Reviewed, UniProtKB/Swiss-Prot P54707 (AT12A_HUMAN)

Names and origin

Protein names

Recommended name:
    Potassium-transporting ATPase alpha chain 2
    EC=3.6.3.10
Alternative name(s):
    Proton pump
    Non-gastric H(+)/K(+) ATPase subunit alpha

Gene names

Name:	ATP12A
Synonyms:	ATP1AL1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1039 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Function	Catalyzes the hydrolysis of ATP coupled with the exchange of H+ and K+ ions across the plasma membrane. Responsible for potassium absorption in various tissues.
Catalytic activity	ATP + H2O + H+(In) + K+(Out) = ADP + phosphate + H+(Out) + K+(In).
Subunit structure	Composed of two subunits: alpha (catalytic) and beta.
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Found in skin and kidney. Ref.10
Sequence similarities	Belongs to the cation transport ATPase (P-type) family. Type IIC subfamily.

Ontologies

Keywords
Biological process	Hydrogen ion transport Ion transport Potassium transport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding Potassium
Molecular function	Hydrolase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	ATP biosynthetic process Inferred from electronic annotation. Source: InterPro potassium ion transport Inferred from electronic annotation. Source: UniProtKB-KW proton transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	hydrogen:potassium-exchanging ATPase complex Ref.2 Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW hydrogen:potassium-exchanging ATPase activity Inferred from electronic annotation. Source: EC magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW potassium ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P54707-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P54707-2)

The sequence of this isoform differs from the canonical sequence as follows:
     266-266: E → EASTSPV

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1039	1039	Potassium-transporting ATPase alpha chain 2		PRO_0000046260
Regions
	Topological domain	1 – 102	102	Cytoplasmic Potential
	Transmembrane	103 – 123	21	Potential
	Topological domain	124 – 146	23	Lumenal Potential
	Transmembrane	147 – 167	21	Potential
	Topological domain	168 – 303	136	Cytoplasmic Potential
	Transmembrane	304 – 323	20	Potential
	Topological domain	324 – 335	12	Lumenal Potential
	Transmembrane	336 – 353	18	Potential
	Topological domain	354 – 787	434	Cytoplasmic Potential
	Transmembrane	788 – 807	20	Potential
	Topological domain	808 – 817	10	Lumenal Potential
	Transmembrane	818 – 838	21	Potential
	Topological domain	839 – 858	20	Cytoplasmic Potential
	Transmembrane	859 – 881	23	Potential
	Topological domain	882 – 933	52	Lumenal Potential
	Transmembrane	934 – 953	20	Potential
	Topological domain	954 – 967	14	Cytoplasmic Potential
	Transmembrane	968 – 986	19	Potential
	Topological domain	987 – 1001	15	Lumenal Potential
	Transmembrane	1002 – 1022	21	Potential
	Topological domain	1023 – 1039	17	Cytoplasmic Potential
Sites
	Active site	391	1	4-aspartylphosphate intermediate By similarity
	Metal binding	732	1	Magnesium By similarity
	Metal binding	736	1	Magnesium By similarity
Amino acid modifications
	Modified residue	958	1	Phosphoserine; by PKA By similarity
Natural variations
	Alternative sequence	266	1	E → EASTSPV in isoform 2.		VSP_034640
	Natural variant	863	1	P → L: dbSNP rs2289909.		VAR_020186
Experimental info
	Sequence conflict	3	1	Q → QLFQ in AAC37589. Ref.2
	Sequence conflict	145	1	V → VRLWGVQV in CAA49477. Ref.7
	Sequence conflict	225 – 227	3	Missing in CAA49477. Ref.7
	Sequence conflict	266	1	E → V in CAA49477. Ref.7
	Sequence conflict	382	1	L → P in AAA35576. Ref.9
	Sequence conflict	724 – 727	4	DAVV → VGGQ in CAA49478. Ref.7
	Sequence conflict	772 – 773	2	SI → LH in CAA49478. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 22, 2008. Version 3. Checksum: C906897E11FA406C	FASTA	1,039	115,511
	10 20 30 40 50 60 MHQKTPEIYS VELSGTKDIV KTDKGDGKEK YRGLKNNCLE LKKKNHKEEF QKELHLDDHK 70 80 90 100 110 120 LSNRELEEKY GTDIIMGLSS TRAAELLARD GPNSLTPPKQ TPEIVKFLKQ MVGGFSILLW 130 140 150 160 170 180 VGAFLCWIAY GIQYSSDKSA SLNNVYLGCV LGLVVILTGI FAYYQEAKST NIMSSFNKMI 190 200 210 220 230 240 PQQALVIRDS EKKTIPSEQL VVGDIVEVKG GDQIPADIRV LSSQGCRVDN SSLTGESEPQ 250 260 270 280 290 300 PRSSEFTHEN PLETKNICFY STTCLEGTVT GMVINTGDRT IIGHIASLAS GVGNEKTPIA 310 320 330 340 350 360 IEIEHFVHIV AGVAVSIGIL FFIIAVSLKY QVLDSIIFLI GIIVANVPEG LLATVTVTLS 370 380 390 400 410 420 LTAKRMAKKN CLVKNLEAVE TLGSTSIICS DKTGTLTQNR MTVAHLWFDN QIFVADTSED 430 440 450 460 470 480 HSNQVFDQSS RTWASLSKII TLCNRAEFKP GQENVPIMKK AVIGDASETA LLKFSEVILG 490 500 510 520 530 540 DVMEIRKRNR KVAEIPFNST NKFQLSIHEM DDPHGKRFLM VMKGAPERIL EKCSTIMING 550 560 570 580 590 600 EEHPLDKSTA KTFHTAYMEL GGLGERVLGF CHLYLPADEF PETYSFDIDA MNFPTSNLCF 610 620 630 640 650 660 VGLLSMIDPP RSTVPDAVTK CRSAGIKVIM VTGDHPITAK AIAKSVGIIS ANSETVEDIA 670 680 690 700 710 720 HRLNIAVEQV NKRDAKAAVV TGMELKDMSS EQLDEILANY QEIVFARTSP QQKLIIVEGC 730 740 750 760 770 780 QRQDAVVAVT GDGVNDSPAL KKADIGIAMG IAGSDAAKNA ADMVLLDDNF ASIVTGVEEG 790 800 810 820 830 840 RLIFDNLKKT IAYSLTKNIA ELCPFLIYII VGLPLPIGTI TILFIDLGTD IIPSIALAYE 850 860 870 880 890 900 KAESDIMNRK PRHKNKDRLV NQPLAVYSYL HIGLMQALGA FLVYFTVYAQ EGFLPRTLIN 910 920 930 940 950 960 LRVEWEKDYV NDLKDSYGQE WTRYQREYLE WTGYTAFFVG ILVQQIADLI IRKTRRNSIF 970 980 990 1000 1010 1020 QQGLFRNKVI WVGITSQIII GLILSYGLGS VTALSFTMLR AQYWFVAVPH AILIWVYDEV 1030 RKLFIRLYPG SWWDKNMYY
