AT12A_RABIT
ID AT12A_RABIT Reviewed; 1094 AA.
AC Q9TV52; Q9TSI2; Q9TV53;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Potassium-transporting ATPase alpha chain 2;
DE AltName: Full=HK alpha 2 {ECO:0000303|PubMed:9950954};
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 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] (ISOFORMS LONG AND SHORT).
RC STRAIN=New Zealand white; TISSUE=Kidney cortex;
RX PubMed=9950954; DOI=10.1152/ajprenal.1999.276.2.f237;
RA Campbell W.G., Weiner I.D., Wingo C.S., Cain B.D.;
RT "H-K-ATPase in the RCCT-28A rabbit cortical collecting duct cell line.";
RL Am. J. Physiol. 276:F237-F245(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
RC TISSUE=Renal collecting duct;
RX PubMed=10469371; DOI=10.1046/j.1523-1755.1999.00638.x;
RA Fejes-Toth G., Naray-Fejes-Toth A., Velazquez H.;
RT "Intrarenal distribution of the colonic H,K-ATPase mRNA in rabbit.";
RL Kidney Int. 56:1029-1036(1999).
RN [3]
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).
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 (By similarity). In the
CC airway epithelium, may play a primary role in mucus acidification
CC regulating its viscosity and clearance (By similarity).
CC {ECO:0000250|UniProtKB:P54707, ECO:0000250|UniProtKB:Q9Z1W8}.
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 X(+)/K(+) ATPase pump is composed of a catalytic alpha
CC subunit and an auxiliary non-catalytic beta subunit. The alpha subunit
CC pairs with the beta subunit of gastric H(+)/K(+) ATPase ATP4B or the
CC beta subunit of Na(+)/K(+) ATPases ATP1B1 and ATP1B3; this interaction
CC is required for the formation of a functionally active pump and its
CC targeting at 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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long; Synonyms=2c;
CC IsoId=Q9TV52-1; Sequence=Displayed;
CC Name=Short; Synonyms=2a;
CC IsoId=Q9TV52-2; Sequence=VSP_000413;
CC -!- TISSUE SPECIFICITY: Found in the skin, kidney, distal colon and brain.
CC In the kidney it is found in the connecting tubule, cortical collecting
CC duct and outer medullary collecting duct while in the brain it is
CC specific to choroid plexus and cortex. {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}.
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DR EMBL; AF023128; AAB80941.1; -; mRNA.
DR EMBL; AF023129; AAC13887.1; -; mRNA.
DR EMBL; AF106063; AAD11800.1; -; mRNA.
DR RefSeq; NP_001075496.1; NM_001082027.1. [Q9TV52-1]
DR AlphaFoldDB; Q9TV52; -.
DR SMR; Q9TV52; -.
DR STRING; 9986.ENSOCUP00000006379; -.
DR PRIDE; Q9TV52; -.
DR GeneID; 100008669; -.
DR KEGG; ocu:100008669; -.
DR CTD; 479; -.
DR eggNOG; KOG0203; Eukaryota.
DR InParanoid; Q9TV52; -.
DR OrthoDB; 388324at2759; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
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: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 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 2: Evidence at transcript level;
KW Alternative splicing; ATP-binding; Cell membrane; Hydrogen ion transport;
KW Ion transport; Magnesium; Membrane; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Potassium; Potassium transport; Reference proteome; Sodium;
KW Sodium transport; Translocase; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..1094
FT /note="Potassium-transporting ATPase alpha chain 2"
FT /id="PRO_0000046262"
FT TOPO_DOM 56..157
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 158..178
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 179..201
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 202..222
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 223..358
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 359..378
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 379..390
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 391..408
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 409..842
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 843..862
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 863..872
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 873..893
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 894..913
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 914..936
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 937..988
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 989..1008
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1009..1022
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1023..1041
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1042..1056
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1057..1077
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1078..1094
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 286..305
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 8..23
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 446
FT /note="4-aspartylphosphate intermediate"
FT /evidence="ECO:0000250"
FT BINDING 787
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 791
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT MOD_RES 1013
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..63
FT /note="MAGGAHRADRATGEERKEGGGRWRAPHSPSPPGPRGCPVPLKAAAQSLCRKP
FT TWGRYCTLLLF -> MR (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:10469371,
FT ECO:0000303|PubMed:9950954"
FT /id="VSP_000413"
FT CONFLICT 300
FT /note="G -> E (in Ref. 2; AAD11800)"
FT /evidence="ECO:0000305"
FT CONFLICT 421
FT /note="V -> M (in Ref. 2; AAD11800)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1094 AA; 120966 MW; 2A8926D8135AE92C CRC64;
MAGGAHRADR ATGEERKEGG GRWRAPHSPS PPGPRGCPVP LKAAAQSLCR KPTWGRYCTL
LLFQRKLEIY SVELHAATDI KKKEGRDGKK DNDLELKRNQ QKEELKKELD LDDHKLSNKE
LETKYGTDII RGLSSTRAAE LLAQNGPNAL TPPKQTPEII KFLKQMVGGF SILLWVGAVL
CWIAFGIQYV SNPSASLDRV YLGTVLAVVV ILTGIFAYYQ EAKSTNIMAS FCKMIPQQAV
VIRDSEKKVI PAEQLVVGDI VEIKGGDQIP ADIRLLSAQG CKVDNSSLTG ESEPQSRSSG
FTHENPLETK NITFYSTTCL EGTATGMVIN TGDRTIIGRI ASLASGVGNE KTPIAIEIEH
FVHIVAGVAV SVGILFFIIA VCMKYHVLDA IIFLIAIIVA NVPEGLLATV TVALSLTAKR
VAKKNCLVKN LEAVETLGST SIICSDKTGT LTQNRMTVAH LWFDNQIFVA DTSEDNLNQG
FDQSSGTWTS LSKIIALCNR AEFKPGEESV PIMKRVVVGD ASETALLKFS EVILGDVMEI
RKRNHKVVEI PFNSTNKFQL SIHQTEDPND KRFLLVMKGA PERILEKCST IMINGKEQPL
DKSMAQAFHT AYMELGGLGE RVLGFCHFYL PADEFPETYS FDSESMNFPT SNLCFVGLLS
MIDPPRSTVP DAVTKCRSAG IKVIMVTGDH PITAKAIAKS VGIISANSET VEDIAKRCNI
AVEQVNKRDA KAAVVTGMEL KDMSPEQLDE LLANYPEIVF ARTSPQQKLI IVEGCQRQDA
VVAVTGDGVN DSPALKKADI GVAMGITGSD AAKNAADMIL LDDNFSSIVT GVEEGRLIFD
NLKKTIAYTL TKNIAELCPF LIYIILGLPL PIGTITLLFI DLGTDIIPSI ALAYEKAESD
IMNRKPRHKK KDRLVNQQLA VYSYLHIGLM QALGAFLVYF TVYAQQGFRP TSLFHLRIAW
DSDHLNDLED NYGQEWTSYQ RQYLEWTGYT AFFVGIMVQQ IADLIIRKTR KNSIFKQGLF
RNKVIWVGIA SQIIVALLLS YGLGSITALN FTMLKAQYWF VAVPHAILIW VYDEMRKLFI
RLYPGSWWDK NMYY
