FunctionRequired 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.
Tissue specificityHighly 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 diseaseDefects 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.
Developmental stageHighly expressed in fetal oocytes, and in hematopoietic cells of the fetal liver and bone marrow (at protein level).
DomainThe C-terminal 24 residues of isoform 2 are required for its function.
Post-translational modificationsMonoubiquitinated 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.
Cellular localizationNucleus. Concentrates in nuclear foci during S phase and upon genotoxic stress.
Immunofluorescence analysis using a 1/200 dilution of ab81768. FANCD2 colocalizes in vivo with another protein in SiHa cells after cell exposure to IR. Proliferating SiHa cells were exposed to 10 Gy of IR and double color immunofluorescence staining was performed after 8 h. Images were captured in a Kodak digital image system on a Leica fluorescence microscope.
Immunfluorescence analysis using a 1/200 dilution of ab81768. FANCD2 colocalizes in vivo with another protein in U2OS cells after cell exposure to IR. Proliferating U2OS cells were exposed to 10 Gy of IR and double color immunofluorescence staining was performed after 8 h. Images were captured in a Kodak digital image system on a Leica fluorescence microscope.
Western blot - FANCD2 antibody (Biotin) (ab81768)
Anti-FANCD2 antibody (Biotin) (ab81768) at 1/10000 dilution + HeLa whole cell extract
Predicted band size : 166 kDa Observed band size : 166 kDa Additional bands at : 150 kDa,<50 kDa. We are unsure as to the identity of these extra bands.
References for Anti-FANCD2 antibody (Biotin) (ab81768)
has not yet been referenced specifically in any publications.
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