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Q13733 (AT1A4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sodium/potassium-transporting ATPase subunit alpha-4

Short name=Na(+)/K(+) ATPase alpha-4 subunit
EC=3.6.3.9
Alternative name(s):
Sodium pump subunit alpha-4
Gene names
Name:ATP1A4
Synonyms:ATP1AL2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1029 AA.
Sequence statusComplete.
Protein existenceEvidence 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. Plays a role in sperm motility.

Catalytic activity

ATP + H2O + Na+(In) + K+(Out) = ADP + phosphate + Na+(Out) + K+(In).

Enzyme regulation

Specifically inhibited by an endogenous cardiac glycoside, ouabain. Ref.1

Subunit structure

Composed of three subunits: alpha (catalytic), beta and gamma.

Subcellular location

Cell membrane; Multi-pass membrane protein. Note: In mature sperm, located in the principle piece of the sperm flagellum. Ref.1

Tissue specificity

Specifically expressed in testis. Found in very low levels in skeletal muscle. Expressed in mature sperm (at protein level).

Sequence similarities

Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIC subfamily. [View classification]

Sequence caution

The sequence AAQ07964.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence BAC05228.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Biological processIon transport
Potassium transport
Sodium transport
Sodium/potassium transport
Transport
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransmembrane
Transmembrane helix
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
Potassium
Sodium
   Molecular functionHydrolase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processATP biosynthetic process

Inferred from electronic annotation. Source: InterPro

ATP hydrolysis coupled proton transport

Traceable author statement Ref.5. Source: UniProtKB

fertilization

Inferred from electronic annotation. Source: Ensembl

ion transmembrane transport

Traceable author statement. Source: Reactome

potassium ion transport

Traceable author statement Ref.5. Source: UniProtKB

regulation of cellular pH

Inferred from direct assay PubMed 12112599. Source: UniProtKB

regulation of membrane potential

Inferred from electronic annotation. Source: Ensembl

sodium ion transmembrane transport

Traceable author statement Ref.5. Source: GOC

sodium ion transport

Traceable author statement Ref.5. Source: UniProtKB

sperm motility

Inferred from direct assay PubMed 12112599. Source: UniProtKB

spermatogenesis

Inferred from electronic annotation. Source: Ensembl

transmembrane transport

Traceable author statement. Source: Reactome

   Cellular_componentintegral component of plasma membrane

Non-traceable author statement Ref.5. Source: UniProtKB

plasma membrane

Traceable author statement. Source: Reactome

sodium:potassium-exchanging ATPase complex

Traceable author statement Ref.5. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

sodium:potassium-exchanging ATPase activity

Traceable author statement Ref.5. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q13733-1)

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: Q13733-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-864: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10291029Sodium/potassium-transporting ATPase subunit alpha-4
PRO_0000046303

Regions

Topological domain1 – 9595Cytoplasmic Potential
Transmembrane96 – 11621Helical; Potential
Topological domain117 – 13923Extracellular Potential
Transmembrane140 – 16021Helical; Potential
Topological domain161 – 296136Cytoplasmic Potential
Transmembrane297 – 31620Helical; Potential
Topological domain317 – 32812Extracellular Potential
Transmembrane329 – 34618Helical; Potential
Topological domain347 – 778432Cytoplasmic Potential
Transmembrane779 – 79820Helical; Potential
Topological domain799 – 80810Extracellular Potential
Transmembrane809 – 82921Helical; Potential
Topological domain830 – 84920Cytoplasmic Potential
Transmembrane850 – 87223Helical; Potential
Topological domain873 – 92452Extracellular Potential
Transmembrane925 – 94420Helical; Potential
Topological domain945 – 95713Cytoplasmic Potential
Transmembrane958 – 97619Helical; Potential
Topological domain977 – 99115Extracellular Potential
Transmembrane992 – 101221Helical; Potential
Topological domain1013 – 102917Cytoplasmic Potential
Region90 – 923Interaction with phosphoinositide-3 kinase By similarity

Sites

Active site38414-aspartylphosphate intermediate By similarity
Metal binding7231Magnesium By similarity
Metal binding7271Magnesium By similarity

Amino acid modifications

Modified residue9491Phosphoserine; by PKA By similarity

Natural variations

Alternative sequence1 – 864864Missing in isoform 2.
VSP_007364
Natural variant831G → D. Ref.5
Corresponds to variant rs6427504 [ dbSNP | Ensembl ].
VAR_048375
Natural variant2971E → K.
Corresponds to variant rs17368402 [ dbSNP | Ensembl ].
VAR_048376
Natural variant5411M → R.
Corresponds to variant rs16831482 [ dbSNP | Ensembl ].
VAR_048377
Natural variant5861M → I.
Corresponds to variant rs7528360 [ dbSNP | Ensembl ].
VAR_048378

