ATP12A ATPase H+/K+ transporting non-gastric alpha2 subunit [Homo sapiens (human)] - Gene

Summary

Official Symbol: ATP12Aprovided by HGNC
Official Full Name: ATPase H+/K+ transporting non-gastric alpha2 subunitprovided by HGNC
Primary source: HGNC:HGNC:13816
See related: Ensembl:ENSG00000075673 MIM:182360; AllianceGenome:HGNC:13816
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: HK; ATP1AL1; H-K-ATPase
Summary: The protein encoded by this gene belongs to the family of P-type cation transport ATPases. This gene encodes a catalytic subunit of the ouabain-sensitive H+/K+ -ATPase that catalyzes the hydrolysis of ATP coupled with the exchange of H(+) and K(+) ions across the plasma membrane. It is also responsible for potassium absorption in various tissues. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]
Expression: Biased expression in esophagus (RPKM 7.0), kidney (RPKM 4.1) and 5 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 13q12.12; 13q12.1-q12.3

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	13	NC_000013.11 (24680408..24712472)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	13	NC_060937.1 (23888443..23920536)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	13	NC_000013.10 (25254546..25286610)

Chromosome 13 - NC_000013.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Study in fresh bronchial samples and in cultured epithelial cells found that ATP12A expressed almost exclusively at the apical side of non-ciliated cells of airway epithelium and in submucosal glands, with much higher expression in cystic fibrosis samples. ATP12A upregulation is associated with depletion of K+ in airway surface liquid, an effect that may have an important role in the barrier function of airway epithelium.
Title: Increased expression of ATP12A proton pump in cystic fibrosis airways.
ATP12A knockdown or inhibition prevented the IL-13 dependent increase in airway surface liquid (ASL) viscosity but did not alter the ASL pH
Title: ATP12A promotes mucus dysfunction during Type 2 airway inflammation.
expressing human ATP12A in cystic fibrosis mouse airways acidified airway surface liquid, impaired defenses, and increased airway bacteria.
Title: Airway acidification initiates host defense abnormalities in cystic fibrosis mice.
Genetic association studies show that carriers of ATP12A rs10507337 C allele or CCTTC haplotype had better pattern of myocardial relaxation as compared to non-carriers.
Title: Left ventricular diastolic function associated with common genetic variation in ATP12A in a general population.
No significantly different expression levels could be detected in the various disease states compared to normal tissue.
Title: Expression of the non-gastric H+/K+ ATPase ATP12A in normal and pathological human prostate tissue.
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
Inhibition of the ATP1AL1 isoenzyme of sodium potassium exchanging ATPase by 8-coumestrol is reported.
Title: Inhibition of the alpha1beta1 isoform of the Na, K-ATPase by 8-methoxycoumestrol without positive inotropic effect in human myocardium--novel aspects of cardiac glycoside pharmacology.
Use of fold recognition methods enables a prediction that the C-terminal domain of the beta subunits of Na,K-ATPase and H,K-ATPase has an immunoglobulin-like fold, which resembles cell adhesion molecules.
Title: A C-terminal lobe of the beta subunit of Na,K-ATPase and H,K-ATPase resembles cell adhesion molecules.
The presence of nongastric H-K-ATPase in rodent prostate apical membranes may indicate its involvement in potassium concentration regulation in secretions of these glands.
Title: Nongastric H-K-ATPase in rodent prostate: lobe-specific expression and apical localization.
Carboxy-terminus of HKalpha(2) facilitates proper folding of tHKalpha(2)/beta(1) complex allowing translocation of heterodimer to plasma membrane where potassium uptake occurs. Otherwise, alpha/beta complex is destined for degradation.
Title: The carboxy terminus of the colonic H(+), K(+)-ATPase alpha-subunit is required for stable beta subunit assembly and function.

Submit: New GeneRIF Correction See all GeneRIFs (13)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D13S999 (e-PCR)
- UniSTS:152332

D13S742 (e-PCR)
- UniSTS:66098

SHGC-12920 (e-PCR)
- UniSTS:37082

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables ATP hydrolysis activity	IEA Inferred from Electronic Annotation more info
enables P-type potassium:proton transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables P-type sodium:potassium-exchanging transporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables P-type sodium:potassium-exchanging transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in establishment or maintenance of transmembrane electrochemical gradient	IEA Inferred from Electronic Annotation more info
involved_in intracellular potassium ion homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in intracellular sodium ion homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in potassium ion import across plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
involved_in proton transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of pH	IEA Inferred from Electronic Annotation more info
involved_in sodium ion export across plasma membrane	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in actin cytoskeleton	IDA Inferred from Direct Assay more info
located_in apical plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in basolateral plasma membrane	IEA Inferred from Electronic Annotation more info
located_in cytosol	IDA Inferred from Direct Assay more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info
located_in plasma membrane	TAS Traceable Author Statement more info
part_of potassium:proton exchanging ATPase complex	TAS Traceable Author Statement more info	PubMed

General protein information

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Preferred Names: potassium-transporting ATPase alpha chain 2

Names: ATPase, H+/K+ transporting, nongastric, alpha polypeptide; ATPase, Na+/K+ transporting, alpha polypeptide-like 1; HK alpha 2; non-gastric Na(+)/K(+) ATPase subunit alpha; sodium pump

NP_001172014.1

EC 7.2.2.13

EC 7.2.2.19

NP_001667.4

EC 7.2.2.13

EC 7.2.2.19

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001185085.2 → NP_001172014.1 potassium-transporting ATPase alpha chain 2 isoform 1

See identical proteins and their annotated locations for NP_001172014.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AK303498, AL157364, BC031609, CA450333, DB216724, U02076

Consensus CDS

CCDS53858.1

UniProtKB/Swiss-Prot

P54707

UniProtKB/TrEMBL

B4E0R9

Related

ENSP00000218548.6, ENST00000218548.10

Conserved Domains (1) summary

TIGR01106
Location:42 → 1045

ATPase-IIC_X-K; sodium or proton efflux -- potassium uptake antiporter, P-type ATPase, alpha subunit
NM_001676.7 → NP_001667.4 potassium-transporting ATPase alpha chain 2 isoform 2

See identical proteins and their annotated locations for NP_001667.4

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice junction at the 5' end of an exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.

Source sequence(s)

AK303498, AL157364, CA450333, DB216724, U02076

Consensus CDS

CCDS31948.1

UniProtKB/Swiss-Prot

P54707, Q13816, Q13817, Q16734, Q5W035, Q8N5U2

Related

ENSP00000371372.3, ENST00000381946.5

Conserved Domains (6) summary

smart00831
Location:56 → 126

Cation_ATPase_N; Cation transporter/ATPase, N-terminus

COG4087
Location:689 → 747

COG4087; Soluble P-type ATPase [General function prediction only]

TIGR01106
Location:42 → 1039

ATPase-IIC_X-K; sodium or proton efflux -- potassium uptake antiporter, P-type ATPase, alpha subunit

pfam00122
Location:150 → 380

E1-E2_ATPase; E1-E2 ATPase

pfam00689
Location:814 → 1024

Cation_ATPase_C; Cation transporting ATPase, C-terminus

pfam13246
Location:442 → 536

Cation_ATPase; Cation transport ATPase (P-type)