6csv

Structural highlights

Disease

CEP63_HUMAN Autosomal recessive primary microcephaly. The disease is caused by mutations affecting the gene represented in this entry.CE152_HUMAN Seckel syndrome;Autosomal recessive primary microcephaly. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.

Function

CEP63_HUMAN Required for normal spindle assembly. Plays a key role in mother-centriole-dependent centriole duplication; the function seems also to involve CEP152, CDK5RAP2 and WDR62 through a stepwise assembled complex at the centrosome that recruits CDK2 required for centriole duplication. Reported to be required for centrosomal recruitment of CEP152; however, this function has been questioned (PubMed:21983783, PubMed:26297806). Also recruits CDK1 to centrosomes (PubMed:21406398). Plays a role in DNA damage response. Following DNA damage, such as double-strand breaks (DSBs), is removed from centrosomes; this leads to the inactivation of spindle assembly and delay in mitotic progression (PubMed:21406398).^{[1] [2] [3]} CE152_HUMAN Necessary for centrosome duplication. Acts as a molecular scaffold facilitating the interaction of PLK4 and CENPJ, 2 molecules involved in centriole formation. Also plays a key role in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles. Overexpression of CEP152 can drive amplification of centrioles.^{[4] [5] [6]}

References

1. ↑ Loffler H, Fechter A, Matuszewska M, Saffrich R, Mistrik M, Marhold J, Hornung C, Westermann F, Bartek J, Kramer A. Cep63 recruits Cdk1 to the centrosome: implications for regulation of mitotic entry, centrosome amplification, and genome maintenance. Cancer Res. 2011 Mar 15;71(6):2129-39. doi: 10.1158/0008-5472.CAN-10-2684. PMID:21406398 doi:http://dx.doi.org/10.1158/0008-5472.CAN-10-2684
2. ↑ Sir JH, Barr AR, Nicholas AK, Carvalho OP, Khurshid M, Sossick A, Reichelt S, D'Santos C, Woods CG, Gergely F. A primary microcephaly protein complex forms a ring around parental centrioles. Nat Genet. 2011 Oct 9;43(11):1147-53. doi: 10.1038/ng.971. PMID:21983783 doi:http://dx.doi.org/10.1038/ng.971
3. ↑ Kodani A, Yu TW, Johnson JR, Jayaraman D, Johnson TL, Al-Gazali L, Sztriha L, Partlow JN, Kim H, Krup AL, Dammermann A, Krogan NJ, Walsh CA, Reiter JF. Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2 and promote centriole duplication. Elife. 2015 Aug 22;4. doi: 10.7554/eLife.07519. PMID:26297806 doi:http://dx.doi.org/10.7554/eLife.07519
4. ↑ Cizmecioglu O, Arnold M, Bahtz R, Settele F, Ehret L, Haselmann-Weiss U, Antony C, Hoffmann I. Cep152 acts as a scaffold for recruitment of Plk4 and CPAP to the centrosome. J Cell Biol. 2010 Nov 15;191(4):731-9. doi: 10.1083/jcb.201007107. Epub 2010 Nov , 8. PMID:21059844 doi:http://dx.doi.org/10.1083/jcb.201007107
5. ↑ Dzhindzhev NS, Yu QD, Weiskopf K, Tzolovsky G, Cunha-Ferreira I, Riparbelli M, Rodrigues-Martins A, Bettencourt-Dias M, Callaini G, Glover DM. Asterless is a scaffold for the onset of centriole assembly. Nature. 2010 Oct 7;467(7316):714-8. doi: 10.1038/nature09445. Epub 2010 Sep 19. PMID:20852615 doi:http://dx.doi.org/10.1038/nature09445
6. ↑ Kalay E, Yigit G, Aslan Y, Brown KE, Pohl E, Bicknell LS, Kayserili H, Li Y, Tuysuz B, Nurnberg G, Kiess W, Koegl M, Baessmann I, Buruk K, Toraman B, Kayipmaz S, Kul S, Ikbal M, Turner DJ, Taylor MS, Aerts J, Scott C, Milstein K, Dollfus H, Wieczorek D, Brunner HG, Hurles M, Jackson AP, Rauch A, Nurnberg P, Karaguzel A, Wollnik B. CEP152 is a genome maintenance protein disrupted in Seckel syndrome. Nat Genet. 2011 Jan;43(1):23-6. doi: 10.1038/ng.725. Epub 2010 Dec 5. PMID:21131973 doi:http://dx.doi.org/10.1038/ng.725