PLM_RAT
ID PLM_RAT Reviewed; 92 AA.
AC O08589;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2002, sequence version 2.
DT 25-MAY-2022, entry version 153.
DE RecName: Full=Phospholemman {ECO:0000250|UniProtKB:P56513};
DE AltName: Full=FXYD domain-containing ion transport regulator 1 {ECO:0000312|RGD:69306};
DE AltName: Full=Sodium/potassium-transporting ATPase subunit FXYD1 {ECO:0000305};
DE Flags: Precursor;
GN Name=Fxyd1 {ECO:0000312|RGD:69306};
GN Synonyms=Plm {ECO:0000303|PubMed:9169143};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart;
RX PubMed=9169143; DOI=10.1006/geno.1997.4665;
RA Chen L.-S.K., Lo C.F., Numann R., Cuddy M.;
RT "Characterization of the human and rat phospholemman (PLM) cDNAs and
RT localization of the human PLM gene to chromosome 19q13.1.";
RL Genomics 41:435-443(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10950925; DOI=10.1006/geno.2000.6274;
RA Sweadner K.J., Rael E.;
RT "The FXYD gene family of small ion transport regulators or channels: cDNA
RT sequence, protein signature sequence, and expression.";
RL Genomics 68:41-56(2000).
RN [3]
RP PROTEIN SEQUENCE OF 70-81, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RA Lubec G., Kang S.U., Lubec S.;
RL Submitted (SEP-2007) to UniProtKB.
RN [4]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=12657675; DOI=10.1523/jneurosci.23-06-02161.2003;
RA Feschenko M.S., Donnet C., Wetzel R.K., Asinovski N.K., Jones L.R.,
RA Sweadner K.J.;
RT "Phospholemman, a single-span membrane protein, is an accessory protein of
RT Na,K-ATPase in cerebellum and choroid plexus.";
RL J. Neurosci. 23:2161-2169(2003).
RN [5]
RP FUNCTION, INTERACTION WITH ATP1A1, DOMAIN, AND ROLE OF PHOSPHORYLATION AT
RP SER-88.
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 INTERACTION WITH ATP1A1, AND PHOSPHORYLATION AT SER-83; SER-88 AND THR-89.
RX PubMed=19339511; DOI=10.1152/ajpcell.00523.2008;
RA Fuller W., Howie J., McLatchie L.M., Weber R.J., Hastie C.J., Burness K.,
RA Pavlovic D., Shattock M.J.;
RT "FXYD1 phosphorylation in vitro and in adult rat cardiac myocytes:
RT threonine 69 is a novel substrate for protein kinase C.";
RL Am. J. Physiol. 296:C1346-C1355(2009).
RN [7]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
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 [8]
RP INTERACTION WITH ATP1A1; ATP1A2; ATP1A3 AND ATP1B1, SUBCELLULAR LOCATION,
RP AND PHOSPHORYLATION AT SER-83 AND SER-88.
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 (By similarity). Inhibits NKA
CC activity in its unphosphorylated state and stimulates activity when
CC phosphorylated (PubMed:17283221). Reduces glutathionylation of the NKA
CC beta-1 subunit ATP1B1, thus reversing glutathionylation-mediated
CC inhibition of ATP1B1 (By similarity). Contributes to female sexual
CC development by maintaining the excitability of neurons which secrete
CC gonadotropin-releasing hormone (By similarity).
CC {ECO:0000250|UniProtKB:P56513, ECO:0000250|UniProtKB:Q9Z239,
CC ECO:0000269|PubMed:17283221}.
