ZBTB32

Last updated

ZBTB32
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases ZBTB32 , FAXF, FAZF, Rog, TZFP, ZNF538, zinc finger and BTB domain containing 32
External IDs OMIM: 605859 MGI: 1891838 HomoloGene: 8661 GeneCards: ZBTB32
Orthologs
SpeciesHumanMouse
Entrez

27033

58206

Ensembl

ENSG00000011590

ENSMUSG00000006310

UniProt

Q9Y2Y4

Q9JKD9

RefSeq (mRNA)

NM_014383
NM_001316902
NM_001316903

NM_021397

RefSeq (protein)

NP_001303831
NP_001303832
NP_055198

NP_067372

Location (UCSC) Chr 19: 35.7 – 35.72 Mb Chr 7: 30.29 – 30.3 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Zinc finger and BTB domain-containing protein 32 is a protein that in humans is encoded by the 1960 bp ZBTB32 gene. The 52 kDa protein (487 aa) is a transcriptional repressor and the gene is expressed in T and B cells upon activation, but also significantly in testis cells. It is a member of the Poxviruses and Zinc-finger (POZ) and Krüppel (POK) family of proteins, [5] [6] and was identified in multiple screens involving either immune cell tumorigenesis or immune cell development.

Contents

The protein recruits histone modification enzymes to chromatin to affect gene activation. [7] ZBTB32 recruits corepressors, such as N-CoR and HDACs to its target genes, induces repressive chromatin states and acts cooperatively with other proteins, e.g. with Blimp-1, [7] to suppress the transcription of genes . [7]

It contains a N-terminal BTB/POZ domain (IPR000210) or a SKP1/BTB/POZ domain (IPR011333), and three C-terminal zinc fingers, Znf_C2H2_sf. (IPR036236), Znf_C2H2_type domain (IPR013087), a Znf_RING/FYVE/PHD domain (IPR013083), followed by a putative UBZ4 domain. [8]

Nomenclature

Zinc finger and BTB domain-containing protein 32 is also known as:

Interactions

Zbtb32 has been shown to interact with:

Immune system

The expression of ZBTB32 is induced by inflammatory cytokines and promotes proliferation of natural killer cells. [14]

Zbtb32 knockout mice show a trend to develop type 1 diabetes, although the difference is not statistically different. Furthermore the Zbtb32 do not show a difference in lymphocyte proliferation, possibly due to compensation from other genes. [15]

Cancer

ZBTB32 is highly expressed in spermatogonial stem cells, in hematopoietic stem and progenitor cells, in diffuse large B-cell lymphoma (DLBCL) and appears to suppress the immune system by silencing the CIITA gene. [16]

The transcription factor gene GATA3 is altered in mammary tumors. Down-regulation of GATA3 expression and activity by the Zinc-finger elbow-related proline domain protein 2 (Zpo2), whereas Zbtb32 facilitates Zpo2 targeting to the GATA3 promoter, results in the development of aggressive breast cancers. [12]

A DNA methylation correlation network was built based on the methylation correlation between differentially methylated genes. A survival analysis of candidate biomarkers was performed. One of eight biomarkers and hub genes identified in colon cancer is ZBTB32. [17]

The expression of Zbtb32 is upregulated after exposure to cisplatin. [18]

Related Research Articles

<span class="mw-page-title-main">GLI1</span> Protein-coding gene in humans

Zinc finger protein GLI1 also known as glioma-associated oncogene is a protein that in humans is encoded by the GLI1 gene. It was originally isolated from human glioblastoma cells.

<span class="mw-page-title-main">Krüppel associated box</span> Protein domain

The Krüppel associated box (KRAB) domain is a category of transcriptional repression domains present in approximately 400 human zinc finger protein-based transcription factors. The KRAB domain typically consists of about 75 amino acid residues, while the minimal repression module is approximately 45 amino acid residues. It is predicted to function through protein-protein interactions via two amphipathic helices. The most prominent interacting protein is called TRIM28 initially visualized as SMP1, cloned as KAP1 and TIF1-beta. Substitutions for the conserved residues abolish repression.

<span class="mw-page-title-main">BCL6</span> Transcription factor for converting Naive T cells to TFH

Bcl-6 is a protein that in humans is encoded by the BCL6 gene. BCL6 is a master transcription factor for regulation of T follicular helper cells proliferation. BCL6 has three evolutionary conserved structural domains. The interaction of these domains with corepressors allows for germinal center development and leads to B cell proliferation.

<span class="mw-page-title-main">Zinc finger and BTB domain-containing protein 16</span> Protein found in humans

Zinc finger and BTB domain-containing protein 16 is a protein that in humans is encoded by the ZBTB16 gene.

<span class="mw-page-title-main">Fanconi anemia, complementation group C</span> Protein-coding gene in the species Homo sapiens

Fanconi anemia group C protein is a protein that in humans is encoded by the FANCC gene. This protein delays the onset of apoptosis and promotes homologous recombination repair of damaged DNA. Mutations in this gene result in Fanconi anemia, a human rare disorder characterized by cancer susceptibility and cellular sensitivity to DNA crosslinks and other damages.

