SRTD2_HUMAN
ID SRTD2_HUMAN Reviewed; 314 AA.
AC Q14140; Q53TS2;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=SERTA domain-containing protein 2;
DE AltName: Full=Transcriptional regulator interacting with the PHD-bromodomain 2;
DE Short=TRIP-Br2;
GN Name=SERTAD2; Synonyms=KIAA0127, TRIPBR2;
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 [LARGE SCALE MRNA].
RC TISSUE=Bone marrow;
RX PubMed=8590280; DOI=10.1093/dnares/2.4.167;
RA Nagase T., Seki N., Tanaka A., Ishikawa K., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. IV. The
RT coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of
RT cDNA clones from human cell line KG-1.";
RL DNA Res. 2:167-174(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Brain cortex;
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 [4]
RP FUNCTION AS COREGULATOR, AND INTERACTION WITH TFDP1.
RX PubMed=11331592; DOI=10.1093/emboj/20.9.2273;
RA Hsu S.-I., Yang C.M., Sim K.G., Hentschel D.M., O'Leary E., Bonventre J.V.;
RT "TRIP-Br: a novel family of PHD zinc finger- and bromodomain-interacting
RT proteins that regulate the transcriptional activity of E2F-1/DP-1.";
RL EMBO J. 20:2273-2285(2001).
RN [5]
RP INTERACTION WITH XPO1, DEVELOPMENTAL STAGE, NUCLEAR EXPORT SIGNAL,
RP UBIQUITINATION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LEU-238; LEU-241
RP AND LEU-243.
RX PubMed=18316374; DOI=10.1074/jbc.m708365200;
RA Cheong J.K., Gunaratnam L., Hsu S.I.;
RT "CRM1-mediated nuclear export is required for 26 S proteasome-dependent
RT degradation of the TRIP-Br2 proto-oncoprotein.";
RL J. Biol. Chem. 283:11661-11676(2008).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=23291629; DOI=10.1038/nm.3056;
RA Liew C.W., Boucher J., Cheong J.K., Vernochet C., Koh H.J., Mallol C.,
RA Townsend K., Langin D., Kawamori D., Hu J., Tseng Y.H., Hellerstein M.K.,
RA Farmer S.R., Goodyear L., Doria A., Blueher M., Hsu S.I., Kulkarni R.N.;
RT "Ablation of TRIP-Br2, a regulator of fat lipolysis, thermogenesis and
RT oxidative metabolism, prevents diet-induced obesity and insulin
RT resistance.";
RL Nat. Med. 19:217-226(2013).
CC -!- FUNCTION: Acts at E2F-responsive promoters as coregulator to integrate
CC signals provided by PHD- and/or bromodomain-containing transcription
CC factors. May act as coactivator as well as corepressor of E2F1-TFDP1
CC and E2F4-TFDP1 complexes on E2F consensus binding sites, which would
CC activate or inhibit E2F-target genes expression. Modulates fat storage
CC by down-regulating the expression of key genes involved in adipocyte
CC lipolysis, thermogenesis and oxidative metabolism.
CC {ECO:0000269|PubMed:11331592}.
CC -!- SUBUNIT: Interacts with XPO1; which mediates nuclear export. Interacts
CC with TFDP1; modulates transactivation activity of TFDP1/E2F complexes.
CC {ECO:0000269|PubMed:11331592, ECO:0000269|PubMed:18316374}.
CC -!- INTERACTION:
CC Q14140; O94817: ATG12; NbExp=3; IntAct=EBI-2822051, EBI-746742;
CC Q14140; Q9NX04: C1orf109; NbExp=3; IntAct=EBI-2822051, EBI-8643161;
CC Q14140; O00311: CDC7; NbExp=3; IntAct=EBI-2822051, EBI-374980;
CC Q14140; P61024: CKS1B; NbExp=3; IntAct=EBI-2822051, EBI-456371;
CC Q14140; Q9UI47-2: CTNNA3; NbExp=3; IntAct=EBI-2822051, EBI-11962928;
CC Q14140; Q6ZVH7: ESPNL; NbExp=3; IntAct=EBI-2822051, EBI-12831272;
CC Q14140; Q9NRZ9-6: HELLS; NbExp=3; IntAct=EBI-2822051, EBI-12003732;
CC Q14140; Q86VF2-5: IGFN1; NbExp=3; IntAct=EBI-2822051, EBI-11955401;
CC Q14140; Q92993: KAT5; NbExp=3; IntAct=EBI-2822051, EBI-399080;
CC Q14140; Q9HBI0: PARVG; NbExp=3; IntAct=EBI-2822051, EBI-3921217;
CC Q14140; Q92569: PIK3R3; NbExp=3; IntAct=EBI-2822051, EBI-79893;
CC Q14140; O60733: PLA2G6; NbExp=3; IntAct=EBI-2822051, EBI-12089905;
CC Q14140; O43741: PRKAB2; NbExp=3; IntAct=EBI-2822051, EBI-1053424;
CC Q14140; Q7Z7C7: STRA8; NbExp=3; IntAct=EBI-2822051, EBI-12036261;
CC Q14140; Q63HR2: TNS2; NbExp=3; IntAct=EBI-2822051, EBI-949753;
CC Q14140; Q96C55: ZNF524; NbExp=3; IntAct=EBI-2822051, EBI-10283126;
CC Q14140; Q9P0T4: ZNF581; NbExp=3; IntAct=EBI-2822051, EBI-745520;
CC Q14140; P10073: ZSCAN22; NbExp=3; IntAct=EBI-2822051, EBI-10178224;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:18316374}. Cytoplasm
CC {ECO:0000269|PubMed:18316374}. Note=Exported out of the nucleus via its
CC NES in a XPO1-dependent manner. Once in the cytoplasm, is degraded by
CC the proteasome.
CC -!- TISSUE SPECIFICITY: Expressed in adipose tissue.
CC {ECO:0000269|PubMed:23291629}.
CC -!- DEVELOPMENTAL STAGE: Transcript levels remain constant in all phases of
CC the cell cycle. In contrast, protein levels accumulate at the G1/S
CC phase boundary and decrease progressively through S phase until G2/M
CC phase is reached, residual expression is observed in the G2/M and early
CC G1 phases. {ECO:0000269|PubMed:18316374}.
CC -!- PTM: Polyubiquitinated, which promotes proteasomal degradation.
CC {ECO:0000269|PubMed:18316374}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA09476.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; D50917; BAA09476.2; ALT_INIT; mRNA.
DR EMBL; AC007365; AAY14766.1; -; Genomic_DNA.
DR EMBL; BC074788; AAH74788.1; -; mRNA.
DR EMBL; BC074789; AAH74789.1; -; mRNA.
DR EMBL; BC101639; AAI01640.1; -; mRNA.
DR EMBL; BC101641; AAI01642.1; -; mRNA.
DR CCDS; CCDS33210.1; -.
DR RefSeq; NP_055570.1; NM_014755.2.
DR RefSeq; XP_005264726.1; XM_005264669.2.
DR RefSeq; XP_011531507.1; XM_011533205.2.
DR AlphaFoldDB; Q14140; -.
DR SMR; Q14140; -.
DR BioGRID; 115136; 37.
DR IntAct; Q14140; 19.
DR STRING; 9606.ENSP00000326933; -.
DR iPTMnet; Q14140; -.
DR PhosphoSitePlus; Q14140; -.
DR BioMuta; SERTAD2; -.
DR DMDM; 3123047; -.
DR MassIVE; Q14140; -.
DR PaxDb; Q14140; -.
DR PeptideAtlas; Q14140; -.
DR PRIDE; Q14140; -.
DR ProteomicsDB; 59842; -.
DR Antibodypedia; 16073; 140 antibodies from 18 providers.
DR DNASU; 9792; -.
DR Ensembl; ENST00000313349.3; ENSP00000326933.3; ENSG00000179833.4.
DR GeneID; 9792; -.
DR KEGG; hsa:9792; -.
DR MANE-Select; ENST00000313349.3; ENSP00000326933.3; NM_014755.3; NP_055570.1.
DR UCSC; uc002sde.3; human.
DR CTD; 9792; -.
DR DisGeNET; 9792; -.
DR GeneCards; SERTAD2; -.
DR HGNC; HGNC:30784; SERTAD2.
DR HPA; ENSG00000179833; Tissue enhanced (bone).
DR MIM; 617851; gene.
DR neXtProt; NX_Q14140; -.
DR OpenTargets; ENSG00000179833; -.
DR PharmGKB; PA134948884; -.
DR VEuPathDB; HostDB:ENSG00000179833; -.
DR eggNOG; ENOG502QUG8; Eukaryota.
DR GeneTree; ENSGT00530000063867; -.
DR HOGENOM; CLU_065586_0_0_1; -.
DR InParanoid; Q14140; -.
DR OMA; FCAVSPP; -.
DR OrthoDB; 1188137at2759; -.
DR PhylomeDB; Q14140; -.
DR TreeFam; TF331620; -.
DR PathwayCommons; Q14140; -.
DR SignaLink; Q14140; -.
DR BioGRID-ORCS; 9792; 16 hits in 1081 CRISPR screens.
DR ChiTaRS; SERTAD2; human.
DR GenomeRNAi; 9792; -.
DR Pharos; Q14140; Tbio.
DR PRO; PR:Q14140; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q14140; protein.
DR Bgee; ENSG00000179833; Expressed in cartilage tissue and 208 other tissues.
DR Genevisible; Q14140; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0003713; F:transcription coactivator activity; IEA:Ensembl.
DR GO; GO:0030308; P:negative regulation of cell growth; IDA:MGI.
DR InterPro; IPR009263; SERTA_dom.
DR Pfam; PF06031; SERTA; 1.
DR PROSITE; PS51053; SERTA; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Nucleus; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..314
FT /note="SERTA domain-containing protein 2"
FT /id="PRO_0000191613"
FT DOMAIN 33..80
FT /note="SERTA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00396"
FT REGION 77..119
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 181..222
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 235..311
FT /note="Required for transactivation activity"
FT MOTIF 238..243
FT /note="Nuclear export signal (NES)"
FT COMPBIAS 83..98
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 181..208
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 238
FT /note="L->A: Abolishes the interaction with XPO1 as well as
FT the nuclear export and the subsequent proteasomal
FT degradation."
FT /evidence="ECO:0000269|PubMed:18316374"
FT MUTAGEN 241
FT /note="L->A: Slight resistance to proteasomal degradation,
FT no effect on the interaction with XPO1 neither on nuclear
FT export."
FT /evidence="ECO:0000269|PubMed:18316374"
FT MUTAGEN 243
FT /note="L->A: Slight decrease of interaction with XPO1 and
FT resistance to proteasomal degradation, no effect on nuclear
FT export."
FT /evidence="ECO:0000269|PubMed:18316374"
SQ SEQUENCE 314 AA; 33897 MW; E43107FC565AAC31 CRC64;
MLGKGGKRKF DEHEDGLEGK IVSPCDGPSK VSYTLQRQTI FNISLMKLYN HRPLTEPSLQ
KTVLINNMLR RIQEELKQEG SLRPMFTPSS QPTTEPSDSY REAPPAFSHL ASPSSHPCDL
GSTTPLEACL TPASLLEDDD DTFCTSQAMQ PTAPTKLSPP ALLPEKDSFS SALDEIEELC
PTSTSTEAAT AATDSVKGTS SEAGTQKLDG PQESRADDSK LMDSLPGNFE ITTSTGFLTD
LTLDDILFAD IDTSMYDFDP CTSSSGTASK MAPVSADDLL KTLAPYSSQP VTPSQPFKMD
LTELDHIMEV LVGS