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 (By similarity). Interacts with the catalytic alpha-1 subunit ATP1A1
CC (PubMed:17283221, PubMed:19339511, PubMed:23532852). Also interacts
CC with the catalytic alpha-2 and alpha-3 subunits ATP1A2 and ATP1A3
CC (PubMed:23532852). Very little interaction with ATP1A1, ATP1A2 or
CC ATP1A3 when phosphorylated at Ser-83 (PubMed:23532852). Interacts with
CC the non-catalytic beta-1 subunit ATP1B1 (PubMed:23532852). Oxidative
CC stress decreases interaction with ATP1A1 but increases interaction with
CC ATP1B1 (By similarity). {ECO:0000250|UniProtKB:O00168,
CC ECO:0000250|UniProtKB:P56513, ECO:0000250|UniProtKB:Q3SZX0,
CC ECO:0000250|UniProtKB:Q9Z239, ECO:0000269|PubMed:17283221,
CC ECO:0000269|PubMed:19339511, ECO:0000269|PubMed:23532852}.
CC -!- SUBCELLULAR LOCATION: Cell membrane, sarcolemma
CC {ECO:0000269|PubMed:23532852}; Single-pass type I membrane protein
CC {ECO:0000255}. Apical cell membrane {ECO:0000269|PubMed:12657675};
CC Single-pass type I membrane protein {ECO:0000255}. Membrane, caveola
CC {ECO:0000269|PubMed:23532852}. Cell membrane, sarcolemma, T-tubule
CC {ECO:0000269|PubMed:23532852}. Note=Detected in the apical cell
CC membrane in brain (PubMed:12657675). In myocytes, localizes to
CC sarcolemma, t-tubules and intercalated disks (PubMed:23532852).
CC {ECO:0000269|PubMed:12657675, ECO:0000269|PubMed:23532852}.
CC -!- TISSUE SPECIFICITY: In adult brain, highest levels are found in the
CC cerebellum and in the lateral, third and fourth ventricles of the
CC choroid plexus (at protein level) (PubMed:12657675). Also detected in
CC cells of a portion of the ependymal lining of the lateral ventricle on
CC its rostral surface posterior to the caudate putamen (at protein level)
CC (PubMed:12657675). Expressed in a subset of neurons which secrete
CC gonadotropin-releasing hormone (PubMed:19187398).
CC {ECO:0000269|PubMed:12657675, ECO:0000269|PubMed:19187398}.
CC -!- DEVELOPMENTAL STAGE: In the medial basal hypothalamus, levels are low
CC at birth and increase during neonatal and infantile development to
CC reach a maximum during the mid-to-late juvenile period at postnatal
CC days 24-30. {ECO:0000269|PubMed:19187398}.
CC -!- DOMAIN: The cytoplasmic domain is sufficient to regulate
CC sodium/potassium-transporting ATPase activity.
CC {ECO:0000269|PubMed:17283221}.
CC -!- PTM: Major plasma membrane substrate for cAMP-dependent protein kinase
CC (PKA) and protein kinase C (PKC) in several different tissues (By
CC similarity). Phosphorylated in response to insulin and adrenergic
CC stimulation (By similarity). Phosphorylation at Ser-88 stimulates
CC sodium/potassium-transporting ATPase activity while the
CC unphosphorylated form inhibits sodium/potassium-transporting ATPase
CC activity (PubMed:17283221). Phosphorylation increases tetramerization,
CC decreases binding to ATP1A1 and reduces inhibition of ATP1A1 activity
CC (By similarity). Phosphorylation at Ser-83 leads to greatly reduced
CC interaction with ATP1A1, ATP1A2 and ATP1A3 (PubMed:23532852). May be
CC phosphorylated by DMPK (By similarity). {ECO:0000250|UniProtKB:O00168,
CC ECO:0000250|UniProtKB:P56513, ECO:0000269|PubMed:17283221,
CC ECO:0000269|PubMed:23532852}.
CC -!- PTM: Palmitoylation increases half-life and stability and is enhanced
CC upon phosphorylation at Ser-88 by PKA. {ECO:0000250|UniProtKB:O00168}.
CC -!- SIMILARITY: Belongs to the FXYD family. {ECO:0000305}.
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DR EMBL; U72246; AAC53169.1; -; mRNA.
DR RefSeq; XP_006228901.1; XM_006228839.3.
DR RefSeq; XP_008757406.1; XM_008759184.2.
