RAD17_HUMAN
ID RAD17_HUMAN Reviewed; 681 AA.
AC O75943; A8K8X2; D3DWA5; O75714; Q7Z3S4; Q9UNK7; Q9UNR7; Q9UNR8; Q9UPF5;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 29-MAR-2005, sequence version 2.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Cell cycle checkpoint protein RAD17;
DE Short=hRad17;
DE AltName: Full=RF-C/activator 1 homolog;
GN Name=RAD17; Synonyms=R24L;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=9878245; DOI=10.1006/geno.1998.5587;
RA Dean F.B., Lian L., O'Donnell M.;
RT "cDNA cloning and gene mapping of human homologs for Schizosaccharomyces
RT pombe rad17, rad1, and hus1 and cloning of homologs from mouse,
RT Caenorhabditis elegans, and Drosophila melanogaster.";
RL Genomics 54:424-436(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, AND INTERACTION
RP WITH RAD1.
RC TISSUE=Neuroblastoma;
RX PubMed=9660800; DOI=10.1074/jbc.273.29.18340;
RA Parker A.E., Van de Weyer I., Laus M.C., Verhasselt P., Luyten W.H.M.L.;
RT "Identification of a human homologue of the Schizosaccharomyces pombe
RT rad17+ checkpoint gene.";
RL J. Biol. Chem. 273:18340-18346(1998).
RN [3]
RP ERRATUM OF PUBMED:9660800.
RA Parker A.E., Van de Weyer I., Laus M.C., Verhasselt P., Luyten W.H.M.L.;
RL J. Biol. Chem. 274:24438-24438(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, SUBCELLULAR
RP LOCATION, AND VARIANT ARG-557.
RC TISSUE=Fibroblast;
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND ALTERNATIVE SPLICING.
RC TISSUE=Thymus;
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 [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 2), AND TISSUE
RP SPECIFICITY.
RC TISSUE=Fetal brain;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, AND FUNCTION.
RC TISSUE=Cervix carcinoma;
RX PubMed=10208430; DOI=10.1038/sj.onc.1202469;
RA Li L., Peterson C.A., Kanter-Smoler G., Wei Y.-F., Ramagli L.S.,
RA Sunnerhagen P., Siciliano M.J., Legerski R.J.;
RT "hRAD17, a structural homolog of the Schizosaccharomyces pombe RAD17 cell
RT cycle checkpoint gene, stimulates p53 accumulation.";
RL Oncogene 18:1689-1699(1999).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Liver;
RX PubMed=11715513;
RA Han Y., Zhu Y.;
RT "Human hR24L gene is involved in DNA excision repair and recombination
RT repair.";
RL Zhonghua Yi Xue Za Zhi 79:941-943(1999).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), INDUCTION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Colon, and Fibroblast;
RX PubMed=11602352; DOI=10.1016/s0378-1119(01)00692-8;
RA Chen M.-S., Higashikubo R., Laszlo A., Roti Roti J.;
RT "Multiple alternative splicing forms of human RAD17 and their differential
RT response to ionizing radiation.";
RL Gene 277:145-152(2001).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Fetal brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [13]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ILE-32; LEU-487; GLU-535
RP AND ARG-557.
RG NIEHS SNPs program;
RL Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases.
RN [14]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [15]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT ARG-557.
RC TISSUE=Brain;
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 [16]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH SNU13.
RX PubMed=10593953; DOI=10.1074/jbc.274.51.36544;
RA Chang M.-S., Sasaki H., Campbell M.S., Kraeft S.-K., Sutherland R.,
RA Yang C.-Y., Liu Y., Auclair D., Hao L., Sonoda H., Ferland L.H., Chen L.B.;
RT "HRad17 colocalizes with NHP2L1 in the nucleolus and redistributes after UV
RT irradiation.";
RL J. Biol. Chem. 274:36544-36549(1999).
