P26678 (PPLA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cardiac phospholamban
Short name=PLB

Gene names

Name:	PLN
Synonyms:	PLB

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	52 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Phospholamban has been postulated to regulate the activity of the calcium pump of cardiac sarcoplasmic reticulum.
Subunit structure	Homopentamer. Interacts with HAX1. Ref.8
Subcellular location	Mitochondrion membrane; Single-pass membrane protein. Sarcoplasmic reticulum By similarity.
Tissue specificity	Heart.
Post-translational modification	Phosphorylated at Thr-17 by CaMK2, and in response to beta-adrenergic stimulation. Phosphorylation by DMPK may stimulate sarcoplasmic reticulum calcium uptake in cardiomyocytes. Ref.6 Ref.7
Involvement in disease	Cardiomyopathy, dilated 1P (CMD1P) [MIM:609909]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12 Ref.13 Cardiomyopathy, familial hypertrophic 18 (CMH18) [MIM:613874]: A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5
Sequence similarities	Belongs to the phospholamban family.

Ontologies

Keywords
Cellular component	Membrane Mitochondrion Sarcoplasmic reticulum
Disease	Cardiomyopathy Disease mutation
Domain	Transmembrane Transmembrane helix
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	adrenergic receptor signaling pathway involved in heart process Inferred from electronic annotation. Source: Compara blood circulation Non-traceable author statement PubMed 8406504. Source: ProtInc calcium ion transport Inferred from electronic annotation. Source: Compara cardiac muscle tissue development Inferred from electronic annotation. Source: Compara cytosolic calcium ion homeostasis Inferred by curator PubMed 19708671. Source: BHF-UCL negative regulation of calcium ion binding Inferred from direct assay PubMed 19708671. Source: BHF-UCL negative regulation of calcium ion import Inferred from sequence or structural similarity PubMed 12032137. Source: BHF-UCL negative regulation of calcium-transporting ATPase activity Inferred from direct assay PubMed 19708671. Source: BHF-UCL negative regulation of heart rate Inferred from mutant phenotype Ref.13. Source: BHF-UCL regulation of cardiac muscle cell contraction Inferred by curator PubMed 19708671. Source: BHF-UCL regulation of cardiac muscle cell membrane potential Inferred by curator PubMed 19708671. Source: BHF-UCL regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion Inferred from electronic annotation. Source: Compara regulation of relaxation of cardiac muscle Inferred by curator PubMed 19708671. Source: BHF-UCL regulation of ryanodine-sensitive calcium-release channel activity Inferred from electronic annotation. Source: Compara regulation of the force of heart contraction Inferred by curator PubMed 19708671. Source: BHF-UCL regulation of the force of heart contraction by cardiac conduction Inferred from electronic annotation. Source: Compara relaxation of cardiac muscle Traceable author statement PubMed 22679139. Source: BHF-UCL
Cellular_component	endoplasmic reticulum Inferred from sequence or structural similarity. Source: BHF-UCL integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW membrane Inferred from direct assay PubMed 19708671. Source: BHF-UCL mitochondrial membrane Inferred from electronic annotation. Source: UniProtKB-SubCell perinuclear region of cytoplasm Inferred from sequence or structural similarity. Source: BHF-UCL protein complex Inferred from electronic annotation. Source: Compara sarcoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-SubCell vesicle Inferred from electronic annotation. Source: Compara
Molecular_function	ATPase binding Inferred from sequence or structural similarity PubMed 12032137. Source: BHF-UCL ATPase inhibitor activity Inferred from direct assay PubMed 19708671. Source: BHF-UCL calcium channel regulator activity Inferred from electronic annotation. Source: InterPro identical protein binding Inferred from sequence or structural similarity. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DMPK	Q09013	4	EBI-692836,EBI-692774

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 52

52

Cardiac phospholamban

PRO_0000191244

Regions

Topological domain

1 – 31

31

Cytoplasmic Potential

Transmembrane

32 – 52

21

Helical; Potential

Region

16 – 22

7

Involved in HAX1 binding

Amino acid modifications

Modified residue

1

1

N-acetylmethionine By similarity

Modified residue

16

1

Phosphoserine; by PKA and DMPK Ref.6

Modified residue

17

1

Phosphothreonine; by CaMK2 Ref.7

Natural variations

Natural variant

9

1

R → C in CMD1P; impairs phosphorylation by PKA. Ref.12

VAR_025989

Natural variant

14

1

Missing in CMD1P; destabilizes the homopentamer. Ref.13

VAR_025990

Secondary structure

1

.

