ID FACD2_HUMAN Reviewed; 1451 AA. AC Q9BXW9; Q2LA86; Q69YP9; Q6PJN7; Q9BQ06; Q9H9T9; DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot. DT 26-NOV-2014, sequence version 2. DT 27-MAR-2024, entry version 196. DE RecName: Full=Fanconi anemia group D2 protein; DE Short=Protein FACD2; GN Name=FANCD2; Synonyms=FACD; 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 [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), FUNCTION, RP TISSUE SPECIFICITY, VARIANTS FANCD2 GLY-126; TRP-302 AND HIS-1236, AND RP VARIANT LEU-714. RC TISSUE=Lymphoblast; RX PubMed=11239453; DOI=10.1016/s1097-2765(01)00172-1; RA Timmers C., Taniguchi T., Hejna J., Reifsteck C., Lucas L., Bruun D., RA Thayer M., Cox B., Olson S., D'Andrea A.D., Moses R., Grompe M.; RT "Positional cloning of a novel Fanconi anemia gene, FANCD2."; RL Mol. Cell 7:241-248(2001). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-33; MET-61; HIS-65; RP MET-172; ALA-193; GLN-328; VAL-446; ARG-456; PRO-623; LEU-714; ARG-865 AND RP VAL-901. RG NIEHS SNPs program; RL Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RC TISSUE=Lung; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 161-860 (ISOFORM 1). RC TISSUE=Teratocarcinoma; 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 MRNA] OF 502-1451 (ISOFORM 3). RC TISSUE=Melanoma; 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 [6] RP FUNCTION, SUBCELLULAR LOCATION, UBIQUITINATION AT LYS-561, MUTAGENESIS OF RP LYS-561, INTERACTION WITH BRCA1, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=11239454; DOI=10.1016/s1097-2765(01)00173-3; RA Garcia-Higuera I., Taniguchi T., Ganesan S., Meyn M.S., Timmers C., RA Hejna J., Grompe M., D'Andrea A.D.; RT "Interaction of the Fanconi anemia proteins and BRCA1 in a common RT pathway."; RL Mol. Cell 7:249-262(2001). RN [7] RP FUNCTION, UBIQUITINATION, AND MUTAGENESIS OF LYS-561. RX PubMed=12239151; DOI=10.1182/blood-2002-01-0278; RA Taniguchi T., Garcia-Higuera I., Andreassen P.R., Gregory R.C., Grompe M., RA D'Andrea A.D.; RT "S-phase-specific interaction of the Fanconi anemia protein, FANCD2, with RT BRCA1 and RAD51."; RL Blood 100:2414-2420(2002). RN [8] RP FUNCTION, PHOSPHORYLATION AT SER-222 AND SER-1404, MUTAGENESIS OF SER-222; RP LYS-561; SER-1257; SER-1401; SER-1404 AND SER-1418, AND IDENTIFICATION BY RP MASS SPECTROMETRY. RX PubMed=12086603; DOI=10.1016/s0092-8674(02)00747-x; RA Taniguchi T., Garcia-Higuera I., Xu B., Andreassen P.R., Gregory R.C., RA Kim S.-T., Lane W.S., Kastan M.B., D'Andrea A.D.; RT "Convergence of the Fanconi anemia and ataxia telangiectasia signaling RT pathways."; RL Cell 109:459-472(2002). RN [9] RP SUBCELLULAR LOCATION, AND INTERACTION WITH FANCE. RX PubMed=12093742; DOI=10.1093/emboj/cdf355; RA Pace P., Johnson M., Tan W.M., Mosedale G., Sng C., Hoatlin M.E., RA de Winter J.P., Joenje H., Gergely F., Patel K.J.; RT "FANCE: the link between Fanconi anaemia complex assembly and activity."; RL EMBO J. 21:3414-3423(2002). RN [10] RP INTERACTION WITH FANCE. RX PubMed=12649160; DOI=10.1182/blood-2002-11-3517; RA Gordon S.M., Buchwald M.; RT "Fanconi anemia protein complex: mapping protein interactions in the yeast RT 2- and 3-hybrid systems."; RL Blood 102:136-141(2003). RN [11] RP INTERACTION WITH MEN1, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=12874027; RA Jin S., Mao H., Schnepp R.W., Sykes S.M., Silva A.C., D'Andrea A.D., RA Hua X.; RT "Menin associates with FANCD2, a protein involved in repair of DNA RT damage."; RL Cancer Res. 63:4204-4210(2003). RN [12] RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND FUNCTION. RX PubMed=14517836; DOI=10.1002/path.1450; RA Hoelzel M., van Diest P.J., Bier P., Wallisch M., Hoatlin M.E., Joenje H., RA de Winter J.P.; RT "FANCD2 protein is expressed in proliferating cells of human tissues that RT are cancer-prone in Fanconi anaemia."; RL J. Pathol. 201:198-203(2003). RN [13] RP UBIQUITINATION BY FANCL. RX PubMed=12973351; DOI=10.1038/ng1241; RA Meetei A.R., de Winter J.P., Medhurst A.L., Wallisch M., Waisfisz Q., RA van de Vrugt H.J., Oostra A.B., Yan Z., Ling C., Bishop C.E., Hoatlin M.E., RA Joenje H., Wang W.; RT "A novel ubiquitin ligase is deficient in Fanconi anemia."; RL Nat. Genet. 35:165-170(2003). RN [14] RP PHOSPHORYLATION BY ATR. RX PubMed=14988723; DOI=10.1038/sj.emboj.7600113; RA Pichierri P., Rosselli F.; RT "The DNA crosslink-induced S-phase checkpoint depends on ATR-CHK1 and ATR- RT NBS1-FANCD2 pathways."; RL EMBO J. 23:1178-1187(2004). RN [15] RP INTERACTION WITH BLM. RX PubMed=15257300; DOI=10.1038/sj.emboj.7600277; RA Pichierri P., Franchitto A., Rosselli F.; RT "BLM and the FANC proteins collaborate in a common pathway in response to RT stalled replication forks."; RL EMBO J. 23:3154-3163(2004). RN [16] RP FUNCTION, PHOSPHORYLATION BY ATR, AND UBIQUITINATION. RX PubMed=15314022; DOI=10.1101/gad.1196104; RA Andreassen P.R., D'Andrea A.D., Taniguchi T.; RT "ATR couples FANCD2 monoubiquitination to the DNA-damage response."; RL Genes Dev. 18:1958-1963(2004). RN [17] RP FUNCTION, AND INTERACTION WITH BRCA2. RX PubMed=15115758; DOI=10.1093/hmg/ddh135; RA Hussain S., Wilson J.B., Medhurst A.L., Hejna J., Witt E., Ananth S., RA Davies A., Masson J.-Y., Moses R., West S.C., de Winter J.P., Ashworth A., RA Jones N.J., Mathew C.G.; RT "Direct interaction of FANCD2 with BRCA2 in DNA damage response pathways."; RL Hum. Mol. Genet. 13:1241-1248(2004). RN [18] RP FUNCTION. RX PubMed=15377654; DOI=10.1074/jbc.m407160200; RA Freie B.W., Ciccone S.L.M., Li X., Plett P.A., Orschell C.M., Srour E.F., RA Hanenberg H., Schindler D., Lee S.-H., Clapp D.W.; RT "A role for the Fanconi anemia C protein in maintaining the DNA damage- RT induced G2 checkpoint."; RL J. Biol. Chem. 279:50986-50993(2004). RN [19] RP UBIQUITINATION, AND INTERACTION WITH BRCA2. RX PubMed=15199141; DOI=10.1128/mcb.24.13.5850-5862.2004; RA Wang X.Z., Andreassen P.R., D'Andrea A.D.; RT "Functional interaction of monoubiquitinated FANCD2 and BRCA2/FANCD1 in RT chromatin."; RL Mol. Cell. Biol. 24:5850-5862(2004). RN [20] RP UBIQUITINATION. RX PubMed=15502827; DOI=10.1038/ng1458; RA Meetei A.R., Levitus M., Xue Y., Medhurst A.L., Zwaan M., Ling C., RA Rooimans M.A., Bier P., Hoatlin M., Pals G., de Winter J.P., Wang W., RA Joenje H.; RT "X-linked inheritance of Fanconi anemia complementation group B."; RL Nat. Genet. 36:1219-1224(2004). RN [21] RP FUNCTION, TISSUE SPECIFICITY, MUTAGENESIS OF LYS-561, AND CHARACTERIZATION RP (ISOFORM 2). RX PubMed=15454491; DOI=10.1182/blood-2003-11-3997; RA Montes de Oca R., Andreassen P.R., Margossian S.P., Gregory R.C., RA Taniguchi T., Wang X.Z., Houghtaling S., Grompe M., D'Andrea A.D.; RT "Regulated interaction of the Fanconi anemia protein, FANCD2, with RT chromatin."; RL Blood 105:1003-1009(2005). RN [22] RP FUNCTION. RX PubMed=15661754; DOI=10.1093/hmg/ddi065; RA Howlett N.G., Taniguchi T., Durkin S.G., D'Andrea A.D., Glover T.W.; RT "The Fanconi anemia pathway is required for the DNA replication stress RT response and for the regulation of common fragile site stability."; RL Hum. Mol. Genet. 14:693-701(2005). RN [23] RP FUNCTION. RX PubMed=15671039; DOI=10.1074/jbc.m414669200; RA Ohashi A., Zdzienicka M.Z., Chen J., Couch F.J.; RT "FANCD2 functions independently of BRCA2 and RAD51 associated homologous RT recombination in response to DNA damage."; RL J. Biol. Chem. 280:14877-14883(2005). RN [24] RP INTERACTION WITH USP1, AND DEUBIQUITINATION. RX PubMed=15694335; DOI=10.1016/j.molcel.2005.01.008; RA Nijman S.M.B., Huang T.T., Dirac A.M.G., Brummelkamp T.R., Kerkhoven R.M., RA D'Andrea A.D., Bernards R.; RT "The deubiquitinating enzyme USP1 regulates the Fanconi Anemia pathway."; RL Mol. Cell 17:331-339(2005). RN [25] RP UBIQUITINATION. RX PubMed=16116422; DOI=10.1038/ng1626; RA Meetei A.R., Medhurst A.L., Ling C., Xue Y., Singh T.R., Bier P., RA Steltenpool J., Stone S., Dokal I., Mathew C.G., Hoatlin M., Joenje H., RA de Winter J.P., Wang W.; RT "A human ortholog of archaeal DNA repair protein Hef is defective in RT Fanconi anemia complementation group M."; RL Nat. Genet. 37:958-963(2005). RN [26] RP FUNCTION, AND MUTAGENESIS OF SER-222 AND LYS-561. RX PubMed=15650050; DOI=10.1073/pnas.0407796102; RA Nakanishi K., Yang Y.-G., Pierce A.J., Taniguchi T., Digweed M., RA D'Andrea A.D., Wang Z.-Q., Jasin M.; RT "Human Fanconi anemia monoubiquitination pathway promotes homologous DNA RT repair."; RL Proc. Natl. Acad. Sci. U.S.A. 102:1110-1115(2005). RN [27] RP UBIQUITINATION. RX PubMed=16916645; DOI=10.1016/j.molcel.2006.06.024; RA Machida Y.J., Machida Y., Chen Y., Gurtan A.M., Kupfer G.M., D'Andrea A.D., RA Dutta A.; RT "UBE2T is the E2 in the Fanconi anemia pathway and undergoes negative RT autoregulation."; RL Mol. Cell 23:589-596(2006). RN [28] RP INTERACTION WITH FANCI. RX PubMed=17412408; DOI=10.1016/j.cell.2007.03.009; RA Smogorzewska A., Matsuoka S., Vinciguerra P., McDonald E.R. III, RA Hurov K.E., Luo J., Ballif B.A., Gygi S.P., Hofmann K., D'Andrea A.D., RA Elledge S.J.; RT "Identification of the FANCI protein, a monoubiquitinated FANCD2 paralog RT required for DNA repair."; RL Cell 129:289-301(2007). RN [29] RP INTERACTION WITH FANCI. RX PubMed=17460694; DOI=10.1038/nsmb1252; RA Sims A.E., Spiteri E., Sims R.J. III, Arita A.G., Lach F.P., Landers T., RA Wurm M., Freund M., Neveling K., Hanenberg H., Auerbach A.D., Huang T.T.; RT "FANCI is a second monoubiquitinated member of the Fanconi anemia RT pathway."; RL Nat. Struct. Mol. Biol. 14:564-567(2007). RN [30] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-592 AND SER-1412, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [31] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [32] RP UBIQUITINATION AT LYS-561, AND MUTAGENESIS OF LYS-561. RX PubMed=19111657; DOI=10.1016/j.molcel.2008.12.003; RA Alpi A.F., Pace P.E., Babu M.M., Patel K.J.; RT "Mechanistic insight into site-restricted monoubiquitination of FANCD2 by RT Ube2t, FANCL, and FANCI."; RL Mol. Cell 32:767-777(2008). RN [33] RP INTERACTION WITH BRCA2; FANCG AND XRCC3. RX PubMed=18212739; DOI=10.1038/sj.onc.1211034; RA Wilson J.B., Yamamoto K., Marriott A.S., Hussain S., Sung P., Hoatlin M.E., RA Mathew C.G., Takata M., Thompson L.H., Kupfer G.M., Jones N.J.; RT "FANCG promotes formation of a newly identified protein complex containing RT BRCA2, FANCD2 and XRCC3."; RL Oncogene 27:3641-3652(2008). RN [34] RP INTERACTION WITH DCLRE1B. RX PubMed=18469862; DOI=10.1038/onc.2008.139; RA Bae J.B., Mukhopadhyay S.S., Liu L., Zhang N., Tan J., Akhter S., Liu X., RA Shen X., Li L., Legerski R.J.; RT "Snm1B/Apollo mediates replication fork collapse and S Phase checkpoint RT activation in response to DNA interstrand cross-links."; RL Oncogene 27:5045-5056(2008). RN [35] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1412, AND IDENTIFICATION BY RP 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 [36] 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 [37] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [38] RP SUBCELLULAR LOCATION. RX PubMed=19465922; DOI=10.1038/ncb1882; RA Chan K.L., Palmai-Pallag T., Ying S., Hickson I.D.; RT "Replication stress induces