SIN3A_HUMAN
ID SIN3A_HUMAN Reviewed; 1273 AA.
AC Q96ST3; B2RNS5; Q8N8N4; Q8NC83; Q8WV18; Q96L98; Q9UFQ1;
DT 24-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 24-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=Paired amphipathic helix protein Sin3a;
DE AltName: Full=Histone deacetylase complex subunit Sin3a;
DE AltName: Full=Transcriptional corepressor Sin3a;
GN Name=SIN3A {ECO:0000312|HGNC:HGNC:19353};
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] {ECO:0000305, ECO:0000312|EMBL:AAP97288.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Guo J.H., Yu L.;
RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAH18973.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, and Uterus {ECO:0000312|EMBL:AAH18973.1};
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-1026.
RC TISSUE=Brain, and Teratocarcinoma;
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] {ECO:0000305, ECO:0000312|EMBL:AAP97288.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-620.
RA Bu X., Fu Y., Jiang S., Avraham S., Avraham H.;
RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 913-1273.
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] {ECO:0000305}
RP INTERACTION WITH SFPQ.
RX PubMed=11259580; DOI=10.1128/mcb.21.7.2298-2311.2001;
RA Mathur M., Tucker P.W., Samuels H.H.;
RT "PSF is a novel corepressor that mediates its effect through Sin3A and the
RT DNA binding domain of nuclear hormone receptors.";
RL Mol. Cell. Biol. 21:2298-2311(2001).
RN [7]
RP INTERACTION WITH OGT, AND FUNCTION.
RX PubMed=12150998; DOI=10.1016/s0092-8674(02)00810-3;
RA Yang X., Zhang F., Kudlow J.E.;
RT "Recruitment of O-GlcNAc transferase to promoters by corepressor mSin3A:
RT coupling protein O-GlcNAcylation to transcriptional repression.";
RL Cell 110:69-80(2002).
RN [8] {ECO:0000305}
RP INTERACTION WITH SFPQ.
RX PubMed=11897684; DOI=10.1210/endo.143.4.8748;
RA Sewer M.B., Nguyen V.Q., Huang C.J., Tucker P.W., Kagawa N., Waterman M.R.;
RT "Transcriptional activation of human CYP17 in H295R adrenocortical cells
RT depends on complex formation among p54(nrb)/NonO, protein-associated
RT splicing factor, and SF-1, a complex that also participates in repression
RT of transcription.";
RL Endocrinology 143:1280-1290(2002).
RN [9] {ECO:0000305}
RP INTERACTION WITH DACH1.
RX PubMed=14525983; DOI=10.1074/jbc.m310021200;
RA Wu K., Yang Y., Wang C., Davoli M.A., D'Amico M., Li A., Cveklova K.,
RA Kozmik Z., Lisanti M.P., Russell R.G., Cvekl A., Pestell R.G.;
RT "DACH1 inhibits transforming growth factor-beta signaling through binding
RT Smad4.";
RL J. Biol. Chem. 278:51673-51684(2003).
RN [10] {ECO:0000305}
RP INTERACTION WITH HCFC1.
RX PubMed=12670868; DOI=10.1101/gad.252103;
RA Wysocka J., Myers M.P., Laherty C.D., Eisenman R.N., Herr W.;
RT "Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4
RT methyltransferase are tethered together selectively by the cell-
RT proliferation factor HCF-1.";
RL Genes Dev. 17:896-911(2003).
RN [11]
RP INTERACTION WITH SAP130; SUDS3; ARID4B; HDAC1 AND HDAC2.
RX PubMed=12724404; DOI=10.1128/mcb.23.10.3456-3467.2003;
RA Fleischer T.C., Yun U.J., Ayer D.E.;
RT "Identification and characterization of three new components of the mSin3A
RT corepressor complex.";
RL Mol. Cell. Biol. 23:3456-3467(2003).
RN [12]
RP INTERACTION WITH BRMS1L.
