ID ATP4A_CANLF Reviewed; 1034 AA. AC P50996; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 04-NOV-2026, entry version 167. 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; OS Canis lupus familiaris (Dog) (Canis familiaris). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis. OX NCBI_TaxID=9615; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Stomach; RX PubMed=8250881; DOI=10.1006/bbrc.1993.2385; RA Song I., Mortell M.P., Gantz I., Brown D.R., Yamada T.; RT "Molecular cloning and structural analysis of canine gastric H+,K(+)- RT ATPase."; RL Biochem. Biophys. Res. Commun. 196:1240-1247(1993). 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=K(+)(out) + ATP + H2O + H(+)(in) = K(+)(in) + ADP + phosphate CC + 2 H(+)(out); 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:0000250|UniProtKB:P20648}; Multi-pass membrane protein CC {ECO:0000255}. Note=Localized in the apical canalicular membrane of CC parietal cells. {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}. 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; L11568; AAA30848.1; -; mRNA. DR PIR; JN0903; JN0903. DR RefSeq; NP_001003342.1; NM_001003342.1. DR AlphaFoldDB; P50996; -. DR SMR; P50996; -. DR FunCoup; P50996; 15. DR STRING; 9615.ENSCAFP00000055733; -. DR PaxDb; 9615-ENSCAFP00000055733; -. DR GeneID; 431686; -. DR KEGG; cfa:431686; -. DR CTD; 495; -. DR eggNOG; KOG0203; Eukaryota. DR InParanoid; P50996; -. DR OMA; AACVMLQ; -. DR OrthoDB; 158672at2759; -. DR Proteomes; UP000805418; Unplaced. DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0005524; F:ATP binding; IEA:InterPro. 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; ISS:UniProtKB. DR GO; GO:0005391; F:P-type sodium:potassium-exchanging transporter activity; IEA:TreeGrafter. 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:1990573; P:potassium ion import across plasma membrane; 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 FunFam; 3.40.50.1000:FF:000001; Phospholipid-transporting ATPase IC; 1. DR FunFam; 1.20.1110.10:FF:000079; Sodium/potassium-transporting ATPase subunit alpha; 1. DR FunFam; 2.70.150.10:FF:000003; Sodium/potassium-transporting ATPase subunit alpha; 1. DR FunFam; 3.40.1110.10:FF:000001; Sodium/potassium-transporting ATPase subunit alpha; 1. DR FunFam; 3.40.50.1000:FF:000083; Sodium/potassium-transporting ATPase subunit alpha; 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; IPR059000; ATPase_P-type_domA. DR InterPro; IPR050510; Cation_transp_ATPase_P-type. 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; PF08282; Hydrolase_3; 1. DR PRINTS; PR00119; CATATPASE. DR PRINTS; PR00121; NAKATPASE. DR SFLD; SFLDG00002; C1.7:_P-type_atpase_like; 1. 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. PE 2: Evidence at transcript 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..1034 FT /note="Potassium-transporting ATPase alpha chain 1" FT /id="PRO_0000046252" FT TOPO_DOM 1..97 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 98..118 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 119..141 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 142..162 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 163..298 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 299..318 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 319..330 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 331..348 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 349..782 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 783..802 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 803..812 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 813..833 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 834..853 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 854..876 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 877..928 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 929..948 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 949..962 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 963..981 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 982..996 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 997..1017 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1018..1034 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 14..41 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 225..245 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 26..39 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 225..239 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 386 FT /note="4-aspartylphosphate intermediate" 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 340 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /evidence="ECO:0000250|UniProtKB:P19156" FT BINDING 342 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /evidence="ECO:0000250|UniProtKB:P19156" FT BINDING 344 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /evidence="ECO:0000250|UniProtKB:P19156" FT BINDING 386 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P19156" FT BINDING 388 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P19156" FT BINDING 727 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P19156" FT BINDING 731 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250" FT BINDING 796 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /evidence="ECO:0000250|UniProtKB:P19156" FT BINDING 821 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 462 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6PIE5" FT MOD_RES 600 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P50993" FT MOD_RES 839 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P09626" FT MOD_RES 953 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000250" SQ SEQUENCE 1034 AA; 114106 MW; 452AE1185C0D62E8 CRC64; MGKAENYEMY SVELGPGPGG DMAAKMSKKK AGKGGGKKKE KLENMKKEME INDHQLSVAE LEQKYQTSAT KGLSASLAAD LLLRDGPNAL RPPRGTPEYV KFARQLAGGL QCLMWVAAAI CLIAFAIQAS EGDLTTDDNL YLALALIAVV VVTGCFGYYQ EFKSTNIIAS FKNLVPQQAT VIRDGDKFQI NADQLVVGDL VEMKGGDRVP ADIRILQAQG CKVDNSSLTG ESEPQTRSPE CTHESPLETR NIALFSTMCL EGTAQGLVVN TGDRTIIGRI ASLASGVENE KTPIAIEIEH FVDIIAGLAI LFGATFFVVA MCIGYTFLRA MVFFMAIVVA YVPEGLLATV TVCLSLTAKR LASKNCVVKN LEAVETLGSK SVICSDKTGT LTQNSMTVSN LWFDNHIHTA DTTEDQSGQK FDQSSETWRA LCRVLTLCNR AAFKSGQDAV PVPKRIVIGD ASETALLKFS ELTLGNAMGY RERFPKVCEI PFNSTNKFQL SIHTLEDPRD PRHVLVMKGA PERVLERCSS ILIKGQELPL DEQWREAFQT AYLSLGGLGE RVLGFCQLYL SEKDYPPGYA FDVEAMNFPT SGLCFAGLVS MIDPPRATVP DAVLKCRTAG IRVIMVTGDH PITAKAIAAS VGIISEGSET VEDIAARLRV PVDQVNRKDA RACVINGMQL KDMDPSELVE ALRTHPEMVF ARTSPQQKLV IVESCQRLGA IVAVTGDGVN DSPALKKADI GVAMGIAGSD AAKNAADMIL LDDNFASIVT GVEQGRLIFD NLKKSIAYTL TKNIPELTPY LIYITVSVPL PLGCITILFI ELCTDIFPSV SLAYEKAESD IMHLRPRNPK RDRLVNEPLA AYSYFQIGAI QSFAGFTDYF TAMAQEGWFP LLCVGLRPYW ENHHLQDLQD SYGQEWTFGQ RLYQQYTCYT VFFISIEMCQ IADVLIRKTR RLSAFQQGFF RNRILVIAIV FQVCIGCFLC YCPGMPNIFN FMPIRYQWWL VPMPFGLLIF VYDEIRKLGV RCCPGSWWDQ ELYY //