Sarcolipin

SLN
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 1JDM
Identifiers
Aliases	SLN , sarcolipin
External IDs	OMIM: 602203; GeneCards: SLN; OMA:SLN - orthologs
Gene location (Human) Chr. Chromosome 11 (human) [1] Band 11q22.3 Start 107,707,378 bp [1] End 107,719,693 bp [1]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in thoracic diaphragm triceps brachii muscle glutes biceps brachii Skeletal muscle tissue of biceps brachii Skeletal muscle tissue of rectus abdominis muscle of thigh quadriceps femoris muscle vastus lateralis muscle body of tongue n/a More reference expression data BioGPS More reference expression data
Gene ontology Molecular function ATPase binding enzyme inhibitor activity enzyme regulator activity protein binding Cellular component integral component of membrane endoplasmic reticulum membrane membrane endoplasmic reticulum sarcoplasmic reticulum membrane sarcoplasmic reticulum Biological process positive regulation of protein depolymerization negative regulation of protein-containing complex disassembly negative regulation of calcium ion binding regulation of calcium ion transport negative regulation of catalytic activity negative regulation of calcium ion transmembrane transporter activity calcium ion transport negative regulation of calcium ion import sarcoplasmic reticulum calcium ion transport regulation of relaxation of muscle regulation of ATPase-coupled calcium transmembrane transporter activity positive regulation of cold-induced thermogenesis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6588 n/a Ensembl ENSG00000170290 n/a UniProt O00631 n/a RefSeq (mRNA) NM_003063 n/a RefSeq (protein) NP_003054 n/a Location (UCSC) Chr 11: 107.71 – 107.72 Mb n/a PubMed search [2] n/a
Wikidata
View/Edit Human

Sarcolipin is a micropeptide protein that in humans is encoded by the SLN gene. ^{[3] [4]}

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. The SLN gene encodes a small transmembrane proteolipid that regulates several sarcoplasmic reticulum Ca²⁺-ATPases by reducing the accumulation of Ca²⁺ in the sarcoplasmic reticulum without affecting the rate of ATP hydrolysis. ^[4]

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. ^[5]

Sarcolipin is an important mediator of muscle based non shivering thermogenesis (NST). It causes the sarcoplasmic reticulum Ca²⁺-ATPases to stop pumping Ca²⁺ ions but continue futilely hydrolysing ATP, thus releasing the energy as heat. ^{[6] [7]} Sarcolipin mediated heat production is very important for many organisms to maintain a warm body. In mammals thermogenesis by skeletal muscles is complemented by thermogenesis in the brown adipose tissue and beige adipose tissue. ^[8] Sarcolipin mediated heat production in contractile muscles helps endothermic fish like the opah heat its body. Some fishes like the billfishes have a specialised brain heater tissue that is derived from muscles that cannot contract but specialise in producing heat using sarcolipin.

Interactions

SLN (gene) has been shown to interact with PLN ^{[9] [10]} and ATP2A1. ^{[9] [10]}

References

1. GRCh38: Ensembl release 89: ENSG00000170290 – Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. Odermatt A, Taschner PE, Scherer SW, Beatty B, Khanna VK, Cornblath DR, et al. (November 1997). "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. hdl: 2066/25426 . PMID   9367679. S2CID   41989102.
4. "Entrez Gene: SLN sarcolipin".
5. 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". Proceedings of the National Academy of Sciences of the United States of America. 104 (45): 17867–72. Bibcode:2007PNAS..10417867B. doi: 10.1073/pnas.0707722104 . PMC   2077025 . PMID   17971438.
6. Bal NC, Periasamy M (March 2020). "Uncoupling of sarcoendoplasmic reticulum calcium ATPase pump activity by sarcolipin as the basis for muscle non-shivering thermogenesis". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 375 (1793) 20190135. doi:10.1098/rstb.2019.0135. PMC   7017432 . PMID   31928193.
7. Legendre LJ, Davesne D (March 2020). "The evolution of mechanisms involved in vertebrate endothermy". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 375 (1793) 20190136. doi: 10.1098/rstb.2019.0136 . PMC   7017440 . PMID   31928191.
8. Reilly SM, Saltiel RA (22 October 2015). "A Futile Approach to Fighting Obesity?". Cell. 163 (3): 539–540. doi: 10.1016/j.cell.2015.10.006 . PMID   26496598. S2CID   10336243.
9. 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". Proceedings of the National Academy of Sciences of the United States of America. 100 (9): 5040–5. Bibcode:2003PNAS..100.5040A. doi: 10.1073/pnas.0330962100 . PMC   154294 . PMID   12692302.
10. 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)". The Journal of Biological Chemistry. 277 (30): 26725–8. doi: 10.1074/jbc.C200269200 . PMID   12032137.

Further reading

• Lanfranchi G, Muraro T, Caldara F, Pacchioni B, Pallavicini A, Pandolfo D, et al. (January 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 Research. 6 (1): 35–42. doi: 10.1101/gr.6.1.35 . PMID   8681137.
• Odermatt A, Becker S, Khanna VK, Kurzydlowski K, Leisner E, Pette D, MacLennan DH (May 1998). "Sarcolipin regulates the activity of SERCA1, the fast-twitch skeletal muscle sarcoplasmic reticulum Ca2+-ATPase". The Journal of Biological Chemistry. 273 (20): 12360–9. doi: 10.1074/jbc.273.20.12360 . PMID   9575189.
• Smith WS, Broadbridge R, East JM, Lee AG (January 2002). "Sarcolipin uncouples hydrolysis of ATP from accumulation of Ca2+ by the Ca2+-ATPase of skeletal-muscle sarcoplasmic reticulum". The Biochemical Journal. 361 (Pt 2): 277–86. doi:10.1042/0264-6021:3610277. PMC   1222307 . PMID   11772399.
• Mascioni A, Karim C, Barany G, Thomas DD, Veglia G (January 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 (July 2002). "Sarcolipin inhibits polymerization of phospholamban to induce superinhibition of sarco(endo)plasmic reticulum Ca2+-ATPases (SERCAs)". The Journal of Biological Chemistry. 277 (30): 26725–8. doi: 10.1074/jbc.C200269200 . PMID   12032137.
• Minamisawa S, Wang Y, Chen J, Ishikawa Y, Chien KR, Matsuoka R (March 2003). "Atrial chamber-specific expression of sarcolipin is regulated during development and hypertrophic remodeling". The Journal of Biological Chemistry. 278 (11): 9570–5. doi: 10.1074/jbc.M213132200 . PMID   12645548.
• 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". Proceedings of the National Academy of Sciences of the United States of America. 100 (9): 5040–5. Bibcode:2003PNAS..100.5040A. doi: 10.1073/pnas.0330962100 . PMC   154294 . PMID   12692302.
• Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, et al. (September 2004). "Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions". Genome Research. 14 (9): 1711–8. doi:10.1101/gr.2435604. PMC   515316 . PMID   15342556.
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID   16189514. S2CID   4427026.
• Vittorini S, Storti S, Parri MS, Cerillo AG, Clerico A (2007). "SERCA2a, phospholamban, sarcolipin, and ryanodine receptors gene expression in children with congenital heart defects". Molecular Medicine. 13 (1–2): 105–11. doi:10.2119/2006-00054.Vittorini. PMC   1869624 . PMID   17515962.