ATNG_HUMAN
ID ATNG_HUMAN Reviewed; 66 AA.
AC P54710; Q15332; Q53YC1; Q9GZP3; Q9GZQ7;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2002, sequence version 3.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Sodium/potassium-transporting ATPase subunit gamma;
DE Short=Na(+)/K(+) ATPase subunit gamma;
DE AltName: Full=FXYD domain-containing ion transport regulator 2;
DE AltName: Full=Sodium pump gamma chain;
GN Name=FXYD2; Synonyms=ATP1C, ATP1G1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=9048881; DOI=10.1016/s0167-4781(96)00219-9;
RA Kim J.W., Lee Y., Lee I.A., Kang H.B., Choe Y.K., Choe I.S.;
RT "Cloning and expression of human cDNA encoding Na+, K(+)-ATPase gamma-
RT subunit.";
RL Biochim. Biophys. Acta 1350:133-135(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE (ISOFORMS 1 AND 2).
RX PubMed=11112438; DOI=10.1006/bbrc.2000.3907;
RA Sweadner K.J., Wetzel R.K., Arystarkhova E.;
RT "Genomic organization of the human FXYD2 gene encoding the gamma subunit of
RT the Na,K-ATPase.";
RL Biochem. Biophys. Res. Commun. 279:196-201(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP HOMG2 ARG-41.
RX PubMed=11062458; DOI=10.1038/81543;
RA Meij I.C., Koenderink J.B., van Bokhoven H., Assink K.F.H.,
RA Groenestege W.T., de Pont J.J.H.H.M., Bindels R.J.M., Monnens L.A.H.,
RA van den Heuvel L.P.W.J., Knoers N.V.A.M.;
RT "Dominant isolated renal magnesium loss is caused by misrouting of the
RT Na+,K+-ATPase gamma-subunit.";
RL Nat. Genet. 26:265-266(2000).
RN [4]
RP ERRATUM OF PUBMED:11062458.
RA Meij I.C., Koenderink J.B., van Bokhoven H., Assink K.F.H.,
RA Groenestege W.T., de Pont J.J.H.H.M., Bindels R.J.M., Monnens L.A.H.,
RA van den Heuvel L.P.W.J., Knoers N.V.A.M.;
RL Nat. Genet. 27:125-125(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Kidney;
RA Austruy E., Belley L., Millasot P., Junien C., Jeanpierre C.;
RT "Characterization of the human cDNA with partial homology with the gamma
RT subunit of sodium potassium ATPase of rat, mouse, rabbit and sheep.";
RL Submitted (APR-1995) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Bone marrow, and Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: May be involved in forming the receptor site for cardiac
CC glycoside binding or may modulate the transport function of the sodium
CC ATPase.
CC -!- SUBUNIT: Regulatory subunit of the sodium/potassium-transporting ATPase
CC which is composed of a catalytic alpha subunit, an auxiliary non-
CC catalytic beta subunit and an additional regulatory subunit.
CC {ECO:0000250|UniProtKB:O13001}.
CC -!- INTERACTION:
CC P54710-2; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-13084584, EBI-781551;
CC P54710-2; O43765: SGTA; NbExp=5; IntAct=EBI-13084584, EBI-347996;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type III
CC membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=A;
CC IsoId=P54710-1; Sequence=Displayed;
CC Name=2; Synonyms=B;
CC IsoId=P54710-2; Sequence=VSP_001580;
CC -!- TISSUE SPECIFICITY: Expressed in the distal convoluted tubule in the
CC kidney. Found on basolateral membranes of nephron epithelial cells.
CC -!- DISEASE: Hypomagnesemia 2 (HOMG2) [MIM:154020]: A disorder due to
CC primary renal wasting of magnesium. Plasma levels of other electrolytes
CC are normal. The only abnormality found, in addition to low magnesium
CC levels, is lowered renal excretion of calcium resulting in
CC hypocalciuria. {ECO:0000269|PubMed:11062458}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the FXYD family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB09425.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAA60152.1; Type=Erroneous translation; Note=Wrong choice of frame.; Evidence={ECO:0000305};
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DR EMBL; U50743; AAB09425.1; ALT_FRAME; mRNA.
DR EMBL; AF316896; AAG37906.1; -; Genomic_DNA.
DR EMBL; AF316896; AAG37907.1; -; Genomic_DNA.
DR EMBL; AF241235; AAG34359.1; -; Genomic_DNA.
DR EMBL; AF241235; AAG34360.1; -; Genomic_DNA.
DR EMBL; AF241236; AAG34361.1; -; mRNA.
DR EMBL; X86400; CAA60152.1; ALT_SEQ; mRNA.
DR EMBL; BT006721; AAP35367.1; -; mRNA.
DR EMBL; BC013289; AAH13289.1; -; mRNA.
DR EMBL; BC005302; AAH05302.1; -; mRNA.
DR CCDS; CCDS8385.1; -. [P54710-2]
DR CCDS; CCDS8386.1; -. [P54710-1]
DR PIR; S54159; S54159.
DR RefSeq; NP_001671.2; NM_001680.4. [P54710-1]
DR RefSeq; NP_067614.1; NM_021603.3. [P54710-2]
DR PDB; 2MKV; NMR; -; A=9-66.
DR PDBsum; 2MKV; -.
DR AlphaFoldDB; P54710; -.
DR BMRB; P54710; -.
DR SMR; P54710; -.
DR BioGRID; 106976; 8.
DR ComplexPortal; CPX-125; Sodium:potassium-exchanging ATPase complex.
DR IntAct; P54710; 5.
DR STRING; 9606.ENSP00000292079; -.
DR ChEMBL; CHEMBL2095186; -.
DR DrugBank; DB09020; Bisacodyl.
DR DrugBank; DB00606; Cyclothiazide.
DR DrugBank; DB13620; Potassium gluconate.
DR DrugBank; DB09479; Rubidium Rb-82.
DR DrugBank; DB16690; Tegoprazan.
DR DrugBank; DB11590; Thimerosal.
DR DrugCentral; P54710; -.
DR TCDB; 1.A.27.2.1; the phospholemman (plm) family.
DR GlyGen; P54710; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P54710; -.
DR BioMuta; FXYD2; -.
DR DMDM; 20141251; -.
DR jPOST; P54710; -.
DR MassIVE; P54710; -.
DR MaxQB; P54710; -.
DR PaxDb; P54710; -.
DR PeptideAtlas; P54710; -.
DR PRIDE; P54710; -.
DR ProteomicsDB; 56698; -. [P54710-1]
DR ProteomicsDB; 56699; -. [P54710-2]
DR Antibodypedia; 32392; 100 antibodies from 24 providers.
DR DNASU; 486; -.
DR Ensembl; ENST00000260287.2; ENSP00000260287.2; ENSG00000137731.14. [P54710-2]
DR Ensembl; ENST00000292079.7; ENSP00000292079.2; ENSG00000137731.14. [P54710-1]
DR Ensembl; ENST00000528014.5; ENSP00000432430.1; ENSG00000137731.14. [P54710-2]
DR Ensembl; ENST00000532119.5; ENSP00000436414.1; ENSG00000137731.14. [P54710-2]
DR GeneID; 486; -.
DR KEGG; hsa:486; -.
DR MANE-Select; ENST00000292079.7; ENSP00000292079.2; NM_001680.5; NP_001671.2.
DR UCSC; uc001prj.2; human. [P54710-1]
DR CTD; 486; -.
DR DisGeNET; 486; -.
DR GeneCards; FXYD2; -.
DR HGNC; HGNC:4026; FXYD2.
DR HPA; ENSG00000137731; Tissue enhanced (kidney, pancreas, salivary gland).
DR MalaCards; FXYD2; -.
