ID RAD9A_HUMAN Reviewed; 391 AA. AC Q99638; B2RCZ8; Q6FI29; Q96C41; DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1997, sequence version 1. DT 27-MAR-2024, entry version 166. DE RecName: Full=Cell cycle checkpoint control protein RAD9A; DE Short=hRAD9; DE EC=3.1.11.2 {ECO:0000269|PubMed:10713044}; DE AltName: Full=DNA repair exonuclease rad9 homolog A; GN Name=RAD9A; 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]. RX PubMed=8943031; DOI=10.1073/pnas.93.24.13890; RA Lieberman H.B., Hopkins K.M., Nass M., Demetrick D., Davey S.; RT "A human homolog of the Schizosaccharomyces pombe rad9+ checkpoint control RT gene."; RL Proc. Natl. Acad. Sci. U.S.A. 93:13890-13895(1996). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS PHE-3; ALA-100; ARG-239 AND RP THR-307. RG NIEHS SNPs program; RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Trachea; 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 [5] 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Testis; 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 [7] RP PROTEIN SEQUENCE OF 270-280; 326-329; 373-383 AND 385-390, IDENTIFICATION RP BY MASS SPECTROMETRY, PHOSPHORYLATION AT SER-272; SER-277; SER-328; RP SER-341; SER-375; SER-380 AND SER-387, AND MUTAGENESIS OF SER-272; SER-277; RP SER-328; SER-341; SER-375; SER-380 AND SER-387. RX PubMed=12709442; DOI=10.1074/jbc.m301544200; RA Roos-Mattjus P., Hopkins K.M., Oestreich A.J., Vroman B.T., Johnson K.L., RA Naylor S., Lieberman H.B., Karnitz L.M.; RT "Phosphorylation of human Rad9 is required for genotoxin-activated RT checkpoint signaling."; RL J. Biol. Chem. 278:24428-24437(2003). RN [8] RP INTERACTION WITH HUS1 AND RAD1. RX PubMed=10359610; DOI=10.1091/mbc.10.6.1985; RA St Onge R.P., Udell C.M., Casselman R., Davey S.; RT "The human G2 checkpoint control protein hRAD9 is a nuclear phosphoprotein RT that forms complexes with hRAD1 and hHUS1."; RL Mol. Biol. Cell 10:1985-1995(1999). RN [9] RP INTERACTION WITH HUS1 AND RAD1. RX PubMed=10777662; DOI=10.1006/geno.2000.6142; RA Hang H., Lieberman H.B.; RT "Physical interaction among human checkpoint control proteins HUS1p, RAD1p, RT and RAD9p, and implications for the regulation of cell cycle progression."; RL Genomics 65:24-33(2000). RN [10] RP FUNCTION IN EXONUCLEASE ACTIVITY, AND CATALYTIC ACTIVITY. RX PubMed=10713044; DOI=10.1074/jbc.275.11.7451; RA Bessho T., Sancar A.; RT "Human DNA damage checkpoint protein hRAD9 is a 3' to 5' exonuclease."; RL J. Biol. Chem. 275:7451-7454(2000). RN [11] RP IDENTIFICATION IN THE 9-1-1 COMPLEX ASSOCIATED WITH HDAC1. RX PubMed=10846170; DOI=10.1074/jbc.m000168200; RA Cai R.L., Yan-Neale Y., Cueto M.A., Xu H., Cohen D.; RT "HDAC1, a histone deacetylase, forms a complex with Hus1 and Rad9, two G2/M RT checkpoint Rad proteins."; RL J. Biol. Chem. 275:27909-27916(2000). RN [12] RP IDENTIFICATION IN THE 9-1-1 COMPLEX ASSOCIATED WITH RAD17. 