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FXYD1 FXYD domain containing ion transport regulator 1 [ Homo sapiens (human) ]

Gene ID: 5348, updated on 2-Nov-2024

Summary

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Official Symbol
FXYD1provided by HGNC
Official Full Name
FXYD domain containing ion transport regulator 1provided by HGNC
Primary source
HGNC:HGNC:4025
See related
Ensembl:ENSG00000266964 MIM:602359; AllianceGenome:HGNC:4025
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
PLM
Summary
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]
Expression
Broad expression in liver (RPKM 47.5), heart (RPKM 45.3) and 14 other tissues See more
Orthologs
mouse all
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Genomic context

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See FXYD1 in Genome Data Viewer
Location:
19q13.12
Exon count:
12
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (35137188..35143109)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (37681906..37687737)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (35629728..35634013)

Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene FXYD domain containing ion transport regulator 3 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:35613161-35614050 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:35614051-35614938 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14456 Neighboring gene microRNA 6887 Neighboring gene leucine rich repeat LGI family member 4 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:35632134-35632696 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:35633820-35634380 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:35634381-35634942 Neighboring gene FXYD domain containing ion transport regulator 7 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:35642007-35642406 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr19:35643105-35643656 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:35644606-35645470 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14457 Neighboring gene FXYD domain containing ion transport regulator 5

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Amino acid substitutions in the FXYD motif enhance phospholemman-induced modulation of cardiac L-type calcium channels. Guo K, et al. Am J Physiol Cell Physiol, 2010 Nov. PMID 20720179, Free PMC Article
  2. Protein kinase C and cyclic AMP-dependent protein kinase phosphorylate phospholemman, an insulin and adrenaline-regulated membrane phosphoprotein, at specific sites in the carboxy terminal domain. Walaas SI, et al. Biochem J, 1994 Dec 1. PMID 7999001, Free PMC Article
  3. Expression mode and prognostic value of FXYD family members in colon cancer. Jin M, et al. Aging (Albany NY), 2021 Jul 15. PMID 34270462, Free PMC Article
  4. Role of phospholemman phosphorylation sites in mediating kinase-dependent regulation of the Na+-K+-ATPase. Han F, et al. Am J Physiol Cell Physiol, 2010 Dec. PMID 20861470, Free PMC Article
  5. A study of the membrane association and regulatory effect of the phospholemman cytoplasmic domain. Hughes E, et al. Biochim Biophys Acta, 2011 Apr. PMID 21130070

See all (44) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Expression mode and prognostic value of FXYD family members in colon cancer.
    Title: Expression mode and prognostic value of FXYD family members in colon cancer.
  2. FXYD protein isoforms differentially modulate human Na/K pump function.
    Title: FXYD protein isoforms differentially modulate human Na/K pump function.
  3. Blood flow restriction augmented exercise-induced increases in muscle FXYD1 and PGC-1alpha mRNA in men
    Title: Increased FXYD1 and PGC-1α mRNA after blood flow-restricted running is related to fibre type-specific AMPK signalling and oxidative stress in human muscle.
  4. Study demonstrated that the expression of FXYD1, FXYD3 and FXYD5 is elevated in the lungs of Acute respiratory distress syndrome patients
    Title: FXYD1 negatively regulates Na(+)/K(+)-ATPase activity in lung alveolar epithelial cells.
  5. a period of high-intensity training with reduced training volume increases expression and phosphorylation levels of FXYD1, which may affect Na(+)/K(+) pump activity and muscle K(+) homeostasis during intense exercise.
    Title: Intensive training and reduced volume increases muscle FXYD1 expression and phosphorylation at rest and during exercise in athletes.
  6. Stopped-flow experiments using the dye RH421 show that FXYD1 slows the conformational transition E2(2K)ATP --> E1(3Na)ATP but does not affect 3NaE1P --> E2P3Na.
    Title: Molecular Mechanisms and Kinetic Effects of FXYD1 and Phosphomimetic Mutants on Purified Human Na,K-ATPase.
  7. the evolutionary conservation of G-quadruplex forming sequences with the confirmation of G-quadruplex formation in vitro by two FXYD1 homologues
    Title: G-quadruplex formation of FXYD1 pre-mRNA indicates the possibility of regulating expression of its protein product.
  8. Phospholemman is the target of a variety of post-translational modifications and these can dynamically alter the activity of the Na pump. [Review]
    Title: Novel regulation of cardiac Na pump via phospholemman.
  9. PLM regulates important ion transporters in the heart and offers a tempting target for development of drugs to treat heart failure.
    Title: Coordinated regulation of cardiac Na(+)/Ca (2+) exchanger and Na (+)-K (+)-ATPase by phospholemman (FXYD1).
  10. Intracellular trafficking of FXYD1 (phospholemman) and FXYD7 proteins in Xenopus oocytes and mammalian cells.
    Title: Intracellular trafficking of FXYD1 (phospholemman) and FXYD7 proteins in Xenopus oocytes and mammalian cells.
Submit: New GeneRIF Correction See all GeneRIFs (27)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See Variation Viewer (GRCh37.p13)

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC44983

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables chloride channel activity TAS
Traceable Author Statement
more info
 PubMed 
enables sodium channel regulator activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables sodium channel regulator activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables transmembrane transporter binding ISS
Inferred from Sequence or Structural Similarity
more info
  
