Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10317)
Regulator Name Endothelial PAS domain-containing protein 1 (EPAS1)
Synonyms
BHLHE73, HIF2A, MOP2, PASD2; Basic-helix-loop-helix-PAS protein MOP2; Class E basic helix-loop-helix protein 73; HIF-1-alpha-like factor; Hypoxia-inducible factor 2-alpha; Member of PAS protein 2; PAS domain-containing protein 2
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Gene Name EPAS1
Gene ID 2034
Regulator Type Protein coding
Uniprot ID Q99814
Sequence
MTADKEKKRSSSERRKEKSRDAARCRRSKETEVFYELAHELPLPHSVSSHLDKASIMRLA
ISFLRTHKLLSSVCSENESEAEADQQMDNLYLKALEGFIAVVTQDGDMIFLSENISKFMG
LTQVELTGHSIFDFTHPCDHEEIRENLSLKNGSGFGKKSKDMSTERDFFMRMKCTVTNRG
RTVNLKSATWKVLHCTGQVKVYNNCPPHNSLCGYKEPLLSCLIIMCEPIQHPSHMDIPLD
SKTFLSRHSMDMKFTYCDDRITELIGYHPEELLGRSAYEFYHALDSENMTKSHQNLCTKG
QVVSGQYRMLAKHGGYVWLETQGTVIYNPRNLQPQCIMCVNYVLSEIEKNDVVFSMDQTE
SLFKPHLMAMNSIFDSSGKGAVSEKSNFLFTKLKEEPEELAQLAPTPGDAIISLDFGNQN
FEESSAYGKAILPPSQPWATELRSHSTQSEAGSLPAFTVPQAAAPGSTTPSATSSSSSCS
TPNSPEDYYTSLDNDLKIEVIEKLFAMDTEAKDQCSTQTDFNELDLETLAPYIPMDGEDF
QLSPICPEERLLAENPQSTPQHCFSAMTNIFQPLAPVAPHSPFLLDKFQQQLESKKTEPE
HRPMSSIFFDAGSKASLPPCCGQASTPLSSMGGRSNTQWPPDPPLHFGPTKWAVGDQRTE
FLGAAPLGPPVSPPHVSTFKTRSAKGFGARGPDVLSPAMVALSNKLKLKRQLEYEEQAFQ
DLSGGDPPGGSTSHLMWKRMKNLRGGSCPLMPDKPLSANVPNDKFTQNPMRGLGHPLRHL
PLPQPPSAISPGENSKSRFPPQCYATQYQDYSLSSAHKVSGMASRLLGPSFESYLLPELT
RYDCEVNVPVLGSSTLLQGGDLLRALDQAT

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Function
Transcription factor involved in the induction of oxygen regulated genes. Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters. Regulates the vascular endothelial growth factor (VEGF) expression and seems to be implicated in the development of blood vessels and the tubular system of lung. May also play a role in the formation of the endothelium that gives rise to the blood brain barrier. Potent activator of the Tie-2 tyrosine kinase expression. Activation requires recruitment of transcriptional coactivators such as CREBBP and probably EP300. Interaction with redox regulatory protein APEX1 seems to activate CTAD.

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HGNC ID
HGNC:3374
KEGG ID hsa:2034
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
EPAS1 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).
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Cystine/glutamate transporter (SLC7A11) [Driver; Suppressor]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Suppressor
Responsed Disease Degenerative arthritis ICD-11: FA05
 Disease Info 
Responsed Drug D-Mannose Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 hCDs (Chondrocytes)
In Vivo Model
C57BL/6 J mice (8 weeks old, female) were purchased from Dossy Experimental Animal Limited Company (Chengdu, China). For surgery, mice were anaesthetized with pentobarbital sodium (100 mg/kg, injected intraperitoneally) and subjected to unilateral ACLT procedures. 28 The sham group received a skin incision and suturing without patellar dislocation or ligament transection. For virus injection, mice were intraarticularly injected with 1 x 109 pfu (8 ul) of mock or AdEpas1 virus after one week of surgery. For Fer1 (MCE, Monmouth Junction, HY100579) injection, mice were intraarticularly injected with 1 mg/kg Fer1 or with vehicle two weeks after surgery, the injection was repeated once a week.

