ZNHIT sinkkisormiproteiinit. Kuusi(1-6) ZNHIT- geeniä. Niissä ei ole transkiptiotekijöitä. (Vappuaattokaranteenia pandemian päivinä)

•  ZNHIT1, (7q22.1) CG1L, ZNFN4A1

 https://www.ncbi.nlm.nih.gov/gene/?term=ZNHIT

Preferred Names

zinc finger HIT domain-containing protein 1

Names

H_DJ0747G18.14

cyclin-G1-binding protein 1

p18 Hamlet

p18Hamlet

putative cyclin G1 interacting protein

zinc finger protein subfamily 4A member 1

zinc finger protein, subfamily 4A (HIT domain containing), member 1

zinc finger, HIT domain containing 1

zinc finger, HIT type 1

1. Low ZNHIT1 expression is associated with breast cancer.
2. Study reports that p18(Hamlet) can also mediate the cell cycle arrest induced in response to gamma-irradiation, by participating in the p53-dependent upregulation of the cell cycle inhibitor p21(Cip1) (CDKN1A).
3. p18(Hamlet) is a new cell-fate regulator that links the p38 MAPK and p53 pathways and contributes to the establishment of p53-regulated stress responses.

• ZNHIT2, (11q13.1),  C11orf5, FON

HIT zinc finger

This presumed zinc finger contains up to 6 cysteine residues that could coordinate zinc. The domain is named after the HIT protein. This domain is also found in the Thyroid receptor interacting protein 3 (TRIP-3) that specifically interact with the ligand binding domain of the thyroid receptor.
https://www.ncbi.nlm.nih.gov/gene/?term=ZNHIT2 

1. The interaction between RUVBL1/RUVBL2 and the U5 small nuclear ribonucleoprotein is mostly mediated by the previously uncharacterized factor ZNHIT2.
2. The unique three-dimensional structure of the zinc finger HIT domain revealed a novel zinc-binding fold, as a new member of the treble clef domain family

• ZNHIT3 (17q12) , Hit1, PEHO, TRIP3

https://www.ncbi.nlm.nih.gov/gene/9326

Preferred Names

zinc finger HIT domain-containing protein 3

Names

HNF-4a coactivator

TR-interacting protein 3

TRIP-3

thyroid hormone receptor interactor 3

thyroid receptor interacting protein 3

zinc finger, HIT domain containing 3

zinc finger, HIT type 3

1. results suggest that loss-of-function missense mutation of znhit3 underlies PEHO syndrome. Progressive encephalopathy with oedema, hypsarrhythmia, and optic atrophy (PEHO)
2. Results solve the structure of a complex resulting from interaction between protein fragments of human NUFIP1 and its cofactor ZNHIT3, and emphasize their imbrication. Also, it seems that the complexes involving NUFIP1, ZNHIT3, and SNU13 share strong structural similarities between human and yeast, suggesting that the initial steps of the box C/D snoRNP assembly process are conserved among species.
3. Results identify TRIP3 as a novel regulator of PPARgamma-mediated adipocyte differentiation.
4. A high GYPC gene expression is associated with an unfavorable outcome, in contrast, a high TRIP3 gene expression is associated with a favorable outcome in childhood ALL.

• ZNHIT4(2p13.1), INO80,

 HMGA1L4, HMGIYL4, IES2, PAP-1BP, PAPA-1, PAPA1, hIes2
 https://www.ncbi.nlm.nih.gov/gene/?term=ZNHIT4

Preferred Names

INO80 complex subunit B

Names

IES2 homolog

PAP (Pim-1 associated protein) associated protein 1

PAP-1 binding protein

PAP-1-associated protein 1

high mobility group AT-hook 1-like 4

zinc finger HIT domain-containing protein 4

zinc finger, HIT type 4

 Knockdown of INO80 complex subunit B (INO80B; ZNHIT4) by siRNA enhances the early stages of HIV-1 replication in HeLa-CD4 cells infected with viral pseudotypes HIV89.6R and HIV8.2N

1. Susceptibility allele-specific loss of miR-1324-mediated silencing of the INO80B chromatin-assembly complex gene in pre-eclampsia. Oudejans CB, et al. Hum Mol Genet, 2015 Jan 1. PMID 25143393
2. A novel nucleolar protein, PAPA-1, induces growth arrest as a result of cell cycle arrest at the G1 phase. Kuroda TS, et al. Gene, 2004 Sep 29. PMID 15556297
3. PAPA-1 Is a nuclear binding partner of IGFBP-2 and modulates its growth-promoting actions. Miyako K, et al. Mol Endocrinol, 2009 Feb. PMID 19095771, Free PMC Article
4. E2F6 associates with BRG1 in transcriptional regulation. Leung JY, et al. PLoS One, 2012. PMID 23082233, Free PMC Article
5. YY1 functions with INO80 to activate transcription. Cai Y, et al. Nat Struct Mol Biol, 2007 Sep. PMID 17721549

