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Protein

GTPase KRas

Gene

Kras

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Ras proteins bind GDP/GTP and possess intrinsic GTPase activity (By similarity). Plays an important role in the regulation of cell proliferation (PubMed:6474169, PubMed:1352876).By similarity2 Publications

Enzyme regulationi

Alternates between an inactive form bound to GDP and an active form bound to GTP. Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by a GTPase-activating protein (GAP). Interaction with SOS1 promotes exchange of bound GDP by GTP.By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi10 – 189GTPBy similarity
Nucleotide bindingi29 – 357GTPBy similarity
Nucleotide bindingi59 – 602GTPBy similarity
Nucleotide bindingi116 – 1194GTPBy similarity

GO - Molecular functioni

  1. GDP binding Source: Ensembl
  2. GMP binding Source: Ensembl
  3. GTPase activity Source: MGI
  4. GTP binding Source: UniProtKB-KW
  5. protein complex binding Source: MGI

GO - Biological processi

  1. actin cytoskeleton organization Source: MGI
  2. cytokine-mediated signaling pathway Source: Ensembl
  3. endocrine signaling Source: CACAO
  4. epithelial tube branching involved in lung morphogenesis Source: MGI
  5. homeostasis of number of cells within a tissue Source: MGI
  6. metabolic process Source: GOC
  7. negative regulation of cell differentiation Source: MGI
  8. negative regulation of neuron apoptotic process Source: MGI
  9. positive regulation of cell proliferation Source: UniProtKB
  10. positive regulation of gene expression Source: MGI
  11. positive regulation of MAP kinase activity Source: Ensembl
  12. positive regulation of NF-kappaB transcription factor activity Source: Ensembl
  13. positive regulation of nitric-oxide synthase activity Source: Ensembl
  14. positive regulation of protein phosphorylation Source: MGI
  15. positive regulation of Rac protein signal transduction Source: MGI
  16. Ras protein signal transduction Source: MGI
  17. regulation of long-term neuronal synaptic plasticity Source: MGI
  18. regulation of synaptic transmission, GABAergic Source: MGI
  19. response to glucocorticoid Source: Ensembl
  20. response to mineralocorticoid Source: Ensembl
  21. social behavior Source: Ensembl
  22. striated muscle cell differentiation Source: MGI
  23. visual learning Source: MGI
Complete GO annotation...

Keywords - Ligandi

GTP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_275935. RAF phosphorylates MEK.
REACT_276076. SHC1 events in ERBB4 signaling.
REACT_278498. Downstream signal transduction.
REACT_285497. GRB2 events in EGFR signaling.
REACT_286571. SHC1 events in EGFR signaling.
REACT_288801. SOS-mediated signalling.
REACT_293097. Activation of RAS in B cells.
REACT_296095. p38MAPK events.
REACT_299722. VEGFR2 mediated cell proliferation.
REACT_301936. DAP12 signaling.
REACT_309034. MEK activation.
REACT_309710. RAF activation.
REACT_314186. FCERI mediated MAPK activation.
REACT_317270. Constitutive Signaling by EGFRvIII.
REACT_320246. Signalling to RAS.
REACT_321421. SHC-mediated cascade.
REACT_321592. SHC1 events in ERBB2 signaling.
REACT_325060. EGFR Transactivation by Gastrin.
REACT_326306. Signaling by FGFR mutants.
REACT_327089. GRB2 events in ERBB2 signaling.
REACT_327841. Signaling by SCF-KIT.
REACT_332809. FRS2-mediated cascade.
REACT_333309. SHC-mediated signalling.
REACT_339798. NCAM signaling for neurite out-growth.
REACT_341964. Tie2 Signaling.
REACT_344438. Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants.

Names & Taxonomyi

Protein namesi
Recommended name:
GTPase KRas
Alternative name(s):
K-Ras 2
Ki-Ras
c-K-ras
c-Ki-ras
Cleaved into the following chain:
Gene namesi
Name:Kras
Synonyms:Kras2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:96680. Kras.

Subcellular locationi

  1. Cell membrane By similarity; Lipid-anchor By similarity; Cytoplasmic side By similarity
  2. Cytoplasm By similarity

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. extrinsic component of cytoplasmic side of plasma membrane Source: UniProtKB
  3. focal adhesion Source: MGI
  4. membrane Source: MGI
  5. membrane raft Source: Ensembl
  6. mitochondrion Source: Ensembl
  7. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi12 – 121G → D: Activates oncogene.
Mutagenesisi164 – 1641R → A: Loss of GTP-binding activity.