DR MIM; 154020; phenotype.
DR MIM; 601814; gene.
DR neXtProt; NX_P54710; -.
DR OpenTargets; ENSG00000137731; -.
DR Orphanet; 34528; Autosomal dominant primary hypomagnesemia with hypocalciuria.
DR PharmGKB; PA28442; -.
DR VEuPathDB; HostDB:ENSG00000137731; -.
DR eggNOG; ENOG502SGMI; Eukaryota.
DR GeneTree; ENSGT00940000153062; -.
DR HOGENOM; CLU_171208_4_0_1; -.
DR InParanoid; P54710; -.
DR OMA; HRQVNED; -.
DR PhylomeDB; P54710; -.
DR TreeFam; TF333443; -.
DR PathwayCommons; P54710; -.
DR Reactome; R-HSA-5578775; Ion homeostasis.
DR Reactome; R-HSA-936837; Ion transport by P-type ATPases.
DR Reactome; R-HSA-9679191; Potential therapeutics for SARS.
DR SignaLink; P54710; -.
DR SIGNOR; P54710; -.
DR BioGRID-ORCS; 486; 7 hits in 1063 CRISPR screens.
DR GeneWiki; FXYD2; -.
DR GenomeRNAi; 486; -.
DR Pharos; P54710; Tclin.
DR PRO; PR:P54710; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P54710; protein.
DR Bgee; ENSG00000137731; Expressed in metanephros cortex and 98 other tissues.
DR Genevisible; P54710; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005890; C:sodium:potassium-exchanging ATPase complex; ISS:BHF-UCL.
DR GO; GO:0001671; F:ATPase activator activity; ISS:ARUK-UCL.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; ISS:ARUK-UCL.
DR GO; GO:0017080; F:sodium channel regulator activity; IEA:Ensembl.
DR GO; GO:0010248; P:establishment or maintenance of transmembrane electrochemical gradient; IC:ComplexPortal.
DR GO; GO:1903408; P:positive regulation of P-type sodium:potassium-exchanging transporter activity; ISS:ARUK-UCL.
DR GO; GO:1990573; P:potassium ion import across plasma membrane; ISS:BHF-UCL.
DR GO; GO:1902600; P:proton transmembrane transport; IC:ComplexPortal.
DR GO; GO:0036376; P:sodium ion export across plasma membrane; ISS:BHF-UCL.
DR GO; GO:0055085; P:transmembrane transport; ISS:BHF-UCL.
DR InterPro; IPR000272; Ion-transport_regulator_FXYD.
DR Pfam; PF02038; ATP1G1_PLM_MAT8; 1.
DR PROSITE; PS01310; FXYD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Disease variant; Ion transport;
KW Membrane; Potassium; Potassium transport; Primary hypomagnesemia;
KW Reference proteome; Sodium; Sodium transport; Sodium/potassium transport;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..66
FT /note="Sodium/potassium-transporting ATPase subunit gamma"
FT /id="PRO_0000148185"
FT TRANSMEM 29..46
FT /note="Helical"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..8
FT /note="MTGLSMDG -> MDRWYL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11062458,
FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.6"
FT /id="VSP_001580"
FT VARIANT 41
FT /note="G -> R (in HOMG2; fails to localize to plasma
FT membrane; dbSNP:rs28938168)"
FT /evidence="ECO:0000269|PubMed:11062458"
FT /id="VAR_013280"
FT HELIX 20..23
FT /evidence="ECO:0007829|PDB:2MKV"
FT HELIX 26..51
FT /evidence="ECO:0007829|PDB:2MKV"
FT STRAND 52..55
FT /evidence="ECO:0007829|PDB:2MKV"
SQ SEQUENCE 66 AA; 7283 MW; D00F21B5C01ACE75 CRC64;
MTGLSMDGGG SPKGDVDPFY YDYETVRNGG LIFAGLAFIV GLLILLSRRF RCGGNKKRRQ
INEDEP
