Molecule Information

General Information of the Molecule (ID: Mol00716)

• Name: Zinc finger and BTB domain-containing protein 7A (ZBTB7A) ,Homo sapiens
• Synonyms: Factor binding IST protein 1; FBI-1; Factor that binds to inducer of short transcripts protein 1; HIV-1 1st-binding protein 1; Leukemia/lymphoma-related factor; POZ and Krueppel erythroid myeloid ontogenic factor; POK erythroid myeloid ontogenic factor; Pokemon; Pokemon 1; TTF-I-interacting peptide 21; TIP21; Zinc finger protein 857A; FBI1; LRF; ZBTB7; ZNF857A
• Molecule Type: Protein
• Gene Name: ZBTB7A
• Gene ID: 51341
• Location: chr19:4043303-4066899[-]
• Sequence:
  MAGGVDGPIGIPFPDHSSDILSGLNEQRTQGLLCDVVILVEGREFPTHRSVLAACSQYFK
  KLFTSGAVVDQQNVYEIDFVSAEALTALMDFAYTATLTVSTANVGDILSAARLLEIPAVS
  HVCADLLDRQILAADAGADAGQLDLVDQIDQRNLLRAKEYLEFFQSNPMNSLPPAAAAAA
  ASFPWSAFGASDDDLDATKEAVAAAVAAVAAGDCNGLDFYGPGPPAERPPTGDGDEGDSN
  PGLWPERDEDAPTGGLFPPPVAPPAATQNGHYGRGGEEEAASLSEAAPEPGDSPGFLSGA
  AEGEDGDGPDVDGLAASTLLQQMMSSVGRAGAAAGDSDEESRADDKGVMDYYLKYFSGAH
  DGDVYPAWSQKVEKKIRAKAFQKCPICEKVIQGAGKLPRHIRTHTGEKPYECNICKVRFT
  RQDKLKVHMRKHTGEKPYLCQQCGAAFAHNYDLKNHMRVHTGLRPYQCDSCCKTFVRSDH
  LHRHLKKDGCNGVPSRRGRKPRVRGGAPDPSPGATATPGAPAQPSSPDARRNGQEKHFKD
  EDEDEDVASPDGLGRLNVAGAGGGGDSGGGPGAATDGNFTAGLA
• Function: Transcription factor that represses the transcription of a wide range of genes involved in cell proliferation and differentiation. Directly and specifically binds to the consensus sequence 5'-[GA][CA]GACCCCCCCCC-3' and represses transcription both by regulating the organization of chromatin and through the direct recruitment of transcription factors to gene regulatory regions. Negatively regulates SMAD4 transcriptional activity in the TGF-beta signaling pathway through these two mechanisms. That is, recruits the chromatin regulator HDAC1 to the SMAD4-DNA complex and in parallel prevents the recruitment of the transcriptional activators CREBBP and EP300. Collaborates with transcription factors like RELA to modify the accessibility of gene transcription regulatory regions to secondary transcription factors. Also directly interacts with transcription factors like SP1 to prevent their binding to DNA. Functions as an androgen receptor/AR transcriptional corepressor by recruiting NCOR1 and NCOR2 to the androgen response elements/ARE on target genes. Thereby, negatively regulates androgen receptor signaling and androgen-induced cell proliferation. Involved in the switch between fetal and adult globin expression during erythroid cells maturation. Through its interaction with the NuRD complex regulates chromatin at the fetal globin genes to repress their transcription. Specifically represses the transcription of the tumor suppressor ARF isoform from the CDKN2A gene. Efficiently abrogates E2F1-dependent CDKN2A transactivation. Regulates chondrogenesis through the transcriptional repression of specific genes via a mechanism that also requires histone deacetylation. Regulates cell proliferation through the transcriptional regulation of genes involved in glycolysis. Involved in adipogenesis through the regulation of genes involved in adipocyte differentiation. Plays a key role in the differentiation of lymphoid progenitors into B and T lineages. Promotes differentiation towards the B lineage by inhibiting the T-cell instructive Notch signaling pathway through the specific transcriptional repression of Notch downstream target genes. Also regulates osteoclast differentiation. May also play a role, independently of its transcriptional activity, in double-strand break repair via classical non-homologous end joining/cNHEJ. Recruited to double-strand break sites on damage DNA, interacts with the DNA-dependent protein kinase complex and directly regulates its stability and activity in DNA repair. May also modulate the splicing activity of KHDRBS1 toward BCL2L1 in a mechanism which is histone deacetylase-dependent and thereby negatively regulates the pro-apoptotic effect of KHDRBS1.
• Uniprot ID: ZBT7A_HUMAN
• Ensembl ID: ENSG00000178951
• HGNC ID: HGNC:18078

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Osteosarcoma [1]

• Resistant Disease: Osteosarcoma [ICD-11: 2B51.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: ZBTB7A/LINC00473/IL24 signaling pathway; Regulation; hsa04630
• In Vitro Model: MG63 cells; Bone marrow; Homo sapiens (Human); CVCL_0426
• In Vitro Model: U2OS cells; Bone; Homo sapiens (Human); CVCL_0042
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Elevated ZBTB7A inhibits cisplatin-induced apoptosis by repressing LINC00473 expression. The ZBTB7A-LINC00473-IL24 signaling axis plays an important role in regulating osteosarcoma chemoresistance.

References

• Ref 1: ZBTB7A Enhances Osteosarcoma Chemoresistance by Transcriptionally Repressing lncRNALINC00473-IL24 Activity. Neoplasia. 2017 Nov;19(11):908-918. doi: 10.1016/j.neo.2017.08.008. Epub 2017 Sep 21.