Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10330)
Regulator Name Fanconi anemia group D2 protein (FANCD2)
Synonyms
FACD
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Gene Name FANCD2
Gene ID 2177
Regulator Type Protein coding
Uniprot ID Q9BXW9
Sequence
MVSKRRLSKSEDKESLTEDASKTRKQPLSKKTKKSHIANEVEENDSIFVKLLKISGIILK
TGESQNQLAVDQIAFQKKLFQTLRRHPSYPKIIEEFVSGLESYIEDEDSFRNCLLSCERL
QDEEASMGASYSKSLIKLLLGIDILQPAIIKTLFEKLPEYFFENKNSDEINIPRLIVSQL
KWLDRVVDGKDLTTKIMQLISIAPENLQHDIITSLPEILGDSQHADVGKELSDLLIENTS
LTVPILDVLSSLRLDPNFLLKVRQLVMDKLSSIRLEDLPVIIKFILHSVTAMDTLEVISE
LREKLDLQHCVLPSRLQASQVKLKSKGRASSSGNQESSGQSCIILLFDVIKSAIRYEKTI
SEAWIKAIENTASVSEHKVFDLVMLFIIYSTNTQTKKYIDRVLRNKIRSGCIQEQLLQST
FSVHYLVLKDMCSSILSLAQSLLHSLDQSIISFGSLLYKYAFKFFDTYCQQEVVGALVTH
ICSGNEAEVDTALDVLLELVVLNPSAMMMNAVFVKGILDYLDNISPQQIRKLFYVLSTLA
FSKQNEASSHIQDDMHLVIRKQLSSTVFKYKLIGIIGAVTMAGIMAADRSESPSLTQERA
NLSDEQCTQVTSLLQLVHSCSEQSPQASALYYDEFANLIQHEKLDPKALEWVGHTICNDF
QDAFVVDSCVVPEGDFPFPVKALYGLEEYDTQDGIAINLLPLLFSQDFAKDGGPVTSQES
GQKLVSPLCLAPYFRLLRLCVERQHNGNLEEIDGLLDCPIFLTDLEPGEKLESMSAKERS
FMCSLIFLTLNWFREIVNAFCQETSPEMKGKVLTRLKHIVELQIILEKYLAVTPDYVPPL
GNFDVETLDITPHTVTAISAKIRKKGKIERKQKTDGSKTSSSDTLSEEKNSECDPTPSHR
GQLNKEFTGKEEKTSLLLHNSHAFFRELDIEVFSILHCGLVTKFILDTEMHTEATEVVQL
GPPELLFLLEDLSQKLESMLTPPIARRVPFLKNKGSRNIGFSHLQQRSAQEIVHCVFQLL
TPMCNHLENIHNYFQCLAAENHGVVDGPGVKVQEYHIMSSCYQRLLQIFHGLFAWSGFSQ
PENQNLLYSALHVLSSRLKQGEHSQPLEELLSQSVHYLQNFHQSIPSFQCALYLIRLLMV
ILEKSTASAQNKEKIASLARQFLCRVWPSGDKEKSNISNDQLHALLCIYLEHTESILKAI
EEIAGVGVPELINSPKDASSSTFPTLTRHTFVVFFRVMMAELEKTVKKIEPGTAADSQQI
HEEKLLYWNMAVRDFSILINLIKVFDSHPVLHVCLKYGRLFVEAFLKQCMPLLDFSFRKH
REDVLSLLETFQLDTRLLHHLCGHSKIHQDTRLTQHVPLLKKTLELLVCRVKAMLTLNNC
REAFWLGNLKNRDLQGEEIKSQNSQESTADESEDDMSSQASKSKATEDGEEDEVSAGEKE
QDSDESYDDSD

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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.

