PLM_CANLF
ID PLM_CANLF Reviewed; 92 AA.
AC P56513;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 1.
DT 25-MAY-2022, entry version 109.
DE RecName: Full=Phospholemman {ECO:0000303|PubMed:1710217};
DE AltName: Full=FXYD domain-containing ion transport regulator 1 {ECO:0000250|UniProtKB:O00168};
DE AltName: Full=Sodium/potassium-transporting ATPase subunit FXYD1 {ECO:0000305};
DE Flags: Precursor;
GN Name=FXYD1 {ECO:0000250|UniProtKB:O00168};
GN Synonyms=PLM {ECO:0000250|UniProtKB:O00168};
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 21-92, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND PHOSPHORYLATION.
RC TISSUE=Heart ventricle;
RX PubMed=1710217; DOI=10.1016/s0021-9258(18)99137-4;
RA Palmer C.J., Scott B.T., Jones L.R.;
RT "Purification and complete sequence determination of the major plasma
RT membrane substrate for cAMP-dependent protein kinase and protein kinase C
RT in myocardium.";
RL J. Biol. Chem. 266:11126-11130(1991).
RN [2]
RP SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=9486665; DOI=10.1161/01.res.82.3.367;
RA Chen Z., Jones L.R., O'Brian J.J., Moorman J.R., Cala S.E.;
RT "Structural domains in phospholemman: a possible role for the carboxyl
RT terminus in channel inactivation.";
RL Circ. Res. 82:367-374(1998).
RN [3]
RP FUNCTION.
RX PubMed=12169672; DOI=10.1073/pnas.182267299;
RA Crambert G., Fuzesi M., Garty H., Karlish S., Geering K.;
RT "Phospholemman (FXYD1) associates with Na,K-ATPase and regulates its
RT transport properties.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:11476-11481(2002).
RN [4]
RP INTERACTION WITH ATP1A1, AND PHOSPHORYLATION AT SER-83 AND SER-88.
RX PubMed=16943195; DOI=10.1074/jbc.m606254200;
RA Bossuyt J., Despa S., Martin J.L., Bers D.M.;
RT "Phospholemman phosphorylation alters its fluorescence resonance energy
RT transfer with the Na/K-ATPase pump.";
RL J. Biol. Chem. 281:32765-32773(2006).
RN [5]
RP PHOSPHORYLATION AT SER-83; SER-88 AND THR-89, AND MUTAGENESIS OF SER-83;
RP 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 [6]
RP PHOSPHORYLATION, AND MUTAGENESIS OF SER-83 AND SER-88.
RX PubMed=20861470; DOI=10.1152/ajpcell.00027.2010;
RA Han F., Bossuyt J., Martin J.L., Despa S., Bers D.M.;
RT "Role of phospholemman phosphorylation sites in mediating kinase-dependent
RT regulation of the Na+-K+-ATPase.";
RL Am. J. Physiol. 299:C1363-C1369(2010).
RN [7]
RP PHOSPHORYLATION AT SER-83 AND SER-88, AND MUTAGENESIS OF SER-83 AND SER-88.
RX PubMed=21220422; DOI=10.1074/jbc.m110.198036;
RA Song Q., Pallikkuth S., Bossuyt J., Bers D.M., Robia S.L.;
RT "Phosphomimetic mutations enhance oligomerization of phospholemman and
RT modulate its interaction with the Na/K-ATPase.";
RL J. Biol. Chem. 286:9120-9126(2011).
RN [8]
RP FUNCTION, INTERACTION WITH ATP1A1 AND ATP1B1, GLUTATHIONYLATION AT CYS-62,
RP AND MUTAGENESIS OF CYS-60; CYS-62 AND LYS-63.
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).
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:12169672). Inhibits NKA
CC activity in its unphosphorylated state and stimulates activity when
CC phosphorylated (By similarity). Reduces glutathionylation of the NKA
CC beta-1 subunit ATP1B1, thus reversing glutathionylation-mediated
CC inhibition of ATP1B1 (PubMed:21454534). Contributes to female sexual
CC development by maintaining the excitability of neurons which secrete
CC gonadotropin-releasing hormone (By similarity).
CC {ECO:0000250|UniProtKB:O08589, ECO:0000250|UniProtKB:Q9Z239,
CC ECO:0000269|PubMed:12169672, 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 (By similarity). Interacts with the catalytic alpha-1 subunit ATP1A1
CC (PubMed:16943195, PubMed:21454534). Also interacts with the catalytic
CC alpha-2 and alpha-3 subunits ATP1A2 and ATP1A3 (By similarity). Very
CC little interaction with the alpha subunits ATP1A1, ATP1A2 or ATP1A3
CC when phosphorylated at Ser-83 (By similarity). Interacts with non-
CC catalytic beta-1 subunit ATP1B1 (PubMed:21454534). Oxidative stress
CC decreases interaction with ATP1A1 but increases interaction with ATP1B1
CC (PubMed:21454534). {ECO:0000250|UniProtKB:O00168,
CC ECO:0000250|UniProtKB:O08589, ECO:0000250|UniProtKB:Q3SZX0,
CC ECO:0000250|UniProtKB:Q9Z239, ECO:0000269|PubMed:16943195,
CC ECO:0000269|PubMed:21454534}.
