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FLASH GENE

Symbol

ZBTB16

contributors: mct/pgu - updated : 13-12-2023

HGNC name	zinc finger and BTB domain containing 16
HGNC id	12930

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_006006 7 splicing 8494 NP_005997 74.27 673 - 2016 26676652 a 7 exons variant lacking exon 2 encoding for the same product as variant 2 also called AS-Ia NM_001354750 7 splicing 8754 NP_001341679 - 673 stomach 2016 26676652 splicing exon 1, long 5'UTR lacking BTB/POZ domain also called AS-II NM_001354751 7 splicing 8375 NP_001341680 - 673 testis 2016 26676652 splicing exon 1, long 5'UTR lacking BTB/POZ domain also called AS-III NM_001354752 5 splicing 8240 NP_001341681 - 644 heart, placenta and stomach 2016 26676652 splicing exon 1, long 5'UTR lacking BTB/POZ domain also called AS-IV NM_001018011 7 splicing 8400 NP_001018011 74.27 673 - 2016 26676652 a 7 exons variant lacking exon 1 encoding for the same product as variant 1 also called AS-Ib

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Hearing/Equilibrium ear inner cochlea Corti highly Homo sapiens Adult Nervous brain       highly Homo sapiens Adult Reproductive male system prostate     highly Respiratory lung       lowly Urinary kidney       lowly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow     lowly Connective adipose brown   highly Homo sapiens Adult Muscular striatum skeletal   highly

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic progenitor cell not specific adipocyte Homo sapiens Adult Reproductive spermatocyte

cell lineage
cell lines	early myeloid cell lines
fluid/secretion

at STAGE

Text	in limb bud (anterior to posterior patterning in axial and appendicular skeleton)

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a BTB/POZ (zinc finger N-terminal) interaction domain
	nine krueppel-type C-terminal zinc finger motifs
	C terminal RD2 domain

conjugated

MetalloP

HOMOLOGY

interspecies	homolog to murine Zbtb16 (96.73 pc)
	homolog to rattus Zbtb16 (96.14 pc)

Homologene

FAMILY	zinc finger protein family
	CHC2 type, krueppel-like

CATEGORY

regulatory , transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
	intracellular,nucleus,nucleoplasm,nuclear bodies,PML
	intracellular,nucleus,chromatin/chromosome
text	with MTDH, colocalize to nuclear bodies containing histone deacetylases, which are known to promote ZBTB16-mediated repression

basic FUNCTION	recruiting nuclear histone deacetylase through nuclear corepressor N-COR
	co-expression of ZBTB16 and RB1 results in enhancement of transcriptional repression of ZBTB16 and E2F/Rb target genes, indicating functional co-operation between the two proteins
	DNA sequence-specific transcriptional repressor
	playing a key role in human myeloid development
	regulator of HOX gene expression and of myeloid maturation
	spermatogonia-specific transcription factor in the testis that is required to regulate self-renewal and maintenance of the stem cell pool
	playing a significant stimulatory role in megakaryocytic development, seemingly mediated in part by induction of TpoR expression at transcriptional level
	activates CXCR4 translation in megakaryopoiesis
	may be involved in a general mechanism in the regulation of hematopoiesis, linking lineage-specific transcription factors, miRNAs and key mRNA targets, particularly growth factor/chemokine receptors
	also required for stem-cell self-renewal and maintenance in adult male germ cells
	invariant natural killer T cells -specific transcription factor that is necessary for full functionality (
	during homeostasis, restricts proliferation and differentiation of cord blood-derived myeloid progenitors to maintain a balance between the progenitor and mature cell compartments
	may play a role in differentiation of hematopoietic progenitors
	regulates the expression of genes involved in cell growth and apoptosis including c-myc
	sufficient to promote T cell effector functions and ZBTB16 acts independently of SAP- and Fyn-mediated signaling pathways
	opposes MTOR activity and define a cellular signaling network controlling spermatogonial progenitor cells (SPC) homeostasis whereby MTOR integrates mitogenic signals received by SPCs and determines their sensitivity to self-renewal stimuli
	role for ZBTB16-mediated DDIT4 expression in inhibiting MTOR activation in spermatogonial progenitor cells
	is remarkable in that it is a transcription factor capable of inducing an effector program in the absence of T cell agonist interactions or cell division
	transports CUL3 to the nucleus, where the two proteins are associated within a chromatin-modifying complex
	regulates the expression of a surprisingly small set of genes, many with known immune functions, and of a limited number of genes essential for NKT cell function
	implicated as a novel determinant of substrate utilization in brown adipocytes and of adiposity
	is essential for nearly all of the unique characteristics of NKT cells including their rapid and potent response to antigen
	stably repressed in non-innate T cells and TCR-mediated signaling was not sufficient to induce PLZF in conventional T cells
	ZBTB16 acts as a downstream transcriptional regulator of SP7
	associated with active enhancers, appears to restrain their activity as an epigenetic gatekeeper of hematopoietic aging
	is a key factor in inhibiting differentiation of spermatogonial progenitor cells (SPCs)
	ZBTB16 may play an important role in modulating the odontoblastic differentiation of dental pulp stem cells (DPSCs) and act as a regulator of SP7

