Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10377)
Regulator Name Sorting nexin-5 (SNX5)
Gene Name SNX5
Gene ID 27131
Regulator Type Protein coding
Uniprot ID Q9Y5X3
Sequence
MAAVPELLQQQEEDRSKLRSVSVDLNVDPSLQIDIPDALSERDKVKFTVHTKTTLPTFQS
PEFSVTRQHEDFVWLHDTLIETTDYAGLIIPPAPTKPDFDGPREKMQKLGEGEGSMTKEE
FAKMKQELEAEYLAVFKKTVSSHEVFLQRLSSHPVLSKDRNFHVFLEYDQDLSVRRKNTK
EMFGGFFKSVVKSADEVLFTGVKEVDDFFEQEKNFLINYYNRIKDSCVKADKMTRSHKNV
ADDYIHTAACLHSLALEEPTVIKKYLLKVAELFEKLRKVEGRVSSDEDLKLTELLRYYML
NIEAAKDLLYRRTKALIDYENSNKALDKARLKSKDVKLAEAHQQECCQKFEQLSESAKEE
LINFKRKRVAAFRKNLIEMSELEIKHARNNVSLLQSCIDLFKNN

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Family Sorting nexin family
Function
Involved in several stages of intracellular trafficking. Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)) or phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2). Acts in part as component of the retromer membrane- deforming SNX-BAR subcomplex. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX-BAR subcomplex functions to deform the donor membrane into a tubular profile called endosome-to-TGN transport carrier (ETC) (Probable). Does not have in vitro vesicle-to-membrane remodeling activity. Involved in retrograde transport of lysosomal enzyme receptor IGF2R. May function as link between endosomal transport vesicles and dynactin (Probable). Plays a role in the internalization of EGFR after EGF stimulation (Probable). Involved in EGFR endosomal sorting and degradation; the function involves PIP5K1C isoform 3 and is retromer- independent. Together with PIP5K1C isoform 3 facilitates HGS interaction with ubiquitinated EGFR, which initiates EGFR sorting to intraluminal vesicles (ILVs) of the multivesicular body for subsequent lysosomal degradation (Probable). Involved in E-cadherin sorting and degradation; inhibits PIP5K1C isoform 3-mediated E-cadherin degradation. Plays a role in macropinocytosis.

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HGNC ID
HGNC:14969
KEGG ID hsa:27131
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
SNX5 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
Phospholipid hydroperoxide glutathione peroxidase (GPX4) [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 Parkinson disease ICD-11: 8A00
 Disease Info 
Pathway Response Glutathione metabolism hsa00480
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 PC12 cells Adrenal gland pheochromocytoma Rattus norvegicus CVCL_0481
In Vivo Model
All animal maintenance and experiments were approved by The Ethical Committee of Guangzhou University of Chinese Medicine. A total of 36 SD rats (Sprague-Dawley; male; 230-260 g; 8-9-weeks old) were divided randomly into two study groups (n = 18 rats/group), i.e., the sham group (unilateral injection of the equal volume of saline) and model group (unilateral injection of 20 g of 6-OHDA). All surgical procedures were performed under (10 mg/kgxylazine, and 100 mg/kg ketamine, intraperitoneal administration) anesthesia using stereotactic apparatus (RWD, Shenzhen, China). The rats received either unilateral injections of 5 ul of 6-OHDA (Sigma-Aldrich, Germany; 4 ug/ul, dissolved in PBS) or 5 ul of saline into MFB (left medial forebrain bundle) at the rate of 1 ul/min. Injection coordinates were as follows (with reference to bregma): anteroposterior (A/P) = - 2.2 mm, lateral (LAT) = 1.5 mm, and dorsoventral (D/V) = 8.0 mm. The rats were placed in animal holding room (humidity: 50 ± 5%; temperature: 21 ± 1 ; 12-h dark/light cycle).

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Response regulation This study investigated the mechanism by which PD-specific SE driven SNX5 promoted the ferroptosis level in Parkinson's disease models. The results showed that the GPX4 expression level significantly reduced.
Parkinson disease [ICD-11: 8A00]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Sorting nexin-5 (SNX5) Protein coding
 Regulator Info 
Pathway Response Glutathione metabolism hsa00480
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 PC12 cells Adrenal gland pheochromocytoma Rattus norvegicus CVCL_0481
In Vivo Model
All animal maintenance and experiments were approved by The Ethical Committee of Guangzhou University of Chinese Medicine. A total of 36 SD rats (Sprague-Dawley; male; 230-260 g; 8-9-weeks old) were divided randomly into two study groups (n = 18 rats/group), i.e., the sham group (unilateral injection of the equal volume of saline) and model group (unilateral injection of 20 g of 6-OHDA). All surgical procedures were performed under (10 mg/kgxylazine, and 100 mg/kg ketamine, intraperitoneal administration) anesthesia using stereotactic apparatus (RWD, Shenzhen, China). The rats received either unilateral injections of 5 ul of 6-OHDA (Sigma-Aldrich, Germany; 4 ug/ul, dissolved in PBS) or 5 ul of saline into MFB (left medial forebrain bundle) at the rate of 1 ul/min. Injection coordinates were as follows (with reference to bregma): anteroposterior (A/P) = - 2.2 mm, lateral (LAT) = 1.5 mm, and dorsoventral (D/V) = 8.0 mm. The rats were placed in animal holding room (humidity: 50 ± 5%; temperature: 21 ± 1 ; 12-h dark/light cycle).

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Response regulation This study investigated the mechanism by which PD-specific SE driven SNX5 promoted the ferroptosis level in Parkinson's disease models. The results showed that the GPX4 expression level significantly reduced.
References
Ref 1 Super-enhancer-driven Sorting Nexin 5 expression promotes dopaminergic neuronal ferroptosis in Parkinson's disease models. Biochem Biophys Res Commun. 2021 Aug 27;567:35-41. doi: 10.1016/j.bbrc.2021.06.024. Epub 2021 Jun 13.