PLM_RABIT
ID PLM_RABIT Reviewed; 92 AA.
AC G1TZA0;
DT 27-SEP-2017, integrated into UniProtKB/Swiss-Prot.
DT 19-OCT-2011, sequence version 1.
DT 03-AUG-2022, entry version 41.
DE RecName: Full=Phospholemman {ECO:0000250|UniProtKB:P56513};
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 Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986 {ECO:0000312|Proteomes:UP000001811};
RN [1] {ECO:0000312|Proteomes:UP000001811}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Thorbecke {ECO:0000312|Proteomes:UP000001811};
RG The Genome Sequencing Platform;
RA Di Palma F., Heiman D., Young S., Gnerre S., Johnson J., Lander E.S.,
RA Lindblad-Toh K.;
RT "Genome Sequence of Oryctolagus cuniculus (European rabbit).";
RL Submitted (AUG-2009) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000305}
RP TISSUE SPECIFICITY, AND GLUTATHIONYLATION.
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. Inhibits NKA activity in its
CC unphosphorylated state and stimulates activity when phosphorylated.
CC Reduces glutathionylation of the NKA beta-1 subunit ATP1B1, thus
CC reversing glutathionylation-mediated inhibition of ATP1B1. Contributes
CC to female sexual development by maintaining the excitability of neurons
CC which secrete gonadotropin-releasing hormone.
CC {ECO:0000250|UniProtKB:O08589, ECO:0000250|UniProtKB:P56513,
CC ECO:0000250|UniProtKB:Q9Z239}.
CC -!- SUBUNIT: Homotetramer. Monomer. Regulatory subunit of the
CC sodium/potassium-transporting ATPase (NKA) which is composed of a
CC catalytic alpha subunit, a non-catalytic beta subunit and an additional
CC regulatory subunit. The monomeric form associates with NKA while the
CC oligomeric form does not. Interacts with the catalytic alpha-1 subunit
CC ATP1A1. Also interacts with the catalytic alpha-2 and alpha-3 subunits
CC ATP1A2 and ATP1A3. Very little interaction with ATP1A1, ATP1A2 or
CC ATP1A3 when phosphorylated at Ser-83. Interacts with the non-catalytic
CC beta-1 subunit ATP1B1. Oxidative stress decreases interaction with
CC ATP1A1 but increases interaction with ATP1B1.
CC {ECO:0000250|UniProtKB:O00168, ECO:0000250|UniProtKB:O08589,
CC ECO:0000250|UniProtKB:P56513, ECO:0000250|UniProtKB:Q3SZX0,
CC ECO:0000250|UniProtKB:Q9Z239}.
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 -!- TISSUE SPECIFICITY: Expressed in ventricular myocytes (at protein
CC level). {ECO:0000269|PubMed:21454534}.
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 -!- PTM: Glutathionylated. {ECO:0000269|PubMed:21454534}.
CC -!- SIMILARITY: Belongs to the FXYD family. {ECO:0000305}.
CC -!- CAUTION: The glutathionylation site found in orthologs is not conserved
CC here, possibly due to a gene model error, but the protein has been
CC shown to be glutathionylated. {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 AlphaFoldDB; G1TZA0; -.
DR SMR; G1TZA0; -.
DR STRING; 9986.ENSOCUP00000022422; -.
DR eggNOG; ENOG502S5XM; Eukaryota.
DR HOGENOM; CLU_171208_2_0_1; -.
DR InParanoid; G1TZA0; -.
DR OMA; FTMANAE; -.
DR TreeFam; TF333443; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005901; C:caveola; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0014704; C:intercalated disc; 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:0010734; P:negative regulation of protein glutathionylation; ISS:UniProtKB.
DR GO; GO:0006813; P:potassium ion transport; IEA:UniProtKB-KW.
DR GO; GO:0043269; P:regulation of ion transport; IEA:InterPro.
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_5003423826"
FT TOPO_DOM 22..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 67..92
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 67..84
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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:0000250|UniProtKB:P56513"
FT MOD_RES 88
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:P56513"
FT MOD_RES 89
FT /note="Phosphothreonine; by PKC"
FT /evidence="ECO:0000250|UniProtKB:P56513"
SQ SEQUENCE 92 AA; 10509 MW; 33E98A3F5DD37476 CRC64;
MAYLHHTLLV CMGLLAMANA EAPQEQDPFT YDYQSLRIGG LIIAGILFIL GILIILKRGA
WERFDTARRT GEPDEEEGTF RSSIRRLSTR RR
