ZIC5 | |||||||||||||||||||||||||
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Identifiers | |||||||||||||||||||||||||
Aliases | ZIC5 , Zic family member 5 | ||||||||||||||||||||||||
External IDs | OMIM: 617896 MGI: 1929518 HomoloGene: 11301 GeneCards: ZIC5 | ||||||||||||||||||||||||
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Species | Human | Mouse | |||||||||||||||||||||||
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Location (UCSC) | Chr 13: 99.96 – 99.97 Mb | n/a | |||||||||||||||||||||||
PubMed search | [2] | [3] | |||||||||||||||||||||||
Wikidata | |||||||||||||||||||||||||
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ZIC5 is a member of the Zinc finger of the cerebellum (ZIC) protein family. [4] ZIC5 is located on chromosome 13 in a divergently transcribed gene pair with the closely related gene ZIC2 . [5] It has been suggested that this tandem arrangement allows ZIC2 and ZIC5 to share regulatory elements and causes the two genes to have very similar expression patterns. [5]
ZIC5 is classified as a ZIC protein due to conservation of the five C2H2 zinc fingers, which enables the protein to interact with DNA and regulate transcription. Similar to other ZIC family members, ZIC5 is also able to interact with TCF proteins in order to inhibit canonical Wnt signalling. Mutation or loss of ZIC5 has not been associated with any congenital defects in humans. however, loss of Zic5 in mice causes a range of phenotypes including neural crest defects, neural tube defects, hydrocephaly and skeletal defects, indicating multiple functions during early development. [6] [7] Experiments in Xenopus also support the idea that Zic5 can regulate formation of neural crest, suggesting this function is conserved across species. [8]
ZIC5 has recently been found to be regulated by the post-translational modification SUMOylation in order to alter the DNA and protein binding properties of ZIC5 to promote neural crest specification. [9] Several other genes involved in the specification of neural crest, including Pax6, Sox9 and Sox10, also been found to be regulated by the same postranslational modification, suggesting that SUMOylation may have a widespread role in formation of the neural crest.
Xenopus is a genus of highly aquatic frogs native to sub-Saharan Africa. Twenty species are currently described within it. The two best-known species of this genus are Xenopus laevis and Xenopus tropicalis, which are commonly studied as model organisms for developmental biology, cell biology, toxicology, neuroscience and for modelling human disease and birth defects.
Neural crest cells are a temporary group of cells unique to vertebrates that arise from the embryonic ectoderm germ layer, and in turn give rise to a diverse cell lineage—including melanocytes, craniofacial cartilage and bone, smooth muscle, peripheral and enteric neurons and glia.
Zinc finger protein GLI1 also known as glioma-associated oncogene is a protein that in humans is encoded by the GLI1 gene. It was originally isolated from human glioblastoma cells.
Zinc finger protein GLI2 also known as GLI family zinc finger 2 is a protein that in humans is encoded by the GLI2 gene. The protein encoded by this gene is a transcription factor.
Zinc finger protein GLI3 is a protein that in humans is encoded by the GLI3 gene.
Zinc finger E-box-binding homeobox 2 is a protein that in humans is encoded by the ZEB2 gene. 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.
Early growth response protein 2 is a protein that in humans is encoded by the EGR2 gene. EGR2 is a transcription regulatory factor, containing three zinc finger DNA-binding sites, and is highly expressed in a population of migrating neural crest cells. It is later expressed in the neural crest derived cells of the cranial ganglion. The protein encoded by Krox20 contains two cys2his2-type zinc fingers. Krox20 gene expression is restricted to the early hindbrain development. It is evolutionarily conserved in vertebrates, humans, mice, chicks, and zebra fish. In addition, the amino acid sequence and most aspects of the embryonic gene pattern is conserved among vertebrates, further implicating its role in hindbrain development. When the Krox20 is deleted in mice, the protein coding ability of the Krox20 gene is diminished. These mice are unable to survive after birth and exhibit major hindbrain defects. These defects include but are not limited to defects in formation of cranial sensory ganglia, partial fusion of the trigeminal nerve (V) with the facial (VII) and auditory (VII) nerves, the proximal nerve roots coming off of these ganglia were disorganized and intertwined among one another as they entered the brainstem, and there was fusion of the glossopharyngeal (IX) nerve complex.
Zinc finger protein SNAI2 is a transcription factor that in humans is encoded by the SNAI2 gene. It promotes the differentiation and migration of certain cells and has roles in initiating gastrulation.
Sal-like protein 4(SALL4) is a transcription factor encoded by a member of the Spalt-like (SALL) gene family, SALL4. The SALL genes were identified based on their sequence homology to Spalt, which is a homeotic gene originally cloned in Drosophila melanogaster that is important for terminal trunk structure formation in embryogenesis and imaginal disc development in the larval stages. There are four human SALL proteins with structural homology and playing diverse roles in embryonic development, kidney function, and cancer. The SALL4 gene encodes at least three isoforms, termed A, B, and C, through alternative splicing, with the A and B forms being the most studied. SALL4 can alter gene expression changes through its interaction with many co-factors and epigenetic complexes. It is also known as a key embryonic stem cell (ESC) factor.
Segment polarity protein dishevelled homolog DVL-2 is a protein that in humans is encoded by the DVL2 gene.
ZIC3 is a member of the Zinc finger of the cerebellum (ZIC) protein family.
Zinc finger protein ZIC2 is a protein that in humans is encoded by the ZIC2 gene. ZIC2 is a member of the Zinc finger of the cerebellum (ZIC) protein family.
Protein odd-skipped-related 1 is a transcription factor that in humans is encoded by the OSR1 gene. The OSR1 and OSR2 transcription factors participate in the normal development of body parts such as the kidney.
ZIC1 is a member of the Zinc finger of the cerebellum (ZIC) protein family.
Zinc finger protein 423 is a protein that in humans is encoded by the ZNF423 gene.
Homeobox protein GBX-2 is a protein that in humans is encoded by the GBX2 gene.
SOX1 is a gene that encodes a transcription factor with a HMG-box DNA-binding domain and functions primarily in neurogenesis. SOX1, SOX2 and SOX3, members of the SOX gene family, contain transcription factors related to SRY, the testis-determining factor.
The TCF/LEF family is a group of genes that encode transcription factors which bind to DNA through a SOX-like high mobility group domain. They are involved in the Wnt signaling pathway, particularly during embryonic and stem-cell development, but also had been found to play a role in cancer and diabetes. TCF/LEF factors recruit the coactivator beta-catenin to enhancer elements of genes they target. They can also recruit members of the Groucho family of corepressors.
Neural crest cells are multipotent cells required for the development of cells, tissues and organ systems. A subpopulation of neural crest cells are the cardiac neural crest complex. This complex refers to the cells found amongst the midotic placode and somite 3 destined to undergo epithelial-mesenchymal transformation and migration to the heart via pharyngeal arches 3, 4 and 6.
Retinal homeobox protein Rx also known as retina and anterior neural fold homeobox is a protein that in humans is encoded by the RAX gene. The RAX gene is located on chromosome 18 in humans, mice, and rats.