Human Gene FANCL (ENST00000233741.9) from GENCODE V44
Description: Homo sapiens FA complementation group L (FANCL), transcript variant 2, mRNA. (from RefSeq NM_018062) RefSeq Summary (NM_018062): This gene encodes a ubiquitin ligase that is a member of the Fanconi anemia complementation group (FANC). Members of this group are related by their assembly into a common nuclear protein complex rather than by sequence similarity. This gene encodes the protein for complementation group L that mediates monoubiquitination of FANCD2 as well as FANCI. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2018]. Gencode Transcript: ENST00000233741.9 Gencode Gene: ENSG00000115392.13 Transcript (Including UTRs) Position: hg38 chr2:58,159,247-58,241,325 Size: 82,079 Total Exon Count: 14 Strand: - Coding Region Position: hg38 chr2:58,159,765-58,241,313 Size: 81,549 Coding Exon Count: 14
ID:FANCL_HUMAN DESCRIPTION: RecName: Full=E3 ubiquitin-protein ligase FANCL; EC=6.3.2.-; AltName: Full=Fanconi anemia group L protein; AltName: Full=Fanconi anemia-associated polypeptide of 43 kDa; Short=FAAP43; FUNCTION: Ubiquitin ligase protein that mediates monoubiquitination of FANCD2, a key step in the DNA damage pathway. Also mediates monoubiquitination of FANCI. May stimulate the ubiquitin release from UBE2W. 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. In complex with FANCF, FANCA and FANCG, but not with FANCC, nor FANCE, interacts with HES1; this interaction may be essential for the stability and nuclear localization of FA core complex proteins. Interacts with FANCI. Interacts (via the RING- type zinc finger) with UBE2T and UBE2W. SUBCELLULAR LOCATION: Cytoplasm. Nucleus. DOMAIN: The UBC-RWD region (URD) region mediates interaction with FANCI and FANCD2 (PubMed:21775430). PTM: The RING-type zinc finger domain is monoubiquitinated in the presence of UBE2T and UBE2W. DISEASE: Defects in FANCL are the cause of Fanconi anemia complementation group L (FANCL) [MIM:614083]. FANCL is a disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, 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.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/FANCL";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9NW38
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
AK225147 - Homo sapiens mRNA for Fanconi anemia, complementation group L variant, clone: CBL06036. BC037570 - Homo sapiens Fanconi anemia, complementation group L, mRNA (cDNA clone IMAGE:5242176), with apparent retained intron. BC009042 - Homo sapiens Fanconi anemia, complementation group L, mRNA (cDNA clone MGC:8831 IMAGE:3870828), complete cds. BC041627 - Homo sapiens Fanconi anemia, complementation group L, mRNA (cDNA clone IMAGE:4552098), with apparent retained intron. BC054517 - Homo sapiens Fanconi anemia, complementation group L, mRNA (cDNA clone MGC:60295 IMAGE:5180184), complete cds. AK001197 - Homo sapiens cDNA FLJ10335 fis, clone NT2RM2000669. AK309671 - Homo sapiens cDNA, FLJ99712. AK297736 - Homo sapiens cDNA FLJ51649 complete cds, highly similar to Ubiquitin ligase protein FANCL (EC 6.3.2.-). CU691100 - Synthetic construct Homo sapiens gateway clone IMAGE:100021418 5' read FANCL mRNA. JD344607 - Sequence 325631 from Patent EP1572962. JD538519 - Sequence 519543 from Patent EP1572962.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa04120 - Ubiquitin mediated proteolysis
Reactome (by CSHL, EBI, and GO)
Protein Q9NW38 (Reactome details) participates in the following event(s):
R-HSA-6785126 FA core complex assembles at DNA interstrand crosslinks (ICLs) R-HSA-6786155 POLN binds ICL-DNA R-HSA-6785342 FANCD2:FANCI complex and UBE2T bind ICL-DNA associated with the FA core complex R-HSA-6786171 FANCD2 deubiquitination by USP1:WDR48 R-HSA-6788385 The complex of ATR and ATRIP is recruited to ICL-DNA R-HSA-6785732 DNA nucleases bind monoubiquitinated ID2 complex R-HSA-6785361 Monoubiquitination of FANCD2:FANCI R-HSA-6788392 ATR phosphorylates RPA2, FANCI, FANCD2 and FANCM at ICL-DNA R-HSA-6783310 Fanconi Anemia Pathway R-HSA-73894 DNA Repair
US Server
