This gene encodes a member of a family of small membrane proteins that share a 35-amino acid signature sequence domain, beginning with the sequence PFXYD and containing 7 invariant and 6 highly conserved amino acids. The approved human gene nomenclature for the family is FXYD-domain containing ion transport regulator. Mouse FXYD5 has been termed RIC (Related to Ion Channel). FX... See more...

Aliases for FXYD1 Gene

Aliases for FXYD1 Gene

  • FXYD Domain Containing Ion Transport Regulator 1 2 3 5
  • Phospholemman 2 3 4
  • Sodium/Potassium-Transporting ATPase Subunit FXYD1 3 4
  • PLM 3 4
  • FXYD Domain-Containing Ion Transport Regulator 1 4
  • FXYD1 5

External Ids for FXYD1 Gene

Previous HGNC Symbols for FXYD1 Gene

  • PLM

Previous GeneCards Identifiers for FXYD1 Gene

  • GC19P036247
  • GC19P036078
  • GC19P040305
  • GC19P040322
  • GC19P040323
  • GC19P040324
  • GC19P035629
  • GC19P032137
  • GC19P035139
  • GC19P037006
  • GC19P037175
  • GC19P037271
  • GC19P037705
  • GC19P035140
  • GC19P035266
  • GC19P035582
  • GC19P036220
  • GC19P036397
  • GC19P036558
  • GC19P036727
  • GC19P036869

Summaries for FXYD1 Gene

Entrez Gene Summary for FXYD1 Gene

  • This gene encodes a member of a family of small membrane proteins that share a 35-amino acid signature sequence domain, beginning with the sequence PFXYD and containing 7 invariant and 6 highly conserved amino acids. The approved human gene nomenclature for the family is FXYD-domain containing ion transport regulator. Mouse FXYD5 has been termed RIC (Related to Ion Channel). FXYD2, also known as the gamma subunit of the Na,K-ATPase, regulates the properties of that enzyme. FXYD1 (phospholemman), FXYD2 (gamma), FXYD3 (MAT-8), FXYD4 (CHIF), and FXYD5 (RIC) have been shown to induce channel activity in experimental expression systems. Transmembrane topology has been established for two family members (FXYD1 and FXYD2), with the N-terminus extracellular and the C-terminus on the cytoplasmic side of the membrane. The protein encoded by this gene is a plasma membrane substrate for several kinases, including protein kinase A, protein kinase C, NIMA kinase, and myotonic dystrophy kinase. It is thought to form an ion channel or regulate ion channel activity. Transcript variants with different 5' UTR sequences have been described in the literature. [provided by RefSeq, Jul 2008]

GeneCards Summary for FXYD1 Gene

FXYD1 (FXYD Domain Containing Ion Transport Regulator 1) is a Protein Coding gene. Diseases associated with FXYD1 include Periodic Limb Movement Disorder and Pneumoconiosis Due To Talc. Among its related pathways are Cardiac conduction and Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds. Gene Ontology (GO) annotations related to this gene include ion channel activity and chloride channel activity. An important paralog of this gene is FXYD6.

UniProtKB/Swiss-Prot Summary for FXYD1 Gene

  • 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.

Gene Wiki entry for FXYD1 Gene

Additional gene information for FXYD1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for FXYD1 Gene

Genomics for FXYD1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for FXYD1 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH19J035136 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 605.9 +3.1 3083 7 ARHGAP35 HNRNPL CREB1 GATAD2A CTCF PRDM10 REST TFE3 ZNF512 RFX1 ENSG00000221857 FXYD7 LGI4 FXYD1 ENSG00000279619 lnc-FAM187B-6 ZNF599 TMEM147-AS1 LSM14A HAUS5
GH19J035293 Enhancer 1 FANTOM5 Ensembl dbSUPER 6 +156.7 156656 1.7 TEAD4 EGR1 ZEB1 ZBTB17 NFIC ZFHX2 BCOR NFIB ZMYM3 KDM1A MAG LSR LGI4 CD22 FXYD1 FXYD7 HPN SCN1B ARHGAP33 ZNF30
GH19J035106 Enhancer 1.4 FANTOM5 Ensembl ENCODE dbSUPER 2.1 -27.9 -27906 5.8 HNRNPL GATAD2A TFE3 IKZF1 RCOR2 JUND ZIC2 PKNOX1 RXRB IKZF2 LGI4 HPN-AS1 FXYD3 MAG HPN FXYD7 FXYD1 ZNF30 SCN1B ZNF302
GH19J035273 Enhancer 0.5 FANTOM5 4.6 +136.0 136028 0.5 PRDM1 ZBTB20 POLR2A ZFP64 RXRA HAMP CD22 FXYD1 5EW4_A-028 USF2 lnc-FAM187B-3
GH19J035134 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 0.7 -2.3 -2262 2.3 HNRNPL CREB1 GATAD2A CTCF PRDM10 REST ZNF629 ZNF692 RCOR2 JUND LGI4 lnc-FAM187B-7 ENSG00000221857 RBM42 PROSER3 LSM14A ZNF792 ZNF599 FXYD7 MAG
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around FXYD1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for FXYD1

