ID AT12A_HUMAN Reviewed; 1039 AA. AC P54707; Q13816; Q13817; Q16734; Q5W035; Q8N5U2; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 22-JUL-2008, sequence version 3. DT 27-MAR-2024, entry version 218. 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 {ECO:0000303|PubMed:16914892}; DE EC=7.2.2.19 {ECO:0000269|PubMed:11341842, ECO:0000269|PubMed:7485470, ECO:0000269|PubMed:8853415}; DE AltName: Full=Non-gastric Na(+)/K(+) ATPase subunit alpha {ECO:0000303|PubMed:9774385}; DE EC=7.2.2.13 {ECO:0000269|PubMed:11341842, ECO:0000269|PubMed:9774385}; DE AltName: Full=Proton pump; DE AltName: Full=Sodium pump {ECO:0000303|PubMed:9774385}; GN Name=ATP12A {ECO:0000303|PubMed:29391451, GN ECO:0000312|HGNC:HGNC:13816}; GN Synonyms=ATP1AL1 {ECO:0000303|PubMed:7485470}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Kidney, and Skin; RX PubMed=8045293; DOI=10.1016/0014-5793(94)00655-5; RA Grishin A.V., Sverdlov V.E., Kostina M.B., Modyanov N.N.; RT "Cloning and characterization of the entire cDNA encoded by ATP1AL1 -- a RT member of the human Na,K/H,K-ATPase gene family."; RL FEBS Lett. 349:144-150(1994). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=8838794; DOI=10.1006/geno.1996.0125; RA Sverdlov V.E., Kostina M.B., Modyanov N.N.; RT "Genomic organization of the human ATP1AL1 gene encoding a ouabain- RT sensitive H,K-ATPase."; RL Genomics 32:317-327(1996). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Trachea; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057823; DOI=10.1038/nature02379; RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L., RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., RA Frankish A.G., Frankland J., French L., Garner P., Garnett J., RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., RA Rogers J., Ross M.T.; RT "The DNA sequence and analysis of human chromosome 13."; RL Nature 428:522-528(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; 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 [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 77-348 AND 681-780. RX PubMed=1847115; DOI=10.1016/0014-5793(91)80091-g; RA Modyanov N.N., Petrukhin K.E., Sverdlov V.E., Grishin A.V., Orlova M.Y., RA Kostina M.B., Makarevich O.I., Broude N.E., Monastyrskaya G.S., RA Sverdlov E.D.; RT "The family of human Na,K-ATPase genes. ATP1AL1 gene is transcriptionally RT competent and probably encodes the related ion transport ATPase."; RL FEBS Lett. 278:91-94(1991). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 183-253. RX PubMed=3035563; DOI=10.1073/pnas.84.12.4039; RA Shull M.M., Lingrel J.B.; RT "Multiple genes encode the human Na+,K+-ATPase catalytic subunit."; RL Proc. Natl. Acad. Sci. U.S.A. 84:4039-4043(1987). RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 357-412. RX PubMed=3036582; DOI=10.1016/0014-5793(87)80677-4; RA Sverdlov E.D., Monastyrskaya G.S., Broude N.E., Ushkaryov Y.A., RA Allikmets R.L., Melkov A.M., Smirnov Y.V., Malyshev I.V., Dulubova I.E., RA Petrukhin K.E., Gryshin A.V., Kiyatkin N.I., Kostina M.B., Sverdlov V.E., RA Modyanov N.N., Ovchinnikov Y.A.; RT "The family of human Na+,K+-ATPase genes. No less than five genes and/or RT pseudogenes related to the alpha-subunit."; RL FEBS Lett. 217:275-278(1987). RN [10] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND SUBUNIT. RX PubMed=7485470; DOI=10.1152/ajpcell.1995.269.4.c992; RA Modyanov N.N., Mathews P.M., Grishin A.V., Beguin P., Beggah A.T., RA Rossier B.C., Horisberger J.D., Geering K.; RT "Human ATP1AL1 gene encodes a ouabain-sensitive H-K-ATPase."; RL Am. J. Physiol. 