AT12A_RAT
ID AT12A_RAT Reviewed; 1036 AA.
AC P54708;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Potassium-transporting ATPase alpha chain 2;
DE AltName: Full=HK alpha 2 {ECO:0000250|UniProtKB:Q9TV52};
DE AltName: Full=Non-gastric H(+)/K(+) ATPase subunit alpha;
DE EC=7.2.2.19 {ECO:0000269|PubMed:10644526, ECO:0000269|PubMed:7560093};
DE AltName: Full=Non-gastric Na(+)/K(+) ATPase subunit alpha;
DE EC=7.2.2.13 {ECO:0000269|PubMed:10644526, ECO:0000269|PubMed:7560093};
DE AltName: Full=Proton pump;
DE AltName: Full=Sodium pump {ECO:0000250|UniProtKB:P54707};
GN Name=Atp12a; Synonyms=Atp1al1;
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 (ISOFORM LONG).
RC STRAIN=Sprague-Dawley; TISSUE=Colon;
RX PubMed=1320029; DOI=10.1016/s0021-9258(18)42276-4;
RA Crowson M.S., Shull G.E.;
RT "Isolation and characterization of a cDNA encoding the putative distal
RT colon H+,K(+)-ATPase. Similarity of deduced amino acid sequence to gastric
RT H+,K(+)-ATPase and Na+,K(+)-ATPase and mRNA expression in distal colon,
RT kidney, and uterus.";
RL J. Biol. Chem. 267:13740-13748(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS LONG AND SHORT).
RC STRAIN=Sprague-Dawley; TISSUE=Kidney;
RX PubMed=9446555; DOI=10.1074/jbc.273.5.2543;
RA Kone B.C., Higham S.C.;
RT "A novel N-terminal splice variant of the rat H+-K+-ATPase alpha2 subunit.
RT Cloning, functional expression, and renal adaptive response to chronic
RT hypokalemia.";
RL J. Biol. Chem. 273:2543-2552(1998).
RN [3]
RP PROTEIN SEQUENCE OF 779-785, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (JUL-2007) to UniProtKB.
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION,
RP AND TISSUE SPECIFICITY.
RX PubMed=7560093; DOI=10.1172/jci118247;
RA Lee J., Rajendran V.M., Mann A.S., Kashgarian M., Binder H.J.;
RT "Functional expression and segmental localization of rat colonic K-
RT adenosine triphosphatase.";
RL J. Clin. Invest. 96:2002-2008(1995).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=9872395; DOI=10.1016/s0014-5793(98)01483-5;
RA Pestov N.B., Romanova L.G., Korneenko T.V., Egorov M.V., Kostina M.B.,
RA Sverdlov V.E., Askari A., Shakhparonov M.I., Modyanov N.N.;
RT "Ouabain-sensitive H,K-ATPase: tissue-specific expression of the mammalian
RT genes encoding the catalytic alpha subunit.";
RL FEBS Lett. 440:320-324(1998).
RN [6]
RP INTERACTION WITH ATP1B3, AND SUBCELLULAR LOCATION.
RX PubMed=9950762; DOI=10.1152/ajpcell.1999.276.2.c350;
RA Sangan P., Kolla S.S., Rajendran V.M., Kashgarian M., Binder H.J.;
RT "Colonic H-K-ATPase beta-subunit: identification in apical membranes and
RT regulation by dietary K depletion.";
RL Am. J. Physiol. 276:C350-C360(1999).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=10644526; DOI=10.1152/ajpcell.2000.278.1.c182;
RA Sangan P., Thevananther S., Sangan S., Rajendran V.M., Binder H.J.;
RT "Colonic H-K-ATPase alpha- and beta-subunits express ouabain-insensitive H-
RT K-ATPase.";
RL Am. J. Physiol. 278:C182-C189(2000).
RN [8]
RP INTERACTION WITH ATP1B1, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=14749213; DOI=10.1152/ajpcell.00393.2003;
RA Pestov N.B., Korneenko T.V., Radkov R., Zhao H., Shakhparonov M.I.,
RA Modyanov N.N.;
RT "Identification of the beta-subunit for nongastric H-K-ATPase in rat
RT anterior prostate.";
RL Am. J. Physiol. 286:C1229-C1237(2004).
CC -!- FUNCTION: The catalytic subunit of a H(+)/K(+) ATPase and/or Na(+)/K(+)
CC ATPase pump which transports K(+) ions in exchange for Na(+) and/or
CC H(+) ions across the apical membrane of epithelial cells. Uses ATP as
CC an energy source to pump K(+) ions into the cell while transporting
CC Na(+) and/or H(+) ions to the extracellular compartment
CC (PubMed:10644526, PubMed:7560093). Involved in the maintenance of
CC electrolyte homeostasis through K(+) ion absorption in kidney and colon
CC (By similarity). In the airway epithelium, may play a primary role in
CC mucus acidification regulating its viscosity and clearance (By
CC similarity). {ECO:0000250|UniProtKB:P54707,
CC ECO:0000250|UniProtKB:Q9Z1W8, ECO:0000269|PubMed:10644526,
CC ECO:0000269|PubMed:7560093}.
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:10644526, ECO:0000269|PubMed:7560093};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22045;
CC Evidence={ECO:0000305|PubMed:10644526, ECO:0000305|PubMed:7560093};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + K(+)(out) + Na(+)(in) = ADP + H(+) + K(+)(in) +
CC Na(+)(out) + phosphate; Xref=Rhea:RHEA:18353, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29101, ChEBI:CHEBI:29103,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC EC=7.2.2.13; Evidence={ECO:0000269|PubMed:10644526,
CC ECO:0000269|PubMed:7560093};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18354;
CC Evidence={ECO:0000305|PubMed:10644526, ECO:0000305|PubMed:7560093};
CC -!- ACTIVITY REGULATION: Up-regulated by K(+) ions in a dose-dependent way.
CC {ECO:0000269|PubMed:10644526, ECO:0000269|PubMed:7560093}.
CC -!- SUBUNIT: The ATPase pump is composed of a catalytic alpha subunit and
CC an auxiliary non-catalytic beta subunit. The alpha subunit pairs with
CC the beta subunit of gastric H(+)/K(+) ATPase ATP4B or the beta subunit
CC of Na(+)/K(+) ATPases ATP1B1 and ATP1B3; this interaction is required
CC for the formation of a functionally active pump and its targeting at
CC the plasma membrane. {ECO:0000250|UniProtKB:P54707,
CC ECO:0000269|PubMed:14749213, ECO:0000269|PubMed:9950762}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:14749213, ECO:0000269|PubMed:7560093,
CC ECO:0000269|PubMed:9950762}; Multi-pass membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long; Synonyms=2a;
CC IsoId=P54708-1; Sequence=Displayed;
CC Name=Short; Synonyms=2b;
CC IsoId=P54708-2; Sequence=VSP_000414;
CC -!- TISSUE SPECIFICITY: Expressed at high levels in distal colon,
CC coagulating and preputial glands; at much lower levels in proximal
CC colon, kidney, uterus, brain, placenta and lung; and at trace levels in
CC heart and forestomach (PubMed:9872395). Expressed in distal colon
CC epithelium (at protein level) (PubMed:7560093). Expressed in anterior
CC prostate (at protein level) (PubMed:14749213).
CC {ECO:0000269|PubMed:14749213, ECO:0000269|PubMed:7560093,
CC ECO:0000269|PubMed:9872395}.
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; M90398; AAA40779.1; -; mRNA.
DR EMBL; U94911; AAB93900.1; -; Genomic_DNA.
DR EMBL; U94912; AAB93901.1; -; mRNA.
DR EMBL; U94913; AAB93902.1; -; mRNA.
DR PIR; A42895; A42895.
DR AlphaFoldDB; P54708; -.
DR SMR; P54708; -.
DR STRING; 10116.ENSRNOP00000028093; -.
DR TCDB; 3.A.3.1.4; the p-type atpase (p-atpase) superfamily.
DR iPTMnet; P54708; -.
DR PhosphoSitePlus; P54708; -.
DR jPOST; P54708; -.
DR PaxDb; P54708; -.
DR PRIDE; P54708; -.
DR UCSC; RGD:620569; rat. [P54708-1]
DR RGD; 620569; Atp12a.
DR eggNOG; KOG0203; Eukaryota.
