cell cycle checkpoint protein RAD17 (hRad17, RF-C/activator 1 homolog, RAD17, R24L)

Function: 1) sustained cell growth 2) maintenance of chromosomal stability 3) ATR-dependent checkpoint activation upon DNA damage 4) weak ATPase activity required for binding to chromatin 5) recruitment of the RAD1-RAD9-HUS1 complex onto chromatin 6) CHEK1 activation 7) sensor of DNA replication progression (putative) 8) homologous recombination (putative) 9) component of a DNA-binding complex containing RFC2, RFC3, RFC4, RFC5 10) interacts with RAD1 & RAD9 within the RAD1-RAD9-HUS1 complex 11) interacts with RAD9B, POLE, NHP2L1, MCM7 12) DNA damage promotes interaction with ATR or ATM & disrupts interaction with the RAD1-RAD9-HUS1 complex 13) induced by X-ray irradiation (isoform 1, 3 & 4) 14) phosphorylation on Ser-646 & Ser-656 is cell cycle-regulated, enhanced by genotoxic stress, & required for activation of checkpoint signaling 15) phosphorylation is mediated by ATR upon UV or replication arrest; it may be mediated both by ATR & ATM upon ionizing radiation 16) phosphorylation on Ser-646 & Ser-656 is required for interaction with RAD1 but dispensable for interaction with RFC3 or RFC4 Compartment: - nucleus - phosphorylated form redistributes to discrete nuclear foci upon DNA damage Alternative splicing: named isoforms=4; isoforms 2 & 3 are most abundant isoforms in non irradiated cells Expression: - ubiquitous at low levels - highly expressed in testis, within germinal epithelium of the seminiferous tubules Pathology: 1) overexpressed in various cancer cell lines 2) overexpressed incolon carcinoma (at protein level) 3) weakly expressed in seminomas

Properties

SIZE: MW = 77 kD entity length = 681 aa COMPARTMENT: cell nucleus MOTIF: ATP-binding site NAME: ATP-binding site SITE: 137-144 binding site SITE: 432-681 FOR-BINDING-OF: DNA replication licensing factor MCM7 MOTIF: Ser phosphorylation site {S646} Ser phosphorylation site {S656}

Database Correlations

OMIM 603139 UniProt O75943 Pfam PF03215

References

UniProt :accession O75943