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Q9NXA8 (SIR5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
NAD-dependent protein deacylase sirtuin-5, mitochondrial

EC=3.5.1.-
Alternative name(s):
Regulatory protein SIR2 homolog 5
SIR2-like protein 5
Gene names
Name:SIRT5
Synonyms:SIR2L5
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length310 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

NAD-dependent lysine demalonylase and desuccinylase that specifically removes malonyl and succinyl groups on target proteins. Activates CPS1 and contributes to the regulation of blood ammonia levels during prolonged fasting: acts by mediating desuccinylation of CPS1, thereby increasing CPS1 activity in response to elevated NAD levels during fasting. Activates SOD1 by mediating its desuccinylation, leading to reduced reactive oxygen species. Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) and a number of other proteins in vitro. Ref.8 Ref.11 Ref.13 Ref.17

Catalytic activity

NAD+ + a malonylprotein = nicotinamide + O-malonyl-ADP-ribose + a protein. Ref.16 Ref.17

NAD+ + a succinylprotein = nicotinamide + O-succinyl-ADP-ribose + a protein. Ref.16 Ref.17

Cofactor

Binds 1 zinc ion per subunit. Ref.17

Enzyme regulation

Inhibited by suramin. NAD-dependent lysine desuccinylase activity is inhibited by physiological nicotinamide concentrations, while deacetylase activity is not. In contrast, resveratrol activates deacetylase activity, while inhibiting desuccinylase activity. Ref.12 Ref.16 Ref.20

Subunit structure

Interacts with CPS1 By similarity. Monomer. Homodimer. Forms homodimers upon suramin binding. Ref.16

Subcellular location

Mitochondrion matrix. Mitochondrion intermembrane space. Cytoplasmcytosol. Nucleus. Note: Mainly mitochondrial. Also present extramitochondrially: a fraction is present in the cytosol and very small amounts are also detected in the nucleus. Ref.7 Ref.8 Ref.10 Ref.14

Isoform 1: Cytoplasm. Mitochondrion Ref.7 Ref.8 Ref.10 Ref.14.

Isoform 2: Mitochondrion Ref.7 Ref.8 Ref.10 Ref.14.

Tissue specificity

Widely expressed. Ref.1

Domain

In contrast to class I sirtuins, class III sirtuins have only weak deacetylase activity. Difference in substrate specificity is probably due to a larger hydrophobic pocket with 2 residues (Tyr-102 and Arg-105) that bind to malonylated and succinylated substrates and define the specificity (Ref.17). HAMAP-Rule MF_03160

Miscellaneous

The mechanism of demalonylation and desuccinylation involves the presence of a 1',2'-cyclic intermediate, suggesting that sirtuins use the ADP-ribose-peptidylamidate mechanism to remove acyl groups from substrate lysine residues (Ref.18).

Sequence similarities

Belongs to the sirtuin family. Class III subfamily.

Contains 1 deacetylase sirtuin-type domain.

Biophysicochemical properties

Kinetic parameters:

KM=6.1 µM for a synthetic histone H3K9 malonyllysine peptide Ref.17

KM=5.8 µM for a synthetic histone H3K9 succinyllysine peptide

KM=8.7 µM for a synthetic GLUD1 peptide malonylated at 'Lys-503'

KM=14 µM for a synthetic GLUD1 peptide succinylated at 'Lys-503'

KM=150 µM for a synthetic ACSS1 peptide malonylated at 'Lys-628'

KM=450 µM for a synthetic ACSS1 peptide succinylated at 'Lys-628'

Ontologies

Keywords
   Cellular componentCytoplasm
Mitochondrion
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransit peptide
   LigandMetal-binding
NAD
Zinc
   Molecular functionHydrolase
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processchromatin silencing