RX PubMed=15451426; DOI=10.1016/j.bbrc.2004.08.227;
RA Nikolaev A.Y., Papanikolaou N.A., Li M., Qin J., Gu W.;
RT "Identification of a novel BRMS1-homologue protein p40 as a component of
RT the mSin3A/p33(ING1b)/HDAC1 deacetylase complex.";
RL Biochem. Biophys. Res. Commun. 323:1216-1222(2004).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-860, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [14]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH SAP30L.
RX PubMed=16820529; DOI=10.1093/nar/gkl401;
RA Viiri K.M., Korkeamaeki H., Kukkonen M.K., Nieminen L.K., Lindfors K.,
RA Peterson P., Maeki M., Kainulainen H., Lohi O.;
RT "SAP30L interacts with members of the Sin3A corepressor complex and targets
RT Sin3A to the nucleolus.";
RL Nucleic Acids Res. 34:3288-3298(2006).
RN [15]
RP INTERACTION WITH PPHLN1.
RX PubMed=17963697; DOI=10.1016/j.bbrc.2007.10.090;
RA Kurita M., Suzuki H., Kawano Y., Aiso S., Matsuoka M.;
RT "CR/periphilin is a transcriptional co-repressor involved in cell cycle
RT progression.";
RL Biochem. Biophys. Res. Commun. 364:930-936(2007).
RN [16]
RP INTERACTION WITH TOPORS, SUMOYLATION BY TOPORS, AND DESUMOYLATION BY SENP2.
RX PubMed=17803295; DOI=10.1021/pr0703674;
RA Pungaliya P., Kulkarni D., Park H.J., Marshall H., Zheng H., Lackland H.,
RA Saleem A., Rubin E.H.;
RT "TOPORS functions as a SUMO-1 E3 ligase for chromatin-modifying proteins.";
RL J. Proteome Res. 6:3918-3923(2007).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10; SER-277; SER-832; SER-940
RP AND SER-1112, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-832 AND SER-1112, AND
RP IDENTIFICATION BY 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 [20]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-469, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [21]
RP INTERACTION WITH SPHK2.
RX PubMed=19729656; DOI=10.1126/science.1176709;
RA Hait N.C., Allegood J., Maceyka M., Strub G.M., Harikumar K.B., Singh S.K.,
RA Luo C., Marmorstein R., Kordula T., Milstien S., Spiegel S.;
RT "Regulation of histone acetylation in the nucleus by sphingosine-1-
RT phosphate.";
RL Science 325:1254-1257(2009).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-832; SER-860; SER-940 AND
RP SER-1112, AND IDENTIFICATION BY 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 [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [24]
RP INTERACTION WITH TET1.
RX PubMed=21490601; DOI=10.1038/nature10066;
RA Williams K., Christensen J., Pedersen M.T., Johansen J.V., Cloos P.A.,
RA Rappsilber J., Helin K.;
RT "TET1 and hydroxymethylcytosine in transcription and DNA methylation
RT fidelity.";
RL Nature 473:343-348(2011).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-832 AND SER-860, AND
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 [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10; SER-832; SER-940 AND
RP SER-1112, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1089, 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 [28]
RP TISSUE SPECIFICITY, INVOLVEMENT IN WITKOS, AND VARIANT WITKOS
RP 1104-ARG--PRO-1273 DEL.
RX PubMed=27399968; DOI=10.1038/ng.3619;
RA Witteveen J.S., Willemsen M.H., Dombroski T.C., van Bakel N.H.,
RA Nillesen W.M., van Hulten J.A., Jansen E.J., Verkaik D.,
RA Veenstra-Knol H.E., van Ravenswaaij-Arts C.M., Wassink-Ruiter J.S.,
RA Vincent M., David A., Le Caignec C., Schieving J., Gilissen C., Foulds N.,
RA Rump P., Strom T., Cremer K., Zink A.M., Engels H., de Munnik S.A.,
RA Visser J.E., Brunner H.G., Martens G.J., Pfundt R., Kleefstra T.,
RA Kolk S.M.;
RT "Haploinsufficiency of MeCP2-interacting transcriptional co-repressor SIN3A
RT causes mild intellectual disability by affecting the development of
RT cortical integrity.";
RL Nat. Genet. 48:877-887(2016).
