RASK_MOUSE
ID RASK_MOUSE Reviewed; 189 AA.
AC P32883; P04200; P08643;
DT 20-MAR-1987, integrated into UniProtKB/Swiss-Prot.
DT 13-AUG-1987, sequence version 1.
DT 03-AUG-2022, entry version 205.
DE RecName: Full=GTPase KRas;
DE EC=3.6.5.2 {ECO:0000250|UniProtKB:P01116};
DE AltName: Full=K-Ras 2;
DE AltName: Full=Ki-Ras;
DE AltName: Full=c-K-ras;
DE AltName: Full=c-Ki-ras;
DE Contains:
DE RecName: Full=GTPase KRas, N-terminally processed;
DE Flags: Precursor;
GN Name=Kras; Synonyms=Kras2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 2A AND 2B).
RX PubMed=4006913; DOI=10.1002/j.1460-2075.1985.tb03760.x;
RA George D.L., Scott A.F., Trusko S., Glick B., Ford E., Dorney D.J.;
RT "Structure and expression of amplified cKi-ras gene sequences in Y1 mouse
RT adrenal tumor cells.";
RL EMBO J. 4:1199-1203(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2B).
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-37, AND FUNCTION.
RX PubMed=6474169; DOI=10.1126/science.6474169;
RA Guerrero I., Villasante A., Corces V., Pellicer A.;
RT "Activation of a c-K-ras oncogene by somatic mutation in mouse lymphomas
RT induced by gamma radiation.";
RL Science 225:1159-1162(1984).
RN [4]
RP NUCLEOTIDE SEQUENCE OF 1-37, AND FUNCTION.
RX PubMed=1352876; DOI=10.1073/pnas.89.13.5804;
RA You M., Wang Y., Stoner G., You L., Maronpot R., Reynolds S.H.,
RA Anderson M.;
RT "Parental bias of Ki-ras oncogenes detected in lung tumors from mouse
RT hybrids.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:5804-5808(1992).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 109-173 (ISOFORM 2B).
RX PubMed=6546797; DOI=10.1093/nar/12.6.2731;
RA George D.L., Scott A.F., de Martinville B., Francke U.;
RT "Amplified DNA in Y1 mouse adrenal tumor cells: isolation of cDNAs
RT complementary to an amplified c-Ki-ras gene and localization of homologous
RT sequences to mouse chromosome 6.";
RL Nucleic Acids Res. 12:2731-2743(1984).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Liver, Lung, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Ras proteins bind GDP/GTP and possess intrinsic GTPase
CC activity (By similarity). Plays an important role in the regulation of
CC cell proliferation (PubMed:6474169, PubMed:1352876). Plays a role in
CC promoting oncogenic events by inducing transcriptional silencing of
CC tumor suppressor genes (TSGs) in colorectal cancer (CRC) cells in a
CC ZNF304-dependent manner (By similarity). {ECO:0000250|UniProtKB:P01116,
CC ECO:0000269|PubMed:1352876, ECO:0000269|PubMed:6474169}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; EC=3.6.5.2;
CC Evidence={ECO:0000250|UniProtKB:P01116};
CC -!- ACTIVITY REGULATION: Alternates between an inactive form bound to GDP
CC and an active form bound to GTP. Activated by a guanine nucleotide-
CC exchange factor (GEF) and inactivated by a GTPase-activating protein
CC (GAP). Interaction with SOS1 promotes exchange of bound GDP by GTP.
CC {ECO:0000250|UniProtKB:P01116}.
CC -!- SUBUNIT: Interacts with PHLPP. Interacts (active GTP-bound form
CC preferentially) with RGS14 (By similarity). Interacts (when
CC farnesylated) with PDE6D; this promotes dissociation from the cell
CC membrane. Interacts with SOS1 (By similarity). Interacts (when
CC farnesylated) with GPR31 (By similarity). Interacts with RAP1GDS1 (By
CC similarity). {ECO:0000250|UniProtKB:P01116,
CC ECO:0000250|UniProtKB:P08644}.
CC -!- SUBUNIT: [Isoform 2B]: Interacts (when farnesylated) with GPR31.
CC {ECO:0000250|UniProtKB:P01116}.