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 [13] RP INTERACTION WITH DNAJC7. RX PubMed=11573955; DOI=10.1006/bbrc.2001.5685; RA Xiang S.L., Kumano T., Iwasaki S.I., Sun X., Yoshioka K., Yamamoto K.C.; RT "The J domain of Tpr2 regulates its interaction with the proapoptotic and RT cell-cycle checkpoint protein, Rad9."; RL Biochem. Biophys. Res. Commun. 287:932-940(2001). RN [14] RP INTERACTION WITH ABL1 AND BCL2L1, PHOSPHORYLATION, PHOSPHORYLATION AT RP TYR-28, AND MUTAGENESIS OF TYR-28. RX PubMed=11971963; DOI=10.1128/mcb.22.10.3292-3300.2002; RA Yoshida K., Komatsu K., Wang H.-G., Kufe D.; RT "c-Abl tyrosine kinase regulates the human Rad9 checkpoint protein in RT response to DNA damage."; RL Mol. Cell. Biol. 22:3292-3300(2002). RN [15] RP INTERACTION WITH RAD9B. RX PubMed=14500360; RA Hopkins K.M., Wang X., Berlin A., Hang H., Thaker H.M., Lieberman H.B.; RT "Expression of mammalian paralogues of HRAD9 and Mrad9 checkpoint control RT genes in normal and cancerous testicular tissue."; RL Cancer Res. 63:5291-5298(2003). RN [16] RP PHOSPHORYLATION, AND SUBCELLULAR LOCATION. RX PubMed=12628935; DOI=10.1093/emboj/cdg134; RA Yoshida K., Wang H.-G., Miki Y., Kufe D.; RT "Protein kinase Cdelta is responsible for constitutive and DNA damage- RT induced phosphorylation of Rad9."; RL EMBO J. 22:1431-1441(2003). RN [17] RP ASSOCIATION OF THE 9-1-1 COMPLEX WITH THE RAD17-RFC COMPLEX, AND ELECTRON RP MICROSCOPY OF THE 9-1-1 AND RAD17-RFC COMPLEXES BOUND TO DNA. 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 [18] RP IDENTIFICATION IN THE 9-1-1 COMPLEX ASSOCIATED WITH POLB. RX PubMed=15314187; DOI=10.1093/nar/gkh652; RA Toueille M., El-Andaloussi N., Frouin I., Freire R., Funk D., Shevelev I., RA Friedrich-Heineken E., Villani G., Hottiger M.O., Huebscher U.; RT "The human Rad9/Rad1/Hus1 damage sensor clamp interacts with DNA polymerase RT beta and increases its DNA substrate utilisation efficiency: implications RT for DNA repair."; RL Nucleic Acids Res. 32:3316-3324(2004). RN [19] RP IDENTIFICATION IN THE 9-1-1 COMPLEX ASSOCIATED WITH FEN1. RX PubMed=15556996; DOI=10.1073/pnas.0407686101; RA Wang W., Brandt P., Rossi M.L., Lindsey-Boltz L., Podust V., Fanning E., RA Sancar A., Bambara R.A.; RT "The human Rad9-Rad1-Hus1 checkpoint complex stimulates flap endonuclease RT 1."; RL Proc. Natl. Acad. Sci. U.S.A. 101:16762-16767(2004). RN [20] RP IDENTIFICATION IN THE 9-1-1 COMPLEX ASSOCIATED WITH LIG1. RX PubMed=15871698; DOI=10.1042/bj20050211; RA Smirnova E., Toueille M., Markkanen E., Huebscher U.; RT "The human checkpoint sensor and alternative DNA clamp Rad9-Rad1-Hus1 RT modulates the activity of DNA ligase I, a component of the long-patch base RT excision repair machinery."; RL Biochem. J. 389:13-17(2005). RN [21] RP IDENTIFICATION IN THE 9-1-1 COMPLEX ASSOCIATED WITH FEN1, AND INTERACTION RP WITH FEN1. RX PubMed=16216273; DOI=10.1016/j.jmb.2005.09.018; RA Friedrich-Heineken E., Toueille M., Taennler B., Buerki C., Ferrari E., RA Hottiger M.O., Huebscher U.; RT "The two DNA clamps Rad9/Rad1/Hus1 complex and proliferating cell nuclear RT antigen differentially regulate flap endonuclease 1 activity."; RL J. Mol. Biol. 353:980-989(2005). RN [22] RP IDENTIFICATION IN THE 9-1-1 COMPLEX ASSOCIATED WITH RPA1 AND RPA2, AND RP INTERACTION WITH RPA1 AND RPA2. RX PubMed=15897895; DOI=10.1038/sj.onc.1208674; RA Wu X., Shell S.M., Zou Y.; RT "Interaction and colocalization of Rad9/Rad1/Hus1 checkpoint complex with RT replication protein A in human cells."; RL Oncogene 24:4728-4735(2005). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-375; SER-380 AND SER-387, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [24] RP FUNCTION, INTERACTION WITH TOPBP1, AND PHOSPHORYLATION AT SER-387. RX PubMed=17575048; DOI=10.1101/gad.1547007; RA Delacroix S., Wagner J.M., Kobayashi M., Yamamoto K., Karnitz L.M.; RT "The Rad9-Hus1-Rad1 (9-1-1) clamp activates checkpoint signaling via RT TopBP1."; RL Genes Dev. 21:1472-1477(2007). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-277 AND SER-387, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [26] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [27] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-277; SER-375 AND SER-387, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [28] RP FUNCTION, INTERACTION WITH TOPBP1, PHOSPHORYLATION AT SER-341 AND SER-387, RP AND MUTAGENESIS OF SER-341 AND SER-387. RX PubMed=20545769; DOI=10.1111/j.1365-2443.2010.01418.x; RA Takeishi Y., Ohashi E., Ogawa K., Masai H., Obuse C., Tsurimoto T.; RT "Casein kinase 2-dependent phosphorylation of human Rad9 mediates the RT interaction between human Rad9-Hus1-Rad1 complex and TopBP1."; RL Genes Cells 15:761-771(2010). RN [29] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-277; SER-375 AND SER-387, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [30] 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 [31] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-387, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [32] RP FUNCTION, AND IDENTIFICATION BY MASS SPECTROMETRY. 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-328 AND SER-387, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and 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] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [35] RP FUNCTION, AND INTERACTION WITH TOPBP1. RX PubMed=31135337; DOI=10.7554/elife.44353; RA Bigot N., Day M., Baldock R.A., Watts F.Z., Oliver A.W., Pearl L.H.; RT "Phosphorylation-mediated interactions with TOPBP1 couple 53BP1 and 9-1-1 RT to control the G1 DNA damage checkpoint."; RL Elife 8:e44353-e44353(2019). RN [36] {ECO:0007744|PDB:6J8Y} RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 1-270 IN COMPLEX WITH RHNO1; RAD1 RP AND HUS1, AND IDENTIFICATION IN THE 9-1-1 COMPLEX. RX PubMed=31776186; DOI=10.1074/jbc.ac119.011816; RA Hara K., Iida N., Tamafune R., Ohashi E., Sakurai H., Ishikawa Y., RA Hishiki A., Hashimoto H.; RT "Structure of the RAD9-RAD1-HUS1 checkpoint clamp bound to RHINO sheds RT light on the other side of the DNA clamp."; RL J. Biol. Chem. 295:899-904(2020). RN [37] {ECO:0007744|PDB:8GNN} RP X-RAY CRYSTALLOGRAPHY (2.12 ANGSTROMS) OF 1-270 IN COMPLEX WITH RAD17; RAD1 RP AND HUS1. 