RAD17_MOUSE
ID RAD17_MOUSE Reviewed; 688 AA.
AC Q6NXW6; O88934; O89024;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 29-MAR-2005, sequence version 2.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Cell cycle checkpoint protein RAD17;
GN Name=Rad17;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=10232579;
RA Bao S., Chang M.-S., Auclair D., Sun Y., Wang Y., Wong W.-K., Zhang J.,
RA Liu Y., Qian X., Sutherland R., Magi-Galluzi C., Weisberg E., Cheng E.Y.S.,
RA Hao L., Sasaki H., Campbell M.S., Kraeft S.-K., Loda M., Lo K.-M.,
RA Chen L.B.;
RT "HRad17, a human homologue of the Schizosaccharomyces pombe checkpoint gene
RT rad17, is overexpressed in colon carcinoma.";
RL Cancer Res. 59:2023-2028(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=9933569; DOI=10.1006/geno.1998.5642;
RA Bluyssen H.A.R., Naus N.C., van Os R.I., Jaspers I., Hoeijmakers J.H.J.,
RA de Klein A.;
RT "Human and mouse homologs of the Schizosaccharomyces pombe rad17+ cell
RT cycle checkpoint control gene.";
RL Genomics 55:219-228(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=10480350; DOI=10.1007/s004399900067;
RA von Deimling F., Scharf J.M., Liehr T., Rothe M., Kelter A.-R., Albers P.,
RA Dietrich W.F., Kunkel L.M., Wernert N., Wirth B.;
RT "Human and mouse RAD17 genes: identification, localization, genomic
RT structure and histological expression pattern in normal testis and
RT seminoma.";
RL Hum. Genet. 105:17-27(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Egg;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PHOSPHORYLATION AT SER-647 AND SER-657.
RX PubMed=11687627; DOI=10.1073/pnas.231364598;
RA Post S.M., Weng Y.-C., Cimprich K., Chen L.B., Xu Y., Lee E.Y.-H.P.;
RT "Phosphorylation of serines 635 and 645 of human Rad17 is cell cycle
RT regulated and is required for G(1)/S checkpoint activation in response to
RT DNA damage.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:13102-13107(2001).
RN [6]
RP PHOSPHORYLATION AT SER-647 AND SER-657.
RX PubMed=14500819; DOI=10.1093/nar/gkg765;
RA Post S.M., Tomkinson A.E., Lee E.Y.-H.P.;
RT "The human checkpoint Rad protein Rad17 is chromatin-associated throughout
RT the cell cycle, localizes to DNA replication sites, and interacts with DNA
RT polymerase epsilon.";
RL Nucleic Acids Res. 31:5568-5575(2003).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15297881; DOI=10.1038/sj.emboj.7600353;
RA Budzowska M., Jaspers I., Essers J., de Waard H., van Drunen E., Hanada K.,
RA Beverloo B., Hendriks R.W., de Klein A., Kanaar R., Hoeijmakers J.H.,
RA Maas A.;
RT "Mutation of the mouse Rad17 gene leads to embryonic lethality and reveals
RT a role in DNA damage-dependent recombination.";
RL EMBO J. 23:3548-3558(2004).
RN [8]
RP PHOSPHORYLATION AT SER-647.
RX PubMed=17376776; DOI=10.1074/jbc.c700019200;
RA Yong W., Bao S., Chen H., Li D., Sanchez E.R., Shou W.;
RT "Mice lacking protein phosphatase 5 are defective in ataxia telangiectasia
RT mutated (ATM)-mediated cell cycle arrest.";
RL J. Biol. Chem. 282:14690-14694(2007).
CC -!- FUNCTION: Essential for sustained cell growth, maintenance of
CC chromosomal stability, and ATR-dependent checkpoint activation upon DNA
CC damage. Has a weak ATPase activity required for binding to chromatin.
CC Participates in the recruitment of the RAD1-RAD9-HUS1 complex and RHNO1
CC onto chromatin, and in CHEK1 activation. May also serve as a sensor of
CC DNA replication progression, and may be involved in homologous
CC recombination (By similarity). Essential for embryonic development. May
CC be involved in homologous recombination. {ECO:0000250,
CC ECO:0000269|PubMed:15297881}.
CC -!- SUBUNIT: Part of a DNA-binding complex containing RFC2, RFC3, RFC4 and
CC RFC5. Interacts with RAD1 and RAD9 within the RAD1-RAD9-HUS1 complex.