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HGNC ID
HGNC:3585
KEGG ID hsa:2177
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
FANCD2 can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
Browse Target
Browse Disease
Transferrin receptor protein 1 (TFRC) [Driver; Suppressor; Marker]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Marker/Suppressor/Driver
Responsed Disease Bone marrow injury ICD-11: PK81
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 mBMSCs (Mouse bone marrow stromal cells)
Response regulation Bone marrow injury remains a serious concern in traditional cancer treatment. FANCD2 regulated genes and/or expression of proteins involved in iron metabolism (e.g., FTH1, TF, TFRC, HAMP, HSPB1, SLC40A1, and STEAP3) and lipid peroxidation (e.g., GPX4).
Heat shock protein beta-1 (HSPB1) [Suppressor; Marker]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Bone marrow injury ICD-11: PK81
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 mBMSCs (Mouse bone marrow stromal cells)
Response regulation Bone marrow injury remains a serious concern in traditional cancer treatment. FANCD2 regulated genes and/or expression of proteins involved in iron metabolism (e.g., FTH1, TF, TFRC, HAMP, HSPB1, SLC40A1, and STEAP3) and lipid peroxidation (e.g., GPX4).
Ferritin heavy chain (FTH1) [Suppressor; Marker]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Bone marrow injury ICD-11: PK81
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 mBMSCs (Mouse bone marrow stromal cells)
Response regulation Bone marrow injury remains a serious concern in traditional cancer treatment. FANCD2 regulated genes and/or expression of proteins involved in iron metabolism (e.g., FTH1, TF, TFRC, HAMP, HSPB1, SLC40A1, and STEAP3) and lipid peroxidation (e.g., GPX4).
Unspecific Target [Unspecific Target]
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [2]
Responsed Disease Glioblastoma ICD-11: 2A00
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
Cell migration
Cell invasion
In Vitro Model
 U87 MG-Red-Fluc cells Glioblastoma Homo sapiens CVCL_5J12
U-251MG cells Astrocytoma Homo sapiens CVCL_0021
In Vivo Model
In this study, 4-week-old specific pathogen free male nude mice were selected and assigned into 4 groups, each of which was respectively injected with U251 cells and U87 cells transfected with NC, hsa-miR-27a-3p angomir, si-TMEM161B-AS1, si-TMEM161B-AS1 + hsa-miR-27a-3p angomir. Each nude mouse was subcutaneously injected with 4 x 105 cells in the right flank area for subcutaneous implantation.

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Response regulation Knockdown of TMEM161B-AS1 down-regulated the expression of FANCD2 and CD44 by sponging hsa-miR-27a-3p, inhibited the proliferation, migration, invasion and promoted apoptosis, ferroptosis of glioma U87 cells and U251 cells. These findings were expected to provide promising therapeutic targets for the treatment of glioma.
Experiment 2 Reporting the Ferroptosis Target of This Regulator [3]
Responsed Disease Osteosarcoma ICD-11: 2B51
 Disease Info 
Pathway Response JAK-STAT signaling pathway hsa04630
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 MG-63 cells Osteosarcoma Homo sapiens CVCL_0426
U2OS cells Osteosarcoma Homo sapiens CVCL_0042
hFOB 1.19 cells Normal Homo sapiens CVCL_3708
In Vivo Model
Thirty BALB/c nude mice (20~22 g, five weeks) were SiPeiFu Biotechnology Co., Ltd. (Beijing, China). Animal experiment was conducted in accordance with China Animal Welfare Legislation and was approved by the Ethics Committee of our hospital. U2OS cells (1 x 106 cells) were subcutaneously injected into mice to establish osteosarcoma mice models. The mice were randomized into Lv-si-NC and Lv-si-FANCD2 groups (n = 6). After modeling, lentivirus-packaged si-FANCD2-1 and si-NC were locally injected into tumor tissues of mice in the Lv-si-FANCD2 and Lv-si-NC groups, respectively. They were euthanized by intraperitoneal injection of sodium pentobarbital (50 mg/kg) after 28 days, the tumor tissues were collected and weight was measured.

