Sarcolipin

Sarcolipin
PDB rendering based on 1jdm.
Available structures PDB Human UniProt search: PDBe, RCSB List of PDB id codes 1JDM​
Identifiers
Symbols	SLN ; MGC12301; MGC125854; MGC125855
External IDs	OMIM: 602203 MGI: 1913652 GeneCards: SLN Gene
Gene ontology Molecular function • enzyme inhibitor activity • protein binding • ATPase binding Cellular component • integral component of membrane • sarcoplasmic reticulum • sarcoplasmic reticulum membrane Biological process • calcium ion transport • negative regulation of catalytic activity • negative regulation of protein complex disassembly • regulation of calcium ion transport • sarcoplasmic reticulum calcium ion transport • negative regulation of calcium ion import • negative regulation of calcium ion transmembrane transporter activity • regulation of relaxation of muscle • negative regulation of calcium ion binding • positive regulation of protein depolymerization • regulation of calcium-transporting ATPase activity Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6588	66402
Ensembl	ENSG00000170290	ENSMUSG00000042045
UniProt	O00631	Q9CQD6
RefSeq (mRNA)	NM_003063	NM_025540
RefSeq (protein)	NP_003054	NP_079816
Location (UCSC)	Chr 11: 107.71 – 107.72 Mb	Chr 9: 53.7 – 53.7 Mb
PubMed search

Sarcolipin is a protein that in humans is encoded by the SLN gene.^[1][2]

Function

Sarcoplasmic reticulum Ca²⁺-ATPases are transmembrane proteins that catalyze the ATP-dependent transport of Ca²⁺ from the cytosol into the lumen of the sarcoplasmic reticulum in muscle cells. This gene encodes a small proteolipid that regulates several sarcoplasmic reticulum Ca²⁺-ATPases. The transmembrane protein interacts with Ca²⁺-ATPases and reduces the accumulation of Ca²⁺ in the sarcoplasmic reticulum without affecting the rate of ATP hydrolysis.^[2]

Ablation of sarcolipin increases atrial Ca²⁺ transient amplitudes and enhanced atrial contractility. Furthermore, atria from sarcolipin-null mice have blunted response to isoproterenol stimulation, implicating sarcolipin as a mediator of beta-adrenergic responses in atria.^[3] Recently it has been shown that SLN is an important mediator of muscle based thermogenesis and loss of sarcolipin predisposes mice to diet-induced obesity thus suggesting its role in energy metabolism and regulation of weight gain ^[4]

Interactions

SLN (gene) has been shown to interact with PLN^[5][6]and ATP2A1.^[5][6]

References

1. Odermatt A, Taschner PE, Scherer SW, Beatty B, Khanna VK, Cornblath DR, Chaudhry V, Yee WC, Schrank B, Karpati G, Breuning MH, Knoers N, MacLennan DH (Jan 1998). "Characterization of the gene encoding human sarcolipin (SLN), a proteolipid associated with SERCA1: absence of structural mutations in five patients with Brody disease". Genomics 45 (3): 541–53. doi:10.1006/geno.1997.4967. PMID 9367679.
2. "Entrez Gene: SLN sarcolipin".
3. Babu GJ, Bhupathy P, Timofeyev V, Petrashevskaya NN, Reiser PJ, Chiamvimonvat N, Periasamy M (November 2007). "Ablation of sarcolipin enhances sarcoplasmic reticulum calcium transport and atrial contractility". Proc. Natl. Acad. Sci. U.S.A. 104 (45): 17867–72. doi:10.1073/pnas.0707722104. PMC 2077025. PMID 17971438.
4. Bal NC, Maurya SK, Sopariwala DH, Sahoo SK, Gupta SC, Shaikh SA, Pant M et al.: Sarcolipin is a newly identified regulator of muscle-based thermogenesis in mammals. Nat Med, 2012. http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.2897.html
5. Asahi M, Sugita Y, Kurzydlowski K, De Leon S, Tada M, Toyoshima C, MacLennan DH (April 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): 5040–5. doi:10.1073/pnas.0330962100. PMC 154294. PMID 12692302.
6. Asahi M, Kurzydlowski K, Tada M, MacLennan DH (July 2002). "Sarcolipin inhibits polymerization of phospholamban to induce superinhibition of sarco(endo)plasmic reticulum Ca2+-ATPases (SERCAs)". J. Biol. Chem. 277 (30): 26725–8. doi:10.1074/jbc.C200269200. PMID 12032137.

Further reading

• Lanfranchi G, Muraro T, Caldara F, et al. (1996). "Identification of 4370 expressed sequence tags from a 3'-end-specific cDNA library of human skeletal muscle by DNA sequencing and filter hybridization.". Genome Res. 6 (1): 35–42. doi:10.1101/gr.6.1.35. PMID 8681137.
• Odermatt A, Becker S, Khanna VK, et al. (1998). "Sarcolipin regulates the activity of SERCA1, the fast-twitch skeletal muscle sarcoplasmic reticulum Ca2+-ATPase.". J. Biol. Chem. 273 (20): 12360–9. doi:10.1074/jbc.273.20.12360. PMID 9575189.
• Smith WS, Broadbridge R, East JM, Lee AG (2002). "Sarcolipin uncouples hydrolysis of ATP from accumulation of Ca2+ by the Ca2+-ATPase of skeletal-muscle sarcoplasmic reticulum.". Biochem. J. 361 (Pt 2): 277–86. doi:10.1042/0264-6021:3610277. PMC 1222307. PMID 11772399.
• Mascioni A, Karim C, Barany G, et al. (2002). "Structure and orientation of sarcolipin in lipid environments.". Biochemistry 41 (2): 475–82. doi:10.1021/bi011243m. PMID 11781085.
• Asahi M, Kurzydlowski K, Tada M, MacLennan DH (2002). "Sarcolipin inhibits polymerization of phospholamban to induce superinhibition of sarco(endo)plasmic reticulum Ca2+-ATPases (SERCAs).". J. Biol. Chem. 277 (30): 26725–8. doi:10.1074/jbc.C200269200. PMID 12032137.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Minamisawa S, Wang Y, Chen J, et al. (2003). "Atrial chamber-specific expression of sarcolipin is regulated during development and hypertrophic remodeling.". J. Biol. Chem. 278 (11): 9570–5. doi:10.1074/jbc.M213132200. PMID 12645548.
• Asahi M, Sugita Y, Kurzydlowski K, et al. (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): 5040–5. doi:10.1073/pnas.0330962100. PMC 154294. PMID 12692302.
• Suzuki Y, Yamashita R, Shirota M, et al. (2004). "Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions.". Genome Res. 14 (9): 1711–8. doi:10.1101/gr.2435604. PMC 515316. PMID 15342556.
• Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network.". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
• Vittorini S, Storti S, Parri MS, et al. (2007). "SERCA2a, phospholamban, sarcolipin, and ryanodine receptors gene expression in children with congenital heart defects.". Mol. Med. 13 (1-2): 105–11. doi:10.2119/2006-00054.Vittorini. PMC 1869624. PMID 17515962.