Full text data of ATP12A
ATP12A
(ATP1AL1)
[Confidence: low (only semi-automatic identification from reviews)]
Potassium-transporting ATPase alpha chain 2; 3.6.3.10 (Non-gastric H(+)/K(+) ATPase subunit alpha; Proton pump)
Potassium-transporting ATPase alpha chain 2; 3.6.3.10 (Non-gastric H(+)/K(+) ATPase subunit alpha; Proton pump)
UniProt
P54707
ID AT12A_HUMAN Reviewed; 1039 AA.
AC P54707; Q13816; Q13817; Q16734; Q5W035; Q8N5U2;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 22-JUL-2008, sequence version 3.
DT 22-JAN-2014, entry version 144.
DE RecName: Full=Potassium-transporting ATPase alpha chain 2;
DE EC=3.6.3.10;
DE AltName: Full=Non-gastric H(+)/K(+) ATPase subunit alpha;
DE AltName: Full=Proton pump;
GN Name=ATP12A; Synonyms=ATP1AL1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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 --
RT a 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T.,
RA Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R.,
RA Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S.,
RA 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.,
RA Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J.,
RA Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E.,
RA Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L.,
RA Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J.,
RA Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S.,
RA Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J.,
RA Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M.,
RA King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A.,
RA Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S.,
RA 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.,
RA Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S.,
RA Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A.,
RA Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L.,
RA Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M.,
RA Hubbard T., Sulston J.E., Beck S., Bentley D.R., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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.,
RA Orlova M.Y., Kostina M.B., Makarevich O.I., Broude N.E.,
RA Monastyrskaya G.S., Sverdlov E.D.;
RT "The family of human Na,K-ATPase genes. ATP1AL1 gene is
RT transcriptionally competent and probably encodes the related ion
RT 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.,
RA Dulubova I.E., Petrukhin K.E., Gryshin A.V., Kiyatkin N.I.,
RA Kostina M.B., Sverdlov V.E., Modyanov N.N., Ovchinnikov Y.A.;
RT "The family of human Na+,K+-ATPase genes. No less than five genes
RT and/or pseudogenes related to the alpha-subunit.";
RL FEBS Lett. 217:275-278(1987).
RN [10]
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
RT mammalian genes encoding the catalytic alpha subunit.";
RL FEBS Lett. 440:320-324(1998).
RN [11]
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).
CC -!- FUNCTION: Catalyzes the hydrolysis of ATP coupled with the
CC exchange of H(+) and K(+) ions across the plasma membrane.
CC Responsible for potassium absorption in various tissues.
CC -!- CATALYTIC ACTIVITY: ATP + H(2)O + H(+)(In) + K(+)(Out) = ADP +
CC phosphate + H(+)(Out) + K(+)(In).
CC -!- SUBUNIT: Composed of two subunits: alpha (catalytic) and beta.
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
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 Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Found in skin and kidney. Detected in prostate
CC basal cells (at protein level). Expression is increased in benign
CC prostate hyperplasia and tumor tissues (at protein level).
CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type)
CC (TC 3.A.3) family. Type IIC subfamily.
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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; CAH72440.1; -; 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 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.
DR RefSeq; NP_001667.4; NM_001676.5.
DR UniGene; Hs.147111; -.
DR ProteinModelPortal; P54707; -.
DR SMR; P54707; 42-1039.
DR IntAct; P54707; 4.
DR MINT; MINT-4656898; -.
DR STRING; 9606.ENSP00000371372; -.
DR BindingDB; P54707; -.
DR ChEMBL; CHEMBL2933; -.
DR DrugBank; DB00736; Esomeprazole.
DR DrugBank; DB00213; Pantoprazole.
DR PhosphoSite; P54707; -.
DR DMDM; 212287925; -.
DR PaxDb; P54707; -.
DR PRIDE; P54707; -.
DR DNASU; 479; -.
DR Ensembl; ENST00000218548; ENSP00000218548; ENSG00000075673.
DR Ensembl; ENST00000381946; ENSP00000371372; ENSG00000075673.
DR GeneID; 479; -.
DR KEGG; hsa:479; -.
DR UCSC; uc001upp.3; human.
DR CTD; 479; -.
DR GeneCards; GC13P025254; -.
DR HGNC; HGNC:13816; ATP12A.
DR HPA; HPA039526; -.
DR MIM; 182360; gene.
DR neXtProt; NX_P54707; -.
DR PharmGKB; PA25104; -.
DR eggNOG; COG0474; -.
DR HOGENOM; HOG000265622; -.
DR HOVERGEN; HBG004298; -.
DR KO; K01544; -.
DR OMA; NLRVEWE; -.
DR OrthoDB; EOG7327N0; -.
DR BRENDA; 3.6.3.10; 2681.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR GeneWiki; ATP12A; -.
DR GenomeRNAi; 479; -.
DR NextBio; 1985; -.
DR PRO; PR:P54707; -.
DR Bgee; P54707; -.
DR CleanEx; HS_ATP12A; -.
DR Genevestigator; P54707; -.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl.
DR GO; GO:0005889; C:hydrogen:potassium-exchanging ATPase complex; TAS:ProtInc.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008900; F:hydrogen:potassium-exchanging ATPase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006754; P:ATP biosynthetic process; IEA:InterPro.
DR GO; GO:0034220; P:ion transmembrane transport; TAS:Reactome.
DR GO; GO:0055075; P:potassium ion homeostasis; IEA:Ensembl.
DR GO; GO:0006885; P:regulation of pH; IEA:Ensembl.
DR Gene3D; 1.20.1110.10; -; 2.
DR Gene3D; 2.70.150.10; -; 2.
DR Gene3D; 3.40.1110.10; -; 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_domN.
DR InterPro; IPR005775; ATPase_P-typ_Na/K_IIC.
DR InterPro; IPR018303; ATPase_P-typ_P_site.
DR InterPro; IPR023298; ATPase_P-typ_TM_dom.
DR InterPro; IPR008250; ATPase_P-typ_transduc_dom_A.
DR InterPro; IPR001757; Cation_transp_P_typ_ATPase.
DR InterPro; IPR023214; HAD-like_dom.
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 SMART; SM00831; Cation_ATPase_N; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR SUPFAM; SSF81660; SSF81660; 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; Complete proteome;
KW Hydrogen ion transport; Hydrolase; Ion transport; Magnesium; Membrane;
KW Metal-binding; Nucleotide-binding; Phosphoprotein; Polymorphism;
KW Potassium; Potassium transport; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1 1039 Potassium-transporting ATPase alpha chain
FT 2.
FT /FTId=PRO_0000046260.
FT TOPO_DOM 1 102 Cytoplasmic (Potential).
FT TRANSMEM 103 123 Helical; (Potential).
FT TOPO_DOM 124 146 Lumenal (Potential).
FT TRANSMEM 147 167 Helical; (Potential).
FT TOPO_DOM 168 303 Cytoplasmic (Potential).
FT TRANSMEM 304 323 Helical; (Potential).
FT TOPO_DOM 324 335 Lumenal (Potential).
FT TRANSMEM 336 353 Helical; (Potential).
FT TOPO_DOM 354 787 Cytoplasmic (Potential).
FT TRANSMEM 788 807 Helical; (Potential).
FT TOPO_DOM 808 817 Lumenal (Potential).
FT TRANSMEM 818 838 Helical; (Potential).
FT TOPO_DOM 839 858 Cytoplasmic (Potential).
FT TRANSMEM 859 881 Helical; (Potential).
FT TOPO_DOM 882 933 Lumenal (Potential).
FT TRANSMEM 934 953 Helical; (Potential).
FT TOPO_DOM 954 967 Cytoplasmic (Potential).
FT TRANSMEM 968 986 Helical; (Potential).
FT TOPO_DOM 987 1001 Lumenal (Potential).
FT TRANSMEM 1002 1022 Helical; (Potential).
FT TOPO_DOM 1023 1039 Cytoplasmic (Potential).
FT ACT_SITE 391 391 4-aspartylphosphate intermediate (By
FT similarity).
FT METAL 732 732 Magnesium (By similarity).
FT METAL 736 736 Magnesium (By similarity).
FT MOD_RES 958 958 Phosphoserine; by PKA (By similarity).
