Full text data of ATP1A1
ATP1A1
[Confidence: high (present in two of the MS resources)]
Sodium/potassium-transporting ATPase subunit alpha-1; Na(+)/K(+) ATPase alpha-1 subunit; 3.6.3.9 (Sodium pump subunit alpha-1; Flags: Precursor)
Sodium/potassium-transporting ATPase subunit alpha-1; Na(+)/K(+) ATPase alpha-1 subunit; 3.6.3.9 (Sodium pump subunit alpha-1; Flags: Precursor)
hRBCD
IPI00006482
IPI00006482 Splice isoform Long of P05023 Sodium/potassium-transporting ATPase alpha-1 chain precu Splice isoform Long of P05023 Sodium/potassium-transporting ATPase alpha-1 chain precu membrane n/a n/a 1 n/a 1 n/a n/a n/a n/a n/a 4 3 n/a 1 n/a n/a n/a n/a n/a n/a integral membrane protein splice isoform Long and Short found at its expected molecular weight found at molecular weight
IPI00006482 Splice isoform Long of P05023 Sodium/potassium-transporting ATPase alpha-1 chain precu Splice isoform Long of P05023 Sodium/potassium-transporting ATPase alpha-1 chain precu membrane n/a n/a 1 n/a 1 n/a n/a n/a n/a n/a 4 3 n/a 1 n/a n/a n/a n/a n/a n/a integral membrane protein splice isoform Long and Short found at its expected molecular weight found at molecular weight
UniProt
P05023
ID AT1A1_HUMAN Reviewed; 1023 AA.
AC P05023; B2RBR6; B7Z2T5; B7Z3U6; F5H3A1; Q16689; Q6LDM4; Q9UCN1;
read moreAC Q9UJ20; Q9UJ21;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 13-AUG-1987, sequence version 1.
DT 22-JAN-2014, entry version 170.
DE RecName: Full=Sodium/potassium-transporting ATPase subunit alpha-1;
DE Short=Na(+)/K(+) ATPase alpha-1 subunit;
DE EC=3.6.3.9;
DE AltName: Full=Sodium pump subunit alpha-1;
DE Flags: Precursor;
GN Name=ATP1A1;
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).
RX PubMed=2430951;
RA Kawakami K., Ohta T., Nojima H., Nagano K.;
RT "Primary structure of the alpha-subunit of human Na,K-ATPase deduced
RT from cDNA sequence.";
RL J. Biochem. 100:389-397(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Retinal pigment epithelium;
RX PubMed=7536695; DOI=10.1016/0378-1119(94)00812-7;
RA Ruiz A., Bhat S.P., Bok D.;
RT "Characterization and quantification of full-length and truncated
RT Na,K-ATPase alpha 1 and beta 1 RNA transcripts expressed in human
RT retinal pigment epithelium.";
RL Gene 155:179-184(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4).
RC TISSUE=Cerebellum;
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=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 1).
RC TISSUE=Brain, Cervix, and Skin;
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 1-61.
RX PubMed=1970326; DOI=10.1016/0888-7543(90)90475-A;
RA Shull M.M., Pugh D.G., Lingrel J.B.;
RT "The human Na, K-ATPase alpha 1 gene: characterization of the 5'-
RT flanking region and identification of a restriction fragment length
RT polymorphism.";
RL Genomics 6:451-460(1990).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 85-148.
RC TISSUE=Placenta;
RA Zhang J.-S., Yang J.X., Fang M.W., Lu S.D.;
RL Submitted (MAR-1996) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 168-189 AND 213-244.
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 [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 198-943 (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=2891135; DOI=10.1073/pnas.84.22.7901;
RA Chehab F.F., Kan Y.W., Law M.L., Hartz J., Kao F.T., Blostein R.;
RT "Human placental Na+,K+-ATPase alpha subunit: cDNA cloning, tissue
RT expression, DNA polymorphism, and chromosomal localization.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:7901-7905(1987).
RN [11]
RP PROTEIN SEQUENCE OF 199-216, AND INTERACTION WITH HLA-DR1.
RX PubMed=1380674; DOI=10.1038/358764a0;
RA Chicz R.M., Urban R.G., Lane W.S., Gorga J.C., Stern L.J.,
RA Vignali D.A.A., Strominger J.L.;
RT "Predominant naturally processed peptides bound to HLA-DR1 are derived
RT from MHC-related molecules and are heterogeneous in size.";
RL Nature 358:764-768(1992).
RN [12]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 253-341 AND 420-444.
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 [13]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 471-619.
RA Ovchinnikov Y.A., Monastyrskaya G.S., Arsenyan S.G., Broude N.E.,
RA Petrukhin K.E., Grishin A.V., Arzamazova N.M., Severtsova I.V.,
RA Modyanov N.N.;
RT "Amino acid sequence of the 17-kilodalton fragment of the cytoplasmic
RT region of the alpha-subunit of NA+,K+-ATPase.";
RL Dokl. Biochem. 288:270-272(1986).
RN [14]
RP SUBCELLULAR LOCATION.
RX PubMed=7711835;
RA Hundal H.S., Maxwell D.L., Ahmed A., Darakhshan F., Mitsumoto Y.,
RA Klip A.;
RT "Subcellular distribution and immunocytochemical localization of Na,K-
RT ATPase subunit isoforms in human skeletal muscle.";
RL Mol. Membr. Biol. 11:255-262(1994).
RN [15]
RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA Hillman R.T., Green R.E., Brenner S.E.;
RT "An unappreciated role for RNA surveillance.";
RL Genome Biol. 5:R8.1-R8.16(2004).
RN [16]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-542, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: This is the catalytic component of the active enzyme,
CC which catalyzes the hydrolysis of ATP coupled with the exchange of
CC sodium and potassium ions across the plasma membrane. This action
CC creates the electrochemical gradient of sodium and potassium ions,
CC providing the energy for active transport of various nutrients.
CC -!- CATALYTIC ACTIVITY: ATP + H(2)O + Na(+)(In) + K(+)(Out) = ADP +
CC phosphate + Na(+)(Out) + K(+)(In).
CC -!- SUBUNIT: Interacts with SIK1 (By similarity). Composed of three
CC subunits: alpha (catalytic), beta and gamma. Binds the HLA class
CC II histocompatibility antigen, DR1.
CC -!- INTERACTION:
CC P13693:TPT1; NbExp=5; IntAct=EBI-358778, EBI-1783169;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC Melanosome. Note=Identified by mass spectrometry in melanosome
CC fractions from stage I to stage IV.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=Long;
CC IsoId=P05023-1; Sequence=Displayed;
CC Name=2; Synonyms=Short;
CC IsoId=P05023-2; Sequence=VSP_000415, VSP_000416;
CC Note=May be produced at very low levels due to a premature stop
CC codon in the mRNA, leading to nonsense-mediated mRNA decay;
CC Name=3;
CC IsoId=P05023-3; Sequence=VSP_044242;
CC Name=4;
CC IsoId=P05023-4; Sequence=VSP_047309;
CC -!- PTM: Phosphorylation on Tyr-10 modulates pumping activity.
CC Dephosphorylation by protein phosphatase 2A (PP2A) following
CC increases in intracellular sodium, leading to increase catalytic
CC activity (By similarity).
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; D00099; BAA00061.1; -; mRNA.
DR EMBL; X04297; CAA27840.1; -; mRNA.
DR EMBL; U16798; AAC50131.1; -; mRNA.
DR EMBL; AK295095; BAH11971.1; -; mRNA.
DR EMBL; AK296362; BAH12332.1; -; mRNA.
DR EMBL; AK314777; BAG37313.1; -; mRNA.
DR EMBL; AL136376; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471122; EAW56644.1; -; Genomic_DNA.
DR EMBL; BC003077; AAH03077.1; -; mRNA.
DR EMBL; BC001330; AAH01330.1; -; mRNA.
DR EMBL; BC050359; AAH50359.1; -; mRNA.
DR EMBL; M30310; AAA51801.1; -; Genomic_DNA.
DR EMBL; M30309; AAA51801.1; JOINED; Genomic_DNA.
DR EMBL; L76938; AAA92713.1; -; Genomic_DNA.
DR EMBL; M16793; AAD56251.1; -; mRNA.
DR EMBL; M16794; AAD56252.1; -; mRNA.
DR EMBL; J03007; AAA51803.1; -; mRNA.
DR EMBL; M27572; AAA35573.1; -; Genomic_DNA.
DR EMBL; M27579; AAA35574.2; -; Genomic_DNA.
DR EMBL; X03757; CAA27390.1; -; mRNA.
DR PIR; A24414; A24414.
DR RefSeq; NP_000692.2; NM_000701.7.