RN [17]
RP INTERACTION WITH THE RAD1/RAD9/HUS1 COMPLEX AND RFC3, AND MUTAGENESIS OF
RP LYS-143.
RX PubMed=10884395; DOI=10.1074/jbc.m005782200;
RA Rauen M., Burtelow M.A., Dufault V.M., Karnitz L.M.;
RT "The human checkpoint protein hRad17 interacts with the PCNA-like proteins
RT hRad1, hHus1, and hRad9.";
RL J. Biol. Chem. 275:29767-29771(2000).
RN [18]
RP FUNCTION, INTERACTION WITH ATM; ATR AND RAD1, PHOSPHORYLATION AT SER-646
RP AND SER-656, AND MUTAGENESIS OF SER-646 AND SER-656.
RX PubMed=11418864; DOI=10.1038/35082110;
RA Bao S., Tibbetts R.S., Brumbaugh K.M., Fang Y., Richardson D.A., Ali A.,
RA Chen S.M., Abraham R.T., Wang X.-F.;
RT "ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic
RT stress responses.";
RL Nature 411:969-974(2001).
RN [19]
RP IDENTIFICATION IN A COMPLEX WITH RFC2; RFC3; RFC4 AND RFC5.
RX PubMed=11572977; DOI=10.1073/pnas.201373498;
RA Lindsey-Boltz L.A., Bermudez V.P., Hurwitz J., Sancar A.;
RT "Purification and characterization of human DNA damage checkpoint Rad
RT complexes.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:11236-11241(2001).
RN [20]
RP FUNCTION, PHOSPHORYLATION AT SER-646 AND SER-656, INTERACTION WITH RFC4,
RP AND MUTAGENESIS OF SER-191; SER-646 AND SER-656.
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 [21]
RP FUNCTION, PHOSPHORYLATION, MUTAGENESIS OF LYS-143, AND SUBCELLULAR
RP LOCATION.
RX PubMed=11799063; DOI=10.1101/gad.950302;
RA Zou L., Cortez D., Elledge S.J.;
RT "Regulation of ATR substrate selection by Rad17-dependent loading of Rad9
RT complexes onto chromatin.";
RL Genes Dev. 16:198-208(2002).
RN [22]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH RFC4.
RX PubMed=12400013; DOI=10.1038/sj.onc.1205872;
RA Dahm K., Huebscher U.;
RT "Colocalization of human Rad17 and PCNA in late S phase of the cell cycle
RT upon replication block.";
RL Oncogene 21:7710-7719(2002).
RN [23]
RP FUNCTION.
RX PubMed=12672690; DOI=10.1101/gad.1065103;
RA Wang X., Zou L., Zheng H., Wei Q., Elledge S.J., Li L.;
RT "Genomic instability and endoreduplication triggered by RAD17 deletion.";
RL Genes Dev. 17:965-970(2003).
RN [24]
RP INTERACTION WITH RAD9B.
RX PubMed=14611806; DOI=10.1016/s0888-7543(03)00200-3;
RA Dufault V.M., Oestreich A.J., Vroman B.T., Karnitz L.M.;
RT "Identification and characterization of RAD9B, a paralog of the RAD9
RT checkpoint gene.";
RL Genomics 82:644-651(2003).
RN [25]
RP FUNCTION, PHOSPHORYLATION AT SER-646 AND SER-656, MUTAGENESIS OF SER-646
RP AND SER-656, AND INTERACTION WITH POLE.
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 [26]
RP FUNCTION, INTERACTION WITH RFC2; RFC3; RFC4 AND RFC5, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=14624239; DOI=10.1371/journal.pbio.0000033;
RA Ellison V., Stillman B.;
RT "Biochemical characterization of DNA damage checkpoint complexes: clamp
RT loader and clamp complexes with specificity for 5' recessed DNA.";
RL PLoS Biol. 1:231-243(2003).
RN [27]
RP FUNCTION, AND INTERACTION WITH RAD1 AND RAD9.
