ID   AT1A4_MOUSE             Reviewed;        1032 AA.
AC   Q9WV27; E9QKL5; Q9R173; Q9WV28;
DT   18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 3.
DT   27-MAR-2024, entry version 185.
DE   RecName: Full=Sodium/potassium-transporting ATPase subunit alpha-4 {ECO:0000305};
DE            Short=Na(+)/K(+) ATPase alpha-4 subunit;
DE            EC=7.2.2.13 {ECO:0000250|UniProtKB:Q64541};
DE   AltName: Full=Sodium pump subunit alpha-4;
GN   Name=Atp1a4 {ECO:0000312|MGI:MGI:1351335}; Synonyms=Atp1al2;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=C57BL/6J, and CD-1; TISSUE=Mammary gland, and Testis;
RX   PubMed=10555956; DOI=10.1021/bi9916168;
RA   Underhill D.A., Canfield V.A., Dahl J.P., Gros P., Levenson R.;
RT   "The Na,K-ATPase alpha4 gene (Atp1a4) encodes a ouabain-resistant alpha
RT   subunit and is tightly linked to the alpha2 gene (Atp1a2) on mouse
RT   chromosome 1.";
RL   Biochemistry 38:14746-14751(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [3]
RP   PROTEIN SEQUENCE OF 173-183; 370-387; 488-498; 606-634; 708-716 AND
RP   736-783, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC   STRAIN=C57BL/6J; TISSUE=Brain;
RA   Lubec G., Kang S.U.;
RL   Submitted (APR-2007) to UniProtKB.
RN   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Kidney;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
CC   -!- FUNCTION: This is the catalytic component of the active enzyme, which
CC       catalyzes the hydrolysis of ATP coupled with the exchange of sodium and
CC       potassium ions across the plasma membrane. This action creates the
CC       electrochemical gradient of sodium and potassium ions, providing the
CC       energy for active transport of various nutrients. Plays a role in sperm
CC       motility (By similarity). {ECO:0000250}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + H2O + K(+)(out) + Na(+)(in) = ADP + H(+) + K(+)(in) +
CC         Na(+)(out) + phosphate; Xref=Rhea:RHEA:18353, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:29101, ChEBI:CHEBI:29103,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC         EC=7.2.2.13; Evidence={ECO:0000250|UniProtKB:Q64541};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18354;
CC         Evidence={ECO:0000250|UniProtKB:Q64541};
CC   -!- ACTIVITY REGULATION: Specifically inhibited by an endogenous cardiac
CC       glycoside, ouabain. {ECO:0000250}.
CC   -!- SUBUNIT: The sodium/potassium-transporting ATPase is composed of a
CC       catalytic alpha subunit, an auxiliary non-catalytic beta subunit and an
CC       additional regulatory subunit. {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC   -!- TISSUE SPECIFICITY: Expressed at high levels in the testis and at low
CC       levels in the epididymis.
CC   -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3)
CC       family. Type IIC subfamily. {ECO:0000305}.
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DR   EMBL; AF164348; AAD43812.1; -; Genomic_DNA.
DR   EMBL; AF164349; AAD43813.1; -; Genomic_DNA.
DR   EMBL; AF164350; AAD43814.1; -; Genomic_DNA.
DR   EMBL; AC074310; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC087061; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS48446.1; -.
DR   RefSeq; NP_038762.1; NM_013734.1.
DR   AlphaFoldDB; Q9WV27; -.
DR   SMR; Q9WV27; -.
DR   BioGRID; 205143; 2.
DR   IntAct; Q9WV27; 1.
DR   STRING; 10090.ENSMUSP00000106874; -.
DR   iPTMnet; Q9WV27; -.
DR   PhosphoSitePlus; Q9WV27; -.
DR   SwissPalm; Q9WV27; -.
DR   EPD; Q9WV27; -.
DR   jPOST; Q9WV27; -.
DR   MaxQB; Q9WV27; -.
DR   PaxDb; 10090-ENSMUSP00000106874; -.
DR   PeptideAtlas; Q9WV27; -.
DR   ProteomicsDB; 277264; -.
DR   Antibodypedia; 55096; 19 antibodies from 5 providers.
DR   Ensembl; ENSMUST00000111243.2; ENSMUSP00000106874.2; ENSMUSG00000007107.7.
DR   GeneID; 27222; -.
DR   KEGG; mmu:27222; -.
DR   UCSC; uc011wwk.1; mouse.
DR   AGR; MGI:1351335; -.
DR   CTD; 480; -.
DR   MGI; MGI:1351335; Atp1a4.
DR   VEuPathDB; HostDB:ENSMUSG00000007107; -.
DR   eggNOG; KOG0203; Eukaryota.
DR   GeneTree; ENSGT00940000162378; -.
DR   HOGENOM; CLU_002360_3_3_1; -.
DR   InParanoid; Q9WV27; -.
