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Reviewed, UniProtKB/Swiss-Prot Q9NXA8 (SIRT5_HUMAN)

Last modified January 19, 2010. Version 80. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    NAD-dependent deacetylase sirtuin-5
    EC=3.5.1.-
Alternative name(s):
    SIR2-like protein 5
Gene names
Name: SIRT5
Synonyms: SIR2L5
OrganismHomo sapiens (Human) [Complete 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 protein deacetylase that activates CPS1 and contributes to the regulation of blood ammonia levels during prolonged fasting. Deacetylates CPS1 and increases CPS1 activity in response to elevated NAD levels during fasting By similarity. Can deacetylate cytochrome c and a number of other proteins (in vitro). Ref.8

Catalytic activity

NAD+ + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein. Ref.11

Cofactor

Binds 1 zinc ion per subunit.

Enzyme regulation

Inhibited by suramin. Ref.11

Subunit structure

Monomer. Homodimer. Forms homodimers upon suramin binding. Interacts with CPS1 By similarity. Ref.11

Subcellular location

Mitochondrion matrix. Mitochondrion intermembrane space Potential Ref.8 Ref.7.

Tissue specificity

Widely expressed. Ref.1

Sequence similarities

Belongs to the sirtuin family.

Contains 1 deacetylase sirtuin-type domain.

Alternative products

This entry describes 2 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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 3636Mitochondrion By similarity
Chain37 – 310274NAD-dependent deacetylase sirtuin-5
PRO_0000110266

Regions

Domain41 – 309269Deacetylase sirtuin-type
Nucleotide binding58 – 7720NAD
Nucleotide binding140 – 1445NAD
Nucleotide binding275 – 2762NAD

Sites

Active site1581Proton acceptor
Metal binding1661Zinc
Metal binding1691Zinc
Metal binding2071Zinc
Metal binding2121Zinc

Natural variations

Alternative sequence286 – 29914RFHFQ…TTLPE → SHLISISSLIIIKN in isoform 2.
VSP_008730
Alternative sequence300 – 31011Missing in isoform 2.
VSP_008731
Natural variant2851F → L: dbSNP rs9464003.
VAR_029042
Natural variant3051E → G: dbSNP rs34162626.
VAR_051980

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.

Checksum: 2EE7C311AAA34CBA
Show »

FASTA29932,674

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: 10381378] [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: 14702039] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Hepatoblastoma.
[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: 17974005] [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: 14574404] [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: 15489334] [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: 16079181] [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: 18680753] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[9]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[10]"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.
[11]"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: 17355872] [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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF083110 mRNA. Translation: AAD40853.1.
AK000355 mRNA. Translation: BAA91107.1.
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.
IPIIPI00010331.
IPI00016807.
RefSeqNP_036373.1.
NP_112534.1.
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[»]
ModBaseSearch...

Protein-protein interaction databases

STRINGQ9NXA8.

Proteomic databases

PRIDEQ9NXA8.

Genome annotation databases

EnsemblENST00000379250; ENSP00000368552; ENSG00000124523; Homo sapiens. [Genome view]
GeneID23408.
KEGGhsa:23408.
NMPDRfig|9606.3.peg.26474.
UCSCuc003naw.1. human.
uc003nay.1. human.

Organism-specific databases

CTD23408.
GeneCardsGC06P013682.
H-InvDBHIX0005588.
HGNCHGNC:14933. SIRT5.
HPAHPA021798.
HPA022002.
HPA022992.
MIM604483. gene.
PharmGKBPA37938.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG18556.
HOGENOMHBG641281.
HOVERGENQ9NXA8.
InParanoidQ9NXA8.
OMAFVHEARL.
OrthoDBEOG9CVJS7.
PhylomeDBQ9NXA8.

Enzyme and pathway databases

Pathway_Interaction_DBhdac_classi_pathway. Signaling events mediated by HDAC Class I.

Gene expression databases

ArrayExpressQ9NXA8.
BgeeQ9NXA8.
CleanExHS_SIRT5.
GenevestigatorQ9NXA8.
GermOnlineENSG00000124523. Homo sapiens.

Family and domain databases

InterProIPR003000. NAD-dep_histone_deAcase_SIR2.
[Graphical view]
PANTHERPTHR11085. SIR2. 1 hit.
PfamPF02146. SIR2. 1 hit.
[Graphical view]
PROSITEPS50305. SIRTUIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB04786. Suramin.
NextBio45587.
SOURCESearch...

Entry information

Entry nameSIRT5_HUMAN
AccessionPrimary (citable) accession number: Q9NXA8
Secondary accession number(s): Q5T294, Q5T295, Q9Y6E6
Entry history
Integrated into UniProtKB/Swiss-Prot: October 31, 2003
Last sequence update: October 31, 2003
Last modified: January 19, 2010
This is version 80 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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

Human chromosome 6

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents