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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:P20648
Protein Name:ATHA aka ATP4A
Length:1035
Molecular Weight:114119.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:7
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate hydronium ion, potassium ion

Cross database links:

Genevestigator: P20648
eggNOG: prNOG12961
HEGENOM: HBG456486
RefSeq: NP_000695.2   
Entrez Gene ID: 495   
Pfam: PF00689    PF00690    PF00122    PF09040    PF00702   
OMIM: 137216  gene
KEGG: hsa:495   

Gene Ontology

GO:0005887 C:integral to plasma membrane
GO:0005524 F:ATP binding
GO:0008900 F:hydrogen:potassium-exchanging ATPase activity
GO:0000287 F:magnesium ion binding
GO:0006754 P:ATP biosynthetic process
GO:0015991 P:ATP hydrolysis coupled proton transport
GO:0006813 P:potassium ion transport

References (4)

[1] “Human gastric (H+ + K+)-ATPase gene. Similarity to (Na+ + K+)-ATPase genes in exon/intron organization but difference in control region.”  Maeda M.et.al.   2160952
[2] “Structure of the human gastric H,K-ATPase gene and comparison of the 5'-flanking sequences of the human and rat genes.”  Newman P.R.et.al.   2176086
[3] “The DNA sequence and biology of human chromosome 19.”  Grimwood J.et.al.   15057824
[4] “The family of human Na+,K+-ATPase genes. No less than five genes and/or pseudogenes related to the alpha-subunit.”  Sverdlov E.D.et.al.   3036582
Structure:
3ixz     

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:	MGKAENYELY SVELGPGPGG DMAAKMSKKK KAGGGGGKRK EKLENMKKEM EINDHQLSVA 
61:	ELEQKYQTSA TKGLSASLAA ELLLRDGPNA LRPPRGTPEY VKFARQLAGG LQCLMWVAAA 
121:	ICLIAFAIQA SEGDLTTDDN LYLAIALIAV VVVTGCFGYY QEFKSTNIIA SFKNLVPQQA 
181:	TVIRDGDKFQ INADQLVVGD LVEMKGGDRV PADIRILAAQ GCKVDNSSLT GESEPQTRSP 
241:	ECTHESPLET RNIAFFSTMC LEGTVQGLVV NTGDRTIIGR IASLASGVEN EKTPIAIEIE 
301:	HFVDIIAGLA ILFGATFFIV AMCIGYTFLR AMVFFMAIVV AYVPEGLLAT VTVCLSLTAK 
361:	RLASKNCVVK NLEAVETLGS TSVICSDKTG TLTQNRMTVS HLWFDNHIHT ADTTEDQSGQ 
421:	TFDQSSETWR ALCRVLTLCN RAAFKSGQDA VPVPKRIVIG DASETALLKF SELTLGNAMG 
481:	YRDRFPKVCE IPFNSTNKFQ LSIHTLEDPR DPRHLLVMKG APERVLERCS SILIKGQELP 
541:	LDEQWREAFQ TAYLSLGGLG ERVLGFCQLY LNEKDYPPGY AFDVEAMNFP SSGLCFAGLV 
601:	SMIDPPRATV PDAVLKCRTA GIRVIMVTGD HPITAKAIAA SVGIISEGSE TVEDIAARLR 
661:	VPVDQVNRKD ARACVINGMQ LKDMDPSELV EALRTHPEMV FARTSPQQKL VIVESCQRLG 
721:	AIVAVTGDGV NDSPALKKAD IGVAMGIAGS DAAKNAADMI LLDDNFASIV TGVEQGRLIF 
781:	DNLKKSIAYT LTKNIPELTP YLIYITVSVP LPLGCITILF IELCTDIFPS VSLAYEKAES 
841:	DIMHLRPRNP KRDRLVNEPL AAYSYFQIGA IQSFAGFTDY FTAMAQEGWF PLLCVGLRAQ 
901:	WEDHHLQDLQ DSYGQEWTFG QRLYQQYTCY TVFFISIEVC QIADVLIRKT RRLSAFQQGF 
961:	FRNKILVIAI VFQVCIGCFL CYCPGMPNIF NFMPIRFQWW LVPLPYGILI FVYDEIRKLG 
1021:	VRCCPGSWWD QELYY