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Protein

Phospholemman

Gene

FXYD1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Associates with and regulates the activity of the sodium/potassium-transporting ATPase (NKA) which transports Na+ out of the cell and K+ into the cell. Inhibits NKA activity in its unphosphorylated state and stimulates activity when phosphorylated. Reduces glutathionylation of the NKA beta-1 subunit ATP1B1, thus reversing glutathionylation-mediated inhibition of ATP1B1. Contributes to female sexual development by maintaining the excitability of neurons which secrete gonadotropin-releasing hormone.By similarity

GO - Molecular functioni

  • chloride channel activity Source: ProtInc
  • ion channel binding Source: BHF-UCL
  • sodium channel regulator activity Source: BHF-UCL

GO - Biological processi

Keywordsi

Biological processIon transport, Potassium transport, Sodium transport, Sodium/potassium transport, Transport
LigandPotassium, Sodium

Enzyme and pathway databases

ReactomeiR-HSA-5578775 Ion homeostasis
R-HSA-936837 Ion transport by P-type ATPases
SIGNORiO00168

Names & Taxonomyi

Protein namesi
Recommended name:
PhospholemmanBy similarity
Alternative name(s):
FXYD domain-containing ion transport regulator 1Imported
Sodium/potassium-transporting ATPase subunit FXYD1Curated
Gene namesi
Name:FXYD1Imported
Synonyms:PLM1 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000266964.5
HGNCiHGNC:4025 FXYD1
MIMi602359 gene
neXtProtiNX_O00168

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini21 – 35ExtracellularSequence analysisAdd BLAST15
Transmembranei36 – 56HelicalSequence analysisAdd BLAST21
Topological domaini57 – 92CytoplasmicSequence analysisAdd BLAST36

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi60C → S: Significantly reduced half-life; when associated with S-62. 1 Publication1
Mutagenesisi62C → S: Significantly reduced half-life; when associated with S-60. 1 Publication1

Organism-specific databases

DisGeNETi5348
OpenTargetsiENSG00000266964
PharmGKBiPA28441

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20By similarityAdd BLAST20
ChainiPRO_000001035921 – 92PhospholemmanAdd BLAST72

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi60S-palmitoyl cysteine1 Publication1
Modified residuei62S-glutathionyl cysteine; alternateBy similarity1
Lipidationi62S-palmitoyl cysteine; alternate1 Publication1
Modified residuei79PhosphothreonineBy similarity1
Modified residuei82PhosphoserineBy similarity1
Modified residuei83Phosphoserine; by PKA and PKCBy similarity1
Modified residuei88Phosphoserine; by PKA1 Publication1
Modified residuei89Phosphothreonine; by PKCBy similarity1

Post-translational modificationi

Major plasma membrane substrate for cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) in several different tissues (By similarity). Phosphorylated in response to insulin and adrenergic stimulation (By similarity). Phosphorylation at Ser-88 stimulates sodium/potassium-transporting ATPase activity while the unphosphorylated form inhibits sodium/potassium-transporting ATPase activity (By similarity). Phosphorylation increases tetramerization, decreases binding to ATP1A1 and reduces inhibition of ATP1A1 activity (By similarity). Phosphorylation at Ser-83 leads to greatly reduced interaction with ATP1A1, ATP1A2 and ATP1A3 (By similarity). May be phosphorylated by DMPK (PubMed:10811636).By similarity1 Publication
Palmitoylation increases half-life and stability and is enhanced upon phosphorylation at Ser-88 by PKA.1 Publication

Keywords - PTMi

Glutathionylation, Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

MaxQBiO00168
PaxDbiO00168
PeptideAtlasiO00168
PRIDEiO00168
ProteomicsDBi47759

PTM databases

iPTMnetiO00168
PhosphoSitePlusiO00168
SwissPalmiO00168

Expressioni

Tissue specificityi

Highest expression in skeletal muscle and heart. Moderate levels in brain, placenta, lung, liver, pancreas, uterus, bladder, prostate, small intestine and colon with mucosal lining. Very low levels in kidney, colon and small intestine without mucosa, prostate without endothelial lining, spleen, and testis.1 Publication

Gene expression databases

BgeeiENSG00000266964 Expressed in 90 organ(s), highest expression level in tibial nerve
CleanExiHS_FXYD1
ExpressionAtlasiO00168 baseline and differential
GenevisibleiO00168 HS

Organism-specific databases

HPAiHPA026873

Interactioni

Subunit structurei

Homotetramer (PubMed:16597826). Monomer (PubMed:17511473). Regulatory subunit of the sodium/potassium-transporting ATPase (NKA) which is composed of a catalytic alpha subunit, an auxiliary non-catalytic beta subunit and an additional regulatory subunit (By similarity). The monomeric form associates with NKA while the oligomeric form does not (By similarity). Interacts with the catalytic alpha-1 subunit ATP1A1 (By similarity). Also interacts with the catalytic alpha-2 and alpha-3 subunits ATP1A2 and ATP1A3 (By similarity). Very little interaction with ATP1A1, ATP1A2 or ATP1A3 when phosphorylated at Ser-83 (By similarity). Interacts with the non-catalytic beta-1 subunit ATP1B1 (By similarity). Oxidative stress decreases interaction with ATP1A1 but increases interaction with ATP1B1 (By similarity).By similarity2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111363, 16 interactors
STRINGi9606.ENSP00000343314

Structurei

Secondary structure

192
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO00168
SMRiO00168
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO00168

Family & Domainsi

Domaini

The cytoplasmic domain is sufficient to regulate sodium/potassium-transporting ATPase activity.By similarity