FT VAR_SEQ 266 266 E -> EASTSPV (in isoform 2).
FT /FTId=VSP_034640.
FT VARIANT 863 863 P -> L (in dbSNP:rs2289909).
FT /FTId=VAR_020186.
FT CONFLICT 3 3 Q -> QLFQ (in Ref. 2; AAC37589).
FT CONFLICT 145 145 V -> VRLWGVQV (in Ref. 7; CAA49477).
FT CONFLICT 225 227 Missing (in Ref. 7; CAA49477).
FT CONFLICT 266 266 E -> V (in Ref. 7; CAA49477).
FT CONFLICT 382 382 L -> P (in Ref. 9; AAA35576).
FT CONFLICT 724 727 DAVV -> VGGQ (in Ref. 7; CAA49478).
FT CONFLICT 772 773 SI -> LH (in Ref. 7; CAA49478).
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
//
ID AT12A_HUMAN Reviewed; 1039 AA.
AC P54707; Q13816; Q13817; Q16734; Q5W035; Q8N5U2;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 22-JUL-2008, sequence version 3.
DT 22-JAN-2014, entry version 144.
DE RecName: Full=Potassium-transporting ATPase alpha chain 2;
DE EC=3.6.3.10;
DE AltName: Full=Non-gastric H(+)/K(+) ATPase subunit alpha;
DE AltName: Full=Proton pump;
GN Name=ATP12A; Synonyms=ATP1AL1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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 --
RT a 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T.,
RA Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R.,
RA Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S.,
RA 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.,
RA Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J.,
RA Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E.,
RA Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L.,
RA Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J.,
RA Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S.,
RA Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J.,
RA Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M.,
RA King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A.,
RA Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S.,
RA 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.,
RA Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S.,
RA Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A.,
RA Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L.,
RA Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M.,
RA Hubbard T., Sulston J.E., Beck S., Bentley D.R., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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.,
RA Orlova M.Y., Kostina M.B., Makarevich O.I., Broude N.E.,
RA Monastyrskaya G.S., Sverdlov E.D.;
RT "The family of human Na,K-ATPase genes. ATP1AL1 gene is
RT transcriptionally competent and probably encodes the related ion
RT 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.,
RA Dulubova I.E., Petrukhin K.E., Gryshin A.V., Kiyatkin N.I.,
RA Kostina M.B., Sverdlov V.E., Modyanov N.N., Ovchinnikov Y.A.;
RT "The family of human Na+,K+-ATPase genes. No less than five genes
RT and/or pseudogenes related to the alpha-subunit.";
RL FEBS Lett. 217:275-278(1987).
RN [10]
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
RT mammalian genes encoding the catalytic alpha subunit.";
RL FEBS Lett. 440:320-324(1998).
RN [11]
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).
CC -!- FUNCTION: Catalyzes the hydrolysis of ATP coupled with the
CC exchange of H(+) and K(+) ions across the plasma membrane.
CC Responsible for potassium absorption in various tissues.
CC -!- CATALYTIC ACTIVITY: ATP + H(2)O + H(+)(In) + K(+)(Out) = ADP +
CC phosphate + H(+)(Out) + K(+)(In).
CC -!- SUBUNIT: Composed of two subunits: alpha (catalytic) and beta.
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
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 Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Found in skin and kidney. Detected in prostate
CC basal cells (at protein level). Expression is increased in benign
CC prostate hyperplasia and tumor tissues (at protein level).
CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type)
CC (TC 3.A.3) family. Type IIC subfamily.
CC -----------------------------------------------------------------------
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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; CAH72440.1; -; 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 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.
DR RefSeq; NP_001667.4; NM_001676.5.
DR UniGene; Hs.147111; -.
DR ProteinModelPortal; P54707; -.
DR SMR; P54707; 42-1039.
DR IntAct; P54707; 4.
DR MINT; MINT-4656898; -.
DR STRING; 9606.ENSP00000371372; -.
DR BindingDB; P54707; -.
DR ChEMBL; CHEMBL2933; -.
DR DrugBank; DB00736; Esomeprazole.
DR DrugBank; DB00213; Pantoprazole.
DR PhosphoSite; P54707; -.
DR DMDM; 212287925; -.
DR PaxDb; P54707; -.
