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 03-AUG-2022, entry version 172.
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). Localized in the apical canalicular
CC membrane of parietal cells (By similarity).
CC {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; P09626; -.
DR PRIDE; P09626; -.
DR UCSC; RGD:2177; rat.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
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; 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:0030007; P:cellular potassium ion homeostasis; IBA:GO_Central.
DR GO; GO:0006883; P:cellular sodium ion homeostasis; IBA:GO_Central.
DR GO; GO:0001696; P:gastric acid secretion; TAS:RGD.
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: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; -; 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..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
