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Cell cycle checkpoint protein RAD17

 RAD17_MOUSE             Reviewed;         688 AA.
Q6NXW6; O88934; O89024;
29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
29-MAR-2005, sequence version 2.
12-AUG-2020, entry version 133.
RecName: Full=Cell cycle checkpoint protein RAD17;
Name=Rad17;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
PubMed=10232579;
Bao S., Chang M.-S., Auclair D., Sun Y., Wang Y., Wong W.-K., Zhang J.,
Liu Y., Qian X., Sutherland R., Magi-Galluzi C., Weisberg E., Cheng E.Y.S.,
Hao L., Sasaki H., Campbell M.S., Kraeft S.-K., Loda M., Lo K.-M.,
Chen L.B.;
"HRad17, a human homologue of the Schizosaccharomyces pombe checkpoint gene
rad17, is overexpressed in colon carcinoma.";
Cancer Res. 59:2023-2028(1999).
[2]
NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
TISSUE=Brain;
PubMed=9933569; DOI=10.1006/geno.1998.5642;
Bluyssen H.A.R., Naus N.C., van Os R.I., Jaspers I., Hoeijmakers J.H.J.,
de Klein A.;
"Human and mouse homologs of the Schizosaccharomyces pombe rad17+ cell
cycle checkpoint control gene.";
Genomics 55:219-228(1999).
[3]
NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
TISSUE=Testis;
PubMed=10480350; DOI=10.1007/s004399900067;
von Deimling F., Scharf J.M., Liehr T., Rothe M., Kelter A.-R., Albers P.,
Dietrich W.F., Kunkel L.M., Wernert N., Wirth B.;
"Human and mouse RAD17 genes: identification, localization, genomic
structure and histological expression pattern in normal testis and
seminoma.";
Hum. Genet. 105:17-27(1999).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
STRAIN=C57BL/6J; TISSUE=Egg;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project:
the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[5]
PHOSPHORYLATION AT SER-647 AND SER-657.
PubMed=11687627; DOI=10.1073/pnas.231364598;
Post S.M., Weng Y.-C., Cimprich K., Chen L.B., Xu Y., Lee E.Y.-H.P.;
"Phosphorylation of serines 635 and 645 of human Rad17 is cell cycle
regulated and is required for G(1)/S checkpoint activation in response to
DNA damage.";
Proc. Natl. Acad. Sci. U.S.A. 98:13102-13107(2001).
[6]
PHOSPHORYLATION AT SER-647 AND SER-657.
PubMed=14500819; DOI=10.1093/nar/gkg765;
Post S.M., Tomkinson A.E., Lee E.Y.-H.P.;
"The human checkpoint Rad protein Rad17 is chromatin-associated throughout
the cell cycle, localizes to DNA replication sites, and interacts with DNA
polymerase epsilon.";
Nucleic Acids Res. 31:5568-5575(2003).
[7]
FUNCTION, AND DISRUPTION PHENOTYPE.
PubMed=15297881; DOI=10.1038/sj.emboj.7600353;
Budzowska M., Jaspers I., Essers J., de Waard H., van Drunen E., Hanada K.,
Beverloo B., Hendriks R.W., de Klein A., Kanaar R., Hoeijmakers J.H.,
Maas A.;
"Mutation of the mouse Rad17 gene leads to embryonic lethality and reveals
a role in DNA damage-dependent recombination.";
EMBO J. 23:3548-3558(2004).
[8]
PHOSPHORYLATION AT SER-647.
PubMed=17376776; DOI=10.1074/jbc.c700019200;
Yong W., Bao S., Chen H., Li D., Sanchez E.R., Shou W.;
"Mice lacking protein phosphatase 5 are defective in ataxia telangiectasia
mutated (ATM)-mediated cell cycle arrest.";
J. Biol. Chem. 282:14690-14694(2007).
-!- FUNCTION: Essential for sustained cell growth, maintenance of
chromosomal stability, and ATR-dependent checkpoint activation upon DNA
damage. Has a weak ATPase activity required for binding to chromatin.
Participates in the recruitment of the RAD1-RAD9-HUS1 complex and RHNO1
onto chromatin, and in CHEK1 activation. May also serve as a sensor of
DNA replication progression, and may be involved in homologous
recombination (By similarity). Essential for embryonic development. May
be involved in homologous recombination. {ECO:0000250,
ECO:0000269|PubMed:15297881}.
-!- SUBUNIT: Part of a DNA-binding complex containing RFC2, RFC3, RFC4 and
RFC5. Interacts with RAD1 and RAD9 within the RAD1-RAD9-HUS1 complex.
