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Database: UniProt
Entry: ATP4A_RAT
LinkDB: ATP4A_RAT
Original site: ATP4A_RAT 
ID   ATP4A_RAT               Reviewed;        1033 AA.
AC   P09626; P70511; P97892; Q63253; Q6LD86;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   24-JAN-2024, entry version 178.
DE   RecName: Full=Potassium-transporting ATPase alpha chain 1;
DE            EC=7.2.2.19 {ECO:0000269|PubMed:20921224, ECO:0000269|PubMed:22448261};
DE   AltName: Full=Gastric H(+)/K(+) ATPase subunit alpha {ECO:0000303|PubMed:1849840};
DE   AltName: Full=Proton pump;
GN   Name=Atp4a; Synonyms=Hka;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=3023364; DOI=10.1016/s0021-9258(19)75957-2;
RA   Shull G.E., Lingrel J.B.;
RT   "Molecular cloning of the rat stomach (H+ + K+)-ATPase.";
RL   J. Biol. Chem. 261:16788-16791(1986).
RN   [2]
RP   SEQUENCE REVISION.
RA   Shull G.E.;
RL   Submitted (FEB-1987) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 54-507.
RX   PubMed=7840253; DOI=10.1152/ajprenal.1995.268.1.f99;
RA   Ahn K.Y., Kone B.C.;
RT   "Expression and cellular localization of mRNA encoding the 'gastric'
RT   isoform of H(+)-K(+)-ATPase alpha-subunit in rat kidney.";
RL   Am. J. Physiol. 268:F99-F109(1995).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-50.
RC   TISSUE=Liver;
RA   Song I., Mortell P., Gantz I., Marino L.R., Yamada T.;
RL   Submitted (FEB-1993) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 177-260 AND 436-466.
RC   STRAIN=Sprague-Dawley;
RX   PubMed=1849840; DOI=10.1016/0014-5793(91)80404-q;
RA   Oshiman K., Motajima K., Mahmood S., Shimada A., Tamura S., Maeda M.,
RA   Futai M.;
RT   "Control region and gastric specific transcription of the rat H+,K(+)-
RT   ATPase alpha subunit gene.";
RL   FEBS Lett. 281:250-254(1991).
RN   [6]
RP   FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LYS-791 AND GLU-820.
RX   PubMed=20921224; DOI=10.1074/jbc.m110.133470;
RA   Duerr K.L., Seuffert I., Friedrich T.;
RT   "Deceleration of the E1P-E2P transition and ion transport by mutation of
RT   potentially salt bridge-forming residues Lys-791 and Glu-820 in gastric
RT   H+/K+-ATPase.";
RL   J. Biol. Chem. 285:39366-39379(2010).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-838, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
RN   [8]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=22448261; DOI=10.1371/journal.pone.0033645;
RA   Duerr K.L., Tavraz N.N., Friedrich T.;
RT   "Control of gastric H,K-ATPase activity by cations, voltage and
RT   intracellular pH analyzed by voltage clamp fluorometry in Xenopus
RT   oocytes.";
RL   PLoS ONE 7:e33645-e33645(2012).
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 (PubMed:20921224, PubMed:22448261). Uses ATP
CC       as an energy source to pump H(+) ions to the gastric lumen while
CC       transporting K(+) ion from the lumen into the cell (PubMed:20921224,
CC       PubMed:22448261). Remarkably generates a million-fold proton gradient
CC       across the gastric parietal cell membrane, acidifying the gastric juice
CC       down to pH 1 (By similarity). Within a transport cycle, the transfer of
CC       a H(+) ion across the membrane is coupled to ATP hydrolysis and is
CC       associated with a transient phosphorylation that shifts the pump
CC       conformation from inward-facing (E1) to outward-facing state (E2). The
CC       release of the H(+) ion in the stomach lumen is followed by binding of
CC       K(+) ion converting the pump conformation back to the E1 state
CC       (PubMed:20921224, PubMed:22448261) (By similarity).
CC       {ECO:0000250|UniProtKB:P19156, ECO:0000250|UniProtKB:Q64436,
CC       ECO:0000269|PubMed:20921224, ECO:0000269|PubMed:22448261}.
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:0000269|PubMed:20921224, ECO:0000269|PubMed:22448261};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22045;
CC         Evidence={ECO:0000305|PubMed:20921224, ECO:0000305|PubMed:22673903};
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:0000250|UniProtKB:P20648}; Multi-pass membrane protein
CC       {ECO:0000255}. Note=Localized in the apical canalicular membrane of
CC       parietal cells (By similarity). {ECO:0000250|UniProtKB:P20648}.
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; J02649; AAA66036.1; -; mRNA.
DR   EMBL; S74801; AAP31528.1; -; mRNA.
DR   EMBL; L11569; AAA72354.1; -; Genomic_DNA.
DR   EMBL; X61934; CAA43938.1; -; Genomic_DNA.
DR   EMBL; X61935; CAA43939.1; -; Genomic_DNA.
DR   PIR; A25344; A25344.
DR   AlphaFoldDB; P09626; -.
DR   SMR; P09626; -.
DR   ComplexPortal; CPX-2183; Hydrogen:potassium-exchanging ATPase complex.
DR   STRING; 10116.ENSRNOP00000028508; -.
DR   BindingDB; P09626; -.
DR   ChEMBL; CHEMBL2095199; -.
DR   iPTMnet; P09626; -.
DR   PhosphoSitePlus; P09626; -.
DR   SwissPalm; P09626; -.
DR   jPOST; P09626; -.
DR   PaxDb; 10116-ENSRNOP00000028508; -.
