FANCL

FANCL
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	3ZQS, 4CCG
Identifiers
Aliases	FANCL, FAAP43, PHF9, POG, Fanconi anemia complementation group L, FA complementation group L
External IDs	OMIM: 608111; MGI: 1914280; HomoloGene: 9987; GeneCards: FANCL; OMA:FANCL - orthologs
Gene location (Human)
Chr.	Chromosome 2 (human)
End	58,241,410 bp
Gene location (Mouse)
Chr.	Chromosome 11 (mouse)
End	26,421,876 bp
RNA expression pattern
	Top expressed in
	pituitary gland; ; anterior pituitary; ; Achilles tendon; ; right adrenal cortex; ; corpus callosum; ; left adrenal cortex; ; C1 segment; ; tibia; ; secondary oocyte; ; right uterine tube;
	Top expressed in
	Paneth cell; ; primitive streak; ; abdominal wall; ; mandibular prominence; ; fetal liver hematopoietic progenitor cell; ; epiblast; ; endocardial cushion; ; maxillary prominence; ; interventricular septum; ; fossa;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	ubiquitin-protein transferase activity; protein binding; metal ion binding; ubiquitin protein ligase binding; ubiquitin protein ligase activity; transferase activity;
Cellular component	cytoplasm; nucleus; nuclear envelope; Fanconi anaemia nuclear complex; nucleoplasm; nuclear body; intracellular membrane-bounded organelle;
Biological process	protein ubiquitination; gamete generation; regulation of cell population proliferation; interstrand cross-link repair; protein monoubiquitination; cellular response to DNA damage stimulus; DNA repair;
	Sources:Amigo / QuickGO
Orthologs
	55120
	67030
	ENSG00000115392
	ENSMUSG00000004018
	Q9NW38
	Q9CR14
	NM_001114636; NM_018062; NM_001374615
	NM_001277273; NM_025923
	NP_001108108; NP_060532; NP_001361544
	NP_001264202; NP_080199
	Wikidata
View/Edit Human	View/Edit Mouse

E3 ubiquitin-protein ligase FANCL is an enzyme that in humans is encoded by the FANCL gene.^[5]

Function

The clinical phenotype of mutational defects in all Fanconi anemia (FA) complementation groups is similar. This phenotype is characterized by progressive bone marrow failure, cancer proneness and typical birth defects.^[13] The main cellular phenotype is hypersensitivity to DNA damage, particularly inter-strand DNA crosslinks.^[14] The FA proteins interact through a multi-protein pathway. DNA interstrand crosslinks are highly deleterious damages that are repaired by homologous recombination involving coordination of FA proteins and breast cancer susceptibility gene 1 (BRCA1).

The Fanconi Anemia (FA) DNA repair pathway is essential for the recognition and repair of DNA interstrand crosslinks (ICL). A critical step in the pathway is the monoubiquitination of FANCD2 by the RING E3 ligase FANCL. FANCL comprises 3 domains, a RING domain that interacts with E2 conjugating enzymes, a central domain required for substrate interaction, and an N-terminal E2-like fold (ELF) domain that interacts with FANCB.^[15] The ELF domain of FANCL is also required to mediate a non-covalent interaction between FANCL and ubiquitin. The ELF domain is required to promote efficient DNA damage-induced FANCD2 monoubiquitination in vertebrate cells, suggesting an important function of FANCB and ubiquitin binding by FANCL in vivo.^[16]

A nuclear complex containing FANCL (as well as FANCA, FANCB, FANCC, FANCE, FANCF, FANCG and FANCM) is essential for the activation of the FANCD2 protein to the mono-ubiquitinated isoform.^[6] In normal, non-mutant, cells FANCD2 is mono-ubiquinated in response to DNA damage. Activated FANCD2 protein co-localizes with BRCA1 (breast cancer susceptibility protein) at ionizing radiation-induced foci and in synaptonemal complexes of meiotic chromosomes (see Figure: Recombinational repair of double strand damage).