Interacts with RAD9B, POLE, SNU13 and MCM7. DNA damage promotes
interaction with ATR or ATM and disrupts interaction with the RAD1-
RAD9-HUS1 complex (By similarity). {ECO:0000250}.
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Note=Phosphorylated form
redistributes to discrete nuclear foci upon DNA damage. {ECO:0000250}.
-!- TISSUE SPECIFICITY: Ubiquitous at low levels. Highly expressed in
testis, where it is expressed in spermatogonia, spermatocytes and
spermatids, but absent in mature spermatozoa (at protein level).
{ECO:0000269|PubMed:10232579, ECO:0000269|PubMed:10480350,
ECO:0000269|PubMed:9933569}.
-!- PTM: Phosphorylated. Phosphorylation on Ser-647 and Ser-657 is cell
cycle-regulated, enhanced by genotoxic stress, and required for
activation of checkpoint signaling. {ECO:0000269|PubMed:11687627,
ECO:0000269|PubMed:14500819, ECO:0000269|PubMed:17376776}.
-!- DISRUPTION PHENOTYPE: Mice show numerous defects in embryonic
development, starting at E8.5. {ECO:0000269|PubMed:15297881}.
-!- SIMILARITY: Belongs to the rad17/RAD24 family. {ECO:0000305}.
---------------------------------------------------------------------------
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EMBL; AF085737; AAC36335.1; -; mRNA.
EMBL; AJ011923; CAA09868.1; -; mRNA.
EMBL; BC066855; AAH66855.1; -; mRNA.
CCDS; CCDS26733.1; -.
RefSeq; NP_001037836.1; NM_001044371.2.
RefSeq; NP_001269940.1; NM_001283011.1.
RefSeq; NP_035363.2; NM_011233.3.
SMR; Q6NXW6; -.
BioGRID; 202559; 1.
DIP; DIP-59315N; -.
IntAct; Q6NXW6; 2.
STRING; 10090.ENSMUSP00000022136; -.
iPTMnet; Q6NXW6; -.
PhosphoSitePlus; Q6NXW6; -.
EPD; Q6NXW6; -.
MaxQB; Q6NXW6; -.
PaxDb; Q6NXW6; -.
PRIDE; Q6NXW6; -.
Antibodypedia; 1389; 621 antibodies.
Ensembl; ENSMUST00000022136; ENSMUSP00000022136; ENSMUSG00000021635.
Ensembl; ENSMUST00000177848; ENSMUSP00000136292; ENSMUSG00000021635.
GeneID; 19356; -.
KEGG; mmu:19356; -.
UCSC; uc007rrc.2; mouse.
CTD; 5884; -.
MGI; MGI:1333807; Rad17.
eggNOG; KOG1970; Eukaryota.
GeneTree; ENSGT00440000039046; -.
HOGENOM; CLU_018598_0_0_1; -.
InParanoid; Q6NXW6; -.
KO; K06662; -.
OMA; EPWVDRY; -.
OrthoDB; 674169at2759; -.
PhylomeDB; Q6NXW6; -.
Reactome; R-MMU-176187; Activation of ATR in response to replication stress.
Reactome; R-MMU-5685938; HDR through Single Strand Annealing (SSA).
Reactome; R-MMU-5693607; Processing of DNA double-strand break ends.
Reactome; R-MMU-5693616; Presynaptic phase of homologous DNA pairing and strand exchange.
Reactome; R-MMU-6804756; Regulation of TP53 Activity through Phosphorylation.
Reactome; R-MMU-69473; G2/M DNA damage checkpoint.
BioGRID-ORCS; 19356; 9 hits in 20 CRISPR screens.
ChiTaRS; Rad17; mouse.
PRO; PR:Q6NXW6; -.
Proteomes; UP000000589; Chromosome 13.
RNAct; Q6NXW6; protein.
Bgee; ENSMUSG00000021635; Expressed in cleaving embryo and 295 other tissues.
Genevisible; Q6NXW6; MM.
GO; GO:0000781; C:chromosome, telomeric region; IEA:Ensembl.
GO; GO:0042025; C:host cell nucleus; IEA:InterPro.
GO; GO:0000790; C:nuclear chromatin; IBA:GO_Central.
GO; GO:0005730; C:nucleolus; ISO:MGI.
GO; GO:0005654; C:nucleoplasm; ISO:MGI.
GO; GO:0031389; C:Rad17 RFC-like complex; IEA:InterPro.
GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO; GO:0003682; F:chromatin binding; IBA:GO_Central.
GO; GO:0003689; F:DNA clamp loader activity; IEA:InterPro.
GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:MGI.
GO; GO:0000077; P:DNA damage checkpoint; ISO:MGI.
