SIRT5

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SIRT5
Protein SIRT5 PDB 2b4y.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases SIRT5, SIR2L5, sirtuin 5
External IDs MGI: 1915596 HomoloGene: 40825 GeneCards: 23408
RNA expression pattern
PBB GE SIRT5 219185 at tn.png

PBB GE SIRT5 221010 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001193267
NM_001242827
NM_012241
NM_031244

NM_178848

RefSeq (protein)

NP_001180196.1
NP_001229756.1
NP_036373.1
NP_112534.1

NP_849179.1

Location (UCSC) Chr 6: 13.57 – 13.62 Mb Chr 13: 43.37 – 43.4 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

Sirtuin (silent mating type information regulation 2 homolog) 5 (S. cerevisiae), also known as SIRT5 is a protein which in humans in encoded by the SIRT5 gene and in other species by the orthologous Sirt5 gene.[3]

This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the sirtuin family are characterized by a sirtuin core domain and belong to the class III of the [histone deacetylase] superfamily, and are dependent on NAD+ as co-factor of enzymatic activities. SIRT5 is one of the three sirtuins localized primarily to the mitochondrion.

Structure[edit]

Alternative splicing of this gene results in two transcript variants.[3] The protein structure of SIRT5 has been resolved and shows high degrees of structural conservation with other sirtuins, such as the ancestral yeast protein and human SIRT2.

Function[edit]

SIRT5 has been found to exhibit enzymatic activities as a deacetylase, desuccinylase, and demalonylase, capable of removing acetyl, succinyl, and malonyl groups from the lysine residues of proteins.[4] SIRT5 deacetylases and regulates carbamoyl phosphate synthetase (CPS1), the rate-limiting and initiating step of the urea cycle in liver mitochondria. Deacetylation of CPS1 stimulates its enzymatic activity. Mice with deletion of SIRT5 show elevated ammonia levels after a prolonged fast, whereas in contrast, mice overexpressing SIRT5 show increased CPS1 activity, suggesting one of the functions of SIRT5 may be to regulate the urea cycle.[5] SIRT5 also interacts with and deacetylates cytochrome c.[6] Large-scale profiling studies of SIRT5 deacetylase activity have uncovered over 700 protein substrates, including proteins localized to the mitochondria, the cytosol and other sub cellular localization. The identities of SIRT5 desuccinylation substrates suggest that SIRT5-mediated desuccinylation may be involved in energy metabolism.[7]

The physiological consequences of SIRT5 molecular functions in human is under investigation but may involved regulations of mitochondrial metabolism.[8]

Interactions[edit]

NAD+

Cytochrome c [9]

Carbamoyl phosphate synthetase (CPS1)

References[edit]

  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ a b "Entrez Gene: SIRT5 sirtuin (silent mating type information regulation 2 homolog) 5 (S. cerevisiae)". 
  4. ^ Du J, Zhou Y, Su X, Yu JJ, Khan S, Jiang H, Kim J, Woo J, Kim JH, Choi BH, He B, Chen W, Zhang S, Cerione RA, Auwerx J, Hao Q, Lin H (2011). "Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase". Science. 334 (6057): 806–9. doi:10.1126/science.1207861. PMC 3217313free to read. PMID 22076378. 
  5. ^ Nakagawa T, Lomb DJ, Haigis MC, Guarente L (2009). "SIRT5 Deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle". Cell. 137 (3): 560–70. doi:10.1016/j.cell.2009.02.026. PMC 2698666free to read. PMID 19410549. 
  6. ^ Schlicker C, Gertz M, Papatheodorou P, Kachholz B, Becker CF, Steegborn C (2008). "Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5". J. Mol. Biol. 382 (3): 790–801. doi:10.1016/j.jmb.2008.07.048. PMID 18680753. 
  7. ^ Park J, Chen Y, Tishkoff DX, Peng C, Tan M, Dai L, Xie Z, Zhang Y, Zwaans BM, Skinner ME, Lombard DB, Zhao Y (2013). "SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways". Mol. Cell. 50 (6): 919–30. doi:10.1016/j.molcel.2013.06.001. PMC 3769971free to read. PMID 23806337. 
  8. ^ Verdin E, Hirschey MD, Finley LW, Haigis MC (2010). "Sirtuin regulation of mitochondria: energy production, apoptosis, and signaling". Trends Biochem. Sci. 35 (12): 669–75. doi:10.1016/j.tibs.2010.07.003. PMC 2992946free to read. PMID 20863707. 
  9. ^ Schlicker C, Gertz M, Papatheodorou P, Kachholz B, Becker CF, Steegborn C (2008). "Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5". J. Mol. Biol. 382 (3): 790–801. doi:10.1016/j.jmb.2008.07.048. PMID 18680753. 

Further reading[edit]