sister-chromatid bridging at fragile site loci RT in mitosis."; RL Nat. Cell Biol. 11:753-760(2009). RN [39] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=19465921; DOI=10.1038/ncb1883; RA Naim V., Rosselli F.; RT "The FANC pathway and BLM collaborate during mitosis to prevent micro- RT nucleation and chromosome abnormalities."; RL Nat. Cell Biol. 11:761-768(2009). RN [40] RP UBIQUITINATION AT LYS-561, INTERACTION WITH MTMR15, AND MUTAGENESIS OF RP LYS-561. RX PubMed=20603015; DOI=10.1016/j.cell.2010.06.021; RA MacKay C., Declais A.C., Lundin C., Agostinho A., Deans A.J., RA MacArtney T.J., Hofmann K., Gartner A., West S.C., Helleday T., RA Lilley D.M., Rouse J.; RT "Identification of KIAA1018/FAN1, a DNA repair nuclease recruited to DNA RT damage by monoubiquitinated FANCD2."; RL Cell 142:65-76(2010). RN [41] RP UBIQUITINATION AT LYS-561, INTERACTION WITH MTMR15, AND MUTAGENESIS OF RP LYS-561. RX PubMed=20603016; DOI=10.1016/j.cell.2010.06.022; RA Kratz K., Schopf B., Kaden S., Sendoel A., Eberhard R., Lademann C., RA Cannavo E., Sartori A.A., Hengartner M.O., Jiricny J.; RT "Deficiency of FANCD2-associated nuclease KIAA1018/FAN1 sensitizes cells to RT interstrand crosslinking agents."; RL Cell 142:77-88(2010). RN [42] RP UBIQUITINATION AT LYS-561, INTERACTION WITH MTMR15, AND MUTAGENESIS OF RP LYS-561. RX PubMed=20603073; DOI=10.1016/j.molcel.2010.06.023; RA Smogorzewska A., Desetty R., Saito T.T., Schlabach M., Lach F.P., RA Sowa M.E., Clark A.B., Kunkel T.A., Harper J.W., Colaiacovo M.P., RA Elledge S.J.; RT "A genetic screen identifies FAN1, a Fanconi anemia-associated nuclease RT necessary for DNA interstrand crosslink repair."; RL Mol. Cell 39:36-47(2010). RN [43] RP INTERACTION WITH POLN. RX PubMed=19995904; DOI=10.1128/mcb.01124-09; RA Moldovan G.L., Madhavan M.V., Mirchandani K.D., McCaffrey R.M., RA Vinciguerra P., D'Andrea A.D.; RT "DNA polymerase POLN participates in cross-link repair and homologous RT recombination."; RL Mol. Cell. Biol. 30:1088-1096(2010). RN [44] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-8; SER-594; SER-717; RP SER-1412; SER-1423; THR-1426 AND SER-1435, VARIANT [LARGE SCALE ANALYSIS] RP LEU-714, AND 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 [45] 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 [46] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1435, 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 [47] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-592; SER-1257 AND SER-1412, RP AND 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 [48] RP FUNCTION, INTERACTION WITH UHRF1 AND UHRF2, SUBCELLULAR LOCATION, AND RP UBIQUITINATION. RX PubMed=30335751; DOI=10.1371/journal.pgen.1007643; RA Motnenko A., Liang C.C., Yang D., Lopez-Martinez D., Yoshikawa Y., Zhan B., RA Ward K.E., Tian J., Haas W., Spingardi P., Kessler B.M., Kriaucionis S., RA Gygi S.P., Cohn M.A.; RT "Identification of UHRF2 as a novel DNA interstrand crosslink sensor RT protein."; RL PLoS Genet. 14:e1007643-e1007643(2018). CC -!- FUNCTION: Required for maintenance of chromosomal stability. Promotes CC accurate and efficient pairing of homologs during meiosis. Involved in CC the repair of DNA double-strand breaks, both by homologous CC recombination and single-strand annealing. May participate in S phase CC and G2 phase checkpoint activation upon DNA damage. Plays a role in CC preventing breakage and loss of missegregating chromatin at the end of CC cell division, particularly after replication stress. Required for the CC targeting, or stabilization, of BLM to non-centromeric abnormal CC structures induced by replicative stress. Promotes BRCA2/FANCD1 loading CC onto damaged chromatin. May also be involved in B-cell immunoglobulin CC isotype switching. {ECO:0000269|PubMed:11239453, CC ECO:0000269|PubMed:11239454, ECO:0000269|PubMed:12086603, CC ECO:0000269|PubMed:12239151, ECO:0000269|PubMed:14517836, CC ECO:0000269|PubMed:15115758, ECO:0000269|PubMed:15314022, CC ECO:0000269|PubMed:15377654, ECO:0000269|PubMed:15454491, CC ECO:0000269|PubMed:15650050, ECO:0000269|PubMed:15661754, CC ECO:0000269|PubMed:15671039, ECO:0000269|PubMed:19465921, CC ECO:0000269|PubMed:30335751}. CC -!- SUBUNIT: Interacts directly with FANCE and FANCI. Interacts with USP1 CC and MEN1. The ubiquitinated form specifically interacts with BRCA1 and CC BLM. Both the nonubiquitinated and the monoubiquitinated forms interact CC with BRCA2; this interaction is mediated by phosphorylated FANCG and CC the complex also includes XCCR3. The ubiquitinated form specifically CC interacts with MTMR15/FAN1 (via UBZ-type zinc finger), leading to CC recruit MTMR15/FAN1 to sites of DNA damage. Interacts with CC DCLRE1B/Apollo (PubMed:11239454, PubMed:12093742, PubMed:12649160, CC PubMed:12874027, PubMed:15115758, PubMed:15199141, PubMed:15257300, CC PubMed:15694335, PubMed:17412408, PubMed:17460694, PubMed:18212739, CC PubMed:18469862, PubMed:20603015, PubMed:20603016, PubMed:20603073). CC Interacts with POLN (PubMed:19995904). Interacts with UHRF1 and UHRF2; CC these interactions promote FANCD2 activation (PubMed:30335751). CC {ECO:0000269|PubMed:11239454, ECO:0000269|PubMed:12093742, CC ECO:0000269|PubMed:12649160, ECO:0000269|PubMed:12874027, CC ECO:0000269|PubMed:15115758, ECO:0000269|PubMed:15199141, CC ECO:0000269|PubMed:15257300, ECO:0000269|PubMed:15694335, CC ECO:0000269|PubMed:17412408, ECO:0000269|PubMed:17460694, CC ECO:0000269|PubMed:18212739, ECO:0000269|PubMed:18469862, CC ECO:0000269|PubMed:19995904, ECO:0000269|PubMed:20603015, CC ECO:0000269|PubMed:20603016, ECO:0000269|PubMed:20603073, CC ECO:0000269|PubMed:30335751}. CC -!