Experimental info

Sequence conflict1551S → W in AAA60941. Ref.5
Sequence conflict991 – 101727ITWWL…LLIRQ → WSFALTAQAGVKWRILGLLQ PLPPRFK in BAC05228. Ref.6

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 10, 2002. Version 3.
Checksum: 69958248424D2C0B

FASTA1,029114,166
        10         20         30         40         50         60 
MGLWGKKGTV APHDQSPRRR PKKGLIKKKM VKREKQKRNM EELKKEVVMD DHKLTLEELS 

        70         80         90        100        110        120 
TKYSVDLTKG HSHQRAKEIL TRGGPNTVTP PPTTPEWVKF CKQLFGGFSL LLWTGAILCF 

       130        140        150        160        170        180 
VAYSIQIYFN EEPTKDNLYL SIVLSVVVIV TGCFSYYQEA KSSKIMESFK NMVPQQALVI 

       190        200        210        220        230        240 
RGGEKMQINV QEVVLGDLVE IKGGDRVPAD LRLISAQGCK VDNSSLTGES EPQSRSPDFT 

       250        260        270        280        290        300 
HENPLETRNI CFFSTNCVEG TARGIVIATG DSTVMGRIAS LTSGLAVGQT PIAAEIEHFI 

       310        320        330        340        350        360 
HLITVVAVFL GVTFFALSLL LGYGWLEAII FLIGIIVANV PEGLLATVTV CLTLTAKRMA 

       370        380        390        400        410        420 
RKNCLVKNLE AVETLGSTST ICSDKTGTLT QNRMTVAHMW FDMTVYEADT TEEQTGKTFT 

       430        440        450        460        470        480 
KSSDTWFMLA RIAGLCNRAD FKANQEILPI AKRATTGDAS ESALLKFIEQ SYSSVAEMRE 

       490        500        510        520        530        540 
KNPKVAEIPF NSTNKYQMSI HLREDSSQTH VLMMKGAPER ILEFCSTFLL NGQEYSMNDE 

       550        560        570        580        590        600 
MKEAFQNAYL ELGGLGERVL GFCFLNLPSS FSKGFPFNTD EINFPMDNLC FVGLISMIDP 

       610        620        630        640        650        660 
PRAAVPDAVS KCRSAGIKVI MVTGDHPITA KAIAKGVGII SEGTETAEEV AARLKIPISK 

       670        680        690        700        710        720 
VDASAAKAIV VHGAELKDIQ SKQLDQILQN HPEIVFARTS PQQKLIIVEG CQRLGAVVAV 

       730        740        750        760        770        780 
TGDGVNDSPA LKKADIGIAM GISGSDVSKQ AADMILLDDN FASIVTGVEE GRLIFDNLKK 

       790        800        810        820        830        840 
SIMYTLTSNI PEITPFLMFI ILGIPLPLGT ITILCIDLGT DMVPAISLAY ESAESDIMKR 

       850        860        870        880        890        900 
LPRNPKTDNL VNHRLIGMAY GQIGMIQALA GFFTYFVILA ENGFRPVDLL GIRLHWEDKY 

       910        920        930        940        950        960 
LNDLEDSYGQ QWTYEQRKVV EFTCQTAFFV TIVVVQWADL IISKTRRNSL FQQGMRNKVL 

       970        980        990       1000       1010       1020 
IFGILEETLL AAFLSYTPGM DVALRMYPLK ITWWLCAIPY SILIFVYDEI RKLLIRQHPD 


GWVERETYY 

« Hide

Isoform 2 [UniParc].

Checksum: 5789093F12A8AC94
Show »

