P06685 (AT1A1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sodium/potassium-transporting ATPase subunit alpha-1
Short name=Na(+)/K(+) ATPase alpha-1 subunit
EC=3.6.3.9

Alternative name(s):
Sodium pump subunit alpha-1

Gene names

Name:

Atp1a1

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	1023 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients.
Catalytic activity	ATP + H2O + Na+(In) + K+(Out) = ADP + phosphate + Na+(Out) + K+(In).
Subunit structure	Composed of three subunits: alpha (catalytic), beta and gamma. Interacts with SIK1. Ref.12
Subcellular location	Cell membrane; Multi-pass membrane protein. Melanosome By similarity.
Post-translational modification	Phosphorylation on Tyr-10 modulates pumping activity. Dephosphorylation by protein phosphatase 2A (PP2A) following increases in intracellular sodium, leading to increase catalytic activity.
Sequence similarities	Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIC subfamily. [View classification]

Ontologies

Keywords
Biological process	Ion transport Potassium transport Sodium transport Sodium/potassium transport Transport
Cellular component	Cell membrane Membrane
Domain	Transmembrane Transmembrane helix
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding Potassium Sodium
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	ATP biosynthetic process Inferred from electronic annotation. Source: InterPro energy coupled proton transport, against electrochemical gradient Traceable author statement. Source: RGD potassium ion import Inferred from direct assay. Source: RGD regulation of sodium ion transport Inferred from direct assay Ref.12. Source: UniProtKB
Cellular component	caveola Inferred from direct assay. Source: RGD endosome Inferred from direct assay. Source: RGD melanosome Inferred from electronic annotation. Source: UniProtKB-SubCell membrane fraction Inferred from direct assay. Source: RGD sodium:potassium-exchanging ATPase complex Inferred from direct assay. Source: RGD
Molecular function	ADP binding Inferred from direct assay. Source: RGD ATP binding Inferred from direct assay. Source: RGD phosphatidylinositol 3-kinase binding Inferred from physical interaction. Source: RGD potassium ion binding Inferred from direct assay. Source: RGD protein domain specific binding Inferred from physical interaction. Source: RGD protein kinase binding Inferred from physical interaction Ref.12. Source: UniProtKB sodium ion binding Inferred from direct assay. Source: RGD sodium:potassium-exchanging ATPase activity Inferred from direct assay Ref.12. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Propeptide

