MOUSE:SIR4

Species (Taxon ID)	Mus musculus (Mouse). (10090)
Gene Name(s)	Sirt4 (synonyms: Sir2l4)
Protein Name(s)	NAD-dependent protein deacetylase sirtuin-4 (ECO:0000255 with HAMAP-Rule:MF_03161) NAD-dependent ADP-ribosyltransferase sirtuin-4 (ECO:0000255 with HAMAP-Rule:MF_03161) Regulatory protein SIR2 homolog 4 (ECO:0000255 with HAMAP-Rule:MF_03161) SIR2-like protein 4 (ECO:0000255 with HAMAP-Rule:MF_03161)
External Links
UniProt	Q8R216
EMBL	AC117735 AC159539 CH466529 CH466529 BC022653
CCDS	CCDS51628.1
RefSeq	NP_001161163.1 NP_598521.1
UniGene	Mm.332616
ProteinModelPortal	Q8R216
SMR	Q8R216
BioGrid	217445
STRING	10090.ENSMUSP00000031499
PhosphoSite	Q8R216
MaxQB	Q8R216
PaxDb	Q8R216
PRIDE	Q8R216
Ensembl	ENSMUST00000112066 ENSMUST00000112067
GeneID	75387
KEGG	mmu:75387
UCSC	uc008zdy.1
CTD	23409
MGI	MGI:1922637
eggNOG	COG0846
GeneTree	ENSGT00740000115330
HOGENOM	HOG000085953
HOVERGEN	HBG059577
InParanoid	Q8R216
KO	K11414
OMA	TPRGVLQ
OrthoDB	EOG7DZ8KF
TreeFam	TF106182
ChiTaRS	Sirt4
NextBio	342886
PRO	PR:Q8R216
Proteomes	UP000000589
Bgee	Q8R216
Genevestigator	Q8R216
GO	GO:0005759 GO:0005739 GO:0003950 GO:0070403 GO:0034979 GO:0008270 GO:0006974 GO:0006541 GO:0046322 GO:0046676 GO:0034983 GO:0046889 GO:0006471 GO:0072350
Gene3D	3.30.1600.10 3.40.50.1220
HAMAP	MF_01967
InterPro	IPR029035 IPR003000 IPR026591 IPR026587 IPR026590
PANTHER	PTHR11085
Pfam	PF02146
SUPFAM	SSF52467
PROSITE	PS50305