DR RefSeq; NP_001153705.1; NM_001160233.1.
DR RefSeq; NP_001153706.1; NM_001160234.1.
DR UniGene; Hs.371889; -.
DR ProteinModelPortal; P05023; -.
DR SMR; P05023; 26-1023.
DR DIP; DIP-38196N; -.
DR IntAct; P05023; 24.
DR MINT; MINT-4998863; -.
DR STRING; 9606.ENSP00000295598; -.
DR BindingDB; P05023; -.
DR ChEMBL; CHEMBL2095186; -.
DR DrugBank; DB00511; Acetyldigitoxin.
DR DrugBank; DB01430; Almitrine.
DR DrugBank; DB01370; Aluminium.
DR DrugBank; DB01244; Bepridil.
DR DrugBank; DB01158; Bretylium.
DR DrugBank; DB01197; Captopril.
DR DrugBank; DB01078; Deslanoside.
DR DrugBank; DB01119; Diazoxide.
DR DrugBank; DB01396; Digitoxin.
DR DrugBank; DB00390; Digoxin.
DR DrugBank; DB00736; Esomeprazole.
DR DrugBank; DB00903; Ethacrynic acid.
DR DrugBank; DB00695; Furosemide.
DR DrugBank; DB00774; Hydroflumethiazide.
DR DrugBank; DB00232; Methyclothiazide.
DR DrugBank; DB01092; Ouabain.
DR DrugBank; DB00213; Pantoprazole.
DR DrugBank; DB01021; Trichlormethiazide.
DR TCDB; 3.A.3.1.1; the p-type atpase (p-atpase) superfamily.
DR PhosphoSite; P05023; -.
DR DMDM; 114374; -.
DR PaxDb; P05023; -.
DR PeptideAtlas; P05023; -.
DR PRIDE; P05023; -.
DR DNASU; 476; -.
DR Ensembl; ENST00000295598; ENSP00000295598; ENSG00000163399.
DR Ensembl; ENST00000369496; ENSP00000358508; ENSG00000163399.
DR Ensembl; ENST00000537345; ENSP00000445306; ENSG00000163399.
DR GeneID; 476; -.
DR KEGG; hsa:476; -.
DR UCSC; uc010oww.2; human.
DR CTD; 476; -.
DR GeneCards; GC01P116915; -.
DR HGNC; HGNC:799; ATP1A1.
DR HPA; CAB018702; -.
DR MIM; 182310; gene.
DR neXtProt; NX_P05023; -.
DR PharmGKB; PA62; -.
DR eggNOG; COG0474; -.
DR HOVERGEN; HBG004298; -.
DR InParanoid; P05023; -.
DR KO; K01539; -.
DR OMA; QFPEGFQ; -.
DR OrthoDB; EOG7327N0; -.
DR PhylomeDB; P05023; -.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR ChiTaRS; ATP1A1; human.
DR GeneWiki; ATPase,_Na%2B/K%2B_transporting,_alpha_1; -.
DR GenomeRNAi; 476; -.
DR NextBio; 1971; -.
DR PRO; PR:P05023; -.
DR ArrayExpress; P05023; -.
DR Bgee; P05023; -.
DR CleanEx; HS_ATP1A1; -.
DR Genevestigator; P05023; -.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl.
DR GO; GO:0005901; C:caveola; IEA:Ensembl.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:BHF-UCL.
DR GO; GO:0005768; C:endosome; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; ISS:BHF-UCL.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005890; C:sodium:potassium-exchanging ATPase complex; TAS:ProtInc.
DR GO; GO:0030315; C:T-tubule; IEA:Ensembl.
DR GO; GO:0043531; F:ADP binding; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0051087; F:chaperone binding; ISS:BHF-UCL.
DR GO; GO:0030955; F:potassium ion binding; IEA:Ensembl.
DR GO; GO:0031402; F:sodium ion binding; IEA:Ensembl.
DR GO; GO:0005391; F:sodium:potassium-exchanging ATPase activity; ISS:UniProtKB.
DR GO; GO:0006754; P:ATP biosynthetic process; IEA:InterPro.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0060081; P:membrane hyperpolarization; IEA:Ensembl.
DR GO; GO:0031947; P:negative regulation of glucocorticoid biosynthetic process; IEA:Ensembl.
DR GO; GO:0045822; P:negative regulation of heart contraction; IEA:Ensembl.
DR GO; GO:0045823; P:positive regulation of heart contraction; IEA:Ensembl.
DR GO; GO:0045989; P:positive regulation of striated muscle contraction; IEA:Ensembl.
DR GO; GO:0010107; P:potassium ion import; IEA:Ensembl.
DR GO; GO:0008217; P:regulation of blood pressure; IEA:Ensembl.
DR GO; GO:0086004; P:regulation of cardiac muscle cell contraction; IEA:Ensembl.
DR GO; GO:0002028; P:regulation of sodium ion transport; ISS:UniProtKB.
DR GO; GO:0002026; P:regulation of the force of heart contraction; IEA:Ensembl.
DR GO; GO:0042493; P:response to drug; 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; 3.
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; Cell membrane; Complete proteome;
KW Direct protein sequencing; Hydrolase; Ion transport; Magnesium;
KW Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Polymorphism; Potassium; Potassium transport; Reference proteome;
KW Sodium; Sodium transport; Sodium/potassium transport; Transmembrane;
KW Transmembrane helix; Transport.
FT PROPEP 1 5
FT /FTId=PRO_0000002483.
FT CHAIN 6 1023 Sodium/potassium-transporting ATPase
FT subunit alpha-1.
FT /FTId=PRO_0000002484.
FT TOPO_DOM 6 87 Cytoplasmic (Potential).
FT TRANSMEM 88 108 Helical; (Potential).
FT TOPO_DOM 109 131 Extracellular (Potential).
FT TRANSMEM 132 152 Helical; (Potential).
FT TOPO_DOM 153 288 Cytoplasmic (Potential).
FT TRANSMEM 289 308 Helical; (Potential).
FT TOPO_DOM 309 320 Extracellular (Potential).
FT TRANSMEM 321 338 Helical; (Potential).
FT TOPO_DOM 339 772 Cytoplasmic (Potential).
FT TRANSMEM 773 792 Helical; (Potential).
FT TOPO_DOM 793 802 Extracellular (Potential).
FT TRANSMEM 803 823 Helical; (Potential).
FT TOPO_DOM 824 843 Cytoplasmic (Potential).
FT TRANSMEM 844 866 Helical; (Potential).
FT TOPO_DOM 867 918 Extracellular (Potential).
FT TRANSMEM 919 938 Helical; (Potential).
FT TOPO_DOM 939 951 Cytoplasmic (Potential).
FT TRANSMEM 952 970 Helical; (Potential).
FT TOPO_DOM 971 985 Extracellular (Potential).
FT TRANSMEM 986 1006 Helical; (Potential).
FT TOPO_DOM 1007 1023 Cytoplasmic (Potential).
FT REGION 82 84 Phosphoinositide-3 kinase binding (By
FT similarity).
FT ACT_SITE 376 376 4-aspartylphosphate intermediate (By
FT similarity).
FT METAL 717 717 Magnesium (By similarity).
FT METAL 721 721 Magnesium (By similarity).
FT BINDING 487 487 ATP (By similarity).
FT MOD_RES 10 10 Phosphotyrosine (By similarity).
FT MOD_RES 16 16 Phosphoserine (By similarity).
FT MOD_RES 260 260 Phosphotyrosine (By similarity).
FT MOD_RES 542 542 Phosphotyrosine.
FT MOD_RES 943 943 Phosphoserine; by PKA (By similarity).
FT VAR_SEQ 1 31 Missing (in isoform 3).
FT /FTId=VSP_044242.
FT VAR_SEQ 2 4 GKG -> AFK (in isoform 4).
FT /FTId=VSP_047309.
FT VAR_SEQ 638 681 NETVEDIAARLNIPVSQVNPRDAKACVVHGSDLKDMTSEQL
FT DDI -> SGPMSRGKSWSSPATQPSSSVSWWCSGPTWSSVR
FT PGGIRSSSRG (in isoform 2).
FT /FTId=VSP_000415.
FT VAR_SEQ 682 1023 Missing (in isoform 2).
FT /FTId=VSP_000416.
FT VARIANT 47 47 S -> I (in dbSNP:rs12564026).
FT /FTId=VAR_048374.
FT CONFLICT 248 248 N -> S (in Ref. 3; BAG37313).
FT CONFLICT 323 323 F -> L (in Ref. 3; BAH11971).
FT CONFLICT 475 475 A -> T (in Ref. 13; CAA27390).
FT CONFLICT 499 499 S -> A (in Ref. 13; CAA27390).
