SIR7_HUMAN
ID SIR7_HUMAN Reviewed; 400 AA.
AC Q9NRC8; A8K2K0; B3KSU8; Q3MIK4; Q9NSZ6; Q9NUS6;
DT 31-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=NAD-dependent protein deacetylase sirtuin-7;
DE EC=2.3.1.286 {ECO:0000269|PubMed:24207024, ECO:0000269|PubMed:26867678, ECO:0000269|PubMed:28426094, ECO:0000269|PubMed:28886238, ECO:0000269|PubMed:30540930, ECO:0000269|PubMed:31075303};
DE AltName: Full=NAD-dependent protein deacylase sirtuin-7;
DE EC=2.3.1.- {ECO:0000269|PubMed:27436229, ECO:0000269|PubMed:31542297};
DE AltName: Full=Regulatory protein SIR2 homolog 7;
DE AltName: Full=SIR2-like protein 7;
GN Name=SIRT7 {ECO:0000303|PubMed:22722849, ECO:0000312|HGNC:HGNC:14935};
GN Synonyms=SIR2L7;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Spleen;
RX PubMed=10873683; DOI=10.1006/bbrc.2000.3000;
RA Frye R.A.;
RT "Phylogenetic classification of prokaryotic and eukaryotic Sir-2 like
RT proteins.";
RL Biochem. Biophys. Res. Commun. 273:793-798(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Cerebellum, Colon, and Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Liver, and Lymph;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 128-400 (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=11953824; DOI=10.1038/sj.bjc.6600156;
RA de Nigris F., Cerutti J., Morelli C., Califano D., Chiariotti L.,
RA Viglietto G., Santelli G., Fusco A.;
RT "Isolation of a SIR-like gene, SIR-T8, that is overexpressed in thyroid
RT carcinoma cell lines and tissues.";
RL Br. J. Cancer 86:917-923(2002).
RN [7]
RP ERRATUM OF PUBMED:11953824.
RX PubMed=12454780; DOI=10.1038/sj.bjc.6600636;
RA De Nigris F., Cerutti J., Morelli C., Califano D., Chiariotti L.,
RA Viglietto G., Santelli G., Fusco A.;
RL Br. J. Cancer 87:1479-1479(2002).
RN [8]
RP SHOWS THAT SIR-T8 IS SIRT7.
RX PubMed=12454781; DOI=10.1038/sj.bjc.6600635;
RA Frye R.A.;
RT "'SIRT8' expressed in thyroid cancer is actually SIRT7.";
RL Br. J. Cancer 87:0-0(2002).
RN [9]
RP SUBCELLULAR LOCATION.
RX PubMed=16079181; DOI=10.1091/mbc.e05-01-0033;
RA Michishita E., Park J.Y., Burneskis J.M., Barrett J.C., Horikawa I.;
RT "Evolutionarily conserved and nonconserved cellular localizations and
RT functions of human SIRT proteins.";
RL Mol. Biol. Cell 16:4623-4635(2005).
RN [10]
RP FUNCTION, IDENTIFICATION IN A RNA POLYMERASE I COMPLEX, ACTIVE SITE,
RP INTERACTION WITH HISTONE H2A AND/OR HISTONE H2B, MUTAGENESIS OF SER-111 AND
RP HIS-187, AND SUBCELLULAR LOCATION.
RX PubMed=16618798; DOI=10.1101/gad.1399706;
RA Ford E., Voit R., Liszt G., Magin C., Grummt I., Guarente L.;
RT "Mammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I
RT transcription.";
RL Genes Dev. 20:1075-1080(2006).
RN [11]
RP FUNCTION, INTERACTION WITH UBTF, PHOSPHORYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=19174463; DOI=10.1242/jcs.042382;
RA Grob A., Roussel P., Wright J.E., McStay B., Hernandez-Verdun D., Sirri V.;
RT "Involvement of SIRT7 in resumption of rDNA transcription at the exit from
RT mitosis.";
RL J. Cell Sci. 122:489-498(2009).
RN [12]
RP SUBCELLULAR LOCATION, INTERACTION WITH MYBBP1A; SMARCA5 AND BAZ1B, AND
RP MUTAGENESIS OF SER-111.
RX PubMed=22586326; DOI=10.1074/mcp.a111.015156;
RA Tsai Y.C., Greco T.M., Boonmee A., Miteva Y., Cristea I.M.;
RT "Functional proteomics establishes the interaction of SIRT7 with chromatin
RT remodeling complexes and expands its role in regulation of RNA polymerase I
RT transcription.";
RL Mol. Cell. Proteomics 11:M111.015156.01-M111.015156.17(2012).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, SUBCELLULAR LOCATION,
RP INTERACTION WITH ELK4, AND MUTAGENESIS OF HIS-187.
