PLM_MOUSE
ID PLM_MOUSE Reviewed; 92 AA.
AC Q9Z239;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Phospholemman {ECO:0000250|UniProtKB:P56513};
DE AltName: Full=FXYD domain-containing ion transport regulator 1 {ECO:0000312|MGI:MGI:1889273};
DE AltName: Full=Sodium/potassium-transporting ATPase subunit FXYD1 {ECO:0000305};
DE Flags: Precursor;
GN Name=Fxyd1 {ECO:0000312|MGI:MGI:1889273};
GN Synonyms=Plm {ECO:0000303|PubMed:11410367};
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=129/SvJ;
RX PubMed=11410367; DOI=10.1016/s0378-1119(01)00497-8;
RA Bogaev R.C., Jia L.G., Kobayashi Y.M., Palmer C.J., Mounsey J.P.,
RA Moorman J.R., Jones L.R., Tucker A.L.;
RT "Gene structure and expression of phospholemman in mouse.";
RL Gene 271:69-79(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Kidney;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Colon;
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).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15563542; DOI=10.1152/ajpheart.00142.2004;
RA Jia L.G., Donnet C., Bogaev R.C., Blatt R.J., McKinney C.E., Day K.H.,
RA Berr S.S., Jones L.R., Moorman J.R., Sweadner K.J., Tucker A.L.;
RT "Hypertrophy, increased ejection fraction, and reduced Na-K-ATPase activity
RT in phospholemman-deficient mice.";
RL Am. J. Physiol. 288:H1982-H1988(2005).
RN [5]
RP INTERACTION WITH ATP1A1.
RX PubMed=17283221; DOI=10.1096/fj.06-7269com;
RA Pavlovic D., Fuller W., Shattock M.J.;
RT "The intracellular region of FXYD1 is sufficient to regulate cardiac Na/K
RT ATPase.";
RL FASEB J. 21:1539-1546(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-79 AND SER-83, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18065526; DOI=10.1152/ajpheart.01332.2007;
RA Bell J.R., Kennington E., Fuller W., Dighe K., Donoghue P., Clark J.E.,
RA Jia L.G., Tucker A.L., Moorman J.R., Marber M.S., Eaton P., Dunn M.J.,
RA Shattock M.J.;
RT "Characterization of the phospholemman knockout mouse heart: depressed left
RT ventricular function with increased Na-K-ATPase activity.";
RL Am. J. Physiol. 294:H613-H621(2008).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18630941; DOI=10.1021/pr800223m;
RA Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H.;
RT "Specific phosphopeptide enrichment with immobilized titanium ion affinity
RT chromatography adsorbent for phosphoproteome analysis.";
RL J. Proteome Res. 7:3957-3967(2008).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19187398; DOI=10.1111/j.1365-2826.2008.01812.x;
RA Garcia-Rudaz C., Deng V., Matagne V., Ronnekleiv O.K., Bosch M., Han V.,
RA Percy A.K., Ojeda S.R.;
RT "FXYD1, a modulator of Na,K-ATPase activity, facilitates female sexual
RT development by maintaining gonadotrophin-releasing hormone neuronal
RT excitability.";
RL J. Neuroendocrinol. 21:108-122(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-79; SER-82 AND SER-83, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Liver, Lung, Pancreas, and
RC Testis;
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).
RN [11]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21454534; DOI=10.1074/jbc.m110.184101;
RA Bibert S., Liu C.C., Figtree G.A., Garcia A., Hamilton E.J., Marassi F.M.,
RA Sweadner K.J., Cornelius F., Geering K., Rasmussen H.H.;
RT "FXYD proteins reverse inhibition of the Na+-K+ pump mediated by
RT glutathionylation of its beta1 subunit.";
RL J. Biol. Chem. 286:18562-18572(2011).
RN [12]
RP SUBUNIT.
RX PubMed=23532852; DOI=10.1074/jbc.m113.460956;
RA Wypijewski K.J., Howie J., Reilly L., Tulloch L.B., Aughton K.L.,
RA McLatchie L.M., Shattock M.J., Calaghan S.C., Fuller W.;
RT "A separate pool of cardiac phospholemman that does not regulate or
RT associate with the sodium pump: multimers of phospholemman in ventricular
RT muscle.";
RL J. Biol. Chem. 288:13808-13820(2013).
CC -!- FUNCTION: Associates with and regulates the activity of the
CC sodium/potassium-transporting ATPase (NKA) which transports Na(+) out
CC of the cell and K(+) into the cell (PubMed:15563542, PubMed:18065526).
CC Inhibits NKA activity in its unphosphorylated state and stimulates
CC activity when phosphorylated (By similarity). Reduces glutathionylation
CC of the NKA beta-1 subunit ATP1B1, thus reversing glutathionylation-
CC mediated inhibition of ATP1B1 (PubMed:21454534). Contributes to female
CC sexual development by maintaining the excitability of neurons which
CC secrete gonadotropin-releasing hormone (PubMed:19187398).
CC {ECO:0000250|UniProtKB:O08589, ECO:0000250|UniProtKB:P56513,
CC ECO:0000269|PubMed:19187398, ECO:0000269|PubMed:21454534}.
CC -!- SUBUNIT: Homotetramer (By similarity). Monomer (By similarity).
CC Regulatory subunit of the sodium/potassium-transporting ATPase (NKA)
CC which is composed of a catalytic alpha subunit, a non-catalytic beta
CC subunit and an additional regulatory subunit (By similarity). The
CC monomeric form associates with NKA while the oligomeric form does not
CC (PubMed:23532852). Interacts with the catalytic alpha-1 subunit ATP1A1
CC (PubMed:17283221). Also interacts with the catalytic alpha-2 and alpha-
CC 3 subunits ATP1A2 and ATP1A3 (By similarity). Very little interaction
CC with the catalytic alpha subunits ATP1A1, ATP1A2 or ATP1A3 when
CC phosphorylated at Ser-83 (By similarity). Interacts with the non-
CC catalytic beta-1 subunit ATP1B1 (By similarity). Oxidative stress
CC decreases interaction with ATP1A1 but increases interaction with ATP1B1
CC (By similarity). {ECO:0000250|UniProtKB:O00168,
CC ECO:0000250|UniProtKB:O08589, ECO:0000250|UniProtKB:Q3SZX0,
CC ECO:0000269|PubMed:17283221, ECO:0000269|PubMed:23532852}.
CC -!- SUBCELLULAR LOCATION: Cell membrane, sarcolemma
CC {ECO:0000250|UniProtKB:P56513}; Single-pass type I membrane protein
CC {ECO:0000255}. Apical cell membrane {ECO:0000250|UniProtKB:O08589};
CC Single-pass type I membrane protein {ECO:0000255}. Membrane, caveola
CC {ECO:0000250|UniProtKB:O08589}. Cell membrane, sarcolemma, T-tubule
CC {ECO:0000250|UniProtKB:O08589}. Note=Detected in the apical cell
CC membrane in brain. In myocytes, localizes to sarcolemma, t-tubules and
CC intercalated disks. {ECO:0000250|UniProtKB:O08589}.
CC -!- DOMAIN: The cytoplasmic domain is sufficient to regulate
CC sodium/potassium-transporting ATPase activity.
CC {ECO:0000250|UniProtKB:O08589}.
CC -!- PTM: Major plasma membrane substrate for cAMP-dependent protein kinase
CC (PKA) and protein kinase C (PKC) in several different tissues.
CC Phosphorylated in response to insulin and adrenergic stimulation.
CC Phosphorylation at Ser-88 stimulates sodium/potassium-transporting
CC ATPase activity while the unphosphorylated form inhibits
CC sodium/potassium-transporting ATPase activity. Phosphorylation
CC increases tetramerization, decreases binding to ATP1A1 and reduces
CC inhibition of ATP1A1 activity. Phosphorylation at Ser-83 leads to
CC greatly reduced interaction with ATP1A1, ATP1A2 and ATP1A3. May be
CC phosphorylated by DMPK. {ECO:0000250|UniProtKB:O00168,
CC ECO:0000250|UniProtKB:O08589, ECO:0000250|UniProtKB:P56513}.
CC -!- PTM: Palmitoylation increases half-life and stability and is enhanced
CC upon phosphorylation at Ser-88 by PKA. {ECO:0000250|UniProtKB:O00168}.
CC -!- DISRUPTION PHENOTYPE: Adults exhibit increased cardiac mass, larger
CC cardiomyocytes, higher ejection fractions (the amount of blood pumped
CC out of the ventricles with each contraction) and reduced
CC sodium/potassium-transporting ATPase (NKA) activity in a mixed strain
CC background of C57BL/6 and 129/SvJ (PubMed:15563542). Decreased cardiac
CC contractile function and increased NKA activity in a congenic C57BL/6
CC background (PubMed:18065526). Increased glutathionylation of the NKA
CC beta subunit ATP1B1 (PubMed:21454534). Decreased excitability of
CC neurons which secrete gonadotropin-releasing hormone and delayed female
CC puberty (PubMed:19187398). {ECO:0000269|PubMed:15563542,
CC ECO:0000269|PubMed:18065526, ECO:0000269|PubMed:19187398,
CC ECO:0000269|PubMed:21454534}.
CC -!- SIMILARITY: Belongs to the FXYD family. {ECO:0000305}.
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DR EMBL; AF091390; AAD11781.1; -; Genomic_DNA.
DR EMBL; AF089734; AAD41683.1; -; mRNA.
DR EMBL; AK002585; BAB22208.1; -; mRNA.
DR EMBL; BC024671; AAH24671.1; -; mRNA.
DR CCDS; CCDS21123.1; -.
DR RefSeq; NP_062376.2; NM_019503.4.
DR RefSeq; NP_443717.1; NM_052991.4.
DR RefSeq; NP_443718.1; NM_052992.3.
DR RefSeq; NP_919302.1; NM_194321.2.
DR RefSeq; XP_006540282.1; XM_006540219.3.
DR AlphaFoldDB; Q9Z239; -.
DR SMR; Q9Z239; -.
DR BioGRID; 207828; 7.
DR STRING; 10090.ENSMUSP00000048460; -.
DR iPTMnet; Q9Z239; -.
DR PhosphoSitePlus; Q9Z239; -.
DR jPOST; Q9Z239; -.
DR MaxQB; Q9Z239; -.
DR PaxDb; Q9Z239; -.
DR PeptideAtlas; Q9Z239; -.
DR PRIDE; Q9Z239; -.
DR ProteomicsDB; 289447; -.
DR Antibodypedia; 65378; 304 antibodies from 31 providers.
DR DNASU; 56188; -.
DR Ensembl; ENSMUST00000039909; ENSMUSP00000048460; ENSMUSG00000036570.
DR Ensembl; ENSMUST00000071697; ENSMUSP00000071617; ENSMUSG00000036570.
DR Ensembl; ENSMUST00000108110; ENSMUSP00000103745; ENSMUSG00000036570.
DR Ensembl; ENSMUST00000205439; ENSMUSP00000146064; ENSMUSG00000036570.
DR Ensembl; ENSMUST00000205778; ENSMUSP00000145818; ENSMUSG00000036570.
DR Ensembl; ENSMUST00000206012; ENSMUSP00000146295; ENSMUSG00000036570.
DR Ensembl; ENSMUST00000206305; ENSMUSP00000145589; ENSMUSG00000036570.
DR Ensembl; ENSMUST00000206328; ENSMUSP00000145712; ENSMUSG00000036570.
DR Ensembl; ENSMUST00000206474; ENSMUSP00000145920; ENSMUSG00000036570.
DR Ensembl; ENSMUST00000206860; ENSMUSP00000146288; ENSMUSG00000036570.
DR GeneID; 56188; -.
DR KEGG; mmu:56188; -.
DR UCSC; uc009ghu.2; mouse.