Traceable author statement Ref.1. Source: ProtInc

negative regulation of reactive oxygen species metabolic process

Inferred from direct assay Ref.13. Source: UniProtKB

peptidyl-lysine demalonylation

Inferred from direct assay Ref.11Ref.17. Source: UniProtKB

peptidyl-lysine desuccinylation

Inferred from direct assay Ref.11Ref.17. Source: UniProtKB

protein ADP-ribosylation

Traceable author statement Ref.1. Source: ProtInc

protein deacetylation

Inferred from direct assay Ref.8. Source: UniProtKB

protein desuccinylation

Inferred from direct assay Ref.13. Source: UniProtKB

   Cellular_componentcytosol

Inferred from direct assay Ref.14. Source: UniProtKB

mitochondrial intermembrane space

Inferred from direct assay Ref.8. Source: UniProtKB

mitochondrial matrix

Inferred from direct assay Ref.8. Source: UniProtKB

mitochondrion

Inferred from direct assay Ref.7Ref.14. Source: UniProtKB

nucleus

Traceable author statement Ref.14. Source: UniProtKB

   Molecular_functionNAD+ ADP-ribosyltransferase activity

Traceable author statement Ref.1. Source: ProtInc

NAD+ binding

Inferred from direct assay Ref.11Ref.17. Source: UniProtKB

protein-malonyllysine demalonylase activity

Inferred from direct assay Ref.11Ref.17. Source: UniProtKB

protein-succinyllysine desuccinylase activity

Inferred from direct assay Ref.11Ref.17Ref.13. Source: UniProtKB

zinc ion binding

Inferred from direct assay Ref.17. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9NXA8-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q9NXA8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     286-299: RFHFQGPCGTTLPE → SHLISISSLIIIKN
     300-310: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q9NXA8-3)

The sequence of this isoform differs from the canonical sequence as follows:
     189-206: Missing.
Note: No experimental confirmation available.
Isoform 4 (identifier: Q9NXA8-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-108: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 3636Mitochondrion By similarity
Chain37 – 310274NAD-dependent protein deacylase sirtuin-5, mitochondrial HAMAP-Rule MF_03160
PRO_0000110266

Regions

Domain41 – 309269Deacetylase sirtuin-type
Nucleotide binding58 – 7720NAD HAMAP-Rule MF_03160
Nucleotide binding140 – 1434NAD HAMAP-Rule MF_03160
Nucleotide binding249 – 2513NAD HAMAP-Rule MF_03160
Nucleotide binding275 – 2773NAD HAMAP-Rule MF_03160

Sites

Active site1581Proton acceptor Ref.17
Metal binding1661Zinc
Metal binding1691Zinc
Metal binding2071Zinc
Metal binding2121Zinc
Binding site1021Substrate
Binding site1051Substrate
Binding site2931NAD; via amide nitrogen

Natural variations

Alternative sequence1 – 108108Missing in isoform 4.
VSP_042291
Alternative sequence189 – 20618Missing in isoform 3.
VSP_042292
Alternative sequence286 – 29914RFHFQ…TTLPE → SHLISISSLIIIKN in isoform 2.
VSP_008730
Alternative sequence300 – 31011Missing in isoform 2.
VSP_008731
Natural variant2851F → L.
Corresponds to variant rs9464003 [ dbSNP | Ensembl ].
VAR_029042
Natural variant3051E → G.
Corresponds to variant rs34162626 [ dbSNP | Ensembl ].
VAR_051980

Experimental info

Mutagenesis691T → A: Abolishes enzyme activity. Ref.12
Mutagenesis1021Y → F: Increases the KM for desuccinylation. Ref.17
Mutagenesis1051R → M: Increases the KM for desuccinylation. Does not affect deacetylase activity. Ref.12 Ref.17
Mutagenesis1581H → A: Abolishes desuccinylation activity. Ref.11 Ref.17
Sequence conflict531I → M in BAG63757. Ref.2

Secondary structure

........................................................... 310
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 31, 2003. Version 2.
Checksum: 022DA32CDB43AC3A

FASTA31033,881
        10         20         30         40         50         60 
MRPLQIVPSR LISQLYCGLK PPASTRNQIC LKMARPSSSM ADFRKFFAKA KHIVIISGAG 

        70         80         90        100        110        120 
VSAESGVPTF RGAGGYWRKW QAQDLATPLA FAHNPSRVWE FYHYRREVMG SKEPNAGHRA 

       130        140        150        160        170        180 
IAECETRLGK QGRRVVVITQ NIDELHRKAG TKNLLEIHGS LFKTRCTSCG VVAENYKSPI 

       190        200        210        220        230        240 
CPALSGKGAP EPGTQDASIP VEKLPRCEEA GCGGLLRPHV VWFGENLDPA ILEEVDRELA 

       250        260        270        280        290        300 
HCDLCLVVGT SSVVYPAAMF APQVAARGVP VAEFNTETTP ATNRFRFHFQ GPCGTTLPEA 

       310 
LACHENETVS 

« Hide

Isoform 2 [UniParc].

Checksum: 2EE7C311AAA34CBA
Show »

FASTA29932,674
Isoform 3 [UniParc].

Checksum: D89A65C251224735
Show »

FASTA29231,994
Isoform 4 [UniParc].

