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

Summary

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

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_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
FXYD protein isoforms differentially modulate human Na/K pump function.
Title: FXYD protein isoforms differentially modulate human Na/K pump function.
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.
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.
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.
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.
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.
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.
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).
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 variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D19S208 (e-PCR), detects polymorphism
- UniSTS:8337

D19S208 (e-PCR), detects polymorphism
- UniSTS:31412

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)

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
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
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
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

NC_000019.10 Reference GRCh38.p14 Primary Assembly

Range

35137188..35143109

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
XM_047438938.1 → XP_047294894.1 phospholemman isoform X1

UniProtKB/Swiss-Prot

A8K196, O00168

Related

ENSP00000467727.1, ENST00000588081.5
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
XM_017026876.3 → XP_016882365.1 phospholemman isoform X2

Conserved Domains (1) summary

pfam02038
Location:42 → 87

ATP1G1_PLM_MAT8; ATP1G1/PLM/MAT8 family