Annotations

Qualifier	GO ID	GO term name	Reference	ECO ID	ECO term name	with/from	Aspect	Notes	Status
	GO:0005743	mitochondrial inner membrane	PMID:18054327^[1]	ECO:0000314			C	Fig. 1	complete CACAO 7183
	GO:0000820	regulation of glutamine family amino acid metabolic process	PMID:23562301^[2]	ECO:0000315			P	Figure 5) SIR4 knock out cells grew significantly faster than wild type cells. Over expression of SIR4 cells were significantly inhibited in their growth as compared to wild type cells.	complete CACAO 7794
involved_in	GO:0046322	negative regulation of fatty acid oxidation	PMID:24043310^[3]	ECO:0000315	mutant phenotype evidence used in manual assertion		P	Seeded From UniProt	complete
enables	GO:0047708	biotinidase activity	GO_REF:0000024	ECO:0000250	sequence similarity evidence used in manual assertion	UniProtKB:Q9Y6E7	F	Seeded From UniProt	complete
involved_in	GO:1904182	regulation of pyruvate dehydrogenase activity	PMID:25525879^[4]	ECO:0000315	mutant phenotype evidence used in manual assertion		P	Seeded From UniProt	complete
enables	GO:0061690	lipoamidase activity	PMID:25525879^[4]	ECO:0000315	mutant phenotype evidence used in manual assertion		F	Seeded From UniProt	complete
involved_in	GO:0000820	regulation of glutamine family amino acid metabolic process	PMID:23562301^[2]	ECO:0000315	mutant phenotype evidence used in manual assertion		P	Seeded From UniProt	complete
part_of	GO:0005743	mitochondrial inner membrane	PMID:18054327^[1]	ECO:0000314	direct assay evidence used in manual assertion		C	Seeded From UniProt	complete
involved_in	GO:0072350	tricarboxylic acid metabolic process	PMID:23663782^[5]	ECO:0000315	mutant phenotype evidence used in manual assertion		P	Seeded From UniProt	complete
involved_in	GO:0072350	tricarboxylic acid metabolic process	PMID:23562301^[2]	ECO:0000315	mutant phenotype evidence used in manual assertion		P	Seeded From UniProt	complete
involved_in	GO:0046889	positive regulation of lipid biosynthetic process	PMID:23746352^[6]	ECO:0000314	direct assay evidence used in manual assertion		P	Seeded From UniProt	complete
involved_in	GO:0046676	negative regulation of insulin secretion	GO_REF:0000024	ECO:0000250	sequence similarity evidence used in manual assertion	UniProtKB:Q9Y6E7	P	Seeded From UniProt	complete
involved_in	GO:0046322	negative regulation of fatty acid oxidation	PMID:23746352^[6]	ECO:0000314	direct assay evidence used in manual assertion		P	Seeded From UniProt	complete
involved_in	GO:0034983	peptidyl-lysine deacetylation	PMID:23746352^[6]	ECO:0000314	direct assay evidence used in manual assertion		P	Seeded From UniProt	complete
enables	GO:0034979	NAD-dependent protein deacetylase activity	PMID:23746352^[6]	ECO:0000314	direct assay evidence used in manual assertion		F	Seeded From UniProt	complete
involved_in	GO:0006974	cellular response to DNA damage stimulus	PMID:23562301^[2]	ECO:0000314	direct assay evidence used in manual assertion		P	Seeded From UniProt	complete
involved_in	GO:0006541	glutamine metabolic process	PMID:23663782^[5]	ECO:0000315	mutant phenotype evidence used in manual assertion		P	Seeded From UniProt	complete
involved_in	GO:0006541	glutamine metabolic process	PMID:23562301^[2]	ECO:0000315	mutant phenotype evidence used in manual assertion		P	Seeded From UniProt	complete
involved_in	GO:0006471	protein ADP-ribosylation	PMID:23663782^[5]	ECO:0000315	mutant phenotype evidence used in manual assertion		P	Seeded From UniProt	complete
part_of	GO:0005759	mitochondrial matrix	PMID:23746352^[6]	ECO:0000314	direct assay evidence used in manual assertion		C	Seeded From UniProt	complete
part_of	GO:0005759	mitochondrial matrix	GO_REF:0000024	ECO:0000250	sequence similarity evidence used in manual assertion	UniProtKB:Q9Y6E7	C	Seeded From UniProt	complete
part_of	GO:0005739	mitochondrion	GO_REF:0000024	ECO:0000250	sequence similarity evidence used in manual assertion	UniProtKB:Q9Y6E7	C	Seeded From UniProt	complete
enables	GO:0003950	NAD+ ADP-ribosyltransferase activity	PMID:23663782^[5]	ECO:0000315	mutant phenotype evidence used in manual assertion		F	Seeded From UniProt	complete
