ATP4A_HUMAN
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 03-AUG-2022, entry version 216.
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). Localized in the apical canalicular
CC membrane of parietal cells (PubMed:24188822).
CC {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}.
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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; 98.
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 DrugCentral; P20648; -.
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; P20648; -.
DR PeptideAtlas; P20648; -.
DR PRIDE; P20648; -.
DR ProteomicsDB; 53770; -.
DR Antibodypedia; 48214; 43 antibodies from 12 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 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; FGIDDYI; -.
DR OrthoDB; 388324at2759; -.
DR PhylomeDB; P20648; -.
DR TreeFam; TF312838; -.
DR BioCyc; MetaCyc:HS02790-MON; -.
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 1077 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 104 other tissues.
DR ExpressionAtlas; P20648; baseline and differential.
DR Genevisible; P20648; HS.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0019829; F:ATPase-coupled cation transmembrane transporter activity; IBA:GO_Central.
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:cellular potassium ion homeostasis; IBA:GO_Central.
DR GO; GO:0006883; P:cellular sodium ion homeostasis; IBA:GO_Central.
DR GO; GO:0034220; P:ion transmembrane transport; TAS:Reactome.
DR GO; GO:1990573; P:potassium ion import across plasma membrane; IBA:GO_Central.
DR GO; GO:1902600; P:proton transmembrane transport; IBA:GO_Central.
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; -; 1.
DR Gene3D; 3.40.50.1000; -; 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 Pfam; PF00689; Cation_ATPase_C; 1.
DR Pfam; PF00690; Cation_ATPase_N; 1.
DR Pfam; PF09040; H-K_ATPase_N; 1.
DR SFLD; SFLDF00027; p-type_atpase; 1.
DR SMART; SM00831; Cation_ATPase_N; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR SUPFAM; SSF81653; SSF81653; 1.
DR SUPFAM; SSF81660; SSF81660; 1.
DR SUPFAM; SSF81665; SSF81665; 1.
DR TIGRFAMs; TIGR01106; ATPase-IIC_X-K; 1.
DR TIGRFAMs; TIGR01494; ATPase_P-type; 2.
DR PROSITE; PS00154; ATPASE_E1_E2; 1.
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