RN [29]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-122; LYS-134 AND LYS-563, 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 [30]
RP INVOLVEMENT IN WITKOS.
RX PubMed=30267900; DOI=10.1016/j.ejmg.2018.09.014;
RA Narumi-Kishimoto Y., Araki N., Migita O., Kawai T., Okamura K.,
RA Nakabayashi K., Kaname T., Ozawa Y., Ozawa H., Takada F., Hata K.;
RT "Novel SIN3A mutation identified in a Japanese patient with Witteveen-Kolk
RT syndrome.";
RL Eur. J. Med. Genet. 62:103547-103547(2019).
CC -!- FUNCTION: Acts as a transcriptional repressor. Corepressor for REST.
CC Interacts with MXI1 to repress MYC responsive genes and antagonize MYC
CC oncogenic activities. Also interacts with MXD1-MAX heterodimers to
CC repress transcription by tethering SIN3A to DNA. Acts cooperatively
CC with OGT to repress transcription in parallel with histone
CC deacetylation. Involved in the control of the circadian rhythms.
CC Required for the transcriptional repression of circadian target genes,
CC such as PER1, mediated by the large PER complex through histone
CC deacetylation. Cooperates with FOXK1 to regulate cell cycle progression
CC probably by repressing cell cycle inhibitor genes expression (By
CC similarity). Required for cortical neuron differentiation and callosal
CC axon elongation (By similarity). {ECO:0000250|UniProtKB:Q60520,
CC ECO:0000269|PubMed:12150998}.
CC -!- SUBUNIT: Interacts with ARID4B, BRMS1L, HCFC1, HDAC1, HDAC2, MXI1,
CC SAP30L, SAP130, SFPQ and TOPORS (PubMed:11259580, PubMed:11897684,
CC PubMed:12670868, PubMed:12724404, PubMed:15451426, PubMed:16820529,
CC PubMed:17803295). Interacts with OGT (via TPRs 1-6); the interaction
CC mediates transcriptional repression in parallel with histone
CC deacetylase (PubMed:12150998). Interacts with BAZ2A, MXD1, MXD3, MXD4,
CC MBD2, DACH1, NCOR1, NR4A2, REST, RLIM, SAP30, SETDB1, SMYD2, and SUDS3
CC (PubMed:14525983). Interacts with PHF12 in a complex composed of HDAC1,
CC PHF12 and SAP30 (By similarity). Interacts with TET1; the interaction
CC recruits SIN3A to gene promoters (PubMed:21490601). The large PER
CC complex involved in the histone deacetylation is composed of at least
CC HDAC1, PER2, SFPQ and SIN3A (By similarity). Interacts with KLF11 (By
CC similarity). Interacts with PPHLN1 (PubMed:17963697). Found in a
CC complex with YY1, GON4L and HDAC1 (By similarity). Interacts (via PAH2)
CC with FOXK1 (By similarity). Interacts with FOXK2 (By similarity). Found
CC in a complex composed of at least SINHCAF, SIN3A, HDAC1, SAP30, RBBP4,
CC OGT and TET1. Interacts with SINHCAF (By similarity). Interacts with
CC SPHK2 (PubMed:19729656). {ECO:0000250|UniProtKB:Q60520,
CC ECO:0000269|PubMed:11259580, ECO:0000269|PubMed:11897684,
CC ECO:0000269|PubMed:12150998, ECO:0000269|PubMed:12670868,
CC ECO:0000269|PubMed:12724404, ECO:0000269|PubMed:14525983,
CC ECO:0000269|PubMed:15451426, ECO:0000269|PubMed:16820529,
CC ECO:0000269|PubMed:17803295, ECO:0000269|PubMed:17963697,
CC ECO:0000269|PubMed:19729656, ECO:0000269|PubMed:21490601}.
