SP3_HUMAN
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 03-AUG-2022, entry version 207.
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}.
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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; 63.
DR ELM; Q02447; -.
DR IntAct; Q02447; 16.
DR MINT; Q02447; -.
DR STRING; 9606.ENSP00000310301; -.
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; Q02447; -.
DR PeptideAtlas; Q02447; -.
DR PRIDE; 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 Antibodypedia; 3887; 412 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 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 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; 76 hits in 1099 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 217 other tissues.
DR ExpressionAtlas; Q02447; baseline and differential.
DR Genevisible; Q02447; HS.
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 transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0001503; P:ossification; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0030217; P:T cell differentiation; IEA:Ensembl.
DR GO; GO:0001829; P:trophectodermal cell differentiation; IEA:Ensembl.
DR InterPro; IPR030452; SP3.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR PANTHER; PTHR23235:SF3; PTHR23235:SF3; 1.
DR Pfam; PF00096; zf-C2H2; 3.
DR SMART; SM00355; ZnF_C2H2; 3.
DR SUPFAM; SSF57667; SSF57667; 2.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 3.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 3.
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