Top Transcription factor binding sites by QIAGEN in the FXYD1 gene promoter:
  • AML1a

Genomic Locations for FXYD1 Gene

Genomic Locations for FXYD1 Gene
chr19:35,137,206-35,143,109
(GRCh38/hg38)
Size:
5,904 bases
Orientation:
Plus strand
chr19:35,629,712-35,634,013
(GRCh37/hg19)
Size:
4,302 bases
Orientation:
Plus strand

Genomic View for FXYD1 Gene

Genes around FXYD1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
FXYD1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for FXYD1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for FXYD1 Gene

Proteins for FXYD1 Gene

  • Protein details for FXYD1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O00168-PLM_HUMAN
    Recommended name:
    Phospholemman
    Protein Accession:
    O00168
    Secondary Accessions:
    • A8K196

    Protein attributes for FXYD1 Gene

    Size:
    92 amino acids
    Molecular mass:
    10441 Da
    Quaternary structure:
    • 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).

    Three dimensional structures from OCA and Proteopedia for FXYD1 Gene

neXtProt entry for FXYD1 Gene

Post-translational modifications for FXYD1 Gene

  • 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).
  • Palmitoylation increases half-life and stability and is enhanced upon phosphorylation at Ser-88 by PKA.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for FXYD1 Gene

Domains & Families for FXYD1 Gene

Gene Families for FXYD1 Gene

Human Protein Atlas (HPA):
  • Predicted membrane proteins

Protein Domains for FXYD1 Gene

InterPro:
Blocks:
  • FXYD protein
ProtoNet:

Suggested Antigen Peptide Sequences for FXYD1 Gene

GenScript: Design optimal peptide antigens:
  • FXYD domain-containing ion transport regulator 1 transcript variant b (C7E9P5_HUMAN)
  • FXYD domain-containing ion transport regulator 1 (PLM_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O00168

UniProtKB/Swiss-Prot:

PLM_HUMAN :
  • The cytoplasmic domain is sufficient to regulate sodium/potassium-transporting ATPase activity.
  • Belongs to the FXYD family.
Domain:
  • The cytoplasmic domain is sufficient to regulate sodium/potassium-transporting ATPase activity.
Family:
  • Belongs to the FXYD family.
genes like me logo Genes that share domains with FXYD1: view

Function for FXYD1 Gene

Molecular function for FXYD1 Gene

UniProtKB/Swiss-Prot 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. 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.

Gene Ontology (GO) - Molecular Function for FXYD1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005254 chloride channel activity TAS 9169143
GO:0017080 sodium channel regulator activity IEA,ISS --
GO:0044325 ion channel binding ISS --
GO:0099106 ion channel regulator activity IEA --
genes like me logo Genes that share ontologies with FXYD1: view
genes like me logo Genes that share phenotypes with FXYD1: view

Animal Models for FXYD1 Gene

MGI Knock Outs for FXYD1:

Animal Model Products

  • Taconic Biosciences Mouse Models for FXYD1

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for FXYD1

Clone Products

No data available for Enzyme Numbers (IUBMB) , Phenotypes From GWAS Catalog , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for FXYD1 Gene

Localization for FXYD1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for FXYD1 Gene

Cell membrane, sarcolemma. Single-pass type I membrane protein. Apical cell membrane. Single-pass type I membrane protein. Membrane, caveola. Cell membrane, sarcolemma, T-tubule. Note=Detected in the apical cell membrane in brain. In myocytes, localizes to sarcolemma, t-tubules and intercalated disks. {ECO:0000250 UniProtKB:O08589}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for FXYD1 gene
Compartment Confidence
plasma membrane 4
extracellular 2
cytoskeleton 2
mitochondrion 2
nucleus 2
endoplasmic reticulum 2
cytosol 2
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Nucleoli (2)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for FXYD1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane NAS,TAS --
GO:0005887 integral component of plasma membrane TAS 9169143
GO:0005890 sodium:potassium-exchanging ATPase complex ISS --
GO:0005901 caveola ISS --
GO:0014704 intercalated disc ISS --
genes like me logo Genes that share ontologies with FXYD1: view

Pathways & Interactions for FXYD1 Gene

genes like me logo Genes that share pathways with FXYD1: view

Pathways by source for FXYD1 Gene

SIGNOR curated interactions for FXYD1 Gene

Other effect:

