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Protein

Sodium/potassium-transporting ATPase subunit alpha-4

Gene

ATP1A4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 activityi

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

Enzyme regulationi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei3844-aspartylphosphate intermediateBy similarity1
Metal bindingi723MagnesiumBy similarity1
Metal bindingi727MagnesiumBy similarity1

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • metal ion binding Source: UniProtKB-KW
  • sodium:potassium-exchanging ATPase activity Source: UniProtKB

GO - Biological processi

  • ATP hydrolysis coupled proton transport Source: UniProtKB
  • cellular potassium ion homeostasis Source: GO_Central
  • cellular sodium ion homeostasis Source: GO_Central
  • fertilization Source: Ensembl
  • flagellated sperm motility Source: UniProtKB
  • ion transmembrane transport Source: Reactome
  • potassium ion import Source: GO_Central
  • potassium ion transport Source: UniProtKB
  • regulation of cardiac conduction Source: Reactome
  • regulation of cellular pH Source: UniProtKB
  • regulation of membrane potential Source: Ensembl
  • sodium ion export from cell Source: GO_Central
  • sodium ion transport Source: UniProtKB
  • spermatogenesis Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Ion transport, Potassium transport, Sodium transport, Sodium/potassium transport, Transport

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding, Potassium, Sodium

Enzyme and pathway databases

BioCyciZFISH:HS05675-MONOMER.
ReactomeiR-HSA-5578775. Ion homeostasis.
R-HSA-936837. Ion transport by P-type ATPases.

Names & Taxonomyi

Protein namesi
Recommended name:
Sodium/potassium-transporting ATPase subunit alpha-4 (EC:3.6.3.9)
Short name:
Na(+)/K(+) ATPase alpha-4 subunit
Alternative name(s):
Sodium pump subunit alpha-4
Gene namesi
Name:ATP1A4
Synonyms:ATP1AL2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:14073. ATP1A4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 95CytoplasmicSequence analysisAdd BLAST95
Transmembranei96 – 116HelicalSequence analysisAdd BLAST21
Topological domaini117 – 139ExtracellularSequence analysisAdd BLAST23
Transmembranei140 – 160HelicalSequence analysisAdd BLAST21
Topological domaini161 – 296CytoplasmicSequence analysisAdd BLAST136
Transmembranei297 – 316HelicalSequence analysisAdd BLAST20
Topological domaini317 – 328ExtracellularSequence analysisAdd BLAST12
Transmembranei329 – 346HelicalSequence analysisAdd BLAST18
Topological domaini347 – 778CytoplasmicSequence analysisAdd BLAST432
Transmembranei779 – 798HelicalSequence analysisAdd BLAST20
Topological domaini799 – 808ExtracellularSequence analysis10
Transmembranei809 – 829HelicalSequence analysisAdd BLAST21
Topological domaini830 – 849CytoplasmicSequence analysisAdd BLAST20
Transmembranei850 – 872HelicalSequence analysisAdd BLAST23
Topological domaini873 – 924ExtracellularSequence analysisAdd BLAST52
Transmembranei925 – 944HelicalSequence analysisAdd BLAST20
Topological domaini945 – 957CytoplasmicSequence analysisAdd BLAST13
Transmembranei958 – 976HelicalSequence analysisAdd BLAST19
Topological domaini977 – 991ExtracellularSequence analysisAdd BLAST15
Transmembranei992 – 1012HelicalSequence analysisAdd BLAST21
Topological domaini1013 – 1029CytoplasmicSequence analysisAdd BLAST17

GO - Cellular componenti

  • integral component of plasma membrane Source: UniProtKB
  • intracellular membrane-bounded organelle Source: GO_Central
  • plasma membrane Source: Reactome
  • sodium:potassium-exchanging ATPase complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi480.
OpenTargetsiENSG00000132681.
PharmGKBiPA65.

Chemistry databases

ChEMBLiCHEMBL2095186.