- INTERACTION: CC Q9BXW9; P51587: BRCA2; NbExp=16; IntAct=EBI-359343, EBI-79792; CC Q9BXW9; P49716: CEBPD; NbExp=8; IntAct=EBI-359343, EBI-7962058; CC Q9BXW9; P00533: EGFR; NbExp=2; IntAct=EBI-359343, EBI-297353; CC Q9BXW9; Q9NVI1: FANCI; NbExp=2; IntAct=EBI-359343, EBI-1013291; CC Q9BXW9; Q16658: FSCN1; NbExp=6; IntAct=EBI-359343, EBI-351076; CC Q9BXW9; O00255: MEN1; NbExp=4; IntAct=EBI-359343, EBI-592789; CC Q9BXW9; P49959: MRE11; NbExp=6; IntAct=EBI-359343, EBI-396513; CC Q9BXW9; O60934: NBN; NbExp=6; IntAct=EBI-359343, EBI-494844; CC Q9BXW9-2; P51587: BRCA2; NbExp=3; IntAct=EBI-596878, EBI-79792; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11239454, CC ECO:0000269|PubMed:12093742, ECO:0000269|PubMed:19465921, CC ECO:0000269|PubMed:19465922, ECO:0000269|PubMed:30335751}. CC Note=Concentrates in nuclear foci during S phase and upon genotoxic CC stress. At the onset of mitosis, excluded from chromosomes and diffuses CC into the cytoplasm, returning to the nucleus at the end of cell CC division. Observed in a few spots localized in pairs on the sister CC chromatids of mitotic chromosome arms and not centromeres, one on each CC chromatids. These foci coincide with common fragile sites and could be CC sites of replication fork stalling. The foci are frequently interlinked CC through BLM-associated ultra-fine DNA bridges. Following aphidicolin CC treatment, targets chromatid gaps and breaks. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=2; CC IsoId=Q9BXW9-2; Sequence=Displayed; CC Name=1; CC IsoId=Q9BXW9-1; Sequence=VSP_057198; CC Name=3; CC IsoId=Q9BXW9-3; Sequence=VSP_013885, VSP_013886; CC Name=4; CC IsoId=Q9BXW9-4; Sequence=VSP_013883, VSP_013884; CC -!- TISSUE SPECIFICITY: Highly expressed in germinal center cells of the CC spleen, tonsil, and reactive lymph nodes, and in the proliferating CC basal layer of squamous epithelium of tonsil, esophagus, oropharynx, CC larynx and cervix. Expressed in cytotrophoblastic cells of the placenta CC and exocrine cells of the pancreas (at protein level). Highly expressed CC in testis, where expression is restricted to maturing spermatocytes. CC {ECO:0000269|PubMed:11239453, ECO:0000269|PubMed:14517836, CC ECO:0000269|PubMed:15454491}. CC -!- DEVELOPMENTAL STAGE: Highly expressed in fetal oocytes, and in CC hematopoietic cells of the fetal liver and bone marrow (at protein CC level). {ECO:0000269|PubMed:14517836}. CC -!- DOMAIN: The C-terminal 24 residues of isoform 2 are required for its CC function. CC -!- PTM: Monoubiquitinated on Lys-561 during S phase and upon genotoxic CC stress by FANCL in complex with E2 ligases UBE2T or UBE2W (isoform 1 CC and isoform 2). Deubiquitinated by USP1 as cells enter G2/M, or once CC DNA repair is completed. Monoubiquitination requires the joint CC intervention of the FANC core complex, including FANCA, FANCB, FANCC, CC FANCE, FANCF, FANCG, and FANCM, and proteins involved in cell cycle CC checkpoints and DNA repair, including RPA1, ATR, CHEK1 and BRCA1, and CC is mediated by FANCL/PHF9. Ubiquitination is required for binding to CC chromatin, interaction with BRCA1, BRCA2 and MTMR15/FAN1, DNA repair, CC and normal cell cycle progression, but not for phosphorylation on Ser- CC 222 or interaction with MEN1. {ECO:0000269|PubMed:11239454, CC ECO:0000269|PubMed:12086603, ECO:0000269|PubMed:15694335, CC ECO:0000269|PubMed:19111657, ECO:0000269|PubMed:20603015, CC ECO:0000269|PubMed:20603016, ECO:0000269|PubMed:20603073, CC ECO:0000269|PubMed:30335751}. CC -!- PTM: Phosphorylated in response to various genotoxic stresses by ATM CC and/or ATR. Upon ionizing radiation, phosphorylated by ATM on Ser-222 CC and Ser-1404. Phosphorylation on Ser-222 is required for S-phase CC checkpoint activation, but not for ubiquitination, foci formation, or CC DNA repair. In contrast, phosphorylation by ATR on other sites may be CC required for ubiquitination and foci formation. CC {ECO:0000269|PubMed:12086603, ECO:0000269|PubMed:15694335}. CC -!- DISEASE: Fanconi anemia complementation group D2 (FANCD2) [MIM:227646]: CC A disorder affecting all bone marrow elements and resulting in anemia, CC leukopenia and thrombopenia. It is associated with cardiac, renal and CC limb malformations, dermal pigmentary changes, and a predisposition to CC the development of malignancies. At the cellular level it is associated CC with hypersensitivity to DNA-damaging agents, chromosomal instability CC (increased chromosome breakage) and defective DNA repair. CC {ECO:0000269|PubMed:11239453}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 1]: Less abundant than isoform 2, may be not CC functional. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAB14132.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/103/FAD"; CC -!