ID FANCL_HUMAN Reviewed; 375 AA. AC Q9NW38; Q6GU60; DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 2. DT 27-MAR-2024, entry version 192. DE RecName: Full=E3 ubiquitin-protein ligase FANCL; DE EC=2.3.2.27 {ECO:0000269|PubMed:12973351, ECO:0000269|PubMed:16916645, ECO:0000269|PubMed:19111657, ECO:0000269|PubMed:19589784}; DE AltName: Full=Fanconi anemia group L protein; DE AltName: Full=Fanconi anemia-associated polypeptide of 43 kDa; DE Short=FAAP43; DE AltName: Full=RING-type E3 ubiquitin transferase FANCL {ECO:0000305}; GN Name=FANCL; Synonyms=PHF9; 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 [LARGE SCALE MRNA] (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 [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Brain, and Eye; 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 IDENTIFICATION BY MASS SPECTROMETRY IN A BRAFT COMPLEX WITH FANCA; FANCC; RP FANCE; FANCF AND FANCG. RX PubMed=12724401; DOI=10.1128/mcb.23.10.3417-3426.2003; RA Meetei A.R., Sechi S., Wallisch M., Yang D., Young M.K., Joenje H., RA Hoatlin M.E., Wang W.; RT "A multiprotein nuclear complex connects Fanconi anemia and Bloom RT syndrome."; RL Mol. Cell. Biol. 23:3417-3426(2003). RN [5] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INVOLVEMENT IN FANCL, RP INTERACTION WITH FANCA; FANCC; FANCF AND FANCG, AND MUTAGENESIS OF CYS-307 RP AND CYS-310. 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 [6] RP IDENTIFICATION IN A COMPLEX WITH FANCA; FANCB; FANCC; FANCE; FANCF AND RP FANCLG. 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 [7] RP IDENTIFICATION IN A COMPLEX WITH FANCA; FANCB; FANCC; FANCE; FANCF; FANCG RP AND FANCM. 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 [8] RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH UBE2T, UBIQUITINATION, AND RP MUTAGENESIS OF CYS-307 AND TRP-341. 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 [9] RP FUNCTION, INTERACTION WITH UBE2T, AND MUTAGENESIS OF CYS-307 AND CYS-310. RX PubMed=17938197; DOI=10.1128/mcb.00504-07; RA Alpi A., Langevin F., Mosedale G., Machida Y.J., Dutta A., Patel K.J.; RT "UBE2T, the Fanconi anemia core complex, and FANCD2 are recruited RT independently to chromatin: a basis for the regulation of FANCD2 RT monoubiquitination."; RL Mol. Cell. Biol. 27:8421-8430(2007). RN [10] RP INTERACTION WITH HES1, AND SUBCELLULAR LOCATION. RX PubMed=18550849; DOI=10.1182/blood-2008-04-152710; RA Tremblay C.S., Huang F.F., Habi O., Huard C.C., Godin C., Levesque G., RA Carreau M.; RT "HES1 is a novel interactor of the Fanconi anemia core complex."; RL Blood 112:2062-2070(2008). RN [11] RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH UBE2T AND UBE2W, AND RP MUTAGENESIS OF 158-TYR-PRO-159; CYS-307 AND CYS-359. 