	Isoform 2. Checksum: 15088FC158FB580A	FASTA	1,045	116,053
	10 20 30 40 50 60 MHQKTPEIYS VELSGTKDIV KTDKGDGKEK YRGLKNNCLE LKKKNHKEEF QKELHLDDHK 70 80 90 100 110 120 LSNRELEEKY GTDIIMGLSS TRAAELLARD GPNSLTPPKQ TPEIVKFLKQ MVGGFSILLW 130 140 150 160 170 180 VGAFLCWIAY GIQYSSDKSA SLNNVYLGCV LGLVVILTGI FAYYQEAKST NIMSSFNKMI 190 200 210 220 230 240 PQQALVIRDS EKKTIPSEQL VVGDIVEVKG GDQIPADIRV LSSQGCRVDN SSLTGESEPQ 250 260 270 280 290 300 PRSSEFTHEN PLETKNICFY STTCLEASTS PVGTVTGMVI NTGDRTIIGH IASLASGVGN 310 320 330 340 350 360 EKTPIAIEIE HFVHIVAGVA VSIGILFFII AVSLKYQVLD SIIFLIGIIV ANVPEGLLAT 370 380 390 400 410 420 VTVTLSLTAK RMAKKNCLVK NLEAVETLGS TSIICSDKTG TLTQNRMTVA HLWFDNQIFV 430 440 450 460 470 480 ADTSEDHSNQ VFDQSSRTWA SLSKIITLCN RAEFKPGQEN VPIMKKAVIG DASETALLKF 490 500 510 520 530 540 SEVILGDVME IRKRNRKVAE IPFNSTNKFQ LSIHEMDDPH GKRFLMVMKG APERILEKCS 550 560 570 580 590 600 TIMINGEEHP LDKSTAKTFH TAYMELGGLG ERVLGFCHLY LPADEFPETY SFDIDAMNFP 610 620 630 640 650 660 TSNLCFVGLL SMIDPPRSTV PDAVTKCRSA GIKVIMVTGD HPITAKAIAK SVGIISANSE 670 680 690 700 710 720 TVEDIAHRLN IAVEQVNKRD AKAAVVTGME LKDMSSEQLD EILANYQEIV FARTSPQQKL 730 740 750 760 770 780 IIVEGCQRQD AVVAVTGDGV NDSPALKKAD IGIAMGIAGS DAAKNAADMV LLDDNFASIV 790 800 810 820 830 840 TGVEEGRLIF DNLKKTIAYS LTKNIAELCP FLIYIIVGLP LPIGTITILF IDLGTDIIPS 850 860 870 880 890 900 IALAYEKAES DIMNRKPRHK NKDRLVNQPL AVYSYLHIGL MQALGAFLVY FTVYAQEGFL 910 920 930 940 950 960 PRTLINLRVE WEKDYVNDLK DSYGQEWTRY QREYLEWTGY TAFFVGILVQ QIADLIIRKT 970 980 990 1000 1010 1020 RRNSIFQQGL FRNKVIWVGI TSQIIIGLIL SYGLGSVTAL SFTMLRAQYW FVAVPHAILI 1030 1040 WVYDEVRKLF IRLYPGSWWD KNMYY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of the entire cDNA encoded by ATP1AL1 --a member of the human Na,K/H,K-ATPase gene family." Grishin A.V., Sverdlov V.E., Kostina M.B., Modyanov N.N. FEBS Lett. 349:144-150(1994) [PubMed: 8045293] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Kidney and Skin.
[2]	"Genomic organization of the human ATP1AL1 gene encoding a ouabain-sensitive H,K-ATPase." Sverdlov V.E., Kostina M.B., Modyanov N.N. Genomics 32:317-327(1996) [PubMed: 8838794] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Trachea.
[4]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed: 15057823] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain.
[7]	"The family of human Na,K-ATPase genes. ATP1AL1 gene is transcriptionally competent and probably encodes the related ion transport ATPase." Modyanov N.N., Petrukhin K.E., Sverdlov V.E., Grishin A.V., Orlova M.Y., Kostina M.B., Makarevich O.I., Broude N.E., Monastyrskaya G.S., Sverdlov E.D. FEBS Lett. 278:91-94(1991) [PubMed: 1847115] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 77-348 AND 681-780.
[8]	"Multiple genes encode the human Na+,K+-ATPase catalytic subunit." Shull M.M., Lingrel J.B. Proc. Natl. Acad. Sci. U.S.A. 84:4039-4043(1987) [PubMed: 3035563] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 183-253.
