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 07-APR-2021, entry version 106. 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; 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M63934; -; NOT_ANNOTATED_CDS; mRNA. DR PIR; A40533; A40533. 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 OMA; FTYDYHT; -. 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:0099106; F:ion channel regulator activity; IEA:InterPro. 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 sodium:potassium-exchanging ATPase 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 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 //