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 27-MAR-2024, entry version 197. DE RecName: Full=Cell cycle checkpoint protein RAD17; DE Short=hRad17; DE AltName: Full=RF-C/activator 1 homolog; GN Name=RAD17 {ECO:0000303|PubMed:9878245, ECO:0000312|HGNC:HGNC:9807}; GN 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 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). RN [34] {ECO:0007744|PDB:8GNN} RP X-RAY CRYSTALLOGRAPHY (2.12 ANGSTROMS) OF 16-26 IN COMPLEX WITH THE 9-1-1 RP COMPLEX, INTERACTION WITH RAD1, AND MUTAGENESIS OF 18-TRP--PHE-23. RX PubMed=36841485; DOI=10.1016/j.jbc.2023.103061; RA Hara K., Hishiki A., Hoshino T., Nagata K., Iida N., Sawada Y., Ohashi E., RA Hashimoto H.; RT "The 9-1-1 DNA clamp subunit RAD1 forms specific interactions with clamp RT loader RAD17, revealing functional implications for binding-protein RT RHINO."; RL J. Biol. Chem. 299:103061-103061(2023). CC -!- FUNCTION: Essential for sustained cell growth, maintenance of CC chromosomal stability, and ATR-dependent checkpoint activation upon DNA CC damage (PubMed:10208430, PubMed:11418864, PubMed:11687627, CC PubMed:11799063, PubMed:12672690, PubMed:14624239, PubMed:15235112). CC Has a weak ATPase activity required for binding to chromatin CC (PubMed:10208430, PubMed:11418864, PubMed:11687627, PubMed:11799063, CC PubMed:12672690, PubMed:14624239, PubMed:15235112). Participates in the CC recruitment of the 9-1-1 (RAD1-RAD9-HUS1) complex and RHNO1 onto CC chromatin, and in CHEK1 activation (PubMed:21659603). May also serve as CC a sensor of DNA replication progression, and may be involved in CC homologous recombination (PubMed:14500819, PubMed:12578958, CC PubMed:15538388). {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 (PubMed:10884395, PubMed:11572977, PubMed:11687627, CC PubMed:12400013, PubMed:14624239). Interacts with RAD1 and RAD9 within CC the 9-1-1 (RAD1-RAD9-HUS1) complex (PubMed:11418864, PubMed:10884395, CC PubMed:12578958, PubMed:9660800, PubMed:36841485). Interacts with CC RAD9B, POLE, SNU13 and MCM7 (PubMed:15538388, PubMed:10593953, CC PubMed:14500819, PubMed:14611806). DNA damage promotes interaction with CC ATR or ATM and disrupts interaction with the 9-1-1 (RAD1-RAD9-HUS1) CC complex (PubMed:11418864, PubMed:10884395, PubMed:12578958). CC {ECO:0000269|PubMed:10593953, ECO:0000269|PubMed:10884395, CC ECO:0000269|PubMed:11418864, ECO:0000269|PubMed:11572977, CC ECO:0000269|PubMed:11687627, ECO:0000269|PubMed:12400013, CC ECO:0000269|PubMed:12578958, ECO:0000269|PubMed:14500819, CC ECO:0000269|PubMed:14611806, ECO:0000269|PubMed:14624239, CC ECO:0000269|PubMed:15538388, ECO:0000269|PubMed:36841485, CC 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. {ECO:0000269|PubMed:11799063}. 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]: Induced by X-ray irradiation. CC {ECO:0000269|PubMed:11602352}. CC -!- INDUCTION: [Isoform 3]: Induced by X-ray irradiation. CC {ECO:0000269|PubMed:11602352}. CC -!- INDUCTION: [Isoform 4]: Induced by X-ray irradiation. CC {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/"; 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; 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 PDB; 7Z6H; EM; 3.59 A; B/K=1-681. DR PDB; 8GNN; X-ray; 2.12 A; D=16-26. DR PDBsum; 7Z6H; -. DR PDBsum; 8GNN; -. DR AlphaFoldDB; O75943; -. DR EMDB; EMD-14527; -. DR SMR; O75943; -. DR BioGRID; 111821; 101. DR ComplexPortal; CPX-7931; DNA replication factor C complex, RAD17 variant. DR CORUM; O75943; -. DR DIP; DIP-24254N; -. DR DIP; DIP-34896N; -. DR IntAct; O75943; 19. DR MINT; O75943; -. DR STRING; 9606.ENSP00000426191; -. DR GlyGen; O75943; 3 sites, 1 O-linked glycan (3 sites). DR iPTMnet; O75943; -. DR PhosphoSitePlus; O75943; -. DR BioMuta; RAD17; -. DR EPD; O75943; -. DR jPOST; O75943; -. DR MassIVE; O75943; -. DR MaxQB; O75943; -. DR PaxDb; 9606-ENSP00000426191; -. DR PeptideAtlas; O75943; -. DR ProteomicsDB; 50304; -. [O75943-1] DR ProteomicsDB; 50305; -. [O75943-2] DR ProteomicsDB; 50306; -. [O75943-3] DR ProteomicsDB; 50307; -. [O75943-4] DR Pumba; O75943; -. DR Antibodypedia; 1389; 733 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 AGR; HGNC:9807; -. 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; YNCLKMA; -. DR OrthoDB; 2881303at2759; -. 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; 670 hits in 1161 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 primordial germ cell in gonad and 104 other cell types or tissues. DR ExpressionAtlas; O75943; baseline and differential. 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:0000077; P:DNA damage checkpoint signaling; IBA:GO_Central. DR GO; GO:0006974; P:DNA damage response; IMP:UniProtKB. 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 CDD; cd18139; HLD_clamp_RarA; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR InterPro; IPR004582; Checkpoint_prot_Rad17_Rad24. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR018324; Rad17/Rad24_fun/met. DR NCBIfam; TIGR00602; rad24; 1. DR PANTHER; PTHR12172; CELL CYCLE CHECKPOINT PROTEIN RAD17; 1. DR PANTHER; PTHR12172:SF2; CELL CYCLE CHECKPOINT PROTEIN RAD17; 1. DR Pfam; PF03215; Rad17; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR Genevisible; O75943; HS. PE 1: Evidence at protein level; KW 3D-structure; 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 MOTIF 17..25 FT /note="RAD1-binding motif" FT /evidence="ECO:0000269|PubMed:36841485" 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 18..23 FT /note="WVDPSF->AADPSA: Strongly reduced interaction with FT RAD1." FT /evidence="ECO:0000269|PubMed:36841485" 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 //