DR CTD; 5348; -.
DR MGI; MGI:1889273; Fxyd1.
DR VEuPathDB; HostDB:ENSMUSG00000036570; -.
DR eggNOG; ENOG502S5XM; Eukaryota.
DR GeneTree; ENSGT00940000153062; -.
DR HOGENOM; CLU_171208_2_0_1; -.
DR InParanoid; Q9Z239; -.
DR OMA; FTMANAE; -.
DR OrthoDB; 1621616at2759; -.
DR PhylomeDB; Q9Z239; -.
DR TreeFam; TF333443; -.
DR Reactome; R-MMU-5578775; Ion homeostasis.
DR Reactome; R-MMU-936837; Ion transport by P-type ATPases.
DR BioGRID-ORCS; 56188; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Fxyd1; mouse.
DR PRO; PR:Q9Z239; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q9Z239; protein.
DR Bgee; ENSMUSG00000036570; Expressed in hindlimb stylopod muscle and 217 other tissues.
DR ExpressionAtlas; Q9Z239; baseline and differential.
DR Genevisible; Q9Z239; MM.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0005901; C:caveola; ISS:UniProtKB.
DR GO; GO:0014704; C:intercalated disc; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0042383; C:sarcolemma; IMP:BHF-UCL.
DR GO; GO:0005890; C:sodium:potassium-exchanging ATPase complex; ISS:UniProtKB.
DR GO; GO:0030315; C:T-tubule; ISS:UniProtKB.
DR GO; GO:0051117; F:ATPase binding; ISO:MGI.
DR GO; GO:0017022; F:myosin binding; ISO:MGI.
DR GO; GO:0017080; F:sodium channel regulator activity; IMP:BHF-UCL.
DR GO; GO:0044325; F:transmembrane transporter binding; ISS:BHF-UCL.
DR GO; GO:0010734; P:negative regulation of protein glutathionylation; ISS:UniProtKB.
DR GO; GO:1903797; P:positive regulation of inorganic anion transmembrane transport; ISO:MGI.
DR GO; GO:0032892; P:positive regulation of organic acid transport; ISO:MGI.
DR GO; GO:1903278; P:positive regulation of sodium ion export across plasma membrane; IMP:BHF-UCL.
DR GO; GO:0006813; P:potassium ion transport; IEA:UniProtKB-KW.
DR GO; GO:0086004; P:regulation of cardiac muscle cell contraction; ISO:MGI.
DR GO; GO:0086036; P:regulation of cardiac muscle cell membrane potential; IMP:BHF-UCL.
DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; ISO:MGI.
DR GO; GO:2000649; P:regulation of sodium ion transmembrane transporter activity; IMP:BHF-UCL.
DR GO; GO:0006814; P:sodium ion transport; IEA:UniProtKB-KW.
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 Cell membrane; Glutathionylation; Ion transport; Lipoprotein; Membrane;
KW Palmitate; Phosphoprotein; Potassium; Potassium transport;
KW Reference proteome; Signal; Sodium; Sodium transport;
KW Sodium/potassium transport; Transmembrane; Transmembrane helix; Transport.
FT SIGNAL 1..20
FT /evidence="ECO:0000250|UniProtKB:P56513"
FT CHAIN 21..92
FT /note="Phospholemman"
FT /id="PRO_0000010360"
FT TOPO_DOM 21..35
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 36..56
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 57..92
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 66..92
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 68..84
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 62
FT /note="S-glutathionyl cysteine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P56513"
FT MOD_RES 79
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 82
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 83
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 88
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:P56513"
FT LIPID 60
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:O00168"
FT LIPID 62
FT /note="S-palmitoyl cysteine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O00168"
SQ SEQUENCE 92 AA; 10323 MW; 0BDB1DC83417F3AD CRC64;
MASPGHILAL CVCLLSMASA EAPQEPDPFT YDYHTLRIGG LTIAGILFIL GILIILSKRC
RCKFNQQQRT GEPDEEEGTF RSSIRRLSSR RR