DR InParanoid; P54708; -.
DR PhylomeDB; P54708; -.
DR Reactome; R-RNO-936837; Ion transport by P-type ATPases.
DR PRO; PR:P54708; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:RGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA: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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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; 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:0055075; P:potassium ion homeostasis; 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:0006885; P:regulation of pH; ISO:RGD.
DR GO; GO:0010038; P:response to metal ion; IDA:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IDA: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; IPR030318; Atp12a.
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; 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 PANTHER; PTHR43294:SF1; PTHR43294:SF1; 1.
DR Pfam; PF00689; Cation_ATPase_C; 1.
DR Pfam; PF00690; Cation_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 Alternative splicing; ATP-binding; Cell membrane;
KW Direct protein sequencing; Hydrogen ion transport; Ion transport;
KW Magnesium; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Potassium; Potassium transport; Reference proteome; Sodium;
KW Sodium transport; Translocase; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..1036
FT /note="Potassium-transporting ATPase alpha chain 2"
FT /id="PRO_0000046263"
FT TOPO_DOM 1..99
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 100..120
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 121..143
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 144..164
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 165..300
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 301..320
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 321..332
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 333..350
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 351..784
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 785..804
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 805..814
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 815..835
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 836..855
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 856..878
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 879..930
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 931..950
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 951..964
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 965..983
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 984..998
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 999..1019
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1020..1036
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..50
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 17..50
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 388
FT /note="4-aspartylphosphate intermediate"
FT /evidence="ECO:0000250"
FT BINDING 729
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 733
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT MOD_RES 955
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..108
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:9446555"
FT /id="VSP_000414"
SQ SEQUENCE 1036 AA; 114975 MW; 453918E65CD4813B CRC64;
MRRKTEIYSV ELNGTKDVKP ADQRDDKKFK GAKNKDLEPN KSHEKEELKK ELDLDDHRLS
NTELEQKYGT NIIQGLSSVR ATELLARDGP NTLTPPKQTP EIIKFLKQMV GGFSILLWIG
AALCWIAFVI QYVNNSASLD NVYLGAILVL VVILTGIFAY YQEAKSTNIM ASFSKMIPQQ
ALVIRDAEKK VISAEQLVVG DVVEIKGGDQ IPADIRLVFS QGCKVDNSSL TGESEPQARS
TEFTHENPLE TKNIGFYSTT CLEGTATGIV INTGDRTIIG RIASLASGVG SEKTPIAIEI
EHFVHIVAGV AVSIDIIFFI TAVCMKYYVL DAIIFLISII VANVPEGLLA TVTVTLSLTA
KRMAKKNCLV KNLEAVETLG STSIICSDKT GTLTQNRMTV AHLWFDNQIF VADTSENQTK
QAFDQSSGTW ASLSKIITLC NRAEFRPGQE SVPIMKRTVV GDASETALLK FSEVILGDVM
GIRKRNHKVA EIPFNSTNKF QLSIHETEDP NNKRFLVVMK GAPERILEKC STIMINGQEQ
PLDKSSADSF HTAYMELGGL GERVLGFCHL YLPAEQFPQS YIFDVDSVNF PTSNFCFVGL
LSMIDPPRST VPDAVSKCRS AGIKVIMVTG DHPITAKAIA KSVGIISANN ETVEDIAKRR
NIAVEQVNKR EAKAAVVTGM ELKDMTPEQL DELLTNYQEI VFARTSPQQK LIIVEGCQRQ
DAIVAVTGDG VNDSPALKKA DIGIAMGIAG SDAAKNAADM VLLDDNFASI VTGVEEGRLI
FDNLKKTIAY TLTKNIAELC PFLIYIVAGL PLPIGTITIL FIDLGTDIIP SIALAYEKAE
SDIMNRKPRH KKKDRLVNTQ LAIYSYLHIG LMQALGGFLV YFTVYAQQGF WPTSLINLRV
AWETDDINDL EDSYGQEWTR YQRKYLEWTG STAFFVAIMI QQIADLIIRK TRRNSIFQQG
LFRNKVIWVG IASQVIVALI LSYGLGSVPA LSFTMLRVQY WFVAVPHAIL IWVYDEMRKL
FIRLYPGSWW DKNMYY
