O15405 (TOX3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
TOX high mobility group box family member 3

Alternative name(s):
CAG trinucleotide repeat-containing gene F9 protein
Trinucleotide repeat-containing gene 9 protein

Gene names

Name:	TOX3
Synonyms:	CAGF9, TNRC9

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	576 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcriptional coactivator of the p300/CBP-mediated trancription complex. Activates transactivation through cAMP response element (CRE) sites. Protects against cell death by inducing antiapoptotic and repressing pro-apoptotic transcripts. Stimulates transcription from the estrogen-responsive or BCL-2 promoters. Required for depolarization-induced transcription activation of the C-FOS promoter in neurons. Associates with chromatin to the estrogen-responsive C3 promoter region. Ref.4
Subunit structure	Homodimer. Interacts with CREB1; the interaction is not depolarization dependent. Interacts with CREBBP (via C-terminus) By similarity. Interacts (via HGM box) with CITED1 (via C-terminus); the interaction increases estrogen-response element (ERE)-dependent transcription and protection against cell death. Interacts with CREB1 (phosphorylated form). Ref.4
Subcellular location	Nucleus Probable.
Tissue specificity	Expressed mainly in epithelial cells. Expressed in the central nervous system (CNS), in the ileum and within the brain in the frontal and occipital lobe. Ref.4
Induction	Up-regulated by GPR39 in neuronal cells. Ref.4
Domain	the C-terminus is required for calcium responsiveness but not for transactivation activity By similarity. The N-terminus is absolutely necessary for transactivation activity By similarity.
Sequence similarities	Contains 1 HMG box DNA-binding domain.

Ontologies

Keywords
Biological process	Apoptosis Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	DNA-binding
Molecular function	Activator
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of neuron apoptotic process Inferred from direct assay Ref.4. Source: UniProtKB positive regulation of transcription, DNA-dependent Inferred from direct assay Ref.4. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	chromatin binding Inferred from direct assay Ref.4. Source: UniProtKB estrogen response element binding Inferred from direct assay Ref.4. Source: UniProtKB protein homodimerization activity Inferred from direct assay Ref.4. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O15405-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O15405-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-28: MDVRFYPAAAGDPASLDFAQCLGYYGYS → MKCQPRSGARRIEERLHYLITTYL
     52-52: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 576	576	TOX high mobility group box family member 3		PRO_0000286353
Regions
	DNA binding	255 – 323	69	HMG box
	Compositional bias	32 – 35	4	Poly-Asn
	Compositional bias	245 – 250	6	Poly-Lys
	Compositional bias	431 – 572	142	Gln-rich
Natural variations
	Alternative sequence	1 – 28	28	MDVRF…YYGYS → MKCQPRSGARRIEERLHYLI TTYL in isoform 2.		VSP_043095
	Alternative sequence	52	1	Missing in isoform 2.		VSP_043096
	Natural variant	128	1	V → M. Corresponds to variant rs16951186 [ dbSNP | Ensembl ].		VAR_055952
	Natural variant	572	1	Q → P. Corresponds to variant rs13332816 [ dbSNP | Ensembl ].		VAR_055953

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 2007. Version 2. Checksum: 0CE15100A96E1478	FASTA	576	63,342
	10 20 30 40 50 60 MDVRFYPAAA GDPASLDFAQ CLGYYGYSKF GNNNNYMNMA EANNAFFAAS EQTFHTPSLG 70 80 90 100 110 120 DEEFEIPPIT PPPESDPALG MPDVLLPFQA LSDPLPSQGS EFTPQFPPQS LDLPSITISR 130 140 150 160 170 180 NLVEQDGVLH SSGLHMDQSH TQVSQYRQDP SLIMRSIVHM TDAARSGVMP PAQLTTINQS 190 200 210 220 230 240 QLSAQLGLNL GGASMPHTSP SPPASKSATP SPSSSINEED ADEANRAIGE KRAAPDSGKK 250 260 270 280 290 300 PKTPKKKKKK DPNEPQKPVS AYALFFRDTQ AAIKGQNPNA TFGEVSKIVA SMWDSLGEEQ 310 320 330 340 350 360 KQVYKRKTEA AKKEYLKALA AYRASLVSKA AAESAEAQTI RSVQQTLAST NLTSSLLLNT 370 380 390 400 410 420 PLSQHGTVSA SPQTLQQSLP RSIAPKPLTM RLPMNQIVTS VTIAANMPSN IGAPLISSMG 430 440 450 460 470 480 TTMVGSAPST QVSPSVQTQQ HQMQLQQQQQ QQQQQMQQMQ QQQLQQHQMH QQIQQQMQQQ 490 500 510 520 530 540 HFQHHMQQHL QQQQQHLQQQ INQQQLQQQL QQRLQLQQLQ HMQHQSQPSP RQHSPVASQI 550 560 570 TSPIPAIGSP QPASQQHQSQ IQSQTQTQVL SQVSIF
	Isoform 2 [UniParc]. Checksum: 4447F1086050C823	FASTA	571	63,100
	10 20 30 40 50 60 MKCQPRSGAR RIEERLHYLI TTYLKFGNNN NYMNMAEANN AFFAASETFH TPSLGDEEFE 70 80 90 100 110 120 IPPITPPPES DPALGMPDVL LPFQALSDPL PSQGSEFTPQ FPPQSLDLPS ITISRNLVEQ 130 140 150 160 170 180 DGVLHSSGLH MDQSHTQVSQ YRQDPSLIMR SIVHMTDAAR SGVMPPAQLT TINQSQLSAQ 190 200 210 220 230 240 LGLNLGGASM PHTSPSPPAS KSATPSPSSS INEEDADEAN RAIGEKRAAP DSGKKPKTPK 250 260 270 280 290 300 KKKKKDPNEP QKPVSAYALF FRDTQAAIKG QNPNATFGEV SKIVASMWDS LGEEQKQVYK 310 320 330 340 350 360 RKTEAAKKEY LKALAAYRAS LVSKAAAESA EAQTIRSVQQ TLASTNLTSS LLLNTPLSQH 370 380 390 400 410 420 GTVSASPQTL QQSLPRSIAP KPLTMRLPMN QIVTSVTIAA NMPSNIGAPL ISSMGTTMVG 430 440 450 460 470 480 SAPSTQVSPS VQTQQHQMQL QQQQQQQQQQ MQQMQQQQLQ QHQMHQQIQQ QMQQQHFQHH 490 500 510 520 530 540 MQQHLQQQQQ HLQQQINQQQ LQQQLQQRLQ LQQLQHMQHQ SQPSPRQHSP VASQITSPIP 550 560 570 AIGSPQPASQ QHQSQIQSQT QTQVLSQVSI F

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[2]	"The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"cDNAs with long CAG trinucleotide repeats from human brain." Margolis R.L., Abraham M.R., Gatchell S.B., Li S.-H., Kidwai A.S., Breschel T.S., Stine O.C., Callahan C., McInnis M.G., Ross C.A. Hum. Genet. 100:114-122(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 246-576 (ISOFORM 1/2). Tissue: Brain.
[4]	"TOX3 is a neuronal survival factor that induces transcription depending on the presence of CITED1 or phosphorylated CREB in the transcriptionally active complex." Dittmer S., Kovacs Z., Yuan S.H., Siszler G., Kogl M., Summer H., Geerts A., Golz S., Shioda T., Methner A. J. Cell Sci. 124:252-260(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, HOMODIMERIZATION, INTERACTION WITH CITED1 AND CREB1, ASSOCIATION WITH CHROMATIN, INDUCTION, TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK299202 mRNA. Translation: BAG61242.1. AC007490 Genomic DNA. No translation available. U80736 mRNA. Translation: AAB91435.1.
IPI	IPI00903025. IPI00929129.
RefSeq	NP_001073899.2. NM_001080430.2. NP_001139660.1. NM_001146188.1.
UniGene	Hs.460789.
3D structure databases
HSSP	HSSP built from PDB template 2CO9 based on UniProtKB Q66JW3.
ProteinModelPortal	O15405.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000385705.
PTM databases
PhosphoSite	O15405.
Proteomic databases
PaxDb	O15405.
PRIDE	O15405.
Protocols and materials databases
DNASU	27324.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000219746; ENSP00000219746; ENSG00000103460. ENST00000407228; ENSP00000385705; ENSG00000103460.
GeneID	27324.
KEGG	hsa:27324.
UCSC	uc002egw.2. human.
Organism-specific databases
CTD	27324.
GeneCards	GC16M052471.
H-InvDB	HIX0013031.
HGNC	HGNC:11972. TOX3.
HPA	HPA040376.
MIM	611416. gene.
neXtProt	NX_O15405.
PharmGKB	PA162406752.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG284736.
HOGENOM	HOG000230949.
HOVERGEN	HBG051183.
OMA	HSLIMRS.
Gene expression databases
ArrayExpress	O15405.
Bgee	O15405.
CleanEx	HS_TOX3.
Genevestigator	O15405.
Family and domain databases
Gene3D	1.10.30.10. 1 hit.
InterPro	IPR009071. HMG_box_dom. [Graphical view]
Pfam	PF00505. HMG_box. 1 hit. [Graphical view]
SMART	SM00398. HMG. 1 hit. [Graphical view]
SUPFAM	SSF47095. HMG-box. 1 hit.
PROSITE	PS00353. HMG_BOX_1. False negative. PS50118. HMG_BOX_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	TOX3. human.
GenomeRNAi	27324.
NextBio	50340.
SOURCE	Search...

Entry information

Entry name

TOX3_HUMAN

Accession

Primary (citable) accession number: O15405
Secondary accession number(s): B4DRD0, B5MCW4

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 2007
Last sequence update:	May 1, 2007
Last modified:	May 1, 2013
This is version 90 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.