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3.A.3.1.2
H+-, K+-ATPase (gastric; H+ efflux; K+ uptake). Two H3O+ may be transported per ATP hydrolyzed.  Howeve, a cryo-electron microscope structure suggests that 1 H+ and 1 K+ are transporter per ATP hydrolyzed, providing the energy needed to generate the one million fold H+ concentration gradient effected by this enzyme (Abe et al. 2012).  The detailed mechanism has been discussed, and the roles of essential residues have been proposed (Shin et al. 2011).  A number of inhibitors of acid secretion have been identified, and these are of pharmacological importance (Shin et al. 2011). The catalytic alpha subunit has ten transmembrane segments with a cluster of intramembranal carboxylic amino acids located in the middle of TMSs 4, 5, 6 and 8. The beta subunit has one TMS with the N terminus in the cytoplasm. The extracellular domain of the beta subunit contains six or seven N-linked glycosylation sites. N-glycosylation is important for enzyme assembly, maturation and sorting (Shin et al. 2009). The cryo-EM structure with bound BYK99, a high-affinity member of K+-competitive, imidazo[1,2-a]pyridine inhibitors, has been solved (Abe et al. 2017).

Accession Number:P51164
Protein Name:ATHB aka ATP4B
Length:291
Molecular Weight:33367.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:1
Location1 / Topology2 / Orientation3: Membrane1 / Single-pass type II membrane protein2
Substrate hydronium ion, potassium ion

Cross database links:

Genevestigator: P51164
eggNOG: prNOG10029
HEGENOM: HBG446583
RefSeq: NP_000696.1   
Entrez Gene ID: 496   
Pfam: PF00287   
OMIM: 137217  gene
KEGG: hsa:496   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0008900 F:hydrogen:potassium-exchanging ATPase activity
GO:0005391 F:sodium:potassium-exchanging ATPase activity
GO:0006754 P:ATP biosynthetic process
GO:0006813 P:potassium ion transport
GO:0015992 P:proton transport
GO:0006814 P:sodium ion transport

References (4)

[1] “cDNA cloning of the beta-subunit of the human gastric H,K-ATPase.”  Ma J.-Y.et.al.   1656976
[2] “The DNA sequence and analysis of human chromosome 13.”  Dunham A.et.al.   15057823
[3] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[4] “GATA-6 DNA binding protein expressed in human gastric adenocarcinoma MKN45 cells.”  Yoshida T.et.al.   9315713

External Searches:

  • Search: DB with
  • BLAST ExPASy (Swiss Institute of Bioinformatics (SIB) BLAST)
  • CDD Search (Conserved Domain Database)
  • Search COGs (Clusters of Orthologous Groups of proteins)
  • 2° Structure (Network Protein Sequence Analysis)

Analyze:

Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MAALQEKKTC GQRMEEFQRY CWNPDTGQML GRTLSRWVWI SLYYVAFYVV MTGLFALCLY 
61:	VLMQTVDPYT PDYQDQLRSP GVTLRPDVYG EKGLEIVYNV SDNRTWADLT QTLHAFLAGY 
121:	SPAAQEDSIN CTSEQYFFQE SFRAPNHTKF SCKFTADMLQ NCSGLADPNF GFEEGKPCFI 
181:	IKMNRIVKFL PSNGSAPRVD CAFLDQPREL GQPLQVKYYP PNGTFSLHYF PYYGKKAQPH 
241:	YSNPLVAAKL LNIPRNAEVA IVCKVMAEHV TFNNPHDPYE GKVEFKLKIE K