DR PRIDE; P54707; -.
DR DNASU; 479; -.
DR Ensembl; ENST00000218548; ENSP00000218548; ENSG00000075673.
DR Ensembl; ENST00000381946; ENSP00000371372; ENSG00000075673.
DR GeneID; 479; -.
DR KEGG; hsa:479; -.
DR UCSC; uc001upp.3; human.
DR CTD; 479; -.
DR GeneCards; GC13P025254; -.
DR HGNC; HGNC:13816; ATP12A.
DR HPA; HPA039526; -.
DR MIM; 182360; gene.
DR neXtProt; NX_P54707; -.
DR PharmGKB; PA25104; -.
DR eggNOG; COG0474; -.
DR HOGENOM; HOG000265622; -.
DR HOVERGEN; HBG004298; -.
DR KO; K01544; -.
DR OMA; NLRVEWE; -.
DR OrthoDB; EOG7327N0; -.
DR BRENDA; 3.6.3.10; 2681.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR GeneWiki; ATP12A; -.
DR GenomeRNAi; 479; -.
DR NextBio; 1985; -.
DR PRO; PR:P54707; -.
DR Bgee; P54707; -.
DR CleanEx; HS_ATP12A; -.
DR Genevestigator; P54707; -.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl.
DR GO; GO:0005889; C:hydrogen:potassium-exchanging ATPase complex; TAS:ProtInc.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008900; F:hydrogen:potassium-exchanging ATPase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006754; P:ATP biosynthetic process; IEA:InterPro.
DR GO; GO:0034220; P:ion transmembrane transport; TAS:Reactome.
DR GO; GO:0055075; P:potassium ion homeostasis; IEA:Ensembl.
DR GO; GO:0006885; P:regulation of pH; IEA:Ensembl.
DR Gene3D; 1.20.1110.10; -; 2.
DR Gene3D; 2.70.150.10; -; 2.
DR Gene3D; 3.40.1110.10; -; 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_domN.
DR InterPro; IPR005775; ATPase_P-typ_Na/K_IIC.
DR InterPro; IPR018303; ATPase_P-typ_P_site.
DR InterPro; IPR023298; ATPase_P-typ_TM_dom.
DR InterPro; IPR008250; ATPase_P-typ_transduc_dom_A.
DR InterPro; IPR001757; Cation_transp_P_typ_ATPase.
DR InterPro; IPR023214; HAD-like_dom.
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 SMART; SM00831; Cation_ATPase_N; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR SUPFAM; SSF81660; SSF81660; 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; Complete proteome;
KW Hydrogen ion transport; Hydrolase; Ion transport; Magnesium; Membrane;
KW Metal-binding; Nucleotide-binding; Phosphoprotein; Polymorphism;
KW Potassium; Potassium transport; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1 1039 Potassium-transporting ATPase alpha chain
FT 2.
FT /FTId=PRO_0000046260.
FT TOPO_DOM 1 102 Cytoplasmic (Potential).
FT TRANSMEM 103 123 Helical; (Potential).
FT TOPO_DOM 124 146 Lumenal (Potential).
FT TRANSMEM 147 167 Helical; (Potential).
FT TOPO_DOM 168 303 Cytoplasmic (Potential).
FT TRANSMEM 304 323 Helical; (Potential).
FT TOPO_DOM 324 335 Lumenal (Potential).
FT TRANSMEM 336 353 Helical; (Potential).
FT TOPO_DOM 354 787 Cytoplasmic (Potential).
FT TRANSMEM 788 807 Helical; (Potential).
FT TOPO_DOM 808 817 Lumenal (Potential).
FT TRANSMEM 818 838 Helical; (Potential).
FT TOPO_DOM 839 858 Cytoplasmic (Potential).
FT TRANSMEM 859 881 Helical; (Potential).
FT TOPO_DOM 882 933 Lumenal (Potential).
FT TRANSMEM 934 953 Helical; (Potential).
FT TOPO_DOM 954 967 Cytoplasmic (Potential).
FT TRANSMEM 968 986 Helical; (Potential).
FT TOPO_DOM 987 1001 Lumenal (Potential).
FT TRANSMEM 1002 1022 Helical; (Potential).
