FANCL_MOUSE
ID FANCL_MOUSE Reviewed; 375 AA.
AC Q9CR14; Q3TGY2; Q9D017;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=E3 ubiquitin-protein ligase FANCL;
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q9NW38};
DE AltName: Full=Fanconi anemia group L protein homolog;
DE AltName: Full=Proliferation of germ cells protein;
DE AltName: Full=RING-type E3 ubiquitin transferase FANCL {ECO:0000305};
GN Name=Fancl; Synonyms=Phf9, Pog;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RC STRAIN=C57BL/6J;
RX PubMed=12417526; DOI=10.1093/hmg/11.24.3047;
RA Agoulnik A.I., Lu B., Zhu Q., Truong C., Ty M.T., Arango N., Chada K.K.,
RA Bishop C.E.;
RT "A novel gene, Pog, is necessary for primordial germ cell proliferation in
RT the mouse and underlies the germ cell deficient mutation, gcd.";
RL Hum. Mol. Genet. 11:3047-3053(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Embryo, Kidney, Small intestine, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Pancreas, and Thymus;
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 FUNCTION.
RX PubMed=12606378; DOI=10.1095/biolreprod.102.014654;
RA Lu B., Bishop C.E.;
RT "Late onset of spermatogenesis and gain of fertility in POG-deficient mice
RT indicate that POG is not necessary for the proliferation of
RT spermatogonia.";
RL Biol. Reprod. 69:161-168(2003).
RN [5]
RP INTERACTION WITH GGN.
RX PubMed=12574169; DOI=10.1074/jbc.m211023200;
RA Lu B., Bishop C.E.;
RT "Mouse GGN1 and GGN3, two germ cell-specific proteins from the single gene
RT Ggn, interact with mouse POG and play a role in spermatogenesis.";
RL J. Biol. Chem. 278:16289-16296(2003).
RN [6]
RP INTERACTION WITH UBE2W, AND SUBCELLULAR LOCATION.
RX PubMed=21229326; DOI=10.1007/s10059-011-0015-9;
RA Zhang Y., Zhou X., Zhao L., Li C., Zhu H., Xu L., Shan L., Liao X., Guo Z.,
RA Huang P.;
RT "UBE2W interacts with FANCL and regulates the monoubiquitination of Fanconi
RT anemia protein FANCD2.";
RL Mol. Cells 31:113-122(2011).
CC -!- FUNCTION: Ubiquitin ligase protein that mediates monoubiquitination of
CC FANCD2, a key step in the DNA damage pathway. Also mediates
CC monoubiquitination of FANCI. May stimulate the ubiquitin release from
CC UBE2W. May be required for proper primordial germ cell proliferation in
CC the embryonic stage, whereas it is probably not needed for
CC spermatogonial proliferation after birth. {ECO:0000269|PubMed:12417526,
CC ECO:0000269|PubMed:12606378}.
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:0000250|UniProtKB:Q9NW38};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Belongs to the multisubunit FA complex composed of FANCA,
CC FANCB, FANCC, FANCE, FANCF, FANCG, FANCL/PHF9 and FANCM (By
CC similarity). In complex with FANCF, FANCA and FANCG, but not with
CC FANCC, nor FANCE, interacts with HES1; this interaction may be
CC essential for the stability and nuclear localization of FA core complex
CC proteins. Interacts with FANCI (By similarity). Interacts with GGN.
CC Interacts (via the RING-type zinc finger) with UBE2T and UBE2W.
CC {ECO:0000250|UniProtKB:Q9NW38, ECO:0000269|PubMed:12574169,
CC ECO:0000269|PubMed:21229326}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21229326}. Nucleus
CC {ECO:0000269|PubMed:21229326}. Note=In the nucleus, colocalizes with
CC UBE2W.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9CR14-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9CR14-2; Sequence=VSP_008552;
CC -!- DOMAIN: The UBC-RWD region (URD) region mediates interaction with FANCI
CC and FANCD2. {ECO:0000250|UniProtKB:Q9NW38}.
CC -!- PTM: The RING-type zinc finger domain is monoubiquitinated in the
CC presence of UBE2T and UBE2W.
CC -!- DISEASE: Note=Defects in Fancl are a cause of the gcd (germ cell
CC deficient) mutant phenotype, which leads to reduced numbers of
CC precursor germ cells and adult sterility, probably due to a reduced
CC precursor germ cells proliferation.
CC -!- CAUTION: Despite its name, it does not contain a PHD-type zinc finger,
CC but contains a RING-type zinc finger. Moreover, PHD-type zinc fingers
CC do not have any ubiquitin ligase activity. {ECO:0000305}.
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; AF513619; AAN64921.1; -; mRNA.
DR EMBL; AK008605; BAB25772.1; -; mRNA.
DR EMBL; AK011520; BAB27674.1; -; mRNA.
DR EMBL; AK011752; BAB27820.1; -; mRNA.
DR EMBL; AK011903; BAB27906.1; -; mRNA.
DR EMBL; AK018018; BAB31039.1; -; mRNA.
DR EMBL; AK076017; BAC36123.1; -; mRNA.
DR EMBL; AK168538; BAE40416.1; -; mRNA.
DR EMBL; BC066181; AAH66181.1; -; mRNA.
DR EMBL; BC032876; AAH32876.1; -; mRNA.
DR CCDS; CCDS24485.1; -. [Q9CR14-1]
DR CCDS; CCDS70152.1; -. [Q9CR14-2]
DR RefSeq; NP_001264202.1; NM_001277273.1. [Q9CR14-2]
DR RefSeq; NP_080199.1; NM_025923.3. [Q9CR14-1]
DR AlphaFoldDB; Q9CR14; -.
DR SMR; Q9CR14; -.
DR BioGRID; 211887; 9.
DR IntAct; Q9CR14; 3.
DR MINT; Q9CR14; -.
DR STRING; 10090.ENSMUSP00000004120; -.
DR PhosphoSitePlus; Q9CR14; -.
DR EPD; Q9CR14; -.
DR MaxQB; Q9CR14; -.
DR PaxDb; Q9CR14; -.
DR PRIDE; Q9CR14; -.
DR ProteomicsDB; 271861; -. [Q9CR14-1]
DR ProteomicsDB; 271862; -. [Q9CR14-2]
DR Antibodypedia; 30496; 234 antibodies from 32 providers.
DR DNASU; 67030; -.
DR Ensembl; ENSMUST00000004120; ENSMUSP00000004120; ENSMUSG00000004018. [Q9CR14-1]
DR Ensembl; ENSMUST00000109509; ENSMUSP00000105135; ENSMUSG00000004018. [Q9CR14-2]
DR GeneID; 67030; -.
DR KEGG; mmu:67030; -.
DR UCSC; uc007ige.2; mouse. [Q9CR14-1]
DR UCSC; uc011xsj.2; mouse. [Q9CR14-2]
DR CTD; 55120; -.
DR MGI; MGI:1914280; Fancl.
DR VEuPathDB; HostDB:ENSMUSG00000004018; -.
DR eggNOG; KOG3268; Eukaryota.
DR GeneTree; ENSGT00390000005537; -.
DR HOGENOM; CLU_045054_0_0_1; -.
DR InParanoid; Q9CR14; -.
DR OMA; HTVFGEC; -.
DR OrthoDB; 1002812at2759; -.
DR PhylomeDB; Q9CR14; -.
DR TreeFam; TF323571; -.
DR Reactome; R-MMU-6783310; Fanconi Anemia Pathway.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 67030; 24 hits in 110 CRISPR screens.
DR ChiTaRS; Fancl; mouse.
DR PRO; PR:Q9CR14; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q9CR14; protein.
DR Bgee; ENSMUSG00000004018; Expressed in dorsal pancreas and 251 other tissues.
DR ExpressionAtlas; Q9CR14; baseline and differential.
DR Genevisible; Q9CR14; MM.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0043240; C:Fanconi anaemia nuclear complex; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005635; C:nuclear envelope; IPI:MGI.
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; ISO:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0006281; P:DNA repair; ISS:UniProtKB.
DR GO; GO:0007276; P:gamete generation; IMP:MGI.
DR GO; GO:0036297; P:interstrand cross-link repair; IEA:InterPro.
DR GO; GO:0006513; P:protein monoubiquitination; ISS:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; IMP:MGI.
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 Alternative splicing; Cytoplasm; DNA damage; DNA repair; Metal-binding;
KW Nucleus; Reference proteome; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..375
FT /note="E3 ubiquitin-protein ligase FANCL"
FT /id="PRO_0000055909"
FT ZN_FING 307..365
FT /note="RING-type"
FT REGION 104..294
FT /note="UBC-RWD region (URD)"
FT /evidence="ECO:0000250"
FT VAR_SEQ 274..279
FT /note="WDPENS -> C (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_008552"
FT CONFLICT 230
FT /note="L -> I (in Ref. 2; BAB27906)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 375 AA; 42527 MW; 33CE1FE964E917DA CRC64;
MDEAEASLLR HFPLLLPQNR EKTVYEGFIS AQGSDFHLRI VLPKDLQLKK ARLLCSLQLK
NILNEYHQVV QQRMKHSPDL MSFMMELKMI LEVALKNKQE LCVQPPSCSF CKDLLTEIGA
IGWDKLACVE SSFSTIKLKA DDASGRKHLI TVKLKAKYPV EPPDCVVDFP VPFSVSWTPQ
SSLVDVYSQF LVALETLKVF WDVMDEIDEK TWVLEPEKPP RSATARRIAL GKNVSIAIEV
DPRHPTMLPE FCFLGADHVT KPLGMKLSGS IHLWDPENSL LQNLKDVLEI DFPARSILEE
SDFSMDCGIC YARHLNGAIP DQVCNNPQCG QPFHEICLYE WLRGLSTSRQ SFNVFFGDCP
YCSKPITLKM SGRKP
