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Phospholamban

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This is an old revision of this page, as edited by 187.158.132.197 (talk) at 11:12, 30 November 2016 (The phospholamban regulates the activity of SERCA2, only present in cardiac muscle cells and it's absent in skeletal muscle cells (because skeletal muscle cells have SERCA1)). The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.

Phospholamban pentamer
Identifiers
SymbolPhospholamban
PfamPF04272
InterProIPR005984
SCOP21fjk / SCOPe / SUPFAM
TCDB1.A.50
OPM superfamily70
OPM protein1zll
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
PLN
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPLN, CMD1P, CMH18, PLB, phospholamban
External IDsOMIM: 172405; MGI: 97622; HomoloGene: 136758; GeneCards: PLN; OMA:PLN - orthologs
Orthologs
SpeciesHumanMouse
Entrez

5350

18821

Ensembl

ENSG00000198523

ENSMUSG00000038583

UniProt

P26678

P61014

RefSeq (mRNA)

NM_002667

NM_001141927
NM_023129

RefSeq (protein)

NP_002658

NP_001135399
NP_075618

Location (UCSC)Chr 6: 118.55 – 118.56 MbChr 10: 53.21 – 53.22 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Phospholamban, also known as PLN or PLB, is a protein that in humans is encoded by the PLN gene.[5] Phospholamban is a 52-amino acid integral membrane protein that regulates the Ca2+ pump in cardiac muscle cells.[6]

Function

This protein is found as a pentamer and is a major substrate for the cAMP-dependent protein kinase (PKA) in cardiac muscle. The protein is an inhibitor of cardiac muscle sarcoplasmic reticulum Ca++-ATPase (SERCA2)[7] in the unphosphorylated state, but inhibition is relieved upon phosphorylation of the protein. The relief of inhibition on Ca++-ATPase leads to faster Ca++ uptake into the sarcoplasmic reticulum, thereby contributing to the lusitropic response elicited in heart by beta-agonists. The protein is a key regulator of Template:SWL. Mutations in this gene are a cause of inherited human dilated cardiomyopathy with refractory congestive heart failure.[8]

When phospholamban is phosphorylated by Template:SWL its ability to inhibit the sarcoplasmic reticulum calcium pump (SERCA) is lost.[9] Thus, activators of PKA, such as the beta-adrenergic agonist epinephrine (released by sympathetic stimulation), may enhance the rate of cardiac myocyte relaxation. In addition, since SERCA is more active, the next action potential will cause an increased release of calcium, resulting in increased contraction (positive inotropic effect). When phospholamban is not phosphorylated, such as when PKA is inactive, it can interact with and inhibit SERCA. The overall effect of phospholamban is to decrease Template:SWL and the rate of Template:SWL, thereby decreasing stroke volume and heart rate, respectively.[10]

Clinical significance

Gene knockout of phospholamban results in animals with hyperdynamic hearts, with little apparent negative consequence.[11]

Mutations in this gene are a cause of inherited human dilated Template:SWL with refractory Template:SWL.[12]

Discovery

Phospholamban was discovered by Arnold Martin Katz and coworkers in 1974.[13]

Interactions

PLN has been shown to interact with SLN[14][15] and ATP2A1.[15][16][17]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000198523 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000038583 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Fujii J, Zarain-Herzberg A, Willard HF, Tada M, MacLennan DH (June 1991). "Structure of the rabbit phospholamban gene, cloning of the human cDNA, and assignment of the gene to human chromosome 6". J. Biol. Chem. 266 (18): 11669–75. PMID 1828805.
  6. ^ Rodriguez P, Kranias EG (December 2005). "Phospholamban: a key determinant of cardiac function and dysfunction". Arch Mal Coeur Vaiss. 98 (12): 1239–43. PMID 16435604.
  7. ^ https://www.ebi.ac.uk/interpro/potm/2004_3/Page2.htm
  8. ^ "Entrez Gene: PLN phospholamban".
  9. ^ Medical Physiology. Philadelphia: Saunders. 2004. ISBN 0-8089-2333-1.
  10. ^ Brittsan AG, Kranias EG (December 2000). "Phospholamban and cardiac contractile function". J. Mol. Cell. Cardiol. 32 (12): 2131–9. doi:10.1006/jmcc.2000.1270. PMID 11112989.
  11. ^ Luo W, Grupp IL, Harrer J, Ponniah S, Grupp G, Duffy JJ, Doetschman T, Kranias EG (September 1994). "Targeted ablation of the phospholamban gene is associated with markedly enhanced myocardial contractility and loss of beta-agonist stimulation". Circ. Res. 75 (3): 401–9. doi:10.1161/01.res.75.3.401. PMID 8062415.
  12. ^ Schmitt JP, Kamisago M, Asahi M, Li GH, Ahmad F, Mende U, Kranias EG, MacLennan DH, Seidman JG, Seidman CE (February 2003). "Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban". Science. 299 (5611): 1410–3. doi:10.1126/science.1081578. PMID 12610310.
  13. ^ Tada M, Kirchberger MA, Repke DI, Katz AM (October 1974). "The stimulation of calcium transport in cardiac sarcoplasmic reticulum by adenosine 3':5'-monophosphate-dependent protein kinase". J Biol Chem. 249 (19): 6174–80. PMID 4371608.
  14. ^ Asahi, Michio; Sugita Yuji; Kurzydlowski Kazimierz; De Leon Stella; Tada Michihiko; Toyoshima Chikashi; MacLennan David H (Apr 2003). "Sarcolipin regulates sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) by binding to transmembrane helices alone or in association with phospholamban". Proc. Natl. Acad. Sci. U.S.A. 100 (9). United States: 5040–5. doi:10.1073/pnas.0330962100. ISSN 0027-8424. PMC 154294. PMID 12692302. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help)
  15. ^ a b Asahi, Michio; Kurzydlowski Kazimierz; Tada Michihiko; MacLennan David H (Jul 2002). "Sarcolipin inhibits polymerization of phospholamban to induce superinhibition of sarco(endo)plasmic reticulum Ca2+-ATPases (SERCAs)". J. Biol. Chem. 277 (30). United States: 26725–8. doi:10.1074/jbc.C200269200. ISSN 0021-9258. PMID 12032137. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help)CS1 maint: unflagged free DOI (link)
  16. ^ Asahi, M; Kimura Y; Kurzydlowski K; Tada M; MacLennan D H (Nov 1999). "Transmembrane helix M6 in sarco(endo)plasmic reticulum Ca(2+)-ATPase forms a functional interaction site with phospholamban. Evidence for physical interactions at other sites". J. Biol. Chem. 274 (46). UNITED STATES: 32855–62. doi:10.1074/jbc.274.46.32855. ISSN 0021-9258. PMID 10551848. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help)CS1 maint: unflagged free DOI (link)
  17. ^ Asahi, M; Green N M; Kurzydlowski K; Tada M; MacLennan D H (Aug 2001). "Phospholamban domain IB forms an interaction site with the loop between transmembrane helices M6 and M7 of sarco(endo)plasmic reticulum Ca2+ ATPases". Proc. Natl. Acad. Sci. U.S.A. 98 (18). United States: 10061–6. doi:10.1073/pnas.181348298. ISSN 0027-8424. PMC 56915. PMID 11526231. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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