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Q9NXA8

- SIR5_HUMAN

UniProt

Q9NXA8 - SIR5_HUMAN

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Protein

NAD-dependent protein deacylase sirtuin-5, mitochondrial

Gene

SIRT5

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.4 Publications

Catalytic activityi

NAD+ + a malonylprotein = nicotinamide + O-malonyl-ADP-ribose + a protein.UniRule annotation
NAD+ + a succinylprotein = nicotinamide + O-succinyl-ADP-ribose + a protein.UniRule annotation

Cofactori

Zn2+1 PublicationUniRule annotationNote: Binds 1 zinc ion per subunit.1 PublicationUniRule annotation

Enzyme regulationi

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.3 Publications

Kineticsi

  1. KM=6.1 µM for a synthetic histone H3K9 malonyllysine peptide1 Publication
  2. KM=5.8 µM for a synthetic histone H3K9 succinyllysine peptide1 Publication
  3. KM=8.7 µM for a synthetic GLUD1 peptide malonylated at 'Lys-503'1 Publication
  4. KM=14 µM for a synthetic GLUD1 peptide succinylated at 'Lys-503'1 Publication
  5. KM=150 µM for a synthetic ACSS1 peptide malonylated at 'Lys-628'1 Publication
  6. KM=450 µM for a synthetic ACSS1 peptide succinylated at 'Lys-628'1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei102 – 1021Substrate
Binding sitei105 – 1051Substrate
Active sitei158 – 1581Proton acceptor1 PublicationUniRule annotation
Metal bindingi166 – 1661Zinc
Metal bindingi169 – 1691Zinc
Metal bindingi207 – 2071Zinc
Metal bindingi212 – 2121Zinc
Binding sitei293 – 2931NAD; via amide nitrogen3 PublicationsUniRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi58 – 7720NAD3 PublicationsUniRule annotationAdd
BLAST
Nucleotide bindingi140 – 1434NAD3 PublicationsUniRule annotation
Nucleotide bindingi249 – 2513NAD3 PublicationsUniRule annotation
Nucleotide bindingi275 – 2773NAD3 PublicationsUniRule annotation

GO - Molecular functioni

  1. NAD+ ADP-ribosyltransferase activity Source: ProtInc
  2. NAD+ binding Source: UniProtKB
  3. protein-malonyllysine demalonylase activity Source: UniProtKB
  4. protein-succinyllysine desuccinylase activity Source: UniProtKB
  5. zinc ion binding Source: UniProtKB

GO - Biological processi

  1. chromatin silencing Source: ProtInc
  2. negative regulation of reactive oxygen species metabolic process Source: UniProtKB
  3. peptidyl-lysine demalonylation Source: UniProtKB
  4. peptidyl-lysine desuccinylation Source: UniProtKB
  5. protein ADP-ribosylation Source: ProtInc
  6. protein deacetylation Source: UniProtKB
  7. protein desuccinylation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

Metal-binding, NAD, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
NAD-dependent protein deacylase sirtuin-5, mitochondrialUniRule annotation (EC:3.5.1.-UniRule annotation)
Alternative name(s):
Regulatory protein SIR2 homolog 5UniRule annotation
SIR2-like protein 5UniRule annotation
Gene namesi
Name:SIRT5UniRule annotation
Synonyms:SIR2L5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 6

Organism-specific databases

HGNCiHGNC:14933. SIRT5.

Subcellular locationi

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.
Isoform 1 : Cytoplasm 1 Publication. Mitochondrion 1 PublicationUniRule annotation
Isoform 2 : Mitochondrion 1 PublicationUniRule annotation

GO - Cellular componenti

  1. cytosol Source: UniProtKB
  2. mitochondrial intermembrane space Source: UniProtKB
  3. mitochondrial matrix Source: UniProtKB
  4. mitochondrion Source: UniProtKB
  5. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Mitochondrion, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi69 – 691T → A: Abolishes enzyme activity. 1 Publication
Mutagenesisi102 – 1021Y → F: Increases the KM for desuccinylation. 1 Publication
Mutagenesisi105 – 1051R → M: Increases the KM for desuccinylation. Does not affect deacetylase activity. 2 Publications
Mutagenesisi158 – 1581H → A: Abolishes desuccinylation activity. 2 Publications

Organism-specific databases

PharmGKBiPA37938.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 3636MitochondrionUniRule annotationAdd
BLAST
Chaini37 – 310274NAD-dependent protein deacylase sirtuin-5, mitochondrialPRO_0000110266Add
BLAST

Proteomic databases

MaxQBiQ9NXA8.
PaxDbiQ9NXA8.
PRIDEiQ9NXA8.