CELLULAR PROCESS	cell life, cell death/apoptosis
	nucleotide, transcription
	cell organization/biogenesis

PHYSIOLOGICAL PROCESS

development

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	GATA2 modifying transactivation capacity
	interacting with GATA1, activating thrombopoietin receptor and inducing megakaryocyte development
	interacting with CRMP1 and GNE
	upstream regulator of Runx2/CBFA1
	interacting with ZBTB32 (ZBTB16 differentially participate in the regulation of osteoblastic differentiation via the BMP2 and CBFA1 signaling pathways, respectively)
	ZBTB16 (PLZF) specifically bound to GNAO1
	interacts with RB1 (interaction between ZBTB16 and RB1 is mediated through the RB1 pocket and the region of ZBTB16 that lies between its transcriptional repression (poxvirus and zinc-finger, POZ) and DNA-binding (zinc-finger) domains)
	ZBTB16-mediated control on KIT expression in CD34(+) cells and early erythropoiesis
	interacting protein of MTDH (interact in mammalian cells via the N- and C termini of MTDH and a region C terminal to the RD2 domain of ZBTB16)
	interacting with stress-induced cytokines that can act by interfering with the capacity of ZBTB16 to inhibit proliferation and differentiation
	repressed CEBPA transcription but did not bind to its promoter, indicating indirect regulation
	transcriptional target for the CUX1 repressor (the novel genetic relationship between CUX1 and PLZF could be of relevance to human diseases, such as leukemia)
	mechanistically, SALL4 sequesters ZBTB16 to noncognate chromatin domains to induce expression of KIT, a target of ZBTB16-mediated repression required for differentiation
	prominently associated with CUL3, an E3 ubiquitin ligase previously shown to use BTB domain-containing proteins as adaptors for substrate binding
	USP37 interacted with ZBTB16/RARA through the ZBTB16 moiety and sustained ZBTB16/RARA steady state levels
	potential role for SLAMF6 in the induction of ZBTB16
	RARA-ZBTB16 acts as a modifier oncogene that subverts differentiation in the granulocytic lineage by associating with CEBPA and inhibiting its activity
	HOXA5, HOXC5, HOXB5 interacts with promyelocytic leukemia zinc finger (ZBTB16) biochemically and genetically to restrict SHH expression
	ZBTB16 as an interacting protein of NLRP7
	KAT2A regulates ZBTB16 through acetylation, mediates osteogenic differentiation, and affects orthodontic tooth movement

cell & other

REGULATION

repressed by

FHL2

ASSOCIATED DISORDERS

corresponding disease(s)

APLZF

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral fusion       with RARA, in acute promyelocytic leukaemia and a translocation t(11;17)(q23;21)

Susceptibility

to autism spectrum disorder

Variant & Polymorphism

Candidate gene	represents a promising pleiotropic candidate node for metabolic syndrome
Marker	can be useful as a late marker of osteoblastic differentiation.
	could be a promising tumor biomarker for Gallbladder cancer (GBC)
Therapy target
	System Type Disorder Pubmed osteoarticular bone ostéoporosis Super enhancers targeting ZBTB16 in osteogenesis protect against osteoporosis cancer digestive liver potential therapeutic target in Gall bladder cancer

ANIMAL & CELL MODELS

	Plzf-deficient mice (luxoid, Zbtb16Lu) had severe patterning defects of the limbs and the axial skeleton
	heterozygous mutant (luxoid.Zbtb16(LU)/J) mice deficient in Zbtb16 have hearing and responses to acoustic trauma similar to their wild type littermates but are unable to generate conditioning-induced protection from acoustic trauma