac muscle	TAS	23224879
GO:0060048	Process	Cardiac muscle contraction	TAS	23224879
GO:0071260	Process	Cellular response to mechanical stimulus	IEA
GO:0071383	Process	Cellular response to steroid hormone stimulus	IDA	14742675
GO:0071805	Process	Potassium ion transmembrane transport	IGI	18728015
GO:0086004	Process	Regulation of cardiac muscle cell contraction	IEA
GO:0086009	Process	Membrane repolarization	TAS	23954377
GO:0086012	Process	Membrane depolarization during cardiac muscle cell action potential	TAS	23608603
GO:0086064	Process	Cell communication by electrical coupling involved in cardiac conduction	TAS	19683723
GO:0098655	Process	Cation transmembrane transport	IDA	19372756
GO:0098655	Process	Cation transmembrane transport	IGI	20100892
GO:0150104	Process	Transport across blood-brain barrier	NAS	30280653
GO:1902600	Process	Proton transmembrane transport	IBA	21873635
GO:1903170	Process	Negative regulation of calcium ion transmembrane transport	ISS
GO:1903280	Process	Negative regulation of calcium:sodium antiporter activity	ISS
GO:1903416	Process	Response to glycoside	IC	14742675
GO:1903416	Process	Response to glycoside	ISS
GO:1903561	Component	Extracellular vesicle	HDA	24769233
GO:1903779	Process	Regulation of cardiac conduction	TAS
GO:1990239	Function	Steroid hormone binding	IDA	14742675
GO:1990573	Process	Potassium ion import across plasma membrane	IBA	21873635
GO:1990573	Process	Potassium ion import across plasma membrane	IC	23954377
GO:1990573	Process	Potassium ion import across plasma membrane	IDA	10636900

Other IDs

• MIM: 182340
• HGNC: 800
• e!Ensembl: ENSG00000018625

Protein

• UniProt ID: P50993
• Protein name: Sodium/potassium-transporting ATPase subunit alpha-2 (Na(+)/K(+) ATPase alpha-2 subunit) (EC 7.2.2.13) (Sodium pump subunit alpha-2)
• Protein function: This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium, providing the energy for active transport of various nutrients.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00690	Cation_ATPase_N	41 → 109	Cation transporter/ATPase, N-terminus	Domain
  PF00122	E1-E2_ATPase	161 → 352		Family
  PF13246	Cation_ATPase	424 → 518		Family
  PF00689	Cation_ATPase_C	796 → 1005	Cation transporting ATPase, C-terminus	Family

• Sequence:

  MGRGAGREYSPAATTAENGGGKKKQKEKELDELKKEVAMDDHKLSLDELGRKYQVDLSKG
  LTNQRAQDVLARDGPNALTPPPTTPEWVKFCRQLFGGFSILLWIGAILCFLAYGIQAAME
  DEPSNDNLYLGVVLAAVVIVTGCFSYYQEAKSSKIMDSFKNMVPQQALVIREGEKMQINA
  EEVVVGDLVEVKGGDRVPADLRIISSHGCKVDNSSLTGESEPQTRSPEFTHENPLETRNI
  CFFSTNCVEGTARGIVIATGDRTVMGRIATLASGLEVGRTPIAMEIEHFIQLITGVAVFL
  GVSFFVLSLILGYSWLEAVIFLIGIIVANVPEGLLATVTVCLTLTAKRMARKNCLVKNLE
  AVETLGSTSTICSDKTGTLTQNRMTVAHMWFDNQIHEADTTEDQSGATFDKRSPTWTALS
  RIAGLCNRAVFKAGQENISVSKRDTAGDASESALLKCIELSCGSVRKMRDRNPKVAEIPF
  NSTNKYQLSIHEREDSPQSHVLVMKGAPERILDRCSTILVQGKEIPLDKEMQDAFQNAYM
  ELGGLGERVLGFCQLNLPSGKFPRGFKFDTDELNFPTEKLCFVGLMSMIDPPRAAVPDAV
  GKCRSAGIKVIMVTGDHPITAKAIAKGVGIISEGNETVEDIAARLNIPMSQVNPREAKAC
  VVHGSDLKDMTSEQLDEILKNHTEIVFARTSPQQKLIIVEGCQRQGAIVAVTGDGVNDSP
  ALKKADIGIAMGISGSDVSKQAADMILLDDNFASIVTGVEEGRLIFDNLKKSIAYTLTSN
  IPEITPFLLFIIANIPLPLGTVTILCIDLGTDMVPAISLAYEAAESDIMKRQPRNSQTDK
  LVNERLISMAYGQIGMIQALGGFFTYFVILAENGFLPSRLLGIRLDWDDRTMNDLEDSYG
  QEWTYEQRKVVEFTCHTAFFASIVVVQWADLIICKTRRNSVFQQGMKNKILIFGLLEETA
  LAAFLSYCPGMGVALRMYPLKVTWWFCAFPYSLLIFIYDEVRKLILRRYPGGWVEKETYY
  

• Sequence length: 1020