UniProtKB - O94900 (TOX_HUMAN)
Protein
Thymocyte selection-associated high mobility group box protein TOX
Gene
TOX
Organism
Homo sapiens (Human)
Status
Functioni
Transcriptional regulator with a major role in neural stem cell commitment and corticogenesis as well as in lymphoid cell development and lymphoid tissue organogenesis (By similarity). Binds to GC-rich DNA sequences in the proximity of transcription start sites and may alter chromatin structure, modifying access of transcription factors to DNA. During cortical development, controls the neural stem cell pool by inhibiting the switch from proliferative to differentiating progenitors. Beyond progenitor cells, promotes neurite outgrowth in newborn neurons migrating to reach the cortical plate. May activate or repress critical genes for neural stem cell fate such as SOX2, EOMES and ROBO2 (By similarity). Plays an essential role in the development of lymphoid tissue-inducer (LTi) cells, a subset necessary for the formation of secondary lymphoid organs: peripheral lymph nodes and Peyer's patches. Acts as a developmental checkpoint and regulates thymocyte positive selection toward T cell lineage commitment. Required for the development of various T cell subsets, including CD4-positive helper T cells, CD8-positive cytotoxic T cells, regulatory T cells and CD1D-dependent natural killer T (NKT) cells. Required for the differentiation of common lymphoid progenitors (CMP) to innate lymphoid cells (ILC) (By similarity). May regulate the NOTCH-mediated gene program, promoting differentiation of the ILC lineage. Required at the progenitor phase of NK cell development in the bone marrow to specify NK cell lineage commitment (PubMed:21126536) (By similarity). Upon chronic antigen stimulation, diverts T cell development by promoting the generation of exhaustive T cells, while suppressing effector and memory T cell programming. May regulate the expression of genes encoding inhibitory receptors such as PDCD1 and induce the exhaustion program, to prevent the overstimulation of T cells and activation-induced cell death (By similarity).By similarity1 Publication
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
DNA bindingi | 261 – 329 | HMG boxPROSITE-ProRule annotationAdd BLAST | 69 |
GO - Molecular functioni
- chromatin DNA binding Source: UniProtKB
GO - Biological processi
- CD4-positive, alpha-beta T cell lineage commitment Source: UniProtKB
- CD4-positive, CD25-positive, alpha-beta regulatory T cell lineage commitment Source: UniProtKB
- CD8-positive, alpha-beta T cell lineage commitment Source: UniProtKB
- cerebral cortex neuron differentiation Source: UniProtKB
- chromatin organization Source: UniProtKB-KW
- leukocyte differentiation Source: GO_Central
- lymph node development Source: Ensembl
- natural killer cell differentiation Source: UniProtKB
- NK T cell lineage commitment Source: UniProtKB
- Peyer's patch development Source: Ensembl
- positive regulation of DNA demethylation Source: UniProtKB
- positive regulation of natural killer cell differentiation Source: Ensembl
- positive regulation of neural precursor cell proliferation Source: UniProtKB
- positive regulation of neuron projection development Source: UniProtKB
- regulation of positive thymic T cell selection Source: UniProtKB
- regulation of transcription by RNA polymerase II Source: GO_Central
Keywordsi
Molecular function | Chromatin regulator, DNA-binding |
Biological process | Neurogenesis, Transcription, Transcription regulation |
Enzyme and pathway databases
PathwayCommonsi | O94900 |
Names & Taxonomyi
Protein namesi | Recommended name: Thymocyte selection-associated high mobility group box protein TOX1 PublicationAlternative name(s): Thymus high mobility group box protein TOX1 Publication |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:18988, TOX |
MIMi | 606863, gene |
neXtProti | NX_O94900 |
VEuPathDBi | HostDB:ENSG00000198846.5 |
Subcellular locationi
Nucleus
- Nucleus PROSITE-ProRule annotation
Nucleus
- nucleus Source: UniProtKB
Keywords - Cellular componenti
NucleusPathology & Biotechi
Organism-specific databases
DisGeNETi | 9760 |
OpenTargetsi | ENSG00000198846 |
PharmGKBi | PA162406704 |
Miscellaneous databases
Pharosi | O94900, Tbio |
Genetic variation databases
BioMutai | TOX |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000244569 | 1 – 526 | Thymocyte selection-associated high mobility group box protein TOXAdd BLAST | 526 |
Proteomic databases
EPDi | O94900 |
jPOSTi | O94900 |
MassIVEi | O94900 |
MaxQBi | O94900 |
PaxDbi | O94900 |
PeptideAtlasi | O94900 |
PRIDEi | O94900 |
ProteomicsDBi | 50531 |
TopDownProteomicsi | O94900 |
PTM databases
iPTMneti | O94900 |
PhosphoSitePlusi | O94900 |
Expressioni
Tissue specificityi
Expressed in NK cells (PubMed:21126536). Highly expressed in tumor-infiltrating CD8-positive T cells (at protein level) (PubMed:31207604).2 Publications
Inductioni
Up-regulated during differentiation of NK cells from CD34-positive hematopoietic cells in the presence of IL15. Down-regulated in mature NK cells.1 Publication
Gene expression databases
Bgeei | ENSG00000198846, Expressed in cerebral cortex and 183 other tissues |
Genevisiblei | O94900, HS |
Organism-specific databases
HPAi | ENSG00000198846, Tissue enriched (lymphoid) |
Interactioni
Subunit structurei
Interacts with HBO1 complex composed at least of KAT7/HBO1, ING4, MEAF6, and JADE2; this complex is involved in histone acetylation.
Interacts with DNMT1, LEO1, PAF1, SAP130 and SIN3A; these interactors regulate chromatin remodeling.
Interacts with an array of proteins involved in RNA processing and translation and DNA replication.
By similarityBinary interactionsi
Hide detailsO94900
Protein-protein interaction databases
BioGRIDi | 115107, 8 interactors |
IntActi | O94900, 8 interactors |
STRINGi | 9606.ENSP00000354842 |
Miscellaneous databases
RNActi | O94900, protein |
Family & Domainsi
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 237 – 256 | Nuclear localization signalSequence analysisAdd BLAST | 20 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 417 – 420 | Poly-Pro | 4 |
Phylogenomic databases
eggNOGi | KOG0381, Eukaryota |
GeneTreei | ENSGT00940000159497 |
HOGENOMi | CLU_030650_2_0_1 |
InParanoidi | O94900 |
OMAi | LAMQQPI |
OrthoDBi | 818359at2759 |
PhylomeDBi | O94900 |
TreeFami | TF106481 |
Family and domain databases
Gene3Di | 1.10.30.10, 1 hit |
InterProi | View protein in InterPro IPR009071, HMG_box_dom IPR036910, HMG_box_dom_sf |
Pfami | View protein in Pfam PF00505, HMG_box, 1 hit |
SMARTi | View protein in SMART SM00398, HMG, 1 hit |
SUPFAMi | SSF47095, SSF47095, 1 hit |
PROSITEi | View protein in PROSITE PS50118, HMG_BOX_2, 1 hit |
i Sequence
Sequence statusi: Complete.
O94900-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MDVRFYPPPA QPAAAPDAPC LGPSPCLDPY YCNKFDGENM YMSMTEPSQD
60 70 80 90 100
YVPASQSYPG PSLESEDFNI PPITPPSLPD HSLVHLNEVE SGYHSLCHPM
110 120 130 140 150
NHNGLLPFHP QNMDLPEITV SNMLGQDGTL LSNSISVMPD IRNPEGTQYS
160 170 180 190 200
SHPQMAAMRP RGQPADIRQQ PGMMPHGQLT TINQSQLSAQ LGLNMGGSNV
210 220 230 240 250
PHNSPSPPGS KSATPSPSSS VHEDEGDDTS KINGGEKRPA SDMGKKPKTP
260 270 280 290 300
KKKKKKDPNE PQKPVSAYAL FFRDTQAAIK GQNPNATFGE VSKIVASMWD
310 320 330 340 350
GLGEEQKQVY KKKTEAAKKE YLKQLAAYRA SLVSKSYSEP VDVKTSQPPQ
360 370 380 390 400
LINSKPSVFH GPSQAHSALY LSSHYHQQPG MNPHLTAMHP SLPRNIAPKP
410 420 430 440 450
NNQMPVTVSI ANMAVSPPPP LQISPPLHQH LNMQQHQPLT MQQPLGNQLP
460 470 480 490 500
MQVQSALHSP TMQQGFTLQP DYQTIINPTS TAAQVVTQAM EYVRSGCRNP
510 520
PPQPVDWNND YCSSGGMQRD KALYLT
Sequence cautioni
The sequence BAA34528 differs from that shown. Reason: Erroneous initiation.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 9 | P → V in AAH16665 (PubMed:15489334).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_064759 | 267 | A → T Found in a renal cell carcinoma sample; somatic mutation. 1 Publication | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB018351 mRNA Translation: BAA34528.2 Different initiation. BC016665 mRNA Translation: AAH16665.1 |
CCDSi | CCDS34897.1 |
RefSeqi | NP_055544.1, NM_014729.2 |
Genome annotation databases
Ensembli | ENST00000361421; ENSP00000354842; ENSG00000198846 |
GeneIDi | 9760 |
KEGGi | hsa:9760 |
UCSCi | uc003xtw.1, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB018351 mRNA Translation: BAA34528.2 Different initiation. BC016665 mRNA Translation: AAH16665.1 |
CCDSi | CCDS34897.1 |
RefSeqi | NP_055544.1, NM_014729.2 |
3D structure databases
BMRBi | O94900 |
SMRi | O94900 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 115107, 8 interactors |
IntActi | O94900, 8 interactors |
STRINGi | 9606.ENSP00000354842 |
PTM databases
iPTMneti | O94900 |
PhosphoSitePlusi | O94900 |
Genetic variation databases
BioMutai | TOX |
Proteomic databases
EPDi | O94900 |
jPOSTi | O94900 |
MassIVEi | O94900 |
MaxQBi | O94900 |
PaxDbi | O94900 |
PeptideAtlasi | O94900 |
PRIDEi | O94900 |
ProteomicsDBi | 50531 |
TopDownProteomicsi | O94900 |
Protocols and materials databases
Antibodypediai | 11831, 159 antibodies |
DNASUi | 9760 |
Genome annotation databases
Ensembli | ENST00000361421; ENSP00000354842; ENSG00000198846 |
GeneIDi | 9760 |
KEGGi | hsa:9760 |
UCSCi | uc003xtw.1, human |
Organism-specific databases
CTDi | 9760 |
DisGeNETi | 9760 |
GeneCardsi | TOX |
HGNCi | HGNC:18988, TOX |
HPAi | ENSG00000198846, Tissue enriched (lymphoid) |
MIMi | 606863, gene |
neXtProti | NX_O94900 |
OpenTargetsi | ENSG00000198846 |
PharmGKBi | PA162406704 |
VEuPathDBi | HostDB:ENSG00000198846.5 |
HUGEi | Search... |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0381, Eukaryota |
GeneTreei | ENSGT00940000159497 |
HOGENOMi | CLU_030650_2_0_1 |
InParanoidi | O94900 |
OMAi | LAMQQPI |
OrthoDBi | 818359at2759 |
PhylomeDBi | O94900 |
TreeFami | TF106481 |
Enzyme and pathway databases
PathwayCommonsi | O94900 |
Miscellaneous databases
BioGRID-ORCSi | 9760, 6 hits in 1006 CRISPR screens |
ChiTaRSi | TOX, human |
GeneWikii | TOX |
GenomeRNAii | 9760 |
Pharosi | O94900, Tbio |
PROi | PR:O94900 |
RNActi | O94900, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000198846, Expressed in cerebral cortex and 183 other tissues |
Genevisiblei | O94900, HS |
Family and domain databases
Gene3Di | 1.10.30.10, 1 hit |
InterProi | View protein in InterPro IPR009071, HMG_box_dom IPR036910, HMG_box_dom_sf |
Pfami | View protein in Pfam PF00505, HMG_box, 1 hit |
SMARTi | View protein in SMART SM00398, HMG, 1 hit |
SUPFAMi | SSF47095, SSF47095, 1 hit |
PROSITEi | View protein in PROSITE PS50118, HMG_BOX_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | TOX_HUMAN | |
Accessioni | O94900Primary (citable) accession number: O94900 Secondary accession number(s): Q96AV5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 27, 2006 |
Last sequence update: | June 27, 2006 | |
Last modified: | April 7, 2021 | |
This is version 146 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 8
Human chromosome 8: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot