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Gene Review

FANCL  -  Fanconi anemia, complementation group L

Homo sapiens

Synonyms: E3 ubiquitin-protein ligase FANCL, FAAP43, FLJ10335, Fanconi anemia group L protein, Fanconi anemia-associated polypeptide of 43 kDa, ...
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Disease relevance of FANCL

  • We previously purified a Fanconi anemia core complex containing the FANCL ubiquitin ligase and six other Fanconi anemia-associated proteins [1].
  • Altered Expression of FANCL Confers Mitomycin C Sensitivity in Calu-6 Lung Cancer Cells [2].
  • We studied seven SNPs in FANCA, FANCL and FANCD2 in a total of 897 consecutive and non-related sporadic breast cancer cases and 1033 unaffected controls from the Spanish population [3].



High impact information on FANCL

  • Here we report a new component of a Fanconi anemia protein complex, called PHF9, which possesses E3 ubiquitin ligase activity in vitro and is essential for FANCD2 monoubiquitination in vivo [4].
  • UBE2T binds to FANCL, the ubiquitin ligase subunit of the Fanconi anemia core complex, and is required for the monoubiquitination of FANCD2 in vivo [5].
  • We demonstrate a direct interaction between FANCB and FANCL and that a complex of these proteins binds FANCA [6] .

Biological context of FANCL


Anatomical context of FANCL


Associations of FANCL with chemical compounds

  • The PHD of FANCL also shares sequence similarity to the canonical RING finger of c-CBL, including a conserved tryptophan required for E2 binding by c-CBL [11] .
  • Monoclonal antibody PHF-9 recognizes phosphorylated serine 404 of tau protein and labels paired helical filaments [12].

Regulatory relationships of FANCL

  • This monoubiquitination is stimulated by the presence of the FANCL protein and inactivates UBE2T [5].

Other interactions of FANCL

  • Here we found that FANCL, but not BRCA1, evolutionarily co-exists with FANCD2 in several species [9].


  1. A human ortholog of archaeal DNA repair protein Hef is defective in Fanconi anemia complementation group M. 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. Nat. Genet. (2005) [Pubmed]
  2. Altered Expression of FANCL Confers Mitomycin C Sensitivity in Calu-6 Lung Cancer Cells. Zhang, J., Wang, X., Lin, C.J., Couch, F.J., Fei, P. Cancer Biol. Ther. (2006) [Pubmed]
  3. FANCD2 associated with sporadic breast cancer risk. Barroso, E., Milne, R.L., Fernández, L.P., Zamora, P., Arias, J.I., Benítez, J., Ribas, G. Carcinogenesis (2006) [Pubmed]
  4. A novel ubiquitin ligase is deficient in Fanconi anemia. 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. Nat. Genet. (2003) [Pubmed]
  5. UBE2T is the E2 in the Fanconi anemia pathway and undergoes negative autoregulation. Machida, Y.J., Machida, Y., Chen, Y., Gurtan, A.M., Kupfer, G.M., D'Andrea, A.D., Dutta, A. Mol. Cell (2006) [Pubmed]
  6. Evidence for subcomplexes in the Fanconi anemia pathway. Medhurst, A.L., Laghmani, e.l. .H., Steltenpool, J., Ferrer, M., Fontaine, C., de Groot, J., Rooimans, M.A., Scheper, R.J., Meetei, A.R., Wang, W., Joenje, H., de Winter, J.P. Blood (2006) [Pubmed]
  7. Drosophila homologs of FANCD2 and FANCL function in DNA repair. Marek, L.R., Bale, A.E. DNA Repair (Amst.) (2006) [Pubmed]
  8. Mouse GGN1 and GGN3, two germ cell-specific proteins from the single gene Ggn, interact with mouse POG and play a role in spermatogenesis. Lu, B., Bishop, C.E. J. Biol. Chem. (2003) [Pubmed]
  9. FANCL replaces BRCA1 as the likely ubiquitin ligase responsible for FANCD2 monoubiquitination. Meetei, A.R., Yan, Z., Wang, W. Cell Cycle (2004) [Pubmed]
  10. Late onset of spermatogenesis and gain of fertility in POG-deficient mice indicate that POG is not necessary for the proliferation of spermatogonia. Lu, B., Bishop, C.E. Biol. Reprod. (2003) [Pubmed]
  11. The WD40 Repeats of FANCL Are Required for Fanconi Anemia Core Complex Assembly. Gurtan, A.M., Stuckert, P., D'Andrea, A.D. J. Biol. Chem. (2006) [Pubmed]
  12. Monoclonal antibody PHF-9 recognizes phosphorylated serine 404 of tau protein and labels paired helical filaments. Zemlan, F.P., Dean, G.E. J. Neurosci. Res. (1996) [Pubmed]
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