1 – 5

5

PRO_0000002489

Chain

6 – 1023

1018

Sodium/potassium-transporting ATPase subunit alpha-1

PRO_0000002490

Regions

Topological domain

6 – 87

82

Cytoplasmic Potential

Transmembrane

88 – 108

21

Helical; Potential

Topological domain

109 – 131

23

Extracellular Potential

Transmembrane

132 – 152

21

Helical; Potential

Topological domain

153 – 288

136

Cytoplasmic Potential

Transmembrane

289 – 308

20

Helical; Potential

Topological domain

309 – 320

12

Extracellular Potential

Transmembrane

321 – 338

18

Helical; Potential

Topological domain

339 – 772

434

Cytoplasmic Potential

Transmembrane

773 – 792

20

Helical; Potential

Topological domain

793 – 802

10

Extracellular Potential

Transmembrane

803 – 823

21

Helical; Potential

Topological domain

824 – 843

20

Cytoplasmic Potential

Transmembrane

844 – 866

23

Helical; Potential

Topological domain

867 – 918

52

Extracellular Potential

Transmembrane

919 – 938

20

Helical; Potential

Topological domain

939 – 951

13

Cytoplasmic Potential

Transmembrane

952 – 970

19

Helical; Potential

Topological domain

971 – 985

15

Extracellular Potential

Transmembrane

986 – 1006

21

Helical; Potential

Topological domain

1007 – 1023

17

Cytoplasmic Potential

Region

82 – 84

3

Phosphoinositide-3 kinase binding

Sites

Active site

376

1

4-aspartylphosphate intermediate By similarity

Metal binding

717

1

Magnesium By similarity

Metal binding

721

1

Magnesium By similarity

Amino acid modifications

Modified residue

10

1

Phosphotyrosine Ref.9

Modified residue

16

1

Phosphoserine; by PKC

Modified residue

23

1

Phosphoserine; by PKC

Modified residue

47

1

Phosphoserine By similarity

Modified residue

55

1

Phosphotyrosine By similarity

Modified residue

217

1

Phosphoserine By similarity

Modified residue

219

1

Phosphothreonine By similarity

Modified residue

228

1

Phosphoserine By similarity

Modified residue

260

1

Phosphotyrosine By similarity

Modified residue

452

1

Phosphoserine By similarity

Modified residue

943

1

Phosphoserine; by PKA

Experimental info

Mutagenesis

16

1

S → A: Dopamine fails to increase phosphoinositide-3 kinase activity and to promote its interaction with Na(+)/K(+) ATPase.

Mutagenesis

83

1

P → R: Dopamine fails to increase phosphoinositide-3 kinase activity and to promote its interaction with Na(+)/K(+) ATPase.

Sequence conflict

68 – 69

2

AA → PV in AAA41671. Ref.3

Sequence conflict

175

1

G → E in AAA41671. Ref.3

Sequence conflict

188

1

G → V in AAA41671. Ref.3

Sequence conflict

335

1

G → V in AAA41671. Ref.3

Secondary structure

1

.

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1023

Helix Strand Turn

Details...