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: Component of the 9-1-1 cell-cycle checkpoint response complex CC that plays a major role in DNA repair (PubMed:10713044, CC PubMed:17575048, PubMed:20545769, PubMed:21659603, PubMed:31135337). CC The 9-1-1 complex is recruited to DNA lesion upon damage by the RAD17- CC replication factor C (RFC) clamp loader complex (PubMed:21659603). Acts CC then as a sliding clamp platform on DNA for several proteins involved CC in long-patch base excision repair (LP-BER) (PubMed:21659603). The 9-1- CC 1 complex stimulates DNA polymerase beta (POLB) activity by increasing CC its affinity for the 3'-OH end of the primer-template and stabilizes CC POLB to those sites where LP-BER proceeds; endonuclease FEN1 cleavage CC activity on substrates with double, nick, or gap flaps of distinct CC sequences and lengths; and DNA ligase I (LIG1) on long-patch base CC excision repair substrates (PubMed:21659603). The 9-1-1 complex is CC necessary for the recruitment of RHNO1 to sites of double-stranded CC breaks (DSB) occurring during the S phase (PubMed:21659603). RAD9A CC possesses 3'->5' double stranded DNA exonuclease activity CC (PubMed:10713044). {ECO:0000269|PubMed:10713044, CC ECO:0000269|PubMed:17575048, ECO:0000269|PubMed:20545769, CC ECO:0000269|PubMed:21659603, ECO:0000269|PubMed:31135337}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Exonucleolytic cleavage in the 3'- to 5'-direction to yield CC nucleoside 5'-phosphates.; EC=3.1.11.2; CC Evidence={ECO:0000269|PubMed:10713044}; CC -!- SUBUNIT: Component of the toroidal 9-1-1 (RAD9-RAD1-HUS1) complex, CC composed of RAD9A, RAD1 and HUS1 (PubMed:10359610, PubMed:10777662, CC PubMed:10846170, PubMed:15314187, PubMed:15897895, PubMed:15556996, CC PubMed:10884395, PubMed:16216273, PubMed:15871698, PubMed:17575048, CC PubMed:20545769, PubMed:31135337). The 9-1-1 complex associates with CC LIG1, POLB, FEN1, RAD17, HDAC1, RPA1 and RPA2 (PubMed:15556996, CC PubMed:15897895, PubMed:10884395, PubMed:15871698, PubMed:16216273). CC The 9-1-1 complex associates with the RAD17-RFC complex CC (PubMed:12578958). RAD9A interacts with BCL2L1, FEN1, RAD9B, ABL1, CC RPA1, ATAD5 and RPA2 (PubMed:14500360, PubMed:12628935, CC PubMed:11971963). Interacts with DNAJC7 (PubMed:11573955). Interacts CC (when phosphorylated) with TOPBP1 (PubMed:17575048, PubMed:20545769, CC PubMed:31135337). {ECO:0000269|PubMed:10359610, CC ECO:0000269|PubMed:10777662, ECO:0000269|PubMed:10846170, CC ECO:0000269|PubMed:10884395, ECO:0000269|PubMed:11573955, CC ECO:0000269|PubMed:11971963, ECO:0000269|PubMed:12578958, CC ECO:0000269|PubMed:12628935, ECO:0000269|PubMed:14500360, CC ECO:0000269|PubMed:15314187, ECO:0000269|PubMed:15556996, CC ECO:0000269|PubMed:15871698, ECO:0000269|PubMed:15897895, CC ECO:0000269|PubMed:16216273, ECO:0000269|PubMed:17575048, CC ECO:0000269|PubMed:20545769, ECO:0000269|PubMed:31135337}. CC -!- INTERACTION: CC Q99638; O60921: HUS1; NbExp=13; IntAct=EBI-2606224, EBI-1056174; CC Q99638; O60671: RAD1; NbExp=2; IntAct=EBI-2606224, EBI-721835; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12628935}. CC -!