CREBZF Gene

HGNC Family	Basic leucine zipper proteins
Name	CREB/ATF bZIP transcription factor
Description	Enables identical protein binding activity. Involved in negative regulation of gene expression, epigenetic; regulation of DNA-templated transcription; and response to virus. Located in mitochondrion and nucleoplasm. Part of RNA polymerase II transcription regulator complex. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CREBZF, also known as Zhangfei or SMILE, is a multifunctional transcriptional coregulator in the ATF/CREB family that modulates diverse cellular processes by partnering with key transcription factors and signaling molecules. It exists as distinct isoforms and exerts context‐dependent functions in stress responses, cellular growth, differentiation, and apoptosis. For example, CREBZF interacts with ATF4 via its leucine‐zipper domain to enhance binding to cAMP response elements and potentiate the transcriptional response to mitogenic signals."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " It also associates with the nuclear receptor coregulator SHP to modulate estrogen receptor signaling in a cell type–specific manner."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Through its interaction with p53 and its ability to displace Mdm2, CREBZF promotes p53 stabilization and activation, thereby enhancing p53‐dependent transcription and apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, CREBZF suppresses the unfolded protein response by binding to Xbp1s and inducing its proteasomal degradation, thus contributing to endoplasmic reticulum stress regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In neuronal models, CREBZF drives growth arrest and differentiation in medulloblastoma cells by influencing the expression of factors such as Brn3a and the NGF receptor trkA, leading to downstream activation of MAPK cascades and eventual cell death."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Its roles extend to reproductive tissues, where CREBZF isoforms are differentially expressed, influencing embryo implantation in the uterus and promoting apoptosis and autophagy in ovarian granulosa cells via modulation of ERK1/2 and mTOR signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Furthermore, dysregulation of CREBZF has been linked to tumorigenesis in several cancers—including osteosarcoma, breast, and gastric carcinomas—by impacting cell cycle regulators and interacting with signaling cascades such as the BMP pathway (via Smads) as well as by engaging in microRNA-mediated networks."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "12"}]}, {"type": "t", "text": " Finally, CREBZF expression is induced upon amino acid deprivation; its promoter contains an amino acid response element reminiscent of that found in CHOP, suggesting it functions as an amino acid stress sensor."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Collectively, these observations underscore how CREBZF integrates metabolic cues and stress signals to fine-tune transcriptional programs that govern cell fate decisions in both normal physiology and disease.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Melissa R Hogan, Gregory P Cockram, Rui Lu "}, {"type": "b", "children": [{"type": "t", "text": "Cooperative interaction of Zhangfei and ATF4 in transactivation of the cyclic AMP response element."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2005.11.046"}], "href": "https://doi.org/10.1016/j.febslet.2005.11.046"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16343488"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16343488"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yuan-Bin Xie, Ok-Hee Lee, Balachandar Nedumaran, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SMILE, a new orphan nuclear receptor SHP-interacting protein, regulates SHP-repressed estrogen receptor transactivation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20080782"}], "href": "https://doi.org/10.1042/BJ20080782"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18657049"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18657049"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Irene López-Mateo, M Ángeles Villaronga, Susana Llanos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The transcription factor CREBZF is a novel positive regulator of p53."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/cc.22133"}], "href": "https://doi.org/10.4161/cc.22133"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22983008"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22983008"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Rui Zhang, Noreen Rapin, Zhengxin Ying, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Zhangfei/CREB-ZF - a potential regulator of the unfolded protein response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0077256"}], "href": "https://doi.org/10.1371/journal.pone.0077256"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24155933"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24155933"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Timothy W Bodnarchuk, Scott Napper, Noreen Rapin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mechanism for the induction of cell death in ONS-76 medulloblastoma cells by Zhangfei/CREB-ZF."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurooncol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11060-012-0927-z"}], "href": "https://doi.org/10.1007/s11060-012-0927-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22798206"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22798206"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ximena Valderrama, Noreen Rapin, Valerie M K Verge, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Zhangfei induces the expression of the nerve growth factor receptor, trkA, in medulloblastoma cells and causes their differentiation or apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurooncol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11060-008-9682-6"}], "href": "https://doi.org/10.1007/s11060-008-9682-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18719857"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18719857"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Pengfei Lin, Fenglei Chen, Nan Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CREBZF expression and hormonal regulation in the mouse uterus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Reprod Biol Endocrinol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1477-7827-11-110"}], "href": "https://doi.org/10.1186/1477-7827-11-110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24325733"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24325733"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Fenglei Chen, Xin Wen, Pengfei Lin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activation of CREBZF Increases Cell Apoptosis in Mouse Ovarian Granulosa Cells by Regulating the ERK1/2 and mTOR Signaling Pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms19113517"}], "href": "https://doi.org/10.3390/ijms19113517"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30413092"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30413092"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Rui Zhang, Vikram Misra "}, {"type": "b", "children": [{"type": "t", "text": "Effects of cyclic AMP response element binding protein-Zhangfei (CREBZF) on the unfolded protein response and cell growth are exerted through the tumor suppressor p53."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/cc.27053"}], "href": "https://doi.org/10.4161/cc.27053"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24200963"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24200963"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Jun Fang, Gaohui Jiang, Weiguo Mao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Up-regulation of long noncoding RNA MBNL1-AS1 suppresses breast cancer progression by modulating miR-423-5p/CREBZF axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bioengineered (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/21655979.2022.2026728"}], "href": "https://doi.org/10.1080/21655979.2022.2026728"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35094653"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35094653"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Yu Jin Kim, Seongtae Jeong, Woon Yong Jung, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miRNAs as potential biomarkers for the progression of gastric cancer inhibit CREBZF and regulate migration of gastric adenocarcinoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Med Sci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/ijms.42654"}], "href": "https://doi.org/10.7150/ijms.42654"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32218690"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32218690"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Jae-Ho Lee, Geun Taek Lee, Seok Joo Kwon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CREBZF, a novel Smad8-binding protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biochem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11010-012-1353-4"}], "href": "https://doi.org/10.1007/s11010-012-1353-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22707059"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22707059"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Yani Zhang, Yaping Jin, Tegan A Williams, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Amino acid deprivation induces CREBZF/Zhangfei expression via an AARE-like element in the promoter."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2009.12.059"}], "href": "https://doi.org/10.1016/j.bbrc.2009.12.059"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20026304"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20026304"}]}]}]}
Synonyms	ZF, SMILE
Proteins	ZHANG_HUMAN
NCBI Gene ID	58487
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CREBZF has 6,070 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 108 datasets.

Click the + buttons to view associations for CREBZF from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CREBZF Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CREBZF gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of CREBZF gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of CREBZF gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of CREBZF gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of CREBZF gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CREBZF gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of CREBZF gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CREBZF gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CREBZF gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of CREBZF gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CREBZF gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of CREBZF gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CREBZF gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CREBZF gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CREBZF gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of CREBZF gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing CREBZF protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CREBZF gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CREBZF protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CREBZF protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CREBZF protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with CREBZF protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of CREBZF gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CREBZF gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with CREBZF gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of CREBZF protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CREBZF gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CREBZF gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with CREBZF gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with CREBZF gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CREBZF gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at CREBZF gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CREBZF gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CREBZF gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing CREBZF from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of CREBZF gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with CREBZF gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing CREBZF from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of CREBZF gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of CREBZF gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.