CEP164

This gene encodes a centrosomal protein involved in microtubule organization, DNA damage response, and chromosome segregation. The encoded protein is required for assembly of primary cilia and localizes to mature centrioles. Defects in this gene are a cause of nephronophthisis-related ciliopathies. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

Full Name

Centrosomal Protein 164

Function

Plays a role in microtubule organization and/or maintenance for the formation of primary cilia (PC), a microtubule-based structure that protrudes from the surface of epithelial cells. Plays a critical role in G2/M checkpoint and nuclear divisions. A key player in the DNA damage-activated ATR/ATM signaling cascade since it is required for the proper phosphorylation of H2AX, RPA, CHEK2 and CHEK1. Plays a critical role in chromosome segregation, acting as a mediator required for the maintenance of genomic stability through modulation of MDC1, RPA and CHEK1.

Biological Process

Cell division Source: UniProtKB-KW
Ciliary basal body-plasma membrane docking Source: Reactome
Cilium assembly Source: UniProtKB
DNA repair Source: UniProtKB-KW
G2/M transition of mitotic cell cycle Source: Reactome
Regulation of G2/M transition of mitotic cell cycle Source: Reactome

Cellular Location

Centriole; Nucleus. Localizes specifically to very distally located appendage structures on the mature centriole from which initiate PC formation (PubMed:26337392). Persisted at centrioles throughout mitosis. Expressed in chromatin-enriched nuclear fraction of HeLa cells. In response to DNA damage, it translocates to nuclear foci that contain the DNA damage response proteins KAT5/TIP60 and CHEK1.

Involvement in disease

Nephronophthisis 15 (NPHP15): An autosomal recessive disorder characterized by the association of nephronophthisis with Leber congenital amaurosis and retinal degeneration, often resulting in blindness during childhood. Additional features include seizures, cerebellar vermis hypoplasia, facial dysmorphism, bronchiectasis and liver failure. Nephronophthisis is a chronic tubulo-interstitial nephritis that progresses to end-stage renal failure.

PTM

Phosphorylation at Ser-186 is induced upon DNA-damage caused by treatment with IR irradiation, UV irradiation, hydroxyurea or amphidicolin. Also MDC1-mediated chromatin remodeling is critical for DNA damage-induced phosphorylation.