FT CONFLICT 502 502 Q -> R (in Ref. 13; CAA27390).
FT CONFLICT 523 523 L -> I (in Ref. 13; CAA27390).
FT CONFLICT 892 892 D -> G (in Ref. 3; BAH11971).
SQ SEQUENCE 1023 AA; 112896 MW; F3C6FDE04FB3F667 CRC64;
MGKGVGRDKY EPAAVSEQGD KKGKKGKKDR DMDELKKEVS MDDHKLSLDE LHRKYGTDLS
RGLTSARAAE ILARDGPNAL TPPPTTPEWI KFCRQLFGGF SMLLWIGAIL CFLAYSIQAA
TEEEPQNDNL YLGVVLSAVV IITGCFSYYQ EAKSSKIMES FKNMVPQQAL VIRNGEKMSI
NAEEVVVGDL VEVKGGDRIP ADLRIISANG CKVDNSSLTG ESEPQTRSPD FTNENPLETR
NIAFFSTNCV EGTARGIVVY TGDRTVMGRI ATLASGLEGG QTPIAAEIEH FIHIITGVAV
FLGVSFFILS LILEYTWLEA VIFLIGIIVA NVPEGLLATV TVCLTLTAKR MARKNCLVKN
LEAVETLGST STICSDKTGT LTQNRMTVAH MWFDNQIHEA DTTENQSGVS FDKTSATWLA
LSRIAGLCNR AVFQANQENL PILKRAVAGD ASESALLKCI ELCCGSVKEM RERYAKIVEI
PFNSTNKYQL SIHKNPNTSE PQHLLVMKGA PERILDRCSS ILLHGKEQPL DEELKDAFQN
AYLELGGLGE RVLGFCHLFL PDEQFPEGFQ FDTDDVNFPI DNLCFVGLIS MIDPPRAAVP
DAVGKCRSAG IKVIMVTGDH PITAKAIAKG VGIISEGNET VEDIAARLNI PVSQVNPRDA
KACVVHGSDL KDMTSEQLDD ILKYHTEIVF ARTSPQQKLI IVEGCQRQGA IVAVTGDGVN
DSPALKKADI GVAMGIAGSD VSKQAADMIL LDDNFASIVT GVEEGRLIFD NLKKSIAYTL
TSNIPEITPF LIFIIANIPL PLGTVTILCI DLGTDMVPAI SLAYEQAESD IMKRQPRNPK
TDKLVNERLI SMAYGQIGMI QALGGFFTYF VILAENGFLP IHLLGLRVDW DDRWINDVED
SYGQQWTYEQ RKIVEFTCHT AFFVSIVVVQ WADLVICKTR RNSVFQQGMK NKILIFGLFE
ETALAAFLSY CPGMGVALRM YPLKPTWWFC AFPYSLLIFV YDEVRKLIIR RRPGGWVEKE
TYY
//
ID AT1A1_HUMAN Reviewed; 1023 AA.
AC P05023; B2RBR6; B7Z2T5; B7Z3U6; F5H3A1; Q16689; Q6LDM4; Q9UCN1;
read moreAC Q9UJ20; Q9UJ21;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 13-AUG-1987, sequence version 1.
DT 22-JAN-2014, entry version 170.
DE RecName: Full=Sodium/potassium-transporting ATPase subunit alpha-1;
DE Short=Na(+)/K(+) ATPase alpha-1 subunit;
DE EC=3.6.3.9;
DE AltName: Full=Sodium pump subunit alpha-1;
DE Flags: Precursor;
GN Name=ATP1A1;
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).
RX PubMed=2430951;
RA Kawakami K., Ohta T., Nojima H., Nagano K.;
RT "Primary structure of the alpha-subunit of human Na,K-ATPase deduced
RT from cDNA sequence.";
RL J. Biochem. 100:389-397(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Retinal pigment epithelium;
RX PubMed=7536695; DOI=10.1016/0378-1119(94)00812-7;
RA Ruiz A., Bhat S.P., Bok D.;
RT "Characterization and quantification of full-length and truncated
RT Na,K-ATPase alpha 1 and beta 1 RNA transcripts expressed in human
RT retinal pigment epithelium.";
RL Gene 155:179-184(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4).
RC TISSUE=Cerebellum;
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=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 1).
RC TISSUE=Brain, Cervix, and Skin;
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 1-61.
RX PubMed=1970326; DOI=10.1016/0888-7543(90)90475-A;
RA Shull M.M., Pugh D.G., Lingrel J.B.;
RT "The human Na, K-ATPase alpha 1 gene: characterization of the 5'-
RT flanking region and identification of a restriction fragment length
RT polymorphism.";
RL Genomics 6:451-460(1990).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 85-148.
RC TISSUE=Placenta;
RA Zhang J.-S., Yang J.X., Fang M.W., Lu S.D.;
RL Submitted (MAR-1996) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 168-189 AND 213-244.
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 [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 198-943 (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=2891135; DOI=10.1073/pnas.84.22.7901;
RA Chehab F.F., Kan Y.W., Law M.L., Hartz J., Kao F.T., Blostein R.;
RT "Human placental Na+,K+-ATPase alpha subunit: cDNA cloning, tissue
RT expression, DNA polymorphism, and chromosomal localization.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:7901-7905(1987).
RN [11]
RP PROTEIN SEQUENCE OF 199-216, AND INTERACTION WITH HLA-DR1.
RX PubMed=1380674; DOI=10.1038/358764a0;
RA Chicz R.M., Urban R.G., Lane W.S., Gorga J.C., Stern L.J.,
RA Vignali D.A.A., Strominger J.L.;
RT "Predominant naturally processed peptides bound to HLA-DR1 are derived
RT from MHC-related molecules and are heterogeneous in size.";
RL Nature 358:764-768(1992).
RN [12]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 253-341 AND 420-444.
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 [13]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 471-619.
RA Ovchinnikov Y.A., Monastyrskaya G.S., Arsenyan S.G., Broude N.E.,
RA Petrukhin K.E., Grishin A.V., Arzamazova N.M., Severtsova I.V.,
RA Modyanov N.N.;
RT "Amino acid sequence of the 17-kilodalton fragment of the cytoplasmic
RT region of the alpha-subunit of NA+,K+-ATPase.";
RL Dokl. Biochem. 288:270-272(1986).
RN [14]
RP SUBCELLULAR LOCATION.
RX PubMed=7711835;
RA Hundal H.S., Maxwell D.L., Ahmed A., Darakhshan F., Mitsumoto Y.,
RA Klip A.;
RT "Subcellular distribution and immunocytochemical localization of Na,K-
RT ATPase subunit isoforms in human skeletal muscle.";
RL Mol. Membr. Biol. 11:255-262(1994).
RN [15]
RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA Hillman R.T., Green R.E., Brenner S.E.;
RT "An unappreciated role for RNA surveillance.";
RL Genome Biol. 5:R8.1-R8.16(2004).
RN [16]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-542, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: This is the catalytic component of the active enzyme,
CC which catalyzes the hydrolysis of ATP coupled with the exchange of
CC sodium and potassium ions across the plasma membrane. This action
CC creates the electrochemical gradient of sodium and potassium ions,
CC providing the energy for active transport of various nutrients.
CC -!- CATALYTIC ACTIVITY: ATP + H(2)O + Na(+)(In) + K(+)(Out) = ADP +
CC phosphate + Na(+)(Out) + K(+)(In).
CC -!- SUBUNIT: Interacts with SIK1 (By similarity). Composed of three
CC subunits: alpha (catalytic), beta and gamma. Binds the HLA class
CC II histocompatibility antigen, DR1.
CC -!- INTERACTION:
CC P13693:TPT1; NbExp=5; IntAct=EBI-358778, EBI-1783169;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC Melanosome. Note=Identified by mass spectrometry in melanosome
CC fractions from stage I to stage IV.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=Long;
CC IsoId=P05023-1; Sequence=Displayed;
CC Name=2; Synonyms=Short;
CC IsoId=P05023-2; Sequence=VSP_000415, VSP_000416;
CC Note=May be produced at very low levels due to a premature stop
CC codon in the mRNA, leading to nonsense-mediated mRNA decay;
CC Name=3;
CC IsoId=P05023-3; Sequence=VSP_044242;
CC Name=4;
CC IsoId=P05023-4; Sequence=VSP_047309;
CC -!- PTM: Phosphorylation on Tyr-10 modulates pumping activity.
CC Dephosphorylation by protein phosphatase 2A (PP2A) following
CC increases in intracellular sodium, leading to increase catalytic
CC activity (By similarity).
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; D00099; BAA00061.1; -; mRNA.
DR EMBL; X04297; CAA27840.1; -; mRNA.