FT TOPO_DOM 1023 1039 Cytoplasmic (Potential).
FT ACT_SITE 391 391 4-aspartylphosphate intermediate (By
FT similarity).
FT METAL 732 732 Magnesium (By similarity).
FT METAL 736 736 Magnesium (By similarity).
FT MOD_RES 958 958 Phosphoserine; by PKA (By similarity).
FT VAR_SEQ 266 266 E -> EASTSPV (in isoform 2).
FT /FTId=VSP_034640.
FT VARIANT 863 863 P -> L (in dbSNP:rs2289909).
FT /FTId=VAR_020186.
FT CONFLICT 3 3 Q -> QLFQ (in Ref. 2; AAC37589).
FT CONFLICT 145 145 V -> VRLWGVQV (in Ref. 7; CAA49477).
FT CONFLICT 225 227 Missing (in Ref. 7; CAA49477).
FT CONFLICT 266 266 E -> V (in Ref. 7; CAA49477).
FT CONFLICT 382 382 L -> P (in Ref. 9; AAA35576).
FT CONFLICT 724 727 DAVV -> VGGQ (in Ref. 7; CAA49478).
FT CONFLICT 772 773 SI -> LH (in Ref. 7; CAA49478).
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
//
MIM
182360
*RECORD*
*FIELD* NO
182360
*FIELD* TI
*182360 ATPase, H+/K+ TRANSPORTING, NONGASTRIC, ALPHA POLYPEPTIDE; ATP12A
;;HYDROGEN/POTASSIUM-EXCHANGING ATPase 12A;;
read moreATPase, Na+/K+ TRANSPORTING, ALPHA POLYPEPTIDE-LIKE 1; ATP1AL1;;
SODIUM/POTASSIUM-ATPase, ALPHA POLYPEPTIDE-LIKE
*FIELD* TX
CLONING
By screening human kidney and skin cDNA libraries, Grishin et al. (1994)
cloned ATP12A, which they called ATP1AL1. The deduced 1,039-amino acid
protein has a calculated molecular mass of 114.5 kD. ATP1AL1 has all the
features of catalytic subunits of P-type ion-transporting ATPases,
including a catalytic phosphorylation site (asp391), components of the
ATP-binding site (asp732 and asp736), and 10 potential transmembrane
domains spaced throughout the molecule. Highest ATP1AL1 expression was
detected in skin.
Using immunofluorescence analysis of transfected MDCK canine kidney
cells, Reinhardt et al. (2002) showed that human ATP1AL1 localized to
the apical plasma membrane when coexpressed with gastric H,K-ATPase beta
subunit (ATP4B; 137217).
GENE FUNCTION
Grishin and Caplan (1998) showed that the ATP1AL1-ATP4B heterodimer
functioned predominantly as an Na,K-ATPase rather than an H,K-ATPase
when expressed in transfected HEK293 cells. The Na+ extrusion activity
was sensitive to 1 millimolar ouabain, an inhibitor of Na,K-ATPases, but
not to 1 micromolar ouabain.
Reinhardt et al. (2002) showed that coexpression of ATP1AL1 and ATP4B
was necessary for trafficking of the ion pump to the plasma membrane of
MDCK cells. In this system, the ATP1AL1-ATP4B dimer functioned as a
proton pump. Phorbol ester-mediated activation of protein kinase C (see
PRKCA; 176960) led to clathrin (see CLTC; 118955)-dependent
internalization and intracellular accumulation of the dimer, leading to
reduced proton extrusion capacity. Internalization and inactivation of
the ion pump was prevented by a PKC blocker.
GENE STRUCTURE
Sverdlov et al. (1996) showed that the ATP1AL1 gene contains 23 exons
and spans 32 kb. A CpG island was identified in the 5-prime flanking
region and 2 potential polyadenylation signals were found in the 3-prime
untranslated region that may function in a tissue-specific manner.
MAPPING
An alpha subunit gene for sodium-potassium ATPase of unknown function
was isolated by molecular cloning and mapped to 13q21-q31 by Southern
analysis of DNA from panels of rodent/human somatic cell hybrids
(Yang-Feng et al., 1988). In the CEPH consortium linkage map of
chromosome 13 reported by Bowcock et al. (1993), the ATP1AL1 locus was
much more proximally situated, being the most centromeric of the
expressed genes tested and proximal to ATRC1 at 13q12.3.
