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   24-NOV-2009, entry version 77.
DE   RecName: Full=E3 ubiquitin-protein ligase FANCL;
DE            EC=6.3.2.-;
DE   AltName: Full=Fanconi anemia group L protein;
DE   AltName: Full=Fanconi anemia-associated polypeptide of 43 kDa;
DE            Short=FAAP43;
GN   Name=FANCL; Synonyms=PHF9;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   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.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA   Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA   Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA   Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA   Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA   Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA   Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA   Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA   Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA   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.,
RA   Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA   Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA   Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA   Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA   Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA   Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA   Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA   Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA   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.,
RA   Waterston R.H., Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2
RT   and 4.";
RL   Nature 434:724-731(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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
RT   project: 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;
RP   FANCC; FANCE; FANCF AND FANCG.
RX   MEDLINE=22610328; PubMed=12724401;
RX   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, SUBCELLULAR LOCATION, DISEASE, INTERACTION WITH FANCA;
RP   FANCC; FANCF AND FANCG, AND MUTAGENESIS OF CYS-307 AND CYS-310.
RX   MEDLINE=22879927; 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.,
RA   Hoatlin M.E., 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;
RP   FANCG 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.,
RA   Joenje H., 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).
CC   -!- FUNCTION: Ubiquitin ligase protein that mediates ubiquitination of
CC       FANCD2, a key step in the DNA damage pathway. May be required for
CC       proper primordial germ cell proliferation in the embryonic stage,
CC       whereas it is probably not needed for spermatogonial proliferation
CC       after birth.
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,
CC       FANCF, FANCG, FANCL/PHF9 and FANCM. The complex is not found in FA
CC       patients.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
CC   -!- DISEASE: Defects in FANCL are a cause of Fanconi anemia (FA)
CC       [MIM:227650]. FA is a genetically heterogeneous, autosomal
CC       recessive disorder characterized by progressive pancytopenia, a
CC       diverse assortment of congenital malformations, and a
CC       predisposition to the development of malignancies. At the cellular
CC       level it is associated with hypersensitivity to DNA-damaging
CC       agents, chromosomal instability (increased chromosome breakage),
CC       and defective DNA repair.
CC   -!- SIMILARITY: Contains 1 RING-type zinc finger.
CC   -!- CAUTION: Although PubMed:12724401 reports that it contains a PHD-
CC       type zinc finger, it contains a RING-type zinc finger. Moreover,
CC       PHD-type zinc fingers do not have any ubiquitin ligase activity.
CC   -!- WEB RESOURCE: Name=Fanconi Anemia Mutation Database;
CC       URL="http://www.rockefeller.edu/fanconi/mutate/jumpl.html";
CC   -!- WEB RESOURCE: Name=GeneReviews;
CC       URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/FANCL";
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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   IPI; IPI00018099; -.
DR   RefSeq; NP_001108108.1; -.
DR   RefSeq; NP_060532.2; -.
DR   UniGene; Hs.708194; -.
DR   IntAct; Q9NW38; 1.
DR   STRING; Q9NW38; -.
DR   PRIDE; Q9NW38; -.
DR   Ensembl; ENST00000233741; ENSP00000233741; ENSG00000115392; Homo sapiens.
DR   GeneID; 55120; -.
DR   KEGG; hsa:55120; -.
DR   UCSC; uc002rzw.2; human.
DR   CTD; 55120; -.
DR   GeneCards; GC02M058298; -.
DR   H-InvDB; HIX0002071; -.
DR   HGNC; HGNC:20748; FANCL.
DR   MIM; 227650; phenotype.
DR   MIM; 608111; gene+phenotype.
DR   Orphanet; 84; Fanconi anemia.
DR   PharmGKB; PA134887656; -.
DR   HOGENOM; Q9NW38; -.
DR   HOVERGEN; Q9NW38; -.
DR   Pathway_Interaction_DB; bard1pathway; BARD1 signaling events.
DR   Reactome; REACT_216; DNA Repair.
DR   NextBio; 58768; -.
DR   ArrayExpress; Q9NW38; -.
DR   Bgee; Q9NW38; -.
DR   CleanEx; HS_FANCL; -.
DR   Genevestigator; Q9NW38; -.
DR   GermOnline; ENSG00000115392; Homo sapiens.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR   GO; GO:0005515; F:protein binding; IEA:InterPro.
DR   GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR   GO; GO:0019941; P:modification-dependent protein catabolic pr...; IEA:UniProtKB-KW.
DR   InterPro; IPR019162; Fanconi_anemia_FancL_WD-rpt.
DR   InterPro; IPR001841; Znf_RING.
DR   Pfam; PF09765; WD-3; 1.
DR   SMART; SM00184; RING; 1.
DR   PROSITE; PS00518; ZF_RING_1; FALSE_NEG.
DR   PROSITE; PS50089; ZF_RING_2; FALSE_NEG.
PE   1: Evidence at protein level;
KW   Complete proteome; Cytoplasm; DNA damage; DNA repair; Fanconi anemia;
KW   Ligase; Metal-binding; Nucleus; Polymorphism; Ubl conjugation pathway;
KW   Zinc; Zinc-finger.
FT   CHAIN         1    375       E3 ubiquitin-protein ligase FANCL.
FT                                /FTId=PRO_0000055908.
FT   ZN_FING     307    365       RING-type.
FT   VARIANT     144    144       S -> F (in dbSNP:rs36059257).
FT                                /FTId=VAR_052082.
FT   MUTAGEN     307    307       C->A: Abolishes ubiquitin ligase
FT                                activity.
FT   MUTAGEN     310    310       C->A: Abolishes ubiquitin ligase
FT                                activity.
FT   CONFLICT     77     77       S -> P (in Ref. 1; BAA91548).
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
//