RX PubMed=22722849; DOI=10.1038/nature11043;
RA Barber M.F., Michishita-Kioi E., Xi Y., Tasselli L., Kioi M., Moqtaderi Z.,
RA Tennen R.I., Paredes S., Young N.L., Chen K., Struhl K., Garcia B.A.,
RA Gozani O., Li W., Chua K.F.;
RT "SIRT7 links H3K18 deacetylation to maintenance of oncogenic
RT transformation.";
RL Nature 487:114-118(2012).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=24207024; DOI=10.1016/j.molcel.2013.10.010;
RA Chen S., Seiler J., Santiago-Reichelt M., Felbel K., Grummt I., Voit R.;
RT "Repression of RNA polymerase I upon stress is caused by inhibition of RNA-
RT dependent deacetylation of PAF53 by SIRT7.";
RL Mol. Cell 52:303-313(2013).
RN [15]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-388, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [16]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=26907567; DOI=10.1021/acschembio.5b01084;
RA Tong Z., Wang Y., Zhang X., Kim D.D., Sadhukhan S., Hao Q., Lin H.;
RT "SIRT7 is activated by DNA and deacetylates histone H3 in the chromatin
RT context.";
RL ACS Chem. Biol. 11:742-747(2016).
RN [17]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, AND MUTAGENESIS OF HIS-187.
RX PubMed=26867678; DOI=10.1038/ncomms10734;
RA Chen S., Blank M.F., Iyer A., Huang B., Wang L., Grummt I., Voit R.;
RT "SIRT7-dependent deacetylation of the U3-55k protein controls pre-rRNA
RT processing.";
RL Nat. Commun. 7:10734-10734(2016).
RN [18]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP SER-111 AND HIS-187.
RX PubMed=27436229; DOI=10.1038/ncomms12235;
RA Li L., Shi L., Yang S., Yan R., Zhang D., Yang J., He L., Li W., Yi X.,
RA Sun L., Liang J., Cheng Z., Shi L., Shang Y., Yu W.;
RT "SIRT7 is a histone desuccinylase that functionally links to chromatin
RT compaction and genome stability.";
RL Nat. Commun. 7:12235-12235(2016).
RN [19]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=27997115; DOI=10.1021/acschembio.6b00954;
RA Tong Z., Wang M., Wang Y., Kim D.D., Grenier J.K., Cao J., Sadhukhan S.,
RA Hao Q., Lin H.;
RT "SIRT7 is an RNA-activated protein lysine deacylase.";
RL ACS Chem. Biol. 12:300-310(2017).
RN [20]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=28147277; DOI=10.1016/j.celrep.2017.01.009;
RA Yu J., Qin B., Wu F., Qin S., Nowsheen S., Shan S., Zayas J., Pei H.,
RA Lou Z., Wang L.;
RT "Regulation of serine-threonine kinase Akt activation by NAD+-dependent
RT deacetylase SIRT7.";
RL Cell Rep. 18:1229-1240(2017).
RN [21]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP SER-111.
RX PubMed=28886238; DOI=10.1111/febs.14259;
RA Mo Y., Lin R., Liu P., Tan M., Xiong Y., Guan K.L., Yuan H.X.;
RT "SIRT7 deacetylates DDB1 and suppresses the activity of the CRL4 E3 ligase
RT complexes.";
RL FEBS J. 284:3619-3636(2017).
RN [22]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=28790157; DOI=10.1101/gad.300624.117;
RA Song C., Hotz-Wagenblatt A., Voit R., Grummt I.;
RT "SIRT7 and the DEAD-box helicase DDX21 cooperate to resolve genomic R loops
RT and safeguard genome stability.";
RL Genes Dev. 31:1370-1381(2017).
RN [23]
RP UBIQUITINATION, DEUBIQUITINATION BY USP7, AND ACTIVITY REGULATION.
RX PubMed=28655758; DOI=10.1074/jbc.m117.780130;
RA Jiang L., Xiong J., Zhan J., Yuan F., Tang M., Zhang C., Cao Z., Chen Y.,
RA Lu X., Li Y., Wang H., Wang L., Wang J., Zhu W.G., Wang H.;
RT "Ubiquitin-specific peptidase 7 (USP7)-mediated deubiquitination of the
RT histone deacetylase SIRT7 regulates gluconeogenesis.";
RL J. Biol. Chem. 292:13296-13311(2017).
RN [24]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=28426094; DOI=10.1093/nar/gkx053;
RA Blank M.F., Chen S., Poetz F., Schnoelzer M., Voit R., Grummt I.;
RT "SIRT7-dependent deacetylation of CDK9 activates RNA polymerase II
RT transcription.";
RL Nucleic Acids Res. 45:2675-2686(2017).
RN [25]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=30540930; DOI=10.1016/j.celrep.2018.11.051;
RA Iyer-Bierhoff A., Krogh N., Tessarz P., Ruppert T., Nielsen H., Grummt I.;
RT "SIRT7-dependent deacetylation of fibrillarin controls histone H2A
RT methylation and rRNA synthesis during the cell cycle.";
RL Cell Rep. 25:2946-2954(2018).
RN [26]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION,
RP METHYLATION AT ARG-388, AND MUTAGENESIS OF ARG-388.
RX PubMed=30420520; DOI=10.15252/embr.201846377;
RA Yan W.W., Liang Y.L., Zhang Q.X., Wang D., Lei M.Z., Qu J., He X.H.,
RA Lei Q.Y., Wang Y.P.;
RT "Arginine methylation of SIRT7 couples glucose sensing with mitochondria
RT biogenesis.";
RL EMBO Rep. 19:0-0(2018).
