ID ATP4A_HUMAN Reviewed; 1035 AA. AC P20648; O00738; DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot. DT 29-MAY-2007, sequence version 5. DT 27-MAR-2024, entry version 225. DE RecName: Full=Potassium-transporting ATPase alpha chain 1; DE EC=7.2.2.19 {ECO:0000250|UniProtKB:P09626}; DE AltName: Full=Gastric H(+)/K(+) ATPase subunit alpha; DE AltName: Full=Proton pump; GN Name=ATP4A {ECO:0000312|HGNC:HGNC:819}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-265. RX PubMed=2160952; DOI=10.1016/s0021-9258(19)38807-6; RA Maeda M., Oshiman K., Tamura S., Futai M.; RT "Human gastric (H+ + K+)-ATPase gene. Similarity to (Na+ + K+)-ATPase genes RT in exon/intron organization but difference in control region."; RL J. Biol. Chem. 265:9027-9032(1990). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2176086; DOI=10.1089/dna.1990.9.749; RA Newman P.R., Greeb J., Keeton T.P., Reyes A.A., Shull G.E.; RT "Structure of the human gastric H,K-ATPase gene and comparison of the 5'- RT flanking sequences of the human and rat genes."; RL DNA Cell Biol. 9:749-762(1990). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 355-401. RC TISSUE=Brain, and Placenta; RX PubMed=3036582; DOI=10.1016/0014-5793(87)80677-4; RA Sverdlov E.D., Monastyrskaya G.S., Broude N.E., Ushkaryov Y.A., RA Allikmets R.L., Melkov A.M., Smirnov Y.V., Malyshev I.V., Dulubova I.E., RA Petrukhin K.E., Gryshin A.V., Kiyatkin N.I., Kostina M.B., Sverdlov V.E., RA Modyanov N.N., Ovchinnikov Y.A.; RT "The family of human Na+,K+-ATPase genes. No less than five genes and/or RT pseudogenes related to the alpha-subunit."; RL FEBS Lett. 217:275-278(1987). RN [5] RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION. RX PubMed=24188822; DOI=10.1016/j.febslet.2013.10.030; RA Fujii T., Awaka S.Y., Takahashi Y., Fujita K., Tsuji H., Shimizu T., RA Gomi T., Tsukada K., Sakai H.; RT "Modulation of H(+),K(+)-ATPase activity by the molecular chaperone ERp57 RT highly expressed in gastric parietal cells."; RL FEBS Lett. 587:3898-3905(2013). CC -!- FUNCTION: The catalytic subunit of the gastric H(+)/K(+) ATPase pump CC which transports H(+) ions in exchange for K(+) ions across the apical CC membrane of parietal cells. Uses ATP as an energy source to pump H(+) CC ions to the gastric lumen while transporting K(+) ion from the lumen CC into the cell (By similarity). Remarkably generates a million-fold CC proton gradient across the gastric parietal cell membrane, acidifying CC the gastric juice down to pH 1 (By similarity). Within a transport CC cycle, the transfer of a H(+) ion across the membrane is coupled to ATP CC hydrolysis and is associated with a transient phosphorylation that CC shifts the pump conformation from inward-facing (E1) to outward-facing CC state (E2). The release of the H(+) ion in the stomach lumen is CC followed by binding of K(+) ion converting the pump conformation back CC to the E1 state (By similarity). {ECO:0000250|UniProtKB:P09626, CC ECO:0000250|UniProtKB:P19156, ECO:0000250|UniProtKB:Q64436}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H(+)(in) + H2O + K(+)(out) = ADP + 2 H(+)(out) + CC K(+)(in) + phosphate; Xref=Rhea:RHEA:22044, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29103, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=7.2.2.19; CC Evidence={ECO:0000250|UniProtKB:P09626}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22045; CC Evidence={ECO:0000250|UniProtKB:P09626}; CC -!- SUBUNIT: The gastric H(+)/K(+) ATPase pump is composed of the catalytic CC alpha subunit ATP4A and the regulatory beta subunit ATP4B. Interacts CC (via the P-domain) with ATP4B (via N-terminus); this interaction CC stabilizes the lumenal-open E2 conformation state and prevents the CC reverse reaction of the transport cycle. CC {ECO:0000250|UniProtKB:P19156}. CC -!