*FIELD* RF
1. Bowcock, A. M.; Gerken, S. C.; Barnes, R. I.; Shiang, R.; Jabs,
E. W.; Warren, A. C.; Antonarakis, S.; Retief, A. E.; Vergnaud, G.;
Leppert, M.; Lalouel, J.-M.; White, R. L.; Cavalli-Sforza, L. L.:
The CEPH consortium linkage map of human chromosome 13. Genomics 16:
486-496, 1993.
2. Grishin, A. V.; Caplan, M. J.: ATP1AL1, a member of the non-gastric
H,K-ATPase family, functions as a sodium pump. J. Biol. Chem. 273:
27772-27778, 1998.
3. Grishin, A. V.; Sverdlov, V. E.; Kostina, M. B.; Modyanov, N. N.
: Cloning and characterization of the entire cDNA encoded by ATP1AL1--a
member of the human Na,K/H,K-ATPase gene family. FEBS Lett. 349:
144-150, 1994.
4. Reinhardt, J.; Kosch, M.; Lerner, M.; Bertram, H.; Lemke, D.; Oberleithner,
H.: Stimulation of protein kinase C pathway mediates endocytosis
of human nongastric H(+)-K(+)-ATPase, ATP1AL1. Am. J. Physiol. Renal
Physiol. 283: F335-F343, 2002.
5. Sverdlov, V. E.; Kostina, M. B.; Modyanov, N. N.: Genomic organization
of the human ATP1AL1 gene encoding a ouabain-sensitive H,K-ATPase. Genomics 32:
317-327, 1996.
6. Yang-Feng, T. L.; Schneider, J. W.; Lindgren, V.; Shull, M. M.;
Benz, E. J., Jr.; Lingrel, J. B.; Francke, U.: Chromosomal localization
of human Na+,K+-ATPase alpha- and beta-subunit genes. Genomics 2:
128-138, 1988.
*FIELD* CN
Patricia A. Hartz - updated: 11/20/2009
Alan F. Scott - updated: 4/18/1996
*FIELD* CD
Victor A. McKusick: 12/8/1987
*FIELD* ED
mgross: 01/06/2010
mgross: 1/6/2010
terry: 11/20/2009
carol: 10/27/2009
alopez: 12/23/1998
alopez: 7/16/1997
terry: 4/18/1996
mark: 4/18/1996
carol: 5/26/1993
supermim: 3/16/1992
carol: 8/5/1991
supermim: 3/20/1990
ddp: 10/27/1989
root: 7/8/1988
*RECORD*
*FIELD* NO
182360
*FIELD* TI
*182360 ATPase, H+/K+ TRANSPORTING, NONGASTRIC, ALPHA POLYPEPTIDE; ATP12A
;;HYDROGEN/POTASSIUM-EXCHANGING ATPase 12A;;
read moreATPase, Na+/K+ TRANSPORTING, ALPHA POLYPEPTIDE-LIKE 1; ATP1AL1;;
SODIUM/POTASSIUM-ATPase, ALPHA POLYPEPTIDE-LIKE
*FIELD* TX
CLONING
By screening human kidney and skin cDNA libraries, Grishin et al. (1994)
cloned ATP12A, which they called ATP1AL1. The deduced 1,039-amino acid
protein has a calculated molecular mass of 114.5 kD. ATP1AL1 has all the
features of catalytic subunits of P-type ion-transporting ATPases,
including a catalytic phosphorylation site (asp391), components of the
ATP-binding site (asp732 and asp736), and 10 potential transmembrane
domains spaced throughout the molecule. Highest ATP1AL1 expression was
detected in skin.
Using immunofluorescence analysis of transfected MDCK canine kidney
cells, Reinhardt et al. (2002) showed that human ATP1AL1 localized to
the apical plasma membrane when coexpressed with gastric H,K-ATPase beta
subunit (ATP4B; 137217).
GENE FUNCTION
Grishin and Caplan (1998) showed that the ATP1AL1-ATP4B heterodimer
functioned predominantly as an Na,K-ATPase rather than an H,K-ATPase
when expressed in transfected HEK293 cells. The Na+ extrusion activity
was sensitive to 1 millimolar ouabain, an inhibitor of Na,K-ATPases, but
not to 1 micromolar ouabain.
Reinhardt et al. (2002) showed that coexpression of ATP1AL1 and ATP4B
was necessary for trafficking of the ion pump to the plasma membrane of
MDCK cells. In this system, the ATP1AL1-ATP4B dimer functioned as a
proton pump. Phorbol ester-mediated activation of protein kinase C (see
PRKCA; 176960) led to clathrin (see CLTC; 118955)-dependent
internalization and intracellular accumulation of the dimer, leading to
reduced proton extrusion capacity. Internalization and inactivation of
the ion pump was prevented by a PKC blocker.
GENE STRUCTURE
Sverdlov et al. (1996) showed that the ATP1AL1 gene contains 23 exons
and spans 32 kb. A CpG island was identified in the 5-prime flanking
region and 2 potential polyadenylation signals were found in the 3-prime
untranslated region that may function in a tissue-specific manner.
MAPPING
An alpha subunit gene for sodium-potassium ATPase of unknown function
was isolated by molecular cloning and mapped to 13q21-q31 by Southern
analysis of DNA from panels of rodent/human somatic cell hybrids
(Yang-Feng et al., 1988). In the CEPH consortium linkage map of
chromosome 13 reported by Bowcock et al. (1993), the ATP1AL1 locus was
much more proximally situated, being the most centromeric of the
expressed genes tested and proximal to ATRC1 at 13q12.3.
*FIELD* RF
1. Bowcock, A. M.; Gerken, S. C.; Barnes, R. I.; Shiang, R.; Jabs,
E. W.; Warren, A. C.; Antonarakis, S.; Retief, A. E.; Vergnaud, G.;
Leppert, M.; Lalouel, J.-M.; White, R. L.; Cavalli-Sforza, L. L.:
The CEPH consortium linkage map of human chromosome 13. Genomics 16:
486-496, 1993.
2. Grishin, A. V.; Caplan, M. J.: ATP1AL1, a member of the non-gastric
H,K-ATPase family, functions as a sodium pump. J. Biol. Chem. 273:
27772-27778, 1998.
3. Grishin, A. V.; Sverdlov, V. E.; Kostina, M. B.; Modyanov, N. N.
: Cloning and characterization of the entire cDNA encoded by ATP1AL1--a
member of the human Na,K/H,K-ATPase gene family. FEBS Lett. 349:
144-150, 1994.
4. Reinhardt, J.; Kosch, M.; Lerner, M.; Bertram, H.; Lemke, D.; Oberleithner,
H.: Stimulation of protein kinase C pathway mediates endocytosis
of human nongastric H(+)-K(+)-ATPase, ATP1AL1. Am. J. Physiol. Renal
Physiol. 283: F335-F343, 2002.
5. Sverdlov, V. E.; Kostina, M. B.; Modyanov, N. N.: Genomic organization
of the human ATP1AL1 gene encoding a ouabain-sensitive H,K-ATPase. Genomics 32:
317-327, 1996.
6. Yang-Feng, T. L.; Schneider, J. W.; Lindgren, V.; Shull, M. M.;
Benz, E. J., Jr.; Lingrel, J. B.; Francke, U.: Chromosomal localization
of human Na+,K+-ATPase alpha- and beta-subunit genes. Genomics 2:
128-138, 1988.
*FIELD* CN
Patricia A. Hartz - updated: 11/20/2009
Alan F. Scott - updated: 4/18/1996
*FIELD* CD
Victor A. McKusick: 12/8/1987
*FIELD* ED
mgross: 01/06/2010
mgross: 1/6/2010
terry: 11/20/2009
carol: 10/27/2009
alopez: 12/23/1998
alopez: 7/16/1997
terry: 4/18/1996
mark: 4/18/1996
carol: 5/26/1993
supermim: 3/16/1992
carol: 8/5/1991
supermim: 3/20/1990
ddp: 10/27/1989
root: 7/8/1988