PLN phospholamban [Homo sapiens] - Gene

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Summary

Official Symbol: PLNprovided by HGNC
Official Full Name: phospholambanprovided by HGNC
Primary source: HGNC:9080
Locus tag: RP3-509L4.2
See related: Ensembl:ENSG00000198523; HPRD:01395; MIM:172405; Vega:OTTHUMG00000015462
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: PLB; CMD1P; CMH18
Summary: The protein encoded by this gene is found as a pentamer and is a major substrate for the cAMP-dependent protein kinase in cardiac muscle. The encoded protein is an inhibitor of cardiac muscle sarcoplasmic reticulum Ca(2+)-ATPase in the unphosphorylated state, but inhibition is relieved upon phosphorylation of the protein. The subsequent activation of the Ca(2+) pump leads to enhanced muscle relaxation rates, thereby contributing to the inotropic response elicited in heart by beta-agonists. The encoded protein is a key regulator of cardiac diastolic function. Mutations in this gene are a cause of inherited human dilated cardiomyopathy with refractory congestive heart failure. [provided by RefSeq, Jul 2008]

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Genomic context

Location :: 6q22.1

Sequence :: Chromosome: 6; NC_000006.11 (118869442..118881587)

See PLN in Epigenomics, MapViewer

Chromosome 6 - NC_000006.11 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

both topology and function of PLN are shaped by the interactions with lipids, which fine-tune the regulation of SERCA
Title: Structural topology of phospholamban pentamer in lipid bilayers by a hybrid solution and solid-state NMR method.
PLN gene mutations were not found to be associated with HCM in the study group.
Title: Phospholamban gene mutations are not associated with hypertrophic cardiomyopathy in patients from southern Poland.
Lethal Arg9Cys phospholamban mutation hinders Ca2+-ATPase regulation and phosphorylation by protein kinase A.
Title: Lethal Arg9Cys phospholamban mutation hinders Ca2+-ATPase regulation and phosphorylation by protein kinase A.
Mutations in PLN are rare in frequency, yet the small size of the genetic locus may make it amenable to inclusion on HCM gene test panels.
Title: PLN-encoded phospholamban mutation in a large cohort of hypertrophic cardiomyopathy cases: summary of the literature and implications for genetic testing.
In this study, they investigated the effects of PLB phosphorylation and mutation on the interaction between a PLB oligomer and SERCA in the context of 2D crystals.
Title: Phosphorylation and mutation of phospholamban alter physical interactions with the sarcoplasmic reticulum calcium pump.
Study conclude that PLN is enriched in the ER due to COP I-mediated transport that is dependent on its intact di-arginine motif and that the N-terminal di-arginine motif may act as a general ER retrieval sequence.
Title: Endoplasmic reticulum protein targeting of phospholamban: a common role for an N-terminal di-arginine motif in ER retention?
Observational study, meta-analysis, and genome-wide association study of gene-disease association. (HuGE Navigator)
Title: Genome-wide association analysis identifies multiple loci related to resting heart rate.
Observational study of genetic testing. (HuGE Navigator)
Title: A novel custom resequencing array for dilated cardiomyopathy.
Three steps in the kinetic reaction with calcium-dependent ATPase (SERCA) are affected by the presence of PLB: binding of the first calcium ion, a subsequent conformational change in SERCA, and binding of the second calcium ion.
Title: Effects of phospholamban transmembrane mutants on the calcium affinity, maximal activity, and cooperativity of the sarcoplasmic reticulum calcium pump.
These data demonstrate that alphaKAP exhibits a novel interaction with SERCA2a and may serve to spatially position CaMKII isoforms at the SR and to uniquely modulate the phosphorylation of PLN.
Title: Alpha-kinase anchoring protein alphaKAP interacts with SERCA2A to spatially position Ca2+/calmodulin-dependent protein kinase II and modulate phospholamban phosphorylation.

Submit: New GeneRIF Correction See all (39)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

Cardiomyopathy, familial hypertrophic, 18

MIM: 613874

Common genetic variation near the phospholamban gene is associated with cardiac repolarisation: meta-analysis of three genome-wide association studies.

Common variants at ten loci influence QT interval duration in the QTGEN Study.

Common variants at ten loci modulate the QT interval duration in the QTSCD Study.

Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction.

Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data.

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Products	Interactant	Other Gene	Source	Pubs	Description
P26678	O14983	ATP2A1	HPRD	PubMed
P26678	P16615	ATP2A2	HPRD	PubMed
P26678	Q09013	DMPK	HPRD	PubMed
P26678	P26678	PLN	HPRD	PubMed
P26678	Q16821	PPP1R3A	HPRD	PubMed
P26678	P17612	PRKACA	HPRD	PubMed
P26678	P23297	S100A1	HPRD	PubMed
P26678	O00631	SLN	HPRD	PubMed
BioGRID:111365	BioGRID:106977	ATP2A1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:111365	BioGRID:106978	ATP2A2	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:111365	BioGRID:111499	PPP1R3A	BioGRID	PubMed	Reconstituted Complex
BioGRID:111365	BioGRID:112474	SLN	BioGRID	PubMed	Affinity Capture-Western

Function	Evidence Code	Pubs
ATPase inhibitor activity	IEA Inferred from Electronic Annotation more info
calcium channel regulator activity	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
blood circulation	NAS Non-traceable Author Statement more info	PubMed
cardiac muscle tissue development	IEA Inferred from Electronic Annotation more info
cellular calcium ion homeostasis	IEA Inferred from Electronic Annotation more info
negative regulation of heart contraction	IEA Inferred from Electronic Annotation more info
regulation of calcium ion transport	ISS Inferred from Sequence or Structural Similarity more info
regulation of the force of heart contraction	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
integral to membrane	IEA Inferred from Electronic Annotation more info
membrane	IEA Inferred from Electronic Annotation more info
mitochondrial membrane	IEA Inferred from Electronic Annotation more info
mitochondrion	IEA Inferred from Electronic Annotation more info
protein complex	IEA Inferred from Electronic Annotation more info
sarcoplasmic reticulum	IEA Inferred from Electronic Annotation more info
vesicle	IEA Inferred from Electronic Annotation more info

General protein information

Preferred Names: cardiac phospholamban

Names: cardiac phospholamban

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NCBI Reference Sequences (RefSeq)

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.

Genomic

NG_009082.1 RefSeqGene

Range

5001..17146

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_002667.3 → NP_002658.1 cardiac phospholamban

Status: REVIEWED

Source sequence(s)

BC005269, BP259965, M63603

Consensus CDS

CCDS5120.1

UniProtKB/Swiss-Prot

P26678

UniProtKB/TrEMBL

Q5R352

Related

ENSP00000350132, OTTHUMP00000017092, ENST00000357525, OTTHUMT00000041993

Conserved Domains (1) summary

cl04465
Location:1 – 29
Blast Score: 101

Phospholamban; Phospholamban

RefSeqs of Annotated Genomes: Build 37.3

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

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000006.11 Reference GRCh37.p5 Primary Assembly

Range

118869442..118881587

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000138.1 Alternate HuRef

Range

116451106..116463257

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AF177764.1	AAD55950.1
genomic	CH471051.2	EAW48198.1
genomic	Z99496.1	CAI21610.1
mRNA	AK311799.1	BAG34742.1
mRNA	BC005269.1	AAH05269.1
mRNA	BP259965.1	None
mRNA	M60411.1	AAA60109.1
mRNA	M63603.1	AAA60083.1
other-genetic	DQ893034.2	ABM83960.1
other-genetic	DQ896146.2	ABM87145.1