DR EMBL; U16798; AAC50131.1; -; mRNA.
DR EMBL; AK295095; BAH11971.1; -; mRNA.
DR EMBL; AK296362; BAH12332.1; -; mRNA.
DR EMBL; AK314777; BAG37313.1; -; mRNA.
DR EMBL; AL136376; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471122; EAW56644.1; -; Genomic_DNA.
DR EMBL; BC003077; AAH03077.1; -; mRNA.
DR EMBL; BC001330; AAH01330.1; -; mRNA.
DR EMBL; BC050359; AAH50359.1; -; mRNA.
DR EMBL; M30310; AAA51801.1; -; Genomic_DNA.
DR EMBL; M30309; AAA51801.1; JOINED; Genomic_DNA.
DR EMBL; L76938; AAA92713.1; -; Genomic_DNA.
DR EMBL; M16793; AAD56251.1; -; mRNA.
DR EMBL; M16794; AAD56252.1; -; mRNA.
DR EMBL; J03007; AAA51803.1; -; mRNA.
DR EMBL; M27572; AAA35573.1; -; Genomic_DNA.
DR EMBL; M27579; AAA35574.2; -; Genomic_DNA.
DR EMBL; X03757; CAA27390.1; -; mRNA.
DR PIR; A24414; A24414.
DR RefSeq; NP_000692.2; NM_000701.7.
DR RefSeq; NP_001153705.1; NM_001160233.1.
DR RefSeq; NP_001153706.1; NM_001160234.1.
DR UniGene; Hs.371889; -.
DR ProteinModelPortal; P05023; -.
DR SMR; P05023; 26-1023.
DR DIP; DIP-38196N; -.
DR IntAct; P05023; 24.
DR MINT; MINT-4998863; -.
DR STRING; 9606.ENSP00000295598; -.
DR BindingDB; P05023; -.
DR ChEMBL; CHEMBL2095186; -.
DR DrugBank; DB00511; Acetyldigitoxin.
DR DrugBank; DB01430; Almitrine.
DR DrugBank; DB01370; Aluminium.
DR DrugBank; DB01244; Bepridil.
DR DrugBank; DB01158; Bretylium.
DR DrugBank; DB01197; Captopril.
DR DrugBank; DB01078; Deslanoside.
DR DrugBank; DB01119; Diazoxide.
DR DrugBank; DB01396; Digitoxin.
DR DrugBank; DB00390; Digoxin.
DR DrugBank; DB00736; Esomeprazole.
DR DrugBank; DB00903; Ethacrynic acid.
DR DrugBank; DB00695; Furosemide.
DR DrugBank; DB00774; Hydroflumethiazide.
DR DrugBank; DB00232; Methyclothiazide.
DR DrugBank; DB01092; Ouabain.
DR DrugBank; DB00213; Pantoprazole.
DR DrugBank; DB01021; Trichlormethiazide.
DR TCDB; 3.A.3.1.1; the p-type atpase (p-atpase) superfamily.
DR PhosphoSite; P05023; -.
DR DMDM; 114374; -.
DR PaxDb; P05023; -.
DR PeptideAtlas; P05023; -.
DR PRIDE; P05023; -.
DR DNASU; 476; -.
DR Ensembl; ENST00000295598; ENSP00000295598; ENSG00000163399.
DR Ensembl; ENST00000369496; ENSP00000358508; ENSG00000163399.
DR Ensembl; ENST00000537345; ENSP00000445306; ENSG00000163399.
DR GeneID; 476; -.
DR KEGG; hsa:476; -.
DR UCSC; uc010oww.2; human.
DR CTD; 476; -.
DR GeneCards; GC01P116915; -.
DR HGNC; HGNC:799; ATP1A1.
DR HPA; CAB018702; -.
DR MIM; 182310; gene.
DR neXtProt; NX_P05023; -.
DR PharmGKB; PA62; -.
DR eggNOG; COG0474; -.
DR HOVERGEN; HBG004298; -.
DR InParanoid; P05023; -.
DR KO; K01539; -.
DR OMA; QFPEGFQ; -.
DR OrthoDB; EOG7327N0; -.
DR PhylomeDB; P05023; -.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR ChiTaRS; ATP1A1; human.
DR GeneWiki; ATPase,_Na%2B/K%2B_transporting,_alpha_1; -.
DR GenomeRNAi; 476; -.
DR NextBio; 1971; -.
DR PRO; PR:P05023; -.
DR ArrayExpress; P05023; -.
DR Bgee; P05023; -.
DR CleanEx; HS_ATP1A1; -.
DR Genevestigator; P05023; -.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl.
DR GO; GO:0005901; C:caveola; IEA:Ensembl.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:BHF-UCL.
DR GO; GO:0005768; C:endosome; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; ISS:BHF-UCL.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005890; C:sodium:potassium-exchanging ATPase complex; TAS:ProtInc.
DR GO; GO:0030315; C:T-tubule; IEA:Ensembl.
DR GO; GO:0043531; F:ADP binding; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0051087; F:chaperone binding; ISS:BHF-UCL.
DR GO; GO:0030955; F:potassium ion binding; IEA:Ensembl.
DR GO; GO:0031402; F:sodium ion binding; IEA:Ensembl.
DR GO; GO:0005391; F:sodium:potassium-exchanging ATPase activity; ISS:UniProtKB.
DR GO; GO:0006754; P:ATP biosynthetic process; IEA:InterPro.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0060081; P:membrane hyperpolarization; IEA:Ensembl.
DR GO; GO:0031947; P:negative regulation of glucocorticoid biosynthetic process; IEA:Ensembl.
DR GO; GO:0045822; P:negative regulation of heart contraction; IEA:Ensembl.
DR GO; GO:0045823; P:positive regulation of heart contraction; IEA:Ensembl.
DR GO; GO:0045989; P:positive regulation of striated muscle contraction; IEA:Ensembl.
DR GO; GO:0010107; P:potassium ion import; IEA:Ensembl.
DR GO; GO:0008217; P:regulation of blood pressure; IEA:Ensembl.
DR GO; GO:0086004; P:regulation of cardiac muscle cell contraction; IEA:Ensembl.
DR GO; GO:0002028; P:regulation of sodium ion transport; ISS:UniProtKB.
DR GO; GO:0002026; P:regulation of the force of heart contraction; IEA:Ensembl.
DR GO; GO:0042493; P:response to drug; 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; 3.
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; Cell membrane; Complete proteome;
KW Direct protein sequencing; Hydrolase; Ion transport; Magnesium;
KW Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Polymorphism; Potassium; Potassium transport; Reference proteome;
KW Sodium; Sodium transport; Sodium/potassium transport; Transmembrane;
KW Transmembrane helix; Transport.
FT PROPEP 1 5
FT /FTId=PRO_0000002483.
FT CHAIN 6 1023 Sodium/potassium-transporting ATPase
FT subunit alpha-1.
FT /FTId=PRO_0000002484.
FT TOPO_DOM 6 87 Cytoplasmic (Potential).
FT TRANSMEM 88 108 Helical; (Potential).
FT TOPO_DOM 109 131 Extracellular (Potential).
FT TRANSMEM 132 152 Helical; (Potential).
FT TOPO_DOM 153 288 Cytoplasmic (Potential).
FT TRANSMEM 289 308 Helical; (Potential).
FT TOPO_DOM 309 320 Extracellular (Potential).
FT TRANSMEM 321 338 Helical; (Potential).
FT TOPO_DOM 339 772 Cytoplasmic (Potential).
FT TRANSMEM 773 792 Helical; (Potential).
FT TOPO_DOM 793 802 Extracellular (Potential).
FT TRANSMEM 803 823 Helical; (Potential).
FT TOPO_DOM 824 843 Cytoplasmic (Potential).
FT TRANSMEM 844 866 Helical; (Potential).
FT TOPO_DOM 867 918 Extracellular (Potential).
FT TRANSMEM 919 938 Helical; (Potential).
FT TOPO_DOM 939 951 Cytoplasmic (Potential).
FT TRANSMEM 952 970 Helical; (Potential).
FT TOPO_DOM 971 985 Extracellular (Potential).
FT TRANSMEM 986 1006 Helical; (Potential).
FT TOPO_DOM 1007 1023 Cytoplasmic (Potential).
FT REGION 82 84 Phosphoinositide-3 kinase binding (By
FT similarity).
FT ACT_SITE 376 376 4-aspartylphosphate intermediate (By
FT similarity).
FT METAL 717 717 Magnesium (By similarity).
FT METAL 721 721 Magnesium (By similarity).
FT BINDING 487 487 ATP (By similarity).
FT MOD_RES 10 10 Phosphotyrosine (By similarity).