- PTM: Constitutively phosphorylated on serine and threonine amino acids CC in absence of DNA damage (PubMed:12628935). Hyperphosphorylated by CC PRKCD and ABL1 upon DNA damage (PubMed:11971963, PubMed:12709442). Its CC phosphorylation by PRKCD may be required for the formation of the 9-1-1 CC complex (PubMed:12628935). Phosphorylated at Ser-341 and Ser-387 by CC CK2, promoting interaction with TOPBP1 (PubMed:17575048, CC PubMed:20545769). {ECO:0000269|PubMed:11971963, CC ECO:0000269|PubMed:12628935, ECO:0000269|PubMed:12709442, CC ECO:0000269|PubMed:17575048, ECO:0000269|PubMed:20545769}. CC -!- SIMILARITY: Belongs to the rad9 family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/rad9a/"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/42031/RAD9A"; 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; U53174; AAB39928.1; -; mRNA. DR EMBL; CR536508; CAG38746.1; -; mRNA. DR EMBL; AY766122; AAU89725.1; -; Genomic_DNA. DR EMBL; AK315348; BAG37745.1; -; mRNA. DR EMBL; CH471076; EAW74605.1; -; Genomic_DNA. DR EMBL; BC014848; AAH14848.1; -; mRNA. DR CCDS; CCDS8159.1; -. DR RefSeq; NP_001230153.1; NM_001243224.1. DR RefSeq; NP_004575.1; NM_004584.2. DR PDB; 3A1J; X-ray; 2.50 A; A=1-266. DR PDB; 3G65; X-ray; 2.90 A; A=1-270. DR PDB; 3GGR; X-ray; 3.20 A; A=1-270. DR PDB; 6HM5; X-ray; 2.33 A; B=380-390. DR PDB; 6J8Y; X-ray; 2.40 A; A=1-270. DR PDB; 7Z6H; EM; 3.59 A; A=1-391. DR PDB; 8GNN; X-ray; 2.12 A; A=1-270. DR PDB; 8JZY; X-ray; 1.50 A; B=296-314. DR PDBsum; 3A1J; -. DR PDBsum; 3G65; -. DR PDBsum; 3GGR; -. DR PDBsum; 6HM5; -. DR PDBsum; 6J8Y; -. DR PDBsum; 7Z6H; -. DR PDBsum; 8GNN; -. DR PDBsum; 8JZY; -. DR AlphaFoldDB; Q99638; -. DR EMDB; EMD-14527; -. DR SMR; Q99638; -. DR BioGRID; 111820; 73. DR ComplexPortal; CPX-1829; Checkpoint clamp complex. DR CORUM; Q99638; -. DR DIP; DIP-24255N; -. DR DIP; DIP-40930N; -. DR IntAct; Q99638; 10. DR MINT; Q99638; -. DR STRING; 9606.ENSP00000311360; -. DR GlyGen; Q99638; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q99638; -. DR PhosphoSitePlus; Q99638; -. DR BioMuta; RAD9A; -. DR DMDM; 74717382; -. DR CPTAC; CPTAC-5930; -. DR CPTAC; CPTAC-5931; -. DR EPD; Q99638; -. DR jPOST; Q99638; -. DR MassIVE; Q99638; -. DR MaxQB; Q99638; -. DR PaxDb; 9606-ENSP00000311360; -. DR PeptideAtlas; Q99638; -. DR ProteomicsDB; 78371; -. DR Pumba; Q99638; -. DR Antibodypedia; 1880; 1255 antibodies from 38 providers. DR CPTC; Q99638; 1 antibody. DR DNASU; 5883; -. DR Ensembl; ENST00000307980.7; ENSP00000311360.2; ENSG00000172613.8. DR GeneID; 5883; -. DR KEGG; hsa:5883; -. DR MANE-Select; ENST00000307980.7; ENSP00000311360.2; NM_004584.3; NP_004575.1. DR UCSC; uc001okr.4; human. DR AGR; HGNC:9827; -. DR CTD; 5883; -. DR DisGeNET; 5883; -. DR GeneCards; RAD9A; -. DR HGNC; HGNC:9827; RAD9A. DR HPA; ENSG00000172613; Low tissue specificity. DR MIM; 603761; gene. DR neXtProt; NX_Q99638; -. DR OpenTargets; ENSG00000172613; -. DR PharmGKB; PA294; -. DR VEuPathDB; HostDB:ENSG00000172613; -. DR eggNOG; KOG2810; Eukaryota. DR GeneTree; ENSGT00390000005767; -. DR InParanoid; Q99638; -. DR OMA; YQLHDAL; -. DR OrthoDB; 3061362at2759; -. DR PhylomeDB; Q99638; -. DR TreeFam; TF101212; -. DR PathwayCommons; Q99638; -. 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; Q99638; -. DR SIGNOR; Q99638; -. DR BioGRID-ORCS; 5883; 599 hits in 1164 CRISPR screens. DR ChiTaRS; RAD9A; human. DR EvolutionaryTrace; Q99638; -. DR GeneWiki; RAD9A; -. DR GenomeRNAi; 5883; -. DR Pharos; Q99638; Tbio. DR PRO; PR:Q99638; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q99638; Protein. DR Bgee; ENSG00000172613; Expressed in right uterine tube and 135 other cell types or tissues. DR ExpressionAtlas; Q99638; baseline and differential. DR GO; GO:0030896; C:checkpoint clamp complex; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0008408; F:3'-5' exonuclease activity; IDA:UniProtKB. DR GO; GO:0008311; F:double-stranded DNA 3'-5' DNA exonuclease activity; IEA:UniProtKB-EC. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0042826; F:histone deacetylase binding; IPI:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB. DR GO; GO:0017124; F:SH3 domain binding; IPI:UniProtKB. DR GO; GO:0071479; P:cellular response to ionizing radiation; IDA:UniProtKB. DR GO; GO:0000077; P:DNA damage checkpoint signaling; IMP:UniProtKB. DR GO; GO:0006974; P:DNA damage response; IDA:UniProtKB. DR GO; GO:0006281; P:DNA repair; IBA:GO_Central. DR GO; GO:0000076; P:DNA replication checkpoint signaling; IBA:GO_Central. DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IEA:Ensembl. DR GO; GO:0031573; P:mitotic intra-S DNA damage checkpoint signaling; IBA:GO_Central. DR GO; GO:1902231; P:positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage; IEA:Ensembl. DR CDD; cd00577; PCNA; 1. DR Gene3D; 3.70.10.10; -; 1. DR InterPro; IPR046938; DNA_clamp_sf. DR InterPro; IPR026584; Rad9. DR InterPro; IPR007268; Rad9/Ddc1. DR PANTHER; PTHR15237:SF1; CELL CYCLE CHECKPOINT CONTROL PROTEIN RAD9A; 1. DR PANTHER; PTHR15237; DNA REPAIR PROTEIN RAD9; 1. DR Pfam; PF04139; Rad9; 1. DR PIRSF; PIRSF009303; Cell_cycle_RAD9; 1. DR SUPFAM; SSF55979; DNA clamp; 1. DR Genevisible; Q99638; HS. PE 1: Evidence at protein level; KW 3D-structure; Direct protein sequencing; DNA damage; Exonuclease; KW Hydrolase; Nuclease; Nucleus; Phosphoprotein; Reference proteome. FT CHAIN 1..391 FT /note="Cell cycle checkpoint control protein RAD9A" FT /id="PRO_0000225000" FT REGION 51..91 FT /note="Possesses 3'-5' exonuclease activity" FT REGION 266..391 FT /note="Sufficient for interaction with ABL1" FT /evidence="ECO:0000269|PubMed:11971963" FT REGION 268..301 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 319..391 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 28 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:11971963" FT MOD_RES 272 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:12709442" FT MOD_RES 277 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:12709442, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231" FT MOD_RES 328 