enables	GO:0003950	NAD+ ADP-ribosyltransferase activity	GO_REF:0000024	ECO:0000250	sequence similarity evidence used in manual assertion	UniProtKB:Q9Y6E7	F	Seeded From UniProt	complete
acts_upstream_of_or_within	GO:1904182	regulation of pyruvate dehydrogenase activity	GO_REF:0000096	ECO:0000266	sequence orthology evidence used in manual assertion	UniProtKB:Q9Y6E7	P	Seeded From UniProt	complete
acts_upstream_of_or_within	GO:1903217	negative regulation of protein processing involved in protein targeting to mitochondrion	GO_REF:0000096	ECO:0000266	sequence orthology evidence used in manual assertion	RGD:1310413	P	Seeded From UniProt	complete
enables	GO:0061690	lipoamidase activity	GO_REF:0000096	ECO:0000266	sequence orthology evidence used in manual assertion	UniProtKB:Q9Y6E7	F	Seeded From UniProt	complete
enables	GO:0047708	biotinidase activity	GO_REF:0000096	ECO:0000266	sequence orthology evidence used in manual assertion	UniProtKB:Q9Y6E7	F	Seeded From UniProt	complete
acts_upstream_of_or_within	GO:0046676	negative regulation of insulin secretion	PMID:16959573^[7]	ECO:0000316	genetic interaction evidence used in manual assertion	MGI:MGI:95753	P	Seeded From UniProt	complete
acts_upstream_of_or_within	GO:0046676	negative regulation of insulin secretion	PMID:16959573^[7]	ECO:0000315	mutant phenotype evidence used in manual assertion	MGI:MGI:3769237	P	Seeded From UniProt	complete
acts_upstream_of_or_within	GO:0046676	negative regulation of insulin secretion	GO_REF:0000096	ECO:0000266	sequence orthology evidence used in manual assertion	UniProtKB:Q9Y6E7	P	Seeded From UniProt	complete
acts_upstream_of_or_within	GO:0046322	negative regulation of fatty acid oxidation	GO_REF:0000096	ECO:0000266	sequence orthology evidence used in manual assertion	UniProtKB:Q9Y6E7	P	Seeded From UniProt	complete
acts_upstream_of_or_within	GO:0010667	negative regulation of cardiac muscle cell apoptotic process	GO_REF:0000096	ECO:0000266	sequence orthology evidence used in manual assertion	RGD:1310413	P	Seeded From UniProt	complete
part_of	GO:0005759	mitochondrial matrix	GO_REF:0000096	ECO:0000266	sequence orthology evidence used in manual assertion	UniProtKB:Q9Y6E7	C	Seeded From UniProt	complete
part_of	GO:0005739	mitochondrion	PMID:26767982^[8]	ECO:0000314	direct assay evidence used in manual assertion		C	Seeded From UniProt	complete
part_of	GO:0005739	mitochondrion	PMID:17923681^[9]	ECO:0000314	direct assay evidence used in manual assertion		C	Seeded From UniProt	complete
part_of	GO:0005739	mitochondrion	PMID:16959573^[7]	ECO:0000314	direct assay evidence used in manual assertion		C	Seeded From UniProt	complete
part_of	GO:0005739	mitochondrion	GO_REF:0000096	ECO:0000266	sequence orthology evidence used in manual assertion	UniProtKB:Q9Y6E7	C	Seeded From UniProt	complete
part_of	GO:0005739	mitochondrion	GO_REF:0000096	ECO:0000266	sequence orthology evidence used in manual assertion	RGD:1310413	C	Seeded From UniProt	complete
enables	GO:0003950	NAD+ ADP-ribosyltransferase activity	PMID:16959573^[7]	ECO:0000266	sequence orthology evidence used in manual assertion	UniProtKB:Q9Y6E7	F	Seeded From UniProt	complete
enables	GO:0003950	NAD+ ADP-ribosyltransferase activity	GO_REF:0000096	ECO:0000266	sequence orthology evidence used in manual assertion	UniProtKB:Q9Y6E7	F	Seeded From UniProt	complete
involved_in	GO:1903217	negative regulation of protein processing involved in protein targeting to mitochondrion	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:G3V641 ensembl:ENSRNOP00000001523	P	Seeded From UniProt	complete
involved_in	GO:0071456	cellular response to hypoxia	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:G3V641 ensembl:ENSRNOP00000001523	P	Seeded From UniProt	complete
involved_in	GO:0010667	negative regulation of cardiac muscle cell apoptotic process	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:G3V641 ensembl:ENSRNOP00000001523	P	Seeded From UniProt	complete
part_of	GO:0005739	mitochondrion	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:G3V641 ensembl:ENSRNOP00000001523	C	Seeded From UniProt	complete