Checksum: 051C7D4BE508D66B
Show »

FASTA20221,689

References

« Hide 'large scale' references
[1]"Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity."
Frye R.A.
Biochem. Biophys. Res. Commun. 260:273-279(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
Tissue: Testis.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3 AND 4).
Tissue: Amygdala, Hepatoblastoma and Testis.
[3]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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] (ISOFORM 1).
Tissue: Eye.
[7]"Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins."
Michishita E., Park J.Y., Burneskis J.M., Barrett J.C., Horikawa I.
Mol. Biol. Cell 16:4623-4635(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[8]"Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5."
Schlicker C., Gertz M., Papatheodorou P., Kachholz B., Becker C.F.W., Steegborn C.
J. Mol. Biol. 382:790-801(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[9]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"Distinct regulation of mitochondrial localization and stability of two human Sirt5 isoforms."
Matsushita N., Yonashiro R., Ogata Y., Sugiura A., Nagashima S., Fukuda T., Inatome R., Yanagi S.
Genes Cells 16:190-202(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION (ISOFORMS 1 AND 2).
[11]"The first identification of lysine malonylation substrates and its regulatory enzyme."
Peng C., Lu Z., Xie Z., Cheng Z., Chen Y., Tan M., Luo H., Zhang Y., He W., Yang K., Zwaans B.M., Tishkoff D., Ho L., Lombard D., He T.C., Dai J., Verdin E., Ye Y., Zhao Y.
Mol. Cell. Proteomics 10:M111.012658.01-M111.012658.12(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, NAD-BINDING, MUTAGENESIS OF HIS-158.
[12]"Sirt5 deacylation activities show differential sensitivities to nicotinamide inhibition."
Fischer F., Gertz M., Suenkel B., Lakshminarasimhan M., Schutkowski M., Steegborn C.
PLoS ONE 7:E45098-E45098(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, MUTAGENESIS OF THR-69 AND ARG-105.
[13]"SIRT5 desuccinylates and activates SOD1 to eliminate ROS."
Lin Z.F., Xu H.B., Wang J.Y., Lin Q., Ruan Z., Liu F.B., Jin W., Huang H.H., Chen X.
Biochem. Biophys. Res. Commun. 441:191-195(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[14]"SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[15]"Crystal structure of human sirtuin homolog 5 in complex with NAD."
Structural genomics consortium (SGC)
Submitted (FEB-2006) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 34-302 IN COMPLEX WITH NAD AND ZINC IONS.
[16]"Structural basis of inhibition of the human NAD+-dependent deacetylase SIRT5 by suramin."
Schuetz A., Min J., Antoshenko T., Wang C.-L., Allali-Hassani A., Dong A., Loppnau P., Vedadi M., Bochkarev A., Sternglanz R., Plotnikov A.N.
Structure 15:377-389(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.06 ANGSTROMS) OF 34-302 IN COMPLEXES WITH ZINC IONS; SURAMIN AND ADP-RIBOSE, CATALYTIC ACTIVITY, ENZYME REGULATION, SUBUNIT.
[17]"Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase."
Du J., Zhou Y., Su X., Yu J.J., Khan S., Jiang H., Kim J., Woo J., Kim J.H., Choi B.H., He B., Chen W., Zhang S., Cerione R.A., Auwerx J., Hao Q., Lin H.
Science 334:806-809(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 34-302 IN COMPLEX WITH NAD; ZINC IONS AND SUCCINYLATED PEPTIDE, COFACTOR, ACTIVE SITE, BIOPHYSICOCHEMICAL PROPERTIES, FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF TYR-102; ARG-105 AND HIS-158.
[18]"The bicyclic intermediate structure provides insights into the desuccinylation mechanism of human sirtuin 5 (SIRT5)."
Zhou Y., Zhang H., He B., Du J., Lin H., Cerione R.A., Hao Q.
J. Biol. Chem. 287:28307-28314(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 34-302 IN COMPLEX WITH NAD; ZINC IONS AND SUCCINYLATED PEPTIDE, REACTION MECHANISM.
[19]"Synthesis of carba-NAD and the structures of its ternary complexes with SIRT3 and SIRT5."
Szczepankiewicz B.G., Dai H., Koppetsch K.J., Qian D., Jiang F., Mao C., Perni R.B.
J. Org. Chem. 77:7319-7329(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.94 ANGSTROMS) OF 36-302 IN COMPLEX WITH CARBA-NAD AND ZINC IONS.
[20]"A molecular mechanism for direct sirtuin activation by resveratrol."
Gertz M., Nguyen G.T., Fischer F., Suenkel B., Schlicker C., Franzel B., Tomaschewski J., Aladini F., Becker C., Wolters D., Steegborn C.
PLoS ONE 7:E49761-E49761(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 34-302 IN COMPLEX WITH PROTEIN PEPTIDE; ZINC IONS AND RESVERATROL, ENZYME REGULATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF083110 mRNA. Translation: AAD40853.1.
AK000355 mRNA. Translation: BAA91107.1.
AK294162 mRNA. Translation: BAG57485.1.
AK302467 mRNA. Translation: BAG63757.1.
AM393414 mRNA. Translation: CAL38292.1.
AL441883 Genomic DNA. Translation: CAI19837.1.
AL441883 Genomic DNA. Translation: CAI19838.1.
CH471087 Genomic DNA. Translation: EAW55332.1.
BC000126 mRNA. Translation: AAH00126.1.
CCDSCCDS4526.1. [Q9NXA8-1]
CCDS4527.1. [Q9NXA8-2]
CCDS54966.1. [Q9NXA8-3]
CCDS56398.1. [Q9NXA8-4]
RefSeqNP_001180196.1. NM_001193267.2. [Q9NXA8-3]
NP_001229756.1. NM_001242827.1. [Q9NXA8-4]
NP_036373.1. NM_012241.4. [Q9NXA8-1]
NP_112534.1. NM_031244.3. [Q9NXA8-2]
XP_005249024.1. XM_005248967.2. [Q9NXA8-1]
XP_005249025.1. XM_005248968.2. [Q9NXA8-1]
UniGeneHs.567431.
Hs.594133.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2B4YX-ray1.90A/B/C/D34-302[»]
2NYRX-ray2.06A/B34-302[»]
3RIGX-ray2.00A/B34-302[»]
3RIYX-ray1.55A/B34-302[»]
4F4UX-ray2.00A/B34-302[»]
4F56X-ray1.70A/B34-302[»]
4G1CX-ray1.94A/B36-302[»]
4HDAX-ray2.60A/B34-302[»]
ProteinModelPortalQ9NXA8.
SMRQ9NXA8. Positions 34-302.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116980. 80 interactions.
IntActQ9NXA8. 1 interaction.
STRING9606.ENSP00000368552.

