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Zinc finger E-box-binding homeobox 2 (previously also known as SMADIP1, SIP1) is a protein that in humans is encoded by the ZEB2 gene on chromosome 2. 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.

Introduction

It is ubiquitously expressed in many tissues and cell types.[BioGPS link]  functions in .[Refs] It is associated with cancer pathogenesis and schizophrenia, and mutations in this gene have been linked to Mowat-Wilson syndrome.

Gene
The ZEB2 gene resides on chromosome 2 at the band 2q22.3 and contains 15 exons. This gene produces 2 isoforms through alternative splicing.

Protein
ZEB2 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. The structure of the homeodomain is shown on the right.

Function
ZEB2 interacts with receptor-mediated, activated full-length SMADs. 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.

ZEB2 transcripts are found in tissues differentiated from the neural crest such as the cranial nerve ganglia, dorsal root ganglia, sympathetic ganglionic chains, and the enteric nervous system. 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
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 gene as a whole. These deficits of ZEB2 protein interferes with the development of many organs. Many of the symptoms can be explained by the irregular development of the structures from the neural crest.

Hirschsprug'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.