269:C992-C997(1995). RN [11] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND SUBUNIT. RX PubMed=8853415; DOI=10.1152/ajprenal.1996.271.3.f539; RA Grishin A.V., Bevensee M.O., Modyanov N.N., Rajendran V., Boron W.F., RA Caplan M.J.; RT "Functional expression of the cDNA encoded by the human ATP1AL1 gene."; RL Am. J. Physiol. 271:F539-F551(1996). RN [12] 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 [13] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=9774385; DOI=10.1074/jbc.273.43.27772; RA Grishin A.V., Caplan M.J.; RT "ATP1AL1, a member of the non-gastric H,K-ATPase family, functions as a RT sodium pump."; RL J. Biol. Chem. 273:27772-27778(1998). RN [14] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL RP PROPERTIES. RX PubMed=11341842; DOI=10.1021/bi010191y; RA Adams G., Tillekeratne M., Yu C., Pestov N.B., Modyanov N.N.; RT "Catalytic function of nongastric H,K-ATPase expressed in Sf-21 insect RT cells."; RL Biochemistry 40:5765-5776(2001). RN [15] RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-329. RX PubMed=16914892; DOI=10.1159/000095169; RA Lerner M., Lemke D., Bertram H., Schillers H., Oberleithner H., RA Caplan M.J., Reinhardt J.; RT "An extracellular loop of the human non-gastric H,K-ATPase alpha-subunit is RT involved in apical plasma membrane polarization."; RL Cell. Physiol. Biochem. 18:75-84(2006). RN [16] RP TISSUE SPECIFICITY. RX PubMed=22179016; DOI=10.1159/000335860; RA Streif D., Iglseder E., Hauser-Kronberger C., Fink K.G., Jakab M., RA Ritter M.; RT "Expression of the non-gastric H+/K+ ATPase ATP12A in normal and RT pathological human prostate tissue."; RL Cell. Physiol. Biochem. 28:1287-1294(2011). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [18] RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION BY IL13. RX PubMed=29391451; DOI=10.1038/s41598-018-20444-8; RA Lennox A.T., Coburn S.L., Leech J.A., Heidrich E.M., Kleyman T.R., RA Wenzel S.E., Pilewski J.M., Corcoran T.E., Myerburg M.M.; RT "ATP12A promotes mucus dysfunction during Type 2 airway inflammation."; RL Sci. Rep. 8:2109-2109(2018). 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:9774385, PubMed:7485470, PubMed:8853415, PubMed:11341842). CC Involved in the maintenance of electrolyte homeostasis through K(+) ion CC absorption in kidney and colon (By similarity). In the airway CC epithelium, may play a primary role in mucus acidification regulating CC its viscosity and clearance (PubMed:29391451). CC {ECO:0000250|UniProtKB:Q9Z1W8, ECO:0000269|PubMed:11341842, CC ECO:0000269|PubMed:29391451, ECO:0000269|PubMed:7485470, CC ECO:0000269|PubMed:8853415, ECO:0000269|PubMed:9774385}. 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:11341842, ECO:0000269|PubMed:7485470, CC ECO:0000269|PubMed:8853415}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22045; CC Evidence={ECO:0000305|PubMed:11341842, ECO:0000305|PubMed:7485470, CC ECO:0000305|PubMed:8853415}; 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:11341842, CC ECO:0000269|PubMed:9774385}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18354; CC Evidence={ECO:0000305|PubMed:11341842, ECO:0000305|PubMed:9774385}; CC -!