Beta strand

394 – 396

3

Beta strand

403 – 405

3

Helix

416 – 427

12

Beta strand

431 – 435

5

Beta strand

438 – 440

3

Beta strand

447 – 449

3

Turn

451 – 453

3

Helix

454 – 461

8

Turn

462 – 464

3

Helix

467 – 473

7

Beta strand

478 – 480

3

Beta strand

489 – 494

6

Beta strand

496 – 500

5

Beta strand

502 – 509

8

Helix

511 – 515

5

Beta strand

518 – 521

4

Helix

532 – 546

15

Turn

562 – 564

3

Turn

572 – 574

3

Sequences

	Sequence		Length	Mass (Da)
	P06685 [UniParc]. Last modified January 1, 1988. Version 1. Checksum: 85E98233EE6C18E9	FASTA	1,023	113,054
	10 20 30 40 50 60 MGKGVGRDKY EPAAVSEHGD KKSKKAKKER DMDELKKEVS MDDHKLSLDE LHRKYGTDLS 70 80 90 100 110 120 RGLTPARAAE ILARDGPNAL TPPPTTPEWV KFCRQLFGGF SMLLWIGAIL CFLAYGIRSA 130 140 150 160 170 180 TEEEPPNDDL YLGVVLSAVV IITGCFSYYQ EAKSSKIMES FKNMVPQQAL VIRNGEKMSI 190 200 210 220 230 240 NAEDVVVGDL VEVKGGDRIP ADLRIISANG CKVDNSSLTG ESEPQTRSPD FTNENPLETR 250 260 270 280 290 300 NIAFFSTNCV EGTARGIVVY TGDRTVMGRI ATLASGLEGG QTPIAEEIEH FIHLITGVAV 310 320 330 340 350 360 FLGVSFFILS LILEYTWLEA VIFLIGIIVA NVPEGLLATV TVCLTLTAKR MARKNCLVKN 370 380 390 400 410 420 LEAVETLGST STICSDKTGT LTQNRMTVAH MWFDNQIHEA DTTENQSGVS FDKTSATWFA 430 440 450 460 470 480 LSRIAGLCNR AVFQANQENL PILKRAVAGD ASESALLKCI EVCCGSVMEM REKYTKIVEI 490 500 510 520 530 540 PFNSTNKYQL SIHKNPNASE PKHLLVMKGA PERILDRCSS ILLHGKEQPL DEELKDAFQN 550 560 570 580 590 600 AYLELGGLGE RVLGFCHLLL PDEQFPEGFQ FDTDEVNFPV DNLCFVGLIS MIDPPRAAVP 610 620 630 640 650 660 DAVGKCRSAG IKVIMVTGDH PITAKAIAKG VGIISEGNET VEDIAARLNI PVNQVNPRDA 670 680 690 700 710 720 KACVVHGSDL KDMTSEELDD ILRYHTEIVF ARTSPQQKLI IVEGCQRQGA IVAVTGDGVN 730 740 750 760 770 780 DSPALKKADI GVAMGIVGSD VSKQAADMIL LDDNFASIVT GVEEGRLIFD NLKKSIAYTL 790 800 810 820 830 840 TSNIPEITPF LIFIIANIPL PLGTVTILCI DLGTDMVPAI SLAYEQAESD IMKRQPRNPK 850 860 870 880 890 900 TDKLVNERLI SMAYGQIGMI QALGGFFTYF VILAENGFLP FHLLGIRETW DDRWINDVED 910 920 930 940 950 960 SYGQQWTYEQ RKIVEFTCHT AFFVSIVVVQ WADLVICKTR RNSVFQQGMK NKILIFGLFE 970 980 990 1000 1010 1020 ETALAAFLSY CPGMGAALRM YPLKPTWWFC AFPYSLLIFV YDEVRKLIIR RRPGGWVEKE TYY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of three distinct forms of the Na+,K+-ATPase alpha-subunit from rat brain." Shull G.E., Greeb J., Lingrel J.B. Biochemistry 25:8125-8132(1986) [PubMed: 3028470] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain and Kidney.
[2]	"Primary structures of two types of alpha-subunit of rat brain Na+,K+,-ATPase deduced from cDNA sequences." Hara Y., Urayama O., Kawakami K., Nojima H., Nagamune H., Kojima T., Ohta T., Nagano K., Nakao M. J. Biochem. 102:43-58(1987) [PubMed: 2822682] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[3]	"Three differentially expressed Na,K-ATPase alpha subunit isoforms: structural and functional implications." Herrera V.L.M., Emanuel J.R., Ruiz-Opazo N., Levenson R., Nadal-Ginard B. J. Cell Biol. 105:1855-1865(1987) [PubMed: 2822726] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"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]. Tissue: Prostate.
[5]	Lubec G., Kang S.U. Submitted (JUL-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 157-162; 597-605; 630-647; 662-671 AND 744-773, MASS SPECTROMETRY. Strain: Sprague-Dawley. Tissue: Brain.
[6]	"Molecular cloning of rat brain Na,K-ATPase alpha-subunit cDNA." Schneider J.W., Mercer R.W., Caplan M., Emanuel J.R., Sweadner K.J., Benz E.J. Jr., Levenson R. Proc. Natl. Acad. Sci. U.S.A. 82:6357-6361(1985) [PubMed: 2994074] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 489-533. Tissue: Brain.
[7]	"Cloning and analysis of the 5'-flanking region of rat Na+/K(+)-ATPase alpha 1 subunit gene." Yagawa Y., Kawakami K., Nagano K. Biochim. Biophys. Acta 1049:286-292(1990) [PubMed: 2166579] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-41.
[8]	"Identification of the phosphorylation site for cAMP-dependent protein kinase on Na+,K(+)-ATPase and effects of site-directed mutagenesis." Fisone G., Cheng S.X.-J., Nairn A.C., Czernik A.J., Hemmings H.C. Jr., Hoeoeg J.-O., Bertorello A.M., Kaiser R., Bergman T., Joernvall H., Aperia A., Greengard P. J. Biol. Chem. 269:9368-9373(1994) [PubMed: 7510709] [Abstract] Cited for: PHOSPHORYLATION BY CAMP-DEPENDENT KINASE.
[9]	"Insulin-induced stimulation of Na+,K(+)-ATPase activity in kidney proximal tubule cells depends on phosphorylation of the alpha-subunit at Tyr-10." Feraille E., Carranza M.L., Gonin S., Beguin P., Pedemonte C., Rousselot M., Caverzasio J., Geering K., Martin P.Y., Favre H. Mol. Biol. Cell 10:2847-2859(1999) [PubMed: 10473631] [Abstract] Cited for: PHOSPHORYLATION AT TYR-10.
[10]	"Structural basis for species-specific differences in the phosphorylation of Na,K-ATPase by protein kinase C." Feschenko M.S., Sweadner K.J. J. Biol. Chem. 270:14072-14077(1995) [PubMed: 7775468] [Abstract] Cited for: PROTEIN SEQUENCE OF N-TERMINUS, PHOSPHORYLATION BY PROTEIN KINASE C.
[11]	"Phosphoinositide-3 kinase binds to a proline-rich motif in the Na+, K+-ATPase alpha subunit and regulates its trafficking." Yudowski G.A., Efendiev R., Pedemonte C.H., Katz A.I., Berggren P.-O., Bertorello A.M. Proc. Natl. Acad. Sci. U.S.A. 97:6556-6561(2000) [PubMed: 10823893] [Abstract] Cited for: BINDING SITE FOR PHOSPHOINOSITIDE-3 KINASE, MUTAGENESIS.
[12]	"SIK1 is part of a cell sodium-sensing network that regulates active sodium transport through a calcium-dependent process." Sjostrom M., Stenstrom K., Eneling K., Zwiller J., Katz A.I., Takemori H., Bertorello A.M. Proc. Natl. Acad. Sci. U.S.A. 104:16922-16927(2007) [PubMed: 17939993] [Abstract] Cited for: PHOSPHORYLATION, DEPHOSPHORYLATION, INTERACTION WITH SIK1.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M14511 mRNA. Translation: AAA40775.1.
X05882 mRNA. Translation: CAA29306.1.
M28647 mRNA. Translation: AAA41671.1.
BC061968 mRNA. Translation: AAH61968.1.
M11733 mRNA. Translation: AAA40783.1.
X53233 Genomic DNA. Translation: CAA37325.1.
X53234 Genomic DNA. Translation: CAA37326.1.