PTM databases

PhosphoSiteiQ9NXA8.

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiQ9NXA8.
CleanExiHS_SIRT5.
ExpressionAtlasiQ9NXA8. baseline and differential.
GenevestigatoriQ9NXA8.

Organism-specific databases

HPAiHPA021798.
HPA022002.
HPA022992.

Interactioni

Subunit structurei

Interacts with CPS1 (By similarity). Monomer. Homodimer. Forms homodimers upon suramin binding.By similarity6 Publications

Protein-protein interaction databases

BioGridi116980. 82 interactions.
IntActiQ9NXA8. 1 interaction.
STRINGi9606.ENSP00000368552.

Structurei

Secondary structure

1
310
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi40 – 4910Combined sources
Beta strandi51 – 577Combined sources
Helixi59 – 613Combined sources
Helixi63 – 653Combined sources
Beta strandi70 – 723Combined sources
Helixi73 – 753Combined sources
Helixi82 – 854Combined sources
Helixi88 – 936Combined sources
Helixi95 – 10915Combined sources
Helixi116 – 12914Combined sources
Turni130 – 1323Combined sources
Beta strandi134 – 1407Combined sources
Helixi145 – 1495Combined sources
Beta strandi153 – 1564Combined sources
Beta strandi159 – 1668Combined sources
Turni167 – 1693Combined sources
Beta strandi172 – 1743Combined sources
Beta strandi178 – 1814Combined sources
Helixi182 – 1843Combined sources
Beta strandi190 – 1934Combined sources
Helixi201 – 2033Combined sources
Helixi209 – 2113Combined sources
Beta strandi215 – 2206Combined sources
Helixi229 – 24113Combined sources
Beta strandi243 – 2497Combined sources
Beta strandi252 – 2554Combined sources
Helixi257 – 2593Combined sources
Helixi260 – 2667Combined sources
Beta strandi271 – 2777Combined sources
Helixi282 – 2843Combined sources
Beta strandi285 – 2917Combined sources
Helixi293 – 3019Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
ProteinModelPortaliQ9NXA8.
SMRiQ9NXA8. Positions 34-302.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9NXA8.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini41 – 309269Deacetylase sirtuin-typeUniRule annotationAdd
BLAST

Domaini

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 (PubMed:22076378).1 Publication

Sequence similaritiesi

Belongs to the sirtuin family. Class III subfamily.UniRule annotation
Contains 1 deacetylase sirtuin-type domain.UniRule annotation

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiCOG0846.
GeneTreeiENSGT00740000115330.
HOGENOMiHOG000085950.
HOVERGENiHBG056009.
InParanoidiQ9NXA8.
KOiK11415.
OMAiFNMIDLA.
OrthoDBiEOG77Q4XG.
PhylomeDBiQ9NXA8.
TreeFamiTF106183.