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 [12] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF CYS-307. RX PubMed=19589784; DOI=10.1074/jbc.c109.038075; RA Longerich S., San Filippo J., Liu D., Sung P.; RT "FANCI binds branched DNA and is monoubiquitinated by UBE2T-FANCL."; RL J. Biol. Chem. 284:23182-23186(2009). RN [13] RP IDENTIFICATION IN THE FA COMPLEX. RX PubMed=22343915; DOI=10.1182/blood-2011-10-385963; RA Ali A.M., Pradhan A., Singh T.R., Du C., Li J., Wahengbam K., Grassman E., RA Auerbach A.D., Pang Q., Meetei A.R.; RT "FAAP20: a novel ubiquitin-binding FA nuclear core-complex protein required RT for functional integrity of the FA-BRCA DNA repair pathway."; RL Blood 119:3285-3294(2012). RN [14] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [15] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 109-294, INTERACTION WITH FANCI RP AND UBE2T, AND MUTAGENESIS OF 127-VAL-TYR-128; LEU-149; PHE-166; RP 212-TRP--LEU-214; LEU-248; PHE-252; LEU-254 AND ILE-265. RX PubMed=21775430; DOI=10.1074/jbc.m111.244632; RA Hodson C., Cole A.R., Lewis L.P., Miles J.A., Purkiss A., Walden H.; RT "Structural analysis of human FANCL, the E3 ligase in the Fanconi anemia RT pathway."; RL J. Biol. Chem. 286:32628-32637(2011). RN [16] {ECO:0007744|PDB:4CCG} RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 299-373 IN COMPLEX WITH ZINC, RP FUNCTION, INTERACTION WITH UBE2T, AND MUTAGENESIS OF ILE-309; TYR-311 AND RP TRP-341. RX PubMed=24389026; DOI=10.1016/j.str.2013.12.004; RA Hodson C., Purkiss A., Miles J.A., Walden H.; RT "Structure of the human FANCL RING-Ube2T complex reveals determinants of RT cognate E3-E2 selection."; RL Structure 22:337-344(2014). CC -!- FUNCTION: Ubiquitin ligase protein that mediates monoubiquitination of CC FANCD2 in the presence of UBE2T, a key step in the DNA damage pathway CC (PubMed:12973351, PubMed:16916645, PubMed:17938197, PubMed:19111657, CC PubMed:24389026). Also mediates monoubiquitination of FANCI CC (PubMed:19589784). May stimulate the ubiquitin release from UBE2W. May CC be required for proper primordial germ cell proliferation in the CC embryonic stage, whereas it is probably not needed for spermatogonial CC proliferation after birth. {ECO:0000269|PubMed:12973351, CC ECO:0000269|PubMed:16916645, ECO:0000269|PubMed:17938197, CC ECO:0000269|PubMed:19111657, ECO:0000269|PubMed:19589784, CC ECO:0000269|PubMed:24389026}. CC -!- CATALYTIC ACTIVITY: CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; CC EC=2.3.2.27; Evidence={ECO:0000269|PubMed:12973351, CC ECO:0000269|PubMed:16916645, ECO:0000269|PubMed:19111657, CC ECO:0000269|PubMed:19589784}; CC -!- PATHWAY: Protein modification; protein ubiquitination. CC -!- SUBUNIT: Interacts with GGN (By similarity). Belongs to the CC multisubunit FA complex composed of FANCA, FANCB, FANCC, FANCE, FANCF, CC FANCG, FANCL/PHF9 and FANCM (PubMed:12973351, PubMed:15502827, CC PubMed:16116422, PubMed:22343915). The complex is not found in FA CC patients. In complex with FANCF, FANCA and FANCG, but not with FANCC, CC nor FANCE, interacts with HES1; this interaction may be essential for CC the stability and nuclear localization of FA core complex proteins CC (PubMed:18550849). Interacts with FANCI (PubMed:21775430). Directly