DR   OMA; NGQEYSM; -.
DR   OrthoDB; 203629at2759; -.
DR   PhylomeDB; Q9WV27; -.
DR   TreeFam; TF312838; -.
DR   Reactome; R-MMU-5578775; Ion homeostasis.
DR   Reactome; R-MMU-936837; Ion transport by P-type ATPases.
DR   BioGRID-ORCS; 27222; 0 hits in 77 CRISPR screens.
DR   PRO; PR:Q9WV27; -.
DR   Proteomes; UP000000589; Chromosome 1.
DR   RNAct; Q9WV27; Protein.
DR   Bgee; ENSMUSG00000007107; Expressed in seminiferous tubule of testis and 26 other cell types or tissues.
DR   GO; GO:0042995; C:cell projection; IBA:GO_Central.
DR   GO; GO:0097733; C:photoreceptor cell cilium; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0120200; C:rod photoreceptor outer segment; ISO:MGI.
DR   GO; GO:0005890; C:sodium:potassium-exchanging ATPase complex; ISO:MGI.
DR   GO; GO:0097225; C:sperm midpiece; ISO:MGI.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR   GO; GO:0019829; F:ATPase-coupled monoatomic cation transmembrane transporter activity; ISO:MGI.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0005391; F:P-type sodium:potassium-exchanging transporter activity; IDA:MGI.
DR   GO; GO:0051649; P:establishment of localization in cell; IMP:MGI.
DR   GO; GO:0009566; P:fertilization; IMP:MGI.
DR   GO; GO:0030317; P:flagellated sperm motility; IMP:MGI.
DR   GO; GO:0030007; P:intracellular potassium ion homeostasis; IBA:GO_Central.
DR   GO; GO:0006883; P:intracellular sodium ion homeostasis; IBA:GO_Central.
DR   GO; GO:1990573; P:potassium ion import across plasma membrane; IBA:GO_Central.
DR   GO; GO:0071805; P:potassium ion transmembrane transport; ISO:MGI.
DR   GO; GO:1902600; P:proton transmembrane transport; IBA:GO_Central.
DR   GO; GO:0030641; P:regulation of cellular pH; ISS:UniProtKB.
DR   GO; GO:0042391; P:regulation of membrane potential; IMP:MGI.
DR   GO; GO:0036376; P:sodium ion export across plasma membrane; IBA:GO_Central.
DR   GO; GO:0035725; P:sodium ion transmembrane transport; ISO:MGI.
DR   GO; GO:0006814; P:sodium ion transport; IMP:MGI.
DR   GO; GO:0007283; P:spermatogenesis; IMP:MGI.
DR   CDD; cd02608; P-type_ATPase_Na-K_like; 1.
DR   Gene3D; 3.40.1110.10; Calcium-transporting ATPase, cytoplasmic domain N; 1.
DR   Gene3D; 2.70.150.10; Calcium-transporting ATPase, cytoplasmic transduction domain A; 1.
DR   Gene3D; 1.20.1110.10; Calcium-transporting ATPase, transmembrane domain; 1.
DR   Gene3D; 3.40.50.1000; HAD superfamily/HAD-like; 1.
DR   InterPro; IPR006068; ATPase_P-typ_cation-transptr_C.
DR   InterPro; IPR004014; ATPase_P-typ_cation-transptr_N.
DR   InterPro; IPR023299; ATPase_P-typ_cyto_dom_N.
DR   InterPro; IPR018303; ATPase_P-typ_P_site.
DR   InterPro; IPR023298; ATPase_P-typ_TM_dom_sf.
DR   InterPro; IPR008250; ATPase_P-typ_transduc_dom_A_sf.
DR   InterPro; IPR036412; HAD-like_sf.
DR   InterPro; IPR023214; HAD_sf.
DR   InterPro; IPR005775; P-type_ATPase_IIC.
DR   InterPro; IPR001757; P_typ_ATPase.
DR   InterPro; IPR044492; P_typ_ATPase_HD_dom.
DR   NCBIfam; TIGR01106; ATPase-IIC_X-K; 1.
DR   NCBIfam; TIGR01494; ATPase_P-type; 2.
DR   PANTHER; PTHR43294; SODIUM/POTASSIUM-TRANSPORTING ATPASE SUBUNIT ALPHA; 1.
DR   PANTHER; PTHR43294:SF3; SODIUM_POTASSIUM-TRANSPORTING ATPASE SUBUNIT ALPHA-4; 1.
DR   Pfam; PF13246; Cation_ATPase; 1.
DR   Pfam; PF00689; Cation_ATPase_C; 1.
DR   Pfam; PF00690; Cation_ATPase_N; 1.
DR   Pfam; PF00122; E1-E2_ATPase; 1.
DR   Pfam; PF00702; Hydrolase; 1.
DR   PRINTS; PR00119; CATATPASE.