Gene Ontology (GO) - Biological Process for FXYD1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006811 ion transport IEA --
GO:0006813 potassium ion transport IEA --
GO:0006814 sodium ion transport IEA --
GO:0006821 chloride transport TAS 9169143
GO:0006936 muscle contraction TAS 9169143
genes like me logo Genes that share ontologies with FXYD1: view

Drugs & Compounds for FXYD1 Gene

(2) Drugs for FXYD1 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Chloride ion Experimental Pharma 0
cyclic amp Experimental Pharma 0
genes like me logo Genes that share compounds with FXYD1: view

Transcripts for FXYD1 Gene

mRNA/cDNA for FXYD1 Gene

4 REFSEQ mRNAs :
15 NCBI additional mRNA sequence :
11 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for FXYD1

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for FXYD1 Gene

No ASD Table

Relevant External Links for FXYD1 Gene

GeneLoc Exon Structure for
FXYD1

Expression for FXYD1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for FXYD1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for FXYD1 Gene

This gene is overexpressed in Muscle - Skeletal (x5.1).

Protein differential expression in normal tissues from HIPED for FXYD1 Gene

This gene is overexpressed in Adrenal (45.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for FXYD1 Gene



Protein tissue co-expression partners for FXYD1 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for FXYD1

SOURCE GeneReport for Unigene cluster for FXYD1 Gene:

Hs.442498

mRNA Expression by UniProt/SwissProt for FXYD1 Gene:

O00168-PLM_HUMAN
Tissue specificity: 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.

Evidence on tissue expression from TISSUES for FXYD1 Gene

  • Nervous system(4.7)
  • Heart(4.7)
  • Lung(4.4)
  • Muscle(4.2)
  • Liver(3.6)
  • Intestine(2.5)
  • Kidney(2.5)
  • Skin(2.3)
genes like me logo Genes that share expression patterns with FXYD1: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for FXYD1 Gene

Orthologs for FXYD1 Gene

This gene was present in the common ancestor of chordates.

Orthologs for FXYD1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia FXYD1 30 31
  • 99.64 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia FXYD1 30 31
  • 91.67 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia FXYD1 30 31
  • 89.13 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Fxyd1 30
  • 86.23 (n)
Mouse
(Mus musculus)
Mammalia Fxyd1 30 17 31
  • 84.42 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia FXYD1 31
  • 30 (a)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia FXYD1 31
  • 66 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia fxyd1 30
  • 64.71 (n)
Str.13949 30
Zebrafish
(Danio rerio)
Actinopterygii fxyd6l 31
  • 35 (a)
ManyToMany
Species where no ortholog for FXYD1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for FXYD1 Gene

ENSEMBL:
Gene Tree for FXYD1 (if available)
TreeFam:
Gene Tree for FXYD1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for FXYD1: view image

Paralogs for FXYD1 Gene

Paralogs for FXYD1 Gene

(5) SIMAP similar genes for FXYD1 Gene using alignment to 3 proteins:

  • PLM_HUMAN
  • C7E9P5_HUMAN
  • K7EQG4_HUMAN
genes like me logo Genes that share paralogs with FXYD1: view

Variants for FXYD1 Gene

Additional dbSNP identifiers (rs#s) for FXYD1 Gene

Structural Variations from Database of Genomic Variants (DGV) for FXYD1 Gene

Variant ID Type Subtype PubMed ID
esv2718490 CNV deletion 23290073
nsv953282 CNV deletion 24416366

Variation tolerance for FXYD1 Gene

Residual Variation Intolerance Score: 61.7% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for FXYD1 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
FXYD1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for FXYD1 Gene

Disorders for FXYD1 Gene

MalaCards: The human disease database

(11) MalaCards diseases for FXYD1 Gene - From: DISEASES and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search FXYD1 in MalaCards View complete list of genes associated with diseases
genes like me logo Genes that share disorders with FXYD1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for FXYD1 Gene

Publications for FXYD1 Gene

  1. Characterization of the human and rat phospholemman (PLM) cDNAs and localization of the human PLM gene to chromosome 19q13.1. (PMID: 9169143) Chen LS … Cuddy M (Genomics 1997) 2 3 4
  2. Expression and distribution of Na, K-ATPase isoforms in the human uterus. (PMID: 20065300) Floyd RV … Mobasheri A (Reproductive sciences (Thousand Oaks, Calif.) 2010) 3 23
  3. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4
  4. The FXYD gene family of small ion transport regulators or channels: cDNA sequence, protein signature sequence, and expression. (PMID: 10950925) Sweadner KJ … Rael E (Genomics 2000) 3 4
  5. Phospholemman is a substrate for myotonic dystrophy protein kinase. (PMID: 10811636) Mounsey JP … Moorman JR (The Journal of biological chemistry 2000) 3 4

Products for FXYD1 Gene

  • Signalway ELISA kits for FXYD1
  • Signalway Proteins for FXYD1

Sources for FXYD1 Gene