<span class="mw-page-title-main">FANCA</span> Protein-coding gene in the species Homo sapiens

Fanconi anaemia, complementation group A, also known as FAA, FACA and FANCA, is a protein which in humans is encoded by the FANCA gene. It belongs to the Fanconi anaemia complementation group (FANC) family of genes of which 12 complementation groups are currently recognized and is hypothesised to operate as a post-replication repair or a cell cycle checkpoint. FANCA proteins are involved in inter-strand DNA cross-link repair and in the maintenance of normal chromosome stability that regulates the differentiation of haematopoietic stem cells into mature blood cells.

<span class="mw-page-title-main">FANCD2</span> Protein-coding gene in the species Homo sapiens

Fanconi anemia group D2 protein is a protein that in humans is encoded by the FANCD2 gene. The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ, FANCL, FANCM, FANCN and FANCO.

<span class="mw-page-title-main">FANCG</span> Protein-coding gene in the species Homo sapiens

Fanconi anemia group G protein is a protein that in humans is encoded by the FANCG gene.

<span class="mw-page-title-main">ZBTB17</span> Protein-coding gene in the species Homo sapiens

Zinc finger and BTB domain-containing protein 17 is a protein that in humans is encoded by the ZBTB17 gene.

<span class="mw-page-title-main">BACH1</span> Protein-coding gene in the species Homo sapiens

Transcription regulator protein BACH1 is a protein that in humans is encoded by the BACH1 gene.

<span class="mw-page-title-main">ZBTB33</span> Protein-coding gene in the species Homo sapiens

Transcriptional regulator Kaiso is a protein that in humans is encoded by the ZBTB33 gene. This gene encodes a transcriptional regulator with bimodal DNA-binding specificity, which binds to methylated CGCG and also to the non-methylated consensus KAISO-binding site TCCTGCNA. The protein contains an N-terminal POZ/BTB domain and 3 C-terminal zinc finger motifs. It recruits the N-CoR repressor complex to promote histone deacetylation and the formation of repressive chromatin structures in target gene promoters. It may contribute to the repression of target genes of the Wnt signaling pathway, and may also activate transcription of a subset of target genes by the recruitment of catenin delta-2 (CTNND2). Its interaction with catenin delta-1 (CTNND1) inhibits binding to both methylated and non-methylated DNA. It also interacts directly with the nuclear import receptor Importin-α2, which may mediate nuclear import of this protein. Alternatively spliced transcript variants encoding the same protein have been identified.

<span class="mw-page-title-main">FANCF</span> Protein-coding gene in the species Homo sapiens

Fanconi anemia group F protein is a protein that in humans is encoded by the FANCF gene.

<span class="mw-page-title-main">RNF4</span> Protein-coding gene in the species Homo sapiens

RING finger protein 4 is a protein that in humans is encoded by the RNF4 gene.

<span class="mw-page-title-main">ZBTB7A</span> Protein-coding gene in the species Homo sapiens

Zinc finger and BTB domain-containing protein 7A is a protein that in humans is encoded by the ZBTB7A gene.

<span class="mw-page-title-main">ZNF238</span> Protein-coding gene in humans

Zinc finger protein 238 is a zinc finger containing transcription factor that in humans is encoded by the ZNF238 gene.

<span class="mw-page-title-main">PATZ1</span> Protein-coding gene in the species Homo sapiens

POZ-, AT hook-, and zinc finger-containing protein 1 is a protein that in humans is encoded by the PATZ1 gene.

<span class="mw-page-title-main">ZNF24</span> Protein-coding gene in the species Homo sapiens

Zinc finger protein 24 is a protein that in humans is encoded by the ZNF24 gene.

<span class="mw-page-title-main">ZFP161</span> Protein-coding gene in the species Homo sapiens

Zinc finger protein 161 homolog is a protein that in humans is encoded by the ZFP161 gene.

<span class="mw-page-title-main">BTB/POZ domain</span>

The BTB/POZ domain is a common structural domain contained within some proteins. It is present near the N-terminus of a fraction of zinc finger proteins and in proteins that contain the Kelch motif and a family of pox virus proteins. The BTB/POZ domain mediates homomeric dimerisation and in some instances heteromeric dimerisation. The structure of the dimerised PLZF BTB/POZ domain has been solved and consists of a tightly intertwined homodimer. The central scaffolding of the protein is made up of a cluster of alpha-helices flanked by short beta-sheets at both the top and bottom of the molecule. BTB/POZ domains from several zinc finger proteins have been shown to mediate transcriptional repression and to interact with components of histone deacetylase co-repressor complexes including N-CoR and SMRT. The POZ or BTB domain is also known as BR-C/Ttk or ZiN.