CC -!- INTERACTION:
CC P32883; Q01279: Egfr; NbExp=3; IntAct=EBI-644267, EBI-6296235;
CC P32883; P04049: RAF1; Xeno; NbExp=2; IntAct=EBI-644267, EBI-365996;
CC P32883-2; Q99N57: Raf1; NbExp=3; IntAct=EBI-644285, EBI-397757;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P01116};
CC Lipid-anchor {ECO:0000250|UniProtKB:P01116}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:P01116}. Endomembrane system
CC {ECO:0000250|UniProtKB:P01116}. Cytoplasm
CC {ECO:0000250|UniProtKB:P01116}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2B]: Cell membrane
CC {ECO:0000250|UniProtKB:P01116}; Lipid-anchor
CC {ECO:0000250|UniProtKB:P01116}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Isoforms differ in the C-terminal region which is encoded by
CC two alternative exons (IVA and IVB).;
CC Name=2A;
CC IsoId=P32883-1; Sequence=Displayed;
CC Name=2B;
CC IsoId=P32883-2, P08643-1;
CC Sequence=VSP_011142, VSP_011143;
CC -!- PTM: Acetylation at Lys-104 prevents interaction with guanine
CC nucleotide exchange factors (GEFs). {ECO:0000250|UniProtKB:P01116}.
CC -!- PTM: Ubiquitinated by the BCR(LZTR1) E3 ubiquitin ligase complex at
CC Lys-170 in a non-degradative manner, leading to inhibit Ras signaling
CC by decreasing Ras association with membranes.
CC {ECO:0000250|UniProtKB:P01112}.
CC -!- PTM: Palmitoylated at Lys-182, Lys-184 and Lys-185. Lysine-
CC depalmitoylation by SIRT2 promotes its localization to endomembranes in
CC endocytic pathways. {ECO:0000250|UniProtKB:P01116}.
CC -!- MISCELLANEOUS: This gene is amplified in the mouse adrenal tumor Y1
CC cells, and is also directly linked to lung tumor susceptibility.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Ras family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X02452; CAA26295.1; -; Genomic_DNA.
DR EMBL; X02453; CAA26295.1; JOINED; Genomic_DNA.
DR EMBL; X02454; CAA26295.1; JOINED; Genomic_DNA.
DR EMBL; X02456; CAA26295.1; JOINED; Genomic_DNA.
DR EMBL; X02455; CAA26296.1; -; Genomic_DNA.
DR EMBL; BC004642; AAH04642.1; -; mRNA.
DR EMBL; BC010202; AAH10202.1; -; mRNA.
DR EMBL; K01927; AAA40037.1; -; Genomic_DNA.
DR EMBL; X00485; CAA25160.1; -; mRNA.
DR CCDS; CCDS20693.1; -. [P32883-2]
DR PIR; A01365; TVMSK.
DR PIR; B01365; TVMS2K.
DR RefSeq; NP_067259.4; NM_021284.6. [P32883-2]
DR RefSeq; XP_006506981.1; XM_006506918.3. [P32883-1]
DR AlphaFoldDB; P32883; -.
DR BMRB; P32883; -.
DR SMR; P32883; -.
DR BioGRID; 201012; 26.
DR DIP; DIP-29362N; -.
DR IntAct; P32883; 7.
DR MINT; P32883; -.
DR iPTMnet; P32883; -.
DR PhosphoSitePlus; P32883; -.
DR SwissPalm; P32883; -.
DR EPD; P32883; -.
DR jPOST; P32883; -.
DR PaxDb; P32883; -.
DR PeptideAtlas; P32883; -.
DR PRIDE; P32883; -.
DR ProteomicsDB; 255109; -. [P32883-1]
DR ProteomicsDB; 255110; -. [P32883-2]
DR Antibodypedia; 24248; 927 antibodies from 39 providers.
DR DNASU; 16653; -.
DR Ensembl; ENSMUST00000032399; ENSMUSP00000032399; ENSMUSG00000030265. [P32883-2]
DR Ensembl; ENSMUST00000111710; ENSMUSP00000107339; ENSMUSG00000030265. [P32883-1]
DR GeneID; 16653; -.
DR KEGG; mmu:16653; -.
DR UCSC; uc009eri.2; mouse. [P32883-1]
DR CTD; 3845; -.
DR MGI; MGI:96680; Kras.
DR VEuPathDB; HostDB:ENSMUSG00000030265; -.
DR eggNOG; KOG0395; Eukaryota.
DR GeneTree; ENSGT00940000155871; -.
DR HOGENOM; CLU_041217_9_8_1; -.
DR InParanoid; P32883; -.
DR OMA; CCSGCVV; -.
DR OrthoDB; 1259506at2759; -.