Polymorphism and mutation databases

BioMutaiATP1A4.
DMDMi23830899.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000463031 – 1029Sodium/potassium-transporting ATPase subunit alpha-4Add BLAST1029

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei949Phosphoserine; by PKABy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ13733.
MaxQBiQ13733.
PaxDbiQ13733.
PeptideAtlasiQ13733.
PRIDEiQ13733.

PTM databases

iPTMnetiQ13733.
PhosphoSitePlusiQ13733.
SwissPalmiQ13733.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000132681.
CleanExiHS_ATP1A4.
ExpressionAtlasiQ13733. baseline and differential.
GenevisibleiQ13733. HS.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi106970. 9 interactors.
IntActiQ13733. 1 interactor.
STRINGi9606.ENSP00000357060.

Structurei

3D structure databases

ProteinModelPortaliQ13733.
SMRiQ13733.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni90 – 92Interaction with phosphoinositide-3 kinaseBy similarity3

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0203. Eukaryota.
COG0474. LUCA.
GeneTreeiENSGT00850000132256.
HOVERGENiHBG004298.
InParanoidiQ13733.
KOiK01539.
OMAiKSSDTWF.
OrthoDBiEOG091G01BB.
PhylomeDBiQ13733.
TreeFamiTF312838.

Family and domain databases

Gene3Di1.20.1110.10. 2 hits.
2.70.150.10. 2 hits.
3.40.1110.10. 1 hit.
InterProiIPR006068. ATPase_P-typ_cation-transptr_C.
IPR004014. ATPase_P-typ_cation-transptr_N.
IPR023299. ATPase_P-typ_cyto_domN.
IPR018303. ATPase_P-typ_P_site.
IPR023298. ATPase_P-typ_TM_dom.
IPR008250. ATPase_P-typ_transduc_dom_A.
IPR023214. HAD-like_dom.
IPR005775. P-type_ATPase_IIC.
IPR001757. P_typ_ATPase.
[Graphical view]
PfamiPF00689. Cation_ATPase_C. 1 hit.
PF00690. Cation_ATPase_N. 1 hit.
PF00122. E1-E2_ATPase. 1 hit.
[Graphical view]
SMARTiSM00831. Cation_ATPase_N. 1 hit.
[Graphical view]
SUPFAMiSSF56784. SSF56784. 2 hits.
SSF81660. SSF81660. 1 hit.
TIGRFAMsiTIGR01106. ATPase-IIC_X-K. 1 hit.
TIGR01494. ATPase_P-type. 2 hits.
PROSITEiPS00154. ATPASE_E1_E2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q13733-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MGLWGKKGTV APHDQSPRRR PKKGLIKKKM VKREKQKRNM EELKKEVVMD
60 70 80 90 100
DHKLTLEELS TKYSVDLTKG HSHQRAKEIL TRGGPNTVTP PPTTPEWVKF
110 120 130 140 150
CKQLFGGFSL LLWTGAILCF VAYSIQIYFN EEPTKDNLYL SIVLSVVVIV
160 170 180 190 200
TGCFSYYQEA KSSKIMESFK NMVPQQALVI RGGEKMQINV QEVVLGDLVE
210 220 230 240 250
IKGGDRVPAD LRLISAQGCK VDNSSLTGES EPQSRSPDFT HENPLETRNI
260 270 280 290 300
CFFSTNCVEG TARGIVIATG DSTVMGRIAS LTSGLAVGQT PIAAEIEHFI
310 320 330 340 350
HLITVVAVFL GVTFFALSLL LGYGWLEAII FLIGIIVANV PEGLLATVTV
360 370 380 390 400
CLTLTAKRMA RKNCLVKNLE AVETLGSTST ICSDKTGTLT QNRMTVAHMW
410 420 430 440 450
FDMTVYEADT TEEQTGKTFT KSSDTWFMLA RIAGLCNRAD FKANQEILPI
460 470 480 490 500
AKRATTGDAS ESALLKFIEQ SYSSVAEMRE KNPKVAEIPF NSTNKYQMSI
510 520 530 540 550
HLREDSSQTH VLMMKGAPER ILEFCSTFLL NGQEYSMNDE MKEAFQNAYL
560 570 580 590 600
ELGGLGERVL GFCFLNLPSS FSKGFPFNTD EINFPMDNLC FVGLISMIDP
610 620 630 640 650
PRAAVPDAVS KCRSAGIKVI MVTGDHPITA KAIAKGVGII SEGTETAEEV
660 670 680 690 700
AARLKIPISK VDASAAKAIV VHGAELKDIQ SKQLDQILQN HPEIVFARTS
710 720 730 740 750
PQQKLIIVEG CQRLGAVVAV TGDGVNDSPA LKKADIGIAM GISGSDVSKQ
760 770 780 790 800
AADMILLDDN FASIVTGVEE GRLIFDNLKK SIMYTLTSNI PEITPFLMFI
810 820 830 840 850
ILGIPLPLGT ITILCIDLGT DMVPAISLAY ESAESDIMKR LPRNPKTDNL
860 870 880 890 900
VNHRLIGMAY GQIGMIQALA GFFTYFVILA ENGFRPVDLL GIRLHWEDKY
910 920 930 940 950
LNDLEDSYGQ QWTYEQRKVV EFTCQTAFFV TIVVVQWADL IISKTRRNSL
960 970 980 990 1000
FQQGMRNKVL IFGILEETLL AAFLSYTPGM DVALRMYPLK ITWWLCAIPY
1010 1020
SILIFVYDEI RKLLIRQHPD GWVERETYY
Length:1,029
Mass (Da):114,166
Last modified:October 10, 2002 - v3
Checksum:i69958248424D2C0B
GO
Isoform 2 (identifier: Q13733-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-864: Missing.

