FANCL_HUMAN
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 03-AUG-2022, entry version 183.
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; 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; Q5BKX5-3: C19orf54; NbExp=3; IntAct=EBI-2339898, EBI-11976299;
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. Nucleus.
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";
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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 SMR; Q9NW38; -.
DR BioGRID; 120429; 67.
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; Q9NW38; -.
DR PeptideAtlas; Q9NW38; -.
DR PRIDE; Q9NW38; -.
DR ProteomicsDB; 82894; -. [Q9NW38-1]
DR ProteomicsDB; 82895; -. [Q9NW38-2]
DR Antibodypedia; 30496; 234 antibodies from 32 providers.
DR DNASU; 55120; -.
DR Ensembl; ENST00000233741.9; ENSP00000233741.5; ENSG00000115392.12. [Q9NW38-1]
DR Ensembl; ENST00000402135.7; ENSP00000385021.3; ENSG00000115392.12. [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 CTD; 55120; -.
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; HTVFGEC; -.
DR OrthoDB; 1002812at2759; -.
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 SignaLink; Q9NW38; -.
DR SIGNOR; Q9NW38; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 55120; 102 hits in 1123 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 199 other tissues.
DR ExpressionAtlas; Q9NW38; baseline and differential.
DR Genevisible; Q9NW38; HS.
DR GO; GO:0000785; C:chromatin; IDA:ComplexPortal.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
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:cellular response to DNA damage stimulus; 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; IC:ComplexPortal.
DR GO; GO:0006513; P:protein monoubiquitination; IDA:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; IEA:Ensembl.
DR Gene3D; 3.10.110.10; -; 1.
DR Gene3D; 3.10.110.20; -; 1.
DR Gene3D; 3.30.40.10; -; 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; PTHR13206; 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.
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..365
FT /note="RING-type"
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