CC interacts (via the RING-type zinc finger) with UBE2T and UBE2W CC (PubMed:16916645, PubMed:17938197, PubMed:19111657, PubMed:21775430, CC PubMed:24389026). {ECO:0000250|UniProtKB:Q9CR14, CC ECO:0000269|PubMed:12973351, ECO:0000269|PubMed:15502827, CC ECO:0000269|PubMed:16116422, ECO:0000269|PubMed:16916645, CC ECO:0000269|PubMed:17938197, ECO:0000269|PubMed:18550849, CC ECO:0000269|PubMed:19111657, ECO:0000269|PubMed:21775430, CC ECO:0000269|PubMed:22343915, ECO:0000269|PubMed:24389026}. CC -!- INTERACTION: CC Q9NW38; Q5BKX5-3: ACTMAP; NbExp=3; IntAct=EBI-2339898, EBI-11976299; CC Q9NW38; Q3KP44: ANKRD55; NbExp=3; IntAct=EBI-2339898, EBI-14493093; CC Q9NW38; Q9BQD7: ANTKMT; NbExp=3; IntAct=EBI-2339898, EBI-713602; CC Q9NW38; O43307: ARHGEF9; NbExp=3; IntAct=EBI-2339898, EBI-3447299; CC Q9NW38; A2RRN7: CADPS; NbExp=3; IntAct=EBI-2339898, EBI-10179719; CC Q9NW38; Q5T4B2: CERCAM; NbExp=3; IntAct=EBI-2339898, EBI-12261896; CC Q9NW38; Q9NX63: CHCHD3; NbExp=6; IntAct=EBI-2339898, EBI-743375; CC Q9NW38; Q9GZU7: CTDSP1; NbExp=3; IntAct=EBI-2339898, EBI-751587; CC Q9NW38; Q6BCY4-2: CYB5R2; NbExp=3; IntAct=EBI-2339898, EBI-12102608; CC Q9NW38; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-2339898, EBI-3867333; CC Q9NW38; O95865: DDAH2; NbExp=3; IntAct=EBI-2339898, EBI-749139; CC Q9NW38; Q8NF50-2: DOCK8; NbExp=3; IntAct=EBI-2339898, EBI-10174653; CC Q9NW38; Q9NRA8: EIF4ENIF1; NbExp=3; IntAct=EBI-2339898, EBI-301024; CC Q9NW38; P15976-2: GATA1; NbExp=3; IntAct=EBI-2339898, EBI-9090198; CC Q9NW38; P28799: GRN; NbExp=3; IntAct=EBI-2339898, EBI-747754; CC Q9NW38; Q9BSH5: HDHD3; NbExp=3; IntAct=EBI-2339898, EBI-745201; CC Q9NW38; P09016: HOXD4; NbExp=3; IntAct=EBI-2339898, EBI-12822515; CC Q9NW38; Q02363: ID2; NbExp=3; IntAct=EBI-2339898, EBI-713450; CC Q9NW38; Q8IYA8: IHO1; NbExp=3; IntAct=EBI-2339898, EBI-8638439; CC Q9NW38; Q9UKT9: IKZF3; NbExp=3; IntAct=EBI-2339898, EBI-747204; CC Q9NW38; Q9BVG8: KIFC3; NbExp=3; IntAct=EBI-2339898, EBI-2125614; CC Q9NW38; Q9BVG8-5: KIFC3; NbExp=3; IntAct=EBI-2339898, EBI-14069005; CC Q9NW38; Q8IUC1: KRTAP11-1; NbExp=3; IntAct=EBI-2339898, EBI-1052037; CC Q9NW38; Q52LG2: KRTAP13-2; NbExp=3; IntAct=EBI-2339898, EBI-11953846; CC Q9NW38; Q3LI70: KRTAP19-6; NbExp=3; IntAct=EBI-2339898, EBI-12805508; CC Q9NW38; Q9BRK4: LZTS2; NbExp=3; IntAct=EBI-2339898, EBI-741037; CC Q9NW38; A6NJ78-4: METTL15; NbExp=3; IntAct=EBI-2339898, EBI-10174029; CC Q9NW38; Q6PF18: MORN3; NbExp=3; IntAct=EBI-2339898, EBI-9675802; CC Q9NW38; P49720: PSMB3; NbExp=3; IntAct=EBI-2339898, EBI-603340; CC Q9NW38; Q8IUH3: RBM45; NbExp=3; IntAct=EBI-2339898, EBI-2512147; CC Q9NW38; Q9UFD9: RIMBP3; NbExp=3; IntAct=EBI-2339898, EBI-10182375; CC Q9NW38; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-2339898, EBI-396669; CC Q9NW38; Q9BWG6: SCNM1; NbExp=3; IntAct=EBI-2339898, EBI-748391; CC Q9NW38; Q96H20: SNF8; NbExp=3; IntAct=EBI-2339898, EBI-747719; CC Q9NW38; Q8IXS7: SRGAP3; NbExp=3; IntAct=EBI-2339898, EBI-18616594; CC Q9NW38; Q9Y2D8: SSX2IP; NbExp=3; IntAct=EBI-2339898, EBI-2212028; CC Q9NW38; Q12800: TFCP2; NbExp=3; IntAct=EBI-2339898, EBI-717422; CC Q9NW38; Q5W5X9-3: TTC23; NbExp=3; IntAct=EBI-2339898, EBI-9090990; CC Q9NW38; Q6NVU6: UFSP1; NbExp=3; IntAct=EBI-2339898, EBI-12068150; CC Q9NW38; Q9UDW3: ZMAT5; NbExp=3; IntAct=EBI-2339898, EBI-7850213; CC Q9NW38; Q9NZL3: ZNF224; NbExp=3; IntAct=EBI-2339898, EBI-12357267; CC Q9NW38; Q9P0T4: ZNF581; NbExp=3; IntAct=EBI-2339898, EBI-745520; CC Q9NW38; Q6NX45: ZNF774; NbExp=3; IntAct=EBI-2339898, EBI-10251462; CC Q9NW38-1; Q9NPD8: UBE2T; NbExp=3; IntAct=EBI-16088720, EBI-2130165; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9CR14}. Nucleus CC {ECO:0000250|UniProtKB:Q9CR14}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9NW38-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9NW38-2; Sequence=VSP_041727; CC -!- DOMAIN: The UBC-RWD region (URD) region mediates interaction with FANCI CC and FANCD2. {ECO:0000269|PubMed:21775430}. CC -!- PTM: The RING-type zinc finger domain is monoubiquitinated in the CC presence of UBE2T and UBE2W. CC -!- DISEASE: Fanconi anemia complementation group L (FANCL) [MIM:614083]: A CC 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:12973351}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- CAUTION: Although PubMed:12724401 reports that it contains a PHD-type CC zinc finger, it contains a RING-type zinc finger. Moreover, PHD-type CC zinc fingers do not have any ubiquitin ligase activity. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Fanconi Anemia Mutation Database; CC URL="https://www2.rockefeller.edu/fanconi/genes/jumpl"; 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; AK001197; BAA91548.1; -; mRNA. DR EMBL; AC007250; AAY15020.1; -; Genomic_DNA. DR EMBL; BC009042; AAH09042.1; -; mRNA. DR EMBL; BC054517; AAH54517.1; -; mRNA. DR EMBL; BC037570; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS1860.1; -. [Q9NW38-1] DR CCDS; CCDS46294.1; -. [Q9NW38-2] DR RefSeq; NP_001108108.1; NM_001114636.1. [Q9NW38-2] DR RefSeq; NP_060532.2; NM_018062.3. [Q9NW38-1] DR PDB; 3ZQS; X-ray; 2.00 A; A/B=109-294. DR PDB; 4CCG; X-ray; 2.40 A; X/Y=288-375. DR PDB; 7KZP; EM; 3.10 A; L/M=1-375. DR PDB; 7KZQ; EM; 4.20 A; L/M=1-375. DR PDB; 7KZR; EM; 4.20 A; L/M=1-375. DR PDB; 7KZS; EM; 4.20 A; L/M=1-375. DR PDB; 7KZT; EM; 4.20 A; L/M=1-375. DR PDB; 7KZV; EM; 4.20 A; L/M=1-375. DR PDBsum; 3ZQS; -. DR PDBsum; 4CCG; -. DR PDBsum; 7KZP; -. DR PDBsum; 7KZQ; -. DR PDBsum; 7KZR; -. DR PDBsum; 7KZS; -. DR PDBsum; 7KZT; -. DR PDBsum; 7KZV; -. DR AlphaFoldDB; Q9NW38; -. DR EMDB; EMD-23085; -. DR EMDB; EMD-23086; -. DR EMDB; EMD-23087; -. DR EMDB; EMD-23088; -. DR EMDB; EMD-23089; -. DR EMDB; EMD-23090; -. DR SMR; Q9NW38; -. DR BioGRID; 120429; 72. DR ComplexPortal; CPX-6263; Fanconi anemia ubiquitin ligase complex. DR CORUM; Q9NW38; -. DR DIP; DIP-43975N; -. DR IntAct; Q9NW38; 54. DR MINT; Q9NW38; -. DR STRING; 9606.ENSP00000385021; -. DR iPTMnet; Q9NW38; -. DR PhosphoSitePlus; Q9NW38; -. DR BioMuta; FANCL; -. DR DMDM; 116241360; -. DR EPD; Q9NW38; -. DR jPOST; Q9NW38; -. DR MassIVE; Q9NW38; -. DR MaxQB; Q9NW38; -. DR PaxDb; 9606-ENSP00000385021; -. DR PeptideAtlas; Q9NW38; -. DR ProteomicsDB; 82894; -. [Q9NW38-1] DR ProteomicsDB; 82895; -. [Q9NW38-2] DR Pumba; Q9NW38; -. DR Antibodypedia; 30496; 247 antibodies from 32 providers. DR DNASU; 55120; -. DR Ensembl; ENST00000233741.9; ENSP00000233741.5; ENSG00000115392.13. [Q9NW38-1] DR Ensembl; ENST00000402135.8; ENSP00000385021.3; ENSG00000115392.13. [Q9NW38-2] DR GeneID; 55120; -. DR KEGG; hsa:55120; -. DR MANE-Select; ENST00000233741.9; ENSP00000233741.5; NM_018062.4; NP_060532.2. DR UCSC; uc002rzw.5; human. [Q9NW38-1] DR AGR; HGNC:20748; -. DR DisGeNET; 55120; -. DR GeneCards; FANCL; -. DR GeneReviews; FANCL; -. DR HGNC; HGNC:20748; FANCL. DR HPA; ENSG00000115392; Low tissue specificity. DR MalaCards; FANCL; -. DR MIM; 608111; gene. DR MIM; 614083; phenotype. DR neXtProt; NX_Q9NW38; -. DR OpenTargets; ENSG00000115392; -. DR Orphanet; 84; Fanconi anemia. DR PharmGKB; PA134887656; -. DR VEuPathDB; HostDB:ENSG00000115392; -. DR eggNOG; KOG3268; Eukaryota. DR GeneTree; ENSGT00390000005537; -. DR InParanoid; Q9NW38; -. DR OMA; NRPFHAK; -. DR OrthoDB; 11501at2759; -. DR PhylomeDB; Q9NW38; -. DR TreeFam; TF323571; -. DR BRENDA; 2.3.2.27; 2681. DR PathwayCommons; Q9NW38; -. DR Reactome; R-HSA-6783310; Fanconi Anemia Pathway. DR Reactome; R-HSA-9833482; PKR-mediated signaling. DR SignaLink; Q9NW38; -. DR SIGNOR; Q9NW38; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 55120; 111 hits in 1207 CRISPR screens. DR ChiTaRS; FANCL; human. DR GeneWiki; FANCL; -. DR GenomeRNAi; 55120; -. DR Pharos; Q9NW38; Tbio. DR PRO; PR:Q9NW38; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q9NW38; Protein. DR Bgee; ENSG00000115392; Expressed in pituitary gland and 201 other cell types or tissues. DR ExpressionAtlas; Q9NW38; baseline and differential. DR GO; GO:0000785; C:chromatin; IDA:ComplexPortal. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0043240; C:Fanconi anaemia nuclear complex; IDA:UniProtKB. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0016604; C:nuclear body; IDA:HPA. DR GO; GO:0005635; C:nuclear envelope; IEA:Ensembl. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:MGI. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB. DR GO; GO:0006974; P:DNA damage response; IMP:UniProtKB. DR GO; GO:0006281; P:DNA repair; IMP:UniProtKB. DR GO; GO:0007276; P:gamete generation; IEA:Ensembl. DR GO; GO:0036297; P:interstrand cross-link repair; NAS:ComplexPortal. DR GO; GO:0006513; P:protein monoubiquitination; IDA:UniProtKB. DR GO; GO:0042127; P:regulation of cell population proliferation; IEA:Ensembl. DR CDD; cd16490; RING-CH-C4HC3_FANCL; 1. DR Gene3D; 3.10.110.20; RWD domain-like; 1. DR Gene3D; 3.10.110.10; Ubiquitin Conjugating Enzyme; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR026848; Fancl. DR InterPro; IPR026850; FANCL_C. DR InterPro; IPR043898; FANCL_d2. DR InterPro; IPR044037; FANCL_d3. DR InterPro; IPR043003; FANCL_d3_sf. DR InterPro; IPR019162; FancL_WD-rpt_cont_dom. DR InterPro; IPR016135; UBQ-conjugating_enzyme/RWD. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR PANTHER; PTHR13206:SF0; E3 UBIQUITIN-PROTEIN LIGASE FANCL; 1. DR PANTHER; PTHR13206; UBIQUITIN LIGASE PROTEIN PHF9 FANCONI ANEMIA GROUP L PROTEIN; 1. DR Pfam; PF11793; FANCL_C; 1. DR Pfam; PF09765; FANCL_d1; 1. DR Pfam; PF18890; FANCL_d2; 1. DR Pfam; PF18891; FANCL_d3; 1. DR SMART; SM01197; FANCL_C; 1. DR SUPFAM; SSF57850; RING/U-box; 1. DR Genevisible; Q9NW38; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm; DNA damage; KW DNA repair; Fanconi anemia; Metal-binding; Nucleus; Reference proteome; KW Transferase; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:22814378" FT CHAIN 2..375 FT /note="E3 ubiquitin-protein ligase FANCL" FT /id="PRO_0000055908" FT ZN_FING 307..363 FT /note="RING-type; degenerate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175" FT REGION 104..294 FT /note="UBC-RWD region (URD)" FT BINDING 307 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0007744|PDB:4CCG" FT BINDING 310 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0007744|PDB:4CCG" FT BINDING 324 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0007744|PDB:4CCG" FT BINDING 329 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0007744|PDB:4CCG" FT BINDING 334 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0007744|PDB:4CCG" FT BINDING 337 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0007744|PDB:4CCG" FT BINDING 359 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0007744|PDB:4CCG" FT BINDING 362 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0007744|PDB:4CCG" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:22814378" FT VAR_SEQ 178 FT /note="T -> TPQVNS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_041727" FT VARIANT 144 FT /note="S -> F (in dbSNP:rs36059257)" FT /id="VAR_052082" FT MUTAGEN 127..128 FT /note="VY->AA: No effect on interaction with FANCI and FT FANCD2." FT /evidence="ECO:0000269|PubMed:21775430" FT MUTAGEN 149 FT /note="L->A: No effect on interaction with FANCI and FT FANCD2; when associated with A-166." FT /evidence="ECO:0000269|PubMed:21775430" FT MUTAGEN 158..159 FT /note="YP->AA: Abolishes UBE2T charging." FT /evidence="ECO:0000269|PubMed:19111657" FT MUTAGEN 166 FT /note="F->A: Does not affect interaction with FANCI and FT FANCD2; when associated with A-149." FT /evidence="ECO:0000269|PubMed:21775430" FT MUTAGEN 212..214 FT /note="WVL->AVA: Impairs interaction with FANCI and FT FANCD2." FT /evidence="ECO:0000269|PubMed:21775430" FT MUTAGEN 248 FT /note="L->A: Impairs interaction with FANCI and FANCD2; FT when associated with A-252, A-254 and A-265." FT /evidence="ECO:0000269|PubMed:21775430" FT MUTAGEN 252 FT /note="F->A: Impairs interaction with FANCI and FANCD2; FT when associated with A-248, A-254 and A-265." FT /evidence="ECO:0000269|PubMed:21775430" FT MUTAGEN 254 FT /note="L->A: Impairs interaction with FANCI and FANCD2; FT