Q9NRC8 (SIR7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
NAD-dependent protein deacetylase sirtuin-7
EC=3.5.1.-

Alternative name(s):
Regulatory protein SIR2 homolog 7
SIR2-like protein 7

Gene names

Name:	SIRT7
Synonyms:	SIR2L7

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	400 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	NAD-dependent protein deacetylase that specifically mediates deacetylation of histone H3 at 'Lys-18' (H3K18Ac). In contrast to other histone deacetylases, displays selectivity for a single histone mark, H3K18Ac, directly linked to control of gene expression. H3K18Ac is mainly present around the transcription start site of genes and has been linked to activation of nuclear hormone receptors. SIRT7 thereby acts as a transcription repressor. Moreover, H3K18 hypoacetylation has been reported as a marker of malignancy in various cancers and seems to maintain the transformed phenotype of cancer cells. These data suggest that SIRT7 may play a key role in oncogenic transformation by suppresses expression of tumor suppressor genes by locus-specific deacetylation of H3K18Ac at promoter regions. Also required to restore the transcription of ribosomal RNA (rRNA) at the exit from mitosis: promotes the association of RNA polymerase I with the rDNA promoter region and coding region. Stimulates transcription activity of the RNA polymerase I complex. May also deacetylate p53/TP53 and promotes cell survival, however such data need additional confirmation. Ref.10 Ref.11 Ref.13
Catalytic activity	NAD+ + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein. Ref.13
Cofactor	Binds 1 zinc ion per subunit By similarity.
Subunit structure	Interacts with UBTF and the RNA polymerase I complex. Interacts with components of the B-WICH complex, such as MYBBP1A, SMARCA5/SNF2H and BAZ1B/WSTF. Interacts with ELK4, leading to stabilization at target promoters for H3K18Ac deacetylation. Interacts with histone H2A and/or histone H2B. Ref.10 Ref.11 Ref.12 Ref.13
Subcellular location	Cytoplasm. Nucleus › nucleolus. Note: Located close to the nuclear membrane when in the cytoplasm. Associated with chromatin. Associated with rDNA promoter and transcribed region. Associated with nucleolar organizer regions during mitosis. Ref.6 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13
Post-translational modification	Phosphorylated during mitosis Probable. Ref.11
Miscellaneous	Overexpressed in human thyroid carcinoma cell lines and tissues, but not in adenomas.
Sequence similarities	Belongs to the sirtuin family. Class IV subfamily. Contains 1 deacetylase sirtuin-type domain.
Caution	Was originally (Ref.6) termed SIR-T8/SIRT8. This was later retracted (Ref.7). See also Ref.8.
Sequence caution	The sequence CAB70848.2 differs from that shown. Reason:

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Ligand	Metal-binding NAD Zinc
Molecular function	Chromatin regulator Hydrolase Repressor
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	histone H3 deacetylation Inferred from direct assay Ref.13. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.13. Source: UniProtKB positive regulation of transcription on exit from mitosis Inferred from mutant phenotype Ref.11. Source: UniProtKB rRNA transcription Inferred from mutant phenotype Ref.11. Source: UniProtKB
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleolus organizer region Inferred from direct assay Ref.11. Source: UniProtKB
Molecular_function	NAD+ binding Inferred from electronic annotation. Source: InterPro NAD-dependent histone deacetylase activity (H3-K18 specific) Inferred from direct assay Ref.13. Source: UniProtKB chromatin binding Inferred from direct assay Ref.13. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9NRC8-1)

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.

Isoform 2 (identifier: Q9NRC8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     162-183: QHVVSQNCDGLHLRSGLPRTAI → RALGGWYTCQGPGRAPWCPVGN
     184-400: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: Q9NRC8-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-30: MAAGGLSRSERKAAERVRRLREEQQRERLR → MPGPRRRSPSACP
     336-400: WQDPIFSLATPLRAGEEGSHSRKSLCRSREEAPPGDRGAPLSSAPILGGWFGRGCTKRTKRKKVT → VL