- ACTIVITY REGULATION: The ATPase activity is regulated by monovalent CC cations and pH. Up-regulated by K(+) ions in a dose-dependent way. CC Down-regulated by Na(+) ions (PubMed:11341842). Inhibited by CC Na(+)/K(+)-ATPase inhibitor ouabain and H(+)/K(+)-ATPase inhibitor SCH- CC 28080 with an intermediate sensitivity to completely resistant CC Na(+)/K(+)-ATPases and highly sensitive H(+)/K(+)-ATPases CC (PubMed:7485470, PubMed:8853415, PubMed:11341842). CC {ECO:0000269|PubMed:11341842, ECO:0000269|PubMed:7485470, CC ECO:0000269|PubMed:8853415}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC pH dependence: CC Optimum pH is 7.2-7.8. {ECO:0000269|PubMed:11341842}; 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:P54708, CC ECO:0000269|PubMed:7485470, ECO:0000269|PubMed:8853415}. CC -!- SUBCELLULAR LOCATION: Apical cell membrane CC {ECO:0000269|PubMed:16914892}; Multi-pass membrane protein CC {ECO:0000255}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P54707-1; Sequence=Displayed; CC Name=2; CC IsoId=P54707-2; Sequence=VSP_034640; CC -!- TISSUE SPECIFICITY: Expressed in airway epithelial cells (at protein CC level) (PubMed:29391451). Found in skin and kidney. Detected in CC prostate basal cells (at protein level). Expression is increased in CC benign prostate hyperplasia and tumor tissues (at protein level). CC {ECO:0000269|PubMed:22179016, ECO:0000269|PubMed:29391451, CC ECO:0000269|PubMed:9872395}. CC -!- INDUCTION: Up-regulated by inflammatory cytokine IL13. CC {ECO:0000269|PubMed:29391451}. 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; U02076; AAB37755.1; -; mRNA. DR EMBL; L42563; AAC37589.2; -; Genomic_DNA. DR EMBL; L42558; AAC37589.2; JOINED; Genomic_DNA. DR EMBL; L42559; AAC37589.2; JOINED; Genomic_DNA. DR EMBL; L42565; AAC37589.2; JOINED; Genomic_DNA. DR EMBL; L42566; AAC37589.2; JOINED; Genomic_DNA. DR EMBL; L42567; AAC37589.2; JOINED; Genomic_DNA. DR EMBL; L42560; AAC37589.2; JOINED; Genomic_DNA. DR EMBL; L42561; AAC37589.2; JOINED; Genomic_DNA. DR EMBL; L42568; AAC37589.2; JOINED; Genomic_DNA. DR EMBL; L42562; AAC37589.2; JOINED; Genomic_DNA. DR EMBL; L42569; AAC37589.2; JOINED; Genomic_DNA. DR EMBL; AK292968; BAF85657.1; -; mRNA. DR EMBL; AL157364; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471075; EAX08346.1; -; Genomic_DNA. DR EMBL; CH471075; EAX08345.1; -; Genomic_DNA. DR EMBL; BC031609; AAH31609.1; -; mRNA. DR EMBL; X69823; CAA49477.1; -; Genomic_DNA. DR EMBL; X69824; CAA49478.1; -; Genomic_DNA. DR EMBL; M16797; AAA51802.1; -; mRNA. DR EMBL; M27574; AAA35576.1; -; Genomic_DNA. DR CCDS; CCDS31948.1; -. [P54707-1] DR CCDS; CCDS53858.1; -. [P54707-2] DR PIR; A26641; A26641. DR PIR; D27795; D27795. DR PIR; E27397; E27397. DR PIR; I38401; I38401. DR PIR; S13028; S13028. DR PIR; S31504; S31504. DR RefSeq; NP_001172014.1; NM_001185085.1. [P54707-2] DR RefSeq; NP_001667.4; NM_001676.5. [P54707-1] DR AlphaFoldDB; P54707; -. DR SMR; P54707; -. DR BioGRID; 106969; 216. DR IntAct; P54707; 58. DR STRING; 9606.ENSP00000218548; -. DR