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Protein

NAD-dependent protein lipoamidase sirtuin-4, mitochondrial

Gene

SIRT4

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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. 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 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

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Transferase

Keywords - Biological processi

DNA damage

Keywords - Ligandi

Metal-binding, NAD, Zinc

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

Subcellular locationi

  • Mitochondrion matrix UniRule annotation

GO - Cellular componenti

  • mitochondrial inner membrane Source: Ensembl
  • mitochondrial matrix Source: UniProtKB
  • mitochondrion Source: UniProtKB
Complete GO annotation...

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).UniRule annotation

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000028210.

Structurei

3D structure databases

ProteinModelPortaliQ1JQC6.
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
Contains 1 deacetylase sirtuin-type domain.UniRule annotation

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG2683. Eukaryota.
COG0846. LUCA.
GeneTreeiENSGT00850000132288.
HOGENOMiHOG000085953.
HOVERGENiHBG059577.
InParanoidiQ1JQC6.
KOiK11414.
OMAiQVLNPTW.
OrthoDBiEOG091G0DTB.
TreeFamiTF106182.

Family and domain databases

Gene3Di3.30.1600.10. 2 hits.
3.40.50.1220. 3 hits.
HAMAPiMF_01967. Sirtuin_ClassII. 1 hit.
InterProiIPR029035. DHS-like_NAD/FAD-binding_dom.
IPR003000. Sirtuin.
IPR026591. Sirtuin_cat_small_dom.
IPR026587. Sirtuin_class_II.
IPR026590. Ssirtuin_cat_dom.
[Graphical view]
PANTHERiPTHR11085. PTHR11085. 2 hits.
PfamiPF02146. SIR2. 1 hit.
[Graphical view]
SUPFAMiSSF52467. SSF52467. 1 hit.
PROSITEiPS50305. SIRTUIN. 1 hit.
[Graphical view]

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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ1JQC6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000028210.

Proteomic databases

PaxDbiQ1JQC6.
PRIDEiQ1JQC6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000028210; ENSBTAP00000028210; ENSBTAG00000021168.
GeneIDi519328.
KEGGibta:519328.

Organism-specific databases

CTDi23409.

Phylogenomic databases

eggNOGiKOG2683. Eukaryota.
COG0846. LUCA.
GeneTreeiENSGT00850000132288.
HOGENOMiHOG000085953.
HOVERGENiHBG059577.
InParanoidiQ1JQC6.
KOiK11414.
OMAiQVLNPTW.
OrthoDBiEOG091G0DTB.
TreeFamiTF106182.

Gene expression databases

BgeeiENSBTAG00000021168.

Family and domain databases

Gene3Di3.30.1600.10. 2 hits.
3.40.50.1220. 3 hits.
HAMAPiMF_01967. Sirtuin_ClassII. 1 hit.
InterProiIPR029035. DHS-like_NAD/FAD-binding_dom.
IPR003000. Sirtuin.
IPR026591. Sirtuin_cat_small_dom.
IPR026587. Sirtuin_class_II.
IPR026590. Ssirtuin_cat_dom.
[Graphical view]
PANTHERiPTHR11085. PTHR11085. 2 hits.
PfamiPF02146. SIR2. 1 hit.
[Graphical view]
SUPFAMiSSF52467. SSF52467. 1 hit.
PROSITEiPS50305. SIRTUIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSIR4_BOVIN
AccessioniPrimary (citable) accession number: Q1JQC6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: June 13, 2006
Last modified: October 5, 2016
This is version 78 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.