ZEB2

From Wikipedia, the free encyclopedia
Jump to: navigation, search
ZEB2
Protein ZEB2 PDB 2da7.png
Available structures
PDB Ortholog search: PDBe RCSB
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
Gene location (Human)
Chromosome 2 (human)
Chr. Chromosome 2 (human)[1]
Chromosome 2 (human)
Genomic location for ZEB2
Genomic location for ZEB2
Band 2q22.3 Start 144,364,364 bp[1]
End 144,524,583 bp[1]
RNA expression pattern
PBB GE ZEB2 203603 s at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001171653
NM_014795

RefSeq (protein)

NP_001165124
NP_055610

Location (UCSC) Chr 2: 144.36 – 144.52 Mb Chr 2: 44.98 – 45.12 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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.

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 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.[8]

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.[9]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000169554 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026872 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ a b "Entrez Gene: ZEB2 zinc finger E-box binding homeobox 2". 
  6. ^ Bassez G, Camand OJ, Cacheux V, Kobetz A, Dastot-Le Moal F, Marchant D, Catala M, Abitbol M, Goossens M (March 2004). "Pleiotropic and diverse expression of ZFHX1B gene transcripts during mouse and human development supports the various clinical manifestations of the "Mowat-Wilson" syndrome". Neurobiology of Disease. 15 (2): 240–50. doi:10.1016/j.nbd.2003.10.004. PMID 15006694. 
  7. ^ Bürglin, TR, Affolter, M, (2015). "Homeodomain proteins: an update". Chromosoma. 125 (3): x. doi:10.1007/s00412-015-0543-8. PMC 4901127Freely accessible. PMID 26464018. 
  8. ^ Dastot-Le Moal F, Wilson M, Mowat D, Collot N, Niel F, Goossens M (April 2007). "ZFHX1B mutations in patients with Mowat-Wilson syndrome". Human Mutation. 28 (4): 313–21. doi:10.1002/humu.20452. PMID 17203459. 
  9. ^ Saunders CJ, Zhao W, Ardinger HH (November 2009). "Comprehensive ZEB2 gene analysis for Mowat-Wilson syndrome in a North American cohort: a suggested approach to molecular diagnostics". American Journal of Medical Genetics Part A. 149A (11): 2527–31. doi:10.1002/ajmg.a.33067. PMID 19842203. 

Further reading[edit]

External links[edit]