DR PhylomeDB; P32883; -.
DR TreeFam; TF312796; -.
DR Reactome; R-MMU-1169092; Activation of RAS in B cells.
DR Reactome; R-MMU-1250347; SHC1 events in ERBB4 signaling.
DR Reactome; R-MMU-1433557; Signaling by SCF-KIT.
DR Reactome; R-MMU-171007; p38MAPK events.
DR Reactome; R-MMU-179812; GRB2 events in EGFR signaling.
DR Reactome; R-MMU-180336; SHC1 events in EGFR signaling.
DR Reactome; R-MMU-186763; Downstream signal transduction.
DR Reactome; R-MMU-1963640; GRB2 events in ERBB2 signaling.
DR Reactome; R-MMU-210993; Tie2 Signaling.
DR Reactome; R-MMU-2179392; EGFR Transactivation by Gastrin.
DR Reactome; R-MMU-2424491; DAP12 signaling.
DR Reactome; R-MMU-2871796; FCERI mediated MAPK activation.
DR Reactome; R-MMU-375165; NCAM signaling for neurite out-growth.
DR Reactome; R-MMU-4086398; Ca2+ pathway.
DR Reactome; R-MMU-5218921; VEGFR2 mediated cell proliferation.
DR Reactome; R-MMU-5621575; CD209 (DC-SIGN) signaling.
DR Reactome; R-MMU-5654688; SHC-mediated cascade:FGFR1.
DR Reactome; R-MMU-5654693; FRS-mediated FGFR1 signaling.
DR Reactome; R-MMU-5654699; SHC-mediated cascade:FGFR2.
DR Reactome; R-MMU-5654700; FRS-mediated FGFR2 signaling.
DR Reactome; R-MMU-5654704; SHC-mediated cascade:FGFR3.
DR Reactome; R-MMU-5654706; FRS-mediated FGFR3 signaling.
DR Reactome; R-MMU-5654712; FRS-mediated FGFR4 signaling.
DR Reactome; R-MMU-5654719; SHC-mediated cascade:FGFR4.
DR Reactome; R-MMU-5658442; Regulation of RAS by GAPs.
DR Reactome; R-MMU-5673000; RAF activation.
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR Reactome; R-MMU-5674135; MAP2K and MAPK activation.
DR Reactome; R-MMU-5675221; Negative regulation of MAPK pathway.
DR Reactome; R-MMU-8849471; PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases.
DR Reactome; R-MMU-8851805; MET activates RAS signaling.
DR Reactome; R-MMU-8951936; RUNX3 regulates p14-ARF.
DR Reactome; R-MMU-9607240; FLT3 Signaling.
DR Reactome; R-MMU-9634635; Estrogen-stimulated signaling through PRKCZ.
DR Reactome; R-MMU-9648002; RAS processing.
DR Reactome; R-MMU-9674555; Signaling by CSF3 (G-CSF).
DR BioGRID-ORCS; 16653; 11 hits in 78 CRISPR screens.
DR ChiTaRS; Kras; mouse.
DR PRO; PR:P32883; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; P32883; protein.
DR Bgee; ENSMUSG00000030265; Expressed in ureteric bud tip and 254 other tissues.
DR ExpressionAtlas; P32883; baseline and differential.
DR Genevisible; P32883; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0012505; C:endomembrane system; IEA:UniProtKB-SubCell.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0003925; F:G protein activity; IEA:UniProtKB-EC.
DR GO; GO:0019003; F:GDP binding; ISO:MGI.
DR GO; GO:0019002; F:GMP binding; ISO:MGI.
DR GO; GO:0005525; F:GTP binding; IBA:GO_Central.
DR GO; GO:0003924; F:GTPase activity; IGI:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0030275; F:LRR domain binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0030036; P:actin cytoskeleton organization; IGI:MGI.
DR GO; GO:0008283; P:cell population proliferation; IGI:MGI.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; ISO:MGI.
DR GO; GO:0038002; P:endocrine signaling; IMP:CACAO.
DR GO; GO:0060441; P:epithelial tube branching involved in lung morphogenesis; IDA:MGI.
DR GO; GO:0021897; P:forebrain astrocyte development; IMP:MGI.
DR GO; GO:0014009; P:glial cell proliferation; IGI:MGI.
DR GO; GO:0048873; P:homeostasis of number of cells within a tissue; IGI:MGI.
DR GO; GO:0030857; P:negative regulation of epithelial cell differentiation; IDA:MGI.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IGI:MGI.
