Contents

ZEB2

Protein-coding gene in the species Homo sapiens

ZEB2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2DA7
Identifiers
Aliases	ZEB2, HSPC082, SIP-1, SIP1, SMADIP1, ZFHX1B, zinc finger E-box binding homeobox 2
External IDs	OMIM: 605802; MGI: 1344407; HomoloGene: 8868; GeneCards: ZEB2; OMA:ZEB2 - orthologs
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2q22.3 Start 144,364,364 bp[1] End 144,521,057 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2|2 B Start 44,873,644 bp[2] End 45,007,407 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in sural nerve monocyte C1 segment Achilles tendon corpus callosum internal globus pallidus inferior ganglion of vagus nerve epithelium of colon granulocyte amygdala Top expressed in Rostral migratory stream stroma of bone marrow belly cord human fetus dentate gyrus iris dentate gyrus of hippocampal formation granule cell subdivision of hippocampus Region I of hippocampus proper body of femur More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding phosphatase regulator activity metal ion binding protein binding nucleic acid binding DNA-binding transcription repressor activity, RNA polymerase II-specific DNA-binding transcription activator activity, RNA polymerase II-specific R-SMAD binding sequence-specific DNA binding DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component nucleus nucleolus cytosol Biological process regulation of transcription, DNA-templated nervous system development transcription, DNA-templated positive regulation of melanin biosynthetic process negative regulation of transcription by RNA polymerase II neural crest cell migration somitogenesis neural tube closure transcription by RNA polymerase II central nervous system development corpus callosum morphogenesis hippocampus development cell proliferation in forebrain corticospinal tract morphogenesis positive regulation of Wnt signaling pathway positive regulation of JUN kinase activity positive regulation of melanocyte differentiation positive regulation of transcription by RNA polymerase II developmental pigmentation embryonic morphogenesis collateral sprouting positive regulation of axonogenesis mammillary axonal complex development melanocyte migration positive regulation of lens fiber cell differentiation regulation of melanosome organization Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 9839 24136 Ensembl ENSG00000169554 ENSMUSG00000026872 UniProt O60315 Q9R0G7 RefSeq (mRNA) NM_001171653 NM_014795 NM_015753 NM_001289521 NM_001355288 NM_001355289 NM_001355290 NM_001355291 RefSeq (protein) NP_001165124 NP_055610 NP_001276450 NP_056568 NP_001342217 NP_001342218 NP_001342219 NP_001342220 Location (UCSC) Chr 2: 144.36 – 144.52 Mb Chr 2: 44.87 – 45.01 Mb PubMed search [3] [4]
Wikidata
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Zinc finger E-box-binding homeobox 2 is a protein that in humans is encoded by the ZEB2 gene.^[5] The ZEB2 protein is a transcription factor that plays a role in the transforming growth factor β (TGFβ) signaling pathways that are essential during early fetal development.^[6]

Function[edit]

ZEB2 (previously also known as SMADIP1, SIP1) and its mammalian paralog ZEB1 belongs to the Zeb family within the ZF (zinc finger) class of homeodomain transcription factors. ZEB2 protein has 8 zinc fingers and 1 homeodomain.^[7] The structure of the homeodomain shown on the right.

ZEB2 interacts with receptor-mediated, activated full-length SMADs.^[5] The activation of TGFβ receptors brings about the phosphorylation of intracellular effector molecules, R-SMADs. ZEB2 is an R-SMAD-binding protein and acts as a transcriptional corepressor. It is involved in the timing of the conversion of neuroepithelial cells into radial glial cells in early development, a mechanism thought to allow for the large differences in brain size between humans and other mammals.^[8]

ZEB2 transcripts are found in tissues differentiated from the neural crest such as the cranial nerve ganglia, dorsal root ganglia, sympathetic ganglionic chains, the enteric nervous system and melanocytes. ZEB2 is also found in tissues that are not derived from the neural crest, including the wall of the digestive tract, kidneys, and skeletal muscles.

Clinical significance[edit]

Mutations in the ZEB2 gene are associated with the Mowat–Wilson syndrome. This disease exhibits mutations and even complete deletions of the ZEB2 gene. Mutations of the gene can cause the gene to produce nonfunctional ZEB2 proteins or inactivate the function of the gene as a whole. These deficits of ZEB2 protein interfere with the development of many organs. Many of the symptoms can be explained by the irregular development of the structures from the neural crest.^[9]

Hirschsprung's disease also has many symptoms that can be explained by lack of ZEB2 during development of the digestive tract nerves. This disease causes severe constipation and enlargement of the colon.^[10]

The risk of hepatocellular carcinoma and cirrhosis in chronic hepatitis B has been reported to be associated with a single-nucleotide polymorphism in the promoter region of ZEB2, designated rs3806475, under a recessive model of inheritance.^[11]

References[edit]

^ Liu WX, Yang L, Yan HM, Yan LN, Zhang XL, Ma N, Tang LM, Gao X, Liu DW (2021). Argentiero A, Mehta R, Wang S (eds.). "Germline Variants and Genetic Interactions of Several EMT Regulatory Genes Increase the Risk of HBV-Related Hepatocellular Carcinoma". Frontiers in Oncology. 11. doi:10.3389/fonc.2021.564477. PMC 8226114. PMID 34178612. This article incorporates text from this source, which is available under the CC BY 4.0 license.

Further reading[edit]

External links[edit]

• GeneReviews/NIH/NCBI/UW entry on Mowat-Wilson syndrome
• ZEB2+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)