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Rabbit Anti-phospho-FANCD2 (Ser222)  antibody (bs-3015R)  
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產(chǎn)品編號 bs-3015R
英文名稱 Rabbit Anti-phospho-FANCD2 (Ser222)  antibody
中文名稱 磷酸化FANCD2抗體
別    名 FANCD2 (phospho S222); FANCD2 (phospho Ser222); p-FANCD2 (phospho S222); FA 4; FA D2; FA4; FAC D2; FACD 2; FACD; FACD2; FAD; FAD2; FANC D2; FANCD 2; FANCD; Protein FACD2; Type 4 Fanconi pancytopenia; FACD2_HUMAN; Fanconi anemia group D2 protein; Protein FACD2.  
產(chǎn)品類型 磷酸化抗體 
研究領(lǐng)域 腫瘤  染色質(zhì)和核信號  轉(zhuǎn)錄調(diào)節(jié)因子  
抗體來源 Rabbit
克隆類型 Polyclonal
交叉反應(yīng) Human (predicted: Mouse,Rat,Pig,Cow,Dog)
產(chǎn)品應(yīng)用 WB=1:500-2000,IHC-P=1:100-500,IHC-F=1:100-500,IF=1:100-500,ELISA=1:5000-10000
not yet tested in other applications.
optimal dilutions/concentrations should be determined by the end user.
理論分子量 162kDa
細胞定位 細胞核 
性    狀 Liquid
濃    度 1mg/ml
免 疫 原 KLH conjugated Synthesised phosphopeptide derived from human FANCD2 around the phosphorylation site of Ser222: GD(p-S)QH 
亞    型 IgG
純化方法 affinity purified by Protein A
緩 沖 液 0.01M TBS (pH7.4) with 1% BSA, 0.02% Proclin300 and 50% Glycerol.
保存條件 Shipped at 4℃. Store at -20℃ for one year. Avoid repeated freeze/thaw cycles.
注意事項 This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
PubMed PubMed
產(chǎn)品介紹 Fanconi Anemia (FANC) is a human autosomal-recessive cancer susceptibility disorder characterized by congenital defects, progressive bone marrow failure, and cellular hypersensitivity to mitomycin C (MMC). The FANC subunit D2 protein is vital for cellular resistance to DNA cross-linking and the arrest of DNA synthesis after ionizing radiation. DNA damage activates the monoubiquitination of FANC D2, targeting nuclear foci containing the BRCA 1 protein.

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.

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.

Subcellular Location:
Nucleus. Note=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.

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.

Post-translational modifications:
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.
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.
Defects in FANCD2 are a cause of Fanconi anemia complementation group D type 2 (FANCD2) [MIM:227646]. 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.

SWISS:
Q9BXW9

Gene ID:
2177

Database links:

Entrez Gene: 2177 Human

Entrez Gene: 211651 Mouse

Entrez Gene: 312641 Rat

Omim: 613984 Human

SwissProt: Q9BXW9 Human

SwissProt: Q80V62 Mouse

SwissProt: Q6IV68 Rat

Unigene: 208388 Human

Unigene: 160061 Mouse

Unigene: 203979 Rat



    FANCD2是一種在DNA損傷修復(fù)過程中起重要作用的蛋白質(zhì),其作作用在于通過修補DNA損傷或促進有缺陷細胞自殺來預(yù)防癌癥,所以低水平的FANCD2會導致DNA損傷,從而誘發(fā)癌癥。
    有學者認為:FANCD2是個重要的抵御癌癥蛋白,而香煙會破壞它的制造過程當然還可能包含有其他蛋白,但至少FANCD2是關(guān)鍵的主要蛋白,因為含有非常高水平FANCD2的細胞能夠抵御香煙的毒害作用。
    FANCD2蛋白在保護肺細胞抵御香煙威脅時有重要作用;FANCD2蛋白是負責修復(fù)受損DNA的重要蛋白,而受香煙燃燒產(chǎn)生的煙霧影響的肺細胞很少產(chǎn)生FANCD2蛋白,沒有FANCD2蛋白,受損的DNA導致腫瘤細胞增殖擴散并無法控制。研究結(jié)果表明,F(xiàn)ANCD2蛋白在保護肺細胞抵御香煙威脅時有重要作用,也可解釋為什麼香煙燃燒產(chǎn)生的煙霧對肺細胞具有如此大的危害。  
產(chǎn)品圖片
Tissue/cell: human gastric carcinoma; 4% Paraformaldehyde-fixed and paraffin-embedded; Antigen retrieval: citrate buffer ( 0.01M, pH 6.0 ), Boiling bathing for 15min; Block endogenous peroxidase by 3% Hydrogen peroxide for 30min; Blocking buffer (normal goat serum,C-0005) at 37℃ for 20 min; Incubation: Anti-phospho-FANCD2(Ser222) Polyclonal Antibody, Unconjugated(bs-3015R) 1:200, overnight at 4°C, followed by conjugation to the secondary antibody(SP-0023) and DAB(C-0010) staining
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