CC Interacts with RAD9B, POLE, SNU13 and MCM7. DNA damage promotes
CC interaction with ATR or ATM and disrupts interaction with the RAD1-
CC RAD9-HUS1 complex (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Note=Phosphorylated form
CC redistributes to discrete nuclear foci upon DNA damage. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Ubiquitous at low levels. Highly expressed in
CC testis, where it is expressed in spermatogonia, spermatocytes and
CC spermatids, but absent in mature spermatozoa (at protein level).
CC {ECO:0000269|PubMed:10232579, ECO:0000269|PubMed:10480350,
CC ECO:0000269|PubMed:9933569}.
CC -!- PTM: Phosphorylated. Phosphorylation on Ser-647 and Ser-657 is cell
CC cycle-regulated, enhanced by genotoxic stress, and required for
CC activation of checkpoint signaling. {ECO:0000269|PubMed:11687627,
CC ECO:0000269|PubMed:14500819, ECO:0000269|PubMed:17376776}.
CC -!- DISRUPTION PHENOTYPE: Mice show numerous defects in embryonic
CC development, starting at E8.5. {ECO:0000269|PubMed:15297881}.
CC -!- SIMILARITY: Belongs to the rad17/RAD24 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF085737; AAC36335.1; -; mRNA.
DR EMBL; AJ011923; CAA09868.1; -; mRNA.
DR EMBL; BC066855; AAH66855.1; -; mRNA.
DR CCDS; CCDS26733.1; -.
DR RefSeq; NP_001037836.1; NM_001044371.2.
DR RefSeq; NP_001269940.1; NM_001283011.1.
DR RefSeq; NP_035363.2; NM_011233.3.
DR AlphaFoldDB; Q6NXW6; -.
DR BioGRID; 202559; 1.
DR DIP; DIP-59315N; -.
DR IntAct; Q6NXW6; 2.
DR STRING; 10090.ENSMUSP00000022136; -.
DR iPTMnet; Q6NXW6; -.
DR PhosphoSitePlus; Q6NXW6; -.
DR EPD; Q6NXW6; -.
DR MaxQB; Q6NXW6; -.
DR PaxDb; Q6NXW6; -.
DR PRIDE; Q6NXW6; -.
DR ProteomicsDB; 300303; -.
DR Antibodypedia; 1389; 661 antibodies from 41 providers.
DR DNASU; 19356; -.
DR Ensembl; ENSMUST00000022136; ENSMUSP00000022136; ENSMUSG00000021635.
DR Ensembl; ENSMUST00000177848; ENSMUSP00000136292; ENSMUSG00000021635.
DR GeneID; 19356; -.
DR KEGG; mmu:19356; -.
DR UCSC; uc007rrc.2; mouse.
DR CTD; 5884; -.
DR MGI; MGI:1333807; Rad17.
DR VEuPathDB; HostDB:ENSMUSG00000021635; -.
DR eggNOG; KOG1970; Eukaryota.
DR GeneTree; ENSGT00440000039046; -.
DR HOGENOM; CLU_018598_0_0_1; -.
DR InParanoid; Q6NXW6; -.
DR OMA; GLRVQEW; -.
DR OrthoDB; 674169at2759; -.
DR PhylomeDB; Q6NXW6; -.
DR Reactome; R-MMU-176187; Activation of ATR in response to replication stress.
DR Reactome; R-MMU-5685938; HDR through Single Strand Annealing (SSA).
DR Reactome; R-MMU-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-MMU-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-MMU-69473; G2/M DNA damage checkpoint.
DR BioGRID-ORCS; 19356; 28 hits in 110 CRISPR screens.
DR ChiTaRS; Rad17; mouse.
DR PRO; PR:Q6NXW6; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; Q6NXW6; protein.
DR Bgee; ENSMUSG00000021635; Expressed in cleaving embryo and 259 other tissues.
DR ExpressionAtlas; Q6NXW6; baseline and differential.
DR Genevisible; Q6NXW6; MM.
DR GO; GO:0000781; C:chromosome, telomeric region; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0031389; C:Rad17 RFC-like complex; IEA:InterPro.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003682; F:chromatin binding; IBA:GO_Central.
DR GO; GO:0003689; F:DNA clamp loader activity; IEA:InterPro.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:MGI.