involved_in	GO:1904182	regulation of pyruvate dehydrogenase activity	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:Q9Y6E7 ensembl:ENSP00000202967	P	Seeded From UniProt	complete
enables	GO:0061690	lipoamidase activity	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:Q9Y6E7 ensembl:ENSP00000202967	F	Seeded From UniProt	complete
enables	GO:0047708	biotinidase activity	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:Q9Y6E7 ensembl:ENSP00000202967	F	Seeded From UniProt	complete
involved_in	GO:0046676	negative regulation of insulin secretion	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:Q9Y6E7 ensembl:ENSP00000202967	P	Seeded From UniProt	complete
involved_in	GO:0046322	negative regulation of fatty acid oxidation	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:Q9Y6E7 ensembl:ENSP00000202967	P	Seeded From UniProt	complete
part_of	GO:0005759	mitochondrial matrix	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:Q9Y6E7 ensembl:ENSP00000202967	C	Seeded From UniProt	complete
part_of	GO:0005739	mitochondrion	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:Q9Y6E7 ensembl:ENSP00000202967	C	Seeded From UniProt	complete
enables	GO:0003950	NAD+ ADP-ribosyltransferase activity	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:Q9Y6E7 ensembl:ENSP00000202967	F	Seeded From UniProt	complete
enables	GO:0070403	NAD+ binding	GO_REF:0000002	ECO:0000256	match to sequence model evidence used in automatic assertion	InterPro:IPR003000	F	Seeded From UniProt	complete
enables	GO:0070403	NAD+ binding	GO_REF:0000104	ECO:0000256	match to sequence model evidence used in automatic assertion	UniRule:UR000376616	F	Seeded From UniProt	complete
part_of	GO:0005759	mitochondrial matrix	GO_REF:0000104	ECO:0000256	match to sequence model evidence used in automatic assertion	UniRule:UR000376616	C	Seeded From UniProt	complete
enables	GO:0034979	NAD-dependent protein deacetylase activity	GO_REF:0000104	ECO:0000256	match to sequence model evidence used in automatic assertion	UniRule:UR000376616	F	Seeded From UniProt	complete
involved_in	GO:0006471	protein ADP-ribosylation	GO_REF:0000104	ECO:0000256	match to sequence model evidence used in automatic assertion	UniRule:UR000376616	P	Seeded From UniProt	complete
involved_in	GO:0006476	protein deacetylation	GO_REF:0000104	ECO:0000256	match to sequence model evidence used in automatic assertion	UniRule:UR000376616	P	Seeded From UniProt	complete
enables	GO:0008270	zinc ion binding	GO_REF:0000104	ECO:0000256	match to sequence model evidence used in automatic assertion	UniRule:UR000376616	F	Seeded From UniProt	complete
enables	GO:0003950	NAD+ ADP-ribosyltransferase activity	GO_REF:0000104	ECO:0000256	match to sequence model evidence used in automatic assertion	UniRule:UR000376616	F	Seeded From UniProt	complete
enables	GO:0046872	metal ion binding	GO_REF:0000037	ECO:0000322	imported manually asserted information used in automatic assertion	UniProtKB-KW:KW-0479	F	Seeded From UniProt	complete
involved_in	GO:0006974	cellular response to DNA damage stimulus	GO_REF:0000037	ECO:0000322	imported manually asserted information used in automatic assertion	UniProtKB-KW:KW-0227	P	Seeded From UniProt	complete
part_of	GO:0005739	mitochondrion	GO_REF:0000037	ECO:0000322	imported manually asserted information used in automatic assertion	UniProtKB-KW:KW-0496	C	Seeded From UniProt	complete
enables	GO:0016740	transferase activity	GO_REF:0000037	ECO:0000322	imported manually asserted information used in automatic assertion	UniProtKB-KW:KW-0808	F	Seeded From UniProt	complete
enables	GO:0016787	hydrolase activity	GO_REF:0000037	ECO:0000322	imported manually asserted information used in automatic assertion	UniProtKB-KW:KW-0378	F	Seeded From UniProt	complete
part_of	GO:0005759	mitochondrial matrix	GO_REF:0000039	ECO:0000322	imported manually asserted information used in automatic assertion	UniProtKB-SubCell:SL-0170	C	Seeded From UniProt	complete
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Notes