Chemistry

ChEMBLCHEMBL2163183.
DrugBankDB04786. Suramin.

PTM databases

PhosphoSiteQ9NXA8.

Polymorphism databases

DMDM38258652.

Proteomic databases

MaxQBQ9NXA8.
PaxDbQ9NXA8.
PRIDEQ9NXA8.

Protocols and materials databases

DNASU23408.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000359782; ENSP00000352830; ENSG00000124523. [Q9NXA8-3]
ENST00000379262; ENSP00000368564; ENSG00000124523. [Q9NXA8-2]
ENST00000397350; ENSP00000380509; ENSG00000124523. [Q9NXA8-4]
ENST00000606117; ENSP00000476228; ENSG00000124523. [Q9NXA8-1]
GeneID23408.
KEGGhsa:23408.
UCSCuc003naw.3. human. [Q9NXA8-2]
uc003nax.3. human. [Q9NXA8-1]
uc011dit.2. human. [Q9NXA8-3]

Organism-specific databases

CTD23408.
GeneCardsGC06P013574.
HGNCHGNC:14933. SIRT5.
HPAHPA021798.
HPA022002.
HPA022992.
MIM604483. gene.
neXtProtNX_Q9NXA8.
PharmGKBPA37938.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0846.
HOGENOMHOG000085950.
HOVERGENHBG056009.
InParanoidQ9NXA8.
KOK11415.
OMAFNMIDLA.
OrthoDBEOG77Q4XG.
PhylomeDBQ9NXA8.
TreeFamTF106183.

Gene expression databases

BgeeQ9NXA8.
CleanExHS_SIRT5.
GenevestigatorQ9NXA8.

Family and domain databases

Gene3D3.30.1600.10. 2 hits.
3.40.50.1220. 3 hits.
HAMAPMF_01121. Sirtuin_ClassIII.
InterProIPR029035. DHS-like_NAD/FAD-binding_dom.
IPR003000. Sirtuin.
IPR026591. Sirtuin_cat_small_dom.
IPR027546. Sirtuin_class_III.
IPR026590. Ssirtuin_cat_dom.
[Graphical view]
PANTHERPTHR11085. PTHR11085. 1 hit.
PfamPF02146. SIR2. 1 hit.
[Graphical view]
SUPFAMSSF52467. SSF52467. 1 hit.
PROSITEPS50305. SIRTUIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9NXA8.
GeneWikiSIRT5.
GenomeRNAi23408.
NextBio45587.
PROQ9NXA8.
SOURCESearch...

Entry information

Entry nameSIR5_HUMAN
AccessionPrimary (citable) accession number: Q9NXA8
Secondary accession number(s): B4DFM4 expand/collapse secondary AC list , B4DYJ5, F5H5Z9, Q5T294, Q5T295, Q9Y6E6
Entry history
Integrated into UniProtKB/Swiss-Prot: October 31, 2003
Last sequence update: October 31, 2003
Last modified: July 9, 2014
This is version 122 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM