General Information of the Ferroptosis Regulator (ID: REG10247)
Regulator Name Rapamycin-insensitive companion of mTOR (RICTOR)
Synonyms
AVO3 homolog
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Gene Name RICTOR
Gene ID 253260
Regulator Type Protein coding
Uniprot ID Q6R327
Sequence
MAAIGRGRSLKNLRVRGRNDSGEENVPLDLTREPSDNLREILQNVARLQGVSNMRKLGHL
NNFTKLLCDIGHSEEKLGFHYEDIIICLRLALLNEAKEVRAAGLRALRYLIQDSSILQKV
LKLKVDYLIARCIDIQQSNEVERTQALRLVRKMITVNASLFPSSVTNSLIAVGNDGLQER
DRMVRACIAIICELALQNPEVVALRGGLNTILKNVIDCQLSRINEALITTILHLLNHPKT
RQYVRADVELERILAPYTDFHYRHSPDTAEGQLKEDREARFLASKMGIIATFRSWAGIIN
LCKPGNSGIQSLIGVLCIPNMEIRRGLLEVLYDIFRLPLPVVTEEFIEALLSVDPGRFQD
SWRLSDGFVAAEAKTILPHRARSRPDLMDNYLALILSAFIRNGLLEGLVEVITNSDDHIS
VRATILLGELLHMANTILPHSHSHHLHCLPTLMNMAASFDIPKEKRLRASAALNCLKRFH
EMKKRGPKPYSLHLDHIIQKAIATHQKRDQYLRVQKDIFILKDTEEALLINLRDSQVLQH
KENLEWNWNLIGTILKWPNVNLRNYKDEQLHRFVRRLLYFYKPSSKLYANLDLDFAKAKQ
LTVVGCQFTEFLLESEEDGQGYLEDLVKDIVQWLNASSGMKPERSLQNNGLLTTLSQHYF
LFIGTLSCHPHGVKMLEKCSVFQCLLNLCSLKNQDHLLKLTVSSLDYSRDGLARVILSKI
LTAATDACRLYATKHLRVLLRANVEFFNNWGIELLVTQLHDKNKTISSEALDILDEACED
KANLHALIQMKPALSHLGDKGLLLLLRFLSIPKGFSYLNERGYVAKQLEKWHREYNSKYV
DLIEEQLNEALTTYRKPVDGDNYVRRSNQRLQRPHVYLPIHLYGQLVHHKTGCHLLEVQN
IITELCRNVRTPDLDKWEEIKKLKASLWALGNIGSSNWGLNLLQEENVIPDILKLAKQCE
VLSIRGTCVYVLGLIAKTKQGCDILKCHNWDAVRHSRKHLWPVVPDDVEQLCNELSSIPS
TLSLNSESTSSRHNSESESVPSSMFILEDDRFGSSSTSTFFLDINEDTEPTFYDRSGPIK
DKNSFPFFASSKLVKNRILNSLTLPNKKHRSSSDPKGGKLSSESKTSNRRIRTLTEPSVD
FNHSDDFTPISTVQKTLQLETSFMGNKHIEDTGSTPSIGENDLKFTKNFGTENHRENTSR
ERLVVESSTSSHMKIRSQSFNTDTTTSGISSMSSSPSRETVGVDATTMDTDCGSMSTVVS
TKTIKTSHYLTPQSNHLSLSKSNSVSLVPPGSSHTLPRRAQSLKAPSIATIKSLADCNFS
YTSSRDAFGYATLKRLQQQRMHPSLSHSEALASPAKDVLFTDTITMKANSFESRLTPSRF
MKALSYASLDKEDLLSPINQNTLQRSSSVRSMVSSATYGGSDDYIGLALPVDINDIFQVK
DIPYFQTKNIPPHDDRGARAFAHDAGGLPSGTGGLVKNSFHLLRQQMSLTEIMNSIHSDA
SLFLESTEDTGLQEHTDDNCLYCVCIEILGFQPSNQLSAICSHSDFQDIPYSDWCEQTIH
NPLEVVPSKFSGISGCSDGVSQEGSASSTKSTELLLGVKTIPDDTPMCRILLRKEVLRLV
INLSSSVSTKCHETGLLTIKEKYPQTFDDICLYSEVSHLLSHCTFRLPCRRFIQELFQDV
QFLQMHEEAEAVLATPPKQPIVDTSAES

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Family RICTOR family
Function
Subunit of mTORC2, which regulates cell growth and survival in response to hormonal signals. mTORC2 is activated by growth factors, but, in contrast to mTORC1, seems to be nutrient-insensitive. mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum-induced formation of stress-fibers or F-actin. mTORC2 plays a critical role in AKT1 'Ser-473' phosphorylation, which may facilitate the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDK1 which is a prerequisite for full activation. mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422'. mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657'. Plays an essential role in embryonic growth and development.

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HGNC ID
HGNC:28611
KEGG ID hsa:253260
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
RICTOR 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]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Suppressor
Responsed Disease Thymoma ICD-11: 2C27
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
mBMCs (Mouse blood mononuclear cells)
EL4 cells (BCMA expression) cells Thymoma Mus musculus CVCL_0255
In Vivo Model
A total of 1 x 106 naive SMARTA (CD45.1) cells were adoptively transferred into naive WT congenic recipient mice (CD45.2). On the following day, the recipients were intraperitoneally infected with 1 x 10++6PFU of LCMV Arm. BM cells were collected from WT C57BL/6J mice and KO mice.

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Response regulation The mTOR kinase can be assembled into two structurally and functionally distinct complexes, mTORC1 and mTORC2, both of which share the same catalytic subunit mTOR but differ in two scaffold subunits, Raptor for mTORC1 and Rictor for mTORC2, respectively. mTORC2 inactivation resulted in the impaired phosphorylation of downstream AKT and GSK3B kinases, which induced aberrant mitochondrial reactive oxygen species (ROS) accumulation and ensuing ferroptosis-causative lipid peroxidation in virus-specific memory CD4T cells; furthermore, the disruption of this signaling cascade also inhibited glutathione peroxidase 4 (GPX4) in thymoma cells.
Thymoma [ICD-11: 2C27]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Rapamycin-insensitive companion of mTOR (RICTOR) Protein coding
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
mBMCs (Mouse blood mononuclear cells)
EL4 cells (BCMA expression) cells Thymoma Mus musculus CVCL_0255
In Vivo Model
A total of 1 x 106 naive SMARTA (CD45.1) cells were adoptively transferred into naive WT congenic recipient mice (CD45.2). On the following day, the recipients were intraperitoneally infected with 1 x 10++6PFU of LCMV Arm. BM cells were collected from WT C57BL/6J mice and KO mice.

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Response regulation The mTOR kinase can be assembled into two structurally and functionally distinct complexes, mTORC1 and mTORC2, both of which share the same catalytic subunit mTOR but differ in two scaffold subunits, Raptor for mTORC1 and Rictor for mTORC2, respectively. mTORC2 inactivation resulted in the impaired phosphorylation of downstream AKT and GSK3B kinases, which induced aberrant mitochondrial reactive oxygen species (ROS) accumulation and ensuing ferroptosis-causative lipid peroxidation in virus-specific memory CD4T cells; furthermore, the disruption of this signaling cascade also inhibited glutathione peroxidase 4 (GPX4) in thymoma cells.
References
Ref 1 The kinase complex mTORC2 promotes the longevity of virus-specific memory CD4(+) T cells by preventing ferroptosis. Nat Immunol. 2022 Feb;23(2):303-317. doi: 10.1038/s41590-021-01090-1. Epub 2021 Dec 23.