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O15405 (TOX3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 102. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length576 AA.
Sequence statusComplete.
Protein existenceEvidence 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.

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 576576TOX high mobility group box family member 3
PRO_0000286353

Regions

DNA binding255 – 32369HMG box
Compositional bias32 – 354Poly-Asn
Compositional bias245 – 2506Poly-Lys
Compositional bias431 – 572142Gln-rich

Natural variations

Alternative sequence1 – 2828MDVRF…YYGYS → MKCQPRSGARRIEERLHYLI TTYL in isoform 2.
VSP_043095
Alternative sequence521Missing in isoform 2.
VSP_043096
Natural variant1281V → M.
Corresponds to variant rs16951186 [ dbSNP | Ensembl ].
VAR_055952
Natural variant5721Q → P.
Corresponds to variant rs13332816 [ dbSNP | Ensembl ].
VAR_055953

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 1, 2007. Version 2.
Checksum: 0CE15100A96E1478

FASTA57663,342
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 4447F1086050C823
Show »

FASTA57163,100

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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.
CCDSCCDS54008.1. [O15405-2]
CCDS54009.1. [O15405-1]
RefSeqNP_001073899.2. NM_001080430.2. [O15405-1]
NP_001139660.1. NM_001146188.1. [O15405-2]
UniGeneHs.460789.

3D structure databases

ProteinModelPortalO15405.
SMRO15405. Positions 219-335.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid118139. 1 interaction.
IntActO15405. 1 interaction.
MINTMINT-2795739.
STRING9606.ENSP00000385705.

PTM databases

PhosphoSiteO15405.

Proteomic databases

MaxQBO15405.
PaxDbO15405.
PRIDEO15405.

Protocols and materials databases

DNASU27324.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000219746; ENSP00000219746; ENSG00000103460. [O15405-1]
ENST00000407228; ENSP00000385705; ENSG00000103460. [O15405-2]
GeneID27324.
KEGGhsa:27324.
UCSCuc002egw.2. human. [O15405-1]
uc010vgt.1. human. [O15405-2]

Organism-specific databases

CTD27324.
GeneCardsGC16M052471.
H-InvDBHIX0013031.
HGNCHGNC:11972. TOX3.
HPAHPA040376.
MIM611416. gene.
neXtProtNX_O15405.
PharmGKBPA162406752.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG284736.
HOGENOMHOG000230949.
HOVERGENHBG051183.
OMAPMNQIVA.
OrthoDBEOG7R834J.
PhylomeDBO15405.
TreeFamTF106481.

Gene expression databases

ArrayExpressO15405.
BgeeO15405.
CleanExHS_TOX3.
GenevestigatorO15405.

Family and domain databases

Gene3D1.10.30.10. 1 hit.
InterProIPR009071. HMG_box_dom.
[Graphical view]
PfamPF00505. HMG_box. 1 hit.
[Graphical view]
SMARTSM00398. HMG. 1 hit.
[Graphical view]
SUPFAMSSF47095. SSF47095. 1 hit.
PROSITEPS50118. HMG_BOX_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTOX3. human.
GenomeRNAi27324.
NextBio50340.
PROO15405.
SOURCESearch...

Entry information

Entry nameTOX3_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 102 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM