ID SP3_HUMAN Reviewed; 781 AA. AC Q02447; A0AVL9; B4E2B7; Q69B26; Q69B27; Q8TD56; Q8WWU4; Q9BQR1; DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot. DT 16-MAY-2003, sequence version 3. DT 24-JAN-2024, entry version 215. DE RecName: Full=Transcription factor Sp3; DE AltName: Full=SPR-2; GN Name=SP3; 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 5), AND VARIANT ALA-164. RX PubMed=12297010; DOI=10.5483/bmbrep.2002.35.3.273; RA Hernandez E.M., Johnson A., Notario V., Chen A., Richert J.R.; RT "AUA as a translation initiation site in vitro for the human transcription RT factor Sp3."; RL J. Biochem. Mol. Biol. 35:273-282(2002). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 6), ALTERNATIVE INITIATION RP (ISOFORMS 2; 3 AND 4), AND VARIANT ALA-164. RX PubMed=15474306; DOI=10.1016/j.gene.2004.06.055; RA Moran K.M., Crusio R.H., Chan C.H., Grekova M.C., Richert J.R.; RT "Human transcription factor Sp3: genomic structure, identification of a RT processed pseudogene, and transcript analysis."; RL Gene 341:235-247(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Trachea; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Lung; 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 [GENOMIC DNA] OF 1-135. RX PubMed=12411611; DOI=10.1093/oxfordjournals.molbev.a004026; RA Oleksiak M.F., Crawford D.L.; RT "5' genomic structure of human Sp3."; RL Mol. Biol. Evol. 19:2026-2029(2002). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 13-112. RA Meyer-Grahle U.; RT "Regulation of hTERT-gene transcription by SP3."; RL Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 71-781, AND SEQUENCE REVISION. RC TISSUE=T-cell; RA Kingsley C., Winoto A.; RL Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 129-781. RX PubMed=1341900; DOI=10.1128/mcb.12.10.4251-4261.1992; RA Kingsley C., Winoto A.; RT "Cloning of GT box-binding proteins: a novel Sp1 multigene family RT regulating T-cell receptor gene expression."; RL Mol. Cell. Biol. 12:4251-4261(1992). RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 85-781, AND VARIANT ALA-164. RC TISSUE=Uterus; RX PubMed=1454515; DOI=10.1093/nar/20.21.5519; RA Hagen G., Mueller S., Beato M., Suske G.; RT "Cloning by recognition site screening of two novel GT box binding RT proteins: a family of Sp1 related genes."; RL Nucleic Acids Res. 20:5519-5525(1992). RN [10] RP FUNCTION. RX PubMed=9278495; DOI=10.1093/nar/25.18.3712; RA Ihn H., Trojanowska M.; RT "Sp3 is a transcriptional activator of the human alpha2(I) collagen gene."; RL Nucleic Acids Res. 25:3712-3717(1997). RN [11] RP FUNCTION, AND INTERACTION WITH HLTF. RX PubMed=10391891; DOI=10.1074/jbc.274.28.19573; RA Ding H., Benotmane A.M., Suske G., Collen D., Belayew A.; RT "Functional interactions between Sp1 or Sp3 and the helicase-like RT transcription factor mediate basal expression from the human plasminogen RT activator inhibitor-1 gene."; RL J. Biol. Chem. 274:19573-19580(1999). RN [12] RP ACETYLATION AT LYS-551, FUNCTION, AND MUTAGENESIS OF 551-LYS--GLU-557. RX PubMed=11812829; DOI=10.1093/nar/29.24.4994; RA Braun H., Koop R., Ertmer A., Nacht S., Suske G.; RT "Transcription factor Sp3 is regulated by acetylation."; RL Nucleic Acids Res. 29:4994-5000(2001). RN [13] RP INTERACTION WITH HDAC1 AND HDAC2. RX PubMed=12176973; DOI=10.1074/jbc.c200378200; RA Sun J.M., Chen H.Y., Moniwa M., Litchfield D.W., Seto E., Davie J.R.; RT "The transcriptional repressor Sp3 is associated with CK2-phosphorylated RT histone deacetylase 2."; RL J. Biol. Chem. 277:35783-35786(2002). RN [14] RP SUMOYLATION AT LYS-120 AND LYS-551, SUBCELLULAR LOCATION, FUNCTION, AND RP MUTAGENESIS OF LYS-120 AND LYS-551. RX PubMed=12419227; DOI=10.1016/s1097-2765(02)00682-2; RA Ross S., Best J.L., Zon L.I., Gill G.; RT "SUMO-1 modification represses Sp3 transcriptional activation and modulates RT its subnuclear localization."; RL Mol. Cell 10:831-842(2002). RN [15] RP INTERACTION WITH HDAC1 AND EP300, ACETYLATION, AND FUNCTION. RX PubMed=12837748; DOI=10.1074/jbc.m305961200; RA Ammanamanchi S., Freeman J.W., Brattain M.G.; RT "Acetylated SP3 is a transcriptional activator."; RL J. Biol. Chem. 278:35775-35780(2003). RN [16] RP SUMOYLATION, ALTERNATIVE PRODUCTS, LACK OF GLYCOSYLATION, AND FUNCTION. RX PubMed=15247228; DOI=10.1074/jbc.m404989200; RA Sapetschnig A., Koch F., Rischitor G., Mennenga T., Suske G.; RT "Complexity of translationally controlled transcription factor Sp3 isoform RT expression."; RL J. Biol. Chem. 279:42095-42105(2004). RN [17] RP SUMOYLATION AT LYS-551, FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP 551-LYS--GLU-553. RX PubMed=15494207; DOI=10.1016/j.cellsig.2004.06.007; RA Spengler M.L., Kennett S.B., Moorefield K.S., Simmons S.O., Brattain M.G., RA Horowitz J.M.; RT "Sumoylation of internally initiated Sp3 isoforms regulates transcriptional RT repression via a Trichostatin A-insensitive mechanism."; RL Cell. Signal. 17:153-166(2005). RN [18] RP ACETYLATION AT LYS-551, AND FUNCTION. RX PubMed=15554904; DOI=10.1042/bj20041101; RA Ehlting C., Haussinger D., Bode J.G.; RT "Sp3 is involved in the regulation of SOCS3 gene expression."; RL Biochem. J. 387:737-745(2005). RN [19] RP SUMOYLATION AT LYS-551, FUNCTION OF ISOFORMS, AND MUTAGENESIS OF LYS-551. RX PubMed=16781829; DOI=10.1016/j.gene.2006.04.015; RA Ellis D.J., Dehm S.M., Bonham K.; RT "The modification of Sp3 isoforms by SUMOylation has differential effects RT on the SRC1A promoter."; RL Gene 379:68-78(2006). RN [20] RP FUNCTION, DEACETYLATION, INTERACTION WITH HDAC1, AND MUTAGENESIS OF RP LYS-551. RX PubMed=17548428; DOI=10.1096/fj.07-8621com; RA Wooten-Blanks L.G., Song P., Senkal C.E., Ogretmen B.; RT "Mechanisms of ceramide-mediated repression of the human telomerase reverse RT transcriptase promoter via deacetylation of Sp3 by histone deacetylase 1."; RL FASEB J. 21:3386-3397(2007). RN [21] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=18187045; DOI=10.1016/j.advenzreg.2007.11.016; RA Davie J.R., He S., Li L., Sekhavat A., Espino P., Drobic B., Dunn K.L., RA Sun J.M., Chen H.Y., Yu J., Pritchard S., Wang X.; RT "Nuclear organization and chromatin dynamics -- Sp1, Sp3 and histone RT deacetylases."; RL Adv. Enzyme Regul. 48:189-208(2008). RN [22] RP SUMOYLATION AT LYS-551, AND FUNCTION OF ISOFORMS. RX PubMed=18617891; DOI=10.1038/embor.2008.127; RA Stielow B., Sapetschnig A., Wink C., Kraeger I., Suske G.; RT "SUMO-modified Sp3 represses transcription by provoking local RT heterochromatic gene silencing."; RL EMBO Rep. 9:899-906(2008). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-73; SER-563 AND SER-646, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-73, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-73, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [26] RP INTERACTION WITH MEIS2 AND PBX1. RX PubMed=21746878; DOI=10.1128/mcb.01456-10; RA Bjerke G.A., Hyman-Walsh C., Wotton D.; RT "Cooperative transcriptional activation by Klf4, Meis2, and Pbx1."; RL Mol. Cell. Biol. 31:3723-3733(2011). RN [27] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [28] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-73, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [29] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-73, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [30] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-551, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). RN [31] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-551, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25114211; DOI=10.1073/pnas.1413825111; RA Impens F., Radoshevich L., Cossart P., Ribet D.; RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by RT external stimuli."; RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014). RN [32] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-551, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033; RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V., RA Vertegaal A.C.; RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage."; RL Cell Rep. 10:1778-1791(2015). RN [33] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-551, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25755297; DOI=10.1074/mcp.o114.044792; RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V., RA Vertegaal A.C.; RT "System-wide analysis of SUMOylation dynamics in response to replication RT stress reveals novel small ubiquitin-like modified target proteins and RT acceptor lysines relevant for genome stability."; RL Mol. Cell. Proteomics 14:1419-1434(2015). RN [34] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-551 AND LYS-593, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [35] RP 9AATAD MOTIF. RX PubMed=31375868; DOI=10.1007/s00018-019-03251-w; RA Piskacek M., Havelka M., Jendruchova K., Knight A., Keegan L.P.; RT "The evolution of the 9aaTAD domain in Sp2 proteins: inactivation with RT valines and intron reservoirs."; RL Cell. Mol. Life Sci. 77:1793-1810(2020). CC -!- FUNCTION: Transcriptional factor that can act as an activator or CC repressor depending on isoform and/or post-translational modifications. CC Binds to GT and GC boxes promoter elements. Competes with SP1 for the CC GC-box promoters. Weak activator of transcription but can activate a CC number of genes involved in different processes such as cell-cycle CC regulation, hormone-induction and house-keeping. CC {ECO:0000269|PubMed:10391891, ECO:0000269|PubMed:11812829, CC ECO:0000269|PubMed:12419227, ECO:0000269|PubMed:12837748, CC ECO:0000269|PubMed:15247228, ECO:0000269|PubMed:15494207, CC ECO:0000269|PubMed:15554904, ECO:0000269|PubMed:16781829, CC ECO:0000269|PubMed:17548428, ECO:0000269|PubMed:18187045, CC ECO:0000269|PubMed:18617891, ECO:0000269|PubMed:9278495}. CC -!- SUBUNIT: Interacts with HLTF; the interaction may be required for basal CC transcriptional activity of HLTF. Interacts with HDAC1; the interaction CC deacetylates SP3 and regulates its transcriptional activity. Interacts CC with HDAC2 (preferably the CK2-phosphorylated form); the interaction CC deacetylates SP3 and regulates its transcriptional activity. Interacts CC with MEIS2 isoform 4 and PBX1 isoform PBX1a. CC {ECO:0000269|PubMed:10391891, ECO:0000269|PubMed:12176973, CC ECO:0000269|PubMed:12837748, ECO:0000269|PubMed:17548428, CC ECO:0000269|PubMed:21746878}. CC -!- INTERACTION: CC Q02447; Q96Q77: CIB3; NbExp=3; IntAct=EBI-348158, EBI-10292696; CC Q02447; P03372: ESR1; NbExp=4; IntAct=EBI-348158, EBI-78473; CC Q02447; P42858: HTT; NbExp=4; IntAct=EBI-348158, EBI-466029; CC Q02447; Q6MZP7: LIN54; NbExp=3; IntAct=EBI-348158, EBI-1389411; CC Q02447; Q96BD5: PHF21A; NbExp=3; IntAct=EBI-348158, EBI-745085; CC Q02447; Q7Z3K3: POGZ; NbExp=3; IntAct=EBI-348158, EBI-1389308; CC Q02447; P14678-2: SNRPB; NbExp=3; IntAct=EBI-348158, EBI-372475; CC Q02447; Q5MJ10: SPANXN2; NbExp=3; IntAct=EBI-348158, EBI-12023934; CC -!