FT MOD_RES 16 16 Phosphoserine (By similarity).
FT MOD_RES 260 260 Phosphotyrosine (By similarity).
FT MOD_RES 542 542 Phosphotyrosine.
FT MOD_RES 943 943 Phosphoserine; by PKA (By similarity).
FT VAR_SEQ 1 31 Missing (in isoform 3).
FT /FTId=VSP_044242.
FT VAR_SEQ 2 4 GKG -> AFK (in isoform 4).
FT /FTId=VSP_047309.
FT VAR_SEQ 638 681 NETVEDIAARLNIPVSQVNPRDAKACVVHGSDLKDMTSEQL
FT DDI -> SGPMSRGKSWSSPATQPSSSVSWWCSGPTWSSVR
FT PGGIRSSSRG (in isoform 2).
FT /FTId=VSP_000415.
FT VAR_SEQ 682 1023 Missing (in isoform 2).
FT /FTId=VSP_000416.
FT VARIANT 47 47 S -> I (in dbSNP:rs12564026).
FT /FTId=VAR_048374.
FT CONFLICT 248 248 N -> S (in Ref. 3; BAG37313).
FT CONFLICT 323 323 F -> L (in Ref. 3; BAH11971).
FT CONFLICT 475 475 A -> T (in Ref. 13; CAA27390).
FT CONFLICT 499 499 S -> A (in Ref. 13; CAA27390).
FT CONFLICT 502 502 Q -> R (in Ref. 13; CAA27390).
FT CONFLICT 523 523 L -> I (in Ref. 13; CAA27390).
FT CONFLICT 892 892 D -> G (in Ref. 3; BAH11971).
SQ SEQUENCE 1023 AA; 112896 MW; F3C6FDE04FB3F667 CRC64;
MGKGVGRDKY EPAAVSEQGD KKGKKGKKDR DMDELKKEVS MDDHKLSLDE LHRKYGTDLS
RGLTSARAAE ILARDGPNAL TPPPTTPEWI KFCRQLFGGF SMLLWIGAIL CFLAYSIQAA
TEEEPQNDNL YLGVVLSAVV IITGCFSYYQ EAKSSKIMES FKNMVPQQAL VIRNGEKMSI
NAEEVVVGDL VEVKGGDRIP ADLRIISANG CKVDNSSLTG ESEPQTRSPD FTNENPLETR
NIAFFSTNCV EGTARGIVVY TGDRTVMGRI ATLASGLEGG QTPIAAEIEH FIHIITGVAV
FLGVSFFILS LILEYTWLEA VIFLIGIIVA NVPEGLLATV TVCLTLTAKR MARKNCLVKN
LEAVETLGST STICSDKTGT LTQNRMTVAH MWFDNQIHEA DTTENQSGVS FDKTSATWLA
LSRIAGLCNR AVFQANQENL PILKRAVAGD ASESALLKCI ELCCGSVKEM RERYAKIVEI
PFNSTNKYQL SIHKNPNTSE PQHLLVMKGA PERILDRCSS ILLHGKEQPL DEELKDAFQN
AYLELGGLGE RVLGFCHLFL PDEQFPEGFQ FDTDDVNFPI DNLCFVGLIS MIDPPRAAVP
DAVGKCRSAG IKVIMVTGDH PITAKAIAKG VGIISEGNET VEDIAARLNI PVSQVNPRDA
KACVVHGSDL KDMTSEQLDD ILKYHTEIVF ARTSPQQKLI IVEGCQRQGA IVAVTGDGVN
DSPALKKADI GVAMGIAGSD VSKQAADMIL LDDNFASIVT GVEEGRLIFD NLKKSIAYTL
TSNIPEITPF LIFIIANIPL PLGTVTILCI DLGTDMVPAI SLAYEQAESD IMKRQPRNPK
TDKLVNERLI SMAYGQIGMI QALGGFFTYF VILAENGFLP IHLLGLRVDW DDRWINDVED
SYGQQWTYEQ RKIVEFTCHT AFFVSIVVVQ WADLVICKTR RNSVFQQGMK NKILIFGLFE
ETALAAFLSY CPGMGVALRM YPLKPTWWFC AFPYSLLIFV YDEVRKLIIR RRPGGWVEKE
TYY
//
MIM
182310
*RECORD*
*FIELD* NO
182310
*FIELD* TI
*182310 ATPase, Na+/K+ TRANSPORTING, ALPHA-1 POLYPEPTIDE; ATP1A1
;;SODIUM-POTASSIUM-ATPase, ALPHA-1 POLYPEPTIDE;;
read moreNa,K-ATPase, ALPHA-A CATALYTIC POLYPEPTIDE
*FIELD* TX
DESCRIPTION
The ATP1A1 gene encodes the alpha-1 isoform of the Na(+),K(+)-ATPase (EC
3.6.1.9), an integral membrane protein responsible for establishing and
maintaining the electrochemical gradients of Na and K ions across the
plasma membrane. As these gradients are essential for osmoregulation,
for sodium-coupled transport of a variety of organic and inorganic
molecules, and for electrical excitability of nerve and muscle, the
enzyme plays an essential role in cellular physiology. It is composed of
at least 2 subunits, a large catalytic subunit (alpha) and a smaller
glycoprotein subunit (beta) (ATP1B1; 182330). ATP1A1 and ATP1A2 (182340)
are isoforms of the catalytic subunit. Kidney contains predominantly
ATP1A1, whereas both subunits are found in brain, adipose tissue, and
skeletal muscle (summary by Shull and Lingrel, 1987).
CLONING
Shull and Lingrel (1987) identified separate genes encoding the alpha
(ATP1A1) and alpha(+) (ATP1A2; 182340) isoforms. In addition, they
isolated 2 other genes, termed alpha-C (ATP1A3; 182350) and alpha-D
(ATP1A4; 607321), one of which is physically linked to the ATP1A2 gene;
these genes showed nucleotide and deduced amino acid homology to the
catalytic subunit cDNA sequences but did not correspond to any
previously identified isoforms.
Chehab et al. (1987) cloned from human placenta a 2.2-kb clone
comprising a major portion of the coding sequence of the alpha subunit.
They found that its sequence was identical to that encoding the alpha
subunit of the human kidney and HeLa cells. Southern blot analysis
revealed a RFLP.
MAPPING
Kent et al. (1987) used a panel of mouse-hamster somatic cell hybrids
and restriction fragment length polymorphisms between 2 mouse species
(Mus musculus and Mus spretus) to determine the chromosomal localization
of genes encoding the alpha and beta subunits of Na,K-ATPase. Three
isoforms of the alpha subunit mapped to 3 different chromosomes: alpha-1
to mouse chromosome 3; alpha-2 to mouse chromosome 7; and alpha-3 to
mouse chromosome 1. The beta-subunit gene mapped to the same region of
chromosome 1 but was not tightly linked to the alpha-3 gene.
Sverdlov et al. (1987) demonstrated intra-individual RFLPs in DNA
isolated from different tissues of mouse, rabbit, and humans. They
suggested that these tissue-specific RFLPs could be the result of
rearrangements in the gene loci for the alpha and beta subunits of
ATPase.
By hybridization to flow-sorted chromosomes and by in situ
hybridization, Chehab et al. (1987) showed that the gene for the alpha
subunit is on chromosome 1p13-p11. Yang-Feng et al. (1988) assigned the
ATP1A1 gene to 1p21-cen by Southern analysis of DNA from panels of
rodent/human somatic cell hybrid lines. The gene for this type of alpha
chain appears to be expressed in most tissues.
MOLECULAR GENETICS
Based on observations that the ATP1A1 and NKCC2 (SLC12A1; 600839) genes
interactively increase susceptibility to hypertension in the Dahl
salt-sensitive hypertensive rat model, Glorioso et al. (2001) genotyped
a relatively genetically homogeneous cohort in northern Sardinia to find
whether parallel molecular genetic mechanisms exist in human essential
hypertension. Their data indicated that ATP1A1 and NKCC2 are candidate
interacting hypertension susceptibility loci in human essential
hypertension.
- Somatic Mutation
Beuschlein et al. (2013) performed exome sequencing of
aldosterone-producing adenomas and identified somatic hotspot mutations
in the ATP1A1 gene, encoding a sodium/potassium ATPase alpha subunit,
and the ATP2B3 (300014) gene, encoding a calcium ATPase, in 3 and 2 of
the 9 aldosterone-producing adenomas, respectively. These ATPases are
expressed in adrenal cells and control sodium, potassium, and calcium
ion homeostasis. Functional in vitro studies of the ATP1A1 mutants
showed loss of pump activity and strongly reduced affinity for
potassium. Electrophysiologic ex vivo studies on primary adrenal adenoma
cells provided further evidence for inappropriate depolarization of
cells with ATPase alterations. In a collection of 308
aldosterone-producing adenomas, Beuschlein et al. (2013) found 16 (5.2%)
somatic mutations in ATP1A1 and 5 (1.6%) in ATP2B3. Mutation-positive
cases showed male dominance, increased plasma aldosterone
concentrations, and lower potassium concentrations compared with
mutation-negative cases.