DR GO; GO:0051402; P:neuron apoptotic process; IGI:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:2000774; P:positive regulation of cellular senescence; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:MGI.
DR GO; GO:0060252; P:positive regulation of glial cell proliferation; IGI:MGI.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; ISO:MGI.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR GO; GO:0051000; P:positive regulation of nitric-oxide synthase activity; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0035022; P:positive regulation of Rac protein signal transduction; IGI:MGI.
DR GO; GO:0016601; P:Rac protein signal transduction; IGI:MGI.
DR GO; GO:0007265; P:Ras protein signal transduction; IMP:MGI.
DR GO; GO:0048169; P:regulation of long-term neuronal synaptic plasticity; IGI:MGI.
DR GO; GO:0031647; P:regulation of protein stability; ISS:UniProtKB.
DR GO; GO:0032228; P:regulation of synaptic transmission, GABAergic; IGI:MGI.
DR GO; GO:0035914; P:skeletal muscle cell differentiation; IGI:MGI.
DR GO; GO:0051146; P:striated muscle cell differentiation; IGI:MGI.
DR GO; GO:0060509; P:type I pneumocyte differentiation; IDA:MGI.
DR GO; GO:0008542; P:visual learning; IGI:MGI.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR InterPro; IPR020849; Small_GTPase_Ras-type.
DR PANTHER; PTHR24070; PTHR24070; 1.
DR Pfam; PF00071; Ras; 1.
DR SMART; SM00174; RHO; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51421; RAS; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cell membrane; Cytoplasm; GTP-binding;
KW Hydrolase; Isopeptide bond; Lipoprotein; Membrane; Methylation;
KW Nucleotide-binding; Palmitate; Prenylation; Proto-oncogene;
KW Reference proteome; Ubl conjugation.
FT CHAIN 1..186
FT /note="GTPase KRas"
FT /id="PRO_0000326482"
FT INIT_MET 1
FT /note="Removed; alternate"
FT /evidence="ECO:0000250|UniProtKB:P01116"
FT CHAIN 2..186
FT /note="GTPase KRas, N-terminally processed"
FT /id="PRO_0000082643"
FT PROPEP 187..189
FT /note="Removed in mature form"
FT /evidence="ECO:0000250|UniProtKB:P01116"
FT /id="PRO_0000281293"
FT REGION 166..185
FT /note="Hypervariable region"
FT MOTIF 32..40
FT /note="Effector region"
FT BINDING 10..18
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P01116"
FT BINDING 29..35
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P01116"
FT BINDING 59..60
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P01116"
FT BINDING 116..119
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P01116"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P01116"
FT MOD_RES 2
FT /note="N-acetylthreonine; in GTPase KRas, N-terminally
FT processed"
FT /evidence="ECO:0000250|UniProtKB:P01116"
FT MOD_RES 104
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P01116"
FT MOD_RES 186
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000250|UniProtKB:P01116"
FT LIPID 180
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P01116"
FT LIPID 182
FT /note="N6-palmitoyl lysine"
FT /evidence="ECO:0000250|UniProtKB:P01116"
FT LIPID 184
FT /note="N6-palmitoyl lysine"
FT /evidence="ECO:0000250|UniProtKB:P01116"
FT LIPID 185
FT /note="N6-palmitoyl lysine"
FT /evidence="ECO:0000250|UniProtKB:P01116"
FT LIPID 186
FT /note="S-farnesyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P01116"
FT CROSSLNK 170
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P01116"
FT VAR_SEQ 151..153
FT /note="RVE -> GVD (in isoform 2B)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:6546797"
FT /id="VSP_011142"
FT VAR_SEQ 165..189
FT /note="QYRLKKISKEEKTPGCVKIKKCVIM -> KHKEKMSKDGKKKKKKSRTRCTV
FT M (in isoform 2B)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:6546797"
FT /id="VSP_011143"
SQ SEQUENCE 189 AA; 21656 MW; 97345422E01D2C81 CRC64;
MTEYKLVVVG AGGVGKSALT IQLIQNHFVD EYDPTIEDSY RKQVVIDGET CLLDILDTAG
QEEYSAMRDQ YMRTGEGFLC VFAINNTKSF EDIHHYREQI KRVKDSEDVP MVLVGNKCDL
PSRTVDTKQA QELARSYGIP FIETSAKTRQ RVEDAFYTLV REIRQYRLKK ISKEEKTPGC
VKIKKCVIM
