ATP4A_RABIT
ID ATP4A_RABIT Reviewed; 1035 AA.
AC P27112;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Potassium-transporting ATPase alpha chain 1;
DE EC=7.2.2.19 {ECO:0000269|PubMed:24188822};
DE AltName: Full=Gastric H(+)/K(+) ATPase subunit alpha {ECO:0000303|PubMed:1316171};
DE AltName: Full=Proton pump;
GN Name=ATP4A;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=New Zealand white;
RX PubMed=1316171; DOI=10.1016/0167-4781(92)90100-e;
RA Bamberg K., Mercier F., Reuben M.A., Kobayashi Y., Munson K.B., Sachs G.;
RT "cDNA cloning and membrane topology of the rabbit gastric H+/K(+)-ATPase
RT alpha-subunit.";
RL Biochim. Biophys. Acta 1131:69-77(1992).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH ATP4B, AND SUBCELLULAR
RP LOCATION.
RX PubMed=10722662; DOI=10.1074/jbc.275.12.8324;
RA Asano S., Kawada K., Kimura T., Grishin A.V., Caplan M.J., Takeguchi N.;
RT "The roles of carbohydrate chains of the beta-subunit on the functional
RT expression of gastric H(+),K(+)-ATPase.";
RL J. Biol. Chem. 275:8324-8330(2000).
RN [3]
RP INTERACTION WITH ATP4B.
RX PubMed=11909858; DOI=10.1074/jbc.m200523200;
RA Kimura T., Tabuchi Y., Takeguchi N., Asano S.;
RT "Mutational study on the roles of disulfide bonds in the beta-subunit of
RT gastric H+,K+-ATPase.";
RL J. Biol. Chem. 277:20671-20677(2002).
RN [4]
RP FUNCTION, AND CATALYTIC ACTIVITY.
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 (PubMed:10722662, PubMed:24188822). 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:10722662,
CC PubMed:24188822). 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:10722662, PubMed:24188822) (By similarity).
CC {ECO:0000250|UniProtKB:P19156, ECO:0000250|UniProtKB:Q64436,
CC ECO:0000269|PubMed:10722662, ECO:0000269|PubMed:24188822}.
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:24188822, ECO:0000305|PubMed:10722662};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22045;
CC Evidence={ECO:0000305|PubMed:10722662, ECO:0000305|PubMed:24188822};
CC -!- SUBUNIT: The gastric H(+)/K(+) ATPase pump is composed of the catalytic
CC alpha subunit ATP4A and the regulatory beta subunit ATP4B
CC (PubMed:10722662, PubMed:11909858). Interacts (via the P-domain) with
CC ATP4B (via N-terminus); this interaction stabilizes the lumenal-open E2
CC conformation state and prevents the reverse reaction of the transport
CC cycle (By similarity). {ECO:0000250|UniProtKB:P19156,
CC ECO:0000269|PubMed:10722662, ECO:0000269|PubMed:11909858}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P20648}. Cell membrane
CC {ECO:0000269|PubMed:10722662}; 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}.
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DR EMBL; X64694; CAA45927.1; -; mRNA.
DR PIR; S23406; S23406.
DR RefSeq; NP_001095171.1; NM_001101701.1.
DR AlphaFoldDB; P27112; -.
DR SMR; P27112; -.
DR BioGRID; 1172300; 1.
DR STRING; 9986.ENSOCUP00000024135; -.
DR DrugCentral; P27112; -.
DR PRIDE; P27112; -.
DR GeneID; 100009279; -.
DR KEGG; ocu:100009279; -.
DR CTD; 495; -.
DR eggNOG; KOG0203; Eukaryota.
DR InParanoid; P27112; -.
DR OrthoDB; 388324at2759; -.
DR BRENDA; 7.2.2.19; 1749.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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; IEA:UniProtKB-EC.
DR GO; GO:0030955; F:potassium ion binding; ISS:UniProtKB.
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_0000046256"
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"
SQ SEQUENCE 1035 AA; 114202 MW; FCD600AC142CC14A CRC64;
MGKADNYELY SVELGPGPGG DMAAKMSKKK KAGGGGGKRK EKLENMKKEM EINDHQLSVA
ELEQKYQTSA TKGLSARLAA ELLLRDGPNA LRPPRGTPEY VKFARQLAGG LQCLMWVAAA
ICLIAFAIQA SEGDLTTDDN LYLALALIAV VVVTGCFGYY QEFKSTNIIA SFKNLVPQQA
TVIRDGDKFQ INADQLVVGD LVEMKGGDRV PADIRILAAQ GCKVDNSSLT GESEPQTRSP
ECTHESPLET RNIAFFSTMC LEGTAQGLVV NTGDRTIIGR IASLASGVEN EKTPIAIEIE
HFVDIIAGLA ILFGATFFVV AMCIGYTFLR AMVFFMAIVV AYVPEGLLAT VTVCLSLTAK
RLASKNCVVK NLEAVETLGS TSVICSDKTG TLTQNRMTVS HLWFDNHIHT ADTTEDQSGQ
TFDQSSETWR ALCRVLTLCN RAAFKSGQDA VPVPKRIVIG DASETALLKF SELTLGNAMG
YRDRFPKVCE IPFNSTNKFQ LSIHTLEDPR DPRHLLVMKG APERVLERCS SILIKGQELP
LDEQWREAFQ TAYLSLGGLG ERVLGFCHLY LSEKDYPPGY 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 PLLCVGLRPQ
WEDHHLQDLQ DSYGQEWTFG QRLYQQYTCY TVFFISIEMC QIADVLIRKT RRLSAFQQGF
FRNRILVIAI VFQVCIGCFL CYCPGMPNIF NFMPIRFQWW LVPMPFGLLI FVYDEIRKLG
VRCCPGSWWD QELYY
