Fancl Fanconi anemia, complementation group L [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Fanclprovided by MGI
Official Full Name: Fanconi anemia, complementation group Lprovided by MGI
Primary source: MGI:MGI:1914280
See related: Ensembl:ENSMUSG00000004018 AllianceGenome:MGI:1914280
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Pog; gcd; Phf9; 2010322C19Rik; B230118H11Rik
Summary: This gene encodes the complementation group L subunit of the multimeric Fanconi anemia (FA) nuclear complex composed of proteins encoded by over ten Fanconi anemia complementation (FANC) group genes. The FA complex is necessary for protection against DNA damage. This gene product, an E3 ubiquitin ligase, catalyzes and is required for the monoubiquitination of the protein encoded by the Fanconi anemia, complementation group D2 gene, a critical step in the FA pathway (PMID: 12973351, 21229326). In mouse, mutations of this E3 ubiquitin ligase gene can lead to infertility in adult males and females, and a deletion of this gene can cause embryonic lethality in some genetic backgrounds. A pseudogene of this gene has been identified on chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]
Expression: Ubiquitous expression in liver E14 (RPKM 7.9), CNS E11.5 (RPKM 7.5) and 26 other tissues See more
Orthologs: human all
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Genomic context

Location:: 11 A3.3; 11 15.85 cM

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	11	NC_000077.7 (26337084..26421883)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	11	NC_000077.6 (26387084..26471883)

Chromosome 11 - NC_000077.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The authors report the structure of the human FANCL central domain and show that the RING domain is necessary and sufficient for E2 binding.
Title: Structural analysis of human FANCL, the E3 ligase in the Fanconi anemia pathway.
Using HeLa cells and lymphoblasts from Fanconi anemia patients, the authors characterize PHF9 (FANCL) as a ubiquitin ligase and show it is essential for FANCD2 monoubiquitination. The authors state that PHF9 is the human homolog of mouse Pog (Fancl).
Title: MSA-35: a protein identified by human autoantibodies that colocalizes with microtubules.
FANCL increases the activity and expression of beta-catenin, a key pluripotency factor in hematopoietic stem cells.
Title: FANCL ubiquitinates β-catenin and enhances its nuclear function.
UBE2W regulates FANCD2 monoubiquitination by mechanisms different from UBE2T and HRR6.
Title: UBE2W interacts with FANCL and regulates the monoubiquitination of Fanconi anemia protein FANCD2.
Fancl is associated with acute lung injury
Title: Haplotype association mapping of acute lung injury in mice implicates activin a receptor, type 1.
expression of a novel splice variant of FA complementation group L (FANCL), named FAVL, can impair the FA pathway in non-FA tumor cells and act as a tumor promoting factor
Title: FAVL elevation in human tumors disrupts Fanconi anemia pathway signaling and promotes genomic instability and tumor growth.
GGN1 and GGN3, interacted with POG, regulated the localization of POG, and played a role in spermatogenesis.
Title: Mouse GGN1 and GGN3, two germ cell-specific proteins from the single gene Ggn, interact with mouse POG and play a role in spermatogenesis.
unlike in POG-deficient females, the germ cells in POG-deficient males eventually populate the seminiferous tubules at 9 wk, and fertility can be achieved by 12 wk.
Title: Late onset of spermatogenesis and gain of fertility in POG-deficient mice indicate that POG is not necessary for the proliferation of spermatogonia.
Germ cell depletion 2 (gcd2) is a chemically induced recessive mutation that causes infertility in male and female mice.
Title: The mouse gcd2 mutation causes primordial germ cell depletion.
Deletion of Pog causes germ cell deficiency, but is also accompanied by reduced embryonic body weight and sometimes lethality.
Title: A novel gene, Pog, is necessary for primordial germ cell proliferation in the mouse and underlies the germ cell deficient mutation, gcd.

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Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (1) 1 citation
Targeted (2) 1 citation
Transgenic (1) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AW554273 (e-PCR)
- UniSTS:185866

AI447698 (e-PCR)
- UniSTS:160076

AI854003 (e-PCR)
- UniSTS:180166

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin protein ligase activity	IBA Inferred from Biological aspect of Ancestor more info
enables ubiquitin protein ligase activity	IDA Inferred from Direct Assay more info	PubMed
enables ubiquitin protein ligase activity	ISO Inferred from Sequence Orthology more info
enables ubiquitin protein ligase binding	IEA Inferred from Electronic Annotation more info
enables ubiquitin protein ligase binding	ISO Inferred from Sequence Orthology more info
enables ubiquitin-protein transferase activity	IDA Inferred from Direct Assay more info	PubMed
enables ubiquitin-protein transferase activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in DNA damage response	ISO Inferred from Sequence Orthology more info
involved_in DNA damage response	ISS Inferred from Sequence or Structural Similarity more info
involved_in DNA repair	IBA Inferred from Biological aspect of Ancestor more info
involved_in DNA repair	ISO Inferred from Sequence Orthology more info
involved_in DNA repair	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within gamete generation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in interstrand cross-link repair	IEA Inferred from Electronic Annotation more info
involved_in protein monoubiquitination	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein monoubiquitination	ISO Inferred from Sequence Orthology more info
involved_in protein monoubiquitination	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
part_of Fanconi anaemia nuclear complex	ISO Inferred from Sequence Orthology more info
part_of Fanconi anaemia nuclear complex	ISS Inferred from Sequence or Structural Similarity more info
located_in chromatin	IEA Inferred from Electronic Annotation more info
located_in chromatin	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in intracellular membrane-bounded organelle	ISO Inferred from Sequence Orthology more info
located_in nuclear body	IEA Inferred from Electronic Annotation more info
located_in nuclear body	ISO Inferred from Sequence Orthology more info
located_in nuclear envelope	IPI Inferred from Physical Interaction more info	PubMed
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IPI Inferred from Physical Interaction more info	PubMed

General protein information

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Preferred Names: E3 ubiquitin-protein ligase FANCL

Names: PHD finger protein 9; RING-type E3 ubiquitin transferase FANCL; fanconi anemia group L protein homolog; germ cell deficient; proliferation of germ cells protein

NP_001264202.1

EC 2.3.2.27

NP_080199.1

EC 2.3.2.27

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001277273.1 → NP_001264202.1 E3 ubiquitin-protein ligase FANCL isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame acceptor splice site in the coding region compared to variant 1. It encodes isoform 2 which is shorter compared to isoform 1.

Source sequence(s)

AA476004, AF513619, AI854815, AK011903, AW554273

Consensus CDS

CCDS70152.1

UniProtKB/Swiss-Prot

Q9CR14

Related

ENSMUSP00000105135.2, ENSMUST00000109509.8

Conserved Domains (2) summary

pfam09765
Location:15 → 290

WD-3; WD-repeat region

pfam11793
Location:298 → 366

FANCL_C; FANCL C-terminal domain
NM_025923.3 → NP_080199.1 E3 ubiquitin-protein ligase FANCL isoform 1

See identical proteins and their annotated locations for NP_080199.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (1).

Source sequence(s)

AF513619, AI854815

Consensus CDS

CCDS24485.1

UniProtKB/Swiss-Prot

Q3TGY2, Q9CR14, Q9D017

Related

ENSMUSP00000004120.3, ENSMUST00000004120.9

Conserved Domains (2) summary

pfam09765
Location:15 → 295

WD-3; WD-repeat region

pfam11793
Location:303 → 371

FANCL_C; FANCL C-terminal domain

RNA

NR_102382.1 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks two alternate internal exons compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AF513619, AI854815, AW554273, CN455644