TOX3_HUMAN
ID TOX3_HUMAN Reviewed; 576 AA.
AC O15405; B4DRD0; B5MCW4;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=TOX high mobility group box family member 3;
DE AltName: Full=CAG trinucleotide repeat-containing gene F9 protein;
DE AltName: Full=Trinucleotide repeat-containing gene 9 protein;
GN Name=TOX3; Synonyms=CAGF9, TNRC9;
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] (ISOFORM 2).
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 246-576 (ISOFORM 1/2).
RC TISSUE=Brain;
RX PubMed=9225980; DOI=10.1007/s004390050476;
RA Margolis R.L., Abraham M.R., Gatchell S.B., Li S.-H., Kidwai A.S.,
RA Breschel T.S., Stine O.C., Callahan C., McInnis M.G., Ross C.A.;
RT "cDNAs with long CAG trinucleotide repeats from human brain.";
RL Hum. Genet. 100:114-122(1997).
RN [4]
RP FUNCTION, HOMODIMERIZATION, INTERACTION WITH CITED1 AND CREB1, ASSOCIATION
RP WITH CHROMATIN, INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=21172805; DOI=10.1242/jcs.068759;
RA Dittmer S., Kovacs Z., Yuan S.H., Siszler G., Kogl M., Summer H.,
RA Geerts A., Golz S., Shioda T., Methner A.;
RT "TOX3 is a neuronal survival factor that induces transcription depending on
RT the presence of CITED1 or phosphorylated CREB in the transcriptionally
RT active complex.";
RL J. Cell Sci. 124:252-260(2011).
CC -!- FUNCTION: Transcriptional coactivator of the p300/CBP-mediated
CC transcription complex. Activates transactivation through cAMP response
CC element (CRE) sites. Protects against cell death by inducing
CC antiapoptotic and repressing pro-apoptotic transcripts. Stimulates
CC transcription from the estrogen-responsive or BCL-2 promoters. Required
CC for depolarization-induced transcription activation of the C-FOS
CC promoter in neurons. Associates with chromatin to the estrogen-
CC responsive C3 promoter region. {ECO:0000269|PubMed:21172805}.
CC -!- SUBUNIT: Homodimer. Interacts with CREB1; the interaction is not
CC depolarization dependent. Interacts with CREBBP (via C-terminus) (By
CC similarity). Interacts (via HGM box) with CITED1 (via C-terminus); the
CC interaction increases estrogen-response element (ERE)-dependent
CC transcription and protection against cell death. Interacts with CREB1
CC (phosphorylated form). {ECO:0000250, ECO:0000269|PubMed:21172805}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O15405-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O15405-2; Sequence=VSP_043095, VSP_043096;
CC -!- TISSUE SPECIFICITY: Expressed mainly in epithelial cells. Expressed in
CC the central nervous system (CNS), in the ileum and within the brain in
CC the frontal and occipital lobe. {ECO:0000269|PubMed:21172805}.
CC -!- INDUCTION: Up-regulated by GPR39 in neuronal cells.
CC {ECO:0000269|PubMed:21172805}.
CC -!- DOMAIN: the C-terminus is required for calcium responsiveness but not
CC for transactivation activity. {ECO:0000250}.
CC -!- DOMAIN: The N-terminus is absolutely necessary for transactivation
CC activity. {ECO:0000250}.
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DR EMBL; AK299202; BAG61242.1; -; mRNA.
DR EMBL; AC007490; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; U80736; AAB91435.1; -; mRNA.
DR CCDS; CCDS54008.1; -. [O15405-2]
DR CCDS; CCDS54009.1; -. [O15405-1]
DR RefSeq; NP_001073899.2; NM_001080430.3. [O15405-1]
DR RefSeq; NP_001139660.1; NM_001146188.2. [O15405-2]
DR AlphaFoldDB; O15405; -.
DR SMR; O15405; -.
DR BioGRID; 118139; 28.
DR IntAct; O15405; 4.
DR MINT; O15405; -.
DR STRING; 9606.ENSP00000219746; -.
DR GlyGen; O15405; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; O15405; -.
DR PhosphoSitePlus; O15405; -.
DR BioMuta; TOX3; -.
DR EPD; O15405; -.
DR jPOST; O15405; -.
DR MassIVE; O15405; -.
DR MaxQB; O15405; -.
DR PaxDb; O15405; -.
DR PeptideAtlas; O15405; -.
DR PRIDE; O15405; -.
DR ProteomicsDB; 48642; -. [O15405-1]
DR ProteomicsDB; 48643; -. [O15405-2]
DR Antibodypedia; 28333; 345 antibodies from 24 providers.
DR DNASU; 27324; -.
DR Ensembl; ENST00000219746.14; ENSP00000219746.9; ENSG00000103460.17. [O15405-1]
DR Ensembl; ENST00000407228.7; ENSP00000385705.3; ENSG00000103460.17. [O15405-2]
DR GeneID; 27324; -.
DR KEGG; hsa:27324; -.
DR MANE-Select; ENST00000219746.14; ENSP00000219746.9; NM_001080430.4; NP_001073899.2.
DR UCSC; uc002egw.3; human. [O15405-1]
DR CTD; 27324; -.
DR DisGeNET; 27324; -.
DR GeneCards; TOX3; -.
DR HGNC; HGNC:11972; TOX3.
DR HPA; ENSG00000103460; Tissue enhanced (intestine, retina, stomach).
DR MIM; 611416; gene.
DR neXtProt; NX_O15405; -.
DR OpenTargets; ENSG00000103460; -.
DR PharmGKB; PA162406752; -.
DR VEuPathDB; HostDB:ENSG00000103460; -.
DR eggNOG; KOG0381; Eukaryota.
DR GeneTree; ENSGT00940000158043; -.
DR HOGENOM; CLU_030650_1_0_1; -.
DR InParanoid; O15405; -.
DR OMA; QQHHMQL; -.
DR OrthoDB; 1465513at2759; -.
DR PhylomeDB; O15405; -.
DR TreeFam; TF106481; -.
DR PathwayCommons; O15405; -.
DR SignaLink; O15405; -.
DR BioGRID-ORCS; 27324; 13 hits in 1092 CRISPR screens.
DR ChiTaRS; TOX3; human.
DR GenomeRNAi; 27324; -.
DR Pharos; O15405; Tbio.
DR PRO; PR:O15405; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; O15405; protein.
DR Bgee; ENSG00000103460; Expressed in mucosa of sigmoid colon and 150 other tissues.
DR ExpressionAtlas; O15405; baseline and differential.
DR Genevisible; O15405; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0031490; F:chromatin DNA binding; IBA:GO_Central.
DR GO; GO:0051219; F:phosphoprotein binding; IPI:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:GO_Central.
DR GO; GO:0042981; P:regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR Gene3D; 1.10.30.10; -; 1.
DR InterPro; IPR009071; HMG_box_dom.
DR InterPro; IPR036910; HMG_box_dom_sf.
DR Pfam; PF00505; HMG_box; 1.
DR SMART; SM00398; HMG; 1.
DR SUPFAM; SSF47095; SSF47095; 1.
DR PROSITE; PS50118; HMG_BOX_2; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; Apoptosis; DNA-binding; Nucleus;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..576
FT /note="TOX high mobility group box family member 3"
FT /id="PRO_0000286353"
FT DNA_BIND 255..323
FT /note="HMG box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00267"
FT REGION 189..258
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 422..443
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 519..563
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 189..218
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 219..240
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..28
FT /note="MDVRFYPAAAGDPASLDFAQCLGYYGYS -> MKCQPRSGARRIEERLHYLI
FT TTYL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043095"
FT VAR_SEQ 52
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043096"
FT VARIANT 128
FT /note="V -> M (in dbSNP:rs16951186)"
FT /id="VAR_055952"
FT VARIANT 572
FT /note="Q -> P (in dbSNP:rs13332816)"
FT /id="VAR_055953"
SQ SEQUENCE 576 AA; 63342 MW; 0CE15100A96E1478 CRC64;
MDVRFYPAAA GDPASLDFAQ CLGYYGYSKF GNNNNYMNMA EANNAFFAAS EQTFHTPSLG
DEEFEIPPIT PPPESDPALG MPDVLLPFQA LSDPLPSQGS EFTPQFPPQS LDLPSITISR
NLVEQDGVLH SSGLHMDQSH TQVSQYRQDP SLIMRSIVHM TDAARSGVMP PAQLTTINQS
QLSAQLGLNL GGASMPHTSP SPPASKSATP SPSSSINEED ADEANRAIGE KRAAPDSGKK
PKTPKKKKKK DPNEPQKPVS AYALFFRDTQ AAIKGQNPNA TFGEVSKIVA SMWDSLGEEQ
KQVYKRKTEA AKKEYLKALA AYRASLVSKA AAESAEAQTI RSVQQTLAST NLTSSLLLNT
PLSQHGTVSA SPQTLQQSLP RSIAPKPLTM RLPMNQIVTS VTIAANMPSN IGAPLISSMG
TTMVGSAPST QVSPSVQTQQ HQMQLQQQQQ QQQQQMQQMQ QQQLQQHQMH QQIQQQMQQQ
HFQHHMQQHL QQQQQHLQQQ INQQQLQQQL QQRLQLQQLQ HMQHQSQPSP RQHSPVASQI
TSPIPAIGSP QPASQQHQSQ IQSQTQTQVL SQVSIF
