UniProt functional annotation for Q80V62



	UniProt functional annotation for Q80V62

UniProt code: Q80V62.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

Function: Required for maintenance of chromosomal stability. Promotes accurate and efficient pairing of homologs during meiosis. Involved in the repair of DNA double-strand breaks, both by homologous recombination and single-strand annealing. May participate in S phase and G2 phase checkpoint activation upon DNA damage. Plays a role in preventing breakage and loss of missegregating chromatin at the end of cell division, particularly after replication stress (By similarity). Promotes BRCA2/FANCD1 loading onto damaged chromatin. May also be involved in B-cell immunoglobulin isotype switching. {ECO:0000250, ECO:0000269|PubMed:12893777}.

Subunit: Interacts directly with FANCE and FANCI. Interacts with USP1 and MEN1. The ubiquitinated form specifically interacts with BRCA1 and BLM. Both the nonubiquitinated and the monoubiquitinated forms interact with BRCA2; this interaction is mediated by phosphorylated FANCG and the complex also includes XCCR3. The ubiquitinated form specifically interacts with MTMR15/FAN1 (via UBZ-type zinc finger), leading to recruit MTMR15/FAN1 to sites of DNA damage. Interacts with DCLRE1B/Apollo. Interacts with POLN. {ECO:0000250|UniProtKB:Q9BXW9}.

Subcellular location: Nucleus {ECO:0000250}. Note=Concentrates in nuclear foci during S phase and upon genotoxic stress. {ECO:0000250}.

Ptm: Monoubiquitinated on Lys-559 during S phase and upon genotoxic stress by FANCL in complex with E2 ligases UBE2T or UBE2W. Deubiquitinated by USP1 as cells enter G2/M, or once DNA repair is completed. Monoubiquitination requires the joint intervention of the FANC core complex, including FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL and FANCM, and proteins involved in cell cycle checkpoints and DNA repair, including RPA1, ATR, CHEK1 and BRCA1. Ubiquitination is required for binding to chromatin, interaction with BRCA1, BRCA2 and MTMR15/FAN1, DNA repair, and normal cell cycle progression (By similarity). {ECO:0000250}.

Ptm: Phosphorylated on several sites including Ser-220 and Ser-1399 in response to genotoxic stress. {ECO:0000250}.

Disruption phenotype: Mice display delayed pre- and postnatal development, defects in germ-cell development, and increase incidence of microphthalmia and tumors of epithelial cell origin. {ECO:0000269|PubMed:12893777}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



Function:		Required for maintenance of chromosomal stability. Promotes accurate and efficient pairing of homologs during meiosis. Involved in the repair of DNA double-strand breaks, both by homologous recombination and single-strand annealing. May participate in S phase and G2 phase checkpoint activation upon DNA damage. Plays a role in preventing breakage and loss of missegregating chromatin at the end of cell division, particularly after replication stress (By similarity). Promotes BRCA2/FANCD1 loading onto damaged chromatin. May also be involved in B-cell immunoglobulin isotype switching. {ECO:0000250, ECO:0000269\|PubMed:12893777}.


Subunit:		Interacts directly with FANCE and FANCI. Interacts with USP1 and MEN1. The ubiquitinated form specifically interacts with BRCA1 and BLM. Both the nonubiquitinated and the monoubiquitinated forms interact with BRCA2; this interaction is mediated by phosphorylated FANCG and the complex also includes XCCR3. The ubiquitinated form specifically interacts with MTMR15/FAN1 (via UBZ-type zinc finger), leading to recruit MTMR15/FAN1 to sites of DNA damage. Interacts with DCLRE1B/Apollo. Interacts with POLN. {ECO:0000250\|UniProtKB:Q9BXW9}.
Subcellular location:		Nucleus {ECO:0000250}. Note=Concentrates in nuclear foci during S phase and upon genotoxic stress. {ECO:0000250}.
Ptm:		Monoubiquitinated on Lys-559 during S phase and upon genotoxic stress by FANCL in complex with E2 ligases UBE2T or UBE2W. Deubiquitinated by USP1 as cells enter G2/M, or once DNA repair is completed. Monoubiquitination requires the joint intervention of the FANC core complex, including FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL and FANCM, and proteins involved in cell cycle checkpoints and DNA repair, including RPA1, ATR, CHEK1 and BRCA1. Ubiquitination is required for binding to chromatin, interaction with BRCA1, BRCA2 and MTMR15/FAN1, DNA repair, and normal cell cycle progression (By similarity). {ECO:0000250}.
Ptm:		Phosphorylated on several sites including Ser-220 and Ser-1399 in response to genotoxic stress. {ECO:0000250}.
Disruption phenotype:		Mice display delayed pre- and postnatal development, defects in germ-cell development, and increase incidence of microphthalmia and tumors of epithelial cell origin. {ECO:0000269\|PubMed:12893777}.