CC -!- SUBCELLULAR LOCATION: Cell membrane, sarcolemma
CC {ECO:0000269|PubMed:1710217, ECO:0000269|PubMed:9486665}; Single-pass
CC type I membrane protein {ECO:0000255}. Apical cell membrane
CC {ECO:0000250|UniProtKB:O08589}; Single-pass type I membrane protein
CC {ECO:0000255}. Membrane, caveola {ECO:0000250|UniProtKB:O08589}. Cell
CC membrane, sarcolemma, T-tubule {ECO:0000250|UniProtKB:O08589}.
CC Note=Detected in the apical cell membrane in brain. In myocytes,
CC localizes to sarcolemma, t-tubules and intercalated disks.
CC {ECO:0000250|UniProtKB:O08589}.
CC -!- TISSUE SPECIFICITY: Present in heart, esophagus, stomach, aorta,
CC skeletal muscle, smooth muscle, and liver but absent from brain and
CC kidney. {ECO:0000269|PubMed:1710217}.
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 (PubMed:1710217, PubMed:20861470). Phosphorylated in response to
CC insulin and adrenergic stimulation (By similarity). Phosphorylation at
CC Ser-88 stimulates sodium/potassium-transporting ATPase activity while
CC the unphosphorylated form inhibits sodium/potassium-transporting ATPase
CC activity (By similarity). Phosphorylation increases tetramerization,
CC decreases binding to ATP1A1 and reduces inhibition of ATP1A1 activity
CC (PubMed:21220422). Phosphorylation at Ser-83 leads to greatly reduced
CC interaction with ATP1A1, ATP1A2 and ATP1A3 (By similarity). May be
CC phosphorylated by DMPK (By similarity). {ECO:0000250|UniProtKB:O00168,
CC ECO:0000250|UniProtKB:O08589, ECO:0000269|PubMed:1710217,
CC ECO:0000269|PubMed:20861470, ECO:0000269|PubMed:21220422}.
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; M63934; -; NOT_ANNOTATED_CDS; mRNA.
DR PIR; A40533; A40533.
DR AlphaFoldDB; P56513; -.
DR SMR; P56513; -.
DR STRING; 9612.ENSCAFP00000010530; -.
DR TCDB; 1.A.27.1.1; the phospholemman (plm) family.
DR iPTMnet; P56513; -.
DR PaxDb; P56513; -.
DR eggNOG; ENOG502S5XM; Eukaryota.
DR InParanoid; P56513; -.
DR Proteomes; UP000002254; Unplaced.
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:0042383; C:sarcolemma; IDA:UniProtKB.
DR GO; GO:0005890; C:sodium:potassium-exchanging ATPase complex; ISS:UniProtKB.
DR GO; GO:0030315; C:T-tubule; ISS:UniProtKB.
DR GO; GO:0017080; F:sodium channel regulator activity; IDA:UniProtKB.
DR GO; GO:0010734; P:negative regulation of protein glutathionylation; IDA:UniProtKB.
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:1903406; P:regulation of P-type sodium:potassium-exchanging transporter activity; IDA:UniProtKB.
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:0000269|PubMed:1710217"
FT CHAIN 21..92
FT /note="Phospholemman"
FT /id="PRO_0000010358"
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 65..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:0000269|PubMed:21454534"
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:16943195,
FT ECO:0000269|PubMed:19339511, ECO:0000269|PubMed:21220422"
FT MOD_RES 88
FT /note="Phosphoserine; by PKA and PKC"
FT /evidence="ECO:0000269|PubMed:16943195,
FT ECO:0000269|PubMed:19339511, ECO:0000269|PubMed:21220422"
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 MUTAGEN 60
FT /note="C->A: Does not affect glutathionylation."
FT /evidence="ECO:0000269|PubMed:21454534"
FT MUTAGEN 62
FT /note="C->A: Loss of glutathionylation and loss of ability
FT to reduce glutathionylation of ATP1B1."
FT /evidence="ECO:0000269|PubMed:21454534"
FT MUTAGEN 63
FT /note="K->G: Loss of glutathionylation and loss of ability
FT to reduce glutathionylation of ATP1B1."
FT /evidence="ECO:0000269|PubMed:21454534"
FT MUTAGEN 83
FT /note="S->A: Loss of phosphorylation. Decreased affinity of
FT the sodium/potassium-transporting ATPase for Na(+)."
FT /evidence="ECO:0000269|PubMed:19339511,
FT ECO:0000269|PubMed:20861470"
FT MUTAGEN 83
FT /note="S->E: Phosphomimetic mutant which reduces binding to
FT ATP1A1 and increases FXYD1 oligomerization."
FT /evidence="ECO:0000269|PubMed:21220422"
FT MUTAGEN 88
FT /note="S->A: Loss of phosphorylation. Decreased affinity of
FT the sodium/potassium-transporting ATPase for Na(+)."
FT /evidence="ECO:0000269|PubMed:19339511,
FT ECO:0000269|PubMed:20861470"
FT MUTAGEN 88
FT /note="S->E: Phosphomimetic mutant which reduces binding to
FT ATP1A1 and increases FXYD1 oligomerization."
FT /evidence="ECO:0000269|PubMed:21220422"
FT MUTAGEN 89
FT /note="T->A: Loss of phosphorylation."
FT /evidence="ECO:0000269|PubMed:19339511"
SQ SEQUENCE 92 AA; 10500 MW; 890DE301BF8E740A CRC64;
MAPLHHILVL CVGFLTTATA EAPQEHDPFT YDYQSLRIGG LIIAGILFIL GILIVLSRRC
RCKFNQQQRT GEPDEEEGTF RSSIRRLSTR RR
