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Protein

NAD-dependent protein lipoamidase sirtuin-4, mitochondrial

Gene

SIRT4

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

Acts as NAD-dependent protein lipoamidase, ADP-ribosyl transferase and deacetylase. Catalyzes more efficiently removal of lipoyl- and biotinyl- than acetyl-lysine modifications. Inhibits the pyruvate dehydrogenase complex (PDH) activity via the enzymatic hydrolysis of the lipoamide cofactor from the E2 component, DLAT, in a phosphorylation-independent manner. Catalyzes the transfer of ADP-ribosyl groups onto target proteins, including mitochondrial GLUD1, inhibiting GLUD1 enzyme activity. Acts as a negative regulator of mitochondrial glutamine metabolism by mediating mono ADP-ribosylation of GLUD1: expressed in response to DNA damage and negatively regulates anaplerosis by inhibiting GLUD1, leading to block metabolism of glutamine into tricarboxylic acid cycle and promoting cell cycle arrest. In response to mTORC1 signal, SIRT4 expression is repressed, promoting anaplerosis and cell proliferation. Acts as a tumor suppressor. Also acts as a NAD-dependent protein deacetylase: mediates deacetylation of 'Lys-471' of MLYCD, inhibiting its activity, thereby acting as a regulator of lipid homeostasis. Does not seem to deacetylate PC. Controls fatty acid oxidation by inhibiting PPARA transcriptional activation. Impairs SIRT1:PPARA interaction probably through the regulation of NAD+ levels. Down-regulates insulin secretion (By similarity).UniRule annotationBy similarity

Miscellaneous

According to some authors, ADP-ribosyltransferase activity of sirtuins may be an inefficient side reaction of the deacetylase activity and may not be physiologically relevant.UniRule annotation

Catalytic activityi

NAD+ + a protein = nicotinamide + an N-(ADP-D-ribosyl)-protein.UniRule annotation
NAD+ + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein.UniRule annotation

Cofactori

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei162Proton acceptorUniRule annotation1
Metal bindingi170ZincUniRule annotation1
Metal bindingi173ZincUniRule annotation1
Metal bindingi221ZincUniRule annotation1
Metal bindingi224ZincUniRule annotation1
Binding sitei305NAD; via amide nitrogenUniRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi63 – 83NADUniRule annotationAdd BLAST21
Nucleotide bindingi144 – 147NADUniRule annotation4
Nucleotide bindingi261 – 263NADUniRule annotation3
Nucleotide bindingi287 – 289NADUniRule annotation3

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Transferase
Biological processDNA damage
LigandMetal-binding, NAD, Zinc

Enzyme and pathway databases

ReactomeiR-BTA-2151201 Transcriptional activation of mitochondrial biogenesis

Names & Taxonomyi

Protein namesi
Recommended name:
NAD-dependent protein lipoamidase sirtuin-4, mitochondrialUniRule annotation (EC:3.5.1.-UniRule annotation)
Alternative name(s):
NAD-dependent ADP-ribosyltransferase sirtuin-4UniRule annotation (EC:2.4.2.-UniRule annotation)
NAD-dependent protein deacetylase sirtuin-4UniRule annotation (EC:3.5.1.-UniRule annotation)
Regulatory protein SIR2 homolog 4UniRule annotation
SIR2-like protein 4UniRule annotation
Gene namesi
Name:SIRT4UniRule annotation
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 17

Organism-specific databases

VGNCiVGNC:34633 SIRT4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 29MitochondrionUniRule annotationAdd BLAST29
ChainiPRO_000026045830 – 315NAD-dependent protein lipoamidase sirtuin-4, mitochondrialAdd BLAST286

Proteomic databases

PaxDbiQ1JQC6
PRIDEiQ1JQC6

Expressioni

Gene expression databases

BgeeiENSBTAG00000021168

Interactioni

Subunit structurei

Interacts with GLUD1, IDE and SLC25A5. Interacts with DLAT and PDHX (By similarity). Interacts with MCCC1 (via the biotin carboxylation domain) (By similarity). Interacts with PCCA and PC (By similarity).UniRule annotationBy similarity

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000028210

Structurei

3D structure databases

ProteinModelPortaliQ1JQC6
SMRiQ1JQC6
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini46 – 315Deacetylase sirtuin-typeUniRule annotationAdd BLAST270

Sequence similaritiesi

Belongs to the sirtuin family. Class II subfamily.UniRule annotation

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG2683 Eukaryota
COG0846 LUCA
GeneTreeiENSGT00870000136443
HOGENOMiHOG000085953
HOVERGENiHBG059577
InParanoidiQ1JQC6
KOiK11414
OMAiARQRYWA
OrthoDBiEOG091G0DTB
TreeFamiTF106182

Family and domain databases

Gene3Di3.30.1600.10, 2 hits
HAMAPiMF_01967 Sirtuin_ClassII, 1 hit
InterProiView protein in InterPro
IPR029035 DHS-like_NAD/FAD-binding_dom
IPR003000 Sirtuin
IPR026591 Sirtuin_cat_small_dom_sf
IPR026587 Sirtuin_class_II
IPR026590 Ssirtuin_cat_dom
PfamiView protein in Pfam
PF02146 SIR2, 1 hit
SUPFAMiSSF52467 SSF52467, 1 hit
PROSITEiView protein in PROSITE
PS50305 SIRTUIN, 1 hit

Sequencei

Sequence statusi: Complete.

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

Q1JQC6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRMSFGLTFK RTAKVHWRAN FSQQCSLRST GLFVPPSPPL DPEKVKELQR
60 70 80 90 100
FITLSKRLLV MTGAGISTES GIPDYRSEKV GLYARTDRRP IQHGDFVRSA
110 120 130 140 150
PVRQRYWARN FVGWPQFSSR QPNPAHWALS NWERLGKLHW LVTQNVDALH
160 170 180 190 200
TKAGSQRLTE LHGCMHRVLC LDCGEQTPRG VLQERFQVLN PTWSAEAHGL
210 220 230 240 250
APDGDVFLTE EEVQSFQVPS CSRCGGPLKP DVVFFGDTVK PDKVDFVHKR
260 270 280 290 300
VKEADSLLVV GSSLQVYSGY RFILTAREKK LPIVILNIGP TRSDDLASLK
310
LDSRCGELLP LIDPR
Length:315
Mass (Da):35,588
Last modified:June 13, 2006 - v1
Checksum:i3E3CC7C36AF5E8B1
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC116055 mRNA Translation: AAI16056.1
RefSeqiNP_001069253.1, NM_001075785.1
XP_010812228.1, XM_010813926.2
UniGeneiBt.39710

Genome annotation databases

EnsembliENSBTAT00000028210; ENSBTAP00000028210; ENSBTAG00000021168
GeneIDi519328
KEGGibta:519328

Similar proteinsi

Entry informationi

Entry nameiSIR4_BOVIN
AccessioniPrimary (citable) accession number: Q1JQC6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: June 13, 2006
Last modified: April 25, 2018
This is version 86 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

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