when associated with A-248, A-252 and A-265." FT /evidence="ECO:0000269|PubMed:21775430" FT MUTAGEN 265 FT /note="I->A: Impairs interaction with FANCI and FANCD2; FT when associated with A-248, A-252 and A-254." FT /evidence="ECO:0000269|PubMed:21775430" FT MUTAGEN 307 FT /note="C->A: Abolishes ubiquitin ligase activity." FT /evidence="ECO:0000269|PubMed:12973351, FT ECO:0000269|PubMed:16916645, ECO:0000269|PubMed:17938197, FT ECO:0000269|PubMed:19111657, ECO:0000269|PubMed:19589784" FT MUTAGEN 309 FT /note="I->A: Loss of interaction with UBE2T." FT /evidence="ECO:0000269|PubMed:24389026" FT MUTAGEN 310 FT /note="C->A: Abolishes ubiquitin ligase activity." FT /evidence="ECO:0000269|PubMed:12973351, FT ECO:0000269|PubMed:17938197" FT MUTAGEN 311 FT /note="Y->A: Loss of interaction with UBE2T." FT /evidence="ECO:0000269|PubMed:24389026" FT MUTAGEN 341 FT /note="W->A: Loss of interaction with UBE2T." FT /evidence="ECO:0000269|PubMed:24389026" FT MUTAGEN 341 FT /note="W->G: Abolishes interaction with UBE2T and ubiquitin FT ligase activity." FT /evidence="ECO:0000269|PubMed:16916645" FT MUTAGEN 359 FT /note="C->A: Abolishes ubiquitin ligase activity." FT /evidence="ECO:0000269|PubMed:19111657" FT CONFLICT 77 FT /note="S -> P (in Ref. 1; BAA91548)" FT /evidence="ECO:0000305" FT HELIX 114..121 FT /evidence="ECO:0007829|PDB:3ZQS" FT HELIX 123..125 FT /evidence="ECO:0007829|PDB:3ZQS" FT STRAND 126..129 FT /evidence="ECO:0007829|PDB:3ZQS" FT STRAND 133..141 FT /evidence="ECO:0007829|PDB:3ZQS" FT STRAND 147..153 FT /evidence="ECO:0007829|PDB:3ZQS" FT TURN 156..160 FT /evidence="ECO:0007829|PDB:3ZQS" FT STRAND 164..166 FT /evidence="ECO:0007829|PDB:3ZQS" FT HELIX 183..196 FT /evidence="ECO:0007829|PDB:3ZQS" FT HELIX 198..210 FT /evidence="ECO:0007829|PDB:3ZQS" FT STRAND 213..218 FT /evidence="ECO:0007829|PDB:3ZQS" FT STRAND 225..231 FT /evidence="ECO:0007829|PDB:3ZQS" FT STRAND 234..239 FT /evidence="ECO:0007829|PDB:3ZQS" FT STRAND 250..255 FT /evidence="ECO:0007829|PDB:3ZQS" FT HELIX 257..270 FT /evidence="ECO:0007829|PDB:3ZQS" FT HELIX 271..273 FT /evidence="ECO:0007829|PDB:3ZQS" FT HELIX 280..288 FT /evidence="ECO:0007829|PDB:3ZQS" FT TURN 308..310 FT /evidence="ECO:0007829|PDB:4CCG" FT TURN 327..329 FT /evidence="ECO:0007829|PDB:4CCG" FT HELIX 335..342 FT /evidence="ECO:0007829|PDB:4CCG" FT STRAND 349..351 FT /evidence="ECO:0007829|PDB:4CCG" FT STRAND 354..358 FT /evidence="ECO:0007829|PDB:4CCG" FT TURN 360..362 FT /evidence="ECO:0007829|PDB:4CCG" FT STRAND 365..369 FT /evidence="ECO:0007829|PDB:4CCG" SQ SEQUENCE 375 AA; 42905 MW; E217DF9D64587E5E CRC64; MAVTEASLLR QCPLLLPQNR SKTVYEGFIS AQGRDFHLRI VLPEDLQLKN ARLLCSWQLR TILSGYHRIV QQRMQHSPDL MSFMMELKML LEVALKNRQE LYALPPPPQF YSSLIEEIGT LGWDKLVYAD TCFSTIKLKA EDASGREHLI TLKLKAKYPA ESPDYFVDFP VPFCASWTPQ SSLISIYSQF LAAIESLKAF WDVMDEIDEK TWVLEPEKPP RSATARRIAL GNNVSINIEV DPRHPTMLPE CFFLGADHVV KPLGIKLSRN IHLWDPENSV LQNLKDVLEI DFPARAILEK SDFTMDCGIC YAYQLDGTIP DQVCDNSQCG QPFHQICLYE WLRGLLTSRQ SFNIIFGECP YCSKPITLKM SGRKH //