• ZNHIT5,  (1q32.1) DDX59, 

DEAD-box helicase 59

 https://www.ncbi.nlm.nih.gov/gene/?term=ZNHIT5

Preferred Names

probable ATP-dependent RNA helicase DDX59

Names

DEAD (Asp-Glu-Ala-Asp) box polypeptide 59

DEAD box protein 59

zinc finger HIT domain-containing protein 5

• ZNHIT6, (1p22.3), BCD1, C1orf181, NY-BR-75

 https://www.ncbi.nlm.nih.gov/gene/54680

Preferred Names

box C/D snoRNA protein 1

Names

box C/D snoRNA essential 1 homolog

serologically defined breast cancer antigen NY-BR-75

zinc finger HIT domain-containing protein 6

zinc finger, HIT type 6

1. Proteomic and 3D structure analyses highlight the C/D box snoRNP assembly mechanism and its control. Bizarro J, et al. J Cell Biol, 2014 Nov 24. PMID 25404746, Free PMC Article
2. Humoral immunity to human breast cancer: antigen definition and quantitative analysis of mRNA expression. Scanlan MJ, et al. Cancer Immun, 2001 Mar 30. PMID 12747765
3. A dynamic scaffold of pre-snoRNP factors facilitates human box C/D snoRNP assembly. McKeegan KS, et al. Mol Cell Biol, 2007 Oct. PMID 17636026, Free PMC Article
4. A high-confidence interaction map identifies SIRT1 as a mediator of acetylation of USP22 and the SAGA coactivator complex. Armour SM, et al. Mol Cell Biol, 2013 Apr. PMID 23382074, Free PMC Article
5. R2TP/Prefoldin-like component RUVBL1/RUVBL2 directly interacts with ZNHIT2 to regulate assembly of U5 small nuclear ribonucleoprotein. Cloutier P, et al. Nat Commun, 2017 May 31. PMID 28561026, Free PMC Article

 

Löytyi artikkeli ZBTB-proteiinien ryhmästä: 49 kappaletta.

doi: 10.1007/s12185-016-2035-x

• Review Article
• Published: 01 June 2016

 Suomennosta: Hematopoieettinen kehitys (verisolujen kehittyminen omia linjojaan) säätyy ZBTB- transkriptiotekijöillä.  Eri solu injaspesifiset geenit ja  eri erilaistumisvaiheiden  geenit ilmentyvät koordinoidusti  johtamaan hematopoieettista kehitystä.  Transkriptiotekijöillä on tässä päätehtäviään ja jos niissä on hämminkiä, se ilmenee  erilaisina hematologisina ja immunologisina häiriöinä. Ihmisen  genomista  koodautuu  lähes  1900 transkriptiofaktoria. Niistä on  BTB-domaanin omaavia sinkkisormiproteiineja  49 kappaletta. ( BTB on lythennys englantilaisista  sanoista Broad-complex, Tram-track and Bric a´ brac. Ne ovat nimiä,  joita on annettu  ensimmäisille  geeni-homologeille  ehkä  banaanikärpäsellä tai muulla  tieteen  tarkasti tutkimalla  eliöllä ja sitten on vastaavaa geeniä löytynyt ihmiskunnasta ja näin  geenidomeeninb nimi siirtyy ihmisen geenin osien nimiin jonain käytännöllisenä lyhennyksenä, jolla  geenejä voi  tieteen kirjallisuudessa ryhmittää ja  erottaa  toisistaan). ZBTB-proteiineilla on myös toinen nimi POK- proteiini. BTB domeenia sanotaan myös POZ- domeeniksi, mikä  tulee sanoista  " poxvirus and zinc finger".  Sinkkisormi struktuurilla on oma tyyppinsä näissäkin.    Lisäksi molekyylillä on Krüppel-tyyppisiä  sinkkisormia, mistä  K- kirjain.  (C- terminaaliset  sinkkisormet näyttävät  duaalirakenteisilta näissä proteiineissa PubMed sekvensseissä). 

Regulation of hematopoietic development by ZBTB transcription factors

• Takahiro Maeda 

International Journal of Hematology volume 104, pages310–323(2016)Cite this article

Abstract

Hematopoietic development is governed by the coordinated expression of lineage- and differentiation stage-specific genes. Transcription factors play major roles in this process and their perturbation may underlie hematologic and immunologic disorders. Nearly 1900 transcription factors are encoded in the human genome: of these, 49 BTB (for broad-complex, tram-track and bric à brac)-zinc finger transcription factors referred to as ZBTB or POK proteins have been identified. ZBTB proteins, including BCL6, PLZF, ThPOK and LRF, exhibit a broad spectrum of functions in normal and malignant hematopoiesis. This review summarizes developmental and molecular functions of ZBTB proteins relevant to hematology.

ZBTB protein molecular mechanisms

ZBTB proteins are prototypical TFs consisting of an N-terminal BTB domain functioning in protein–protein interactions and C-terminal C2H2/Krüppel-type zinc fingers, which bind DNA (Fig. 1a). Between those domains lies a linker domain, whose amino acid sequence is less conserved among family proteins (Fig. 1a). The BTB domain was named after three Drosophila genes, broad-complex, tram-track and bric à brac, all encoding proteins essential for Drosophila development [12]. The BTB domain is also known as the POZ (for poxvirus and zinc finger) domain, as it is present in many poxvirus-related proteins [13]; thus ZBTB proteins are sometimes referred as POK (POZ and krüppel-type zinc fingers) proteins.