BindingDB; P54707; -. DR ChEMBL; CHEMBL2933; -. DR TCDB; 3.A.3.1.13; the p-type atpase (p-atpase) superfamily. DR iPTMnet; P54707; -. DR PhosphoSitePlus; P54707; -. DR SwissPalm; P54707; -. DR BioMuta; ATP12A; -. DR DMDM; 212287925; -. DR EPD; P54707; -. DR jPOST; P54707; -. DR MassIVE; P54707; -. DR MaxQB; P54707; -. DR PaxDb; 9606-ENSP00000218548; -. DR PeptideAtlas; P54707; -. DR ProteomicsDB; 56695; -. [P54707-1] DR ProteomicsDB; 56696; -. [P54707-2] DR Antibodypedia; 22475; 151 antibodies from 28 providers. DR DNASU; 479; -. DR Ensembl; ENST00000218548.10; ENSP00000218548.6; ENSG00000075673.12. [P54707-2] DR Ensembl; ENST00000381946.5; ENSP00000371372.3; ENSG00000075673.12. [P54707-1] DR GeneID; 479; -. DR KEGG; hsa:479; -. DR MANE-Select; ENST00000381946.5; ENSP00000371372.3; NM_001676.7; NP_001667.4. DR UCSC; uc001upp.4; human. [P54707-1] DR AGR; HGNC:13816; -. DR CTD; 479; -. DR DisGeNET; 479; -. DR GeneCards; ATP12A; -. DR HGNC; HGNC:13816; ATP12A. DR HPA; ENSG00000075673; Group enriched (esophagus, kidney, lymphoid tissue, placenta, skin). DR MIM; 182360; gene. DR neXtProt; NX_P54707; -. DR OpenTargets; ENSG00000075673; -. DR PharmGKB; PA25104; -. DR VEuPathDB; HostDB:ENSG00000075673; -. DR eggNOG; KOG0203; Eukaryota. DR GeneTree; ENSGT00940000159259; -. DR HOGENOM; CLU_002360_4_3_1; -. DR InParanoid; P54707; -. DR OMA; FQDWSTK; -. DR OrthoDB; 203629at2759; -. DR PhylomeDB; P54707; -. DR TreeFam; TF312838; -. DR BRENDA; 7.2.2.19; 2681. DR PathwayCommons; P54707; -. DR Reactome; R-HSA-936837; Ion transport by P-type ATPases. DR SignaLink; P54707; -. DR BioGRID-ORCS; 479; 8 hits in 1144 CRISPR screens. DR ChiTaRS; ATP12A; human. DR GeneWiki; ATP12A; -. DR GenomeRNAi; 479; -. DR Pharos; P54707; Tchem. DR PRO; PR:P54707; -. DR Proteomes; UP000005640; Chromosome 13. DR RNAct; P54707; Protein. DR Bgee; ENSG00000075673; Expressed in trachea and 72 other cell types or tissues. DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA. DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB. DR GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0005889; C:potassium:proton exchanging ATPase complex; TAS:ProtInc. 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; IDA:UniProtKB. DR GO; GO:0005391; F:P-type sodium:potassium-exchanging transporter activity; IDA: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: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; IEA:Ensembl. 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; SFLDS00003; Haloacid_Dehalogenase; 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; P54707; HS. PE 1: Evidence at protein 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..1039 FT /note="Potassium-transporting ATPase alpha chain 2" FT /id="PRO_0000046260" FT TOPO_DOM 1..102 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 103..123 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 124..146 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 147..167 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 168..303 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 304..323 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 324..335 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 336..353 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 354..787 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 788..807 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 808..817 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 818..838 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 839..858 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 859..881 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 882..933 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 934..953 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 954..967 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 968..986 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 987..1001 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 1002..1022 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1023..1039 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT ACT_SITE 391 FT /note="4-aspartylphosphate intermediate" FT /evidence="ECO:0000250" FT BINDING 732 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250" FT BINDING 736 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250" FT MOD_RES 958 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000250" FT VAR_SEQ 266 FT /note="E -> EASTSPV (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_034640" FT VARIANT 863 FT /note="P -> L (in dbSNP:rs2289909)" FT /id="VAR_020186" FT MUTAGEN 329 FT /note="K->E: Abolishes targeting to the apical plasma FT membrane." FT /evidence="ECO:0000269|PubMed:16914892" FT CONFLICT 3 FT /note="Q -> QLFQ (in Ref. 2; AAC37589)" FT /evidence="ECO:0000305" FT CONFLICT 145 FT /note="V -> VRLWGVQV (in Ref. 7; CAA49477)" FT /evidence="ECO:0000305" FT CONFLICT 225..227 FT /note="Missing (in Ref. 7; CAA49477)" FT /evidence="ECO:0000305" FT CONFLICT 266 FT /note="E -> V (in Ref. 7; CAA49477)" FT /evidence="ECO:0000305" FT CONFLICT 382 FT /note="L -> P (in Ref. 9; AAA35576)" FT /evidence="ECO:0000305" FT CONFLICT 724..727 FT /note="DAVV -> VGGQ (in Ref. 7; CAA49478)" FT /evidence="ECO:0000305" FT CONFLICT 772..773 FT /note="SI -> LH (in Ref. 7; CAA49478)" FT /evidence="ECO:0000305" SQ SEQUENCE 1039 AA; 115511 MW; C906897E11FA406C CRC64; MHQKTPEIYS VELSGTKDIV KTDKGDGKEK YRGLKNNCLE LKKKNHKEEF QKELHLDDHK LSNRELEEKY GTDIIMGLSS TRAAELLARD GPNSLTPPKQ TPEIVKFLKQ MVGGFSILLW VGAFLCWIAY GIQYSSDKSA SLNNVYLGCV LGLVVILTGI FAYYQEAKST NIMSSFNKMI PQQALVIRDS EKKTIPSEQL VVGDIVEVKG GDQIPADIRV LSSQGCRVDN SSLTGESEPQ PRSSEFTHEN PLETKNICFY STTCLEGTVT GMVINTGDRT IIGHIASLAS GVGNEKTPIA IEIEHFVHIV AGVAVSIGIL FFIIAVSLKY QVLDSIIFLI GIIVANVPEG LLATVTVTLS LTAKRMAKKN CLVKNLEAVE TLGSTSIICS DKTGTLTQNR MTVAHLWFDN QIFVADTSED HSNQVFDQSS RTWASLSKII TLCNRAEFKP GQENVPIMKK AVIGDASETA LLKFSEVILG DVMEIRKRNR KVAEIPFNST NKFQLSIHEM DDPHGKRFLM VMKGAPERIL EKCSTIMING EEHPLDKSTA KTFHTAYMEL GGLGERVLGF CHLYLPADEF PETYSFDIDA MNFPTSNLCF VGLLSMIDPP RSTVPDAVTK CRSAGIKVIM VTGDHPITAK AIAKSVGIIS ANSETVEDIA HRLNIAVEQV NKRDAKAAVV TGMELKDMSS EQLDEILANY QEIVFARTSP QQKLIIVEGC QRQDAVVAVT GDGVNDSPAL KKADIGIAMG IAGSDAAKNA ADMVLLDDNF ASIVTGVEEG RLIFDNLKKT IAYSLTKNIA ELCPFLIYII VGLPLPIGTI TILFIDLGTD IIPSIALAYE KAESDIMNRK PRHKNKDRLV NQPLAVYSYL HIGLMQALGA FLVYFTVYAQ EGFLPRTLIN LRVEWEKDYV NDLKDSYGQE WTRYQREYLE WTGYTAFFVG ILVQQIADLI IRKTRRNSIF QQGLFRNKVI WVGITSQIII GLILSYGLGS VTALSFTMLR AQYWFVAVPH AILIWVYDEV RKLFIRLYPG SWWDKNMYY //