Family and domain databases

Gene3Di3.30.1600.10. 2 hits.
3.40.50.1220. 3 hits.
HAMAPiMF_01121. Sirtuin_ClassIII.
InterProiIPR029035. DHS-like_NAD/FAD-binding_dom.
IPR003000. Sirtuin.
IPR026591. Sirtuin_cat_small_dom.
IPR027546. Sirtuin_class_III.
IPR026590. Ssirtuin_cat_dom.
[Graphical view]
PANTHERiPTHR11085. PTHR11085. 1 hit.
PfamiPF02146. SIR2. 1 hit.
[Graphical view]
SUPFAMiSSF52467. SSF52467. 1 hit.
PROSITEiPS50305. SIRTUIN. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q9NXA8-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MRPLQIVPSR LISQLYCGLK PPASTRNQIC LKMARPSSSM ADFRKFFAKA
60 70 80 90 100
KHIVIISGAG VSAESGVPTF RGAGGYWRKW QAQDLATPLA FAHNPSRVWE
110 120 130 140 150
FYHYRREVMG SKEPNAGHRA IAECETRLGK QGRRVVVITQ NIDELHRKAG
160 170 180 190 200
TKNLLEIHGS LFKTRCTSCG VVAENYKSPI CPALSGKGAP EPGTQDASIP
210 220 230 240 250
VEKLPRCEEA GCGGLLRPHV VWFGENLDPA ILEEVDRELA HCDLCLVVGT
260 270 280 290 300
SSVVYPAAMF APQVAARGVP VAEFNTETTP ATNRFRFHFQ GPCGTTLPEA
310
LACHENETVS
Length:310
Mass (Da):33,881
Last modified:October 31, 2003 - v2
Checksum:i022DA32CDB43AC3A
GO
Isoform 2 (identifier: Q9NXA8-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     286-299: RFHFQGPCGTTLPE → SHLISISSLIIIKN
     300-310: Missing.

Note: No experimental confirmation available.

Show »
Length:299
Mass (Da):32,674
Checksum:i2EE7C311AAA34CBA
GO
Isoform 3 (identifier: Q9NXA8-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     189-206: Missing.

Note: No experimental confirmation available.

Show »
Length:292
Mass (Da):31,994
Checksum:iD89A65C251224735
GO
Isoform 4 (identifier: Q9NXA8-4) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-108: Missing.

Note: No experimental confirmation available.

Show »
Length:202
Mass (Da):21,689
Checksum:i051C7D4BE508D66B
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti53 – 531I → M in BAG63757. (PubMed:14702039)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti285 – 2851F → L.
Corresponds to variant rs9464003 [ dbSNP | Ensembl ].
VAR_029042
Natural varianti305 – 3051E → G.
Corresponds to variant rs34162626 [ dbSNP | Ensembl ].
VAR_051980

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 108108Missing in isoform 4. 1 PublicationVSP_042291Add
BLAST
Alternative sequencei189 – 20618Missing in isoform 3. 1 PublicationVSP_042292Add
BLAST
Alternative sequencei286 – 29914RFHFQ…TTLPE → SHLISISSLIIIKN in isoform 2. 1 PublicationVSP_008730Add
BLAST
Alternative sequencei300 – 31011Missing in isoform 2. 1 PublicationVSP_008731Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS4526.1. [Q9NXA8-1]
CCDS4527.1. [Q9NXA8-2]
CCDS54966.1. [Q9NXA8-3]
CCDS56398.1. [Q9NXA8-4]
RefSeqiNP_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]
UniGeneiHs.567431.
Hs.594133.

Genome annotation databases

EnsembliENST00000359782; ENSP00000352830; ENSG00000124523. [Q9NXA8-3]
ENST00000379262; ENSP00000368564; ENSG00000124523. [Q9NXA8-2]
ENST00000397350; ENSP00000380509; ENSG00000124523. [Q9NXA8-4]
ENST00000606117; ENSP00000476228; ENSG00000124523. [Q9NXA8-1]
GeneIDi23408.
KEGGihsa:23408.
UCSCiuc003naw.3. human. [Q9NXA8-2]
uc003nax.3. human. [Q9NXA8-1]
uc011dit.2. human. [Q9NXA8-3]

Polymorphism databases

DMDMi38258652.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 .
CCDSi CCDS4526.1. [Q9NXA8-1 ]
CCDS4527.1. [Q9NXA8-2 ]
CCDS54966.1. [Q9NXA8-3 ]
CCDS56398.1. [Q9NXA8-4 ]
RefSeqi NP_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 ]
UniGenei Hs.567431.
Hs.594133.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2B4Y X-ray 1.90 A/B/C/D 34-302 [» ]
2NYR X-ray 2.06 A/B 34-302 [» ]
3RIG X-ray 2.00 A/B 34-302 [» ]
3RIY X-ray 1.55 A/B 34-302 [» ]
4F4U X-ray 2.00 A/B 34-302 [» ]
4F56 X-ray 1.70 A/B 34-302 [» ]
4G1C X-ray 1.94 A/B 36-302 [» ]
4HDA X-ray 2.60 A/B 34-302 [» ]
ProteinModelPortali Q9NXA8.
SMRi Q9NXA8. Positions 34-302.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 116980. 82 interactions.
IntActi Q9NXA8. 1 interaction.
STRINGi 9606.ENSP00000368552.