DR GO; GO:0000077; P:DNA damage checkpoint signaling; IBA:GO_Central.
DR GO; GO:0006281; P:DNA repair; IBA:GO_Central.
DR GO; GO:0033314; P:mitotic DNA replication checkpoint signaling; IBA:GO_Central.
DR GO; GO:0031573; P:mitotic intra-S DNA damage checkpoint signaling; ISO:MGI.
DR GO; GO:0008156; P:negative regulation of DNA replication; ISO:MGI.
DR GO; GO:0042325; P:regulation of phosphorylation; ISO:MGI.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR004582; Checkpoint_prot_Rad17_Rad24.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR018324; Rad17/Rad24_fun/met.
DR PANTHER; PTHR12172; PTHR12172; 1.
DR SMART; SM00382; AAA; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00602; rad24; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell cycle; Developmental protein; DNA damage;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..688
FT /note="Cell cycle checkpoint protein RAD17"
FT /id="PRO_0000209949"
FT REGION 63..84
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 342..379
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 431..688
FT /note="Interaction with MCM7"
FT /evidence="ECO:0000250"
FT REGION 605..688
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 349..378
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 636..664
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 667..688
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 136..143
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT MOD_RES 55
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9XT62"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75943"
FT MOD_RES 358
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75943"
FT MOD_RES 647
FT /note="Phosphoserine; by ATR"
FT /evidence="ECO:0000269|PubMed:11687627,
FT ECO:0000269|PubMed:14500819, ECO:0000269|PubMed:17376776"
FT MOD_RES 657
FT /note="Phosphoserine; by ATR"
FT /evidence="ECO:0000269|PubMed:11687627,
FT ECO:0000269|PubMed:14500819"
FT CONFLICT 16
FT /note="T -> E (in Ref. 3; CAA09868)"
FT /evidence="ECO:0000305"
FT CONFLICT 86
FT /note="D -> N (in Ref. 4; AAH66855)"
FT /evidence="ECO:0000305"
FT CONFLICT 214
FT /note="D -> V (in Ref. 4; AAH66855)"
FT /evidence="ECO:0000305"
FT CONFLICT 397
FT /note="R -> K (in Ref. 4; AAH66855)"
FT /evidence="ECO:0000305"
FT CONFLICT 444
FT /note="P -> S (in Ref. 4; AAH66855)"
FT /evidence="ECO:0000305"
FT CONFLICT 580
FT /note="Q -> P (in Ref. 3; CAA09868)"
FT /evidence="ECO:0000305"
FT CONFLICT 616..619
FT /note="PHSG -> AQR (in Ref. 3; CAA09868)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 688 AA; 77391 MW; 7A950CA8CDDC8732 CRC64;
MSETFLRPKV SSTKVTDWVA PAFDDFEANT AITTITASSL TFSNSSHRRK YLPSTLESNR
LSARKRGRLS LEQTHGLETS RERLSDNEPW VDKYKPETQH ELAVHKKKIE EVETWLKAQV
LEVKPKQGGS VLLITGPPGC GKTTTIKILS KELGIQVQEW VNPILPDFQK DDYKELLSLE
SNFSVVPYQS QIAVFNDFLL RATKYSKLQM LGDDLTTDKK IILVEELPNQ FYRDPNALHE
ILRKHVQIGR CPLVFIVSDS VSGDNNQRLL FPRNIQEECS VSNISFNPVA PTIMMKFLNR
IVTIEASKNG EKIIVPNKTS LELLCQGCSG DIRSAINSLQ FSSSKGENSS WSKKKRMSLK
SDAAISKSKQ KKKHNSTLEN QEIQAIGGKD VSLFLFRALG KILYCKRAPL TELDSPRLPA
HLSEHDRDTL LVQPEEIVEM SHMPGDFFNL YLHQNYIDFF AEVDDLVPAS EFLSFADILG
GDWNTRSLLR EYSTSVATRG VMHSNKARGF AHCQGGSSFR PLHKPQWFLI QKKYRENCLA
AKALFVDFCL PALCLQTQLL PYLALLTIPM RNKAQISFIQ DVGRLPLKRS FGRLKMEALT
DRELGLIDPD SGDESPHSGG QPAQEAPGEP AQAAQNADPE TWSLPLSQNS GSDLPASQPQ
PFSSKVDMEE EEEEEEDIII EDYDSEET