BIOCHEMICAL FEATURES
- Crystal Structure
Morth et al. (2007) presented the x-ray crystal structure at
3.5-angstrom resolution of the pig renal sodium-potassium-ATPase
(Na+,K(+)-ATPase) with 2 rubidium ions bound (as potassium congeners) in
an occluded state in the transmembrane part of the alpha subunit.
Several of the residues forming the cavity for rubidium/potassium
occlusion in the Na+,K(+)-ATPase are homologous to those binding calcium
in the calcium-ion ATPase of sarcoendoplasmic reticulum (SERCA1;
108730). The beta and gamma subunits specific to the Na+,K(+)-ATPase are
associated with transmembrane helices alpha-M7/alpha-M10, and alpha-M9,
respectively. The gamma subunit corresponds to a fragment of the V-type
ATPase c subunit. The carboxy terminus of the alpha subunit is contained
within a pocket between transmembrane helices and seems to be a novel
regulatory element controlling sodium affinity, possibly influenced by
the membrane potential.
ANIMAL MODEL
In a search for an essential hypertension (145500) gene, Herrera and
Ruiz-Opazo (1990) used an approach that integrated molecular,
transgenic, and genetic analysis to study the Dahl salt-sensitive (S)
and Dahl salt-resistant (R) rat (Dahl et al., 1972, 1974). Because
alpha-1-Na,K-ATPase is the sole active Na+ transporter in the renal
basolateral epithelia throughout the nephron, it was a logical candidate
gene to be considered in the assessment of the abnormal renal sodium
handling in the Dahl S rat. Herrera and Ruiz-Opazo (1990) and Ruiz-Opazo
et al. (1994) purportedly demonstrated a gln276-to-leu (Q276L)
substitution in the Atp1a gene in Dahl S rats. To determine the role of
the Dahl-sensitive Q276L gene variant, Herrera et al. (1998) developed
transgenic Dahl S rats bearing the Dahl R wildtype Atp1a1 cDNA directed
by the cognate wildtype promoter region. Transgenic Dahl S rats
exhibited less rat salt-sensitive hypertension, less hypertensive renal
disease, and longer life span when compared with nontransgenic Dahl S
controls. Chromosome 2 linkage analysis of F2(SxR) male rats detected
cosegregation of the Atp1a1 locus with salt-sensitive hypertension.
These data supported the view that the Atp1a1 gene is a susceptibility
gene for salt-sensitive hypertension in the Dahl S rat model, and
provided the basis for the study of the same locus in human
hypertension.
A putative 1079A-T mutation in the Atp1a1 gene was also proposed in the
New Zealand genetically hypertensive strain of rat, known to have a
blood pressure quantitative trait locus on chromosome 2. Barnard et al.
(2001) appeared to have excluded the existence of this mutation which
would predict a Q276L amino acid substitution in the protein. They
suggested that alternative candidate genes in the region defined by the
rat chromosome 2 hypertension quantitative trait locus should be
examined.
To determine the functional roles of the ATP1A1 and ATP1A2 proteins,
James et al. (1999) generated mice with targeted disruption of either
the Atp1a1 or Atp1a2 gene. Hearts from heterozygous Atp1a2 mice were
hypercontractile as a result of increased calcium transients during the
contractile cycle. In contrast, hearts from heterozygous Atp1a1 mice
were hypocontractile. The different functional roles of these 2 proteins
were further demonstrated since inhibition of the Atp1a2 protein with
ouabain increased the contractility of heterozygous Atp1a1 hearts. These
results illustrated a specific role for the ATP1A2 protein in calcium
signaling during cardiac contraction.
*FIELD* SA
Kawakami et al. (1986); Ovchinnikov et al. (1987)
*FIELD* RF
1. Barnard, R.; Kelly, G.; Manzetti, S. O.; Harris, E. L.: Neither
the New Zealand genetically hypertensive strain nor Dahl salt-sensitive
strain has an A1079T transversion in the alpha-1 isoform of the Na(+),K(+)-ATPase
gene. Hypertension 38: 786-792, 2001.
2. Beuschlein, F.; Boulkroun, S.; Osswald, A.; Wieland, T.; Nielsen,
H. N.; Lichtenauer, U. D.; Penton, D.; Schack, V. R.; Amar, L.; Fischer,
E.; Walther, A.; Tauber, P.; and 18 others: Somatic mutations in
ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary
hypertension. Nature Genet 45: 440-444, 2013.
3. Chehab, F. F.; Kan, Y. W.; Law, M. L.; Hartz, J.; Kao, F.-T.; Blostein,
R.: Human placental Na+,K+-ATPase alpha subunit: cDNA cloning, tissue
expression, DNA polymorphism, and chromosomal localization. Proc.
Nat. Acad. Sci. 84: 7901-7905, 1987.
4. Dahl, L. K.; Heine, M.; Tassinari, L.: Role of genetic factors
in susceptibility to experimental hypertension due to chronic excess
salt ingestion. Nature 194: 480-482, 1972.
5. Dahl, L. K.; Heine, M.; Thompson, K.: Genetic influence of the
kidneys on blood pressure: evidence from chronic renal homografts
in rats with opposite predispositions to hypertension. Circ. Res. 40:
94-101, 1974.
6. Glorioso, N.; Filigheddu, F.; Troffa, C.; Soro, A.; Parpaglia,
P. P.; Tsikoudakis, A.; Myers, R. H.; Herrera, V. L. M.; Ruiz-Opazo,
N.: Interaction of alpha-1-Na,K-ATPase and Na,K,2Cl-cotransporter
genes in human essential hypertension. Hypertension 38: 204-209,
2001.
7. Herrera, V. L. M.; Ruiz-Opazo, N.: Alteration of alpha-1 Na+,K(+)-ATPase
86R-beta(+) influx by a single amino acid substitution. Science 249:
1023-1026, 1990. Note: Erratum: Science 253: 366 only, 1991.
8. Herrera, V. L. M.; Xie, H. X.; Lopez, L. V.; Schork, N. J.; Ruiz-Opazo,
N.: The alpha-1 Na,K-ATPase gene is a susceptibility hypertension
gene in the Dahl salt-sensitive-HSD rat. J. Clin. Invest. 102: 1102-1111,
1998.
9. James, P. F.; Grupp, I. L.; Grupp, G.; Woo, A. L.; Askew, G. R.;
Croyle, M. L.; Walsh, R. A.; Lingrel, J. B.: Identification of a
specific role for the Na,K-ATPase alpha-2 isoform as a regulator of
calcium in the heart. Molec. Cell 3: 555-563, 1999.
10. Kawakami, K.; Ohta, T.; Nojima, H.; Nagano, K.: Primary structure
of the alpha-subunit of human Na,K-ATPase deduced from cDNA sequence. J.
Biochem. 100: 389-397, 1986.
11. Kent, R. B.; Fallows, D. A.; Geissler, E.; Glaser, T.; Emanuel,
J. R.; Lalley, P. A.; Levenson, R.; Housman, D. E.: Genes encoding
alpha and beta subunits of Na,K-ATPase are located on three different
chromosomes in the mouse. Proc. Nat. Acad. Sci. 84: 5369-5373, 1987.
12. Morth, J. P.; Pedersen, B. P.; Toustrup-Jensen, M. S.; Sorensen,
T. L.-M.; Petersen, J.; Andersen, J. P.; Vilsen, B.; Nissen, P.:
Crystal structure of the sodium-potassium pump. Nature 450: 1043-1049,
2007.
13. Ovchinnikov, Y. A.; Monastyrskaya, G. S.; Broude, N. E.; Allikmets,
R. L.; Ushkaryov, Y. A.; Melkov, A. M.; Smirnov, Y. V.; Malyshev,
I. V.; Dulubova, I. E.; Petrukhin, K. E.; Gryshin, A. V.; Sverdlov,
V. E.; Kiyatkin, N. I.; Kostina, M. B.; Modyanov, N. N.; Sverdlov,
E. D.: The family of human Na+,K+-ATPase genes: a partial nucleotide
sequence related to the alpha-subunit. FEBS Lett. 213: 73-80, 1987.
Note: Erratum: FEBS Lett. 214: 375 only, 1987.
