| 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. Required for the targeting, or stabilization, of BLM to non-centromeric abnormal structures induced by replicative stress. Promotes BRCA2/FANCD1 loading onto damaged chromatin. May also be involved in B-cell immunoglobulin isotype switching. |
| Tissue Specificity: |
Highly expressed in germinal center cells of the spleen, tonsil, and reactive lymph nodes, and in the proliferating basal layer of squamous epithelium of tonsil, esophagus, oropharynx, larynx and cervix. Expressed in cytotrophoblastic cells of the placenta and exocrine cells of the pancreas (at protein level). Highly expressed in testis, where expression is restricted to maturing spermatocytes. |
| Involvement in Disease: |
Fanconi anemia complementation group D2: 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. |
| Post-Translational Modification: |
Monoubiquitinated on Lys-561 during S phase and upon genotoxic stress by FANCL in complex with E2 ligases UBE2T or UBE2W (isoform 1 and isoform 2). 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, and FANCM, and proteins involved in cell cycle checkpoints and DNA repair, including RPA1, ATR, CHEK1 and BRCA1, and is mediated by FANCL/PHF9. Ubiquitination is required for binding to chromatin, interaction with BRCA1, BRCA2 and MTMR15/FAN1, DNA repair, and normal cell cycle progression, but not for phosphorylation on Ser-222 or interaction with MEN1. |
| Cellular Location: |
Nucleus.
Concentrates in nuclear foci during S phase and upon genotoxic stress. At the onset of mitosis, excluded from chromosomes and diffuses into the cytoplasm, returning to the nucleus at the end of cell division. Observed in a few spots localized in pairs on the sister chromatids of mitotic chromosome arms and not centromeres, one on each chromatids. These foci coincide with common fragile sites and could be sites of replication fork stalling. The foci are frequently interlinked through BLM-associated ultra-fine DNA bridges. Following aphidicolin treatment, targets chromatid gaps and breaks. |
| Database Links: |
Entrez Gene: 2177?HumanEntrez Gene: 211651?MouseEntrez Gene: 312641?RatOmim: 613984?HumanSwissProt: Q9BXW9?HumanSwissProt: Q80V62?MouseSwissProt: Q6IV68?RatUnigene: 208388?HumanUnigene: 160061?MouseUnigene: 203979?Rat |
| Synonyms: |
DKFZp762A223 AntibodyFA 4 AntibodyFA D2 AntibodyFA4 AntibodyFAC D2 AntibodyFACD AntibodyFACD 2 AntibodyFACD2 AntibodyFACD2_HUMAN AntibodyFAD AntibodyFAD2 AntibodyFANC D2 AntibodyFANCD AntibodyFANCD 2 AntibodyFANCD2 AntibodyFANCONI ANEMIA COMPLEMENTATION GROUP D AntibodyFanconi anemia complementation group D2 AntibodyFanconi anemia group D2 protein AntibodyFANCONI PANCYTOPENIA TYPE 4 AntibodyFLJ23826 AntibodyOTTHUMP00000158853 AntibodyOTTHUMP00000207925 AntibodyProtein FACD2 AntibodyType 4 Fanconi pancytopenia Antibody |
| Information: |
Target information shown above is from the UniProt Consortium. |