Note: No experimental confirmation available.
Show »
Length:165
Mass (Da):19,609
Checksum:i5789093F12A8AC94
GO

Sequence cautioni

The sequence AAQ07964 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAC05228 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti155S → W in AAA60941 (PubMed:7809153).Curated1
Sequence conflicti991 – 1017ITWWL…LLIRQ → WSFALTAQAGVKWRILGLLQ PLPPRFK in BAC05228 (PubMed:14702039).CuratedAdd BLAST27

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04837583G → D.1 PublicationCorresponds to variant rs6427504dbSNPEnsembl.1
Natural variantiVAR_048376297E → K.Corresponds to variant rs17368402dbSNPEnsembl.1
Natural variantiVAR_048377541M → R.Corresponds to variant rs16831482dbSNPEnsembl.1
Natural variantiVAR_048378586M → I.Corresponds to variant rs7528360dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0073641 – 864Missing in isoform 2. 1 PublicationAdd BLAST864

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF506797 mRNA. Translation: AAQ07964.1. Different initiation.
AL121987 Genomic DNA. Translation: CAI15274.1.
AF421887 Genomic DNA. Translation: AAL35818.1.
AF310646
, 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.
CCDSiCCDS1197.1. [Q13733-1]
CCDS44255.1. [Q13733-2]
RefSeqiNP_001001734.1. NM_001001734.1. [Q13733-2]
NP_653300.2. NM_144699.3. [Q13733-1]
UniGeneiHs.662219.

Genome annotation databases

EnsembliENST00000368081; ENSP00000357060; ENSG00000132681. [Q13733-1]
ENST00000470705; ENSP00000433094; ENSG00000132681. [Q13733-2]
GeneIDi480.
KEGGihsa:480.
UCSCiuc001fve.5. human. [Q13733-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF506797 mRNA. Translation: AAQ07964.1. Different initiation.
AL121987 Genomic DNA. Translation: CAI15274.1.
AF421887 Genomic DNA. Translation: AAL35818.1.
AF310646
, 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.
CCDSiCCDS1197.1. [Q13733-1]
CCDS44255.1. [Q13733-2]
RefSeqiNP_001001734.1. NM_001001734.1. [Q13733-2]
NP_653300.2. NM_144699.3. [Q13733-1]
UniGeneiHs.662219.