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Response regulation D-mannose alleviates osteoarthritis (OA) progression by suppressing HIF-2a-mediated chondrocyte sensitivity to ferroptosis. Overexpression of HIF-2a in chondrocytes by Ad- Epas1 intra-articular injection abolished the chondroprotective effect of D-mannose during OA progression and eliminated the role of D-mannose as a ferroptosis suppressor. Also, the RNA and protein levels of the two key ferroptosis suppressors, Gpx4 and Slc7a11, were increased in Dmannosetreated chondrocytes.
Degenerative arthritis [ICD-11: FA05]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Endothelial PAS domain-containing protein 1 (EPAS1) Protein coding
 Regulator Info 
Responsed Drug D-Mannose Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 hCDs (Chondrocytes)
In Vivo Model
C57BL/6 J mice (8 weeks old, female) were purchased from Dossy Experimental Animal Limited Company (Chengdu, China). For surgery, mice were anaesthetized with pentobarbital sodium (100 mg/kg, injected intraperitoneally) and subjected to unilateral ACLT procedures. 28 The sham group received a skin incision and suturing without patellar dislocation or ligament transection. For virus injection, mice were intraarticularly injected with 1 x 109 pfu (8 ul) of mock or AdEpas1 virus after one week of surgery. For Fer1 (MCE, Monmouth Junction, HY100579) injection, mice were intraarticularly injected with 1 mg/kg Fer1 or with vehicle two weeks after surgery, the injection was repeated once a week.

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Response regulation D-mannose alleviates osteoarthritis (OA) progression by suppressing HIF-2a-mediated chondrocyte sensitivity to ferroptosis. Overexpression of HIF-2a in chondrocytes by Ad- Epas1 intra-articular injection abolished the chondroprotective effect of D-mannose during OA progression and eliminated the role of D-mannose as a ferroptosis suppressor. Also, the RNA and protein levels of the two key ferroptosis suppressors, Gpx4 and Slc7a11, were increased in Dmannosetreated chondrocytes.
D-Mannose [Investigative]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Suppressor
Response Target Cystine/glutamate transporter (SLC7A11) Driver; Suppressor
 Target Info 
Responsed Disease Degenerative arthritis ICD-11: FA05
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 hCDs (Chondrocytes)
In Vivo Model
C57BL/6 J mice (8 weeks old, female) were purchased from Dossy Experimental Animal Limited Company (Chengdu, China). For surgery, mice were anaesthetized with pentobarbital sodium (100 mg/kg, injected intraperitoneally) and subjected to unilateral ACLT procedures. 28 The sham group received a skin incision and suturing without patellar dislocation or ligament transection. For virus injection, mice were intraarticularly injected with 1 x 109 pfu (8 ul) of mock or AdEpas1 virus after one week of surgery. For Fer1 (MCE, Monmouth Junction, HY100579) injection, mice were intraarticularly injected with 1 mg/kg Fer1 or with vehicle two weeks after surgery, the injection was repeated once a week.

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Response regulation D-mannose alleviates osteoarthritis (OA) progression by suppressing HIF-2a-mediated chondrocyte sensitivity to ferroptosis. Overexpression of HIF-2a in chondrocytes by Ad- Epas1 intra-articular injection abolished the chondroprotective effect of D-mannose during OA progression and eliminated the role of D-mannose as a ferroptosis suppressor. Also, the RNA and protein levels of the two key ferroptosis suppressors, Gpx4 and Slc7a11, were increased in Dmannosetreated chondrocytes.
References
Ref 1 D-mannose alleviates osteoarthritis progression by inhibiting chondrocyte ferroptosis in a HIF-2-dependent manner. Cell Prolif. 2021 Nov;54(11):e13134. doi: 10.1111/cpr.13134. Epub 2021 Sep 25.