RN [27]
RP FUNCTION.
RX PubMed=29728458; DOI=10.1074/jbc.ac118.003325;
RA Paredes S., Angulo-Ibanez M., Tasselli L., Carlson S.M., Zheng W., Li T.M.,
RA Chua K.F.;
RT "The epigenetic regulator SIRT7 guards against mammalian cellular
RT senescence induced by ribosomal DNA instability.";
RL J. Biol. Chem. 293:11242-11250(2018).
RN [28]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=31075303; DOI=10.1016/j.bbamcr.2019.05.001;
RA Sobuz S.U., Sato Y., Yoshizawa T., Karim F., Ono K., Sawa T., Miyamoto Y.,
RA Oka M., Yamagata K.;
RT "SIRT7 regulates the nuclear export of NF-kappaB p65 by deacetylating
RT Ran.";
RL Biochim. Biophys. Acta 1866:1355-1367(2019).
RN [29]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=30653310; DOI=10.1021/jacs.8b12083;
RA Wang W.W., Angulo-Ibanez M., Lyu J., Kurra Y., Tong Z., Wu B., Zhang L.,
RA Sharma V., Zhou J., Lin H., Gao Y.Q., Li W., Chua K.F., Liu W.R.;
RT "A click chemistry approach reveals the chromatin-dependent histone H3K36
RT deacylase nature of SIRT7.";
RL J. Am. Chem. Soc. 141:2462-2473(2019).
RN [30]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=31542297; DOI=10.1016/j.molcel.2019.08.018;
RA Bao X., Liu Z., Zhang W., Gladysz K., Fung Y.M.E., Tian G., Xiong Y.,
RA Wong J.W.H., Yuen K.W.Y., Li X.D.;
RT "Glutarylation of histone H4 lysine 91 regulates chromatin dynamics.";
RL Mol. Cell 0:0-0(2019).
RN [31]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=31226208; DOI=10.1093/nar/gkz519;
RA Vazquez B.N., Thackray J.K., Simonet N.G., Chahar S., Kane-Goldsmith N.,
RA Newkirk S.J., Lee S., Xing J., Verzi M.P., An W., Vaquero A.,
RA Tischfield J.A., Serrano L.;
RT "SIRT7 mediates L1 elements transcriptional repression and their
RT association with the nuclear lamina.";
RL Nucleic Acids Res. 47:7870-7885(2019).
RN [32]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, ACTIVE SITE, AND
RP MUTAGENESIS OF HIS-187.
RX PubMed=30944854; DOI=10.1126/sciadv.aav1118;
RA Tang M., Li Z., Zhang C., Lu X., Tu B., Cao Z., Li Y., Chen Y., Jiang L.,
RA Wang H., Wang L., Wang J., Liu B., Xu X., Wang H., Zhu W.G.;
RT "SIRT7-mediated ATM deacetylation is essential for its deactivation and DNA
RT damage repair.";
RL Sci. Adv. 5:EAAV1118-EAAV1118(2019).
RN [33] {ECO:0007744|PDB:5IQZ}
RP X-RAY CRYSTALLOGRAPHY (2.33 ANGSTROMS) OF 5-73.
RX PubMed=27287224; DOI=10.1002/prot.25085;
RA Priyanka A., Solanki V., Parkesh R., Thakur K.G.;
RT "Crystal structure of the N-terminal domain of human SIRT7 reveals a three-
RT helical domain architecture.";
RL Proteins 84:1558-1563(2016).
CC -!- FUNCTION: NAD-dependent protein-lysine deacylase that can act both as a
CC deacetylase or deacylase (desuccinylase, depropionylase and
CC deglutarylase), depending on the context (PubMed:22722849,
CC PubMed:26907567, PubMed:30653310, PubMed:31542297). Specifically
CC mediates deacetylation of histone H3 at 'Lys-18' (H3K18Ac)
CC (PubMed:22722849, PubMed:30420520). In contrast to other histone
CC deacetylases, displays strong preference for a specific histone mark,
CC H3K18Ac, directly linked to control of gene expression
CC (PubMed:22722849, PubMed:30653310). H3K18Ac is mainly present around
CC the transcription start site of genes and has been linked to activation
CC of nuclear hormone receptors; SIRT7 thereby acts as a transcription
CC repressor (PubMed:22722849). Moreover, H3K18 hypoacetylation has been
CC reported as a marker of malignancy in various cancers and seems to
CC maintain the transformed phenotype of cancer cells (PubMed:22722849).
CC Also able to mediate deacetylation of histone H3 at 'Lys-36' (H3K36Ac)
CC in the context of nucleosomes (PubMed:30653310). Also mediates
CC deacetylation of non-histone proteins, such as ATM, CDK9, DDX21, DDB1,
CC FBL, FKBP5/FKBP51, GABPB1, RAN, RRP9/U3-55K and POLR1E/PAF53
CC (PubMed:24207024, PubMed:26867678, PubMed:28147277, PubMed:28886238,
CC PubMed:28426094, PubMed:30540930, PubMed:31075303, PubMed:30944854,
CC PubMed:28790157). Enriched in nucleolus where it stimulates
CC transcription activity of the RNA polymerase I complex
CC (PubMed:16618798, PubMed:19174463, PubMed:24207024). Acts by mediating
CC the deacetylation of the RNA polymerase I subunit POLR1E/PAF53, thereby
CC promoting the association of RNA polymerase I with the rDNA promoter
CC region and coding region (PubMed:16618798, PubMed:19174463,
CC PubMed:24207024). In response to metabolic stress, SIRT7 is released
CC from nucleoli leading to hyperacetylation of POLR1E/PAF53 and decreased
CC RNA polymerase I transcription (PubMed:24207024). Required to restore
CC the transcription of ribosomal RNA (rRNA) at the exit from mitosis
CC (PubMed:19174463). Promotes pre-ribosomal RNA (pre-rRNA) cleavage at
CC the 5'-terminal processing site by mediating deacetylation of RRP9/U3-
CC 55K, a core subunit of the U3 snoRNP complex (PubMed:26867678).
CC Mediates 'Lys-37' deacetylation of Ran, thereby regulating the nuclear
CC export of NF-kappa-B subunit RELA/p65 (PubMed:31075303). Acts as a
CC regulator of DNA damage repair by mediating deacetylation of ATM during
CC the late stages of DNA damage response, promoting ATM dephosphorylation
CC and deactivation (PubMed:30944854). Suppresses the activity of the DCX
CC (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes by mediating
CC deacetylation of DDB1, which prevents the interaction between DDB1 and
CC CUL4 (CUL4A or CUL4B) (PubMed:28886238). Activates RNA polymerase II
CC transcription by mediating deacetylation of CDK9, thereby promoting
CC 'Ser-2' phosphorylation of the C-terminal domain (CTD) of RNA
CC polymerase II (PubMed:28426094). Deacetylates FBL, promoting histone-
CC glutamine methyltransferase activity of FBL (PubMed:30540930). Acts as
CC a regulator of mitochondrial function by catalyzing deacetylation of
CC GABPB1 (By similarity). Regulates Akt/AKT1 activity by mediating
CC deacetylation of FKBP5/FKBP51 (PubMed:28147277). Required to prevent R-
CC loop-associated DNA damage and transcription-associated genomic
CC instability by mediating deacetylation and subsequent activation of
CC DDX21, thereby overcoming R-loop-mediated stalling of RNA polymerases
CC (PubMed:28790157). In addition to protein deacetylase activity, also
CC acts as protein-lysine deacylase (PubMed:27436229, PubMed:27997115,
CC PubMed:31542297). Acts as a protein depropionylase by mediating
CC depropionylation of Osterix (SP7), thereby regulating bone formation by
CC osteoblasts (By similarity). Acts as a histone deglutarylase by
CC mediating deglutarylation of histone H4 on 'Lys-91' (H4K91glu); a mark
CC that destabilizes nucleosomes by promoting dissociation of the H2A-H2B
CC dimers from nucleosomes (PubMed:31542297). Acts as a histone
CC desuccinylase: in response to DNA damage, recruited to DNA double-
CC strand breaks (DSBs) and catalyzes desuccinylation of histone H3 on
CC 'Lys-122' (H3K122succ), thereby promoting chromatin condensation and
CC DSB repair (PubMed:27436229). Also promotes DSB repair by promoting
CC H3K18Ac deacetylation, regulating non-homologous end joining (NHEJ) (By
CC similarity). Along with its role in DNA repair, required for chromosome
CC synapsis during prophase I of female meiosis by catalyzing H3K18Ac
CC deacetylation (By similarity). Involved in transcriptional repression
CC of LINE-1 retrotransposon via H3K18Ac deacetylation, and promotes their
CC association with the nuclear lamina (PubMed:31226208). Required to
CC stabilize ribosomal DNA (rDNA) heterochromatin and prevent cellular
CC senescence induced by rDNA instability (PubMed:29728458). Acts as a
CC negative regulator of SIRT1 by preventing autodeacetylation of SIRT1,
CC restricting SIRT1 deacetylase activity (By similarity).