- WEB RESOURCE: Name=Fanconi Anemia Mutation Database; CC URL="https://www2.rockefeller.edu/fanconi/genes/jumpd2"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/fancd2/"; 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; AF230336; AAL05980.1; -; mRNA. DR EMBL; AF273251; AAK18772.1; -; Genomic_DNA. DR EMBL; AF273222; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273223; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273227; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273231; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273235; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273243; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273241; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273239; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273245; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273246; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273247; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273248; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273249; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273250; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273236; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273237; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273238; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273224; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273226; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273228; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273230; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273232; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273234; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273240; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273242; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273244; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273233; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273229; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273225; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273251; AAK18773.1; -; Genomic_DNA. DR EMBL; AF273222; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273223; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273224; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273225; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273226; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273227; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273228; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273229; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273230; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273231; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273232; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273233; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273234; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273235; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273236; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273237; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273238; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273239; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273240; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273241; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273242; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273243; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273244; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273245; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273246; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273247; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273248; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273249; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273250; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF340183; AAK15369.1; -; mRNA. DR EMBL; DQ341263; ABC67466.1; -; Genomic_DNA. DR EMBL; BC013582; AAH13582.1; -; mRNA. DR EMBL; AK022613; BAB14132.1; ALT_INIT; mRNA. DR EMBL; AL832427; CAH10647.1; -; mRNA. DR CCDS; CCDS2595.1; -. [Q9BXW9-1] DR CCDS; CCDS33696.1; -. [Q9BXW9-2] DR RefSeq; NP_001018125.1; NM_001018115.2. [Q9BXW9-2] DR RefSeq; NP_001306913.1; NM_001319984.1. [Q9BXW9-2] DR RefSeq; NP_149075.2; NM_033084.4. [Q9BXW9-1] DR PDB; 6VAA; EM; 3.35 A; B=1-1451. DR PDB; 6VAD; EM; 3.35 A; B=1-1451. DR PDB; 6VAE; EM; 3.50 A; B=1-1451. DR PDB; 6VAF; EM; 3.90 A; B=1-1451. DR PDB; 7AY1; EM; 3.70 A; B=1-1451. DR PDB; 7KZQ; EM; 4.20 A; V=1-1451. DR PDB; 7KZR; EM; 4.20 A; V=1-1451. DR PDB; 7KZS; EM; 4.20 A; V=1-1451. DR PDB; 7KZT; EM; 4.20 A; V=1-1451. DR PDB; 7KZV; EM; 4.20 A; V=1-1451. DR PDB; 7ZF1; EM; 4.14 A; B=1-1451. DR PDB; 8A9J; EM; 2.80 A; B=1-1451. DR PDB; 8A9K; EM; 2.85 A; B=1-1451. DR PDBsum; 6VAA; -. DR PDBsum; 6VAD; -. DR PDBsum; 6VAE; -. DR PDBsum; 6VAF; -. DR PDBsum; 7AY1; -. DR PDBsum; 7KZQ; -. DR PDBsum; 7KZR; -. DR PDBsum; 7KZS; -. DR PDBsum; 7KZT; -. DR PDBsum; 7KZV; -. DR PDBsum; 7ZF1; -. DR PDBsum; 8A9J; -. DR PDBsum; 8A9K; -. DR AlphaFoldDB; Q9BXW9; -. DR EMDB; EMD-11934; -. DR EMDB; EMD-14694; -. DR EMDB; EMD-15284; -. DR EMDB; EMD-21134; -. DR EMDB; EMD-21137; -. DR EMDB; EMD-21138; -. DR EMDB; EMD-21139; -. DR EMDB; EMD-23086; -. DR EMDB; EMD-23087; -. DR EMDB; EMD-23088; -. DR EMDB; EMD-23089; -. DR EMDB; EMD-23090; -. DR SMR; Q9BXW9; -. DR BioGRID; 108474; 870. DR ComplexPortal; CPX-6264; Fanconi anemia ID complex. DR CORUM; Q9BXW9; -. DR DIP; DIP-27606N; -. DR DIP; DIP-29382N; -. DR IntAct; Q9BXW9; 69. DR MINT; Q9BXW9; -. DR STRING; 9606.ENSP00000287647; -. DR ChEMBL; CHEMBL2157857; -. DR GlyGen; Q9BXW9; 3 sites, 1 O-linked glycan (3 sites). DR iPTMnet; Q9BXW9; -. DR PhosphoSitePlus; Q9BXW9; -. DR BioMuta; FANCD2; -. DR DMDM; 67461071; -. DR CPTAC; CPTAC-3227; -. DR CPTAC; CPTAC-3228; -. DR CPTAC; CPTAC-3229; -. DR EPD; Q9BXW9; -. DR jPOST; Q9BXW9; -. DR MassIVE; Q9BXW9; -. DR MaxQB; Q9BXW9; -. DR PaxDb; 9606-ENSP00000287647; -. DR PeptideAtlas; Q9BXW9; -. DR ProteomicsDB; 79531; -. [Q9BXW9-2] DR ProteomicsDB; 79532; -. [Q9BXW9-2] DR ProteomicsDB; 79533; -. [Q9BXW9-3] DR ProteomicsDB; 79534; -. [Q9BXW9-4] DR Pumba; Q9BXW9; -. DR Antibodypedia; 10521; 740 antibodies from 39 providers. DR CPTC; Q9BXW9; 2 antibodies. DR DNASU; 2177; -. DR Ensembl; ENST00000287647.7; ENSP00000287647.3; ENSG00000144554.13. [Q9BXW9-1] DR Ensembl; ENST00000419585.5; ENSP00000398754.1; ENSG00000144554.13. [Q9BXW9-2] DR Ensembl; ENST00000431693.1; ENSP00000399354.1; ENSG00000144554.13. [Q9BXW9-4] DR Ensembl; ENST00000675286.1; ENSP00000502379.1; ENSG00000144554.13. [Q9BXW9-2] DR GeneID; 2177; -. DR KEGG; hsa:2177; -. DR MANE-Select; ENST00000675286.1; ENSP00000502379.1; NM_001018115.3; NP_001018125.1. DR UCSC; uc003buw.4; human. [Q9BXW9-2] DR AGR; HGNC:3585; -. DR CTD; 2177; -. DR DisGeNET; 2177; -. DR GeneCards; FANCD2; -. DR GeneReviews; FANCD2; -. DR HGNC; HGNC:3585; FANCD2. DR HPA; ENSG00000144554; Tissue enhanced (bone marrow, lymphoid tissue). DR MalaCards; FANCD2; -. DR MIM; 227646; phenotype. DR MIM; 613984; gene. DR neXtProt; NX_Q9BXW9; -. DR OpenTargets; ENSG00000144554; -. DR Orphanet; 84; Fanconi anemia. DR PharmGKB; PA27999; -. DR VEuPathDB; HostDB:ENSG00000144554; -. DR eggNOG; KOG4712; Eukaryota. DR GeneTree; ENSGT00390000016970; -. DR HOGENOM; CLU_002068_1_0_1; -. DR InParanoid; Q9BXW9; -. DR OMA; YLYCGAY; -. DR OrthoDB; 8542at2759; -. DR TreeFam; TF101106; -. DR PathwayCommons; Q9BXW9; -. DR Reactome; R-HSA-6783310; Fanconi Anemia Pathway. DR Reactome; R-HSA-6796648; TP53 Regulates Transcription of DNA Repair Genes. DR SignaLink; Q9BXW9; -. DR SIGNOR; Q9BXW9; -. DR BioGRID-ORCS; 2177; 100 hits in 1172 CRISPR screens. DR ChiTaRS; FANCD2; human. DR GeneWiki; FANCD2; -. DR GenomeRNAi; 2177; -. DR Pharos; Q9BXW9; Tbio. DR PRO; PR:Q9BXW9; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q9BXW9; Protein. DR Bgee; ENSG00000144554; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 132 other cell types or tissues. DR ExpressionAtlas; Q9BXW9; baseline and differential. DR GO; GO:0000785; C:chromatin; NAS:ComplexPortal. DR GO; GO:0000793; C:condensed chromosome; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:1990391; C:DNA repair complex; IPI:ComplexPortal. DR GO; GO:0016604; C:nuclear body; IDA:HPA. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:ParkinsonsUK-UCL. DR GO; GO:0070182; F:DNA polymerase binding; IPI:UniProtKB. DR GO; GO:0048854; P:brain morphogenesis; IEA:Ensembl. DR GO; GO:0034599; P:cellular response to oxidative stress; IEA:Ensembl. DR GO; GO:1990918; P:double-strand break repair involved in meiotic recombination; IBA:GO_Central. DR GO; GO:0007276; P:gamete generation; IEA:Ensembl. DR GO; GO:0007129; P:homologous chromosome pairing at meiosis; IBA:GO_Central. DR GO; GO:0036297; P:interstrand cross-link repair; IBA:GO_Central. DR GO; GO:0031573; P:mitotic intra-S DNA damage checkpoint signaling; IBA:GO_Central. DR GO; GO:0097150; P:neuronal stem cell population maintenance; IEA:Ensembl. DR GO; GO:2000348; P:regulation of CD40 signaling pathway; IEA:Ensembl. DR GO; GO:0050727; P:regulation of inflammatory response; IEA:Ensembl. DR GO; GO:0045589; P:regulation of regulatory T cell differentiation; IEA:Ensembl. DR GO; GO:0010332; P:response to gamma radiation; IDA:UniProtKB. DR CDD; cd11721; FANCD2; 1. DR InterPro; IPR029448; FANCD2. DR PANTHER; PTHR32086; FANCONI ANEMIA GROUP D2 PROTEIN; 1. DR PANTHER; PTHR32086:SF0; FANCONI ANEMIA GROUP D2 PROTEIN; 1. DR Pfam; PF14631; FancD2; 1. DR Genevisible; Q9BXW9; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell cycle; Disease variant; KW DNA damage; DNA repair; Fanconi anemia; Isopeptide bond; Nucleus; KW Phosphoprotein; Reference proteome; Ubl conjugation. FT CHAIN 1..1451 FT /note="Fanconi anemia group D2 protein" FT /id="PRO_0000087168" FT REGION 1..291 FT /note="Interaction with FANCE" FT REGION 1..37 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 248..359 FT /note="Interaction with BRCA2" FT REGION 868..906 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1396..1451 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1..26 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1415..1430 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1431..1451 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 8 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 222 FT /note="Phosphoserine; by ATM" FT /evidence="ECO:0000269|PubMed:12086603" FT MOD_RES 592 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17525332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 594 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 717 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 1257 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1401 FT /note="Phosphoserine; by ATM" FT /evidence="ECO:0000305" FT MOD_RES 1404 FT /note="Phosphoserine; by ATM" FT /evidence="ECO:0000269|PubMed:12086603" FT MOD_RES 1412 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17525332, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1423 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 1426 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 1435 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692" FT CROSSLNK 561 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:11239454, FT ECO:0000269|PubMed:19111657, ECO:0000269|PubMed:20603015, FT ECO:0000269|PubMed:20603016, ECO:0000269|PubMed:20603073" FT VAR_SEQ 232..241 FT /note="SDLLIENTSL -> RWINPLSSSK (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_013883" FT VAR_SEQ 242..1451 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_013884" FT VAR_SEQ 1229..1249 FT /note="HTFVVFFRVMMAELEKTVKKI -> FMKRNSSTGTWLFETSVSSST (in FT isoform 3)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_013885" FT VAR_SEQ 1250..1451 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_013886" FT VAR_SEQ 1428..1451 FT /note="DGEEDEVSAGEKEQDSDESYDDSD -> VSLQNPPESGTDGCILLIVLSWWS FT RTLPTYVYCQMLLCPFPFPP (in isoform 1)" FT /id="VSP_057198" FT VARIANT 33 FT /note="K -> R (in dbSNP:rs34691009)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_025827" FT VARIANT 61 FT /note="T -> M (in dbSNP:rs35110529)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_025828" FT VARIANT 65 FT /note="Q -> H (in dbSNP:rs36084488)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_025829" FT VARIANT 126 FT /note="S -> G (in FANCD2; dbSNP:rs764507146)" FT /evidence="ECO:0000269|PubMed:11239453" FT /id="VAR_022559" FT VARIANT 172 FT /note="I -> M (in dbSNP:rs35173688)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_025830" FT VARIANT 193 FT /note="T -> A (in dbSNP:rs34936017)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_025831" FT VARIANT 302 FT /note="R -> W (in FANCD2; dbSNP:rs121917787)" FT /evidence="ECO:0000269|PubMed:11239453" FT /id="VAR_022560" FT VARIANT 328 FT /note="R -> Q (in dbSNP:rs35625434)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_025832" FT VARIANT 446 FT /note="L -> V (in dbSNP:rs34557223)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_025833" FT VARIANT 456 FT /note="L -> R (in dbSNP:rs35782247)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_025834" FT VARIANT 623 FT /note="Q -> P (in dbSNP:rs36070315)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_025835" FT VARIANT 714 FT /note="P -> L (in dbSNP:rs3864017)" FT /evidence="ECO:0000269|PubMed:11239453, ECO:0000269|Ref.2, FT ECO:0007744|PubMed:20068231" FT /id="VAR_022561" FT VARIANT 865 FT /note="K -> R (in dbSNP:rs35546777)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_025836" FT VARIANT 901 FT /note="G -> V (in dbSNP:rs35495399)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_025837" FT VARIANT 1236 FT /note="R -> H (in FANCD2; no effect on ubiquitination; FT dbSNP:rs121917786)" FT /evidence="ECO:0000269|PubMed:11239453" FT /id="VAR_022562" FT MUTAGEN 222 FT /note="S->A: Reduces phosphorylation by ATM. No effect on FT ubiquitination, foci formation or DNA repair ability, but FT impairs S-phase checkpoint activation." FT /evidence="ECO:0000269|PubMed:12086603, FT ECO:0000269|PubMed:15650050" FT MUTAGEN 561 FT /note="K->R: Abolishes ubiquitination; impairs chromatin FT binding, foci formation and DNA repair. Abolishes FT interaction with MTMR15/FAN1. No effect on S-222 FT phosphorylation by ATM." FT /evidence="ECO:0000269|PubMed:11239454, FT ECO:0000269|PubMed:12086603, ECO:0000269|PubMed:12239151, FT ECO:0000269|PubMed:15454491, ECO:0000269|PubMed:15650050, FT ECO:0000269|PubMed:19111657, ECO:0000269|PubMed:20603015, FT ECO:0000269|PubMed:20603016, ECO:0000269|PubMed:20603073" FT MUTAGEN 1257 FT /note="S->A: No effect on phosphorylation by ATM." FT /evidence="ECO:0000269|PubMed:12086603" FT MUTAGEN 1401 FT /note="S->A: Reduces phosphorylation by ATM; when FT associated with A-1404 and A-1418." FT /evidence="ECO:0000269|PubMed:12086603" FT MUTAGEN 1404 FT /note="S->A: Reduces phosphorylation by ATM; when FT associated with A-1401 and A-1418." FT /evidence="ECO:0000269|PubMed:12086603" FT MUTAGEN 1418 FT /note="S->A: Reduces phosphorylation by ATM; when FT associated with A-1401 and A-1404." FT /evidence="ECO:0000269|PubMed:12086603" FT CONFLICT 257 FT /note="N -> D (in Ref. 4; BAB14132)" FT /evidence="ECO:0000305" FT CONFLICT 557 FT /note="L -> S (in Ref. 4; BAB14132)" FT /evidence="ECO:0000305" FT CONFLICT 589 FT /note="R -> G (in Ref. 4; BAB14132)" FT /evidence="ECO:0000305" FT HELIX 47..55 FT /evidence="ECO:0007829|PDB:6VAA" FT STRAND 62..64 FT /evidence="ECO:0007829|PDB:6VAA" FT STRAND 67..70 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 72..85 FT /evidence="ECO:0007829|PDB:6VAA" FT STRAND 86..88 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 89..103 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 107..114 FT /evidence="ECO:0007829|PDB:6VAA" FT STRAND 115..119 FT /evidence="ECO:0007829|PDB:6VAA" FT STRAND 131..134 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 135..140 FT /evidence="ECO:0007829|PDB:6VAA" FT TURN 143..145 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 146..154 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 158..160 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 172..178 FT /evidence="ECO:0007829|PDB:6VAA" FT TURN 179..182 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 189..202 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 205..213 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 215..218 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 221..223 FT /evidence="ECO:0007829|PDB:6VAE" FT HELIX 224..237 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 242..251 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 256..268 FT /evidence="ECO:0007829|PDB:8A9K" FT TURN 269..272 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 275..277 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 278..287 FT /evidence="ECO:0007829|PDB:8A9K" FT STRAND 291..293 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 294..304 FT /evidence="ECO:0007829|PDB:8A9K" FT STRAND 307..309 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 339..353 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 358..370 FT /evidence="ECO:0007829|PDB:8A9K" FT TURN 374..376 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 379..391 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 393..395 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 396..408 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 414..423 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 425..429 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 432..443 FT /evidence="ECO:0007829|PDB:8A9K" FT STRAND 444..447 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 448..464 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 467..481 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 486..502 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 504..508 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 511..515 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 516..520 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 526..540 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 543..545 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 546..562 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 568..585 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 604..620 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 625..641 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 646..663 FT /evidence="ECO:0007829|PDB:8A9K" FT STRAND 665..670 FT /evidence="ECO:0007829|PDB:8A9K" FT STRAND 681..684 FT /evidence="ECO:0007829|PDB:8A9K" FT STRAND 687..689 FT /evidence="ECO:0007829|PDB:6VAA" FT STRAND 695..697 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 700..705 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 727..729 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 730..745 FT /evidence="ECO:0007829|PDB:8A9K" FT STRAND 750..752 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 754..757 FT /evidence="ECO:0007829|PDB:8A9K" FT STRAND 760..762 FT /evidence="ECO:0007829|PDB:8A9K" FT TURN 771..773 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 776..800 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 806..831 FT /evidence="ECO:0007829|PDB:8A9K" FT TURN 843..845 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 846..850 FT /evidence="ECO:0007829|PDB:6VAA" FT TURN 922..924 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 932..937 FT /evidence="ECO:0007829|PDB:8A9K" FT TURN 943..945 FT /evidence="ECO:0007829|PDB:6VAE" FT HELIX 962..979 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 1002..1006 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 1009..1017 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 1020..1035 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 1052..1073 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 1076..1079 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 1084..1095 FT /evidence="ECO:0007829|PDB:8A9K" FT TURN 1096..1098 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 1107..1119 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 1120..1124 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 1128..1144 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 1151..1164 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 1171..1175 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 1179..1192 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 1196..1205 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 1207..1213 FT /evidence="ECO:0007829|PDB:8A9K" FT STRAND 1222..1225 FT /evidence="ECO:0007829|PDB:6VAA" FT TURN 1228..1230 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 1231..1248 FT /evidence="ECO:0007829|PDB:8A9K" FT STRAND 1254..1256 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 1258..1279 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 1280..1282 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 1288..1315 FT /evidence="ECO:0007829|PDB:8A9K" FT STRAND 1316..1320 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 1322..1348 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 1351..1354 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 1357..1377 FT /evidence="ECO:0007829|PDB:8A9K" FT HELIX 1381..1383 FT /evidence="ECO:0007829|PDB:8A9K" FT STRAND 1386..1389 FT /evidence="ECO:0007829|PDB:8A9K" FT STRAND 1394..1396 FT /evidence="ECO:0007829|PDB:8A9K" SQ SEQUENCE 1451 AA; 164128 MW; BF931980ADA67405 CRC64; MVSKRRLSKS EDKESLTEDA SKTRKQPLSK KTKKSHIANE VEENDSIFVK LLKISGIILK TGESQNQLAV DQIAFQKKLF QTLRRHPSYP KIIEEFVSGL ESYIEDEDSF RNCLLSCERL QDEEASMGAS YSKSLIKLLL GIDILQPAII KTLFEKLPEY FFENKNSDEI NIPRLIVSQL KWLDRVVDGK DLTTKIMQLI SIAPENLQHD IITSLPEILG DSQHADVGKE LSDLLIENTS LTVPILDVLS SLRLDPNFLL KVRQLVMDKL SSIRLEDLPV IIKFILHSVT AMDTLEVISE LREKLDLQHC VLPSRLQASQ VKLKSKGRAS SSGNQESSGQ SCIILLFDVI KSAIRYEKTI SEAWIKAIEN TASVSEHKVF DLVMLFIIYS TNTQTKKYID RVLRNKIRSG CIQEQLLQST FSVHYLVLKD MCSSILSLAQ SLLHSLDQSI ISFGSLLYKY AFKFFDTYCQ QEVVGALVTH ICSGNEAEVD TALDVLLELV VLNPSAMMMN AVFVKGILDY LDNISPQQIR KLFYVLSTLA FSKQNEASSH IQDDMHLVIR KQLSSTVFKY KLIGIIGAVT MAGIMAADRS ESPSLTQERA NLSDEQCTQV TSLLQLVHSC SEQSPQASAL YYDEFANLIQ HEKLDPKALE WVGHTICNDF QDAFVVDSCV VPEGDFPFPV KALYGLEEYD TQDGIAINLL PLLFSQDFAK DGGPVTSQES GQKLVSPLCL APYFRLLRLC VERQHNGNLE EIDGLLDCPI FLTDLEPGEK LESMSAKERS FMCSLIFLTL NWFREIVNAF CQETSPEMKG KVLTRLKHIV ELQIILEKYL AVTPDYVPPL GNFDVETLDI TPHTVTAISA KIRKKGKIER KQKTDGSKTS SSDTLSEEKN SECDPTPSHR GQLNKEFTGK EEKTSLLLHN SHAFFRELDI EVFSILHCGL VTKFILDTEM HTEATEVVQL GPPELLFLLE DLSQKLESML TPPIARRVPF LKNKGSRNIG FSHLQQRSAQ EIVHCVFQLL TPMCNHLENI HNYFQCLAAE NHGVVDGPGV KVQEYHIMSS CYQRLLQIFH GLFAWSGFSQ PENQNLLYSA LHVLSSRLKQ GEHSQPLEEL LSQSVHYLQN FHQSIPSFQC ALYLIRLLMV ILEKSTASAQ NKEKIASLAR QFLCRVWPSG DKEKSNISND QLHALLCIYL EHTESILKAI EEIAGVGVPE LINSPKDASS STFPTLTRHT FVVFFRVMMA ELEKTVKKIE PGTAADSQQI HEEKLLYWNM AVRDFSILIN LIKVFDSHPV LHVCLKYGRL FVEAFLKQCM PLLDFSFRKH REDVLSLLET FQLDTRLLHH LCGHSKIHQD TRLTQHVPLL KKTLELLVCR VKAMLTLNNC REAFWLGNLK NRDLQGEEIK SQNSQESTAD ESEDDMSSQA SKSKATEDGE EDEVSAGEKE QDSDESYDDS D //