[9]	"The family of human Na+,K+-ATPase genes. No less than five genes and/or pseudogenes related to the alpha-subunit." Sverdlov E.D., Monastyrskaya G.S., Broude N.E., Ushkaryov Y.A., Allikmets R.L., Melkov A.M., Smirnov Y.V., Malyshev I.V., Dulubova I.E., Petrukhin K.E., Gryshin A.V., Kiyatkin N.I., Kostina M.B., Sverdlov V.E., Modyanov N.N., Ovchinnikov Y.A. FEBS Lett. 217:275-278(1987) [PubMed: 3036582] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 357-412.
[10]	"Ouabain-sensitive H,K-ATPase: tissue-specific expression of the mammalian genes encoding the catalytic alpha subunit." Pestov N.B., Romanova L.G., Korneenko T.V., Egorov M.V., Kostina M.B., Sverdlov V.E., Askari A., Shakhparonov M.I., Modyanov N.N. FEBS Lett. 440:320-324(1998) [PubMed: 9872395] [Abstract] Cited for: TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U02076 mRNA. Translation: AAB37755.1. L42563 , L42558, L42559, L42565, L42566, L42567, L42560, L42561, L42568, L42562, L42569 Genomic DNA. Translation: AAC37589.2. AK292968 mRNA. Translation: BAF85657.1. AL157364 Genomic DNA. Translation: CAH72440.1. CH471075 Genomic DNA. Translation: EAX08346.1. CH471075 Genomic DNA. Translation: EAX08345.1. BC031609 mRNA. Translation: AAH31609.1. X69823 Genomic DNA. Translation: CAA49477.1. X69824 Genomic DNA. Translation: CAA49478.1. M16797 mRNA. Translation: AAA51802.1. M27574 Genomic DNA. Translation: AAA35576.1.
IPI	IPI00008161. IPI00872242.
PIR	A26641. D27795. E27397. I38401. S13028. S31504.
RefSeq	NP_001667.4.
UniGene	Hs.147111
3D structure databases
HSSP	HSSP built from PDB template 1MO7 based on UniProtKB P06685.
ModBase	Search...
PTM databases
PhosphoSite	P54707.
Genome annotation databases
Ensembl	ENSG00000075673. Homo sapiens. [Contig view]
GeneID	479.
KEGG	hsa:479.
NMPDR	fig|9606.3.peg.8639.
Organism-specific databases
GeneCards	GC13P024152.
HGNC	HGNC:13816. ATP12A.
MIM	182360. gene.
PharmGKB	PA25104.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	P54707.
OMA	P54707. CPFLIYI.
Enzyme and pathway databases
BRENDA	3.6.3.10. 247.
Gene expression databases
ArrayExpress	P54707.
Bgee	P54707.
CleanEx	HS_ATP12A.
GermOnline	ENSG00000075673. Homo sapiens.
Family and domain databases
InterPro	IPR008250. ATPase_P-typ_ATPase-assoc-reg. IPR005775. ATPase_P-typ_cation-ex_asu_euk. IPR006069. ATPase_P-typ_cation-exchng_asu. IPR006068. ATPase_P-typ_cation-transptr_C. IPR004014. ATPase_P-typ_cation-transptr_N. IPR001757. ATPase_P-typ_ion-transptr. IPR018303. ATPase_P-typ_phosphor_site. IPR005834. Dehalogen-like_hydro. [Graphical view]
PANTHER	PTHR11939. ATPase_P. 1 hit.
Pfam	PF00689. Cation_ATPase_C. 1 hit. PF00690. Cation_ATPase_N. 1 hit. PF00122. E1-E2_ATPase. 1 hit. PF00702. Hydrolase. 1 hit. [Graphical view]
PRINTS	PR00119. CATATPASE. PR00121. NAKATPASE.
TIGRFAMs	TIGR01106. ATPase-IIC_X-K. 1 hit. TIGR01494. ATPase_P-type. 4 hits.
PROSITE	PS00154. ATPASE_E1_E2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00736. Esomeprazole. DB00213. Pantoprazole.
NextBio	1985.
SOURCE	Search...

Entry information

Entry name

AT12A_HUMAN

Accession

Primary (citable) accession number: P54707
Secondary accession number(s): Q13816 , Q13817, Q16734, Q5W035, Q8N5U2

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	July 22, 2008
Last modified:	June 16, 2009
This is version 96 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)