CC {ECO:0000250|UniProtKB:Q8BKJ9, ECO:0000269|PubMed:16618798,
CC ECO:0000269|PubMed:19174463, ECO:0000269|PubMed:22722849,
CC ECO:0000269|PubMed:24207024, ECO:0000269|PubMed:26867678,
CC ECO:0000269|PubMed:26907567, ECO:0000269|PubMed:27436229,
CC ECO:0000269|PubMed:27997115, ECO:0000269|PubMed:28147277,
CC ECO:0000269|PubMed:28426094, ECO:0000269|PubMed:28790157,
CC ECO:0000269|PubMed:28886238, ECO:0000269|PubMed:29728458,
CC ECO:0000269|PubMed:30420520, ECO:0000269|PubMed:30540930,
CC ECO:0000269|PubMed:30653310, ECO:0000269|PubMed:30944854,
CC ECO:0000269|PubMed:31075303, ECO:0000269|PubMed:31226208,
CC ECO:0000269|PubMed:31542297}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-acetyl-L-lysyl-[protein] + NAD(+) = 2''-O-acetyl-
CC ADP-D-ribose + L-lysyl-[protein] + nicotinamide;
CC Xref=Rhea:RHEA:43636, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10731,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:61930, ChEBI:CHEBI:83767;
CC EC=2.3.1.286; Evidence={ECO:0000255|PROSITE-ProRule:PRU00236,
CC ECO:0000269|PubMed:22722849, ECO:0000269|PubMed:24207024,
CC ECO:0000269|PubMed:26867678, ECO:0000269|PubMed:26907567,
CC ECO:0000269|PubMed:28147277, ECO:0000269|PubMed:28426094,
CC ECO:0000269|PubMed:28790157, ECO:0000269|PubMed:28886238,
CC ECO:0000269|PubMed:30420520, ECO:0000269|PubMed:30540930,
CC ECO:0000269|PubMed:30653310, ECO:0000269|PubMed:30944854,
CC ECO:0000269|PubMed:31075303};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43637;
CC Evidence={ECO:0000269|PubMed:22722849, ECO:0000269|PubMed:26867678,
CC ECO:0000269|PubMed:26907567, ECO:0000269|PubMed:28147277,
CC ECO:0000269|PubMed:28426094, ECO:0000269|PubMed:28790157,
CC ECO:0000269|PubMed:28886238, ECO:0000269|PubMed:30420520,
CC ECO:0000269|PubMed:30540930, ECO:0000269|PubMed:30653310,
CC ECO:0000269|PubMed:30944854, ECO:0000269|PubMed:31075303};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-glutaryl-L-lysyl-[protein] + NAD(+) = 2''-O-
CC glutaryl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide;
CC Xref=Rhea:RHEA:47664, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:11875,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:87828, ChEBI:CHEBI:87829;
CC Evidence={ECO:0000269|PubMed:31542297};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47665;
CC Evidence={ECO:0000269|PubMed:31542297};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-succinyl-L-lysyl-[protein] + NAD(+) = 2''-O-
CC succinyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide;
CC Xref=Rhea:RHEA:47668, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:11877,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:87830, ChEBI:CHEBI:87832;
CC Evidence={ECO:0000269|PubMed:27436229};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47669;
CC Evidence={ECO:0000269|PubMed:27436229};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-propanoyl-L-lysyl-[protein] + NAD(+) = 3''-O-
CC propanoyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide;
CC Xref=Rhea:RHEA:23500, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:13758,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:138019, ChEBI:CHEBI:145015;
CC Evidence={ECO:0000250|UniProtKB:Q8BKJ9};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23501;
CC Evidence={ECO:0000250|UniProtKB:Q8BKJ9};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q9NXA8};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q9NXA8};
CC -!- ACTIVITY REGULATION: NAD-dependent protein-lysine deacetylase and
CC deacylase activities are activated by nucleic acids (PubMed:26907567,
CC PubMed:27997115). Histone deacetylase activity is activated by DNA
CC (PubMed:27997115). Protein-lysine deacylase activity is activated by
CC RNA (PubMed:26907567). H3K18Ac histone deacetylase activity is
CC inhibited by methylation at Arg-388 (PubMed:30420520). H3K18Ac histone
CC deacetylase activity is inhibited by deubiquitination by USP7
CC (PubMed:28655758). {ECO:0000269|PubMed:26907567,
CC ECO:0000269|PubMed:27997115, ECO:0000269|PubMed:28655758,
CC ECO:0000269|PubMed:30420520}.
CC -!- SUBUNIT: Interacts with UBTF and the RNA polymerase I complex
CC (PubMed:16618798, PubMed:19174463). Interacts with components of the B-
CC WICH complex, such as MYBBP1A, SMARCA5/SNF2H and BAZ1B/WSTF
CC (PubMed:22586326). Interacts with ELK4, leading to stabilization at
CC target promoters for H3K18Ac deacetylation (PubMed:22722849). Interacts
CC with histone H2A and/or histone H2B (PubMed:22722849). Interacts with
CC DNMT1 (By similarity). Interacts with SIRT1 (By similarity).
CC {ECO:0000250|UniProtKB:Q8BKJ9, ECO:0000269|PubMed:16618798,
CC ECO:0000269|PubMed:19174463, ECO:0000269|PubMed:22586326,
CC ECO:0000269|PubMed:22722849}.