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 400	400	NAD-dependent protein deacetylase sirtuin-7		PRO_0000110271
Regions
	Domain	90 – 331	242	Deacetylase sirtuin-type
	Nucleotide binding	107 – 126	20	NAD By similarity
	Nucleotide binding	167 – 170	4	NAD By similarity
	Nucleotide binding	268 – 270	3	NAD By similarity
	Nucleotide binding	297 – 299	3	NAD By similarity
	Compositional bias	8 – 74	67	Arg-rich
Sites
	Active site	187	1	Proton acceptor
	Metal binding	195	1	Zinc By similarity
	Metal binding	198	1	Zinc By similarity
	Metal binding	225	1	Zinc By similarity
	Metal binding	228	1	Zinc By similarity
	Binding site	315	1	NAD; via amide nitrogen By similarity
Natural variations
	Alternative sequence	1 – 30	30	MAAGG…RERLR → MPGPRRRSPSACP in isoform 3.		VSP_044396
	Alternative sequence	162 – 183	22	QHVVS…PRTAI → RALGGWYTCQGPGRAPWCPV GN in isoform 2.		VSP_008736
	Alternative sequence	184 – 400	217	Missing in isoform 2.		VSP_008737
	Alternative sequence	336 – 400	65	WQDPI…RKKVT → VL in isoform 3.		VSP_044397
Experimental info
	Mutagenesis	111	1	S → A: Abolishes activation of pre-rRNA synthesis. Ref.10 Ref.12
	Mutagenesis	187	1	H → Y: Abolishes deacetylase activity and activation of pre-rRNA synthesis. Ref.10 Ref.13
	Sequence conflict	71	1	L → Q in BAG52860. Ref.2
	Sequence conflict	384	1	G → S in BAF82954. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 55D7736A864AFE6F	FASTA	400	44,898
	10 20 30 40 50 60 MAAGGLSRSE RKAAERVRRL REEQQRERLR QVSRILRKAA AERSAEEGRL LAESADLVTE 70 80 90 100 110 120 LQGRSRRREG LKRRQEEVCD DPEELRGKVR ELASAVRNAK YLVVYTGAGI STAASIPDYR 130 140 150 160 170 180 GPNGVWTLLQ KGRSVSAADL SEAEPTLTHM SITRLHEQKL VQHVVSQNCD GLHLRSGLPR 190 200 210 220 230 240 TAISELHGNM YIEVCTSCVP NREYVRVFDV TERTALHRHQ TGRTCHKCGT QLRDTIVHFG 250 260 270 280 290 300 ERGTLGQPLN WEAATEAASR ADTILCLGSS LKVLKKYPRL WCMTKPPSRR PKLYIVNLQW 310 320 330 340 350 360 TPKDDWAALK LHGKCDDVMR LLMAELGLEI PAYSRWQDPI FSLATPLRAG EEGSHSRKSL 370 380 390 400 CRSREEAPPG DRGAPLSSAP ILGGWFGRGC TKRTKRKKVT
	Isoform 2 [UniParc]. Checksum: EC211D79031585C2	FASTA	183	20,404
	10 20 30 40 50 60 MAAGGLSRSE RKAAERVRRL REEQQRERLR QVSRILRKAA AERSAEEGRL LAESADLVTE 70 80 90 100 110 120 LQGRSRRREG LKRRQEEVCD DPEELRGKVR ELASAVRNAK YLVVYTGAGI STAASIPDYR 130 140 150 160 170 180 GPNGVWTLLQ KGRSVSAADL SEAEPTLTHM SITRLHEQKL VRALGGWYTC QGPGRAPWCP VGN
	Isoform 3 [UniParc]. Checksum: C0E80615256EEA7A	FASTA	320	35,851
	10 20 30 40 50 60 MPGPRRRSPS ACPQVSRILR KAAAERSAEE GRLLAESADL VTELQGRSRR REGLKRRQEE 70 80 90 100 110 120 VCDDPEELRG KVRELASAVR NAKYLVVYTG AGISTAASIP DYRGPNGVWT LLQKGRSVSA 130 140 150 160 170 180 ADLSEAEPTL THMSITRLHE QKLVQHVVSQ NCDGLHLRSG LPRTAISELH GNMYIEVCTS 190 200 210 220 230 240 CVPNREYVRV FDVTERTALH RHQTGRTCHK CGTQLRDTIV HFGERGTLGQ PLNWEAATEA 250 260 270 280 290 300 ASRADTILCL GSSLKVLKKY PRLWCMTKPP SRRPKLYIVN LQWTPKDDWA ALKLHGKCDD 310 320 VMRLLMAELG LEIPAYSRVL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Phylogenetic classification of prokaryotic and eukaryotic Sir-2 like proteins." Frye R.A. Biochem. Biophys. Res. Commun. 273:793-798(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Spleen.
[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 1; 2 AND 3). Tissue: Cerebellum, Colon and Placenta.
[3]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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: Liver and Lymph.
[5]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 128-400 (ISOFORM 1). Tissue: Testis.
[6]	"Isolation of a SIR-like gene, SIR-T8, that is overexpressed in thyroid carcinoma cell lines and tissues." de Nigris F., Cerutti J., Morelli C., Califano D., Chiariotti L., Viglietto G., Santelli G., Fusco A. Br. J. Cancer 86:917-923(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[7]	Erratum De Nigris F., Cerutti J., Morelli C., Califano D., Chiariotti L., Viglietto G., Santelli G., Fusco A. Br. J. Cancer 87:1479-1479(2002) [PubMed] [Europe PMC] [Abstract]
