Tbio FXYD1 Phospholemman

Protein Summary

Description

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. 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]

Uniprot Accession IDs

• O00168
• A8K196

Gene Name

• FXYD1

Ensembl ID

• ENST00000351325
• ENSP00000343314
• ENSG00000266964
• ENST00000455515
• ENSP00000393611
• ENST00000588081
• ENSP00000467727
• ENST00000588607
• ENSP00000468535
• ENST00000588715
• ENSP00000465289
• ENST00000589209
• ENSP00000466398
• ENST00000612146
• ENSP00000481244

Symbol

• PLM
• PLM

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
disease perturbation	0.95
gene perturbation	0.86
molecular function	0.73
PubMedID	0.69
tissue	0.67

Protein Classes

PANTHER Classes

Protein / Transporter / Ion Channel / Phospholemman

Protein / Enzyme Modulator / Phospholemman

DTO Classes

Protein / Ion Channel / Fxyd Family / Phospholemman

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 264.09   (req: < 5)

Gene RIFs: 24   (req: <= 3)

Antibodies: 266   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 264.09   (req: >= 5)

Gene RIFs: 24   (req: > 3)

Antibodies: 266   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 12

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Expression Data (0 Tissues)

tutorial

No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (61)

Explore Interacting Targets

1 – 10 of 61

• See Interactions on String-DB

NDRG1

Tbio

Novelty:  0.00352631

p_int:  0.9999995

p_ni:  5e-7

Score:  0.221

Data Source:  BioPlex,STRINGDB

NDRG3

Tbio

Novelty:  0.05968882

p_int:  0.999998347

p_ni:  4.4e-7

p_wrong:  0.000001214

Score:  0.355

Data Source:  BioPlex,STRINGDB

NDRG4

Tbio

Novelty:  0.01974969

p_int:  0.999988531

p_ni:  0.000005689

p_wrong:  0.00000578

Score:  0.266

Data Source:  BioPlex,STRINGDB

THNSL1

Tdark

Family:  Enzyme

Novelty:  1.98275016

p_int:  0.999979452

p_ni:  0.000020548

Score:  0.175

Data Source:  BioPlex,STRINGDB

GCHFR

Tbio

Family:  Enzyme

Novelty:  0.04287433

p_int:  0.999206635

p_ni:  0.000793365

Score:  0.157

Data Source:  BioPlex,STRINGDB

ATP6V1D

Tbio

Family:  Enzyme

Novelty:  0.02298626

p_int:  0.997324893

p_ni:  0.002675105

p_wrong:  2e-9

Score:  0.173

Data Source:  BioPlex,STRINGDB

GOPC

Tbio

Novelty:  0.01110168

p_int:  0.990671961

p_ni:  0.009328039

Data Source:  BioPlex

FAM204A

Tdark

Novelty:  0.74892948

p_int:  0.870622443

p_ni:  0.108573801

p_wrong:  0.020803755

Score:  0.345

Data Source:  BioPlex,STRINGDB

PRTFDC1

Tbio

Family:  Enzyme

Novelty:  0.13607881

p_int:  0.83082914

p_ni:  0.02937574

p_wrong:  0.13979512

Score:  0.157

Data Source:  BioPlex,STRINGDB

POLE4

Tdark

Family:  Enzyme

Novelty:  0.23346084

p_int:  0.828618347

p_ni:  0.17130928

p_wrong:  0.000072372

Score:  0.232

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets (8)

Explore Nearest Tclin Targets

Downstream (8)

1 – 5 of 8

ATP1B3

Tclin

Family:  Transporter

KEGG Distance:  1

Common Pathways:  1

1: cAMP signaling pathway

ATP1B2

Tclin

Family:  Transporter

KEGG Distance:  1

Common Pathways:  1

1: cAMP signaling pathway

ATP1B1

Tclin

Family:  Transporter

KEGG Distance:  1

Common Pathways:  1

1: cAMP signaling pathway

ATP1A4

Tclin

Family:  Transporter

KEGG Distance:  1

Common Pathways:  1

1: cAMP signaling pathway

ATP1A3

Tclin

Family:  Transporter

KEGG Distance:  1

Common Pathways:  1

1: cAMP signaling pathway

Pathways (7)

Reactome (6)

KEGG (1)

Cardiac conduction (R-HSA-5576891)

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Find Similar Targets

Items per page:

5

1 – 5 of 6

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Cardiac conduction	137 targets	R-HSA-5576891
Reactome	Ion channel transport	179 targets	R-HSA-983712
Reactome	Ion homeostasis	52 targets	R-HSA-5578775
Reactome	Ion transport by P-type ATPases	55 targets	R-HSA-936837
Reactome	Muscle contraction	202 targets	R-HSA-397014

Name	Explore in Pharos	Explore in Source
Cardiac conduction	137 targets	R-HSA-5576891
Ion channel transport	179 targets	R-HSA-983712
Ion homeostasis	52 targets	R-HSA-5578775
Ion transport by P-type ATPases	55 targets	R-HSA-936837
Muscle contraction	202 targets	R-HSA-397014

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (20)

Functions (3)

Components (8)

Processes (9)

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Items per page:

10

1 – 3 of 3

GO Term	Evidence	Assigned by
ion channel binding	Inferred from Sequence or structural Similarity (ISS)	BHF-UCL
sodium channel regulator activity	Inferred from Sequence or structural Similarity (ISS)	BHF-UCL
chloride channel activity	Traceable Author Statement (TAS)	ProtInc

Disease Associations (null)

No disease associations found

GWAS Traits (16)

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 16

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
serum albumin measurement	EFO_0004535	3	6	8		99.2
calcium measurement	EFO_0004838	1	4	4		97.1
blood protein measurement	EFO_0007937	2	4	4		96.9
sex hormone-binding globulin measurement	EFO_0004696	6	2	6		94.7
mean platelet volume	EFO_0004584	3	3	3		93.3

• Explore on Target Illumination GWAS Analytics (TIGA)

Items per page:

5

1 – 5 of 16

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
serum albumin measurement	EFO_0004535	8		99.2
calcium measurement	EFO_0004838	4		97.1
blood protein measurement	EFO_0007937	4		96.9
sex hormone-binding globulin measurement	EFO_0004696	6		94.7
mean platelet volume	EFO_0004584	3		93.3

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Find similar targets by:

UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Cell membrane
Complete proteome
Glutathionylation
Ion transport
Lipoprotein
Membrane
Palmitate
Phosphoprotein
Potassium

GWAS Trait Find Similar Targets

No Header	No Header
age-related hearing impairment
blood protein measurement
C-reactive protein measurement
calcium measurement
Hodgkins lymphoma
mean platelet volume
mean reticulocyte volume
platelet count
platelet crit
reticulocyte count

MGI Phenotype Find Similar Targets

No Header	No Header
cardiovascular system phenotype
muscle phenotype

IDG Resources

No IDG generated resources found

Orthologs (8)

1 – 5 of 8

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	FXYD domain containing ion transport regulator 1	VGNC:11111	747770
Mouse	FXYD domain-containing ion transport regulator 1	MGI:1889273	56188
Rat	FXYD domain-containing ion transport regulator 1	RGD:69306	58971
Dog	FXYD domain containing ion transport regulator 1	VGNC:41019	476487
Horse	FXYD domain containing ion transport regulator 1	VGNC:18163	100630886

Species	Name	OMA	EggNOG	Inparanoid
Chimp	FXYD domain containing ion transport regulator 1
Mouse	FXYD domain-containing ion transport regulator 1
Rat	FXYD domain-containing ion transport regulator 1
Dog	FXYD domain containing ion transport regulator 1
Horse	FXYD domain containing ion transport regulator 1

Publication Statistics

PubMed Score 264.09

PubMed score by year

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PubTator Score 216.76

PubTator score by year

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Patents

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Related Publications

Text Mined References (37)

GeneRif Annotations (24)

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PMID	Year	Title