CC -!- INTERACTION:
CC Q9NRC8; P28324: ELK4; NbExp=3; IntAct=EBI-716046, EBI-11277718;
CC Q9NRC8; Q16656: NRF1; NbExp=2; IntAct=EBI-716046, EBI-2547810;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:16079181,
CC ECO:0000269|PubMed:19174463, ECO:0000269|PubMed:24207024,
CC ECO:0000269|PubMed:28426094, ECO:0000269|PubMed:28790157,
CC ECO:0000269|PubMed:28886238, ECO:0000269|PubMed:30420520}. Nucleus,
CC nucleoplasm {ECO:0000269|PubMed:24207024, ECO:0000269|PubMed:28790157,
CC ECO:0000269|PubMed:28886238, ECO:0000269|PubMed:31075303}. Chromosome
CC {ECO:0000269|PubMed:27436229, ECO:0000269|PubMed:31226208}. Cytoplasm
CC {ECO:0000269|PubMed:11953824}. Note=Mainly localizes in the nucleolus
CC and nucleoplasm (PubMed:24207024, PubMed:28886238, PubMed:28790157,
CC PubMed:31075303). Associated with rDNA promoter and transcribed region
CC (PubMed:16079181, PubMed:19174463). Associated with nucleolar organizer
CC regions during mitosis (PubMed:16079181, PubMed:19174463). In response
CC to stress, released from nucleolus to nucleoplasm (PubMed:24207024).
CC Associated with chromatin (PubMed:22722849). In response to DNA damage,
CC recruited to DNA double-strand breaks (DSBs) sites (PubMed:27436229)
CC (Probable). Located close to the nuclear membrane when in the cytoplasm
CC (PubMed:11953824). {ECO:0000269|PubMed:11953824,
CC ECO:0000269|PubMed:16079181, ECO:0000269|PubMed:19174463,
CC ECO:0000269|PubMed:22722849, ECO:0000269|PubMed:24207024,
CC ECO:0000269|PubMed:27436229, ECO:0000269|PubMed:28790157,
CC ECO:0000269|PubMed:28886238, ECO:0000269|PubMed:31075303,
CC ECO:0000305|PubMed:30944854}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9NRC8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NRC8-2; Sequence=VSP_008736, VSP_008737;
CC Name=3;
CC IsoId=Q9NRC8-3; Sequence=VSP_044396, VSP_044397;
CC -!- INDUCTION: Overexpressed in thyroid carcinoma cell lines and tissues,
CC but not in adenomas. {ECO:0000269|PubMed:11953824}.
CC -!- PTM: Phosphorylated during mitosis. {ECO:0000305|PubMed:19174463}.
CC -!- PTM: Methylation at Arg-388 by PRMT6 inhibits the H3K18Ac histone
CC deacetylase activity, promoting mitochondria biogenesis and maintaining
CC mitochondria respiration. {ECO:0000269|PubMed:30420520}.
CC -!- PTM: Ubiquitinated via 'Lys-63'-linked ubiquitin chains
CC (PubMed:28655758). Deubiquitinated by USP7, inhibiting the H3K18Ac
CC histone deacetylase activity and regulating gluconeogenesis
CC (PubMed:28655758). {ECO:0000269|PubMed:28655758}.
CC -!- SIMILARITY: Belongs to the sirtuin family. Class IV subfamily.
CC {ECO:0000305}.
CC -!- CAUTION: Was originally termed SIR-T8/SIRT8 (PubMed:11953824). This was
CC later retracted (PubMed:12454780, PubMed:12454781).
CC {ECO:0000303|PubMed:11953824, ECO:0000303|PubMed:12454780,
CC ECO:0000303|PubMed:12454781}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAB70848.2; Type=Miscellaneous discrepancy; Evidence={ECO:0000305};
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DR EMBL; AF233395; AAF43431.1; -; mRNA.
DR EMBL; AK002027; BAA92044.1; -; mRNA.
DR EMBL; AK094326; BAG52860.1; -; mRNA.
DR EMBL; AK290265; BAF82954.1; -; mRNA.
DR EMBL; AC145207; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC017305; AAH17305.1; -; mRNA.
DR EMBL; BC101791; AAI01792.1; -; mRNA.
DR EMBL; BC101793; AAI01794.1; -; mRNA.
DR EMBL; AL137626; CAB70848.2; ALT_SEQ; mRNA.
DR CCDS; CCDS11792.1; -. [Q9NRC8-1]
DR PIR; T46324; T46324.
DR RefSeq; NP_057622.1; NM_016538.2. [Q9NRC8-1]
DR PDB; 5IQZ; X-ray; 2.33 A; A=5-73.
DR PDB; 6G0S; X-ray; 1.48 A; D=269-279.
DR PDBsum; 5IQZ; -.
DR PDBsum; 6G0S; -.
DR AlphaFoldDB; Q9NRC8; -.
DR SMR; Q9NRC8; -.
DR BioGRID; 119602; 740.
DR DIP; DIP-59906N; -.
DR IntAct; Q9NRC8; 10.
DR STRING; 9606.ENSP00000329466; -.
DR BindingDB; Q9NRC8; -.
DR ChEMBL; CHEMBL2163184; -.
DR GlyGen; Q9NRC8; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q9NRC8; -.
DR PhosphoSitePlus; Q9NRC8; -.
DR BioMuta; SIRT7; -.
DR DMDM; 38258650; -.
DR EPD; Q9NRC8; -.
DR jPOST; Q9NRC8; -.
DR MassIVE; Q9NRC8; -.
DR MaxQB; Q9NRC8; -.
DR PaxDb; Q9NRC8; -.
DR PeptideAtlas; Q9NRC8; -.