RX PubMed=12578958; DOI=10.1073/pnas.0437927100;
RA Bermudez V.P., Lindsey-Boltz L.A., Cesare A.J., Maniwa Y., Griffith J.D.,
RA Hurwitz J., Sancar A.;
RT "Loading of the human 9-1-1 checkpoint complex onto DNA by the checkpoint
RT clamp loader hRad17-replication factor C complex in vitro.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:1633-1638(2003).
RN [28]
RP INTERACTION WITH PPP5C, AND PHOSPHORYLATION AT SER-646.
RX PubMed=14871926; DOI=10.1101/gad.1176004;
RA Ali A., Zhang J., Bao S., Liu I., Otterness D., Dean N.M., Abraham R.T.,
RA Wang X.F.;
RT "Requirement of protein phosphatase 5 in DNA-damage-induced ATM
RT activation.";
RL Genes Dev. 18:249-254(2004).
RN [29]
RP FUNCTION, AND INTERACTION WITH MCM7.
RX PubMed=15538388; DOI=10.1038/sj.emboj.7600463;
RA Tsao C.-C., Geisen C., Abraham R.T.;
RT "Interaction between human MCM7 and Rad17 proteins is required for
RT replication checkpoint signaling.";
RL EMBO J. 23:4660-4669(2004).
RN [30]
RP FUNCTION, AND MUTAGENESIS OF LYS-143; SER-646 AND SER-656.
RX PubMed=15235112;
RA Garg R., Callens S., Lim D.-S., Canman C.E., Kastan M.B., Xu B.;
RT "Chromatin association of rad17 is required for an ataxia telangiectasia
RT and rad-related kinase-mediated S-phase checkpoint in response to low-dose
RT ultraviolet radiation.";
RL Mol. Cancer Res. 2:362-369(2004).
RN [31]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [32]
RP FUNCTION.
RX PubMed=21659603; DOI=10.1126/science.1203430;
RA Cotta-Ramusino C., McDonald E.R. III, Hurov K., Sowa M.E., Harper J.W.,
RA Elledge S.J.;
RT "A DNA damage response screen identifies RHINO, a 9-1-1 and TopBP1
RT interacting protein required for ATR signaling.";
RL Science 332:1313-1317(2011).
RN [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-71; SER-86 AND SER-359, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
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. {ECO:0000269|PubMed:10208430,
CC ECO:0000269|PubMed:11418864, ECO:0000269|PubMed:11687627,
CC ECO:0000269|PubMed:11799063, ECO:0000269|PubMed:12578958,
CC ECO:0000269|PubMed:12672690, ECO:0000269|PubMed:14500819,
CC ECO:0000269|PubMed:14624239, ECO:0000269|PubMed:15235112,
CC ECO:0000269|PubMed:15538388, ECO:0000269|PubMed:21659603}.
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. {ECO:0000269|PubMed:10593953,
CC ECO:0000269|PubMed:10884395, ECO:0000269|PubMed:11418864,
CC ECO:0000269|PubMed:11572977, ECO:0000269|PubMed:11687627,
CC ECO:0000269|PubMed:12400013, ECO:0000269|PubMed:12578958,
CC ECO:0000269|PubMed:14500819, ECO:0000269|PubMed:14611806,
CC ECO:0000269|PubMed:14624239, ECO:0000269|PubMed:14871926,
CC ECO:0000269|PubMed:15538388, ECO:0000269|PubMed:9660800}.
