AT1A4_MOUSE
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 03-AUG-2022, entry version 176.
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; 1.
DR IntAct; Q9WV27; 1.
DR STRING; 10090.ENSMUSP00000106874; -.
DR iPTMnet; Q9WV27; -.
DR PhosphoSitePlus; Q9WV27; -.
DR EPD; Q9WV27; -.
DR jPOST; Q9WV27; -.
DR MaxQB; Q9WV27; -.
DR PaxDb; Q9WV27; -.
DR PeptideAtlas; Q9WV27; -.
DR PRIDE; Q9WV27; -.
DR ProteomicsDB; 277264; -.
DR Antibodypedia; 55096; 15 antibodies from 5 providers.
DR Ensembl; ENSMUST00000111243; ENSMUSP00000106874; ENSMUSG00000007107.
DR GeneID; 27222; -.
DR KEGG; mmu:27222; -.
DR UCSC; uc011wwk.1; mouse.
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; NSRVKFD; -.
DR OrthoDB; 388324at2759; -.
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 72 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 25 other tissues.
DR Genevisible; Q9WV27; MM.
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 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:0030007; P:cellular potassium ion homeostasis; IBA:GO_Central.
DR GO; GO:0006883; P:cellular sodium ion homeostasis; IBA:GO_Central.
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: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; -; 1.
DR Gene3D; 3.40.50.1000; -; 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 Pfam; PF00689; Cation_ATPase_C; 1.
DR Pfam; PF00690; Cation_ATPase_N; 1.
DR SFLD; SFLDF00027; p-type_atpase; 1.
DR SMART; SM00831; Cation_ATPase_N; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR SUPFAM; SSF81653; SSF81653; 1.
DR SUPFAM; SSF81660; SSF81660; 1.
DR SUPFAM; SSF81665; SSF81665; 1.
DR TIGRFAMs; TIGR01106; ATPase-IIC_X-K; 1.
DR TIGRFAMs; TIGR01494; ATPase_P-type; 2.
DR PROSITE; PS00154; ATPASE_E1_E2; 1.
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