DR   UCSC; RGD:2177; rat.
DR   AGR; RGD:2177; -.
DR   RGD; 2177; Atp4a.
DR   eggNOG; KOG0203; Eukaryota.
DR   InParanoid; P09626; -.
DR   PhylomeDB; P09626; -.
DR   BRENDA; 7.2.2.19; 5301.
DR   Reactome; R-RNO-936837; Ion transport by P-type ATPases.
DR   PRO; PR:P09626; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; ISO:RGD.
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; ISO:RGD.
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:0001696; P:gastric acid secretion; TAS:RGD.
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:0045851; P:pH reduction; ISO:RGD.
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; ISO:RGD.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; ISO:RGD.
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; SFLDG00002; C1.7:_P-type_atpase_like; 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.
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..1033
FT                   /note="Potassium-transporting ATPase alpha chain 1"
FT                   /id="PRO_0000046257"
FT   TOPO_DOM        1..96
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        97..117
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        118..140
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        141..161
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        162..297
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        298..317
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        318..329
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        330..347
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        348..781
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        782..801
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        802..811
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        812..832
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        833..852
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        853..875
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        876..927
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        928..947
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        948..961
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        962..980
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        981..995
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        996..1016
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1017..1033
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          14..39
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        385
FT                   /note="4-aspartylphosphate intermediate"
FT                   /evidence="ECO:0000250|UniProtKB:P19156"
FT   BINDING         338
FT                   /ligand="K(+)"
FT                   /ligand_id="ChEBI:CHEBI:29103"
FT                   /evidence="ECO:0000250|UniProtKB:P19156"
FT   BINDING         339
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         385
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
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         726
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:P19156"
FT   BINDING         730
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250"
FT   BINDING         795
FT                   /ligand="K(+)"
FT                   /ligand_id="ChEBI:CHEBI:29103"
FT                   /evidence="ECO:0000250|UniProtKB:P19156"
FT   BINDING         820
FT                   /ligand="K(+)"
FT                   /ligand_id="ChEBI:CHEBI:29103"
FT                   /evidence="ECO:0000250|UniProtKB:P19156"
FT   MOD_RES         6
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:P19156"
FT   MOD_RES         9
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:P19156"
FT   MOD_RES         26
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P19156"
FT   MOD_RES         461
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q6PIE5"
FT   MOD_RES         599
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P50993"
FT   MOD_RES         838
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         952
FT                   /note="Phosphoserine; by PKA"
FT                   /evidence="ECO:0000250"
FT   MUTAGEN         791
FT                   /note="K->A,E,R,S: Impaired transport activity."
FT                   /evidence="ECO:0000269|PubMed:20921224"
FT   MUTAGEN         820
FT                   /note="E->A,D,Q: Impaired transport activity."
FT                   /evidence="ECO:0000269|PubMed:20921224"
FT   CONFLICT        3
FT                   /note="K -> KA (in Ref. 4; AAA72354)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1033 AA;  114038 MW;  5A8835BA0CAF987E CRC64;
     MGKENYELYS VELGTGPGGD MAAKMSKKKA GGGGGKKKEK LENMKKEMEM NDHQLSVSEL
     EQKYQTSATK GLKASLAAEL LLRDGPNALR PPRGTPEYVK FARQLAGGLQ CLMWVAAAIC
     LIAFAIQASE GDLTTDDNLY LALALIAVVV VTGCFGYYQE FKSTNIIASF KNLVPQQATV
     IRDGDKFQIN ADQLVVGDLV EMKGGDRVPA DIRILSAQGC KVDNSSLTGE SEPQTRSPEC
     THESPLETRN IAFFSTMCLE GTAQGLVVST GDRTIIGRIA SLASGVENEK TPIAIEIEHF
     VDIIAGLAIL FGATFFVVAM CIGYTFLRAM VFFMAIVVAY VPEGLLATVT VCLSLTAKRL
     ASKNCVVKNL EAVETLGSTS VICSDKTGTL TQNRMTVSHL WFDNHIHTAD TTEDQSGQTF
     DQSSETWRAL CRVLTLCNRA AFKSGQDAVP VPKRIVIGDA SETALLKFSE LTLGNAMGYR
     DRFPKVCEIP FNSTNKFQLS IHTLEDPRDP RHLLVMKGAP ERVLERCSSI LIKGQELPLD
     EQWREAFQTA YLSLGGLGER VLGFCQLYLN EKDYPPGYTF DVEAMNFPSS GLCFAGLVSM
     IDPPRATVPD AVLKCRTAGI RVIMVTGDHP ITAKAIAASV GIISEGSETV EDIAARLRMP
     VDQVNKKDAR ACVINGMQLK DMDPSELVEA LRTHPEMVFA RTSPQQKLVI VESCQRLGAI
     VAVTGDGVND SPALKKADIG VAMGIAGSDA AKNAADMILL DDNFASIVTG VEQGRLIFDN
     LKKSIAYTLT KNIPELTPYL IYITVSVPLP LGCITILFIE LCTDIFPSVS LAYEKAESDI
     MHLRPRNPRR DRLVNEPLAA YSYFQIGAIQ SFAGFADYFT AMAQEGWFPL LCVGLRPQWE
     DHHLQDLQDS YGQEWTFGQR LYQQYTCYTV FFISIEMCQI ADVLIRKTRR LSAFQQGFFR
     NRILVIAIVF QVCIGCFLCY CPGMPNIFNF MPIRFQWWLV PMPFGLLIFV YDEIRKLGVR
     CCPGSWWDQE LYY
//
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