DR RefSeq; XP_017445120.1; XM_017589631.1.
DR AlphaFoldDB; O08589; -.
DR SMR; O08589; -.
DR IntAct; O08589; 2.
DR STRING; 10116.ENSRNOP00000028624; -.
DR iPTMnet; O08589; -.
DR PhosphoSitePlus; O08589; -.
DR SwissPalm; O08589; -.
DR PaxDb; O08589; -.
DR PRIDE; O08589; -.
DR GeneID; 58971; -.
DR UCSC; RGD:69306; rat.
DR CTD; 5348; -.
DR RGD; 69306; Fxyd1.
DR eggNOG; ENOG502S5XM; Eukaryota.
DR HOGENOM; CLU_171208_2_0_1; -.
DR InParanoid; O08589; -.
DR OrthoDB; 1621616at2759; -.
DR PhylomeDB; O08589; -.
DR TreeFam; TF333443; -.
DR Reactome; R-RNO-5578775; Ion homeostasis.
DR Reactome; R-RNO-936837; Ion transport by P-type ATPases.
DR PRO; PR:O08589; -.
DR Proteomes; UP000002494; Unplaced.
DR Genevisible; O08589; RN.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0005901; C:caveola; IDA:RGD.
DR GO; GO:0014704; C:intercalated disc; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0042383; C:sarcolemma; IDA:RGD.
DR GO; GO:0005890; C:sodium:potassium-exchanging ATPase complex; ISS:UniProtKB.
DR GO; GO:0030315; C:T-tubule; IDA:UniProtKB.
DR GO; GO:0051117; F:ATPase binding; IDA:RGD.
DR GO; GO:0017022; F:myosin binding; IDA:RGD.
DR GO; GO:0017080; F:sodium channel regulator activity; ISO:RGD.
DR GO; GO:0007420; P:brain development; IEP:RGD.
DR GO; GO:0010734; P:negative regulation of protein glutathionylation; ISS:UniProtKB.
DR GO; GO:1903797; P:positive regulation of inorganic anion transmembrane transport; IMP:RGD.
DR GO; GO:0032892; P:positive regulation of organic acid transport; IMP:RGD.
DR GO; GO:1903278; P:positive regulation of sodium ion export across plasma membrane; ISS:UniProtKB.
DR GO; GO:0006813; P:potassium ion transport; IEA:UniProtKB-KW.
DR GO; GO:0086004; P:regulation of cardiac muscle cell contraction; IMP:RGD.
DR GO; GO:0086036; P:regulation of cardiac muscle cell membrane potential; ISO:RGD.
DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; IMP:RGD.
DR GO; GO:2000649; P:regulation of sodium ion transmembrane transporter activity; ISO:RGD.
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; Direct protein sequencing; Glutathionylation; Ion transport;
KW Lipoprotein; Membrane; Palmitate; Phosphoprotein; Potassium;
KW Potassium transport; 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_0000010361"
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:0000250|UniProtKB:Q9Z239"
FT MOD_RES 82
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z239"
FT MOD_RES 83
FT /note="Phosphoserine; by PKA and PKC"
FT /evidence="ECO:0000269|PubMed:19339511,
FT ECO:0000269|PubMed:23532852"
FT MOD_RES 88
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:19339511,
FT ECO:0000269|PubMed:23532852"
FT MOD_RES 89
FT /note="Phosphothreonine; by PKC"
FT /evidence="ECO:0000269|PubMed:19339511"
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"
FT CONFLICT 3..5
FT /note="SPG -> PLH (in Ref. 1; AAC53169)"
FT /evidence="ECO:0000305"
FT CONFLICT 43..46
FT /note="IAGI -> AGIL (in Ref. 1; AAC53169)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 92 AA; 10365 MW; 29530D084B3CB7C2 CRC64;
MASPGHILIV CVCLLSMASA EAPQEPDPFT YDYHTLRIGG LTIAGILFIL GILIILSKRC
RCKFNQQQRT GEPDEEEGTF RSSIRRLSTR RR
