FACD2_HUMAN
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 03-AUG-2022, entry version 187.
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 TRP-302 AND HIS-1236, AND VARIANT
RP 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; 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="http://atlasgeneticsoncology.org/Genes/FADID103.html";
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/";
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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 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 AlphaFoldDB; Q9BXW9; -.
DR SMR; Q9BXW9; -.
DR BioGRID; 108474; 851.
DR ComplexPortal; CPX-6264; Fanconi anemia ID complex.
DR CORUM; Q9BXW9; -.
DR DIP; DIP-27606N; -.
DR DIP; DIP-29382N; -.
DR IntAct; Q9BXW9; 65.
DR MINT; Q9BXW9; -.
DR STRING; 9606.ENSP00000287647; -.
DR ChEMBL; CHEMBL2157857; -.
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; Q9BXW9; -.
DR PeptideAtlas; Q9BXW9; -.
DR PRIDE; Q9BXW9; -.
DR ProteomicsDB; 79531; -. [Q9BXW9-2]
DR ProteomicsDB; 79532; -. [Q9BXW9-2]
DR ProteomicsDB; 79533; -. [Q9BXW9-3]
DR ProteomicsDB; 79534; -. [Q9BXW9-4]
DR Antibodypedia; 10521; 653 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 CTD; 2177; -.
DR DisGeNET; 2177; -.
DR GeneCards; FANCD2; -.
DR GeneReviews; FANCD2; -.
DR HGNC; HGNC:3585; FANCD2.
DR HPA; ENSG00000144554; Tissue enhanced (bone).
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; EFFFDIV; -.
DR OrthoDB; 979208at2759; -.
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; 89 hits in 1088 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 ventricular zone and 130 other tissues.
DR ExpressionAtlas; Q9BXW9; baseline and differential.
DR Genevisible; Q9BXW9; HS.
DR GO; GO:0000785; C:chromatin; IC: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:0051090; P:regulation of DNA-binding transcription factor activity; 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; PTHR32086; 1.
DR Pfam; PF14631; FancD2; 1.
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 /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:6VAA"
FT HELIX 270..272
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 275..277
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 278..287
FT /evidence="ECO:0007829|PDB:6VAA"
FT STRAND 291..293
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 294..304
FT /evidence="ECO:0007829|PDB:6VAA"
FT STRAND 307..309
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 340..355
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 359..369
FT /evidence="ECO:0007829|PDB:6VAA"
FT STRAND 373..375
FT /evidence="ECO:0007829|PDB:6VAE"
FT HELIX 379..390
FT /evidence="ECO:0007829|PDB:6VAA"
FT TURN 393..395
FT /evidence="ECO:0007829|PDB:6VAD"
FT HELIX 396..407
FT /evidence="ECO:0007829|PDB:6VAA"
FT TURN 408..410
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 414..424
FT /evidence="ECO:0007829|PDB:6VAA"
FT TURN 425..428
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 429..431
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 432..439
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 441..443
FT /evidence="ECO:0007829|PDB:6VAA"
FT STRAND 444..447
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 448..464
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 467..482
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 486..502
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 504..508
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 511..515
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 516..520
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 526..540
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 543..545
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 550..563
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 568..585
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 605..622
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 625..641
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 648..663
FT /evidence="ECO:0007829|PDB:6VAA"
FT STRAND 665..667
FT /evidence="ECO:0007829|PDB:6VAA"
FT STRAND 681..684
FT /evidence="ECO:0007829|PDB:6VAA"
FT STRAND 687..689
FT /evidence="ECO:0007829|PDB:6VAA"
FT STRAND 691..698
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 700..706
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 730..745
FT /evidence="ECO:0007829|PDB:6VAA"
FT TURN 750..752
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 753..757
FT /evidence="ECO:0007829|PDB:6VAA"
FT STRAND 760..762
FT /evidence="ECO:0007829|PDB:6VAA"
FT STRAND 769..771
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 777..799
FT /evidence="ECO:0007829|PDB:6VAA"
FT STRAND 800..802
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 806..832
FT /evidence="ECO:0007829|PDB:6VAA"
FT TURN 843..845
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 846..850
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 917..923
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 930..937
FT /evidence="ECO:0007829|PDB:6VAA"
FT TURN 943..945
FT /evidence="ECO:0007829|PDB:6VAE"
FT HELIX 962..980
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 1004..1006
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 1009..1019
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 1021..1041
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 1052..1073
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 1076..1079
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 1084..1095
FT /evidence="ECO:0007829|PDB:6VAA"
FT TURN 1096..1098
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 1107..1119
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 1120..1123
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 1129..1142
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 1152..1164
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 1171..1175
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 1179..1192
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 1196..1207
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 1210..1213
FT /evidence="ECO:0007829|PDB:6VAA"
FT STRAND 1222..1225
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 1230..1246
FT /evidence="ECO:0007829|PDB:6VAA"
FT STRAND 1254..1256
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 1258..1280
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 1281..1283
FT /evidence="ECO:0007829|PDB:6VAD"
FT HELIX 1289..1315
FT /evidence="ECO:0007829|PDB:6VAA"
FT STRAND 1316..1319
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 1321..1348
FT /evidence="ECO:0007829|PDB:6VAA"
FT TURN 1351..1354
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 1357..1375
FT /evidence="ECO:0007829|PDB:6VAA"
FT HELIX 1381..1383
FT /evidence="ECO:0007829|PDB:6VAE"
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