- SUBCELLULAR LOCATION: Nucleus. Nucleus, PML body. Note=Localizes to the CC nuclear periphery and in nuclear dots when sumoylated. Some CC localization in PML nuclear bodies. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing, Alternative initiation; Named isoforms=6; CC Name=1; Synonyms=Large, L-Sp3; CC IsoId=Q02447-1; Sequence=Displayed; CC Name=2; CC IsoId=Q02447-2; Sequence=VSP_026701; CC Name=3; Synonyms=M1-Sp3; CC IsoId=Q02447-3; Sequence=VSP_026699; CC Name=4; Synonyms=M2-Sp3; CC IsoId=Q02447-4; Sequence=VSP_026698; CC Name=5; CC IsoId=Q02447-5; Sequence=VSP_026700; CC Name=6; CC IsoId=Q02447-6; Sequence=VSP_026701, VSP_026702; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. CC -!- DOMAIN: The 9aaTAD motif is a transactivation domain present in a large CC number of yeast and animal transcription factors. CC {ECO:0000269|PubMed:31375868}. CC -!- PTM: Not glycosylated. CC -!- PTM: Acetylated by histone acetyltransferase p300, deacetylated by CC HDACs. Acetylation/deacetylation states regulate transcriptional CC activity. Acetylation appears to activate transcription. Alternate CC sumoylation and acetylation at Lys-551 also control transcriptional CC activity. Ceramides can also regulate acetylation/deacetylation events CC through altering the interaction of HDAC with SP3. In vitro, C(18)- CC ceramides, but not C(16)-ceramides, increase the interaction of HDAC1 CC with SP3 and enhance the deacetylation of SP3 and the subsequent CC repression of the TERT promoter. {ECO:0000269|PubMed:11812829, CC ECO:0000269|PubMed:12419227, ECO:0000269|PubMed:12837748, CC ECO:0000269|PubMed:15494207, ECO:0000269|PubMed:15554904, CC ECO:0000269|PubMed:16781829, ECO:0000269|PubMed:18617891}. CC -!- PTM: Sumoylated on all isoforms. Sumoylated on 2 sites in longer CC isoforms with Lys-551 being the major site. Sumoylation at this site CC promotes nuclear localization to the nuclear periphery, nuclear dots CC and PML nuclear bodies. Sumoylation on Lys-551 represses the CC transactivation activity, except for the largest isoform, L-Sp3, which CC has little effect on transactivation. Alternate sumoylation and CC acetylation at Lys-551 also control transcriptional activity. CC {ECO:0000269|PubMed:11812829, ECO:0000269|PubMed:12419227, CC ECO:0000269|PubMed:12837748, ECO:0000269|PubMed:15494207, CC ECO:0000269|PubMed:15554904, ECO:0000269|PubMed:16781829, CC ECO:0000269|PubMed:18617891}. CC -!- MISCELLANEOUS: [Isoform 2]: Produced by alternative initiation at Met- CC 13 of isoform 1. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 3]: Produced by alternative initiation at Met- CC 286 of isoform 1. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 4]: Produced by alternative initiation at Met- CC 303 of isoform 1. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 5]: Produced by alternative splicing. An AUA CC codon is translated into Met and used as a translation initiation site CC (in vitro). {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 6]: Produced by alternative splicing. CC {ECO:0000305}. CC -!