References

See Help:References for how to manage references in GONUTS.

↑ ^1.0 ^1.1 Nakamura, Y et al. (2008) Localization of mouse mitochondrial SIRT proteins: shift of SIRT3 to nucleus by co-expression with SIRT5. Biochem. Biophys. Res. Commun. 366 174-9 PubMed GONUTS page
↑ ^2.0 ^2.1 ^2.2 ^2.3 ^2.4 Jeong, SM et al. (2013) SIRT4 has tumor-suppressive activity and regulates the cellular metabolic response to DNA damage by inhibiting mitochondrial glutamine metabolism. Cancer Cell 23 450-63 PubMed GONUTS page
↑ Laurent, G et al. (2013) SIRT4 represses peroxisome proliferator-activated receptor α activity to suppress hepatic fat oxidation. Mol. Cell. Biol. 33 4552-61 PubMed GONUTS page
↑ ^4.0 ^4.1 Mathias, RA et al. (2014) Sirtuin 4 is a lipoamidase regulating pyruvate dehydrogenase complex activity. Cell 159 1615-25 PubMed GONUTS page
↑ ^5.0 ^5.1 ^5.2 ^5.3 Csibi, A et al. (2013) The mTORC1 pathway stimulates glutamine metabolism and cell proliferation by repressing SIRT4. Cell 153 840-54 PubMed GONUTS page
↑ ^6.0 ^6.1 ^6.2 ^6.3 ^6.4 Laurent, G et al. (2013) SIRT4 coordinates the balance between lipid synthesis and catabolism by repressing malonyl CoA decarboxylase. Mol. Cell 50 686-98 PubMed GONUTS page
↑ ^7.0 ^7.1 ^7.2 ^7.3 Haigis, MC et al. (2006) SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell 126 941-54 PubMed GONUTS page
↑ Martin, J et al. (2016) Nutritional stress exacerbates hepatic steatosis induced by deletion of the histidine nucleotide-binding (Hint2) mitochondrial protein. Am. J. Physiol. Gastrointest. Liver Physiol. 310 G497-509 PubMed GONUTS page
↑ Lombard, DB et al. (2007) Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol. Cell. Biol. 27 8807-14 PubMed GONUTS page

[PMID:18054327-1] 1.0 ^1.1 Nakamura, Y et al. (2008) Localization of mouse mitochondrial SIRT proteins: shift of SIRT3 to nucleus by co-expression with SIRT5. Biochem. Biophys. Res. Commun. 366 174-9 PubMed GONUTS page

[PMID:23562301-2] 2.0 ^2.1 ^2.2 ^2.3 ^2.4 Jeong, SM et al. (2013) SIRT4 has tumor-suppressive activity and regulates the cellular metabolic response to DNA damage by inhibiting mitochondrial glutamine metabolism. Cancer Cell 23 450-63 PubMed GONUTS page

[PMID:24043310-3] Laurent, G et al. (2013) SIRT4 represses peroxisome proliferator-activated receptor α activity to suppress hepatic fat oxidation. Mol. Cell. Biol. 33 4552-61 PubMed GONUTS page

[PMID:25525879-4] 4.0 ^4.1 Mathias, RA et al. (2014) Sirtuin 4 is a lipoamidase regulating pyruvate dehydrogenase complex activity. Cell 159 1615-25 PubMed GONUTS page

[PMID:23663782-5] 5.0 ^5.1 ^5.2 ^5.3 Csibi, A et al. (2013) The mTORC1 pathway stimulates glutamine metabolism and cell proliferation by repressing SIRT4. Cell 153 840-54 PubMed GONUTS page

[PMID:23746352-6] 6.0 ^6.1 ^6.2 ^6.3 ^6.4 Laurent, G et al. (2013) SIRT4 coordinates the balance between lipid synthesis and catabolism by repressing malonyl CoA decarboxylase. Mol. Cell 50 686-98 PubMed GONUTS page

[PMID:16959573-7] 7.0 ^7.1 ^7.2 ^7.3 Haigis, MC et al. (2006) SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell 126 941-54 PubMed GONUTS page

[PMID:26767982-8] Martin, J et al. (2016) Nutritional stress exacerbates hepatic steatosis induced by deletion of the histidine nucleotide-binding (Hint2) mitochondrial protein. Am. J. Physiol. Gastrointest. Liver Physiol. 310 G497-509 PubMed GONUTS page

[PMID:17923681-9] Lombard, DB et al. (2007) Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol. Cell. Biol. 27 8807-14 PubMed GONUTS page

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MOUSE:SIR4

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