Molecule Information

General Information of the Molecule (ID: Mol01951)

• Name: Ras-specific guanine nucleotide-releasing factor 2 (RGRF2) ,Mus musculus
• Synonyms: Rasgrf2; Grf2
• Molecule Type: Protein
• Gene Name: RGRF2
• Gene ID: 19418
• Location: chr13:92,028,519-92,268,164[-]
• Sequence:
  MQKSVRYNEGHALYLAMLARKEGTKRGFLSKKAAEASRWHEKWFALYQNVLFYFEGEQSG
  RPAGMYLLEGCSCERTPAPPRTNAGPAGARDALDKQYYFTVLFGHDGQKPLELRCEEEQA
  GKEWMEAIHQASYADILIEREVLMQKYIHLVQIVETEKIATNQLRHQLEDQDTEIERLKS
  EIVALNKTKERMRPYHVHQEEEDPDIKKIKKVQSFMRGWLCRRKWKTIVQDYICSPHAES
  MRKRNQIVFTMVEAETEYVHQLYILVNGFLRPLRMAASSKKPPINHDDVSSIFLNSETIM
  FLHEIFHQGLKARLANWPTLVLADLFDILLPMLNIYQEFVRNHQYSLQVLANCKQNRDFD
  KLLKQYEANPACEGRMLETFLTYPMFQIPRYIITLHELLAHTPHEHVERKSLEFAKSKLE
  ELSRVMHDEVSDTENIRKNLAIERMIVEGCDILLDTSQTFIRQGSLIQVPSVERGKLSKV
  RLGSLSLKKEGERQCFLFTKHFLICTRSSGGKLHLLKTGGVLSLIQCTLIEEPDGSDDDP
  KGSGHMFGHLDFKIVVEPPDAASFTVVLLAPSRQEKAAWMSDISQCVDNIRCNGLMTIVF
  EENSKVTVPHMIKSDARLHKDDTDICFSKTLNSCKVPQIRYASVERLLERLTDLRFLSID
  FLNTFLHTYRIFTTATVVLAKLSDIYKRPFTSIPVRSLELFFATSQNNREHLVDGKSPRL
  CRKFSSPPPLAVSRTSSPVRARKLSLTSSLNSRIGALDLTNSSSSSSPTTTTHSPAASPP
  PHTAVLESAPADKAGDSADMSPCRSPTTPRHLRYRQPGGQVADSAHCSVSPASAFAIATA
  AAGHGSPPGFNNERTCDKEFIIRRTATNRVLNVLRHWVSKHAQDFELNNELKMNVLNLLE
  EVLRDPDLLPQERKATANILRALSQDDQDDIHLKLEDIIQMTDCPKAECFETLSAMELAE
  QITLLDHIVFRSIPYEEFLGQGWMKLDKNERTPYIMKTSQHFNEMSNLVASQIMNYADIS
  SRANAIEKWVAVADICRCLHNYNGVLEITSALNRSAIYRLKKTWAKVSKQTKALMDKLQK
  TVSSEGRFKNLRETLKNCNPPAVPYLGMYLTDLAFIEEGTPNFTEEGLVNFSKMRMISHI
  IREIRQFQQTAYRIDQQPKVIQYLLDKALVIDEDSLYELSLKIEPRLPA
• Function: Functions as a calcium-regulated nucleotide exchange factor activating both Ras and RAC1 through the exchange of bound GDP for GTP. Preferentially activates HRAS in vivo compared to RRAS based on their different types of prenylation. Functions in synaptic plasticity by contributing to the induction of long term potentiation.
• Uniprot ID: RGRF2_MOUSE
• Ensembl ID: ENSMUSG00000021708

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: 9989
Family: Muridae
Genus: Mus
Species: Mus musculus

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Tryptophan

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Melanoma [1]

• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Resistant Drug: Tryptophan
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• Cell Pathway Regulation: MAPK/RAS signaling pathway; Activation; hsa04010
• In Vivo Model: VillinCreErt2 and VillinCreErt2 APCfl/fl KRASG12D/+ C57BL/6J mouse model; Mus musculus
• Experiment for Molecule Alteration: Amino acid mass spectrometry assay
• Experiment for Drug Resistance: Flow cytometry (SIINFEKL assays); T cell killing assay and clonogenic assay
• Mechanism Description: Sloppiness is defined by ribosomal frameshifting upon tryptophan shortage. MAPK pathway hyperactivation links sloppiness to cancer. Drug-resistant cancer cells remain sloppy and are targeted by T cells.

References

• Ref 1: Oncogene-dependent sloppiness in mRNA translation .Mol Cell. 2021 Nov 18;81(22):4709-4721.e9. doi: 10.1016/j.molcel.2021.09.002. Epub 2021 Sep 24. 10.1016/j.molcel.2021.09.002