Process Evidence Code Pubs
involved_in chloride transmembrane transport IEA
Inferred from Electronic Annotation
more info
  
involved_in chloride transport TAS
Traceable Author Statement
more info
 PubMed 
involved_in muscle contraction TAS
Traceable Author Statement
more info
 PubMed 
involved_in negative regulation of protein glutathionylation ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of sodium ion export across plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of sodium ion export across plasma membrane ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in potassium ion transport IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of cardiac muscle cell membrane potential ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of heart contraction TAS
Traceable Author Statement
more info
 PubMed 
involved_in regulation of sodium ion transmembrane transporter activity ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in sodium ion transport IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in T-tubule ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in apical plasma membrane ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in caveola ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in intercalated disc ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in plasma membrane TAS
Traceable Author Statement
more info
  
located_in sarcolemma ISS
Inferred from Sequence or Structural Similarity
more info
  
part_of sodium:potassium-exchanging ATPase complex ISS
Inferred from Sequence or Structural Similarity
more info
  

General protein information

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Preferred Names
phospholemman
Names
sodium/potassium-transporting ATPase subunit FXYD1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001278717.2 → NP_001265646.1  phospholemman precursor

    See identical proteins and their annotated locations for NP_001265646.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (c) differs in the 5' UTR compared to variant a. Variants a, b, c and d encode the same protein.
    Source sequence(s)
    AC020907, BC032800, BM691130, HY151827
    Consensus CDS
    CCDS12445.1
    UniProtKB/Swiss-Prot
    A8K196, O00168
    Related
    ENSP00000481244.1, ENST00000612146.4
    Conserved Domains (1) summary
    cd20317
    Location:23 → 86
    FXYD1; FXYD domain-containing ion transport regulator 1

  2. NM_001278718.2 → NP_001265647.1  phospholemman precursor

    See identical proteins and their annotated locations for NP_001265647.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (d) differs in the 5' UTR compared to variant a. Variants a, b, c and d encode the same protein.
    Source sequence(s)
    AC020907, BC032800, BM691130, HY111815
    Consensus CDS
    CCDS12445.1
    UniProtKB/Swiss-Prot
    A8K196, O00168
    Related
    ENSP00000465289.1, ENST00000588715.5
    Conserved Domains (1) summary
    cd20317
    Location:23 → 86
    FXYD1; FXYD domain-containing ion transport regulator 1

  3. NM_005031.5 → NP_005022.2  phospholemman precursor

    See identical proteins and their annotated locations for NP_005022.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (a) and variants b, c and d encode the same protein.
    Source sequence(s)
    AC020907, BM691130, BX115036
    Consensus CDS
    CCDS12445.1
    UniProtKB/Swiss-Prot
    A8K196, O00168
    Related
    ENSP00000393611.1, ENST00000455515.6
    Conserved Domains (1) summary
    cd20317
    Location:23 → 86
    FXYD1; FXYD domain-containing ion transport regulator 1

  4. NM_021902.4 → NP_068702.1  phospholemman precursor

    See identical proteins and their annotated locations for NP_068702.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (b) differs in the 5' UTR compared to variant a. Variants a, b, c and d encode the same protein.
    Source sequence(s)
    AC020907, BC032800, BM691130, HY151101
    Consensus CDS
    CCDS12445.1
    UniProtKB/Swiss-Prot
    A8K196, O00168
    Related
    ENSP00000343314.3, ENST00000351325.9
    Conserved Domains (1) summary
    cd20317
    Location:23 → 86
    FXYD1; FXYD domain-containing ion transport regulator 1

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

    Range
    35137188..35143109
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017026874.3 → XP_016882363.1  phospholemman isoform X1

    UniProtKB/Swiss-Prot
    A8K196, O00168
    Conserved Domains (1) summary
    cd20317
    Location:23 → 86
    FXYD1; FXYD domain-containing ion transport regulator 1

  2. XM_047438938.1 → XP_047294894.1  phospholemman isoform X1

    UniProtKB/Swiss-Prot
    A8K196, O00168
    Related
    ENSP00000467727.1, ENST00000588081.5

  3. XM_017026875.3 → XP_016882364.1  phospholemman isoform X2

    Related
    ENSP00000468535.1, ENST00000588607.5
    Conserved Domains (1) summary
    pfam02038
    Location:42 → 87
    ATP1G1_PLM_MAT8; ATP1G1/PLM/MAT8 family

  4. XM_017026876.3 → XP_016882365.1  phospholemman isoform X2

    Conserved Domains (1) summary
    pfam02038
    Location:42 → 87
    ATP1G1_PLM_MAT8; ATP1G1/PLM/MAT8 family

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060943.1 Alternate T2T-CHM13v2.0

    Range
    37681906..37687737
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054321220.1 → XP_054177195.1  phospholemman isoform X1

    UniProtKB/Swiss-Prot
    A8K196, O00168

  2. XM_054321219.1 → XP_054177194.1  phospholemman isoform X1

    UniProtKB/Swiss-Prot
    A8K196, O00168

  3. XM_054321221.1 → XP_054177196.1  phospholemman isoform X2

  4. XM_054321222.1 → XP_054177197.1  phospholemman isoform X2

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O00168.2 GenPept UniProtKB/Swiss-Prot:O00168

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