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 186186GTPase KRasPRO_0000082643Add
BLAST
Initiator methioninei1 – 11Removed; alternateBy similarity
Chaini2 – 186185GTPase KRas, N-terminally processedPRO_0000326482Add
BLAST
Propeptidei187 – 1893Removed in mature formBy similarityPRO_0000281293

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineBy similarity
Modified residuei2 – 21N-acetylthreonine; in GTPase KRas, N-terminally processedBy similarity
Modified residuei104 – 1041N6-acetyllysineBy similarity
Modified residuei118 – 1181S-nitrosocysteineBy similarity
Lipidationi180 – 1801S-palmitoyl cysteineBy similarity
Modified residuei186 – 1861Cysteine methyl ester; in isoform 2ABy similarity
Lipidationi186 – 1861S-farnesyl cysteine; in isoform 2ABy similarity

Post-translational modificationi

Acetylation at Lys-104 prevents interaction with guanine nucleotide exchange factors (GEFs).By similarity

Keywords - PTMi

Acetylation, Lipoprotein, Methylation, Palmitate, Prenylation, S-nitrosylation

Proteomic databases

MaxQBiP32883.
PaxDbiP32883.
PRIDEiP32883.

PTM databases

PhosphoSiteiP32883.

Expressioni

Gene expression databases

BgeeiP32883.
ExpressionAtlasiP32883. baseline and differential.
GenevestigatoriP32883.

Interactioni

Subunit structurei

Interacts with PHLPP. Interacts (active GTP-bound form preferentially) with RGS14 (By similarity). Interacts (when farnesylated) with PDE6D; this promotes dissociation from the cell membrane (By similarity). Interacts with SOS1 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
EgfrQ012793EBI-644267,EBI-6296235
Raf1Q99N573EBI-644285,EBI-397757

Protein-protein interaction databases

BioGridi201012. 1 interaction.
DIPiDIP-29362N.
IntActiP32883. 7 interactions.
MINTiMINT-216577.

Structurei

3D structure databases

SMRiP32883. Positions 1-166.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni166 – 18520Hypervariable regionAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi32 – 409Effector region

Sequence similaritiesi

Belongs to the small GTPase superfamily. Ras family.Curated

Phylogenomic databases

eggNOGiCOG1100.
HOGENOMiHOG000233973.
HOVERGENiHBG009351.
InParanoidiP32883.
KOiK07827.
OMAiKKSRTRC.
OrthoDBiEOG7QVM41.
PhylomeDBiP32883.
TreeFamiTF312796.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR020849. Small_GTPase_Ras.
[Graphical view]
PANTHERiPTHR24070. PTHR24070. 1 hit.
PfamiPF00071. Ras. 1 hit.
[Graphical view]
PRINTSiPR00449. RASTRNSFRMNG.
SMARTiSM00173. RAS. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiPS51421. RAS. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Isoforms differ in the C-terminal region which is encoded by two alternative exons (IVA and IVB).

Isoform 2A (identifier: P32883-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MTEYKLVVVG AGGVGKSALT IQLIQNHFVD EYDPTIEDSY RKQVVIDGET
60 70 80 90 100
CLLDILDTAG QEEYSAMRDQ YMRTGEGFLC VFAINNTKSF EDIHHYREQI
110 120 130 140 150
KRVKDSEDVP MVLVGNKCDL PSRTVDTKQA QELARSYGIP FIETSAKTRQ
160 170 180
RVEDAFYTLV REIRQYRLKK ISKEEKTPGC VKIKKCVIM
Length:189
Mass (Da):21,656
Last modified:August 13, 1987 - v1
Checksum:i97345422E01D2C81
GO
Isoform 2B (identifier: P32883-2) [UniParc] [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     151-153: RVE → GVD
     165-189: QYRLKKISKEEKTPGCVKIKKCVIM → KHKEKMSKDGKKKKKKSRTRCTVM

Show »
Length:188
Mass (Da):21,483
Checksum:iB0A542E8AD158F51
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei151 – 1533RVE → GVD in isoform 2B. 2 PublicationsVSP_011142
Alternative sequencei165 – 18925QYRLK…KCVIM → KHKEKMSKDGKKKKKKSRTR CTVM in isoform 2B. 2 PublicationsVSP_011143Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X02452
, X02453, X02454, X02456 Genomic DNA. Translation: CAA26295.1.
X02455 Genomic DNA. Translation: CAA26296.1.
BC004642 mRNA. Translation: AAH04642.1.
BC010202 mRNA. Translation: AAH10202.1.
K01927 Genomic DNA. Translation: AAA40037.1.
X00485 mRNA. Translation: CAA25160.1.
CCDSiCCDS20693.1. [P32883-2]
PIRiA01365. TVMSK.
B01365. TVMS2K.
RefSeqiNP_067259.4. NM_021284.6. [P32883-2]
XP_006506981.1. XM_006506918.2. [P32883-1]
XP_006536102.1. XM_006536039.1. [P32883-1]
UniGeneiMm.383182.

Genome annotation databases

EnsembliENSMUST00000032399; ENSMUSP00000032399; ENSMUSG00000030265. [P32883-2]
ENSMUST00000111710; ENSMUSP00000107339; ENSMUSG00000030265. [P32883-1]
GeneIDi16653.
KEGGimmu:16653.
UCSCiuc009eri.2. mouse. [P32883-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X02452
, X02453, X02454, X02456 Genomic DNA. Translation: CAA26295.1.
X02455 Genomic DNA. Translation: CAA26296.1.
BC004642 mRNA. Translation: AAH04642.1.
BC010202 mRNA. Translation: AAH10202.1.
K01927 Genomic DNA. Translation: AAA40037.1.
X00485 mRNA. Translation: CAA25160.1.
CCDSiCCDS20693.1. [P32883-2]
PIRiA01365. TVMSK.
B01365. TVMS2K.
RefSeqiNP_067259.4. NM_021284.6. [P32883-2]
XP_006506981.1. XM_006506918.2. [P32883-1]
XP_006536102.1. XM_006536039.1. [P32883-1]
UniGeneiMm.383182.

3D structure databases

SMRiP32883. Positions 1-166.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201012. 1 interaction.
DIPiDIP-29362N.
IntActiP32883. 7 interactions.
MINTiMINT-216577.

PTM databases

PhosphoSiteiP32883.

Proteomic databases

MaxQBiP32883.
PaxDbiP32883.
PRIDEiP32883.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000032399; ENSMUSP00000032399; ENSMUSG00000030265. [P32883-2]
ENSMUST00000111710; ENSMUSP00000107339; ENSMUSG00000030265. [P32883-1]
GeneIDi16653.
KEGGimmu:16653.
UCSCiuc009eri.2. mouse. [P32883-1]

Organism-specific databases

CTDi3845.
MGIiMGI:96680. Kras.

Phylogenomic databases

eggNOGiCOG1100.
HOGENOMiHOG000233973.
HOVERGENiHBG009351.
InParanoidiP32883.
KOiK07827.
OMAiKKSRTRC.
OrthoDBiEOG7QVM41.
PhylomeDBiP32883.
TreeFamiTF312796.

Enzyme and pathway databases

ReactomeiREACT_275935. RAF phosphorylates MEK.
REACT_276076. SHC1 events in ERBB4 signaling.
REACT_278498. Downstream signal transduction.
REACT_285497. GRB2 events in EGFR signaling.
REACT_286571. SHC1 events in EGFR signaling.
REACT_288801. SOS-mediated signalling.
REACT_293097. Activation of RAS in B cells.
REACT_296095. p38MAPK events.
REACT_299722. VEGFR2 mediated cell proliferation.
REACT_301936. DAP12 signaling.
REACT_309034. MEK activation.
REACT_309710. RAF activation.
REACT_314186. FCERI mediated MAPK activation.
REACT_317270. Constitutive Signaling by EGFRvIII.
REACT_320246. Signalling to RAS.
REACT_321421. SHC-mediated cascade.
REACT_321592. SHC1 events in ERBB2 signaling.
REACT_325060. EGFR Transactivation by Gastrin.
REACT_326306. Signaling by FGFR mutants.
REACT_327089. GRB2 events in ERBB2 signaling.
REACT_327841. Signaling by SCF-KIT.
REACT_332809. FRS2-mediated cascade.
REACT_333309. SHC-mediated signalling.
REACT_339798. NCAM signaling for neurite out-growth.
REACT_341964. Tie2 Signaling.
REACT_344438. Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants.

Miscellaneous databases

ChiTaRSiKras. mouse.
NextBioi290345.
PROiP32883.
SOURCEiSearch...

Gene expression databases

BgeeiP32883.
ExpressionAtlasiP32883. baseline and differential.
GenevestigatoriP32883.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR020849. Small_GTPase_Ras.
[Graphical view]
PANTHERiPTHR24070. PTHR24070. 1 hit.
PfamiPF00071. Ras. 1 hit.
[Graphical view]
PRINTSiPR00449. RASTRNSFRMNG.
SMARTiSM00173. RAS. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiPS51421. RAS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Structure and expression of amplified cKi-ras gene sequences in Y1 mouse adrenal tumor cells."
    George D.L., Scott A.F., Trusko S., Glick B., Ford E., Dorney D.J.
    EMBO J. 4:1199-1203(1985) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 2A AND 2B).
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2B).
    Strain: FVB/N.
    Tissue: Mammary tumor.
  3. "Activation of a c-K-ras oncogene by somatic mutation in mouse lymphomas induced by gamma radiation."
    Guerrero I., Villasante A., Corces V., Pellicer A.
    Science 225:1159-1162(1984) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-37, FUNCTION.
  4. "Parental bias of Ki-ras oncogenes detected in lung tumors from mouse hybrids."
    You M., Wang Y., Stoner G., You L., Maronpot R., Reynolds S.H., Anderson M.
    Proc. Natl. Acad. Sci. U.S.A. 89:5804-5808(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE OF 1-37, FUNCTION.
  5. "Amplified DNA in Y1 mouse adrenal tumor cells: isolation of cDNAs complementary to an amplified c-Ki-ras gene and localization of homologous sequences to mouse chromosome 6."
    George D.L., Scott A.F., de Martinville B., Francke U.
    Nucleic Acids Res. 12:2731-2743(1984) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 109-173 (ISOFORM 2B).

Entry informationi

Entry nameiRASK_MOUSE
AccessioniPrimary (citable) accession number: P32883
Secondary accession number(s): P04200, P08643
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 20, 1987
Last sequence update: August 13, 1987
Last modified: April 29, 2015
This is version 146 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

This gene is amplified in the mouse adrenal tumor Y1 cells, and is also directly linked to lung tumor susceptibility.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.