- SUBCELLULAR LOCATION: Apical cell membrane CC {ECO:0000269|PubMed:24188822}; Multi-pass membrane protein CC {ECO:0000255}. Note=Localized in the apical canalicular membrane of CC parietal cells (PubMed:24188822). {ECO:0000269|PubMed:24188822}. CC -!- TISSUE SPECIFICITY: Expressed in gastric parietal cells (at protein CC level). {ECO:0000269|PubMed:24188822}. CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3) CC family. Type IIC subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; J05451; AAA51010.1; -; Genomic_DNA. DR EMBL; M63962; AAA35988.1; -; Genomic_DNA. DR EMBL; AD000090; AAB50172.1; -; Genomic_DNA. DR EMBL; AC002389; AAB64182.1; -; Genomic_DNA. DR EMBL; M27575; AAA35577.1; -; Genomic_DNA. DR CCDS; CCDS12467.1; -. DR PIR; A36558; A35292. DR PIR; C27397; C27397. DR RefSeq; NP_000695.2; NM_000704.2. DR AlphaFoldDB; P20648; -. DR SMR; P20648; -. DR BioGRID; 106985; 102. DR ComplexPortal; CPX-2160; Hydrogen:potassium-exchanging ATPase complex. DR CORUM; P20648; -. DR IntAct; P20648; 13. DR MINT; P20648; -. DR STRING; 9606.ENSP00000262623; -. DR BindingDB; P20648; -. DR ChEMBL; CHEMBL2095173; -. DR DrugBank; DB05351; Dexlansoprazole. DR DrugBank; DB00736; Esomeprazole. DR DrugBank; DB00448; Lansoprazole. DR DrugBank; DB00338; Omeprazole. DR DrugBank; DB00213; Pantoprazole. DR DrugBank; DB13620; Potassium gluconate. DR DrugBank; DB01129; Rabeprazole. DR DrugBank; DB11739; Vonoprazan. DR DrugCentral; P20648; -. DR GuidetoPHARMACOLOGY; 849; -. DR TCDB; 3.A.3.1.2; the p-type atpase (p-atpase) superfamily. DR iPTMnet; P20648; -. DR PhosphoSitePlus; P20648; -. DR SwissPalm; P20648; -. DR BioMuta; ATP4A; -. DR DMDM; 148877240; -. DR EPD; P20648; -. DR jPOST; P20648; -. DR MassIVE; P20648; -. DR MaxQB; P20648; -. DR PaxDb; 9606-ENSP00000262623; -. DR PeptideAtlas; P20648; -. DR ProteomicsDB; 53770; -. DR Antibodypedia; 48214; 47 antibodies from 13 providers. DR DNASU; 495; -. DR Ensembl; ENST00000262623.4; ENSP00000262623.2; ENSG00000105675.9. DR GeneID; 495; -. DR KEGG; hsa:495; -. DR MANE-Select; ENST00000262623.4; ENSP00000262623.2; NM_000704.3; NP_000695.2. DR UCSC; uc002oal.2; human. DR AGR; HGNC:819; -. DR CTD; 495; -. DR DisGeNET; 495; -. DR GeneCards; ATP4A; -. DR HGNC; HGNC:819; ATP4A. DR HPA; ENSG00000105675; Tissue enriched (stomach). DR MalaCards; ATP4A; -. DR MIM; 137216; gene. DR neXtProt; NX_P20648; -. DR OpenTargets; ENSG00000105675; -. DR Orphanet; 464756; Familial gastric type 1 neuroendocrine tumor. DR PharmGKB; PA25113; -. DR VEuPathDB; HostDB:ENSG00000105675; -. DR eggNOG; KOG0203; Eukaryota. DR GeneTree; ENSGT00940000160297; -. DR HOGENOM; CLU_002360_4_1_1; -. DR InParanoid; P20648; -. DR OMA; PVQKDCD; -. DR OrthoDB; 203629at2759; -. DR PhylomeDB; P20648; -. DR TreeFam; TF312838; -. DR BioCyc; MetaCyc:HS02790-MONOMER; -. DR BRENDA; 7.2.2.19; 2681. DR PathwayCommons; P20648; -. DR Reactome; R-HSA-936837; Ion transport by P-type ATPases. DR SignaLink; P20648; -. DR BioGRID-ORCS; 495; 11 hits in 1163 CRISPR screens. DR GenomeRNAi; 495; -. DR Pharos; P20648; Tclin. DR PRO; PR:P20648; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; P20648; Protein. DR Bgee; ENSG00000105675; Expressed in cardia of stomach and 106 other cell types or tissues. DR ExpressionAtlas; P20648; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0005889; C:potassium:proton exchanging ATPase complex; ISO:ComplexPortal. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro. DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB. DR GO; GO:0008900; F:P-type potassium:proton transporter activity; IBA:GO_Central. DR GO; GO:0005391; F:P-type sodium:potassium-exchanging transporter activity; IBA:GO_Central. DR GO; GO:0030955; F:potassium ion binding; ISS:UniProtKB. DR GO; GO:0030007; P:intracellular potassium ion homeostasis; IBA:GO_Central. DR GO; GO:0006883; P:intracellular sodium ion homeostasis; IBA:GO_Central. DR GO; GO:0034220; P:monoatomic ion transmembrane transport; TAS:Reactome. DR GO; GO:0045851; P:pH reduction; IEA:Ensembl. DR GO; GO:1990573; P:potassium ion import across plasma membrane; IBA:GO_Central. DR GO; GO:0071805; P:potassium ion transmembrane transport; ISO:ComplexPortal. DR GO; GO:1902600; P:proton transmembrane transport; IBA:GO_Central. DR GO; GO:0010155; P:regulation of proton transport; IEA:Ensembl. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0036376; P:sodium ion export across plasma membrane; IBA:GO_Central. DR CDD; cd02608; P-type_ATPase_Na-K_like; 1. DR Gene3D; 3.40.1110.10; Calcium-transporting ATPase, cytoplasmic domain N; 1. DR Gene3D; 2.70.150.10; Calcium-transporting ATPase, cytoplasmic transduction domain A; 1. DR Gene3D; 1.20.1110.10; Calcium-transporting ATPase, transmembrane domain; 1. DR Gene3D; 3.40.50.1000; HAD superfamily/HAD-like; 1. DR InterPro; IPR006068; ATPase_P-typ_cation-transptr_C. DR InterPro; IPR004014; ATPase_P-typ_cation-transptr_N. DR InterPro; IPR023299; ATPase_P-typ_cyto_dom_N. DR InterPro; IPR015127; ATPase_P-typ_H/K-transp_N. DR InterPro; IPR018303; ATPase_P-typ_P_site. DR InterPro; IPR023298; ATPase_P-typ_TM_dom_sf. DR InterPro; IPR008250; ATPase_P-typ_transduc_dom_A_sf. DR InterPro; IPR036412; HAD-like_sf. DR InterPro; IPR023214; HAD_sf. DR InterPro; IPR005775; P-type_ATPase_IIC. DR InterPro; IPR001757; P_typ_ATPase. DR InterPro; IPR044492; P_typ_ATPase_HD_dom. DR NCBIfam; TIGR01106; ATPase-IIC_X-K; 1. DR NCBIfam; TIGR01494; ATPase_P-type; 2. DR PANTHER; PTHR43294:SF10; POTASSIUM-TRANSPORTING ATPASE ALPHA CHAIN 1; 1. DR PANTHER; PTHR43294; SODIUM/POTASSIUM-TRANSPORTING ATPASE SUBUNIT ALPHA; 1. DR Pfam; PF13246; Cation_ATPase; 1. DR Pfam; PF00689; Cation_ATPase_C; 1. DR Pfam; PF00690; Cation_ATPase_N; 1. DR Pfam; PF00122; E1-E2_ATPase; 1. DR Pfam; PF09040; H-K_ATPase_N; 1. DR Pfam; PF00702; Hydrolase; 1. DR PRINTS; PR00119; CATATPASE. DR PRINTS; PR00121; NAKATPASE. DR SFLD; SFLDS00003; Haloacid_Dehalogenase; 1. DR SFLD; SFLDF00027; p-type_atpase; 1. DR SMART; SM00831; Cation_ATPase_N; 1. DR SUPFAM; SSF81653; Calcium ATPase, transduction domain A; 1. DR SUPFAM; SSF81665; Calcium ATPase, transmembrane domain M; 1. DR SUPFAM; SSF56784; HAD-like; 1. DR SUPFAM; SSF81660; Metal cation-transporting ATPase, ATP-binding domain N; 1. DR PROSITE; PS00154; ATPASE_E1_E2; 1. DR Genevisible; P20648; HS. PE 1: Evidence at protein level; KW ATP-binding; Cell membrane; Hydrogen ion transport; Ion transport; KW Magnesium; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein; KW Potassium; Potassium transport; Reference proteome; Translocase; KW Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..1035 FT /note="Potassium-transporting ATPase alpha chain 1" FT /id="PRO_0000046253" FT TOPO_DOM 1..98 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 99..119 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 120..142 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 143..163 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 164..299 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 300..319 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 320..331 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 332..349 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 350..783 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 784..803 