GO; GO:0006281; P:DNA repair; IBA:GO_Central.
GO; GO:0007093; P:mitotic cell cycle checkpoint; ISO:MGI.
GO; GO:0033314; P:mitotic DNA replication checkpoint; IBA:GO_Central.
GO; GO:0007275; P:multicellular organism development; IEA:UniProtKB-KW.
GO; GO:0008156; P:negative regulation of DNA replication; ISO:MGI.
GO; GO:0042325; P:regulation of phosphorylation; ISO:MGI.
InterPro; IPR003593; AAA+_ATPase.
InterPro; IPR004582; Checkpoint_prot_Rad17_Rad24.
InterPro; IPR027417; P-loop_NTPase.
InterPro; IPR018324; Rad17/Rad24_fun/met.
PANTHER; PTHR12172; PTHR12172; 1.
SMART; SM00382; AAA; 1.
SUPFAM; SSF52540; SSF52540; 1.
TIGRFAMs; TIGR00602; rad24; 1.
1: Evidence at protein level;
ATP-binding; Cell cycle; Developmental protein; DNA damage;
Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome.
CHAIN 1..688
/note="Cell cycle checkpoint protein RAD17"
/id="PRO_0000209949"
NP_BIND 136..143
/note="ATP"
/evidence="ECO:0000255"
REGION 431..688
/note="Interaction with MCM7"
/evidence="ECO:0000250"
COMPBIAS 669..676
/note="Poly-Glu"
MOD_RES 55
/note="Phosphothreonine"
/evidence="ECO:0000250|UniProtKB:Q9XT62"
MOD_RES 85
/note="Phosphoserine"
/evidence="ECO:0000250|UniProtKB:O75943"
MOD_RES 358
/note="Phosphoserine"
/evidence="ECO:0000250|UniProtKB:O75943"
MOD_RES 647
/note="Phosphoserine; by ATR"
/evidence="ECO:0000269|PubMed:11687627,
ECO:0000269|PubMed:14500819, ECO:0000269|PubMed:17376776"
MOD_RES 657
/note="Phosphoserine; by ATR"
/evidence="ECO:0000269|PubMed:11687627,
ECO:0000269|PubMed:14500819"
CONFLICT 16
/note="T -> E (in Ref. 3; CAA09868)"
/evidence="ECO:0000305"
CONFLICT 86
/note="D -> N (in Ref. 4; AAH66855)"
/evidence="ECO:0000305"
CONFLICT 214
/note="D -> V (in Ref. 4; AAH66855)"
/evidence="ECO:0000305"
CONFLICT 397
/note="R -> K (in Ref. 4; AAH66855)"
/evidence="ECO:0000305"
CONFLICT 444
/note="P -> S (in Ref. 4; AAH66855)"
/evidence="ECO:0000305"
CONFLICT 580
/note="Q -> P (in Ref. 3; CAA09868)"
/evidence="ECO:0000305"
CONFLICT 616..619
/note="PHSG -> AQR (in Ref. 3; CAA09868)"
/evidence="ECO:0000305"
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


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Pathways :
WP414: Cell Cycle and Cell Division
WP31: Cell cycle
WP445: G1 to S cell cycle control
WP1083: Cell cycle
WP348: G1 to S cell cycle control
WP179: Cell cycle
WP840: G1 to S cell cycle control
WP1393: Cell cycle
WP1078: G1 to S cell cycle control
WP964: Cell cycle
WP1782: APC/C-mediated degradation of cell cycle proteins
WP1900: Regulation of mitotic cell cycle
WP413: G1 to S cell cycle control
WP1200: Cell cycle
WP429: Cell cycle
WP45: G1 to S cell cycle control
WP959: G1 to S cell cycle control
WP190: Cell cycle
WP1775: Cell Cycle Checkpoints
WP1566: Citrate cycle (TCA cycle)
WP1792: Cell Cycle, Mitotic
WP844: Cell cycle
WP1195: G1 to S cell cycle control
WP2218: sGC
WP426: Urea cycle and metabolism of amino groups

Related Genes :
[RAD17 R24L] Cell cycle checkpoint protein RAD17 (hRad17) (RF-C/activator 1 homolog)
[Rad17] Cell cycle checkpoint protein RAD17
[RAD17 At5g66130 K2A18.21] Cell cycle checkpoint protein RAD17 (AtRAD17) (Radiation-sensitive protein 17)
[RAD17 YOR368W] DNA damage checkpoint control protein RAD17 (DNA repair exonuclease RAD17)
[rad17 SPAC14C4.13] Checkpoint protein rad17
[RAD1 REC1] Cell cycle checkpoint protein RAD1 (hRAD1) (EC 3.1.11.2) (DNA repair exonuclease rad1 homolog) (Rad1-like DNA damage checkpoint protein)