DR   PRINTS; PR00121; NAKATPASE.
DR   SFLD; SFLDG00002; C1.7:_P-type_atpase_like; 1.
DR   SFLD; SFLDF00027; p-type_atpase; 1.
DR   SMART; SM00831; Cation_ATPase_N; 1.
DR   SUPFAM; SSF81653; Calcium ATPase, transduction domain A; 1.
DR   SUPFAM; SSF81665; Calcium ATPase, transmembrane domain M; 1.
DR   SUPFAM; SSF56784; HAD-like; 1.
DR   SUPFAM; SSF81660; Metal cation-transporting ATPase, ATP-binding domain N; 1.
DR   PROSITE; PS00154; ATPASE_E1_E2; 1.
DR   Genevisible; Q9WV27; MM.
PE   1: Evidence at protein level;
KW   ATP-binding; Cell membrane; Direct protein sequencing; Ion transport;
KW   Magnesium; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW   Potassium; Potassium transport; Reference proteome; Sodium;
KW   Sodium transport; Sodium/potassium transport; Translocase; Transmembrane;
KW   Transmembrane helix; Transport.
FT   CHAIN           1..1032
FT                   /note="Sodium/potassium-transporting ATPase subunit alpha-
FT                   4"
FT                   /id="PRO_0000046304"
FT   TOPO_DOM        1..96
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        97..117
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        118..141
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        142..162
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        163..298
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        299..318
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        319..330
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        331..348
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        349..781
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        782..801
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        802..811
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        812..832
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        833..852
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        853..875
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        876..927
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        928..947
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        948..960
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        961..979
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        980..994
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        995..1015
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1016..1032
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          1..42
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          91..93
FT                   /note="Interaction with phosphoinositide-3 kinase"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        386
FT                   /note="4-aspartylphosphate intermediate"
FT                   /evidence="ECO:0000250"
FT   BINDING         726
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250"
FT   BINDING         730
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         952
FT                   /note="Phosphoserine; by PKA"
FT                   /evidence="ECO:0000250"
FT   CONFLICT        74
FT                   /note="I -> V (in Ref. 1; AAD43812)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        476
FT                   /note="N -> S (in Ref. 1; AAD43813)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        546
FT                   /note="M -> T (in Ref. 1; AAD43813)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1032 AA;  114887 MW;  5B97565BA67AA08C CRC64;
     MEPGKEKEVE APGELNQKPR PSTRSSTTNR QPKMKRRKKD LEELKKEVVM DDHKLTLDEL
     SAKYSVDLTK GLSILEAQDI LFQNGPNVLT PPPTTPEWVK FCRQLFGGFS LLLWTGACLC
     FLAYGIHVNY YKENANKDNL YLGIVLSAVV IITGCFSYYQ EAKSSKIMES FKNMVPQQAL
     VIRDGEKMQI NVRDVVLGDL VEVKGGDQIP ADIRVISAQG CKVDNSSLTG ESEPQSRCPD
     CTHENPLETR NIIFFSTNCV EGTARGIVIA TGDYTVMGRI ASLTSGLQMG KTPIATEIEH
     FIHLITAVAV FLGVSFFWLS IILGYTWLDA VIFLIGIIVA NVPEGLLATV TVCLTLTAKR
     MARKNCLVKN LEAVETLGST STICSDKTGT LTQNRMTVAH LWFDKTVYEA DTSEEQTTGK
     TFPKSSDTWF YLARIAGLCN RADFKPHQES VPIAKRATTG DASESALLKF IEQSYNPVSE
     MRQKNPKVAE IPFNSTNKYQ MSIHLLEDNS EAHVLLMKGA PERIFDFCSS FLLNGQEYPM
     DEEMKMDFQN AYIELGGLGE RVLGFCFLNL PSNFSKGFQF NTDELNFPME NLCFAGLISM
     IDPPRTAVPD AVSKCRSAGI KVIMVTGDHP ITAKAIAKSV GIISEGNDTA EDIAARLNIP
     ISQVNNKSVK AIVVHGSELK DMESQQLDDI LKSYKEIVFA RTSPQQKLII VEGCQRLGAI
     VAVTGDGVND SPALKKADIG IAMGITGSDV SKQAADMILL DDNFASIVTG VEEGRLIFDN
     LKKSIAYTLT SNIPEITPFL LFIILSIPLP LGTITILCID LGTDMVPAIS LAYESPESDI
     MKRLPRNPKT DNLVNNRLIG MAYGQIGMIQ ALAGFFTYFV ILAENGFKPL DLLGIRLYWD
     DTQLNDLEDS YGQQWTYEQR KVVEFTCQTA FFISIVIVQW ADLIICKTRR NSLFKQGMKN
     KILIFGLLEE TVLAAFLSYV PGMDVSLRMY PLKINWWFCA LPYSVLIFVY DEIRKLIIRR
     RPGGWLEKET YY
//