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:12709442, FT ECO:0007744|PubMed:23186163" FT MOD_RES 341 FT /note="Phosphoserine; by CK2" FT /evidence="ECO:0000269|PubMed:12709442, FT ECO:0000269|PubMed:20545769" FT MOD_RES 375 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:12709442, FT ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231" FT MOD_RES 380 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:12709442, FT ECO:0007744|PubMed:17081983" FT MOD_RES 387 FT /note="Phosphoserine; by CK2" FT /evidence="ECO:0000269|PubMed:12709442, FT ECO:0000269|PubMed:17575048, ECO:0000269|PubMed:20545769, FT ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT VARIANT 3 FT /note="C -> F (in dbSNP:rs11575913)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_025410" FT VARIANT 71 FT /note="L -> Q (in dbSNP:rs2422490)" FT /id="VAR_051724" FT VARIANT 100 FT /note="S -> A (in dbSNP:rs2066492)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_025411" FT VARIANT 239 FT /note="H -> R (in dbSNP:rs17880039)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_025412" FT VARIANT 307 FT /note="M -> T (in dbSNP:rs17882466)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_025413" FT MUTAGEN 28 FT /note="Y->F: Abolishes phosphorylation by ABL1." FT /evidence="ECO:0000269|PubMed:11971963" FT MUTAGEN 272 FT /note="S->A: Complete loss of phosphorylation and no loss FT of interaction with the 9-1-1 complex; when associated with FT A-277; A-328; A-341; A-375; A-380 and A-387." FT /evidence="ECO:0000269|PubMed:12709442" FT MUTAGEN 277 FT /note="S->A: Complete loss of phosphorylation and no loss FT of interaction with the 9-1-1 complex; when associated with FT A-272; A-328; A-341; A-375; A-380 and A-387." FT /evidence="ECO:0000269|PubMed:12709442" FT MUTAGEN 328 FT /note="S->A: Complete loss of phosphorylation and no loss FT of interaction with the 9-1-1 complex; when associated with FT A-272; A-277; A-341; A-375; A-380 and A-387." FT /evidence="ECO:0000269|PubMed:12709442" FT MUTAGEN 341 FT /note="S->A: Complete loss of phosphorylation and no loss FT of interaction with the 9-1-1 complex; when associated with FT A-272; A-277; A-328; A-375; A-380 and A-387. Abolished FT phosphorylation by CK2, preventing interaction with TOPBP1; FT when associated with A-387." FT /evidence="ECO:0000269|PubMed:12709442, FT ECO:0000269|PubMed:20545769" FT MUTAGEN 341 FT /note="S->E: Mimics phosphorylation, leading to weak but FT significant interaction with TOPBP1; when associated with FT E-387." FT /evidence="ECO:0000269|PubMed:20545769" FT MUTAGEN 375 FT /note="S->A: Complete loss of phosphorylation and no loss FT of interaction with the 9-1-1 complex; when associated with FT A-272; A-277; A-328; A-341; A-380 and A-387." FT /evidence="ECO:0000269|PubMed:12709442" FT MUTAGEN 380 FT /note="S->A: Complete loss of phosphorylation and no loss FT of interaction with the 9-1-1 complex; when associated with FT A-272; A-277; A-328; A-341; A-375 and A-387." FT /evidence="ECO:0000269|PubMed:12709442" FT MUTAGEN 387 FT /note="S->A: Complete loss of phosphorylation and no loss FT of interaction with the 9-1-1 complex; when associated with FT A-272; A-277; A-328; A-341; A-375 and A-380. Abolished FT phosphorylation by CK2, preventing interaction with TOPBP1; FT when associated with A-341." FT /evidence="ECO:0000269|PubMed:12709442, FT ECO:0000269|PubMed:20545769" FT MUTAGEN 387 FT /note="S->E: Mimics phosphorylation, leading to weak but FT significant interaction with TOPBP1; when associated with FT E-341." FT /evidence="ECO:0000269|PubMed:20545769" FT CONFLICT 12 FT /note="V -> A (in Ref. 2; CAG38746)" FT /evidence="ECO:0000305" FT CONFLICT 130 FT /note="E -> A (in Ref. 6; AAH14848)" FT /evidence="ECO:0000305" FT STRAND 2..6 FT /evidence="ECO:0007829|PDB:8GNN" FT HELIX 9..21 FT /evidence="ECO:0007829|PDB:8GNN" FT STRAND 25..32 FT /evidence="ECO:0007829|PDB:8GNN" FT STRAND 35..41 FT /evidence="ECO:0007829|PDB:8GNN" FT STRAND 43..45 FT /evidence="ECO:0007829|PDB:6J8Y" FT STRAND 47..53 FT /evidence="ECO:0007829|PDB:8GNN" FT HELIX 55..57 FT /evidence="ECO:0007829|PDB:8GNN" FT STRAND 58..62 FT /evidence="ECO:0007829|PDB:8GNN" FT STRAND 66..68 FT /evidence="ECO:0007829|PDB:3A1J" FT STRAND 73..76 FT /evidence="ECO:0007829|PDB:8GNN" FT HELIX 77..83 FT /evidence="ECO:0007829|PDB:8GNN" FT HELIX 87..93 FT /evidence="ECO:0007829|PDB:8GNN" FT STRAND 94..101 FT /evidence="ECO:0007829|PDB:8GNN" FT STRAND 103..106 FT /evidence="ECO:0007829|PDB:3GGR" FT STRAND 107..114 FT /evidence="ECO:0007829|PDB:8GNN" FT HELIX 115..117 FT /evidence="ECO:0007829|PDB:8GNN" FT STRAND 119..124 FT /evidence="ECO:0007829|PDB:8GNN" FT HELIX 138..140 FT /evidence="ECO:0007829|PDB:8GNN" FT STRAND 142..148 FT /evidence="ECO:0007829|PDB:8GNN" FT HELIX 149..156 FT /evidence="ECO:0007829|PDB:8GNN" FT STRAND 165..171 FT /evidence="ECO:0007829|PDB:8GNN" FT TURN 172..174 FT /evidence="ECO:0007829|PDB:8GNN" FT STRAND 175..180 FT /evidence="ECO:0007829|PDB:8GNN" FT STRAND 187..189 FT /evidence="ECO:0007829|PDB:3GGR" FT STRAND 194..199 FT /evidence="ECO:0007829|PDB:8GNN" FT HELIX 201..203 FT /evidence="ECO:0007829|PDB:8GNN" FT STRAND 205..208 FT /evidence="ECO:0007829|PDB:8GNN" FT STRAND 214..218 FT /evidence="ECO:0007829|PDB:8GNN" FT HELIX 219..231 FT /evidence="ECO:0007829|PDB:8GNN" FT STRAND 235..240 FT /evidence="ECO:0007829|PDB:8GNN" FT STRAND 241..245 FT /evidence="ECO:0007829|PDB:3GGR" FT STRAND 247..252 FT /evidence="ECO:0007829|PDB:8GNN" FT STRAND 254..262 FT /evidence="ECO:0007829|PDB:8GNN" FT STRAND 267..269 FT /evidence="ECO:0007829|PDB:3G65" FT STRAND 382..384 FT /evidence="ECO:0007829|PDB:6HM5" SQ SEQUENCE 391 AA; 42547 MW; 4D4D6D4C6E1057D3 CRC64; MKCLVTGGNV KVLGKAVHSL SRIGDELYLE PLEDGLSLRT VNSSRSAYAC FLFAPLFFQQ YQAATPGQDL LRCKILMKSF LSVFRSLAML EKTVEKCCIS LNGRSSRLVV QLHCKFGVRK THNLSFQDCE SLQAVFDPAS CPHMLRAPAR VLGEAVLPFS PALAEVTLGI GRGRRVILRS YHEEEADSTA KAMVTEMCLG EEDFQQLQAQ EGVAITFCLK EFRGLLSFAE SANLNLSIHF DAPGRPAIFT IKDSLLDGHF VLATLSDTDS HSQDLGSPER HQPVPQLQAH STPHPDDFAN DDIDSYMIAM ETTIGNEGSR VLPSISLSPG PQPPKSPGPH SEEEDEAEPS TVPGTPPPKK FRSLFFGSIL APVRSPQGPS PVLAEDSEGE G //