Q9Y6E7 (SIR4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
NAD-dependent protein deacetylase sirtuin-4
EC=3.5.1.-

Alternative name(s):
NAD-dependent ADP-ribosyltransferase sirtuin-4
EC=2.4.2.-
Regulatory protein SIR2 homolog 4
SIR2-like protein 4

Gene names

Name:	SIRT4
Synonyms:	SIR2L4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	314 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	NAD-dependent protein ADP-ribosyl transferase. Catalyzes the transfer of ADP-ribosyl groups onto target proteins, including mitochondrial GLUD1. Inhibits GLUD1 enzyme activity. Down-regulates insulin secretion. Has no detectable protein deacetylase activity. Ref.4 Ref.5
Catalytic activity	NAD+ + a protein = nicotinamide + an N-(ADP-D-ribosyl)-protein. HAMAP-Rule MF_03161 NAD+ + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein. HAMAP-Rule MF_03161
Cofactor	Binds 1 zinc ion per subunit By similarity.
Subunit structure	Interacts with GLUD1, IDE and SLC25A5. Ref.4 Ref.5
Subcellular location	Mitochondrion matrix Ref.4 Ref.5 Ref.6.
Tissue specificity	Detected in vascular smooth muscle and striated muscle. Detected in insulin-producing beta-cells in pancreas islets of Langerhans (at protein level). Widely expressed. Weakly expressed in leukocytes and fetal thymus. Ref.1
Miscellaneous	The reported ADP-ribosyltransferase activity of sirtuins may be an inefficient side reaction of the deacetylase activity and may not be physiologically relevant By similarity. HAMAP-Rule MF_03161
Sequence similarities	Belongs to the sirtuin family. Class II subfamily. Contains 1 deacetylase sirtuin-type domain.
Sequence caution	The sequence AAB95634.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Cellular component	Mitochondrion
Domain	Transit peptide
Ligand	Metal-binding NAD Zinc
Molecular function	Hydrolase Transferase
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	chromatin silencing Traceable author statement Ref.1. Source: ProtInc negative regulation of insulin secretion Inferred from mutant phenotype Ref.5. Source: UniProtKB protein ADP-ribosylation Traceable author statement PubMed 17456799. Source: BHF-UCL protein deacetylation Inferred from electronic annotation. Source: HAMAP
Cellular_component	mitochondrial matrix Inferred from direct assay Ref.4Ref.5. Source: UniProtKB
Molecular_function	NAD+ ADP-ribosyltransferase activity Inferred from direct assay Ref.4Ref.5. Source: UniProtKB NAD+ binding Inferred from electronic annotation. Source: HAMAP hydrolase activity Inferred from electronic annotation. Source: HAMAP zinc ion binding Inferred from electronic annotation. Source: HAMAP
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SLC25A5	P05141	2	EBI-2606540,EBI-355133

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 28	28	Mitochondrion Ref.4 Ref.5
	Chain	29 – 314	286	NAD-dependent protein deacetylase sirtuin-4 HAMAP-Rule MF_03161		PRO_0000110264
Regions
	Domain	45 – 314	270	Deacetylase sirtuin-type
	Nucleotide binding	62 – 82	21	NAD By similarity
	Nucleotide binding	143 – 146	4	NAD By similarity
	Nucleotide binding	260 – 262	3	NAD By similarity
	Nucleotide binding	286 – 288	3	NAD By similarity
Sites
	Active site	161	1	Proton acceptor By similarity
	Metal binding	169	1	Zinc By similarity
	Metal binding	172	1	Zinc By similarity
	Metal binding	220	1	Zinc By similarity
	Metal binding	223	1	Zinc By similarity
	Binding site	304	1	NAD; via amide nitrogen By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q9Y6E7 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 2B76963AD2C3B354	FASTA	314	35,188
	10 20 30 40 50 60 MKMSFALTFR SAKGRWIANP SQPCSKASIG LFVPASPPLD PEKVKELQRF ITLSKRLLVM 70 80 90 100 110 120 TGAGISTESG IPDYRSEKVG LYARTDRRPI QHGDFVRSAP IRQRYWARNF VGWPQFSSHQ 130 140 150 160 170 180 PNPAHWALST WEKLGKLYWL VTQNVDALHT KAGSRRLTEL HGCMDRVLCL DCGEQTPRGV 190 200 210 220 230 240 LQERFQVLNP TWSAEAHGLA PDGDVFLSEE QVRSFQVPTC VQCGGHLKPD VVFFGDTVNP 250 260 270 280 290 300 DKVDFVHKRV KEADSLLVVG SSLQVYSGYR FILTAWEKKL PIAILNIGPT RSDDLACLKL 310 NSRCGELLPL IDPC

