AT12A_MOUSE
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 03-AUG-2022, entry version 173.
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; Q9Z1W8; -.
DR PeptideAtlas; Q9Z1W8; -.
DR PRIDE; Q9Z1W8; -.
DR ProteomicsDB; 277050; -.
DR Antibodypedia; 22475; 139 antibodies from 28 providers.
DR DNASU; 192113; -.
DR Ensembl; ENSMUST00000007340; ENSMUSP00000007340; ENSMUSG00000022229.
DR GeneID; 192113; -.
DR KEGG; mmu:192113; -.
DR UCSC; uc007ubw.2; mouse.
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; NNVMGCV; -.
DR OrthoDB; 388324at2759; -.
DR PhylomeDB; Q9Z1W8; -.
DR TreeFam; TF312838; -.
DR Reactome; R-MMU-936837; Ion transport by P-type ATPases.
DR BioGRID-ORCS; 192113; 0 hits in 71 CRISPR screens.
DR PRO; PR:Q9Z1W8; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q9Z1W8; protein.
DR Bgee; ENSMUSG00000022229; Expressed in left colon and 30 other tissues.
DR Genevisible; Q9Z1W8; MM.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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: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; ISS:UniProtKB.
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; 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; -; 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 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