- SIMILARITY: Belongs to the Sp1 C2H2-type zinc-finger protein family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY070137; AAL58086.1; -; mRNA. DR EMBL; AY441957; AAR30505.1; -; mRNA. DR EMBL; AY441958; AAR30506.1; -; mRNA. DR EMBL; AK304199; BAG65079.1; -; mRNA. DR EMBL; BC126414; AAI26415.1; -; mRNA. DR EMBL; AF494280; AAM12875.1; -; Genomic_DNA. DR EMBL; AJ310752; CAC34575.1; -; mRNA. DR EMBL; M97191; AAA36630.2; -; mRNA. DR EMBL; X68560; CAA48562.1; -; mRNA. DR CCDS; CCDS2254.1; -. [Q02447-1] DR CCDS; CCDS46452.1; -. [Q02447-5] DR PIR; B44489; B44489. DR RefSeq; NP_001017371.3; NM_001017371.4. [Q02447-5] DR RefSeq; NP_001166183.1; NM_001172712.1. DR RefSeq; NP_003102.1; NM_003111.4. [Q02447-1] DR AlphaFoldDB; Q02447; -. DR SMR; Q02447; -. DR BioGRID; 112553; 73. DR ELM; Q02447; -. DR IntAct; Q02447; 18. DR MINT; Q02447; -. DR STRING; 9606.ENSP00000310301; -. DR GlyCosmos; Q02447; 13 sites, 2 glycans. DR GlyGen; Q02447; 13 sites, 2 O-linked glycans (13 sites). DR iPTMnet; Q02447; -. DR PhosphoSitePlus; Q02447; -. DR BioMuta; SP3; -. DR DMDM; 30923147; -. DR EPD; Q02447; -. DR jPOST; Q02447; -. DR MassIVE; Q02447; -. DR MaxQB; Q02447; -. DR PaxDb; 9606-ENSP00000310301; -. DR PeptideAtlas; Q02447; -. DR ProteomicsDB; 58091; -. [Q02447-1] DR ProteomicsDB; 58092; -. [Q02447-2] DR ProteomicsDB; 58093; -. [Q02447-3] DR ProteomicsDB; 58094; -. [Q02447-4] DR ProteomicsDB; 58095; -. [Q02447-5] DR ProteomicsDB; 58096; -. [Q02447-6] DR Pumba; Q02447; -. DR Antibodypedia; 3887; 438 antibodies from 33 providers. DR DNASU; 6670; -. DR Ensembl; ENST00000310015.12; ENSP00000310301.6; ENSG00000172845.18. [Q02447-1] DR Ensembl; ENST00000418194.7; ENSP00000406140.3; ENSG00000172845.18. [Q02447-5] DR GeneID; 6670; -. DR KEGG; hsa:6670; -. DR MANE-Select; ENST00000310015.12; ENSP00000310301.6; NM_003111.5; NP_003102.1. DR UCSC; uc002uig.3; human. [Q02447-1] DR AGR; HGNC:11208; -. DR CTD; 6670; -. DR DisGeNET; 6670; -. DR GeneCards; SP3; -. DR HGNC; HGNC:11208; SP3. DR HPA; ENSG00000172845; Low tissue specificity. DR MIM; 601804; gene. DR neXtProt; NX_Q02447; -. DR OpenTargets; ENSG00000172845; -. DR PharmGKB; PA36045; -. DR VEuPathDB; HostDB:ENSG00000172845; -. DR eggNOG; KOG1721; Eukaryota. DR GeneTree; ENSGT00940000155099; -. DR InParanoid; Q02447; -. DR OMA; TCTQVES; -. DR OrthoDB; 5396935at2759; -. DR PhylomeDB; Q02447; -. DR TreeFam; TF350150; -. DR PathwayCommons; Q02447; -. DR Reactome; R-HSA-3232118; SUMOylation of transcription factors. DR SignaLink; Q02447; -. DR SIGNOR; Q02447; -. DR BioGRID-ORCS; 6670; 80 hits in 1178 CRISPR screens. DR ChiTaRS; SP3; human. DR GeneWiki; Sp3_transcription_factor; -. DR GenomeRNAi; 6670; -. DR Pharos; Q02447; Tbio. DR PRO; PR:Q02447; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q02447; Protein. DR Bgee; ENSG00000172845; Expressed in hair follicle and 219 other cell types or tissues. DR ExpressionAtlas; Q02447; baseline and differential. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IC:UniProtKB. DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell. DR GO; GO:0032993; C:protein-DNA complex; ISS:ARUK-UCL. DR GO; GO:0017053; C:transcription repressor complex; IEA:Ensembl. DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB. DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IEA:Ensembl. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISS:ARUK-UCL. DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:UniProtKB. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL. DR GO; GO:0030183; P:B cell differentiation; IEA:Ensembl. DR GO; GO:0060216; P:definitive hemopoiesis; IEA:Ensembl. DR GO; GO:0048596; P:embryonic camera-type eye morphogenesis; IEA:Ensembl. DR GO; GO:0001892; P:embryonic placenta development; IEA:Ensembl. DR GO; GO:0060136; P:embryonic process involved in female pregnancy; IEA:Ensembl. DR GO; GO:0048706; P:embryonic skeletal system development; IEA:Ensembl. DR GO; GO:0043353; P:enucleate erythrocyte differentiation; IEA:Ensembl. DR GO; GO:0030851; P:granulocyte differentiation; IEA:Ensembl. DR GO; GO:0001889; P:liver development; IEA:Ensembl. DR GO; GO:0030324; P:lung development; IEA:Ensembl. DR GO; GO:0030219; P:megakaryocyte differentiation; IEA:Ensembl. DR GO; GO:0030224; P:monocyte differentiation; IEA:Ensembl. DR GO; GO:0002318; P:myeloid progenitor cell differentiation; IEA:Ensembl. DR GO; GO:0001779; P:natural killer cell differentiation; IEA:Ensembl. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IMP:UniProtKB. DR GO; GO:0001503; P:ossification; IEA:Ensembl. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0030217; P:T cell differentiation; IEA:Ensembl. DR GO; GO:0001829; P:trophectodermal cell differentiation; IEA:Ensembl. DR CDD; cd22537; SP3_N; 1. DR Gene3D; 3.30.160.60; Classic Zinc Finger; 3. DR InterPro; IPR036236; Znf_C2H2_sf. DR InterPro; IPR013087; Znf_C2H2_type. DR PANTHER; PTHR23235; KRUEPPEL-LIKE TRANSCRIPTION FACTOR; 1. DR PANTHER; PTHR23235:SF3; TRANSCRIPTION FACTOR SP3; 1. DR Pfam; PF00096; zf-C2H2; 2. DR SMART; SM00355; ZnF_C2H2; 3. DR SUPFAM; SSF57667; beta-beta-alpha zinc fingers; 2. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 3. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 3. DR Genevisible; Q02447; HS. PE 1: Evidence at protein level; KW Acetylation; Activator; Alternative initiation; Alternative splicing; KW DNA-binding; Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein; KW Reference proteome; Repeat; Repressor; Transcription; KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger. FT CHAIN 1..781 FT /note="Transcription factor Sp3" FT /id="PRO_0000047141" FT ZN_FING 621..645 FT /note="C2H2-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 651..675 FT /note="C2H2-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 681..703 FT /note="C2H2-type 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT REGION 1..53 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 65..88 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 138..237 FT /note="Transactivation domain (Gln-rich)" FT REGION 301..338 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 350..499 FT /note="Transactivation domain (Gln-rich)" FT REGION 534..620 FT /note="Repressor domain" FT MOTIF 461..469 FT /note="9aaTAD" FT /evidence="ECO:0000269|PubMed:31375868" FT COMPBIAS 318..338 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 73 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 551 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000269|PubMed:11812829, FT ECO:0000269|PubMed:15554904" FT MOD_RES 563 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 566 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O70494" FT MOD_RES 646 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT CROSSLNK 120 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000269|PubMed:12419227" FT CROSSLNK 551 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO); alternate" FT CROSSLNK 551 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0007744|PubMed:25114211" FT CROSSLNK 551 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:25218447, FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:25772364, FT ECO:0007744|PubMed:28112733" FT CROSSLNK 593 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 1..302 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000305" FT /id="VSP_026698" FT VAR_SEQ 1..285 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_026699" FT