CC -!- INTERACTION:
CC O75943; Q9UM11: FZR1; NbExp=2; IntAct=EBI-968231, EBI-724997;
CC O75943; P49959: MRE11; NbExp=2; IntAct=EBI-968231, EBI-396513;
CC O75943; O60934: NBN; NbExp=5; IntAct=EBI-968231, EBI-494844;
CC O75943; Q92878: RAD50; NbExp=2; IntAct=EBI-968231, EBI-495494;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10232579,
CC ECO:0000269|PubMed:10593953, ECO:0000269|PubMed:11799063,
CC ECO:0000269|PubMed:12400013}. Note=Phosphorylated form redistributes to
CC discrete nuclear foci upon DNA damage.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=Rad17Sp, FM2;
CC IsoId=O75943-1; Sequence=Displayed;
CC Name=2; Synonyms=Rad17Sp2, FM1;
CC IsoId=O75943-2; Sequence=VSP_013308;
CC Name=3; Synonyms=FM3;
CC IsoId=O75943-3; Sequence=VSP_013306;
CC Name=4; Synonyms=FM4;
CC IsoId=O75943-4; Sequence=VSP_013307, VSP_013309;
CC -!- TISSUE SPECIFICITY: Overexpressed in various cancer cell lines and in
CC colon carcinoma (at protein level). Isoform 2 and isoform 3 are the
CC most abundant isoforms in non irradiated cells (at protein level).
CC Ubiquitous at low levels. Highly expressed in testis, where it is
CC expressed within the germinal epithelium of the seminiferous tubuli.
CC Weakly expressed in seminomas (testicular tumors).
CC {ECO:0000269|PubMed:10208430, ECO:0000269|PubMed:10232579,
CC ECO:0000269|PubMed:10480350, ECO:0000269|PubMed:11602352,
CC ECO:0000269|PubMed:9660800}.
CC -!- INDUCTION: Isoform 1, isoform 3 and isoform 4 are induced by X-ray
CC irradiation. {ECO:0000269|PubMed:11602352}.
CC -!- PTM: Phosphorylated. Phosphorylation on Ser-646 and Ser-656 is cell
CC cycle-regulated, enhanced by genotoxic stress, and required for
CC activation of checkpoint signaling. Phosphorylation is mediated by ATR
CC upon UV or replication arrest, whereas it may be mediated both by ATR
CC and ATM upon ionizing radiation. Phosphorylation on both sites is
CC required for interaction with RAD1 but dispensable for interaction with
CC RFC3 or RFC4. {ECO:0000269|PubMed:11418864,
CC ECO:0000269|PubMed:11687627, ECO:0000269|PubMed:11799063,
CC ECO:0000269|PubMed:14500819, ECO:0000269|PubMed:14871926}.
CC -!- SIMILARITY: Belongs to the rad17/RAD24 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/rad17/";
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DR EMBL; AF076838; AAC95520.1; -; mRNA.
DR EMBL; AJ004977; CAA06251.1; -; mRNA.
DR EMBL; AF112263; AAD38878.1; -; mRNA.
DR EMBL; AF085736; AAC36334.1; -; mRNA.
DR EMBL; AJ001642; CAA04894.1; -; mRNA.
DR EMBL; AJ131296; CAB46364.1; -; Genomic_DNA.
DR EMBL; AJ131297; CAB46364.1; JOINED; Genomic_DNA.
DR EMBL; AJ131298; CAB46364.1; JOINED; Genomic_DNA.
DR EMBL; AJ131299; CAB46364.1; JOINED; Genomic_DNA.
DR EMBL; AJ131300; CAB46364.1; JOINED; Genomic_DNA.
DR EMBL; AJ131301; CAB46364.1; JOINED; Genomic_DNA.
DR EMBL; AJ131302; CAB46364.1; JOINED; Genomic_DNA.
DR EMBL; AJ131303; CAB46364.1; JOINED; Genomic_DNA.
DR EMBL; AJ131304; CAB46364.1; JOINED; Genomic_DNA.
DR EMBL; AJ131305; CAB46364.1; JOINED; Genomic_DNA.
DR EMBL; AJ131306; CAB46364.1; JOINED; Genomic_DNA.
DR EMBL; AJ131307; CAB46364.1; JOINED; Genomic_DNA.
DR EMBL; AJ131308; CAB46364.1; JOINED; Genomic_DNA.
DR EMBL; AF017748; AAD01620.1; -; mRNA.
DR EMBL; AF126424; AAD17334.1; -; mRNA.
DR EMBL; AF098533; AAC97950.1; -; mRNA.
DR EMBL; AF098534; AAC97951.1; -; mRNA.
DR EMBL; AL122068; CAB59244.1; -; mRNA.
DR EMBL; AK292487; BAF85176.1; -; mRNA.
DR EMBL; BX537441; CAD97683.1; -; mRNA.
DR EMBL; AY612854; AAT09763.1; -; Genomic_DNA.
DR EMBL; CH471137; EAW51283.1; -; Genomic_DNA.
DR EMBL; CH471137; EAW51284.1; -; Genomic_DNA.
DR EMBL; CH471137; EAW51285.1; -; Genomic_DNA.
DR EMBL; CH471137; EAW51286.1; -; Genomic_DNA.
DR EMBL; CH471137; EAW51288.1; -; Genomic_DNA.
DR EMBL; BC032304; AAH32304.1; -; mRNA.
DR CCDS; CCDS4003.1; -. [O75943-1]
DR CCDS; CCDS4004.1; -. [O75943-2]
DR CCDS; CCDS4005.1; -. [O75943-4]
DR CCDS; CCDS47226.1; -. [O75943-3]
DR PIR; T34548; T34548.
DR RefSeq; NP_001265551.1; NM_001278622.1. [O75943-2]
DR RefSeq; NP_002864.1; NM_002873.1. [O75943-2]
DR RefSeq; NP_579916.1; NM_133338.2. [O75943-2]
DR RefSeq; NP_579917.1; NM_133339.2. [O75943-1]
DR RefSeq; NP_579918.1; NM_133340.2. [O75943-3]
DR RefSeq; NP_579919.1; NM_133341.2. [O75943-4]
DR RefSeq; NP_579920.1; NM_133342.2. [O75943-2]
DR RefSeq; NP_579921.1; NM_133343.1. [O75943-2]
DR RefSeq; NP_579922.1; NM_133344.2. [O75943-2]
DR RefSeq; XP_016865168.1; XM_017009679.1.
DR RefSeq; XP_016865169.1; XM_017009680.1.
DR RefSeq; XP_016865170.1; XM_017009681.1. [O75943-2]
DR AlphaFoldDB; O75943; -.
DR BioGRID; 111821; 92.
DR CORUM; O75943; -.
DR DIP; DIP-24254N; -.
DR DIP; DIP-34896N; -.
DR IntAct; O75943; 19.
DR MINT; O75943; -.
DR STRING; 9606.ENSP00000426191; -.
DR iPTMnet; O75943; -.
DR PhosphoSitePlus; O75943; -.
DR BioMuta; RAD17; -.
DR EPD; O75943; -.
DR jPOST; O75943; -.
DR MassIVE; O75943; -.
DR MaxQB; O75943; -.
DR PaxDb; O75943; -.
DR PeptideAtlas; O75943; -.
DR PRIDE; O75943; -.
DR ProteomicsDB; 50304; -. [O75943-1]
DR ProteomicsDB; 50305; -. [O75943-2]
DR ProteomicsDB; 50306; -. [O75943-3]
DR ProteomicsDB; 50307; -. [O75943-4]
DR Antibodypedia; 1389; 661 antibodies from 41 providers.
DR DNASU; 5884; -.
DR Ensembl; ENST00000282891.10; ENSP00000282891.6; ENSG00000152942.19. [O75943-4]
DR Ensembl; ENST00000305138.8; ENSP00000303134.4; ENSG00000152942.19. [O75943-2]
DR Ensembl; ENST00000345306.10; ENSP00000311227.7; ENSG00000152942.19. [O75943-2]
DR Ensembl; ENST00000354312.7; ENSP00000346271.3; ENSG00000152942.19. [O75943-2]
DR Ensembl; ENST00000354868.10; ENSP00000346938.5; ENSG00000152942.19. [O75943-2]
DR Ensembl; ENST00000358030.6; ENSP00000350725.2; ENSG00000152942.19. [O75943-3]
DR Ensembl; ENST00000361732.6; ENSP00000355226.2; ENSG00000152942.19. [O75943-2]
DR Ensembl; ENST00000380774.7; ENSP00000370151.3; ENSG00000152942.19. [O75943-1]
DR Ensembl; ENST00000509734.5; ENSP00000426191.1; ENSG00000152942.19. [O75943-1]
DR Ensembl; ENST00000521422.5; ENSP00000427743.1; ENSG00000152942.19. [O75943-3]
DR Ensembl; ENST00000610770.4; ENSP00000478167.1; ENSG00000276618.4.