CC -!- INTERACTION:
CC Q96ST3; P51610: HCFC1; NbExp=6; IntAct=EBI-347218, EBI-396176;
CC Q96ST3; Q13547: HDAC1; NbExp=9; IntAct=EBI-347218, EBI-301834;
CC Q96ST3; Q92769: HDAC2; NbExp=6; IntAct=EBI-347218, EBI-301821;
CC Q96ST3; P42858: HTT; NbExp=4; IntAct=EBI-347218, EBI-466029;
CC Q96ST3; Q9H160: ING2; NbExp=2; IntAct=EBI-347218, EBI-389787;
CC Q96ST3; P51608: MECP2; NbExp=2; IntAct=EBI-347218, EBI-1189067;
CC Q96ST3; Q9UQ80: PA2G4; NbExp=4; IntAct=EBI-347218, EBI-924893;
CC Q96ST3; Q9BUL5: PHF23; NbExp=2; IntAct=EBI-347218, EBI-722852;
CC Q96ST3; P23246: SFPQ; NbExp=2; IntAct=EBI-347218, EBI-355453;
CC Q96ST3; P12755: SKI; NbExp=3; IntAct=EBI-347218, EBI-347281;
CC Q96ST3; P04637: TP53; NbExp=2; IntAct=EBI-347218, EBI-366083;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00810,
CC ECO:0000269|PubMed:16820529}. Nucleus, nucleolus
CC {ECO:0000269|PubMed:16820529}. Note=Recruited to the nucleolus by
CC SAP30L.
CC -!- TISSUE SPECIFICITY: Expressed in the developing brain, with highest
CC levels of expression detected in the ventricular zone of various
CC cortical regions. {ECO:0000269|PubMed:27399968}.
CC -!- PTM: SUMO1 sumoylated by TOPORS. Probably desumoylated by SENP2.
CC {ECO:0000269|PubMed:17803295}.
CC -!- DISEASE: Witteveen-Kolk syndrome (WITKOS) [MIM:613406]: An autosomal
CC dominant syndrome characterized by global developmental delay, mild to
CC severe intellectual disability, and facial dysmorphism. Additional
CC features include short stature, microcephaly, joint hypermotility, and
CC small hands and feet with digital abnormalities. Brain imaging shows
CC dilated ventricles, thin corpus callosum and, in some cases, dysgyria
CC or polymicrogyria. {ECO:0000269|PubMed:27399968,
CC ECO:0000269|PubMed:30267900}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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DR EMBL; AF418569; AAP97288.1; -; mRNA.
DR EMBL; BC018973; AAH18973.1; -; mRNA.
DR EMBL; BC137098; AAI37099.1; -; mRNA.
DR EMBL; BC137099; AAI37100.1; -; mRNA.
DR EMBL; AK027559; BAB55197.1; -; mRNA.
DR EMBL; AK074903; BAC11280.1; -; mRNA.
DR EMBL; AK096477; BAC04801.1; -; mRNA.
DR EMBL; AY044430; AAK95854.1; -; mRNA.
DR EMBL; AL117513; CAB55972.1; -; mRNA.
DR CCDS; CCDS10279.1; -.
DR PIR; T17282; T17282.
DR RefSeq; NP_001138829.1; NM_001145357.1.
DR RefSeq; NP_001138830.1; NM_001145358.1.
DR RefSeq; NP_056292.1; NM_015477.2.
DR RefSeq; XP_006720528.1; XM_006720465.3.
DR RefSeq; XP_006720529.1; XM_006720466.3.
DR RefSeq; XP_006720530.1; XM_006720467.3.
DR AlphaFoldDB; Q96ST3; -.
DR SMR; Q96ST3; -.
DR BioGRID; 117439; 284.
DR ComplexPortal; CPX-3321; SIN3A histone deacetylase complex.
DR ComplexPortal; CPX-3323; SIN3A histone deacetylase complex, ES cell-specific variant.
DR CORUM; Q96ST3; -.
DR DIP; DIP-31515N; -.
DR IntAct; Q96ST3; 108.
DR MINT; Q96ST3; -.
DR STRING; 9606.ENSP00000378402; -.
DR GlyGen; Q96ST3; 8 sites, 2 O-linked glycans (8 sites).
DR iPTMnet; Q96ST3; -.
DR MetOSite; Q96ST3; -.
DR PhosphoSitePlus; Q96ST3; -.
DR SwissPalm; Q96ST3; -.
DR BioMuta; SIN3A; -.
DR DMDM; 37999759; -.
DR EPD; Q96ST3; -.
DR jPOST; Q96ST3; -.
DR MassIVE; Q96ST3; -.
DR MaxQB; Q96ST3; -.
DR PaxDb; Q96ST3; -.
DR PeptideAtlas; Q96ST3; -.
DR PRIDE; Q96ST3; -.
DR ProteomicsDB; 78146; -.
DR Antibodypedia; 3857; 272 antibodies from 37 providers.
DR DNASU; 25942; -.
DR Ensembl; ENST00000360439.8; ENSP00000353622.4; ENSG00000169375.16.
DR Ensembl; ENST00000394947.8; ENSP00000378402.3; ENSG00000169375.16.
DR Ensembl; ENST00000394949.8; ENSP00000378403.4; ENSG00000169375.16.
DR GeneID; 25942; -.
DR KEGG; hsa:25942; -.
DR MANE-Select; ENST00000394947.8; ENSP00000378402.3; NM_001145358.2; NP_001138830.1.
DR UCSC; uc002bai.4; human.
DR CTD; 25942; -.
DR DisGeNET; 25942; -.
DR GeneCards; SIN3A; -.
DR HGNC; HGNC:19353; SIN3A.
DR HPA; ENSG00000169375; Low tissue specificity.
DR MalaCards; SIN3A; -.
DR MIM; 607776; gene.
DR MIM; 613406; phenotype.
DR neXtProt; NX_Q96ST3; -.
DR OpenTargets; ENSG00000169375; -.
DR Orphanet; 94065; 15q24 microdeletion syndrome.
DR Orphanet; 500166; SIN3A-related intellectual disability syndrome due to a point mutation.
DR PharmGKB; PA134993567; -.
DR VEuPathDB; HostDB:ENSG00000169375; -.
DR eggNOG; KOG4204; Eukaryota.
DR GeneTree; ENSGT00940000155491; -.
DR HOGENOM; CLU_001360_0_1_1; -.
DR InParanoid; Q96ST3; -.
DR OMA; MCEEVIK; -.
DR OrthoDB; 253485at2759; -.
DR PhylomeDB; Q96ST3; -.
DR TreeFam; TF106187; -.
DR PathwayCommons; Q96ST3; -.
DR Reactome; R-HSA-3899300; SUMOylation of transcription cofactors.
DR Reactome; R-HSA-400206; Regulation of lipid metabolism by PPARalpha.
DR Reactome; R-HSA-427413; NoRC negatively regulates rRNA expression.
DR Reactome; R-HSA-8936459; RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function.
DR Reactome; R-HSA-9022538; Loss of MECP2 binding ability to 5mC-DNA.
DR Reactome; R-HSA-9022692; Regulation of MECP2 expression and activity.
DR Reactome; R-HSA-9022699; MECP2 regulates neuronal receptors and channels.
DR Reactome; R-HSA-9022702; MECP2 regulates transcription of neuronal ligands.
DR Reactome; R-HSA-9615017; FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes.
DR Reactome; R-HSA-9701898; STAT3 nuclear events downstream of ALK signaling.
DR Reactome; R-HSA-9707564; Cytoprotection by HMOX1.
DR Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production.
DR SignaLink; Q96ST3; -.
DR SIGNOR; Q96ST3; -.
DR BioGRID-ORCS; 25942; 694 hits in 1092 CRISPR screens.
DR ChiTaRS; SIN3A; human.
DR GeneWiki; SIN3A; -.
DR GenomeRNAi; 25942; -.
DR Pharos; Q96ST3; Tbio.
DR PRO; PR:Q96ST3; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q96ST3; protein.
DR Bgee; ENSG00000169375; Expressed in secondary oocyte and 173 other tissues.
DR ExpressionAtlas; Q96ST3; baseline and differential.
DR Genevisible; Q96ST3; HS.
DR GO; GO:0000785; C:chromatin; IBA:GO_Central.
DR GO; GO:0000118; C:histone deacetylase complex; IDA:UniProtKB.
DR GO; GO:0000776; C:kinetochore; IEA:Ensembl.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0016580; C:Sin3 complex; IDA:UniProtKB.
DR GO; GO:0017053; C:transcription repressor complex; IEA:Ensembl.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0003677; F:DNA binding; IEA:Ensembl.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0003723; F:RNA binding; IEA:Ensembl.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL.
DR GO; GO:0003713; F:transcription coactivator activity; IMP:ARUK-UCL.
DR GO; GO:0003714; F:transcription corepressor activity; IMP:ARUK-UCL.
DR GO; GO:0140416; F:transcription regulator inhibitor activity; IDA:BHF-UCL.
DR GO; GO:0002218; P:activation of innate immune response; IMP:BHF-UCL.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:1903351; P:cellular response to dopamine; IEA:Ensembl.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IEA:Ensembl.
DR GO; GO:0021895; P:cerebral cortex neuron differentiation; ISS:UniProtKB.
DR GO; GO:0006260; P:DNA replication; IEA:Ensembl.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IEA:Ensembl.
DR GO; GO:0016575; P:histone deacetylation; IBA:GO_Central.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0030336; P:negative regulation of cell migration; IC:ComplexPortal.
DR GO; GO:0042754; P:negative regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:1901675; P:negative regulation of histone H3-K27 acetylation; IMP:BHF-UCL.
DR GO; GO:1900181; P:negative regulation of protein localization to nucleus; IMP:BHF-UCL.
DR GO; GO:1902455; P:negative regulation of stem cell population maintenance; IC:ComplexPortal.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:2000678; P:negative regulation of transcription regulatory region DNA binding; IMP:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IC:ComplexPortal.
DR GO; GO:0002230; P:positive regulation of defense response to virus by host; IMP:BHF-UCL.
DR GO; GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0031453; P:positive regulation of heterochromatin assembly; IMP:BHF-UCL.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; ISS:UniProtKB.
DR GO; GO:1902459; P:positive regulation of stem cell population maintenance; IC:ComplexPortal.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0006476; P:protein deacetylation; IMP:BHF-UCL.
DR GO; GO:0008104; P:protein localization; IEA:Ensembl.
DR GO; GO:0030516; P:regulation of axon extension; ISS:UniProtKB.
DR GO; GO:0010817; P:regulation of hormone levels; IEA:Ensembl.
DR GO; GO:0043619; P:regulation of transcription from RNA polymerase II promoter in response to oxidative stress; IEA:Ensembl.
DR GO; GO:0051595; P:response to methylglyoxal; IEA:Ensembl.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR Gene3D; 1.20.1160.11; -; 3.
DR InterPro; IPR013194; HDAC_interact_dom.
DR InterPro; IPR003822; PAH.
DR InterPro; IPR036600; PAH_sf.
DR InterPro; IPR039774; Sin3-like.