IPI

IPI00326305.

PIR

A24639.

RefSeq

NP_036636.1. NM_012504.1.

UniGene

Rn.217534.
Rn.2992.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1MO7	NMR	-	A	383-595	[»]
1MO8	NMR	-	A	383-595	[»]

ProteinModelPortal

P06685.

SMR

P06685. Positions 26-1023.

ModBase

Search...

Protein-protein interaction databases

IntAct

P06685. 1 interaction.

MINT

MINT-3089277.

STRING

P06685.

PTM databases

PhosphoSite

P06685.

Proteomic databases

PRIDE

P06685.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

24211.

KEGG

rno:24211.

Organism-specific databases

CTD

476.

RGD

2167. Atp1a1.

Phylogenomic databases

eggNOG

maNOG15809.

HOVERGEN

HBG004298.

Gene expression databases

Genevestigator

P06685.

Family and domain databases

InterPro

IPR023306. ATPase_cation_domN.
IPR008250. ATPase_P-typ_ATPase-assoc-dom.
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.
IPR023300. ATPase_P-typ_cyto_domA.
IPR023299. ATPase_P-typ_cyto_domN.
IPR001757. ATPase_P-typ_ion-transptr.
IPR018303. ATPase_P-typ_P_site.
IPR023298. ATPase_P-typ_TM_dom.
IPR005834. Dehalogen-like_hydro.
IPR023214. HAD-like_dom.
[Graphical view]

Gene3D

G3DSA:2.70.150.10. ATPase_P-typ_cyto_domA. 1 hit.
G3DSA:3.40.1110.10. ATPase_P-typ_cyto_domN. 1 hit.
G3DSA:1.20.1110.10. ATPase_P-typ_TM_dom. 2 hits.

KO

K01539.

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.

SMART

SM00831. Cation_ATPase_N. 1 hit.
[Graphical view]

SUPFAM

SSF81660. ATPase_cation_domN. 1 hit.
SSF56784. HAD-like_dom. 1 hit.

TIGRFAMs

TIGR01106. ATPase-IIC_X-K. 1 hit.
TIGR01494. ATPase_P-type. 2 hits.

PROSITE

PS00154. ATPASE_E1_E2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

602617.

Entry information

Entry name

AT1A1_RAT

Accession

Primary (citable) accession number: P06685
Secondary accession number(s): Q64609

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1988
Last sequence update:	January 1, 1988
Last modified:	November 16, 2011
This is version 132 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program