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 804..813 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 814..834 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 835..854 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 855..877 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 878..929 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 930..949 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 950..963 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 964..982 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 983..997 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 998..1018 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1019..1035 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 1..41 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 387 FT /note="4-aspartylphosphate intermediate" FT /evidence="ECO:0000250|UniProtKB:P19156" FT BINDING 340 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /evidence="ECO:0000250|UniProtKB:P19156" FT BINDING 341 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /evidence="ECO:0000250|UniProtKB:P19156" FT BINDING 343 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /evidence="ECO:0000250|UniProtKB:P19156" FT BINDING 345 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /evidence="ECO:0000250|UniProtKB:P19156" FT BINDING 387 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P19156" FT BINDING 389 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P19156" FT BINDING 728 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P19156" FT BINDING 732 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250" FT BINDING 797 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /evidence="ECO:0000250|UniProtKB:P19156" FT BINDING 822 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /evidence="ECO:0000250|UniProtKB:P19156" FT MOD_RES 7 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P19156" FT MOD_RES 10 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P19156" FT MOD_RES 27 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19156" FT MOD_RES 463 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6PIE5" FT MOD_RES 601 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P50993" FT MOD_RES 840 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P09626" FT MOD_RES 954 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000250" FT VARIANT 265 FT /note="V -> A (in dbSNP:rs2733743)" FT /evidence="ECO:0000269|PubMed:2160952" FT /id="VAR_019428" SQ SEQUENCE 1035 AA; 114119 MW; E320595E7D9E0E28 CRC64; MGKAENYELY SVELGPGPGG DMAAKMSKKK KAGGGGGKRK EKLENMKKEM EINDHQLSVA ELEQKYQTSA TKGLSASLAA ELLLRDGPNA LRPPRGTPEY VKFARQLAGG LQCLMWVAAA ICLIAFAIQA SEGDLTTDDN LYLAIALIAV VVVTGCFGYY QEFKSTNIIA SFKNLVPQQA TVIRDGDKFQ INADQLVVGD LVEMKGGDRV PADIRILAAQ GCKVDNSSLT GESEPQTRSP ECTHESPLET RNIAFFSTMC LEGTVQGLVV NTGDRTIIGR IASLASGVEN EKTPIAIEIE HFVDIIAGLA ILFGATFFIV AMCIGYTFLR AMVFFMAIVV AYVPEGLLAT VTVCLSLTAK RLASKNCVVK NLEAVETLGS TSVICSDKTG TLTQNRMTVS HLWFDNHIHT ADTTEDQSGQ TFDQSSETWR ALCRVLTLCN RAAFKSGQDA VPVPKRIVIG DASETALLKF SELTLGNAMG YRDRFPKVCE IPFNSTNKFQ LSIHTLEDPR DPRHLLVMKG APERVLERCS SILIKGQELP LDEQWREAFQ TAYLSLGGLG ERVLGFCQLY LNEKDYPPGY AFDVEAMNFP SSGLCFAGLV SMIDPPRATV PDAVLKCRTA GIRVIMVTGD HPITAKAIAA SVGIISEGSE TVEDIAARLR VPVDQVNRKD ARACVINGMQ LKDMDPSELV EALRTHPEMV FARTSPQQKL VIVESCQRLG AIVAVTGDGV NDSPALKKAD IGVAMGIAGS DAAKNAADMI LLDDNFASIV TGVEQGRLIF DNLKKSIAYT LTKNIPELTP YLIYITVSVP LPLGCITILF IELCTDIFPS VSLAYEKAES DIMHLRPRNP KRDRLVNEPL AAYSYFQIGA IQSFAGFTDY FTAMAQEGWF PLLCVGLRAQ WEDHHLQDLQ DSYGQEWTFG QRLYQQYTCY TVFFISIEVC QIADVLIRKT RRLSAFQQGF FRNKILVIAI VFQVCIGCFL CYCPGMPNIF NFMPIRFQWW LVPLPYGILI FVYDEIRKLG VRCCPGSWWD QELYY //