DR InterPro; IPR031693; Sin3_C.
DR InterPro; IPR037969; SIN3A.
DR PANTHER; PTHR12346; PTHR12346; 1.
DR PANTHER; PTHR12346:SF2; PTHR12346:SF2; 1.
DR Pfam; PF02671; PAH; 3.
DR Pfam; PF08295; Sin3_corepress; 1.
DR Pfam; PF16879; Sin3a_C; 1.
DR SMART; SM00761; HDAC_interact; 1.
DR SUPFAM; SSF47762; SSF47762; 3.
DR PROSITE; PS51477; PAH; 3.
PE 1: Evidence at protein level;
KW Acetylation; Biological rhythms; Coiled coil; Disease variant; Dwarfism;
KW Intellectual disability; Isopeptide bond; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..1273
FT /note="Paired amphipathic helix protein Sin3a"
FT /id="PRO_0000121537"
FT DOMAIN 119..189
FT /note="PAH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00810"
FT DOMAIN 300..383
FT /note="PAH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00810"
FT DOMAIN 456..525
FT /note="PAH 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00810"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 87..110
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 119..196
FT /note="Interaction with HCFC1"
FT /evidence="ECO:0000269|PubMed:12670868"
FT REGION 205..480
FT /note="Interaction with REST"
FT /evidence="ECO:0000250"
FT REGION 205..297
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 398..446
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 458..525
FT /note="Interaction with SAP30"
FT /evidence="ECO:0000250|UniProtKB:Q60520"
FT REGION 523..850
FT /note="Interaction with NCOR1"
FT /evidence="ECO:0000250|UniProtKB:Q60520"
FT REGION 524..659
FT /note="Interaction with SUDS3 and SAP130"
FT /evidence="ECO:0000269|PubMed:12724404"
FT REGION 687..829
FT /note="Interaction with HDAC1 and ARID4B"
FT /evidence="ECO:0000269|PubMed:12724404"
FT REGION 888..967
FT /note="Interaction with OGT"
FT /evidence="ECO:0000269|PubMed:12150998"
FT REGION 1136..1156
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 903..932
FT /evidence="ECO:0000255"
FT COMPBIAS 216..250
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 264..282
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 283..297
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 408..430
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 10
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:23186163"
FT MOD_RES 277
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 284
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q60520"
FT MOD_RES 469
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 832
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 860
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"
FT MOD_RES 865
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q60520"
FT MOD_RES 875
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q60520"
FT MOD_RES 940
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 1089
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1112
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT CROSSLNK 122