[RAD9A] Cell cycle checkpoint control protein RAD9A (hRAD9) (EC 3.1.11.2) (DNA repair exonuclease rad9 homolog A)
[CHEK1 CHK1] Serine/threonine-protein kinase Chk1 (EC 2.7.11.1) (CHK1 checkpoint homolog) (Cell cycle checkpoint kinase) (Checkpoint kinase-1)
[mrt-2 hpr-1 Y41C4A.14] Cell cycle checkpoint protein RAD1 homolog mrt-2 (EC 3.1.11.2)
[Rad9a Rad9] Cell cycle checkpoint control protein RAD9A (mRAD9) (EC 3.1.11.2) (DNA repair exonuclease rad9 homolog A) (Rad9-like protein)
[RAD17] Cell cycle checkpoint protein RAD17
[NBN NBS NBS1 P95] Nibrin (Cell cycle regulatory protein p95) (Nijmegen breakage syndrome protein 1)
[RAD9B] Cell cycle checkpoint control protein RAD9B (DNA repair exonuclease rad9 homolog B) (hRAD9B)
[RAD17] Cell cycle checkpoint protein RAD17
[DDC1 YPL194W] DNA damage checkpoint protein 1
[HUS1] Checkpoint protein HUS1 (hHUS1)
[RAD24 YER173W SYGP-ORF60] Checkpoint protein RAD24
[Chek1 Chk1] Serine/threonine-protein kinase Chk1 (EC 2.7.11.1) (CHK1 checkpoint homolog) (Checkpoint kinase-1)
[Chek1 Chk1] Serine/threonine-protein kinase Chk1 (EC 2.7.11.1) (CHK1 checkpoint homolog) (Checkpoint kinase-1)
[CHEK1 CHK1] Serine/threonine-protein kinase Chk1 (EC 2.7.11.1) (CHK1 checkpoint homolog) (Checkpoint kinase-1)
[MEC3 PIP3 PSO9 YLR288C L8003.15] DNA damage checkpoint control protein MEC3
[Rad1 Rec1] Cell cycle checkpoint protein RAD1 (mRAD1) (EC 3.1.11.2) (DNA repair exonuclease rad1 homolog) (Rad1-like DNA damage checkpoint protein)
[Hus1] Checkpoint protein HUS1 (mHUS1)
[rad17 LOC101732819] RAD17 checkpoint clamp loader component
[rad1 SPAC1952.07] DNA damage checkpoint control protein rad1
[slc26a2 rad17] RAD17 checkpoint clamp loader component (Solute carrier family 26 member 2)
[RAD17] Cell cycle checkpoint protein RAD17 isoform 2
[CCAR2 DBC1 KIAA1967] Cell cycle and apoptosis regulator protein 2 (Cell division cycle and apoptosis regulator protein 2) (DBIRD complex subunit KIAA1967) (Deleted in breast cancer gene 1 protein) (DBC-1) (DBC.1) (NET35) (p30 DBC)
[Ccar2] Cell cycle and apoptosis regulator protein 2 (Cell division cycle and apoptosis regulator protein 2)
[Rad17] RAD17 checkpoint clamp loader component

Bibliography :
[31574972] Investigation of the Possible Role of RAD9 in Post-Diapaused Embryonic Development of the Brine Shrimp .
[31353086] Human Rad17 C-terminal tail is phosphorylated by concerted action of CK1δ/ε and CK2 to promote interaction with the 9-1-1 complex.
[30061412] Warsaw breakage syndrome DDX11 helicase acts jointly with RAD17 in the repair of bulky lesions and replication through abasic sites.
[29902452] Casein kinase 2 promotes interaction between Rad17 and the 9-1-1 complex through constitutive phosphorylation of the C-terminal tail of human Rad17.
[29485113] ATR kinase regulates its attenuation via PPM1D phosphatase recruitment to chromatin during recovery from DNA replication stress signalling.
[29357057] Functions of Multiple Clamp and Clamp-Loader Complexes in Eukaryotic DNA Replication.
[28666868] The polyanionic C-terminal tail of human Rad17 regulates interaction with the 9-1-1 complex.
[28238011] Human RAD 17 Polymorphism at Codon 546 Is Associated with the Risk of Colorectal Cancer.
[27678521] Prevention of DNA Rereplication Through a Meiotic Recombination Checkpoint Response.
[27453043] A Network of Conserved Synthetic Lethal Interactions for Exploration of Precision Cancer Therapy.