3D structure databases

ProteinModelPortaliQ13733.
SMRiQ13733.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106970. 9 interactors.
IntActiQ13733. 1 interactor.
STRINGi9606.ENSP00000357060.

Chemistry databases

ChEMBLiCHEMBL2095186.

PTM databases

iPTMnetiQ13733.
PhosphoSitePlusiQ13733.
SwissPalmiQ13733.

Polymorphism and mutation databases

BioMutaiATP1A4.
DMDMi23830899.

Proteomic databases

EPDiQ13733.
MaxQBiQ13733.
PaxDbiQ13733.
PeptideAtlasiQ13733.
PRIDEiQ13733.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000368081; ENSP00000357060; ENSG00000132681. [Q13733-1]
ENST00000470705; ENSP00000433094; ENSG00000132681. [Q13733-2]
GeneIDi480.
KEGGihsa:480.
UCSCiuc001fve.5. human. [Q13733-1]

Organism-specific databases

CTDi480.
DisGeNETi480.
GeneCardsiATP1A4.
HGNCiHGNC:14073. ATP1A4.
MIMi607321. gene.
neXtProtiNX_Q13733.
OpenTargetsiENSG00000132681.
PharmGKBiPA65.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0203. Eukaryota.
COG0474. LUCA.
GeneTreeiENSGT00850000132256.
HOVERGENiHBG004298.
InParanoidiQ13733.
KOiK01539.
OMAiKSSDTWF.
OrthoDBiEOG091G01BB.
PhylomeDBiQ13733.
TreeFamiTF312838.

Enzyme and pathway databases

BioCyciZFISH:HS05675-MONOMER.
ReactomeiR-HSA-5578775. Ion homeostasis.
R-HSA-936837. Ion transport by P-type ATPases.

Miscellaneous databases

ChiTaRSiATP1A4. human.
GeneWikiiATP1A4.
GenomeRNAii480.
PROiQ13733.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000132681.
CleanExiHS_ATP1A4.
ExpressionAtlasiQ13733. baseline and differential.
GenevisibleiQ13733. HS.

Family and domain databases

Gene3Di1.20.1110.10. 2 hits.
2.70.150.10. 2 hits.
3.40.1110.10. 1 hit.
InterProiIPR006068. ATPase_P-typ_cation-transptr_C.
IPR004014. ATPase_P-typ_cation-transptr_N.
IPR023299. ATPase_P-typ_cyto_domN.
IPR018303. ATPase_P-typ_P_site.
IPR023298. ATPase_P-typ_TM_dom.
IPR008250. ATPase_P-typ_transduc_dom_A.
IPR023214. HAD-like_dom.
IPR005775. P-type_ATPase_IIC.
IPR001757. P_typ_ATPase.
[Graphical view]
PfamiPF00689. Cation_ATPase_C. 1 hit.
PF00690. Cation_ATPase_N. 1 hit.
PF00122. E1-E2_ATPase. 1 hit.
[Graphical view]
SMARTiSM00831. Cation_ATPase_N. 1 hit.
[Graphical view]
SUPFAMiSSF56784. SSF56784. 2 hits.
SSF81660. SSF81660. 1 hit.
TIGRFAMsiTIGR01106. ATPase-IIC_X-K. 1 hit.
TIGR01494. ATPase_P-type. 2 hits.
PROSITEiPS00154. ATPASE_E1_E2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiAT1A4_HUMAN
AccessioniPrimary (citable) accession number: Q13733
Secondary accession number(s): Q504T2
, Q7Z4I9, Q8TBN8, Q8WXA7, Q8WXH7, Q8WY13
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 18, 2001
Last sequence update: October 10, 2002
Last modified: November 30, 2016
This is version 162 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.