In molecular biology, the BEN domain is a protein domain which is found in diverse proteins including:

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000011590 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000006310 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 Hoatlin ME, Zhi Y, Ball H, Silvey K, Melnick A, Stone S, Arai S, Hawe N, Owen G, Zelent A, Licht JD (December 1999). "A novel BTB/POZ transcriptional repressor protein interacts with the Fanconi anemia group C protein and PLZF". Blood. 94 (11): 3737–47. doi:10.1182/blood.V94.11.3737. PMID   10572087.
  6. ↑ "Entrez Gene: ZBTB32 zinc finger and BTB domain containing 32".
  7. 1 2 3 Yoon HS, Scharer CD, Majumder P, Davis CW, Butler R, Zinzow-Kramer W, Skountzou I, Koutsonanos DG, Ahmed R, Boss JM (2012). "ZBTB32 is an early repressor of the CIITA and MHC class II gene expression during B cell differentiation to plasma cells". Journal of Immunology. 189 (5): 2393–403. doi:10.4049/jimmunol.1103371. PMC   3424359 . PMID   22851713.
  8. ↑ Rizzo AA, Salerno PE, Bezsonova I, Korzhnev DM (September 2014). "NMR structure of the human Rad18 zinc finger in complex with ubiquitin defines a class of UBZ domains in proteins linked to the DNA damage response". Biochemistry. 53 (37): 5895–906. doi:10.1021/bi500823h. PMID   25162118.
  9. ↑ Hoatlin ME, Zhi Y, Ball H, Silvey K, Melnick A, Stone S, Arai S, Hawe N, Owen G, Zelent A, Licht JD (December 1999). "A novel BTB/POZ transcriptional repressor protein interacts with the Fanconi anemia group C protein and PLZF". Blood. 94 (11): 3737–47. doi:10.1182/blood.V94.11.3737. PMID   10572087.
  10. ↑ Reuter TY, Medhurst AL, Waisfisz Q, Zhi Y, Herterich S, Hoehn H, Gross HJ, Joenje H, Hoatlin ME, Mathew CG, Huber PA (October 2003). "Yeast two-hybrid screens imply involvement of Fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport". Experimental Cell Research. 289 (2): 211–21. doi:10.1016/s0014-4827(03)00261-1. PMID   14499622.
  11. ↑ Han SH, Jeon JH, Ju HR, Jung U, Kim KY, Yoo HS, Lee YH, Song KS, Hwang HM, Na YS, Yang Y, Lee KN, Choi I (June 2003). "VDUP1 upregulated by TGF-beta1 and 1,25-dihydorxyvitamin D3 inhibits tumor cell growth by blocking cell-cycle progression". Oncogene. 22 (26): 4035–46. doi: 10.1038/sj.onc.1206610 . PMID   12821938.
  12. 1 2 Shahi P, Wang CY, Lawson DA, Slorach EM, Lu A, Yu Y, Lai MD, Gonzalez Velozo H, Werb Z (2017). "ZNF503/Zpo2 drives aggressive breast cancer progression by down-regulation of GATA3 expression". Proc Natl Acad Sci U S A. 114 (12): 3169–3174. Bibcode:2017PNAS..114.3169S. doi: 10.1073/pnas.1701690114 . PMC   5373372 . PMID   28258171.
  13. ↑ Tsuzuki S, Enver T (May 2002). "Interactions of GATA-2 with the promyelocytic leukemia zinc finger (PLZF) protein, its homologue FAZF, and the t(11;17)-generated PLZF-retinoic acid receptor alpha oncoprotein". Blood. 99 (9): 3404–10. doi: 10.1182/blood.V99.9.3404 . PMID   11964310.
  14. ↑ Beaulieu AM, Madera S, Sun JC (2015). "Molecular Programming of Immunological Memory in Natural Killer Cells". Crossroads Between Innate and Adaptive Immunity V. Advances in Experimental Medicine and Biology. Vol. 850. pp. 81–91. doi:10.1007/978-3-319-15774-0_7. ISBN   978-3-319-15773-3. PMID   26324348.
  15. ↑ Coley WD, Zhao Y, Benck CJ, Liu Y, Hotta-Iwamura C, Rahman MJ, Tarbell KV (2018). "Loss of Zbtb32 in NOD mice does not significantly alter T cell responses". F1000Research. 7: 318. doi: 10.12688/f1000research.13864.1 . PMC   5909056 . PMID   29707204.
  16. ↑ Zhu C, Chen G, Zhao Y, Gao XM, Wang J (2018). "Regulation of the Development and Function of B Cells by ZBTB Transcription Factors". Frontiers in Immunology. 9: 580. doi: 10.3389/fimmu.2018.00580 . PMC   5869932 . PMID   29616049.
  17. ↑ Zhang C, Zhao H, Li J, Liu H, Wang F, Wei Y, Su J, Zhang D, Liu T, Zhang Y (2015). "The identification of specific methylation patterns across different cancers". PLOS ONE. 10 (3): e0120361. Bibcode:2015PLoSO..1020361Z. doi: 10.1371/journal.pone.0120361 . PMC   4361543 . PMID   25774687.
  18. ↑ Sourisseau T, Helissey C, Lefebvre C, Ponsonnailles F, Malka-Mahieu H, Olaussen KA, André F, Vagner S, Soria JC (2016). "Translational regulation of the mRNA encoding the ubiquitin peptidase USP1 involved in the DNA damage response as a determinant of Cisplatin resistance". Cell Cycle. 15 (2): 295–302. doi:10.1080/15384101.2015.1120918. PMC   4825832 . PMID   26825230.

Further reading

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