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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 transcription 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)DescriptionActionsGraphical viewLength
DNA bindingi255 – 323HMG boxPROSITE-ProRule annotationAdd BLAST69

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

  • apoptotic process Source: UniProtKB-KW
  • negative regulation of neuron apoptotic process Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Apoptosis, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000103460-MONOMER.

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
Proteomesi
  • UP000005640 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

DisGeNETi27324.
OpenTargetsiENSG00000103460.
PharmGKBiPA162406752.

Polymorphism and mutation databases

BioMutaiTOX3.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002863531 – 576TOX high mobility group box family member 3Add BLAST576

Proteomic databases

MaxQBiO15405.
PaxDbiO15405.
PeptideAtlasiO15405.
PRIDEiO15405.

PTM databases

iPTMnetiO15405.
PhosphoSitePlusiO15405.

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

BgeeiENSG00000103460.
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

GO - Molecular functioni

  • phosphoprotein binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi118139. 3 interactors.
IntActiO15405. 4 interactors.
MINTiMINT-2795739.
STRINGi9606.ENSP00000219746.

Structurei

3D structure databases

ProteinModelPortaliO15405.
SMRiO15405.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi32 – 35Poly-Asn4
Compositional biasi245 – 250Poly-Lys6
Compositional biasi431 – 572Gln-richAdd BLAST142

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

eggNOGiKOG0381. Eukaryota.
COG5648. LUCA.
GeneTreeiENSGT00560000076898.
HOGENOMiHOG000230949.
HOVERGENiHBG051183.
InParanoidiO15405.
OMAiQYRQDHS.
OrthoDBiEOG091G12A3.
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)DescriptionActionsGraphical viewLength
Natural variantiVAR_055952128V → M.Corresponds to variant rs16951186dbSNPEnsembl.1
Natural variantiVAR_055953572Q → P.Corresponds to variant rs13332816dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0430951 – 28MDVRF…YYGYS → MKCQPRSGARRIEERLHYLI TTYL in isoform 2. 1 PublicationAdd BLAST28
Alternative sequenceiVSP_04309652Missing in isoform 2. 1 Publication1

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_001080430.3. [O15405-1]
NP_001139660.1. NM_001146188.2. [O15405-2]
UniGeneiHs.132574.
Hs.460789.

Genome annotation databases

EnsembliENST00000219746; ENSP00000219746; ENSG00000103460. [O15405-1]
ENST00000407228; ENSP00000385705; ENSG00000103460. [O15405-2]
GeneIDi27324.
KEGGihsa:27324.
UCSCiuc002egw.3. human. [O15405-1]

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_001080430.3. [O15405-1]
NP_001139660.1. NM_001146188.2. [O15405-2]
UniGeneiHs.132574.
Hs.460789.

3D structure databases

ProteinModelPortaliO15405.
SMRiO15405.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118139. 3 interactors.
IntActiO15405. 4 interactors.
MINTiMINT-2795739.
STRINGi9606.ENSP00000219746.

PTM databases

iPTMnetiO15405.
PhosphoSitePlusiO15405.

Polymorphism and mutation databases

BioMutaiTOX3.

Proteomic databases

MaxQBiO15405.
PaxDbiO15405.
PeptideAtlasiO15405.
PRIDEiO15405.

Protocols and materials databases

DNASUi27324.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000219746; ENSP00000219746; ENSG00000103460. [O15405-1]
ENST00000407228; ENSP00000385705; ENSG00000103460. [O15405-2]
GeneIDi27324.
KEGGihsa:27324.
UCSCiuc002egw.3. human. [O15405-1]

Organism-specific databases

CTDi27324.
DisGeNETi27324.
GeneCardsiTOX3.
H-InvDBHIX0013031.
HGNCiHGNC:11972. TOX3.
HPAiHPA040376.
MIMi611416. gene.
neXtProtiNX_O15405.
OpenTargetsiENSG00000103460.
PharmGKBiPA162406752.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0381. Eukaryota.
COG5648. LUCA.
GeneTreeiENSGT00560000076898.
HOGENOMiHOG000230949.
HOVERGENiHBG051183.
InParanoidiO15405.
OMAiQYRQDHS.
OrthoDBiEOG091G12A3.
PhylomeDBiO15405.
TreeFamiTF106481.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000103460-MONOMER.

Miscellaneous databases

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

Gene expression databases

BgeeiENSG00000103460.
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...

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: November 2, 2016
This is version 120 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

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 one 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.