FASTA16519,609

References

« Hide 'large scale' references
[1]"The human Na,K-ATPase alpha 4 isoform is a ouabain-sensitive alpha isoform that is expressed in sperm."
Hlivko J.T., Chakraborty S., Hlivko T.J., Sengupta A., James P.F.
Mol. Reprod. Dev. 73:101-115(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, ENZYME REGULATION.
Tissue: Testis.
[2]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Testis and Urinary bladder.
[4]"Physical mapping and characterization of the human Na,K-ATPase isoform, ATP1A4."
Keryanov S., Gardner K.L.
Gene 292:151-166(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-69 AND 138-1029 (ISOFORM 1).
[5]"A putative fourth Na+,K(+)-ATPase alpha-subunit gene is expressed in testis."
Shamraj O.I., Lingrel J.B.
Proc. Natl. Acad. Sci. U.S.A. 91:12952-12956(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 50-220 (ISOFORM 1), VARIANT ASP-83.
Tissue: Testis.
[6]"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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 549-1017 (ISOFORM 1).
Tissue: Trachea.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF506797 mRNA. Translation: AAQ07964.1. Different initiation.
AL121987 Genomic DNA. Translation: CAI15274.1.
AF421887 Genomic DNA. Translation: AAL35818.1.
AF310646 expand/collapse EMBL AC list , AF430843, AF390027, AY039031 Genomic DNA. Translation: AAK72396.2.
AF459737 mRNA. Translation: AAL66357.1.
AF352828 Genomic DNA. Translation: AAM20793.1.
AH002997 Genomic DNA. Translation: AAA60941.1.
AK098076 mRNA. Translation: BAC05228.1. Different initiation.
BC028297 mRNA. Translation: AAH28297.1.
BC094801 mRNA. Translation: AAH94801.1.
CCDSCCDS1197.1. [Q13733-1]
CCDS44255.1. [Q13733-2]
RefSeqNP_001001734.1. NM_001001734.1. [Q13733-2]
NP_653300.2. NM_144699.3. [Q13733-1]
UniGeneHs.662219.

3D structure databases

ProteinModelPortalQ13733.
SMRQ13733. Positions 38-1029.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106970. 4 interactions.
STRING9606.ENSP00000357060.

Chemistry

BindingDBQ13733.
ChEMBLCHEMBL2095186.

PTM databases

PhosphoSiteQ13733.

Polymorphism databases

DMDM23830899.

Proteomic databases

MaxQBQ13733.
PaxDbQ13733.
PRIDEQ13733.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000368081; ENSP00000357060; ENSG00000132681. [Q13733-1]
ENST00000470705; ENSP00000433094; ENSG00000132681. [Q13733-2]
GeneID480.
KEGGhsa:480.
UCSCuc001fve.4. human. [Q13733-1]
uc001fvh.3. human. [Q13733-2]

Organism-specific databases

CTD480.
GeneCardsGC01P160121.
HGNCHGNC:14073. ATP1A4.
HPACAB033628.
MIM607321. gene.
neXtProtNX_Q13733.
PharmGKBPA65.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0474.
HOVERGENHBG004298.
InParanoidQ13733.
KOK01539.
OMAKSSDTWF.
OrthoDBEOG7327N0.
PhylomeDBQ13733.
TreeFamTF312838.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressQ13733.
BgeeQ13733.
CleanExHS_ATP1A4.
GenevestigatorQ13733.

Family and domain databases

Gene3D1.20.1110.10. 2 hits.
2.70.150.10. 2 hits.
3.40.1110.10. 1 hit.
InterProIPR006068. ATPase_P-typ_cation-transptr_C.
IPR004014. ATPase_P-typ_cation-transptr_N.
IPR023299. ATPase_P-typ_cyto_domN.
IPR005775. ATPase_P-typ_Na/K_IIC.
IPR018303. ATPase_P-typ_P_site.
IPR023298. ATPase_P-typ_TM_dom.
IPR008250. ATPase_P-typ_transduc_dom_A.
IPR001757. Cation_transp_P_typ_ATPase.
IPR023214. HAD-like_dom.
[Graphical view]
PfamPF00689. Cation_ATPase_C. 1 hit.
PF00690. Cation_ATPase_N. 1 hit.
PF00122. E1-E2_ATPase. 1 hit.
PF00702. Hydrolase. 1 hit.
[Graphical view]
PRINTSPR00119. CATATPASE.
SMARTSM00831. Cation_ATPase_N. 1 hit.
[Graphical view]
SUPFAMSSF56784. SSF56784. 2 hits.
SSF81660. SSF81660. 1 hit.
TIGRFAMsTIGR01106. ATPase-IIC_X-K. 1 hit.
TIGR01494. ATPase_P-type. 2 hits.
PROSITEPS00154. ATPASE_E1_E2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSATP1A4. human.
GeneWikiATP1A4.
GenomeRNAi480.
NextBio1989.
PROQ13733.
SOURCESearch...

Entry information

Entry nameAT1A4_HUMAN
AccessionPrimary (citable) accession number: Q13733
Secondary accession number(s): Q504T2 expand/collapse secondary AC list , Q7Z4I9, Q8TBN8, Q8WXA7, Q8WXH7, Q8WY13
Entry history
Integrated into UniProtKB/Swiss-Prot: October 18, 2001
Last sequence update: October 10, 2002
Last modified: July 9, 2014
This is version 138 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM