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Protein

TOX high mobility group box family member 3

Gene

TOX3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi255 – 32369HMG boxPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • chromatin binding Source: UniProtKB
  • estrogen response element binding Source: UniProtKB
  • phosphoprotein binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Apoptosis, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
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 namesi
Name:TOX3
Synonyms:CAGF9, TNRC9
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:11972. TOX3.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA162406752.

Polymorphism and mutation databases

BioMutaiTOX3.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 576576TOX high mobility group box family member 3PRO_0000286353Add
BLAST

Proteomic databases

MaxQBiO15405.
PaxDbiO15405.
PRIDEiO15405.

PTM databases

PhosphoSiteiO15405.

Expressioni

Tissue specificityi

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.1 Publication

Inductioni

Up-regulated by GPR39 in neuronal cells.1 Publication

Gene expression databases

BgeeiO15405.
CleanExiHS_TOX3.
ExpressionAtlasiO15405. baseline and differential.
GenevisibleiO15405. HS.

Organism-specific databases

HPAiHPA040376.

Interactioni

Subunit structurei

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).By similarity1 Publication

Protein-protein interaction databases

BioGridi118139. 1 interaction.
IntActiO15405. 2 interactions.
MINTiMINT-2795739.
STRINGi9606.ENSP00000219746.

Structurei

3D structure databases

ProteinModelPortaliO15405.
SMRiO15405. Positions 219-335.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi32 – 354Poly-Asn
Compositional biasi245 – 2506Poly-Lys
Compositional biasi431 – 572142Gln-richAdd
BLAST

Domaini

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 similaritiesi

Contains 1 HMG box DNA-binding domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG284736.
GeneTreeiENSGT00560000076898.
HOGENOMiHOG000230949.
HOVERGENiHBG051183.
InParanoidiO15405.
OMAiHSLIMRS.
OrthoDBiEOG7R834J.
PhylomeDBiO15405.
TreeFamiTF106481.

Family and domain databases

Gene3Di1.10.30.10. 1 hit.
InterProiIPR009071. HMG_box_dom.
[Graphical view]
PfamiPF00505. HMG_box. 1 hit.
[Graphical view]
SMARTiSM00398. HMG. 1 hit.
[Graphical view]
SUPFAMiSSF47095. SSF47095. 1 hit.
PROSITEiPS50118. HMG_BOX_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O15405-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MDVRFYPAAA GDPASLDFAQ CLGYYGYSKF GNNNNYMNMA EANNAFFAAS
60 70 80 90 100
EQTFHTPSLG DEEFEIPPIT PPPESDPALG MPDVLLPFQA LSDPLPSQGS
110 120 130 140 150
EFTPQFPPQS LDLPSITISR NLVEQDGVLH SSGLHMDQSH TQVSQYRQDP
160 170 180 190 200
SLIMRSIVHM TDAARSGVMP PAQLTTINQS QLSAQLGLNL GGASMPHTSP
210 220 230 240 250
SPPASKSATP SPSSSINEED ADEANRAIGE KRAAPDSGKK PKTPKKKKKK
260 270 280 290 300
DPNEPQKPVS AYALFFRDTQ AAIKGQNPNA TFGEVSKIVA SMWDSLGEEQ
310 320 330 340 350
KQVYKRKTEA AKKEYLKALA AYRASLVSKA AAESAEAQTI RSVQQTLAST
360 370 380 390 400
NLTSSLLLNT PLSQHGTVSA SPQTLQQSLP RSIAPKPLTM RLPMNQIVTS
410 420 430 440 450
VTIAANMPSN IGAPLISSMG TTMVGSAPST QVSPSVQTQQ HQMQLQQQQQ
460 470 480 490 500
QQQQQMQQMQ QQQLQQHQMH QQIQQQMQQQ HFQHHMQQHL QQQQQHLQQQ
510 520 530 540 550
INQQQLQQQL QQRLQLQQLQ HMQHQSQPSP RQHSPVASQI TSPIPAIGSP
560 570
QPASQQHQSQ IQSQTQTQVL SQVSIF
Length:576
Mass (Da):63,342
Last modified:May 1, 2007 - v2
Checksum:i0CE15100A96E1478
GO
Isoform 2 (identifier: O15405-2) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:571
Mass (Da):63,100
Checksum:i4447F1086050C823
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti128 – 1281V → M.
Corresponds to variant rs16951186 [ dbSNP | Ensembl ].
VAR_055952
Natural varianti572 – 5721Q → P.
Corresponds to variant rs13332816 [ dbSNP | Ensembl ].
VAR_055953

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 2828MDVRF…YYGYS → MKCQPRSGARRIEERLHYLI TTYL in isoform 2. 1 PublicationVSP_043095Add
BLAST
Alternative sequencei52 – 521Missing in isoform 2. 1 PublicationVSP_043096

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK299202 mRNA. Translation: BAG61242.1.
AC007490 Genomic DNA. No translation available.
U80736 mRNA. Translation: AAB91435.1.
CCDSiCCDS54008.1. [O15405-2]
CCDS54009.1. [O15405-1]
RefSeqiNP_001073899.2. NM_001080430.2. [O15405-1]
NP_001139660.1. NM_001146188.1. [O15405-2]
UniGeneiHs.460789.

Genome annotation databases

EnsembliENST00000219746; ENSP00000219746; ENSG00000103460.
ENST00000407228; ENSP00000385705; ENSG00000103460. [O15405-2]
GeneIDi27324.
KEGGihsa:27324.
UCSCiuc002egw.2. human. [O15405-1]
uc010vgt.1. human. [O15405-2]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK299202 mRNA. Translation: BAG61242.1.
AC007490 Genomic DNA. No translation available.
U80736 mRNA. Translation: AAB91435.1.
CCDSiCCDS54008.1. [O15405-2]
CCDS54009.1. [O15405-1]
RefSeqiNP_001073899.2. NM_001080430.2. [O15405-1]
NP_001139660.1. NM_001146188.1. [O15405-2]
UniGeneiHs.460789.

3D structure databases

ProteinModelPortaliO15405.
SMRiO15405. Positions 219-335.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118139. 1 interaction.
IntActiO15405. 2 interactions.
MINTiMINT-2795739.
STRINGi9606.ENSP00000219746.

PTM databases

PhosphoSiteiO15405.

Polymorphism and mutation databases

BioMutaiTOX3.

Proteomic databases

MaxQBiO15405.
PaxDbiO15405.
PRIDEiO15405.

Protocols and materials databases

DNASUi27324.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000219746; ENSP00000219746; ENSG00000103460.
ENST00000407228; ENSP00000385705; ENSG00000103460. [O15405-2]
GeneIDi27324.
KEGGihsa:27324.
UCSCiuc002egw.2. human. [O15405-1]
uc010vgt.1. human. [O15405-2]

Organism-specific databases

CTDi27324.
GeneCardsiGC16M052471.
H-InvDBHIX0013031.
HGNCiHGNC:11972. TOX3.
HPAiHPA040376.
MIMi611416. gene.
neXtProtiNX_O15405.
PharmGKBiPA162406752.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG284736.
GeneTreeiENSGT00560000076898.
HOGENOMiHOG000230949.
HOVERGENiHBG051183.
InParanoidiO15405.
OMAiHSLIMRS.
OrthoDBiEOG7R834J.
PhylomeDBiO15405.
TreeFamiTF106481.

Miscellaneous databases

ChiTaRSiTOX3. human.
GenomeRNAii27324.
NextBioi50340.
PROiO15405.
SOURCEiSearch...

Gene expression databases

BgeeiO15405.
CleanExiHS_TOX3.
ExpressionAtlasiO15405. baseline and differential.
GenevisibleiO15405. HS.

Family and domain databases

Gene3Di1.10.30.10. 1 hit.
InterProiIPR009071. HMG_box_dom.
[Graphical view]
PfamiPF00505. HMG_box. 1 hit.
[Graphical view]
SMARTiSM00398. HMG. 1 hit.
[Graphical view]
SUPFAMiSSF47095. SSF47095. 1 hit.
PROSITEiPS50118. HMG_BOX_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. 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.

Entry informationi

Entry nameiTOX3_HUMAN
AccessioniPrimary (citable) accession number: O15405
Secondary accession number(s): B4DRD0, B5MCW4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 2007
Last sequence update: May 1, 2007
Last modified: July 22, 2015
This is version 109 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.