DR PRIDE; Q9NRC8; -.
DR ProteomicsDB; 82334; -. [Q9NRC8-1]
DR ProteomicsDB; 82335; -. [Q9NRC8-2]
DR ABCD; Q9NRC8; 1 sequenced antibody.
DR Antibodypedia; 19848; 506 antibodies from 42 providers.
DR DNASU; 51547; -.
DR Ensembl; ENST00000328666.11; ENSP00000329466.6; ENSG00000187531.14. [Q9NRC8-1]
DR GeneID; 51547; -.
DR KEGG; hsa:51547; -.
DR MANE-Select; ENST00000328666.11; ENSP00000329466.6; NM_016538.3; NP_057622.1.
DR UCSC; uc002kcj.3; human. [Q9NRC8-1]
DR CTD; 51547; -.
DR DisGeNET; 51547; -.
DR GeneCards; SIRT7; -.
DR HGNC; HGNC:14935; SIRT7.
DR HPA; ENSG00000187531; Low tissue specificity.
DR MIM; 606212; gene.
DR neXtProt; NX_Q9NRC8; -.
DR OpenTargets; ENSG00000187531; -.
DR PharmGKB; PA37940; -.
DR VEuPathDB; HostDB:ENSG00000187531; -.
DR eggNOG; KOG1905; Eukaryota.
DR GeneTree; ENSGT00940000159703; -.
DR HOGENOM; CLU_023643_6_2_1; -.
DR InParanoid; Q9NRC8; -.
DR OMA; HFGERGI; -.
DR OrthoDB; 1459156at2759; -.
DR PhylomeDB; Q9NRC8; -.
DR TreeFam; TF106184; -.
DR PathwayCommons; Q9NRC8; -.
DR SignaLink; Q9NRC8; -.
DR SIGNOR; Q9NRC8; -.
DR BioGRID-ORCS; 51547; 33 hits in 1100 CRISPR screens.
DR ChiTaRS; SIRT7; human.
DR GeneWiki; SIRT7; -.
DR GenomeRNAi; 51547; -.
DR Pharos; Q9NRC8; Tbio.
DR PRO; PR:Q9NRC8; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9NRC8; protein.
DR Bgee; ENSG00000187531; Expressed in lower esophagus mucosa and 167 other tissues.
DR ExpressionAtlas; Q9NRC8; baseline and differential.
DR Genevisible; Q9NRC8; HS.
DR GO; GO:0000785; C:chromatin; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005731; C:nucleolus organizer region; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0035861; C:site of double-strand break; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0019213; F:deacetylase activity; IBA:GO_Central.
DR GO; GO:0004407; F:histone deacetylase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070403; F:NAD+ binding; IEA:InterPro.
DR GO; GO:0097372; F:NAD-dependent histone deacetylase activity (H3-K18 specific); IDA:UniProtKB.
DR GO; GO:0034979; F:NAD-dependent protein deacetylase activity; IDA:UniProtKB.
DR GO; GO:0061697; F:protein-glutaryllysine deglutarylase activity; IDA:UniProtKB.
DR GO; GO:0106231; F:protein-propionyllysine depropionylase activity; ISS:UniProtKB.
DR GO; GO:0036055; F:protein-succinyllysine desuccinylase activity; IDA:UniProtKB.
DR GO; GO:0003714; F:transcription corepressor activity; IBA:GO_Central.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:1990258; P:histone glutamine methylation; IDA:UniProtKB.
DR GO; GO:0070932; P:histone H3 deacetylation; IDA:UniProtKB.
DR GO; GO:0016570; P:histone modification; IDA:UniProtKB.
DR GO; GO:0007129; P:homologous chromosome pairing at meiosis; ISS:UniProtKB.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0010529; P:negative regulation of transposition; ISS:UniProtKB.
DR GO; GO:0001649; P:osteoblast differentiation; ISS:UniProtKB.
DR GO; GO:0036049; P:peptidyl-lysine desuccinylation; IDA:UniProtKB.
DR GO; GO:2000234; P:positive regulation of rRNA processing; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0007072; P:positive regulation of transcription involved in exit from mitosis; IMP:UniProtKB.
DR GO; GO:0006476; P:protein deacetylation; IDA:UniProtKB.
DR GO; GO:0061698; P:protein deglutarylation; IDA:UniProtKB.
DR GO; GO:0106230; P:protein depropionylation; ISS:UniProtKB.
DR GO; GO:0062176; P:R-loop disassembly; IDA:UniProtKB.
DR GO; GO:0006282; P:regulation of DNA repair; IDA:UniProtKB.
DR GO; GO:2001032; P:regulation of double-strand break repair via nonhomologous end joining; ISS:UniProtKB.
DR GO; GO:0006111; P:regulation of gluconeogenesis; IMP:UniProtKB.
DR GO; GO:0010821; P:regulation of mitochondrion organization; IMP:UniProtKB.
DR GO; GO:0046825; P:regulation of protein export from nucleus; ISS:UniProtKB.
DR GO; GO:1901836; P:regulation of transcription of nucleolar large rRNA by RNA polymerase I; IDA:UniProtKB.
DR GO; GO:0009303; P:rRNA transcription; IMP:UniProtKB.
DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
DR InterPro; IPR003000; Sirtuin.
DR InterPro; IPR026590; Ssirtuin_cat_dom.
DR Pfam; PF02146; SIR2; 1.
DR SUPFAM; SSF52467; SSF52467; 1.
DR PROSITE; PS50305; SIRTUIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chromatin regulator; Chromosome;
KW Cytoplasm; DNA damage; DNA repair; Metal-binding; Methylation; NAD;
KW Nucleus; Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Transferase; Ubl conjugation; Zinc.
FT CHAIN 1..400
FT /note="NAD-dependent protein deacetylase sirtuin-7"
FT /id="PRO_0000110271"
FT DOMAIN 90..331
FT /note="Deacetylase sirtuin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 354..380
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 9..27
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 354..369
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 187
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:16618798,
FT ECO:0000269|PubMed:22722849, ECO:0000269|PubMed:26867678,
FT ECO:0000269|PubMed:30944854"
FT BINDING 107..126
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9NXA8"
FT BINDING 167..170
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9NXA8"
FT BINDING 195
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 198
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 225
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 228
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 268..270
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9NXA8"
FT BINDING 297..299
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9NXA8"
FT BINDING 315
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9NXA8"
FT MOD_RES 388
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000269|PubMed:30420520"
FT MOD_RES 388
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000269|PubMed:30420520,
FT ECO:0007744|PubMed:24129315"
FT VAR_SEQ 1..30
FT /note="MAAGGLSRSERKAAERVRRLREEQQRERLR -> MPGPRRRSPSACP (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044396"
FT VAR_SEQ 162..183
FT /note="QHVVSQNCDGLHLRSGLPRTAI -> RALGGWYTCQGPGRAPWCPVGN (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_008736"
FT VAR_SEQ 184..400
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_008737"
FT VAR_SEQ 336..400
FT /note="WQDPIFSLATPLRAGEEGSHSRKSLCRSREEAPPGDRGAPLSSAPILGGWFG
FT RGCTKRTKRKKVT -> VL (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044397"
FT MUTAGEN 111
FT /note="S->A: Catalytically inactive mutant; abolishes
FT activation of pre-rRNA synthesis. Abolishes deacetylation
FT of DDB1. Abolished histone desuccinylase activity; when
FT associated with Y-187."
FT /evidence="ECO:0000269|PubMed:16618798,
FT ECO:0000269|PubMed:22586326, ECO:0000269|PubMed:27436229,
FT ECO:0000269|PubMed:28886238"
FT MUTAGEN 187
FT /note="H->Y: Abolishes deacylase and deacetylase activities
FT and activation of pre-rRNA synthesis. Abolished histone
FT desuccinylase activity; when associated with A-111."
FT /evidence="ECO:0000269|PubMed:16618798,
FT ECO:0000269|PubMed:22722849, ECO:0000269|PubMed:26867678,
FT ECO:0000269|PubMed:27436229, ECO:0000269|PubMed:30944854"
FT MUTAGEN 388
FT /note="R->F: Mimics methylation status; impaired histone
FT deacetylase activity."
FT /evidence="ECO:0000269|PubMed:30420520"
FT MUTAGEN 388
FT /note="R->K: Decreased methylation; does not affect histone
FT deacetylase activity."
FT /evidence="ECO:0000269|PubMed:30420520"
FT CONFLICT 71
FT /note="L -> Q (in Ref. 2; BAG52860)"
FT /evidence="ECO:0000305"
FT CONFLICT 384
FT /note="G -> S (in Ref. 2; BAF82954)"
FT /evidence="ECO:0000305"
FT HELIX 8..37
FT /evidence="ECO:0007829|PDB:5IQZ"
FT HELIX 40..42
FT /evidence="ECO:0007829|PDB:5IQZ"
FT HELIX 45..52
FT /evidence="ECO:0007829|PDB:5IQZ"
FT HELIX 55..60
FT /evidence="ECO:0007829|PDB:5IQZ"
SQ SEQUENCE 400 AA; 44898 MW; 55D7736A864AFE6F CRC64;
MAAGGLSRSE RKAAERVRRL REEQQRERLR QVSRILRKAA AERSAEEGRL LAESADLVTE
LQGRSRRREG LKRRQEEVCD DPEELRGKVR ELASAVRNAK YLVVYTGAGI STAASIPDYR
GPNGVWTLLQ KGRSVSAADL SEAEPTLTHM SITRLHEQKL VQHVVSQNCD GLHLRSGLPR
TAISELHGNM YIEVCTSCVP NREYVRVFDV TERTALHRHQ TGRTCHKCGT QLRDTIVHFG
ERGTLGQPLN WEAATEAASR ADTILCLGSS LKVLKKYPRL WCMTKPPSRR PKLYIVNLQW
TPKDDWAALK LHGKCDDVMR LLMAELGLEI PAYSRWQDPI FSLATPLRAG EEGSHSRKSL
CRSREEAPPG DRGAPLSSAP ILGGWFGRGC TKRTKRKKVT
