Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10363)
Regulator Name Charged multivesicular body protein 5 (CHMP5)
Synonyms
C9orf83, SNF7DC2; Chromatin-modifying protein 5; SNF7 domain-containing protein 2; Vacuolar protein sorting-associated protein 60
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Gene Name CHMP5
Gene ID 51510
Regulator Type Protein coding
Uniprot ID Q9NZZ3
Sequence
MNRLFGKAKPKAPPPSLTDCIGTVDSRAESIDKKISRLDAELVKYKDQIKKMREGPAKNM
VKQKALRVLKQKRMYEQQRDNLAQQSFNMEQANYTIQSLKDTKTTVDAMKLGVKEMKKAY
KQVKIDQIEDLQDQLEDMMEDANEIQEALSRSYGTPELDEDDLEAELDALGDELLADEDS
SYLDEAASAPAIPEGVPTDTKNKDGVLVDEFGLPQIPAS

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Family SNF7 family
Function
Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and the budding of enveloped viruses (HIV-1 and other lentiviruses). ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. Involved in HIV-1 p6- and p9-dependent virus release.

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HGNC ID
HGNC:26942
KEGG ID hsa:51510
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
CHMP5 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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Unspecific Target [Unspecific Target]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Responsed Disease Pancreatic cancer ICD-11: 2C10
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 PANC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
In Vivo Model
To generate murine subcutaneous tumors, 5 x 106 PANC1 or HepG2 cells in 100 ul PBS were injected subcutaneously to the right of the dorsal midline in 6- to 8-week-old athymic nude or B6 mice. Once the tumors reached 50-70 mm3 at day 7, mice were randomly allocated into groups and treated with (1S-3R)-RSL3 (30 mg/kg; i.p., once every other day) for 2 weeks.

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Response regulation The accumulation of ESCRT-III subunits (e.g., CHMP5 and CHMP6) in the plasma membrane are increased by classical ferroptosis activators (e.g., erastin and RSL3), which relies on endoplasmic reticulum stress and calcium influx in pancreatic ductal adenocarcinoma cells PANC1.
Pancreatic cancer [ICD-11: 2C10]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Charged multivesicular body protein 5 (CHMP5) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 PANC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
In Vivo Model
To generate murine subcutaneous tumors, 5 x 106 PANC1 or HepG2 cells in 100 ul PBS were injected subcutaneously to the right of the dorsal midline in 6- to 8-week-old athymic nude or B6 mice. Once the tumors reached 50-70 mm3 at day 7, mice were randomly allocated into groups and treated with (1S-3R)-RSL3 (30 mg/kg; i.p., once every other day) for 2 weeks.

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Response regulation The accumulation of ESCRT-III subunits (e.g., CHMP5 and CHMP6) in the plasma membrane are increased by classical ferroptosis activators (e.g., erastin and RSL3), which relies on endoplasmic reticulum stress and calcium influx in pancreatic ductal adenocarcinoma cells PANC1.
References
Ref 1 ESCRT-III-dependent membrane repair blocks ferroptosis. Biochem Biophys Res Commun. 2020 Feb 5;522(2):415-421. doi: 10.1016/j.bbrc.2019.11.110. Epub 2019 Nov 21.