Chemistry

BindingDBi Q9NXA8.
ChEMBLi CHEMBL2163183.
DrugBanki DB04786. Suramin.

PTM databases

PhosphoSitei Q9NXA8.

Polymorphism databases

DMDMi 38258652.

Proteomic databases

MaxQBi Q9NXA8.
PaxDbi Q9NXA8.
PRIDEi Q9NXA8.

Protocols and materials databases

DNASUi 23408.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000359782 ; ENSP00000352830 ; ENSG00000124523 . [Q9NXA8-3 ]
ENST00000379262 ; ENSP00000368564 ; ENSG00000124523 . [Q9NXA8-2 ]
ENST00000397350 ; ENSP00000380509 ; ENSG00000124523 . [Q9NXA8-4 ]
ENST00000606117 ; ENSP00000476228 ; ENSG00000124523 . [Q9NXA8-1 ]
GeneIDi 23408.
KEGGi hsa:23408.
UCSCi uc003naw.3. human. [Q9NXA8-2 ]
uc003nax.3. human. [Q9NXA8-1 ]
uc011dit.2. human. [Q9NXA8-3 ]

Organism-specific databases

CTDi 23408.
GeneCardsi GC06P013574.
HGNCi HGNC:14933. SIRT5.
HPAi HPA021798.
HPA022002.
HPA022992.
MIMi 604483. gene.
neXtProti NX_Q9NXA8.
PharmGKBi PA37938.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0846.
GeneTreei ENSGT00740000115330.
HOGENOMi HOG000085950.
HOVERGENi HBG056009.
InParanoidi Q9NXA8.
KOi K11415.
OMAi FNMIDLA.
OrthoDBi EOG77Q4XG.
PhylomeDBi Q9NXA8.
TreeFami TF106183.

Miscellaneous databases

EvolutionaryTracei Q9NXA8.
GeneWikii SIRT5.
GenomeRNAii 23408.
NextBioi 45587.
PROi Q9NXA8.
SOURCEi Search...

Gene expression databases

Bgeei Q9NXA8.
CleanExi HS_SIRT5.
ExpressionAtlasi Q9NXA8. baseline and differential.
Genevestigatori Q9NXA8.

Family and domain databases

Gene3Di 3.30.1600.10. 2 hits.
3.40.50.1220. 3 hits.
HAMAPi MF_01121. Sirtuin_ClassIII.
InterProi IPR029035. DHS-like_NAD/FAD-binding_dom.
IPR003000. Sirtuin.
IPR026591. Sirtuin_cat_small_dom.
IPR027546. Sirtuin_class_III.
IPR026590. Ssirtuin_cat_dom.
[Graphical view ]
PANTHERi PTHR11085. PTHR11085. 1 hit.
Pfami PF02146. SIR2. 1 hit.
[Graphical view ]
SUPFAMi SSF52467. SSF52467. 1 hit.
PROSITEi PS50305. SIRTUIN. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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.
    , 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. 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. 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. 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. 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. Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 34-302 IN COMPLEX WITH PROTEIN PEPTIDE; ZINC IONS AND RESVERATROL, ENZYME REGULATION.

Entry informationi

Entry nameiSIR5_HUMAN
AccessioniPrimary (citable) accession number: Q9NXA8
Secondary accession number(s): B4DFM4
, B4DYJ5, F5H5Z9, Q5T294, Q5T295, Q9Y6E6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 31, 2003
Last sequence update: October 31, 2003
Last modified: November 26, 2014
This is version 125 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

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.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3