.

.

.

.

.

.

52

Helix Strand Turn

Details...

Helix

4 – 14

11

Beta strand

18 – 20

3

Helix

23 – 50

28

Sequences

	Sequence		Length	Mass (Da)
	P26678 [UniParc]. Last modified August 1, 1992. Version 1. Checksum: 0766304A76A854D3	FASTA	52	6,109
	10 20 30 40 50 MEKVQYLTRS AIRRASTIEM PQQARQKLQN LFINFCLILI CLLLICIIVM LL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure of the rabbit phospholamban gene, cloning of the human cDNA, and assignment of the gene to human chromosome 6." Fujii J., Zarain-Herzberg A., Willard H.F., Tada M., Maclennan D.H. J. Biol. Chem. 266:11669-11675(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Cloning of human cardiac phospholamban." Salvatore C.A., Jacobson M.A. Submitted (MAR-1991) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"The human phospholamban gene: structure and expression." McTiernan C.F., Frye C.S., Lemster B.H., Kinder E.A., Ogletree-Hughes M.L., Moravec C.S., Feldman A.M. J. Mol. Cell. Cardiol. 31:679-692(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Liver.
[5]	"Mutation of the phospholamban promoter associated with hypertrophic cardiomyopathy." Minamisawa S., Sato Y., Tatsuguchi Y., Fujino T., Imamura S., Uetsuka Y., Nakazawa M., Matsuoka R. Biochem. Biophys. Res. Commun. 304:1-4(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN CMH18.
[6]	"Myotonic dystrophy protein kinase phosphorylates phospholamban and regulates calcium uptake in cardiomyocyte sarcoplasmic reticulum." Kaliman P., Catalucci D., Lam J.T., Kondo R., Gutierrez J.C., Reddy S., Palacin M., Zorzano A., Chien K.R., Ruiz-Lozano P. J. Biol. Chem. 280:8016-8021(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-16 BY DMPK.
[7]	"Ca2+-calmodulin-dependent protein kinase expression and signalling in skeletal muscle during exercise." Rose A.J., Kiens B., Richter E.A. J. Physiol. (Lond.) 574:889-903(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-17 BY CAMK2.
[8]	"Phospholamban interacts with HAX-1, a mitochondrial protein with anti-apoptotic function." Vafiadaki E., Sanoudou D., Arvanitis D.A., Catino D.H., Kranias E.G., Kontrogianni-Konstantopoulos A. J. Mol. Biol. 367:65-79(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HAX1.
[9]	"Solution structure of the cytoplasmic domain of phospholamban: phosphorylation leads to a local perturbation in secondary structure." Mortishire-Smith R.J., Pitzenberger S.M., Burke C.J., Middaugh C.R., Garsky V.M., Johnson R.G. Biochemistry 34:7603-7613(1995) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 1-25.
[10]	"Computational searching and mutagenesis suggest a structure for the pentameric transmembrane domain of phospholamban." Adams P.D., Arkin I.T., Engelman D.M., Bruenger A.T. Nat. Struct. Biol. 2:154-162(1995) [PubMed] [Europe PMC] [Abstract] Cited for: 3D-STRUCTURE MODELING.
[11]	"Using experimental information to produce a model of the transmembrane domain of the ion channel phospholamban." Herzyk P., Hubbard R.E. Biophys. J. 74:1203-1214(1998) [PubMed] [Europe PMC] [Abstract] Cited for: 3D-STRUCTURE MODELING.
[12]	"Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban." Schmitt J.P., Kamisago M., Asahi M., Li G.H., Ahmad F., Mende U., Kranias E.G., MacLennan D.H., Seidman J.G., Seidman C.E. Science 299:1410-1413(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CMD1P CYS-9, CHARACTERIZATION OF VARIANT CMD1P CYS-9.
[13]	"A mutation in the human phospholamban gene, deleting arginine 14, results in lethal, hereditary cardiomyopathy." Haghighi K., Kolokathis F., Gramolini A.O., Waggoner J.R., Pater L., Lynch R.A., Fan G.C., Tsiapras D., Parekh R.R., Dorn G.W. II, MacLennan D.H., Kremastinos D.T., Kranias E.G. Proc. Natl. Acad. Sci. U.S.A. 103:1388-1393(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CMD1P ARG-14 DEL, CHARACTERIZATION OF VARIANT CMD1P ARG-14 DEL.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M63603 mRNA. Translation: AAA60083.1.
M60411 mRNA. Translation: AAA60109.1.
AF177764 Genomic DNA. Translation: AAD55950.1.
BC005269 mRNA. Translation: AAH05269.1.

IPI

IPI00000935.

PIR

A40424.

RefSeq

NP_002658.1. NM_002667.3.

UniGene

Hs.170839.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1K9N	model	-	A/B/C/D/E	35-52	[»]
1KCH	model	-	A/B/C/D/E	35-52	[»]
1PLN	model	-	A/B/C/D/E	35-52	[»]
1PLP	NMR	-	A	3-24	[»]
1PSL	model	-	A/B/C/D/E	1-52	[»]
1ZLL	NMR	-	A/B/C/D/E	1-52	[»]
2HYN	NMR	-	A/B/C/D/E	1-52	[»]

DisProt

DP00149.

ProteinModelPortal

P26678.

ModBase

Search...

Protein-protein interaction databases

IntAct

P26678. 2 interactions.

STRING

9606.ENSP00000350132.

Protein family/group databases

TCDB

1.A.50.1.1. phospholamban (Ca2+-channel and Ca2+-ATPase Regulator) (PLB) family.

PTM databases

PhosphoSite

P26678.

Polymorphism databases

DMDM

130774.

Proteomic databases

PaxDb

P26678.

PRIDE

P26678.

Protocols and materials databases

DNASU

5350.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000357525; ENSP00000350132; ENSG00000198523.

GeneID

5350.

KEGG

hsa:5350.

UCSC

uc003pye.3. human.

Organism-specific databases

CTD

5350.

GeneCards

GC06P118869.

HGNC

HGNC:9080. PLN.

HPA

CAB005597.
HPA026900.

MIM

172405. gene.
609909. phenotype.
613874. phenotype.

neXtProt

NX_P26678.

Orphanet

154. Familial isolated dilated cardiomyopathy.
155. Familial isolated hypertrophic cardiomyopathy.

PharmGKB

PA272.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG44917.

HOGENOM

HOG000115660.

HOVERGEN

HBG108280.

InParanoid

P26678.

KO

K05852.

OMA

QHMTRSA.

Gene expression databases

ArrayExpress

P26678.

Bgee

P26678.

CleanEx

HS_PLN.

Genevestigator

P26678.

GermOnline

ENSG00000198523. Homo sapiens.

Family and domain databases

InterPro

IPR005984. P_lamban.
[Graphical view]

PANTHER

PTHR21194. PTHR21194. 1 hit.

Pfam

PF04272. Phospholamban. 1 hit.
[Graphical view]

PIRSF

PIRSF001665. PLB. 1 hit.

ProDom

PD014689. P_lamban. 1 hit.
[Graphical view] [Entries sharing at least one domain]

TIGRFAMs

TIGR01294. P_lamban. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

P26678.

GenomeRNAi

5350.

NextBio

20738.

SOURCE

Search...

Entry information

Entry name

PPLA_HUMAN

Accession

Primary (citable) accession number: P26678

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	August 1, 1992
Last modified:	May 1, 2013
This is version 132 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.