VAR_SEQ 1..69 FT /note="MTAPEKPVKQEEMAALDVDSGGGGGGGGGHGEYLQQQQQHGNGAVAAAAAAQ FT DTQPSPLALLAATCSKI -> M (in isoform 5)" FT /evidence="ECO:0000303|PubMed:12297010" FT /id="VSP_026700" FT VAR_SEQ 1..12 FT /note="Missing (in isoform 2 and isoform 6)" FT /evidence="ECO:0000303|PubMed:15474306, FT ECO:0000303|PubMed:15489334" FT /id="VSP_026701" FT VAR_SEQ 53..93 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000303|PubMed:15474306" FT /id="VSP_026702" FT VARIANT 164 FT /note="T -> A (in dbSNP:rs1047640)" FT /evidence="ECO:0000269|PubMed:12297010, FT ECO:0000269|PubMed:1454515, ECO:0000269|PubMed:15474306" FT /id="VAR_016123" FT MUTAGEN 120 FT /note="K->R: Some loss of sumoylation. Slight increase in FT transcriptional activity. Large increase in transcriptional FT activity; when associated with R-551." FT /evidence="ECO:0000269|PubMed:12419227" FT MUTAGEN 551..553 FT /note="KEE->AAA: Increases transcriptional activity." FT /evidence="ECO:0000269|PubMed:15494207" FT MUTAGEN 551..553 FT /note="KEE->REA: 200-fold increase in transcriptional FT activation." FT /evidence="ECO:0000269|PubMed:15494207" FT MUTAGEN 551..553 FT /note="KEE->RED: 200-fold increase in transcriptional FT activation." FT /evidence="ECO:0000269|PubMed:15494207" FT MUTAGEN 551..552 FT /note="KE->RA: 200-fold increase in transcriptional FT activation." FT MUTAGEN 551..552 FT /note="KE->RD: 200-fold increase in transcriptional FT activation." FT MUTAGEN 551 FT /note="K->Q: A decreased interaction with HDAC1 and FT deacetylation of SP3. Increase of about 4.5% of activity of FT the TERT promoter. Decreased recruitment of HDAC1 and FT increased binding of RNA polymerase II with promoter DNA." FT /evidence="ECO:0000269|PubMed:12419227, FT ECO:0000269|PubMed:16781829, ECO:0000269|PubMed:17548428" FT MUTAGEN 551 FT /note="K->R: Great loss of sumoylation, 20-fold increase in FT transcriptional activity and diffuse nuclear localization. FT Further small increase in transcriptional activity; when FT associated with R-120. Increased interaction with HDAC1 and FT deacetylation of SP3. About 50% decrease in activity of the FT TERT promoter. Enhances recruitment of HDAC1 and inhibits FT binding of RNA polymerase II with promoter DNA." FT /evidence="ECO:0000269|PubMed:12419227, FT ECO:0000269|PubMed:16781829, ECO:0000269|PubMed:17548428" FT CONFLICT 69 FT /note="I -> M (in Ref. 2; AAR30505)" FT /evidence="ECO:0000305" FT CONFLICT 71 FT /note="P -> G (in Ref. 7; AAA36630)" FT /evidence="ECO:0000305" FT CONFLICT 739 FT /note="N -> K (in Ref. 1; AAL58086, 2; AAR30505/AAR30506 FT and 8; CAA48562)" FT /evidence="ECO:0000305" SQ SEQUENCE 781 AA; 81925 MW; DCFD4363509DB49D CRC64; MTAPEKPVKQ EEMAALDVDS GGGGGGGGGH GEYLQQQQQH GNGAVAAAAA AQDTQPSPLA LLAATCSKIG PPSPGDDEEE AAAAAGAPAA AGATGDLASA QLGGAPNRWE VLSATPTTIK DEAGNLVQIP SAATSSGQYV LPLQNLQNQQ IFSVAPGSDS SNGTVSSVQY QVIPQIQSAD GQQVQIGFTG SSDNGGINQE SSQIQIIPGS NQTLLASGTP SANIQNLIPQ TGQVQVQGVA IGGSSFPGQT QVVANVPLGL PGNITFVPIN SVDLDSLGLS GSSQTMTAGI NADGHLINTG QAMDSSDNSE RTGERVSPDI NETNTDTDLF VPTSSSSQLP VTIDSTGILQ QNTNSLTTSS GQVHSSDLQG NYIQSPVSEE TQAQNIQVST AQPVVQHLQL QESQQPTSQA QIVQGITPQT IHGVQASGQN ISQQALQNLQ LQLNPGTFLI QAQTVTPSGQ VTWQTFQVQG VQNLQNLQIQ NTAAQQITLT PVQTLTLGQV AAGGAFTSTP VSLSTGQLPN LQTVTVNSID SAGIQLHPGE NADSPADIRI KEEEPDPEEW QLSGDSTLNT NDLTHLRVQV VDEEGDQQHQ EGKRLRRVAC TCPNCKEGGG RGTNLGKKKQ HICHIPGCGK VYGKTSHLRA HLRWHSGERP FVCNWMYCGK RFTRSDELQR HRRTHTGEKK FVCPECSKRF MRSDHLAKHI KTHQNKKGIH SSSTVLASVE AARDDTLITA GGTTLILANI QQGSVSGIGT VNTSATSNQD ILTNTEIPLQ LVTVSGNETM E //