Sequence similaritiesi

Belongs to the FXYD family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410J08K Eukaryota
ENOG410YYN6 LUCA
GeneTreeiENSGT00530000063932
HOGENOMiHOG000234467
HOVERGENiHBG008212
InParanoidiO00168
KOiK13360
PhylomeDBiO00168
TreeFamiTF333443

Family and domain databases

InterProiView protein in InterPro
IPR000272 Ion-transport_regulator_FXYD
PfamiView protein in Pfam
PF02038 ATP1G1_PLM_MAT8, 1 hit
ProDomiView protein in ProDom or Entries sharing at least one domain
PD005989 PD005989, 1 hit
PROSITEiView protein in PROSITE
PS01310 FXYD, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

O00168-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MASLGHILVF CVGLLTMAKA ESPKEHDPFT YDYQSLQIGG LVIAGILFIL
60 70 80 90
GILIVLSRRC RCKFNQQQRT GEPDEEEGTF RSSIRRLSTR RR
Length:92
Mass (Da):10,441
Last modified:August 30, 2002 - v2
Checksum:i11602EFEAFFD8BD8
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
K7EQG4K7EQG4_HUMAN
FXYD domain-containing ion transpor...
FXYD1
115Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti3S → P in AAC51286 (PubMed:9169143).Curated1
Sequence conflicti5G → H in AAC51286 (PubMed:9169143).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U72245 mRNA Translation: AAC51286.1
AK289811 mRNA Translation: BAF82500.1
BC032800 mRNA Translation: AAH32800.1
CCDSiCCDS12445.1
RefSeqiNP_001265646.1, NM_001278717.1
NP_001265647.1, NM_001278718.1
NP_005022.2, NM_005031.4
NP_068702.1, NM_021902.3
XP_016882363.1, XM_017026874.1
UniGeneiHs.442498

Genome annotation databases

EnsembliENST00000351325; ENSP00000343314; ENSG00000266964
ENST00000455515; ENSP00000393611; ENSG00000266964
ENST00000588081; ENSP00000467727; ENSG00000266964
ENST00000588607; ENSP00000468535; ENSG00000266964
ENST00000588715; ENSP00000465289; ENSG00000266964
ENST00000589209; ENSP00000466398; ENSG00000266964
ENST00000612146; ENSP00000481244; ENSG00000266964
GeneIDi5348
KEGGihsa:5348
UCSCiuc002nyc.5 human

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U72245 mRNA Translation: AAC51286.1
AK289811 mRNA Translation: BAF82500.1
BC032800 mRNA Translation: AAH32800.1
CCDSiCCDS12445.1
RefSeqiNP_001265646.1, NM_001278717.1
NP_001265647.1, NM_001278718.1
NP_005022.2, NM_005031.4
NP_068702.1, NM_021902.3
XP_016882363.1, XM_017026874.1
UniGeneiHs.442498

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2J1Imodel-A/B/C/D32-59[»]
2JO1NMR-A21-92[»]
ProteinModelPortaliO00168
SMRiO00168
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111363, 16 interactors
STRINGi9606.ENSP00000343314

PTM databases

iPTMnetiO00168
PhosphoSitePlusiO00168
SwissPalmiO00168

Proteomic databases

MaxQBiO00168
PaxDbiO00168
PeptideAtlasiO00168
PRIDEiO00168
ProteomicsDBi47759

Protocols and materials databases

DNASUi5348
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000351325; ENSP00000343314; ENSG00000266964
ENST00000455515; ENSP00000393611; ENSG00000266964
ENST00000588081; ENSP00000467727; ENSG00000266964
ENST00000588607; ENSP00000468535; ENSG00000266964
ENST00000588715; ENSP00000465289; ENSG00000266964
ENST00000589209; ENSP00000466398; ENSG00000266964
ENST00000612146; ENSP00000481244; ENSG00000266964
GeneIDi5348
KEGGihsa:5348
UCSCiuc002nyc.5 human

Organism-specific databases

CTDi5348
DisGeNETi5348
EuPathDBiHostDB:ENSG00000266964.5
GeneCardsiFXYD1
HGNCiHGNC:4025 FXYD1
HPAiHPA026873
MIMi602359 gene
neXtProtiNX_O00168
OpenTargetsiENSG00000266964
PharmGKBiPA28441
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J08K Eukaryota
ENOG410YYN6 LUCA
GeneTreeiENSGT00530000063932
HOGENOMiHOG000234467
HOVERGENiHBG008212
InParanoidiO00168
KOiK13360
PhylomeDBiO00168
TreeFamiTF333443

Enzyme and pathway databases

ReactomeiR-HSA-5578775 Ion homeostasis
R-HSA-936837 Ion transport by P-type ATPases
SIGNORiO00168

Miscellaneous databases

EvolutionaryTraceiO00168
GeneWikiiFXYD1
GenomeRNAii5348
PROiPR:O00168
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000266964 Expressed in 90 organ(s), highest expression level in tibial nerve
CleanExiHS_FXYD1
ExpressionAtlasiO00168 baseline and differential
GenevisibleiO00168 HS

Family and domain databases

InterProiView protein in InterPro
IPR000272 Ion-transport_regulator_FXYD
PfamiView protein in Pfam
PF02038 ATP1G1_PLM_MAT8, 1 hit
ProDomiView protein in ProDom or Entries sharing at least one domain
PD005989 PD005989, 1 hit
PROSITEiView protein in PROSITE
PS01310 FXYD, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPLM_HUMAN
AccessioniPrimary (citable) accession number: O00168
Secondary accession number(s): A8K196
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: August 30, 2002
Last modified: September 12, 2018
This is version 150 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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