DR Ensembl; ENST00000611523.4; ENSP00000477962.1; ENSG00000276618.4.
DR Ensembl; ENST00000612044.4; ENSP00000477996.1; ENSG00000276618.4.
DR Ensembl; ENST00000616488.2; ENSP00000484854.1; ENSG00000276618.4.
DR Ensembl; ENST00000616683.4; ENSP00000482775.1; ENSG00000152942.19. [O75943-2]
DR Ensembl; ENST00000616759.4; ENSP00000479160.1; ENSG00000276618.4.
DR Ensembl; ENST00000620889.4; ENSP00000482371.1; ENSG00000276618.4.
DR GeneID; 5884; -.
DR KEGG; hsa:5884; -.
DR MANE-Select; ENST00000354868.10; ENSP00000346938.5; NM_133338.3; NP_579916.1. [O75943-2]
DR UCSC; uc003jwg.4; human. [O75943-1]
DR CTD; 5884; -.
DR DisGeNET; 5884; -.
DR GeneCards; RAD17; -.
DR HGNC; HGNC:9807; RAD17.
DR HPA; ENSG00000152942; Low tissue specificity.
DR MIM; 603139; gene.
DR neXtProt; NX_O75943; -.
DR OpenTargets; ENSG00000152942; -.
DR PharmGKB; PA34167; -.
DR VEuPathDB; HostDB:ENSG00000152942; -.
DR eggNOG; KOG1970; Eukaryota.
DR GeneTree; ENSGT00440000039046; -.
DR HOGENOM; CLU_018598_0_0_1; -.
DR InParanoid; O75943; -.
DR OMA; GLRVQEW; -.
DR OrthoDB; 674169at2759; -.
DR PhylomeDB; O75943; -.
DR BRENDA; 3.6.4.B8; 2681.
DR PathwayCommons; O75943; -.
DR Reactome; R-HSA-176187; Activation of ATR in response to replication stress.
DR Reactome; R-HSA-5685938; HDR through Single Strand Annealing (SSA).
DR Reactome; R-HSA-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-HSA-5693616; Presynaptic phase of homologous DNA pairing and strand exchange.
DR Reactome; R-HSA-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-HSA-69473; G2/M DNA damage checkpoint.
DR Reactome; R-HSA-9709570; Impaired BRCA2 binding to RAD51.
DR SignaLink; O75943; -.
DR SIGNOR; O75943; -.
DR BioGRID-ORCS; 5884; 641 hits in 1084 CRISPR screens.
DR ChiTaRS; RAD17; human.
DR GeneWiki; RAD17; -.
DR GenomeRNAi; 5884; -.
DR Pharos; O75943; Tbio.
DR PRO; PR:O75943; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; O75943; protein.
DR Bgee; ENSG00000152942; Expressed in testis and 103 other tissues.
DR ExpressionAtlas; O75943; baseline and differential.
DR Genevisible; O75943; HS.
DR GO; GO:0005730; C:nucleolus; IDA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; TAS:ProtInc.
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:UniProtKB.
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:0000076; P:DNA replication checkpoint signaling; TAS:ProtInc.
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; IMP:UniProtKB.
DR GO; GO:0008156; P:negative regulation of DNA replication; IMP:UniProtKB.
DR GO; GO:0042325; P:regulation of phosphorylation; IMP:UniProtKB.