14. Ruiz-Opazo, N.; Barany, F.; Hirayama, K.; Herrera, V. L. M.:
Confirmation of mutant alpha-1 Na,K-ATPase gene and transcript in
Dahl salt-sensitive/JR rats. Hypertension 24: 260-270, 1994.
15. Shull, M. M.; Lingrel, J. B.: Multiple genes encode the human
Na+,K+-ATPase catalytic subunit. Proc. Nat. Acad. Sci. 84: 4039-4043,
1987.
16. Sverdlov, E. D.; Broude, N. E.; Sverdlov, V. E.; Monastyrskaya,
G. S.; Grishin, A. V.; Petrukhin, K. E.; Akopyanz, N. S.; Modyanov,
N. N.; Ovchinnikov, Y. A.: Family of Na+,K+-ATPase genes: intra-individual
tissue-specific restriction fragment length polymorphism. FEBS Lett. 221:
129-133, 1987. Note: Erratum: FEBS Lett. 227: 85 only, 1988.
17. 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
Ada Hamosh - updated: 10/23/2013
Ada Hamosh - updated: 4/22/2008
Victor A. McKusick - updated: 8/9/2002
Victor A. McKusick - updated: 11/9/2001
Stylianos E. Antonarakis - updated: 7/20/1999
Victor A. McKusick - updated: 10/6/1998
*FIELD* CD
Victor A. McKusick: 6/26/1987
*FIELD* ED
carol: 10/25/2013
alopez: 10/23/2013
terry: 3/15/2013
carol: 11/9/2012
ckniffin: 11/7/2012
terry: 11/6/2012
terry: 10/3/2012
alopez: 5/15/2008
terry: 4/22/2008
mgross: 10/7/2002
tkritzer: 8/15/2002
tkritzer: 8/13/2002
terry: 8/9/2002
carol: 11/12/2001
terry: 11/9/2001
mgross: 7/21/1999
mgross: 7/20/1999
dkim: 10/13/1998
carol: 10/12/1998
terry: 10/6/1998
alopez: 6/3/1997
supermim: 3/16/1992
carol: 3/2/1992
supermim: 5/1/1990
supermim: 3/20/1990
ddp: 10/27/1989
root: 7/8/1988
*RECORD*
*FIELD* NO
182310
*FIELD* TI
*182310 ATPase, Na+/K+ TRANSPORTING, ALPHA-1 POLYPEPTIDE; ATP1A1
;;SODIUM-POTASSIUM-ATPase, ALPHA-1 POLYPEPTIDE;;
read moreNa,K-ATPase, ALPHA-A CATALYTIC POLYPEPTIDE
*FIELD* TX
DESCRIPTION
The ATP1A1 gene encodes the alpha-1 isoform of the Na(+),K(+)-ATPase (EC
3.6.1.9), an integral membrane protein responsible for establishing and
maintaining the electrochemical gradients of Na and K ions across the
plasma membrane. As these gradients are essential for osmoregulation,
for sodium-coupled transport of a variety of organic and inorganic
molecules, and for electrical excitability of nerve and muscle, the
enzyme plays an essential role in cellular physiology. It is composed of
at least 2 subunits, a large catalytic subunit (alpha) and a smaller
glycoprotein subunit (beta) (ATP1B1; 182330). ATP1A1 and ATP1A2 (182340)
are isoforms of the catalytic subunit. Kidney contains predominantly
ATP1A1, whereas both subunits are found in brain, adipose tissue, and
skeletal muscle (summary by Shull and Lingrel, 1987).
CLONING
Shull and Lingrel (1987) identified separate genes encoding the alpha
(ATP1A1) and alpha(+) (ATP1A2; 182340) isoforms. In addition, they
isolated 2 other genes, termed alpha-C (ATP1A3; 182350) and alpha-D
(ATP1A4; 607321), one of which is physically linked to the ATP1A2 gene;
these genes showed nucleotide and deduced amino acid homology to the
catalytic subunit cDNA sequences but did not correspond to any
previously identified isoforms.
Chehab et al. (1987) cloned from human placenta a 2.2-kb clone
comprising a major portion of the coding sequence of the alpha subunit.
They found that its sequence was identical to that encoding the alpha
subunit of the human kidney and HeLa cells. Southern blot analysis
revealed a RFLP.
MAPPING
Kent et al. (1987) used a panel of mouse-hamster somatic cell hybrids
and restriction fragment length polymorphisms between 2 mouse species
(Mus musculus and Mus spretus) to determine the chromosomal localization
of genes encoding the alpha and beta subunits of Na,K-ATPase. Three
isoforms of the alpha subunit mapped to 3 different chromosomes: alpha-1
to mouse chromosome 3; alpha-2 to mouse chromosome 7; and alpha-3 to
mouse chromosome 1. The beta-subunit gene mapped to the same region of
chromosome 1 but was not tightly linked to the alpha-3 gene.
Sverdlov et al. (1987) demonstrated intra-individual RFLPs in DNA
isolated from different tissues of mouse, rabbit, and humans. They
suggested that these tissue-specific RFLPs could be the result of
rearrangements in the gene loci for the alpha and beta subunits of
ATPase.
By hybridization to flow-sorted chromosomes and by in situ
hybridization, Chehab et al. (1987) showed that the gene for the alpha
subunit is on chromosome 1p13-p11. Yang-Feng et al. (1988) assigned the
ATP1A1 gene to 1p21-cen by Southern analysis of DNA from panels of
rodent/human somatic cell hybrid lines. The gene for this type of alpha
chain appears to be expressed in most tissues.
MOLECULAR GENETICS
Based on observations that the ATP1A1 and NKCC2 (SLC12A1; 600839) genes
interactively increase susceptibility to hypertension in the Dahl
salt-sensitive hypertensive rat model, Glorioso et al. (2001) genotyped
a relatively genetically homogeneous cohort in northern Sardinia to find
whether parallel molecular genetic mechanisms exist in human essential
hypertension. Their data indicated that ATP1A1 and NKCC2 are candidate
interacting hypertension susceptibility loci in human essential
hypertension.
- Somatic Mutation
Beuschlein et al. (2013) performed exome sequencing of
aldosterone-producing adenomas and identified somatic hotspot mutations
in the ATP1A1 gene, encoding a sodium/potassium ATPase alpha subunit,
and the ATP2B3 (300014) gene, encoding a calcium ATPase, in 3 and 2 of
the 9 aldosterone-producing adenomas, respectively. These ATPases are
expressed in adrenal cells and control sodium, potassium, and calcium
ion homeostasis. Functional in vitro studies of the ATP1A1 mutants
showed loss of pump activity and strongly reduced affinity for
potassium. Electrophysiologic ex vivo studies on primary adrenal adenoma
cells provided further evidence for inappropriate depolarization of
cells with ATPase alterations. In a collection of 308
aldosterone-producing adenomas, Beuschlein et al. (2013) found 16 (5.2%)
somatic mutations in ATP1A1 and 5 (1.6%) in ATP2B3. Mutation-positive
cases showed male dominance, increased plasma aldosterone
concentrations, and lower potassium concentrations compared with
mutation-negative cases.
BIOCHEMICAL FEATURES
- Crystal Structure
Morth et al. (2007) presented the x-ray crystal structure at
3.5-angstrom resolution of the pig renal sodium-potassium-ATPase
(Na+,K(+)-ATPase) with 2 rubidium ions bound (as potassium congeners) in
an occluded state in the transmembrane part of the alpha subunit.
Several of the residues forming the cavity for rubidium/potassium
occlusion in the Na+,K(+)-ATPase are homologous to those binding calcium
in the calcium-ion ATPase of sarcoendoplasmic reticulum (SERCA1;
108730). The beta and gamma subunits specific to the Na+,K(+)-ATPase are
associated with transmembrane helices alpha-M7/alpha-M10, and alpha-M9,
respectively. The gamma subunit corresponds to a fragment of the V-type
ATPase c subunit. The carboxy terminus of the alpha subunit is contained
within a pocket between transmembrane helices and seems to be a novel
regulatory element controlling sodium affinity, possibly influenced by
the membrane potential.
ANIMAL MODEL
In a search for an essential hypertension (145500) gene, Herrera and
Ruiz-Opazo (1990) used an approach that integrated molecular,
transgenic, and genetic analysis to study the Dahl salt-sensitive (S)
and Dahl salt-resistant (R) rat (Dahl et al., 1972, 1974). Because
alpha-1-Na,K-ATPase is the sole active Na+ transporter in the renal
basolateral epithelia throughout the nephron, it was a logical candidate
gene to be considered in the assessment of the abnormal renal sodium
handling in the Dahl S rat. Herrera and Ruiz-Opazo (1990) and Ruiz-Opazo
et al. (1994) purportedly demonstrated a gln276-to-leu (Q276L)
substitution in the Atp1a gene in Dahl S rats. To determine the role of
the Dahl-sensitive Q276L gene variant, Herrera et al. (1998) developed
transgenic Dahl S rats bearing the Dahl R wildtype Atp1a1 cDNA directed
by the cognate wildtype promoter region. Transgenic Dahl S rats
exhibited less rat salt-sensitive hypertension, less hypertensive renal
disease, and longer life span when compared with nontransgenic Dahl S
controls. Chromosome 2 linkage analysis of F2(SxR) male rats detected
cosegregation of the Atp1a1 locus with salt-sensitive hypertension.
