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UniProtKB/Swiss-Prot entry Q9NW38


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name FANCL_HUMAN
Primary accession number Q9NW38
Secondary accession number Q6GU60
Integrated into Swiss-Prot on October 10, 2003
Sequence was last modified on October 17, 2006 (Sequence version 2)
Annotations were last modified on    June 16, 2009 (Entry version 71)
Name and origin of the protein
Protein name E3 ubiquitin-protein ligase FANCL
Synonyms EC 6.3.2.-
Fanconi anemia group L protein
Fanconi anemia-associated polypeptide of 43 kDa
FAAP43
Gene name
Name: FANCL
Synonyms: PHF9
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Teratocarcinoma;
DOI=10.1038/ng1285; PubMed=14702039 [NCBI, ExPASy, EBI, Israel, Japan]
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human cDNAs.";
Nat. Genet. 36:40-45(2004).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/nature03466; PubMed=15815621 [NCBI, ExPASy, EBI, Israel, Japan]
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.;
"Generation and annotation of the DNA sequences of human chromosomes 2 and 4.";
Nature 434:724-731(2005).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Brain, and Eye;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[4]
IDENTIFICATION BY MASS SPECTROMETRY IN A BRAFT COMPLEX WITH FANCA; FANCC; FANCE; FANCF AND FANCG.
DOI=10.1128/MCB.23.10.3417-3426.2003; PubMed=12724401 [NCBI, ExPASy, EBI, Israel, Japan]
Meetei A.R., Sechi S., Wallisch M., Yang D., Young M.K., Joenje H., Hoatlin M.E., Wang W.;
"A multiprotein nuclear complex connects Fanconi anemia and Bloom syndrome.";
Mol. Cell. Biol. 23:3417-3426(2003).
[5]
FUNCTION, SUBCELLULAR LOCATION, DISEASE, INTERACTION WITH FANCA; FANCC; FANCF AND FANCG, AND MUTAGENESIS OF CYS-307 AND CYS-310.
DOI=10.1038/ng1241; PubMed=12973351 [NCBI, ExPASy, EBI, Israel, Japan]
Meetei A.R., de Winter J.P., Medhurst A.L., Wallisch M., Waisfisz Q., van de Vrugt H.J., Oostra A.B., Yan Z., Ling C., Bishop C.E., Hoatlin M.E., Joenje H., Wang W.;
"A novel ubiquitin ligase is deficient in Fanconi anemia.";
Nat. Genet. 35:165-170(2003).
[6]
IDENTIFICATION IN A COMPLEX WITH FANCA; FANCB; FANCC; FANCE; FANCF AND FANCLG.
DOI=10.1038/ng1458; PubMed=15502827 [NCBI, ExPASy, EBI, Israel, Japan]
Meetei A.R., Levitus M., Xue Y., Medhurst A.L., Zwaan M., Ling C., Rooimans M.A., Bier P., Hoatlin M., Pals G., de Winter J.P., Wang W., Joenje H.;
"X-linked inheritance of Fanconi anemia complementation group B.";
Nat. Genet. 36:1219-1224(2004).
[7]
IDENTIFICATION IN A COMPLEX WITH FANCA; FANCB; FANCC; FANCE; FANCF; FANCG AND FANCM.
DOI=10.1038/ng1626; PubMed=16116422 [NCBI, ExPASy, EBI, Israel, Japan]
Meetei A.R., Medhurst A.L., Ling C., Xue Y., Singh T.R., Bier P., Steltenpool J., Stone S., Dokal I., Mathew C.G., Hoatlin M., Joenje H., de Winter J.P., Wang W.;
"A human ortholog of archaeal DNA repair protein Hef is defective in Fanconi anemia complementation group M.";
Nat. Genet. 37:958-963(2005).
Comments
  • FUNCTION: Ubiquitin ligase protein that mediates ubiquitination of FANCD2, a key step in the DNA damage pathway. May be required for proper primordial germ cell proliferation in the embryonic stage, whereas it is probably not needed for spermatogonial proliferation after birth.
  • PATHWAY: Protein modification; protein ubiquitination.
  • SUBUNIT: Interacts with GGN (By similarity). Belongs to the multisubunit FA complex composed of FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL/PHF9 and FANCM. The complex is not found in FA patients.
  • SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
  • DISEASE: Defects in FANCL are a cause of Fanconi anemia (FA) [MIM:227650]. FA is a genetically heterogeneous, autosomal recessive disorder characterized by progressive pancytopenia, a diverse assortment of congenital malformations, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage), and defective DNA repair.
  • SIMILARITY: Contains 1 RING-type zinc finger.
  • CAUTION: Although PubMed:12724401 reports that it contains a PHD-type zinc finger, it contains a RING-type zinc finger. Moreover, PHD-type zinc fingers do not have any ubiquitin ligase activity.
  • WEB RESOURCE: Name=Fanconi Anemia Mutation Database; URL="http://www.rockefeller.edu/fanconi/mutate/jumpl.html";.
  • WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=FANCL";.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
AK001197; BAA91548.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AC007250; AAY15020.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC009042; AAH09042.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC054517; AAH54517.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
IPI IPI00018099; -.
RefSeq NP_001108108.1; -.
NP_060532.2; -.
UniGene Hs.708194
3D structure databases
ModBase Q9NW38.
Enzyme and pathway databases
Pathway_Interaction_DB bard1pathway; BARD1 signaling events.
Organism-specific databases
GeneCards GC02M058298; -.
H-InvDB HIX0002071; -.
HGNC HGNC:20748; FANCL.
GenAtlas FANCL.
MIM 227650; phenotype. [NCBI / EBI]
608111; gene+phenotype. [NCBI / EBI]
Orphanet 84; Fanconi anemia.
PharmGKB PA134887656; -.
Gene expression databases
ArrayExpress Q9NW38; -.
Bgee Q9NW38; -.
CleanEx HS_FANCL; -.
GermOnline ENSG00000115392; Homo sapiens.
Ontologies
GO
GO:0005737; Cellular component: cytoplasm (inferred from electronic annotation from UniProtKB-SubCell).
GO:0005634; Cellular component: nucleus (inferred from electronic annotation from UniProtKB-SubCell).
GO:0016874; Molecular function: ligase activity (inferred from electronic annotation from UniProtKB-KW).
GO:0005515; Molecular function: protein binding (inferred from electronic annotation from InterPro).
GO:0008270; Molecular function: zinc ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0006281; Biological process: DNA repair (inferred from electronic annotation from UniProtKB-KW).
GO:0019941; Biological process: modification-dependent protein catabolic process (inferred from electronic annotation from UniProtKB-KW).
QuickGo view.
Family and domain databases
InterPro IPR019162; Fanconi_anemia_FancL_WD-rpt.
IPR001841; Znf_RING.
IPR017907; Znf_RING_CS.
Graphical view of domain structure.
Pfam PF09765; WD-3; 1.
Pfam graphical view of domain structure.
SMART SM00184; RING; 1.
SMART graphical view of domain structure.
PROSITE PS00518; ZF_RING_1; FALSE_NEG.
PS50089; ZF_RING_2; FALSE_NEG.
PROSITE graphical view of domain structure (profiles).
Proteomic databases
PRIDE Q9NW38; -.
Genome annotation databases
Ensembl ENSG00000115392; Homo sapiens. [Contig view]
GeneID 55120; -.
KEGG hsa:55120; -.
Phylogenomic databases
HOGENOM Q9NW38; -.
HOVERGEN Q9NW38; -.
Other
NextBio 58768; -.
SOURCE FANCL; Homo sapiens.
ProtoNet Q9NW38.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
Cytoplasm; DNA damage; DNA repair; Fanconi anemia; Ligase; Metal-binding; Nucleus; Polymorphism; Ubl conjugation pathway; Zinc; Zinc-finger.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
CHAIN   1   375  375     E3 ubiquitin-protein ligase FANCL. PRO_0000055908
ZN_FING   307   365  59     RING-type. 
VARIANT   144   144  1     S -> F (in dbSNP:rs36059257 [NCBI]). VAR_052082 
MUTAGEN   307   307        C->A: Abolishes ubiquitin ligase activity. 
MUTAGEN   310   310        C->A: Abolishes ubiquitin ligase activity. 
CONFLICT   77    77        S -> P (in Ref. 1; BAA91548). 
Sequence information
Length: 375 AA [This is the length of the unprocessed precursor] Molecular weight: 42905 Da [This is the MW of the unprocessed precursor] CRC64: E217DF9D64587E5E [This is a checksum on the sequence]
        10         20         30         40         50         60 
MAVTEASLLR QCPLLLPQNR SKTVYEGFIS AQGRDFHLRI VLPEDLQLKN ARLLCSWQLR 

        70         80         90        100        110        120 
TILSGYHRIV QQRMQHSPDL MSFMMELKML LEVALKNRQE LYALPPPPQF YSSLIEEIGT 

       130        140        150        160        170        180 
LGWDKLVYAD TCFSTIKLKA EDASGREHLI TLKLKAKYPA ESPDYFVDFP VPFCASWTPQ 

       190        200        210        220        230        240 
SSLISIYSQF LAAIESLKAF WDVMDEIDEK TWVLEPEKPP RSATARRIAL GNNVSINIEV 

       250        260        270        280        290        300 
DPRHPTMLPE CFFLGADHVV KPLGIKLSRN IHLWDPENSV LQNLKDVLEI DFPARAILEK 

       310        320        330        340        350        360 
SDFTMDCGIC YAYQLDGTIP DQVCDNSQCG QPFHQICLYE WLRGLLTSRQ SFNIIFGECP 

       370 
YCSKPITLKM SGRKH 

Q9NW38 in FASTA format

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