The BTB domain

The BTB domain exerts two major functions: dimer formation and recruitment of transcriptional regulators (Fig. 1a). Biochemical and structural analyses revealed that the domain forms an obligate homodimer [7], which is essential for ZBTB protein function in some contexts

ZBTB7A:

  For example, wild-type LRF [for Leukemia/lymphoma-Related Factor [14] (also known as FBI-1 [15], POKE-MON [16], OCZF [17]); encoded by ZBTB7A] can rescue germinal center B cell defects observed in Lrf conditional knockout (KO) mice, while a dimerization-deficient LRF mutant cannot [18]. 

 ZBTB27:

 The BTB domain can also mediate heterodimer formation. Among heterodimers identified are LRF and BCL6 (B cell Lymphoma 6; encoded by ZBTB27) 

ZBTB17:

[14], BCL6 and MIZ-1 (Myc-interacting zinc finger protein-1; encoded by ZBTB17) [19],

ZBTB28:

BCL6 and BCL6B (a.k.a. BAZF; encoded by ZBTB28) [20] and 

ZBTB16:

PLZF (Promyelocytic Leukemia Zinc Finger; encoded by ZBTB16) and

 ZBTB32;

 FAZF (also known as ROG [21], PLZP [22], or TZFP [23]; encoded by ZBTB32). 

 It remains unclear whether only BTB domains mediate heteromeric interactions. Higher order oligomerization through the BTB domain has also been reported: PLZF-BTB domain can form oligomers through its N-terminal β-sheet [24], whereas the MIZ-1 BTB domain forms a tetramer [25].

BTB domains can also recruit transcriptional regulators (Fig. 1a). The transcriptional co-repressors NCOR (nuclear receptor co-repressor) and SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) are homologous proteins originally identified as co-repressors for retinoic acid receptors (RARs) and thyroid hormone receptors [26, 27]. These co-repressors function via recruiting histone deacetylases (HDACs), namely HDAC3 [28]. The functional connection between BTB domains and co-repressors became apparent when NCOR and SMRT were identified in a complex with the leukemia-associated RAR fusion proteins, PML-RARα and PLZF-RARα [29–31]. The latter interacts with SMRT/NCOR not only through the C-terminal RAR moiety but also through the N-terminal PLZF-BTB domain [29, 32, 33]. The BCL6 BTB domain was subsequently found to associate with both SMRT and NCOR [34, 35]. Importantly, BTB homodimer formation is a prerequisite to co-repressor recruitment [36]. Structural analysis revealed that a 17 amino acid residue of SMRT, called SMRT-BBD (SMRT-BCL6 binding domain), binds to a surface created by a BTB homodimer [36]. Thus, any potential BCL6 monomer cannot recruit the co-repressor complex. A recent study suggested that BCL6 serves as a critical downstream effector of SMRT/NCOR [37]. ChIP-seq (chromatin immunoprecipitation with massively parallel DNA sequencing) analysis revealed that nearly half of SMRT/NCOR binding sites were reduced or lost in Bcl6 KO macrophages [37]. Furthermore, almost 70 % of DNA occupancy sites are shared between SMRT-BCL6 and NCOR-BCL6 complexes, indicating a high degree of overlap between both co-repressors in the context of BCL6-mediated gene silencing [37]....

ZBTB7C (18q21.1), ZBTB36, ZNF857C, APM-1, APM1

 ZBTB7C, https://www.ncbi.nlm.nih.gov/gene/201501

Official Symbol

ZBTB7C

Official Full Name

zinc finger and BTB domain containing 7C

Also known as

APM1; APM-1; ZBTB36; ZNF857C

Expression

Broad expression in esophagus (RPKM 8.6), skin (RPKM 4.3) and 18 other tissues See more

Orthologs  mouse al

Related articles in PubMed

1. Characterization of a novel human papillomavirus DNA in the cervical carcinoma cell line ME180. Reuter S, et al. J Virol, 1991 Oct. PMID 1716694, Free PMC Article
2. Kr-POK (ZBTB7c) regulates cancer cell proliferation through glutamine metabolism. Hur MW, et al. Biochim Biophys Acta Gene Regul Mech, 2017 Aug. PMID 28571744
3. Integrative Mouse and Human Studies Implicate ANGPT1 and ZBTB7C as Susceptibility Genes to Ischemic Injury. Du R, et al. Stroke, 2015 Dec. PMID 26542693, Free PMC Article CONCLUSIONS: Genetic variations of ANGPT1 and ZBTB7C are associated with increased infarct size in both mice and humans. ZBTB7C may modulate the ischemic response via neuronal apoptosis and dynamic collateralization and, in addition to ANGPT1, may serve as potential novel targets for treatments of cerebral ischemia.
   
4. Adrenomedullin and adrenomedullin binding protein-1 protect endothelium-dependent vascular relaxation in sepsis. Zhou M, et al. Mol Med, 2007 Sep-Oct. PMID 17932560, Free PMC Article Abstract
5. APM-1, a novel human gene, identified by aberrant co-transcription with papillomavirus oncogenes in a cervical carcinoma cell line, encodes a BTB/POZ-zinc finger protein with growth inhibitory activity. Reuter S, et al. EMBO J, 1998 Jan 2. PMID 9427755, Free PMC Article

See all (14) citations in PubMed

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

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

1. Repression of Kr-POK inhibited tumor growth.
2. ZBTB7C genetic variations were significant for susceptibility to ischemic injury in cerebral ischemia.
3. our findings define KR-POK as a transcriptional repressor with a pro-oncogenic role that relies upon binding to p53 and inhibition of its transactivation function.

ZBTB7A (19p13.3), ZBTB7, ZNF857A, FBI-1, FBI-1, TIP21, pokemon

https://www.ncbi.nlm.nih.gov/pubmed/31385585/

Official Symbol

ZBTB7A

Official Full Name

zinc finger and BTB domain containing 7A

Also known as

LRF; FBI1; FBI-1; TIP21; ZBTB7; ZNF857A; pokemon

Expression

Ubiquitous expression in colon (RPKM 8.0), stomach (RPKM 5.5) and 25 other tissues See more

Orthologs mouse all

Preferred Names

zinc finger and BTB domain-containing protein 7A

Names

HIV-1 1st-binding protein 1

HIV-1 inducer of short transcripts binding protein

POK erythroid myeloid ontogenic factor

POZ and Krueppel erythroid myeloid ontogenic factor

TTF-I-interacting peptide 21

factor binding IST protein 1

factor that binds to inducer of short transcripts protein 1

leukemia/lymphoma-related factor, ( LRF)

lymphoma related factor

pokemon 1

zinc finger and BTB domain containing 7A, HIV-1 inducer of short transcripts binding protein

zinc finger protein 857A

  NP_001304919.1  zinc finger and BTB domain-containing protein 7A

ORIGIN      
        1 maggvdgpig ipfpdhssdi lsglneqrtq gllcdvvilv egrefpthrs vlaacsqyfk
       61 klftsgavvd qqnvyeidfv saealtalmd faytatltvs tanvgdilsa arlleipavs
      121 hvcadlldrq ilaadagada gqldlvdqid qrnllrakey leffqsnpmn slppaaaaaa
      181 asfpwsafga sdddldatke avaaavaava agdcngldfy gpgppaerpp tgdgdegdsn
      241 pglwperded aptgglfppp vappaatqng hygrggeeea aslseaapep gdspgflsga
      301 aegedgdgpd vdglaastll qqmmssvgra gaaagdsdee sraddkgvmd yylkyfsgah
      361 dgdvypawsq kvekkiraka fqkcpicekv iqgagklprh irthtgekpy ecnickvrft
      421 rqdklkvhmr khtgekpylc qqcgaafahn ydlknhmrvh tglrpyqcds ccktfvrsdh
      481 lhrhlkkdgc ngvpsrrgrk prvrggapdp spgatatpga paqpsspdar rngqekhfkd
      541 edededvasp dglgrlnvag aggggdsggg pgaatdgnft agla

 

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 encode the same protein.

Conserved Domains (3) summary

sd00017
Location:412 → 432

ZF_C2H2; C2H2 Zn finger [structural motif]

pfam00651
Location:24 → 131

BTB; BTB/POZ domain

pfam13465
Location:425 → 449

zf-H2C2_2; Zinc-finger double domain

Related articles in PubMed

1. ZBTB7A promotes migration, invasion and metastasis of human breast cancer cells through NF-κB-induced epithelial-mesenchymal transition in vitro and in vivo. Mao A, et al. J Biochem, 2019 Dec 1. PMID 31385585
2. LRF acts as an activator and repressor of the human β-like globin gene transcription in a developmental stage dependent manner. Kang J, et al. Biochem Cell Biol, 2019 Aug. PMID 30427207
3. Impact of ZBTB7A hypomethylation and expression patterns on treatment response to hydroxyurea. Chondrou V, et al. Hum Genomics, 2018 Oct 1. PMID 30285874, Free PMC Article
4. Expression of Zinc Finger and BTB Domain-containing 7A in Colorectal Carcinoma. Joo JW, et al. Anticancer Res, 2018 May. PMID 29715100
5. Stable knockdown of ZBTB7A promotes cell proliferation and progression in nasopharyngeal carcinoma. Liu F, et al. Tumori, 2018 Jan-Feb. PMID 29699474

See all (109) citations in PubMed

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

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

1. miR-137 was identified to negatively regulate the expression of ZBTB7, and its abundance is inversely correlated with that of ZBTB7 in renal carcinoma specimens and cell lines.
2. ZBTB7A had a positive association with NR_047538.
3. The high expression of ZBTB7A may promote cell migration, invasion and tumour metastasis, which may be related to EMT events by regulating NF-kappaB.
4. The results indicate that LRF may act as an activator and repressor of the human beta-like globin gene transcription in a manner dependent on developmental stage.
5. ZBTB7A transcriptionally regulates ER-alpha expression in ER-alpha-positive breast cancer cell lines by binding to the ESR1 promoter leading to increased transcription of ER-alpha.
6. Direct epigenetic repression of the transcription-repressive regulators NCOR2 and ZBTB7A by the histone reader protein HP1gamma leads to activation of protumorigenic genes in lung adenocarcinoma.
7. Some forms of hereditary persistence of fetal hemoglobin, a rare benign condition where individuals express the gamma-globin gene throughout adulthood, are caused by point mutations in the gamma-globin gene promoter at regions residing ~115 and 200 bp upstream of the transcription start site. We found that the major fetal globin gene repressors BCL11A and ZBTB7A directly bound to the sites at -115 and -200 bp, respecti...
8. ZBTB7 was upregulated in colorectal cancer and promoted cancer progression.ZBTB7 mediated 5fluorouracil drug resistance in the colorectal cancer cells through NFkappaB signaling.
9. This is one of the very first pharmacoepigenomic studies indicating that the hypomethylation of ZBTB7A during hydroxyurea (HU) treatment enhances the LRF expression, which by its turn suppresses the HbF resumption in the HU non-responders
10. ASXL2 and ZBTB7A mutations were frequently identified in Japanese AML patients with t(8;21), but not in those with inv(16). Further analysis is required to clarify the detailed biological mechanism of AE9a regulation of the cohesin complex.

Protein	Gene	Interaction	Pubs
Tat	tat	Binding of FBI-1 to HIV-1 Tat is mediated by the zinc finger (ZF) domain of FBI-1 (amino acids 377-584) and is diminished by point mutations in Tat at amino acids 18, 30, and 31	PubMed
	tat	FBI-1 is a cellular POZ-domain-containing protein that binds to the HIV-1 LTR and Tat protein and specifically stimulates Tat activity

 

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.

ZBTB6 (9q33.2), ZID, ZNF482

ZBTB6,https://www.ncbi.nlm.nih.gov/gene/10773

Official Symbol  ZBTB6

Official Full Name zinc finger and BTB domain containing 6provided by HGNC

Also known as ZID; ZNF482

Expression Ubiquitous expression in lymph node (RPKM 5.7), thyroid (RPKM 5.5) and 25 other tissues See more Orthologs  mouse all

1. NM_006626.6 → NP_006617.1  zinc finger and BTB domain-containing protein 6
   See identical proteins and their annotated locations for NP_006617.1
   

   Conserved Domains (5) summary

   sd00017
   Location:328 → 348

   ZF_C2H2; C2H2 Zn finger [structural motif]

   pfam00096
   Location:326 → 348

   zf-C2H2; Zinc finger, C2H2 type

   pfam00651
   Location:23 → 127

   BTB; BTB/POZ domain

   pfam13465
   Location:340 → 364

   zf-H2C2_2; Zinc-finger double domain

   pfam15909
   Location:331 → 401

   zf-C2H2_8; C2H2-type zinc ribbon

Related articles in PubMed

1. The POZ domain: a conserved protein-protein interaction motif. Bardwell VJ, et al. Genes Dev, 1994 Jul 15. PMID 795884  Abstract
   We describe a novel zinc finger protein, ZID (zinc finger protein with interaction domain). At its amino terminus ZID contains a 120-amino-acid conserved motif present in a large family of proteins that includes both the otherwise unrelated zinc finger proteins, such as Ttk, GAGA, and ZF5, and a group of poxvirus proteins: We therefore refer to this domain as the POZ (poxvirus and zinc finger) domain. The POZ domains of ZID, Ttk, and GAGA act to inhibit the interaction of their associated finger regions with DNA. This inhibitory effect is not dependent on interactions with other proteins and does not appear dependent on specific interactions between the POZ domain and the finger region. The POZ domain acts as a specific protein-protein interaction domain: The POZ domains of ZID and Ttk can interact with themselves but not with each other, POZ domains from ZF5, or the viral protein SalF17R. However, the POZ domain of GAGA can interact efficiently with the POZ domain of Ttk. In transfection experiments, the ZID POZ domain inhibits DNA binding in NIH-3T3 cells and appears to localize the protein to discrete regions of the nucleus. We discuss the implications of multimerization for the function of POZ domain proteins.
2. NAC1, a POZ/BTB protein that functions as a corepressor. Korutla L, et al. Neurochem Int, 2009 Mar-Apr. PMID 19121354We now demonstrate that NAC1 acts as a corepressor for other POZ/BTB proteins. NAC1 is a POZ/BTB motif containing transcriptional repressor protein. In a mammalian two hybrid assay in neuronal (N2A) cells and non-neuronal (HEK 293T) cells, VP16 activation domain tagged NAC1 resulted in significant reversal of transcriptional inhibition with the Gal4-ZID, Gal4-BCL6, Gal4-ZF5, and kelch proteins Gal4-MAYVEN (KLHL2)   and Gal4-NRP/B fusion proteins. We also observed similar results with another corepressor, BCoR Gal4 fusion protein. NAC1 potentiated ZF5 mediated repression in Gal4-DBD fusion transient assays. GST pulldown assays further confirmed protein-protein interactions between these proteins and NAC1. Both the NAC1 isoforms demonstrated selective interaction through the POZ/BTB domain but not with the non-POZ/BTB region. Endogenous NAC1 and BCL6 physically associated in CNS regions. Strikingly, NAC1 did not interact with the pro-myelocytic leukemia zinc finger protein (PLZF/ZBTB16) ), another POZ/BTB protein that is not found in the adult brain. Therefore, we conclude that NAC1 functions as a corepressor for POZ/BTB proteins expressed in the mature CNS.
3. Functional proteomics mapping of a human signaling pathway. Colland F, et al. Genome Res, 2004 Jul. PMID 15231748, Free PMC Article
4. An atlas of combinatorial transcriptional regulation in mouse and man. Ravasi T, et al. Cell, 2010 Mar 5. PMID 20211142, Free PMC Article
5. A proteome-scale map of the human interactome network. Rolland T, et al. Cell, 2014 Nov 20. PMID 25416956, Free PMC Article

See all (9) citations in PubMed

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ZBTB5 (9p13.2); p21 transkirption vaimentaja

  https://www.ncbi.nlm.nih.gov/gene/9925

1. Expression

   Ubiquitous expression in thyroid (RPKM 6.3), esophagus (RPKM 6.3) and 25 other tissues

2. NM_014872.3 → NP_055687.1  zinc finger and BTB domain-containing protein 5
   
   

   Conserved Domains (4) summary

   smart00225
   Location:25 → 119

   BTB; Broad-Complex, Tramtrack and Bric a brac

   sd00017
   Location:615 → 635

   ZF_C2H2; C2H2 Zn finger [structural motif]

   pfam00651
   Location:14 → 119

   BTB; BTB/POZ domain

   pfam13465
   Location:627 → 652

   zf-H2C2_2; Zinc-finger double domain

ORIGIN      
        1 mdfpghfeqi fqqlnyqrlh gqlcdcvivv gnrhfkahrs vlaacsthfr alfsvaegdq
       61 tmnmiqldse vvtaeafaal idmmytstlm lgesnvmdvl laashlhlns vvkackhylt
      121 trtlpmspps ervqeqsarm qrsfmlqqlg lsivssalns sqngeeqpap msssmrsnld
      181 qrtpfpmrrl hkrkqsaeer arqrlrpsid esaisdvtpe ngpsgvhsre effspdslki
      241 vdnpkadgmt dnqedsaimf dqsfgtqeda qvpsqsdnsa gnmaqlsmas ratqvetsfd
      301 qeaapekssf qcenpevglg ekehmrvvvk seplsspepq devsdvtsqa egsesveveg
      361 vvvsaekidl spessdrsfs dpqsstdrvg dihilevtnn lehkstfsis nflnksrgnn
      421 ftanqnnddn ipnttsdcrl eseapyllsp eagpaggpss apgshvenpf sepadshfvr
      481 pmqevmglpc vqtsgyqgge qfgmdfsrsg lglhssfsrv migsprggas nfpyyrriap
      541 kmpvvtsvrs sqipenstss qlmmngatss fenghpsqpg ppqltrasad vlskckkals
      601 ehnvlvvega rkyackicck tfltltdckk hirvhtgekp yaclkcgkrf sqsshlykhs
      661 kttclrwqss nlpstll

Related articles in PubMed

1. A novel POK family transcription factor, ZBTB5, represses transcription of p21CIP1 gene. Koh DI, et al. J Biol Chem, 2009 Jul 24. PMID 19491398, Free PMC Article Abstract
   Transcriptional repression through chromatin remodeling and histone deacetylation has been postulated as a driving force for tumorigenesis. We isolated and characterized a novel POZ domain Krüppel-like zinc finger transcription repressor, ZBTB5 (zinc finger and BTB domain-containing 5). Serial analysis of gene expression (SAGE) analysis showed that ZBTB5 expression is higher in retinoblastoma and muscle cancer tissues. Immunocytochemistry showed that ZBTB5 was localized to the nucleus, particularly nuclear speckles. ZBTB5 directly repressed transcription of cell cycle arrest gene p21 by binding to the proximal GC-box 5/6 elements and the two distal p53-responsive elements (bp -2323 approximately -2299; bp -1416 approximately -1392). Chromatin immunoprecipitation assays showed that ZBTB5 and p53 competed with each other in occupying the p53 binding elements. ZBTB5 interacted with co-repressor-histone deacetylase complexes such as BCoR (BCL-6-interacting corepressor), NCoR (nuclear receptor corepressor), and SMRT (silencing mediator for retinoid and thyroid receptors) via its POZ domain. These interactions resulted in deacetylation of histones Ac-H3 and Ac-H4 at the proximal promoter, which is important in the transcriptional repression of p21. MTT (3-(4,5-di meth yl thi azol-2-yl)-2,5-diphenyltetrazolium bromide) assays and fluorescent-activated cell sorter analysis revealed that ZBTB5 stimulated both cell proliferation and cell cycle progression, significantly increasing the number of cells in S-phase. Overall, our data suggest that ZBTB5 is a potent transcription repressor of cell cycle arrest gene p21 and a potential proto-oncogene stimulating cell proliferation.

See all (18) citations in PubMed

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 ZBTB5 directly repressed transcription of cell cycle arrest gene p21 by binding to the proximal GC-box 5/6 elements and the two distal p53-responsive elements (bp -2323 to -2299; bp -1416 to -1392)

 

ZBTB16 , (11q23.2), PLZF, ZNF145, Säädellee AT2 reseptoria

 ZBTB16 (11q23.2),
https://www.ncbi.nlm.nih.gov/protein/NP_001018011.1

Official Full Name

zinc finger and BTB domain containing 16

Also known as

PLZF; ZNF145

Summary

This gene is a member of the Krueppel C2H2-type zinc-finger protein family and encodes a zinc finger transcription factor that contains nine Kruppel-type zinc finger domains at the carboxyl terminus. This protein is located in the nucleus, is involved in cell cycle progression, and interacts with a histone deacetylase. Specific instances of aberrant gene rearrangement at this locus have been associated with acute promyelocytic leukemia (APL). Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]

Expression

Broad expression in fat (RPKM 27.9), ovary (RPKM 22.2) and 19 other tissues See more

Orthologs

mouse all

Preferred Names

zinc finger and BTB domain-containing protein 16

Names

promyelocytic leukaemia zinc finger

zinc finger protein 145 (Kruppel-like, expressed in promyelocytic leukemia)

zinc finger protein PLZF

Retrovirus HIV-1 Vif säätää alas  ZBTB16 ilmentymisen T-soluissa, joissa  Vif expressoituu.

Conserved Domains (4) summary

COG5048
Location:448 → 622

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

sd00017
Location:520 → 540

ZF_C2H2; C2H2 Zn finger [structural motif]

pfam00651
Location:25 → 125

BTB; BTB/POZ domain

cl28033
Location:177 → 327

Herpes_ICP4_C; Herpesvirus ICP4-like protein C-terminal region

  
            Summary: This gene is a member of the Krueppel C2H2-type
            zinc-finger protein family and encodes a zinc finger transcription
            factor that contains nine Kruppel-type zinc finger domains at the
            carboxyl terminus. This protein is located in the nucleus, is
            involved in cell cycle progression, and interacts with a histone
            deacetylase. Specific instances of aberrant gene rearrangement at
            this locus have been associated with acute promyelocytic leukemia
            (APL). Alternate transcriptional splice variants have been
            characterized. [provided by RefSeq, Jul 2008].

ORIGIN      
        1 mdltkmgmiq lqnpshptgl lckanqmrla gtlcdvvimv dsqefhahrt vlactskmfe
       61 ilfhrnsqhy tldflspktf qqileyayta tlqakaedld dllyaaeile ieyleeqclk
      121 mletiqasdd ndteatmadg gaeeeedrka rylknifisk hsseesgyas vagqslpgpm
      181 vdqspsvsts fglsamsptk aavdslmtig qsllqgtlqp pagpeeptla gggrhpgvae
      241 vktemmqvde vpsqdspgaa essisggmgd kveergkegp gtptrssvit sarelhygre
      301 esaeqvpppa eagqaptgrp ehpapppekh lgiysvlpnh kadavlsmps svtsglhvqp
      361 alavsmdfst yggllpqgfi qrelfsklge lavgmksesr tigeqcsvcg velpdneave
      421 qhrklhsgmk tygcelcgkr fldslrlrmh llahsagaka fvcdqcgaqf skedalethr
      481 qthtgtdmav fcllcgkrfq aqsalqqhme vhagvrsyic secnrtfpsh talkrhlrsh
      541 tgdhpyecef cgscfrdest lkshkrihtg ekpyecngcg kkfslkhqle thyrvhtgek
      601 pfecklchqr srdysamikh lrthngaspy qcticteycp slssmqkhmk ghkpeeippd
      661 wriektylyl cyv
// 

https://www.scienceopen.com/document_file/080cd021-f521-4ae2-a1c4-96859161b4e3/

PubMedCentral/080cd021-f521-4ae2-a1c4-96859161b4e3.pdf

• “Guimond and Gallo-PayetAngiotensin-AT2 receptor and neuronal physiology

  PLZF (11q28.2) ZBTB16 , ZNF145. 

  Association between the AT2 receptor and the promyelocytic leukemia zinc finger (PLZF)

   protein has been observed using a yeast two-hybrid system (Senbonmatsu et al., 2003). In CHO 

   cells expressing both PLZF and AT2 receptors, Ang II stimulation induces

   co-localization of PLZF with the AT2 receptor, followed by internalization of the complex.

   This observation is in contrast with other studies observing no internalization of

   the AT2receptor following Ang II stimulation (Hunyady et al., 1994;Hein et al., 1997).

   Since internalization of the receptor was observed only in cells expressing PLZF,

   this could represent a new regulatory pathway of AT2 receptor function, specific only

    to selected cell types. However, beside internalization of AT2 receptor, a recent study

   showed that PLZF  was implicated in neuroprotection in a stroke model (Seidelet al., 2011).

   In this study, the authors  showed that PLZF exerts neuroprotective effect in a model of in

   vitro glutamate toxicity.They also showed that overexpression of PLZF in neuronal cells 

  in culture induced a significant increase in AT2 receptor

   expression, suggesting that PLZF could also be implicated in the regulation of AT2receptor 

  expression.    

HERC2115q13), HECT ja RLD domaanin omaava E3 ubikitiiniligaasi 2. G-quadruplex

https://www.ncbi.nlm.nih.gov/gene/8924 

Official Symbol   HERC2

Official Full Name  HECT and RLD domain containing E3 ubiquitin protein ligase 2

Also known as  jdf2; p528; MRT38; SHEP1; D15F37S1

Summary  This gene belongs to the HERC gene family that encodes a group of unusually large proteins, which contain multiple structural domains. All members have at least 1 copy of an N-terminal region showing homology to the cell cycle regulator RCC1 and a C-terminal HECT (homologous to E6-AP C terminus) domain found in a number of E3 ubiquitin protein ligases. Genetic variations in this gene are associated with skin/hair/eye pigmentation variability. Multiple pseudogenes of this gene are located on chromosomes 15 and 16. [provided by RefSeq, Mar 2012]

Expression  Ubiquitous expression in brain (RPKM 8.9), ovary (RPKM 8.1) and 25 other tissues See more Orthologs mouse all

 

Cancer Res. 2018 Nov 15;78(22):6371-6385. doi: 10.1158/0008-5472.CAN-18-1877. Epub 2018 Oct 2.

HERC2 Facilitates BLM and WRN Helicase Complex Interaction with RPA to Suppress G-Quadruplex DNA.

Wu W¹, Rokutanda N¹, Takeuchi J^1,2, Lai Y^1,3, Maruyama R⁴, Togashi Y¹, Nishikawa H⁵, Arai N⁶, Miyoshi Y⁷, Suzuki N², Saeki Y⁶, Tanaka K⁶, Ohta T⁸.Abstract

BLM and WRN are RecQ DNA helicases  essential for genomic stability. Here, we demonstrate that HERC2, a HECT E3 ligase, is critical for their functions to suppress G-quadruplex (G4) DNA.
 HERC2 interacted with BLM, WRN, and replication protein A (RPA) complexes during the S-phase of the cell cycle. Depletion of HERC2 dissociated RPA from BLM and WRN complexes and significantly increased G4 formation. Triple depletion revealed that HERC2 has an epistatic relationship with BLM and WRN in their G4-suppressing function. In vitro, HERC2 released RPA onto single-stranded DNA (ssDNA) rather than anchoring onto RPA-coated ssDNA. CRISPR/Cas9-mediated deletion of the catalytic ubiquitin-binding site of HERC2 inhibited ubiquitination of RPA2, caused RPA accumulation in the helicase complexes, and increased G4, indicating an essential role for E3 activity in the suppression of G4. Both depletion of HERC2 and inactivation of E3 sensitized cells to the G4-interacting compounds telomestatin and pyridostatin. Overall, these results indicate that HERC2 is a master regulator of G4 suppression that affects the sensitivity of cells to G4 stabilizers. Given that HERC2 expression is frequently reduced in many types of cancers, G4 accumulation as a result of HERC2 deficiency may provide a therapeutic target for G4 stabilizers.Significance: HERC2 is revealed as a master regulator of G-quadruplex, a DNA secondary structure that triggers genomic instability and may serve as a potential molecular target in cancer therapy.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/22/6371/F1.large.jpg Cancer Res; 78(22); 6371-85. ©2018 AACR.

©2018 American Association for Cancer Research.

ZBTB3 (11q12.3)

  ZBTB3  (11q12.3) https://www.ncbi.nlm.nih.gov/gene/79842

1. NM_001363108.2 → NP_001350037.1  zinc finger and BTB domain-containing protein 3
   
   Status: VALIDATED

   Source sequence(s)

   AP001160

   Conserved Domains (4) summary

   sd00017
   Location:424 → 444

   ZF_C2H2; C2H2 Zn finger [structural motif]

   pfam00651
   Location:14 → 115

   BTB; BTB/POZ domain

   pfam13465
   Location:437 → 461

   zf-H2C2_2; Zinc-finger double domain

   cl26464
   Location:173 → 401

   Atrophin-1; Atrophin-1 family
   

   Atrophin-1 family

   Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteristic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity

1. Zinc finger and BTB domain-containing protein 3 is essential for the growth of cancer cells. Lim JH. BMB Rep, 2014 Jul. PMID 24856827, Free PMC Article
2. Recruitment of the Mammalian Histone-modifying EMSY Complex to Target Genes Is Regulated by ZNF131. Varier RA, et al. J Biol Chem, 2016 Apr 1. PMID 26841866, Free PMC Article
3. Bcl2-associated athanogene 3 interactome analysis reveals a new role in modulating proteasome activity. Chen Y, et al. Mol Cell Proteomics, 2013 Oct. PMID 23824909, Free PMC Article
4. Functional proteomics mapping of a human signaling pathway. Colland F, et al. Genome Res, 2004 Jul. PMID 15231748, Free PMC Article
5. An atlas of combinatorial transcriptional regulation in mouse and man. Ravasi T, et al. Cell, 2010 Mar 5. PMID 20211142, Free PMC Article

See all (12) citations in PubMed

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

MB Rep. 2014 Jul;47(7):405-10.
Zinc finger and BTB domain-containing protein 3 is essential for the growth of cancer cells.

Lim JH¹.

Author information

Abstract

ZBTB3 belongs to the Zinc finger and BTB/POZ domain containing transcription factor family; however, its biological role has rarely been studied. We demonstrate for the first time, to our knowledge, that ZBTB3 is an essential factor for cancer cell growth via the regulation of the ROS detoxification pathway. Suppression of ZBTB3 using two different short hairpin RNAs in human melanoma, lung carcinoma, and breast carcinoma results in diminished cell growth. In addition, we found that suppression of ZBTB3 activates a caspase cascade, including caspase-9, -3, and PARP leading to cellular apoptosis, resulting from failed ROS detoxification. We identified that ZBTB3 plays an important role in the gene expression of ROS detoxification enzymes. Our results reveal that ZBTB3 may play a critical role in cancer cell growth via the ROS detoxification system. Therefore, therapeutic strategies that target ZBTB3 could be used in selective cancer treatments.

PMID:

24856827

PMCID:

PMC4163853

DOI:

10.5483/bmbrep.2014.47.7.075

[Indexed for MEDLINE]

Free PMC Article