ID   AT12A_MOUSE             Reviewed;        1035 AA.
AC   Q9Z1W8; Q32MR8; Q8VHY2;
DT   23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 3.
DT   27-MAR-2024, entry version 182.
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:0000250|UniProtKB:P54707};
DE   AltName: Full=Non-gastric Na(+)/K(+) ATPase subunit alpha;
DE            EC=7.2.2.13 {ECO:0000250|UniProtKB:P54707};
DE   AltName: Full=Proton pump;
DE   AltName: Full=Sodium pump {ECO:0000250|UniProtKB:P54707};
GN   Name=Atp12a; Synonyms=Atp1al1;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=129/SvJ;
RX   PubMed=11729223; DOI=10.1681/asn.v12122554;
RA   Zhang W., Kuncewicz T., Higham S.C., Kone B.C.;
RT   "Structure, promoter analysis, and chromosomal localization of the murine
RT   H(+)/K(+)-ATPase alpha 2 subunit gene.";
RL   J. Am. Soc. Nephrol. 12:2554-2564(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [3]
RP   PROTEIN SEQUENCE OF 488-498; 624-636; 710-718 AND 755-785, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RC   STRAIN=C57BL/6J; TISSUE=Brain;
RA   Lubec G., Kang S.U.;
RL   Submitted (APR-2007) to UniProtKB.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 868-981, AND TISSUE SPECIFICITY.
RC   STRAIN=C57BL/6J; TISSUE=Skin;
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   [5]
RP   FUNCTION, TISSUE SPECIFICITY, INDUCTION BY DIET, AND DISRUPTION PHENOTYPE.
RX   PubMed=9449685; DOI=10.1172/jci1720;
RA   Meneton P., Schultheis P.J., Greeb J., Nieman M.L., Liu L.H., Clarke L.L.,
RA   Duffy J.J., Doetschman T., Lorenz J.N., Shull G.E.;
RT   "Increased sensitivity to K+ deprivation in colonic H,K-ATPase-deficient
RT   mice.";
RL   J. Clin. Invest. 101:536-542(1998).
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 (By
CC       similarity). Involved in the maintenance of electrolyte homeostasis
CC       through K(+) ion absorption in kidney and colon (PubMed:9449685). In
CC       the airway epithelium, may play a primary role in mucus acidification
CC       regulating its viscosity and clearance (By similarity).
CC       {ECO:0000250|UniProtKB:P54707, ECO:0000269|PubMed:9449685}.
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:0000250|UniProtKB:P54707};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22045;
CC         Evidence={ECO:0000250|UniProtKB:P54707};
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:0000250|UniProtKB:P54707};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18354;
CC         Evidence={ECO:0000250|UniProtKB:P54707};
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:0000250|UniProtKB:P54708}.
CC   -!- SUBCELLULAR LOCATION: Apical cell membrane
CC       {ECO:0000250|UniProtKB:P54707, ECO:0000250|UniProtKB:P54708}; Multi-
CC       pass membrane protein {ECO:0000255}.
CC   -!- TISSUE SPECIFICITY: Found in skin, kidney and distal colon.
CC       {ECO:0000269|PubMed:9449685, ECO:0000269|PubMed:9872395}.
CC   -!- INDUCTION: Up-regulated in kidney and down-regulated in colon in
CC       response to K(+) ion free diet. {ECO:0000269|PubMed:9449685}.
CC   -!- DISRUPTION PHENOTYPE: Mice are born at the expected Mendelian rate.
CC       {ECO:0000269|PubMed:9449685}.
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; AF350499; AAL68709.1; -; Genomic_DNA.
DR   EMBL; BC109011; AAI09012.1; -; mRNA.
DR   EMBL; AF100169; AAD03421.1; -; mRNA.
DR   CCDS; CCDS27148.1; -.
DR   RefSeq; NP_619593.2; NM_138652.2.
DR   AlphaFoldDB; Q9Z1W8; -.
DR   SMR; Q9Z1W8; -.
DR   BioGRID; 228640; 4.
DR   IntAct; Q9Z1W8; 3.
DR   STRING; 10090.ENSMUSP00000007340; -.
DR   iPTMnet; Q9Z1W8; -.
DR   PhosphoSitePlus; Q9Z1W8; -.
DR   EPD; Q9Z1W8; -.
DR   jPOST; Q9Z1W8; -.
DR   MaxQB; Q9Z1W8; -.
DR   PaxDb; 10090-ENSMUSP00000007340; -.
DR   PeptideAtlas; Q9Z1W8; -.
DR   ProteomicsDB; 277050; -.
DR   Antibodypedia; 22475; 151 antibodies from 28 providers.
DR   DNASU; 192113; -.
DR   Ensembl; ENSMUST00000007340.4; ENSMUSP00000007340.3; ENSMUSG00000022229.4.
DR   GeneID; 192113; -.
DR   KEGG; mmu:192113; -.
DR   UCSC; uc007ubw.2; mouse.
DR   AGR; MGI:1926943; -.
DR   CTD; 479; -.
DR   MGI; MGI:1926943; Atp12a.
DR   VEuPathDB; HostDB:ENSMUSG00000022229; -.
DR   eggNOG; KOG0203; Eukaryota.
DR   GeneTree; ENSGT00940000159259; -.
DR   HOGENOM; CLU_002360_4_1_1; -.
DR   InParanoid; Q9Z1W8; -.
DR   OMA; FQDWSTK; -.
DR   OrthoDB; 203629at2759; -.
DR   PhylomeDB; Q9Z1W8; -.
DR   TreeFam; TF312838; -.
DR   Reactome; R-MMU-936837; Ion transport by P-type ATPases.
DR   BioGRID-ORCS; 192113; 0 hits in 76 CRISPR screens.
DR   PRO; PR:Q9Z1W8; -.
DR   Proteomes; UP000000589; Chromosome 14.
DR   RNAct; Q9Z1W8; Protein.
DR   Bgee; ENSMUSG00000022229; Expressed in left colon and 32 other cell types or tissues.
DR   GO; GO:0015629; C:actin cytoskeleton; ISO:MGI.
DR   GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR   GO; GO:0016323; C:basolateral plasma membrane; IMP:MGI.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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; 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:0055075; P:potassium ion homeostasis; IMP:MGI.
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; IMP:MGI.
DR   GO; GO:0010038; P:response to metal ion; ISO:MGI.
DR   GO; GO:0014070; P:response to organic cyclic compound; ISO:MGI.
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; 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:SF1; POTASSIUM-TRANSPORTING ATPASE ALPHA CHAIN 2; 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; 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.
DR   Genevisible; Q9Z1W8; MM.
PE   1: Evidence at protein level;
KW   ATP-binding; Cell membrane; Direct protein sequencing;
KW   Hydrogen ion transport; Ion transport; Magnesium; Membrane; Metal-binding;
KW   Nucleotide-binding; Phosphoprotein; Potassium; Potassium transport;
KW   Reference proteome; Sodium; Sodium transport; Translocase; Transmembrane;
KW   Transmembrane helix; Transport.
FT   CHAIN           1..1035
FT                   /note="Potassium-transporting ATPase alpha chain 2"
FT                   /id="PRO_0000046261"
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..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          22..49
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        387
FT                   /note="4-aspartylphosphate intermediate"
FT                   /evidence="ECO:0000250"
FT   BINDING         728
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250"
FT   BINDING         732
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         954
FT                   /note="Phosphoserine; by PKA"
FT                   /evidence="ECO:0000250"
FT   CONFLICT        464
FT                   /note="E -> K (in Ref. 1; AAL68709)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        975
FT                   /note="I -> M (in Ref. 4; AAD03421)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        981
FT                   /note="S -> F (in Ref. 4; AAD03421)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1035 AA;  114727 MW;  BFB2C26D90305206 CRC64;
     MRRKTEIYSV ELNGTKDVEL ADQKDDKKFK GGKNKDSEPN KSQEEELKKE LDLDDHRLSN
     TDLEQKYGTN IIQGLSSIRA AELLARDGPN ALTPPKQTPE IIKFLKQMVG GFSILLWIGA
     ALCWIAYVIQ YVSSTASLDN VYLGAILVLV VILTGIFAYY QEAKSTNIMA SFSKMIPQQA
     LVIRDAEKKI IPAEQLVVGD VVEIKGGDQI PADIRLVFSQ GCKVDNSSLT GESEPQARST
     EFTHENPLET KNIGFYSTTC LEGTATGIVI NTGDRTIIGR IASLASGVGS EKTPIAIEIE
     HFVHIVAAVA VSVGVIFFIT AVCMKYYVLD AIIFLISIIV ANVPEGLLAT VTVTLSLTAK
     RMAKKNCLVK NLEAVETLGS TSIICSDKTG TLTQNRMTVA HLWFDNQIFV ADTSENQTKQ
     AFDQSSGTWA SLSKIITLCN RAEFRPGQES VPIMKRVVVG DASETALLKF SEVILGDVMD
     IRKRNHKVAE IPFNSTNKFQ LSIHETEDPN DKRFLMVMKG APERILEKCS TIMINGQEQP
     LDKSSADAFH TAYMELGGLG ERVLGFCHLY LPADKFPQSY TFDVDSINFP TSNLCFVGLL
     SMIDPPRSTV PDAVSKCRSA GIKVIMVTGD HPITAKAIAK SVGIISANNE TVEDIAKRRN
     IAVEQVNKRE AKAAVVTGME LKDMTPEQLD ELLINYQEIV FARTSPQQKL IIVEGCQRQD
     AVVAVTGDGV NDSPALKKAD IGIAMGIAGS DAAKNAADMV LLDDNFASIV TGVEEGRLIF
     DNLKKTIAYT LTKNIAELCP FLIYIVAGLP LPIGTITILF IDLGTDIIPS IALAYEKAES
     DIMNRKPRHK KKDRLVNKQL AIYSYLHIGL MQALGGFLVY FTVYAQQGFW PTSLINLRVS
     WETDDINDLE DSYGQEWTRY QRKYLEWTGS TAFFVAIMVQ QIADLIIRKT RRNSIFQQGL
     FRNKVIWVGI ISQIIVALVL SYGLGSVTAL SFTMLRAQYW FVAVPHAILI WVYDEMRKLF
     IRLYPGSWWD KNMYY
//