ZBTB7B (1q21.3), CKROX, THPOK, ZBTB15, ZFP67, ZNF857B

https://www.ncbi.nlm.nih.gov/gene/51043

Official Symbol

ZBTB7B

Official Full Name

zinc finger and BTB domain containing 7B

Also known as

CKROX; THPOK; ZFP67; ZBTB15; ZFP-67; c-KROX; hcKROX; ZNF857B

Summary

This gene encodes a zinc finger-containing transcription factor that acts as a key regulator of lineage commitment of immature T-cell precursors. It is necessary and sufficient for commitment of CD4 lineage, while its absence causes CD8 commitment. It also functions as a transcriptional repressor of type I collagen genes. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2012]

Expression

Broad expression in skin (RPKM 39.5), duodenum (RPKM 31.2) and 25 other tissues See more

Orthologs  mouse all

Preferred Names

zinc finger and BTB domain-containing protein 7B

Names

T-helper-inducing POZ/Krueppel-like factor

krueppel-related zinc finger protein cKrox

zinc finger and BTB domain containing 15

zinc finger protein 67 homolog

zinc finger protein 857B

zinc finger protein Th-POK

 NP_001239335.1  zinc finger and BTB domain-containing protein 7B isoform 2

ORIGIN      
        1 mlqpgphpps pqaaapgeaw pgpsqapwqs leekmgsped dligipfpdh ssellsclne
       61 qrqlghlcdl tirtqgleyr thravlaacs hyfkklfteg gggavmgagg sgtatggaga
      121 gvceldfvgp ealgallefa ytatlttssa nmpavlqaar lleipcviaa cmeilqgsgl
      181 eapspdeddc erarqyleaf atatasgvpn gedsppqvpl pppppppprp varrsrkprk
      241 aflqtkgara nhlvpevptv pahpltyeee evagrvgssg gsgpgdsysp ptgtasppeg
      301 pqsyepyege eeeeelvypp ayglaqgggp plspeelgsd edaidpdlma ylsslhqdnl
      361 apgldsqdkl vrkrrsqmpq ecpvchkiih gagklprhmr thtgekpfac evcgvrftrn
      421 dklkihmrkh tgerpyscph cparflhsyd lknhmhlhtg drpyechlch kafakedhlq
      481 rhlkgqncle vrtrrrrkdd apphypppst aaaspagldl snghldtfrl slarfweqsa
      541 ptgppvstpg ppdddeeega pttpqaegam ess
//

See identical proteins and their annotated locations for NP_001239335.1

Conserved Domains (4) summary

COG5048
Location:379 → 458

COG5048; FOG: Zn-finger [General function prediction only]

sd00017
Location:410 → 430

ZF_C2H2; C2H2 Zn finger [structural motif]

pfam00651
Location:58 → 178

BTB; BTB/POZ domain

pfam13465
Location:450 → 475

zf-H2C2_2; Zinc-finger double domain

1. Th inducing POZ-Kruppel Factor (ThPOK) is a key regulator of the immune response since the early steps of colorectal carcinogenesis. Mariani F, et al. PLoS One, 2013. PMID 23349906, Free PMC Article
2. Transcriptional control of T-cell development. Naito T, et al. Int Immunol, 2011 Nov. PMID 21948191
3. Transcriptional and epigenetic regulation of CD4/CD8 lineage choice. Taniuchi I, et al. Adv Immunol, 2011. PMID 21762816
4. Expanding roles for ThPOK in thymic development. Kappes DJ. Immunol Rev, 2010 Nov. PMID 20969593, Free PMC Article
5. Directing traffic on the NKT-cell highway: a key role for ThPOK. Chakravarti S, et al. Eur J Immunol, 2010 Sep. PMID 20809492

See all (57) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

What's a GeneRIF?

1. In vitro, prolonged activation of naive CD4 T cells in presence of Th1 polarizing cytokines led to the acquisition of perforin-dependent cytotoxic activity. This process was dependent on the Th1 transcription factor Runx3 and was limited by the sustained expression of ThPOK.
2. Authors show that the transcription factor ThPOK binds cooperatively with NF-kappaB to NRCs and mediates their physical proximity with the IFNB1 gene via its ability to oligomerize when bound to DNA.
3. a novel pathway by which TIP60 and ThPOK synergistically suppresses Eomes function and IFNgamma production, which could contribute to the regulation of inflammation.
4. ThPOK may be considered a central regulator of the earliest events in the immune system during colorectal cancer development, decreasing the immune response against cancer cells.
5. The distal regulatory element (DRE) in the Thpok gene also functions as a transcriptional enhancer, with DNA sequences specifically responsible for thymic enhancer activity.
6. ThPOK transgene stably represses CD8 gene expression through the deacetylation of Cd8 loci in CD4 cell lineage commitment.
7. The p65 subunit of NF-kappaB inhibits COL1A1 gene transcription in human dermal and scleroderma fibroblasts through its recruitment on promoter by protein interaction with transcriptional activators (c-Krox, Sp1, and Sp3).
8. comparing the promoter regions of the Th-POK gene between human and mouse, the region 3600 base pairs upstream from the transcription initiation site of the Th-POK gene was highly conserved
9. impairment of Lck-mediated CD4 coreceptor signaling by Nef is an important in vivo mechanism of HIV-1 pathogenesis
10. Thymoma neoplastic epithelial cells can induce Th-POK expression in T-cell subsets similarly to the normal thymic epithelial cells. In addition, there was no significant difference in Runx3 expression in T-cell subsets between normal thymi and thymomas.

J Immunol. 2010 Oct 1;185(7):3960-9. doi: 10.4049/jimmunol.1001462. Epub 2010 Sep 1.

p300-mediated acetylation stabilizes the Th-inducing POK factor.

Zhang M¹, Zhang J, Rui J, Liu X.

 The lineage-specifying factor Th-inducing POK (ThPOK) directs the intrathymic differentiation of CD4 T cells. Although the regulation of ThPOK at the transcription level has been extensively studied, specific posttranslational modifications regulating the activity of ThPOK have not been addressed. In this paper, we show that ThPOK is an unstable protein that is more readily degraded in CD8 T cells compared with CD4 T cells. Among the various proteins that bind ThPOK, acetyltransferase p300 specifically promotes the acetylation of ThPOK at K210, K216, and K339, outcompeting ubiquitination, thereby stabilizing the protein. In CD4 T cells, attenuation of p300-mediated acetylation promotes the degradation of ThPOK. In contrast, mutation of lysines 210, 216, and 339 to arginines stabilizes ThPOK and enhances its ability to suppress the expression of CD8 molecule and cytotoxic effectors in CD8 T cells. Our results reveal an essential role of p300-mediated acetylation in regulating the stability of ThPOK and suggest that such regulation may play a part in CD4/CD8 lineage differentiation.