功能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. Promotes BRCA2/FANCD1 loading onto damaged chromatin. May also be involved in B-cell immunoglobulin isotype switching.
组织特异性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.
疾病相关Defects in FANCD2 are a cause of Fanconi anemia complementation group D type 2 (FANCD2) [MIM:227646]. It 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.
发展阶段Highly expressed in fetal oocytes, and in hematopoietic cells of the fetal liver and bone marrow (at protein level).
结构域The C-terminal 24 residues of isoform 2 are required for its function.
翻译后修饰Monoubiquitinated on Lys-561 during S phase and upon genotoxic stress (isoform 1 and isoform 2). Deubiquitinated by USP1 as cells enter G2/M, or once DNA repair is completed. Monoubiquitination requires the FANCA-FANCB-FANCC-FANCE-FANCF-FANCG-FANCM complex, RPA1 and ATR, 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. Phosphorylated in response to various genotoxic stresses by ATM and/or ATR. Upon ionizing radiation, phosphorylated by ATM on Ser-222 and Ser-1404. Phosphorylation on Ser-222 is required for S-phase checkpoint activation, but not for ubiquitination, foci formation, or DNA repair. In contrast, phosphorylation by ATR on other sites may be required for ubiquitination and foci formation.
细胞定位Nucleus. Concentrates in nuclear foci during S phase and upon genotoxic stress.
Western blot - FANCD2 (phospho S1404) antibody [EPR2278(2)] (ab109542)
All lanes : Anti-FANCD2 (phospho S1404) antibody [EPR2278(2)] (ab109542) at 1/1000 dilution
Lane 1 : HeLa cell lysate, untreated Lane 2 : HeLa cell lysate treated with Alkaline Phosphatase.
Lysates/proteins at 10 µg per lane.
Secondary HRP-labelled goat anti-rabbit at 1/2000 dilution
Predicted band size : 166 kDa
Immunocytochemistry/ Immunofluorescence - Anti-FANCD2 (phospho S1404) antibody [EPR2278(2)] (ab109542)Image courtesy of an Abreview submitted by Dr. Kirk McManus, Univ. of Manitoba/Cancer Care MICB, Canada
ab109542 (1/200) staining FANCD2 (phospho S1404) in HeLa cells (green). Cells were treated with Bleomycin for 2hrs to induce DNA damage, fixed in paraformaldehyde, permeabilized with 0.5% Triton X-100 and counterstained with DAPI in order to highlight the nucleus (red). For further experimental details please refer to Abreview.