Q13733 (AT1A4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1029 AA.
Sequence status	Complete.
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. 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 process	Ion transport Potassium transport Sodium transport Sodium/potassium transport Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding Potassium Sodium
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ATP 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: Compara regulation of cellular pH Inferred from direct assay PubMed 12112599. Source: UniProtKB regulation of membrane potential Inferred from electronic annotation. Source: Compara sperm motility Inferred from direct assay PubMed 12112599. Source: UniProtKB spermatogenesis Inferred from electronic annotation. Source: Compara
Cellular_component	sodium:potassium-exchanging ATPase complex Traceable author statement Ref.5. Source: UniProtKB
Molecular_function	ATP 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1029	1029	Sodium/potassium-transporting ATPase subunit alpha-4		PRO_0000046303
Regions
	Topological domain	1 – 95	95	Cytoplasmic Potential
	Transmembrane	96 – 116	21	Helical; Potential
	Topological domain	117 – 139	23	Extracellular Potential
	Transmembrane	140 – 160	21	Helical; Potential
	Topological domain	161 – 296	136	Cytoplasmic Potential
	Transmembrane	297 – 316	20	Helical; Potential
	Topological domain	317 – 328	12	Extracellular Potential
	Transmembrane	329 – 346	18	Helical; Potential
	Topological domain	347 – 778	432	Cytoplasmic Potential
	Transmembrane	779 – 798	20	Helical; Potential
	Topological domain	799 – 808	10	Extracellular Potential
	Transmembrane	809 – 829	21	Helical; Potential
	Topological domain	830 – 849	20	Cytoplasmic Potential
	Transmembrane	850 – 872	23	Helical; Potential
	Topological domain	873 – 924	52	Extracellular Potential
	Transmembrane	925 – 944	20	Helical; Potential
	Topological domain	945 – 957	13	Cytoplasmic Potential
	Transmembrane	958 – 976	19	Helical; Potential
	Topological domain	977 – 991	15	Extracellular Potential
	Transmembrane	992 – 1012	21	Helical; Potential
	Topological domain	1013 – 1029	17	Cytoplasmic Potential
	Region	90 – 92	3	Interaction with phosphoinositide-3 kinase By similarity
Sites
	Active site	384	1	4-aspartylphosphate intermediate By similarity
	Metal binding	723	1	Magnesium By similarity
	Metal binding	727	1	Magnesium By similarity
Amino acid modifications
	Modified residue	949	1	Phosphoserine; by PKA By similarity
Natural variations
	Alternative sequence	1 – 864	864	Missing in isoform 2.		VSP_007364
	Natural variant	83	1	G → D. Ref.5 Corresponds to variant rs6427504 [ dbSNP | Ensembl ].		VAR_048375
	Natural variant	297	1	E → K. Corresponds to variant rs17368402 [ dbSNP | Ensembl ].		VAR_048376
	Natural variant	541	1	M → R. Corresponds to variant rs16831482 [ dbSNP | Ensembl ].		VAR_048377
	Natural variant	586	1	M → I. Corresponds to variant rs7528360 [ dbSNP | Ensembl ].		VAR_048378
Experimental info
	Sequence conflict	155	1	S → W in AAA60941. Ref.5
	Sequence conflict	991 – 1017	27	ITWWL…LLIRQ → WSFALTAQAGVKWRILGLLQ PLPPRFK in BAC05228. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 10, 2002. Version 3. Checksum: 69958248424D2C0B	FASTA	1,029	114,166
	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
	Isoform 2 [UniParc]. Checksum: 5789093F12A8AC94	FASTA	165	19,609
	10 20 30 40 50 60 MIQALAGFFT YFVILAENGF RPVDLLGIRL HWEDKYLNDL EDSYGQQWTY EQRKVVEFTC 70 80 90 100 110 120 QTAFFVTIVV VQWADLIISK TRRNSLFQQG MRNKVLIFGI LEETLLAAFL SYTPGMDVAL 130 140 150 160 RMYPLKITWW LCAIPYSILI FVYDEIRKLL IRQHPDGWVE RETYY

References

	« Hide 'large scale' referencesShow '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. , 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. , 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 , 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.
IPI	IPI00252122. IPI00375339.
RefSeq	NP_001001734.1. NM_001001734.1. NP_653300.2. NM_144699.3.
UniGene	Hs.662219.
3D structure databases
ProteinModelPortal	Q13733.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000357060.
PTM databases
PhosphoSite	Q13733.
Polymorphism databases
DMDM	23830899.
Proteomic databases
PaxDb	Q13733.
PRIDE	Q13733.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000368081; ENSP00000357060; ENSG00000132681. ENST00000470705; ENSP00000433094; ENSG00000132681.
GeneID	480.
KEGG	hsa:480.
UCSC	uc001fve.4. human. uc001fvh.3. human.
Organism-specific databases
CTD	480.
GeneCards	GC01P160121.
HGNC	HGNC:14073. ATP1A4.
HPA	CAB033628.
MIM	607321. gene.
neXtProt	NX_Q13733.
PharmGKB	PA65.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0474.
HOVERGEN	HBG004298.
InParanoid	Q13733.
KO	K01539.
OMA	SHQRAKE.
OrthoDB	EOG4WDDB0.
PhylomeDB	Q13733.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	Q13733.
Bgee	Q13733.
CleanEx	HS_ATP1A4.
Genevestigator	Q13733.
GermOnline	ENSG00000132681. Homo sapiens.
Family and domain databases
Gene3D	1.20.1110.10. 2 hits. 2.70.150.10. 2 hits. 3.40.1110.10. 1 hit.
InterPro	IPR006068. 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]
PANTHER	PTHR24093. PTHR24093. 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.
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
BindingDB	Q13733.
ChEMBL	CHEMBL4053.
ChiTaRS	ATP1A4. human.
GenomeRNAi	480.
NextBio	1989.
SOURCE	Search...

Entry information

Entry name

AT1A4_HUMAN

Accession

Primary (citable) accession number: Q13733
Secondary accession number(s): Q504T2 , Q7Z4I9, Q8TBN8, Q8WXA7, Q8WXH7, Q8WY13

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 18, 2001
Last sequence update:	October 10, 2002
Last modified:	May 1, 2013
This is version 128 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.