DR Gene3D; 3.40.50.300; -; 1.
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 SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00602; rad24; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cell cycle; DNA damage;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..681
FT /note="Cell cycle checkpoint protein RAD17"
FT /id="PRO_0000209948"
FT REGION 42..61
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 344..377
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 432..681
FT /note="Interaction with MCM7"
FT /evidence="ECO:0000269|PubMed:15538388"
FT REGION 606..681
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 42..58
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 349..377
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 627..664
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 137..144
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 71
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 86
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 359
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 646
FT /note="Phosphoserine; by ATR and ATM"
FT /evidence="ECO:0000269|PubMed:11418864,
FT ECO:0000269|PubMed:11687627, ECO:0000269|PubMed:14500819,
FT ECO:0000269|PubMed:14871926"
FT MOD_RES 656
FT /note="Phosphoserine; by ATR and ATM"
FT /evidence="ECO:0000269|PubMed:11418864,
FT ECO:0000269|PubMed:11687627, ECO:0000269|PubMed:14500819"
FT VAR_SEQ 1..176
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11602352"
FT /id="VSP_013306"
FT VAR_SEQ 1..97
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:11602352"
FT /id="VSP_013307"
FT VAR_SEQ 1..14
FT /note="MSKTFLRPKVSSTK -> MNQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10208430,
FT ECO:0000303|PubMed:10232579, ECO:0000303|PubMed:10480350,
FT ECO:0000303|PubMed:11230166, ECO:0000303|PubMed:11602352,
FT ECO:0000303|PubMed:11715513, ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:17974005,
FT ECO:0000303|PubMed:9660800, ECO:0000303|PubMed:9878245"
FT /id="VSP_013308"
FT VAR_SEQ 98..99
FT /note="ET -> MN (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:11602352"
FT /id="VSP_013309"
FT VARIANT 32
FT /note="V -> I (in dbSNP:rs17229831)"
FT /evidence="ECO:0000269|Ref.13"
FT /id="VAR_021574"
FT VARIANT 487
FT /note="R -> L (in dbSNP:rs17236478)"
FT /evidence="ECO:0000269|Ref.13"
FT /id="VAR_021575"
FT VARIANT 535
FT /note="K -> E (in dbSNP:rs17236485)"
FT /evidence="ECO:0000269|Ref.13"
FT /id="VAR_021576"
FT VARIANT 557
FT /note="L -> R (in dbSNP:rs1045051)"
FT /evidence="ECO:0000269|PubMed:10232579,
FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.13"
FT /id="VAR_021577"
FT MUTAGEN 143
FT /note="K->E: Impairs phosphorylation on S-656. Abolishes
FT interaction with the RAD1-RAD9-HUS1 complex; does not
FT affect interaction with RFC3."
FT /evidence="ECO:0000269|PubMed:10884395,
FT ECO:0000269|PubMed:11799063, ECO:0000269|PubMed:15235112"
FT MUTAGEN 143
FT /note="K->G: Impairs phosphorylation. Impairs interaction
FT with DNA and the RAD1-RAD9-HUS1 complex; does not affect
FT interaction with RFC3."
FT /evidence="ECO:0000269|PubMed:10884395,
FT ECO:0000269|PubMed:11799063, ECO:0000269|PubMed:15235112"
FT MUTAGEN 191
FT /note="S->A: No effect on phosphorylation by ATR."
FT /evidence="ECO:0000269|PubMed:11687627"
FT MUTAGEN 646
FT /note="S->A: Reduces by 50% phosphorylation by ATR, and
FT abolishes interaction with RAD1. Abolishes phosphorylation
FT by ATR and checkpoint activation without affecting
FT interaction with RFC3, RFC4, ATM or ATR; when associated
FT with A-656."
FT /evidence="ECO:0000269|PubMed:11418864,
FT ECO:0000269|PubMed:11687627, ECO:0000269|PubMed:14500819,
FT ECO:0000269|PubMed:15235112"
FT MUTAGEN 646
FT /note="S->D: Abolishes interaction with RAD1; when
FT associated with D-656."