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 134
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 563
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 1104..1273
FT /note="Missing (in WITKOS)"
FT /evidence="ECO:0000269|PubMed:27399968"
FT /id="VAR_081785"
FT VARIANT 1156
FT /note="M -> L (in dbSNP:rs60213317)"
FT /id="VAR_062129"
FT CONFLICT 163
FT /note="G -> R (in Ref. 4; AAK95854)"
FT /evidence="ECO:0000305"
FT CONFLICT 170..177
FT /note="QLFKGHPD -> HYSKGPPI (in Ref. 4; AAK95854)"
FT /evidence="ECO:0000305"
FT CONFLICT 182..192
FT /note="FNTFLPPGYKI -> IQHLFAPWATKM (in Ref. 4; AAK95854)"
FT /evidence="ECO:0000305"
FT CONFLICT 216
FT /note="I -> T (in Ref. 3; BAC04801)"
FT /evidence="ECO:0000305"
FT CONFLICT 386
FT /note="S -> F (in Ref. 4; AAK95854)"
FT /evidence="ECO:0000305"
FT CONFLICT 536
FT /note="E -> D (in Ref. 4; AAK95854)"
FT /evidence="ECO:0000305"
FT CONFLICT 562
FT /note="P -> G (in Ref. 4; AAK95854)"
FT /evidence="ECO:0000305"
FT CONFLICT 575..576
FT /note="PL -> GV (in Ref. 4; AAK95854)"
FT /evidence="ECO:0000305"
FT CONFLICT 595
FT /note="S -> C (in Ref. 4; AAK95854)"
FT /evidence="ECO:0000305"
FT CONFLICT 618..620
FT /note="ELD -> DLM (in Ref. 4; AAK95854)"
FT /evidence="ECO:0000305"
FT CONFLICT 1009
FT /note="Q -> R (in Ref. 3; BAC11280)"
FT /evidence="ECO:0000305"
FT CONFLICT 1247..1248
FT /note="TT -> NN (in Ref. 1; AAP97288)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1273 AA; 145175 MW; E6A329BE0EAD84CD CRC64;
MKRRLDDQES PVYAAQQRRI PGSTEAFPHQ HRVLAPAPPV YEAVSETMQS ATGIQYSVTP
SYQVSAMPQS SGSHGPAIAA VHSSHHHPTA VQPHGGQVVQ SHAHPAPPVA PVQGQQQFQR
LKVEDALSYL DQVKLQFGSQ PQVYNDFLDI MKEFKSQSID TPGVISRVSQ LFKGHPDLIM
GFNTFLPPGY KIEVQTNDMV NVTTPGQVHQ IPTHGIQPQP QPPPQHPSQP SAQSAPAPAQ
PAPQPPPAKV SKPSQLQAHT PASQQTPPLP PYASPRSPPV QPHTPVTISL GTAPSLQNNQ
PVEFNHAINY VNKIKNRFQG QPDIYKAFLE ILHTYQKEQR NAKEAGGNYT PALTEQEVYA
QVARLFKNQE DLLSEFGQFL PDANSSVLLS KTTAEKVDSV RNDHGGTVKK PQLNNKPQRP
SQNGCQIRRH PTGTTPPVKK KPKLLNLKDS SMADASKHGG GTESLFFDKV RKALRSAEAY
ENFLRCLVIF NQEVISRAEL VQLVSPFLGK FPELFNWFKN FLGYKESVHL ETYPKERATE
GIAMEIDYAS CKRLGSSYRA LPKSYQQPKC TGRTPLCKEV LNDTWVSFPS WSEDSTFVSS
KKTQYEEHIY RCEDERFELD VVLETNLATI RVLEAIQKKL SRLSAEEQAK FRLDNTLGGT
SEVIHRKALQ RIYADKAADI IDGLRKNPSI AVPIVLKRLK MKEEEWREAQ RGFNKVWREQ
NEKYYLKSLD HQGINFKQND TKVLRSKSLL NEIESIYDER QEQATEENAG VPVGPHLSLA
YEDKQILEDA AALIIHHVKR QTGIQKEDKY KIKQIMHHFI PDLLFAQRGD LSDVEEEEEE
EMDVDEATGA VKKHNGVGGS PPKSKLLFSN TAAQKLRGMD EVYNLFYVNN NWYIFMRLHQ
ILCLRLLRIC SQAERQIEEE NREREWEREV LGIKRDKSDS PAIQLRLKEP MDVDVEDYYP
AFLDMVRSLL DGNIDSSQYE DSLREMFTIH AYIAFTMDKL IQSIVRQLQH IVSDEICVQV
TDLYLAENNN GATGGQLNTQ NSRSLLESTY QRKAEQLMSD ENCFKLMFIQ SQGQVQLTIE
LLDTEEENSD DPVEAERWSD YVERYMNSDT TSPELREHLA QKPVFLPRNL RRIRKCQRGR
EQQEKEGKEG NSKKTMENVD SLDKLECRFK LNSYKMVYVI KSEDYMYRRT ALLRAHQSHE
RVSKRLHQRF QAWVDKWTKE HVPREMAAET SKWLMGEGLE GLVPCTTTCD TETLHFVSIN
KYRVKYGTVF KAP