References

	« Hide 'large scale' referencesShow '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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Testis.
[2]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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].
[4]	"SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells." Haigis M.C., Mostoslavsky R., Haigis K.M., Fahie K., Christodoulou D.C., Murphy A.J., Valenzuela D.M., Yancopoulos G.D., Karow M., Blander G., Wolberger C., Prolla T.A., Weindruch R., Alt F.W., Guarente L. Cell 126:941-954(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF N-TERMINUS, FUNCTION, INTERACTION WITH GLUD1, SUBCELLULAR LOCATION.
[5]	"Regulation of insulin secretion by SIRT4, a mitochondrial ADP-ribosyltransferase." Ahuja N., Schwer B., Carobbio S., Waltregny D., North B.J., Castronovo V., Maechler P., Verdin E. J. Biol. Chem. 282:33583-33592(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF N-TERMINUS, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH IDE AND SLC25A5.
[6]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF083109 mRNA. Translation: AAD40852.1. AC003982 Genomic DNA. Translation: AAB95634.1. Sequence problems. BC109319 mRNA. Translation: AAI09320.1. BC109320 mRNA. Translation: AAI09321.1.
IPI	IPI00305620.
RefSeq	NP_036372.1. NM_012240.2.
UniGene	Hs.50861.
3D structure databases
ProteinModelPortal	Q9Y6E7.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y6E7. 5 interactions.
STRING	9606.ENSP00000202967.
PTM databases
PhosphoSite	Q9Y6E7.
Polymorphism databases
DMDM	38258657.
Proteomic databases
PaxDb	Q9Y6E7.
PRIDE	Q9Y6E7.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000202967; ENSP00000202967; ENSG00000089163.
GeneID	23409.
KEGG	hsa:23409.
UCSC	uc001tyc.3. human.
Organism-specific databases
CTD	23409.
GeneCards	GC12P120740.
HGNC	HGNC:14932. SIRT4.
HPA	HPA029691. HPA029692.
MIM	604482. gene.
neXtProt	NX_Q9Y6E7.
PharmGKB	PA37937.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0846.
HOGENOM	HOG000085953.
HOVERGEN	HBG059577.
InParanoid	Q9Y6E7.
KO	K11414.
OMA	MHRVLCL.
OrthoDB	EOG4QFWF0.
PhylomeDB	Q9Y6E7.
Enzyme and pathway databases
Pathway_Interaction_DB	hdac_classi_pathway. Signaling events mediated by HDAC Class I.
Gene expression databases
ArrayExpress	Q9Y6E7.
Bgee	Q9Y6E7.
CleanEx	HS_SIRT4.
Genevestigator	Q9Y6E7.
GermOnline	ENSG00000089163. Homo sapiens.
Family and domain databases
Gene3D	3.30.1600.10. 2 hits.
HAMAP	MF_01967. Sirtuin_ClassII.
InterPro	IPR003000. Sirtuin. IPR026591. Sirtuin_cat_small_dom. IPR026587. Sirtuin_ClassII. IPR026590. Ssirtuin_cat_dom. [Graphical view]
PANTHER	PTHR11085. PTHR11085. 1 hit.
Pfam	PF02146. SIR2. 1 hit. [Graphical view]
PROSITE	PS50305. SIRTUIN. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	23409.
NextBio	45593.
SOURCE	Search...

Entry information

Entry name

SIR4_HUMAN

Accession

Primary (citable) accession number: Q9Y6E7
Secondary accession number(s): O43346, Q32M33

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 31, 2003
Last sequence update:	November 1, 1999
Last modified:	May 1, 2013
This is version 103 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.