These data supported the view that the Atp1a1 gene is a susceptibility
gene for salt-sensitive hypertension in the Dahl S rat model, and
provided the basis for the study of the same locus in human
hypertension.
A putative 1079A-T mutation in the Atp1a1 gene was also proposed in the
New Zealand genetically hypertensive strain of rat, known to have a
blood pressure quantitative trait locus on chromosome 2. Barnard et al.
(2001) appeared to have excluded the existence of this mutation which
would predict a Q276L amino acid substitution in the protein. They
suggested that alternative candidate genes in the region defined by the
rat chromosome 2 hypertension quantitative trait locus should be
examined.
To determine the functional roles of the ATP1A1 and ATP1A2 proteins,
James et al. (1999) generated mice with targeted disruption of either
the Atp1a1 or Atp1a2 gene. Hearts from heterozygous Atp1a2 mice were
hypercontractile as a result of increased calcium transients during the
contractile cycle. In contrast, hearts from heterozygous Atp1a1 mice
were hypocontractile. The different functional roles of these 2 proteins
were further demonstrated since inhibition of the Atp1a2 protein with
ouabain increased the contractility of heterozygous Atp1a1 hearts. These
results illustrated a specific role for the ATP1A2 protein in calcium
signaling during cardiac contraction.
*FIELD* SA
Kawakami et al. (1986); Ovchinnikov et al. (1987)
*FIELD* RF
1. Barnard, R.; Kelly, G.; Manzetti, S. O.; Harris, E. L.: Neither
the New Zealand genetically hypertensive strain nor Dahl salt-sensitive
strain has an A1079T transversion in the alpha-1 isoform of the Na(+),K(+)-ATPase
gene. Hypertension 38: 786-792, 2001.
2. Beuschlein, F.; Boulkroun, S.; Osswald, A.; Wieland, T.; Nielsen,
H. N.; Lichtenauer, U. D.; Penton, D.; Schack, V. R.; Amar, L.; Fischer,
E.; Walther, A.; Tauber, P.; and 18 others: Somatic mutations in
ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary
hypertension. Nature Genet 45: 440-444, 2013.
3. Chehab, F. F.; Kan, Y. W.; Law, M. L.; Hartz, J.; Kao, F.-T.; Blostein,
R.: Human placental Na+,K+-ATPase alpha subunit: cDNA cloning, tissue
expression, DNA polymorphism, and chromosomal localization. Proc.
Nat. Acad. Sci. 84: 7901-7905, 1987.
4. Dahl, L. K.; Heine, M.; Tassinari, L.: Role of genetic factors
in susceptibility to experimental hypertension due to chronic excess
salt ingestion. Nature 194: 480-482, 1972.
5. Dahl, L. K.; Heine, M.; Thompson, K.: Genetic influence of the
kidneys on blood pressure: evidence from chronic renal homografts
in rats with opposite predispositions to hypertension. Circ. Res. 40:
94-101, 1974.
6. Glorioso, N.; Filigheddu, F.; Troffa, C.; Soro, A.; Parpaglia,
P. P.; Tsikoudakis, A.; Myers, R. H.; Herrera, V. L. M.; Ruiz-Opazo,
N.: Interaction of alpha-1-Na,K-ATPase and Na,K,2Cl-cotransporter
genes in human essential hypertension. Hypertension 38: 204-209,
2001.
7. Herrera, V. L. M.; Ruiz-Opazo, N.: Alteration of alpha-1 Na+,K(+)-ATPase
86R-beta(+) influx by a single amino acid substitution. Science 249:
1023-1026, 1990. Note: Erratum: Science 253: 366 only, 1991.
8. Herrera, V. L. M.; Xie, H. X.; Lopez, L. V.; Schork, N. J.; Ruiz-Opazo,
N.: The alpha-1 Na,K-ATPase gene is a susceptibility hypertension
gene in the Dahl salt-sensitive-HSD rat. J. Clin. Invest. 102: 1102-1111,
1998.
9. James, P. F.; Grupp, I. L.; Grupp, G.; Woo, A. L.; Askew, G. R.;
Croyle, M. L.; Walsh, R. A.; Lingrel, J. B.: Identification of a
specific role for the Na,K-ATPase alpha-2 isoform as a regulator of
calcium in the heart. Molec. Cell 3: 555-563, 1999.
10. Kawakami, K.; Ohta, T.; Nojima, H.; Nagano, K.: Primary structure
of the alpha-subunit of human Na,K-ATPase deduced from cDNA sequence. J.
Biochem. 100: 389-397, 1986.
11. Kent, R. B.; Fallows, D. A.; Geissler, E.; Glaser, T.; Emanuel,
J. R.; Lalley, P. A.; Levenson, R.; Housman, D. E.: Genes encoding
alpha and beta subunits of Na,K-ATPase are located on three different
chromosomes in the mouse. Proc. Nat. Acad. Sci. 84: 5369-5373, 1987.
12. Morth, J. P.; Pedersen, B. P.; Toustrup-Jensen, M. S.; Sorensen,
T. L.-M.; Petersen, J.; Andersen, J. P.; Vilsen, B.; Nissen, P.:
Crystal structure of the sodium-potassium pump. Nature 450: 1043-1049,
2007.
13. Ovchinnikov, Y. A.; Monastyrskaya, G. S.; Broude, N. E.; Allikmets,
R. L.; Ushkaryov, Y. A.; Melkov, A. M.; Smirnov, Y. V.; Malyshev,
I. V.; Dulubova, I. E.; Petrukhin, K. E.; Gryshin, A. V.; Sverdlov,
V. E.; Kiyatkin, N. I.; Kostina, M. B.; Modyanov, N. N.; Sverdlov,
E. D.: The family of human Na+,K+-ATPase genes: a partial nucleotide
sequence related to the alpha-subunit. FEBS Lett. 213: 73-80, 1987.
Note: Erratum: FEBS Lett. 214: 375 only, 1987.
14. Ruiz-Opazo, N.; Barany, F.; Hirayama, K.; Herrera, V. L. M.:
Confirmation of mutant alpha-1 Na,K-ATPase gene and transcript in
Dahl salt-sensitive/JR rats. Hypertension 24: 260-270, 1994.
15. Shull, M. M.; Lingrel, J. B.: Multiple genes encode the human
Na+,K+-ATPase catalytic subunit. Proc. Nat. Acad. Sci. 84: 4039-4043,
1987.
16. Sverdlov, E. D.; Broude, N. E.; Sverdlov, V. E.; Monastyrskaya,
G. S.; Grishin, A. V.; Petrukhin, K. E.; Akopyanz, N. S.; Modyanov,
N. N.; Ovchinnikov, Y. A.: Family of Na+,K+-ATPase genes: intra-individual
tissue-specific restriction fragment length polymorphism. FEBS Lett. 221:
129-133, 1987. Note: Erratum: FEBS Lett. 227: 85 only, 1988.
17. 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
Ada Hamosh - updated: 10/23/2013
Ada Hamosh - updated: 4/22/2008
Victor A. McKusick - updated: 8/9/2002
Victor A. McKusick - updated: 11/9/2001
Stylianos E. Antonarakis - updated: 7/20/1999
Victor A. McKusick - updated: 10/6/1998
*FIELD* CD
Victor A. McKusick: 6/26/1987
*FIELD* ED
carol: 10/25/2013
alopez: 10/23/2013
terry: 3/15/2013
carol: 11/9/2012
ckniffin: 11/7/2012
terry: 11/6/2012
terry: 10/3/2012
alopez: 5/15/2008
terry: 4/22/2008
mgross: 10/7/2002
tkritzer: 8/15/2002
tkritzer: 8/13/2002
terry: 8/9/2002
carol: 11/12/2001
terry: 11/9/2001
mgross: 7/21/1999
mgross: 7/20/1999
dkim: 10/13/1998
carol: 10/12/1998
terry: 10/6/1998
alopez: 6/3/1997
supermim: 3/16/1992
carol: 3/2/1992
supermim: 5/1/1990
supermim: 3/20/1990
ddp: 10/27/1989
root: 7/8/1988