FT /evidence="ECO:0000269|PubMed:11418864,
FT ECO:0000269|PubMed:11687627, ECO:0000269|PubMed:14500819,
FT ECO:0000269|PubMed:15235112"
FT MUTAGEN 656
FT /note="S->A: Reduces by 50% phosphorylation by ATR, and
FT abolishes interaction with RAD1. Abolishes phosphorylation
FT by ATR and checkpoint activation without affecting
FT interaction with RFC3, RFC4, ATM or ATR; when associated
FT with A-646."
FT /evidence="ECO:0000269|PubMed:11418864,
FT ECO:0000269|PubMed:11687627, ECO:0000269|PubMed:14500819,
FT ECO:0000269|PubMed:15235112"
FT MUTAGEN 656
FT /note="S->D: Abolishes interaction with RAD1; when
FT associated with D-646."
FT /evidence="ECO:0000269|PubMed:11418864,
FT ECO:0000269|PubMed:11687627, ECO:0000269|PubMed:14500819,
FT ECO:0000269|PubMed:15235112"
FT CONFLICT 75
FT /note="I -> V (in Ref. 12; CAD97683)"
FT /evidence="ECO:0000305"
FT CONFLICT 187
FT /note="F -> L (in Ref. 5; AAC36334)"
FT /evidence="ECO:0000305"
FT CONFLICT 194
FT /note="A -> S (in Ref. 7; AAD01620)"
FT /evidence="ECO:0000305"
FT CONFLICT 340
FT /note="L -> P (in Ref. 5; AAC36334)"
FT /evidence="ECO:0000305"
FT CONFLICT 445
FT /note="P -> S (in Ref. 5; AAC36334)"
FT /evidence="ECO:0000305"
FT CONFLICT 462
FT /note="M -> T (in Ref. 5; AAC36334)"
FT /evidence="ECO:0000305"
FT CONFLICT 648
FT /note="N -> D (in Ref. 5; AAC36334)"
FT /evidence="ECO:0000305"
FT CONFLICT 672
FT /note="I -> M (in Ref. 5; AAC36334)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 681 AA; 77055 MW; 796C2BD48F7995A3 CRC64;
MSKTFLRPKV SSTKVTDWVD PSFDDFLECS GVSTITATSL GVNNSSHRRK NGPSTLESSR
FPARKRGNLS SLEQIYGLEN SKEYLSENEP WVDKYKPETQ HELAVHKKKI EEVETWLKAQ
VLERQPKQGG SILLITGPPG CGKTTTLKIL SKEHGIQVQE WINPVLPDFQ KDDFKGMFNT
ESSFHMFPYQ SQIAVFKEFL LRATKYNKLQ MLGDDLRTDK KIILVEDLPN QFYRDSHTLH
EVLRKYVRIG RCPLIFIISD SLSGDNNQRL LFPKEIQEEC SISNISFNPV APTIMMKFLN
RIVTIEANKN GGKITVPDKT SLELLCQGCS GDIRSAINSL QFSSSKGENN LRPRKKGMSL
KSDAVLSKSK RRKKPDRVFE NQEVQAIGGK DVSLFLFRAL GKILYCKRAS LTELDSPRLP
SHLSEYERDT LLVEPEEVVE MSHMPGDLFN LYLHQNYIDF FMEIDDIVRA SEFLSFADIL
SGDWNTRSLL REYSTSIATR GVMHSNKARG YAHCQGGGSS FRPLHKPQWF LINKKYRENC
LAAKALFPDF CLPALCLQTQ LLPYLALLTI PMRNQAQISF IQDIGRLPLK RHFGRLKMEA
LTDREHGMID PDSGDEAQLN GGHSAEESLG EPTQATVPET WSLPLSQNSA SELPASQPQP
FSAQGDMEEN IIIEDYESDG T
