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| WDR62 (WD Repeat-containing Protein 62) |
|---|
| Gene | [WDR62](/genes/WDR62) |
| UniProt | O43371 |
| PDB Structures | Not determined |
| Molecular Weight | 163 kDa |
| Localization | Centrosome, spindle poles |
| Protein Family | WD repeat protein family |
Wdr62 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
This page provides comprehensive information about this protein. See the content below for detailed information.
WDR62 is a centrosomal protein essential for neurogenesis. Mutations cause primary microcephaly with more severe phenotypic features than ASPM mutations, often associated with cortical malformations.
WDR62 has a distinctive architecture:
- WD40 repeat domain (C-terminal) - β-propeller structure for protein interactions
- N-terminal region - contains multiple phosphorylation sites
- Centrosomal targeting sequence - localizes to spindle poles
- Nuclear export signal - shuttles between compartments
- Multiple splice isoforms - generate functional diversity
The WD40 domain forms a 7-bladed β-propeller that serves as a protein interaction platform.
During brain development, WDR62 performs essential functions:
- Centrosome maturation - recruits γ-tubulin and other proteins
- Spindle assembly - ensures proper mitotic apparatus
- Neural progenitor proliferation - maintains progenitor pool
- Cell cycle progression - regulates G2/M transition
- DNA damage response - activates checkpoint signaling
WDR62 mutations cause severe primary microcephaly:
- Frequency - Second most common MCPH gene
- Head circumference - Often >4-5 SD below mean
- Cortical malformations - Lissencephaly, pachygyria
- Clinical features - Seizures, developmental delay
- Additional findings - Abnormal gyral patterns
- Spindle assembly defects - impaired mitotic function
- Centrosomal dysfunction - abnormal microtubule organization
- Cell cycle arrest - G2/M checkpoint activation
- Apoptosis - increased neural progenitor cell death
- Cortical hypoplasia - reduced brain size and complexity
- WDR62 mutations in some Joubert syndrome cases
- Cerebellar and brainstem malformations
- Associated with retinal and renal involvement
- Nicholas AK, et al. (2010). "WDR62 is the second primary microcephaly gene." Nat Genet. 42(3):203-209. DOI:10.1038/ng.534
- Thornton GK, Woods CG. (2009). "Primary microcephaly: all roads lead to the gene." J Med Genet. 46(8):523-528. DOI:10.1136/jmg.2009.066498
- Chen JF, et al. (2014). "Wdr62 is involved in the generation of basal progenitors in the developing cortex." Cell Stem Cell. 15(2):220-232. DOI:10.1016/j.stem.2014.07.006
The study of Wdr62 Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.