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Response regulation FANCD2 silencing could suppress osteosarcoma cell viability, migration, invasion, and tumor growth, and induced ferroptosis by regulating the JAK2/STAT3 axis.
Bone marrow injury [ICD-11: PK81]
 Disease Info 
In total 3 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Fanconi anemia group D2 protein (FANCD2) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 mBMSCs (Mouse bone marrow stromal cells)
Response regulation Bone marrow injury remains a serious concern in traditional cancer treatment. FANCD2 regulated genes and/or expression of proteins involved in iron metabolism (e.g., FTH1, TF, TFRC, HAMP, HSPB1, SLC40A1, and STEAP3) and lipid peroxidation (e.g., GPX4).
Experiment 2 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Fanconi anemia group D2 protein (FANCD2) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 mBMSCs (Mouse bone marrow stromal cells)
Response regulation Bone marrow injury remains a serious concern in traditional cancer treatment. FANCD2 regulated genes and/or expression of proteins involved in iron metabolism (e.g., FTH1, TF, TFRC, HAMP, HSPB1, SLC40A1, and STEAP3) and lipid peroxidation (e.g., GPX4).
Experiment 3 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Fanconi anemia group D2 protein (FANCD2) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 mBMSCs (Mouse bone marrow stromal cells)
Response regulation Bone marrow injury remains a serious concern in traditional cancer treatment. FANCD2 regulated genes and/or expression of proteins involved in iron metabolism (e.g., FTH1, TF, TFRC, HAMP, HSPB1, SLC40A1, and STEAP3) and lipid peroxidation (e.g., GPX4).
Glioblastoma [ICD-11: 2A00]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Fanconi anemia group D2 protein (FANCD2) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
Cell migration
Cell invasion
In Vitro Model
 U87 MG-Red-Fluc cells Glioblastoma Homo sapiens CVCL_5J12
U-251MG cells Astrocytoma Homo sapiens CVCL_0021
In Vivo Model
In this study, 4-week-old specific pathogen free male nude mice were selected and assigned into 4 groups, each of which was respectively injected with U251 cells and U87 cells transfected with NC, hsa-miR-27a-3p angomir, si-TMEM161B-AS1, si-TMEM161B-AS1 + hsa-miR-27a-3p angomir. Each nude mouse was subcutaneously injected with 4 x 105 cells in the right flank area for subcutaneous implantation.

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Response regulation Knockdown of TMEM161B-AS1 down-regulated the expression of FANCD2 and CD44 by sponging hsa-miR-27a-3p, inhibited the proliferation, migration, invasion and promoted apoptosis, ferroptosis of glioma U87 cells and U251 cells. These findings were expected to provide promising therapeutic targets for the treatment of glioma.
Osteosarcoma [ICD-11: 2B51]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [3]
Target Regulator Fanconi anemia group D2 protein (FANCD2) Protein coding
 Regulator Info 
Pathway Response JAK-STAT signaling pathway hsa04630
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 MG-63 cells Osteosarcoma Homo sapiens CVCL_0426
U2OS cells Osteosarcoma Homo sapiens CVCL_0042
hFOB 1.19 cells Normal Homo sapiens CVCL_3708
In Vivo Model
Thirty BALB/c nude mice (20~22 g, five weeks) were SiPeiFu Biotechnology Co., Ltd. (Beijing, China). Animal experiment was conducted in accordance with China Animal Welfare Legislation and was approved by the Ethics Committee of our hospital. U2OS cells (1 x 106 cells) were subcutaneously injected into mice to establish osteosarcoma mice models. The mice were randomized into Lv-si-NC and Lv-si-FANCD2 groups (n = 6). After modeling, lentivirus-packaged si-FANCD2-1 and si-NC were locally injected into tumor tissues of mice in the Lv-si-FANCD2 and Lv-si-NC groups, respectively. They were euthanized by intraperitoneal injection of sodium pentobarbital (50 mg/kg) after 28 days, the tumor tissues were collected and weight was measured.

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Response regulation FANCD2 silencing could suppress osteosarcoma cell viability, migration, invasion, and tumor growth, and induced ferroptosis by regulating the JAK2/STAT3 axis.
References
Ref 1 FANCD2 protects against bone marrow injury from ferroptosis. Biochem Biophys Res Commun. 2016 Nov 18;480(3):443-449. doi: 10.1016/j.bbrc.2016.10.068. Epub 2016 Oct 20.
Ref 2 Over-expression of lncRNA TMEM161B-AS1 promotes the malignant biological behavior of glioma cells and the resistance to temozolomide via up-regulating the expression of multiple ferroptosis-related genes by sponging hsa-miR-27a-3p. Cell Death Discov. 2021 Oct 23;7(1):311. doi: 10.1038/s41420-021-00709-4.
Ref 3 FANCD2 inhibits ferroptosis by regulating the JAK2/STAT3 pathway in osteosarcoma. BMC Cancer. 2023 Feb 22;23(1):179. doi: 10.1186/s12885-023-10626-7.