[8]	"'SIRT8' expressed in thyroid cancer is actually SIRT7." Frye R.A. Br. J. Cancer 87:1479-1479(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SHOWS THAT SIR-T8 IS SIRT7.
[9]	"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.
[10]	"Mammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription." Ford E., Voit R., Liszt G., Magin C., Grummt I., Guarente L. Genes Dev. 20:1075-1080(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, IDENTIFICATION IN A RNA POLYMERASE I COMPLEX, INTERACTION WITH HISTONE H2A AND/OR HISTONE H2B, MUTAGENESIS OF SER-111 AND HIS-187, SUBCELLULAR LOCATION.
[11]	"Involvement of SIRT7 in resumption of rDNA transcription at the exit from mitosis." Grob A., Roussel P., Wright J.E., McStay B., Hernandez-Verdun D., Sirri V. J. Cell Sci. 122:489-498(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH UBTF, PHOSPHORYLATION, SUBCELLULAR LOCATION.
[12]	"Functional proteomics establishes the interaction of SIRT7 with chromatin remodeling complexes and expands its role in regulation of RNA polymerase I transcription." Tsai Y.C., Greco T.M., Boonmee A., Miteva Y., Cristea I.M. Mol. Cell. Proteomics 11:M111.015156.01-M111.015156.17(2012) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH MYBBP1A; SMARCA5 AND BAZ1B, MUTAGENESIS OF SER-111.
[13]	"SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation." Barber M.F., Michishita-Kioi E., Xi Y., Tasselli L., Kioi M., Moqtaderi Z., Tennen R.I., Paredes S., Young N.L., Chen K., Struhl K., Garcia B.A., Gozani O., Li W., Chua K.F. Nature 487:114-118(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH ELK4, MUTAGENESIS OF HIS-187.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF233395 mRNA. Translation: AAF43431.1. AK002027 mRNA. Translation: BAA92044.1. AK094326 mRNA. Translation: BAG52860.1. AK290265 mRNA. Translation: BAF82954.1. AC145207 Genomic DNA. No translation available. BC017305 mRNA. Translation: AAH17305.1. BC101791 mRNA. Translation: AAI01792.1. BC101793 mRNA. Translation: AAI01794.1. AL137626 mRNA. Translation: CAB70848.2. Sequence problems.
IPI	IPI00334648. IPI00383601.
PIR	T46324.
RefSeq	NP_057622.1. NM_016538.2.
UniGene	Hs.514636.
3D structure databases
ProteinModelPortal	Q9NRC8.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-59906N.
IntAct	Q9NRC8. 2 interactions.
MINT	MINT-1424083.
STRING	9606.ENSP00000329466.
Polymorphism databases
DMDM	38258650.
Proteomic databases
PaxDb	Q9NRC8.
PRIDE	Q9NRC8.
Protocols and materials databases
DNASU	51547.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000328666; ENSP00000329466; ENSG00000187531.
GeneID	51547.
KEGG	hsa:51547.
UCSC	uc002kcj.2. human.
Organism-specific databases
CTD	51547.
GeneCards	GC17M079869.
HGNC	HGNC:14935. SIRT7.
HPA	CAB037261.
MIM	606212. gene.
neXtProt	NX_Q9NRC8.
PharmGKB	PA37940.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0846.
HOGENOM	HOG000231240.
HOVERGEN	HBG060028.
InParanoid	Q9NRC8.
KO	K11417.
OMA	WFGRGCA.
OrthoDB	EOG4FN4HW.
PhylomeDB	Q9NRC8.
Enzyme and pathway databases
Pathway_Interaction_DB	hdac_classi_pathway. Signaling events mediated by HDAC Class I. hdac_classiii_pathway. Signaling events mediated by HDAC Class III.
Gene expression databases
ArrayExpress	Q9NRC8.
Bgee	Q9NRC8.
CleanEx	HS_SIRT7.
Genevestigator	Q9NRC8.
GermOnline	ENSG00000187531. Homo sapiens.
Family and domain databases
InterPro	IPR003000. Sirtuin. 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
ChiTaRS	SIRT7. human.
GenomeRNAi	51547.
NextBio	35463912.
SOURCE	Search...

Entry information

Entry name

SIR7_HUMAN

Accession

Primary (citable) accession number: Q9NRC8
Secondary accession number(s): A8K2K0 , B3KSU8, Q3MIK4, Q9NSZ6, Q9NUS6

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 31, 2003
Last sequence update:	October 1, 2000
Last modified:	May 1, 2013
This is version 109 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.