P56513 · PLM_CANLF
- ProteinPhospholemman
- GeneFXYD1
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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 (PubMed:12169672).
Inhibits NKA activity in its unphosphorylated state and stimulates activity when phosphorylated (By similarity).
Reduces glutathionylation of the NKA beta-1 subunit ATP1B1, thus reversing glutathionylation-mediated inhibition of ATP1B1 (PubMed:21454534).
Contributes to female sexual development by maintaining the excitability of neurons which secrete gonadotropin-releasing hormone (By similarity).
Inhibits NKA activity in its unphosphorylated state and stimulates activity when phosphorylated (By similarity).
Reduces glutathionylation of the NKA beta-1 subunit ATP1B1, thus reversing glutathionylation-mediated inhibition of ATP1B1 (PubMed:21454534).
Contributes to female sexual development by maintaining the excitability of neurons which secrete gonadotropin-releasing hormone (By similarity).
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | apical plasma membrane | |
Cellular Component | caveola | |
Cellular Component | intercalated disc | |
Cellular Component | sarcolemma | |
Cellular Component | sodium:potassium-exchanging ATPase complex | |
Cellular Component | T-tubule | |
Molecular Function | sodium channel regulator activity | |
Biological Process | negative regulation of protein glutathionylation | |
Biological Process | positive regulation of sodium ion export across plasma membrane | |
Biological Process | potassium ion transport | |
Biological Process | regulation of P-type sodium:potassium-exchanging transporter activity | |
Biological Process | sodium ion transport |
Keywords
- Biological process
- Ligand
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended namePhospholemman
- Alternative names
Gene names
Organism names
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Carnivora > Caniformia > Canidae > Canis
Accessions
- Primary accessionP56513
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane, sarcolemma ; Single-pass type I membrane protein
Apical cell membrane ; Single-pass type I membrane protein
Note: Detected in the apical cell membrane in brain. In myocytes, localizes to sarcolemma, t-tubules and intercalated disks.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 21-35 | Extracellular | ||||
Sequence: EAPQEHDPFTYDYQS | ||||||
Transmembrane | 36-56 | Helical | ||||
Sequence: LRIGGLIIAGILFILGILIVL | ||||||
Topological domain | 57-92 | Cytoplasmic | ||||
Sequence: SRRCRCKFNQQQRTGEPDEEEGTFRSSIRRLSTRRR |
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 60 | Does not affect glutathionylation. | ||||
Sequence: C → A | ||||||
Mutagenesis | 62 | Loss of glutathionylation and loss of ability to reduce glutathionylation of ATP1B1. | ||||
Sequence: C → A | ||||||
Mutagenesis | 63 | Loss of glutathionylation and loss of ability to reduce glutathionylation of ATP1B1. | ||||
Sequence: K → G | ||||||
Mutagenesis | 83 | Loss of phosphorylation. Decreased affinity of the sodium/potassium-transporting ATPase for Na+. | ||||
Sequence: S → A | ||||||
Mutagenesis | 83 | Phosphomimetic mutant which reduces binding to ATP1A1 and increases FXYD1 oligomerization. | ||||
Sequence: S → E | ||||||
Mutagenesis | 88 | Loss of phosphorylation. Decreased affinity of the sodium/potassium-transporting ATPase for Na+. | ||||
Sequence: S → A | ||||||
Mutagenesis | 88 | Phosphomimetic mutant which reduces binding to ATP1A1 and increases FXYD1 oligomerization. | ||||
Sequence: S → E | ||||||
Mutagenesis | 89 | Loss of phosphorylation. | ||||
Sequence: T → A |
PTM/Processing
Features
Showing features for signal, chain, lipidation, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-20 | |||||
Sequence: MAPLHHILVLCVGFLTTATA | ||||||
Chain | PRO_0000010358 | 21-92 | Phospholemman | |||
Sequence: EAPQEHDPFTYDYQSLRIGGLIIAGILFILGILIVLSRRCRCKFNQQQRTGEPDEEEGTFRSSIRRLSTRRR | ||||||
Lipidation | 60 | S-palmitoyl cysteine | ||||
Sequence: C | ||||||
Modified residue | 62 | S-glutathionyl cysteine; alternate | ||||
Sequence: C | ||||||
Lipidation | 62 | S-palmitoyl cysteine; alternate | ||||
Sequence: C | ||||||
Modified residue | 79 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 82 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 83 | Phosphoserine; by PKA and PKC | ||||
Sequence: S | ||||||
Modified residue | 88 | Phosphoserine; by PKA and PKC | ||||
Sequence: S | ||||||
Modified residue | 89 | Phosphothreonine; by PKC | ||||
Sequence: T |
Post-translational modification
Major plasma membrane substrate for cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) in several different tissues (PubMed:1710217, PubMed:20861470).
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 (PubMed:21220422).
Phosphorylation at Ser-83 leads to greatly reduced interaction with ATP1A1, ATP1A2 and ATP1A3 (By similarity).
May be phosphorylated by DMPK (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 (PubMed:21220422).
Phosphorylation at Ser-83 leads to greatly reduced interaction with ATP1A1, ATP1A2 and ATP1A3 (By similarity).
May be phosphorylated by DMPK (By similarity).
Palmitoylation increases half-life and stability and is enhanced upon phosphorylation at Ser-88 by PKA.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Present in heart, esophagus, stomach, aorta, skeletal muscle, smooth muscle, and liver but absent from brain and kidney.
Interaction
Subunit
Homotetramer (By similarity).
Monomer (By similarity).
Regulatory subunit of the sodium/potassium-transporting ATPase (NKA) which is composed of a catalytic alpha subunit, a 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 (PubMed:16943195, PubMed:21454534).
Also interacts with the catalytic alpha-2 and alpha-3 subunits ATP1A2 and ATP1A3 (By similarity).
Very little interaction with the alpha subunits ATP1A1, ATP1A2 or ATP1A3 when phosphorylated at Ser-83 (By similarity).
Interacts with non-catalytic beta-1 subunit ATP1B1 (PubMed:21454534).
Oxidative stress decreases interaction with ATP1A1 but increases interaction with ATP1B1 (PubMed:21454534).
Monomer (By similarity).
Regulatory subunit of the sodium/potassium-transporting ATPase (NKA) which is composed of a catalytic alpha subunit, a 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 (PubMed:16943195, PubMed:21454534).
Also interacts with the catalytic alpha-2 and alpha-3 subunits ATP1A2 and ATP1A3 (By similarity).
Very little interaction with the alpha subunits ATP1A1, ATP1A2 or ATP1A3 when phosphorylated at Ser-83 (By similarity).
Interacts with non-catalytic beta-1 subunit ATP1B1 (PubMed:21454534).
Oxidative stress decreases interaction with ATP1A1 but increases interaction with ATP1B1 (PubMed:21454534).
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 65-92 | Disordered | ||||
Sequence: NQQQRTGEPDEEEGTFRSSIRRLSTRRR | ||||||
Compositional bias | 68-84 | Basic and acidic residues | ||||
Sequence: QRTGEPDEEEGTFRSSI |
Domain
The cytoplasmic domain is sufficient to regulate sodium/potassium-transporting ATPase activity.
Sequence similarities
Belongs to the FXYD family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length92
- Mass (Da)10,500
- Last updated1998-07-15 v1
- Checksum890DE301BF8E740A
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 68-84 | Basic and acidic residues | ||||
Sequence: QRTGEPDEEEGTFRSSI |
Keywords
- Technical term