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Protein

GTPase KRas

Gene

Kras

Organism
Rattus norvegicus (Rat)
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:3110778). Plays a role in promoting oncogenic events by inducing transcriptional silencing of tumor suppressor genes (TSGs) in colorectal cancer (CRC) cells in a ZNF304-dependent manner (By similarity).By similarity1 Publication

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)DescriptionActionsGraphical viewLength
Nucleotide bindingi10 – 18GTPBy similarity9
Nucleotide bindingi29 – 35GTPBy similarity7
Nucleotide bindingi59 – 60GTPBy similarity2
Nucleotide bindingi116 – 119GTPBy similarity4

GO - Molecular functioni

  • GDP binding Source: RGD
  • GMP binding Source: RGD
  • GTPase activity Source: Ensembl
  • GTP binding Source: UniProtKB-KW
  • LRR domain binding Source: RGD

GO - Biological processi

Complete GO annotation...

Keywords - Ligandi

GTP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-RNO-112412. SOS-mediated signalling.
R-RNO-1169092. Activation of RAS in B cells.
R-RNO-1250347. SHC1 events in ERBB4 signaling.
R-RNO-1433557. Signaling by SCF-KIT.
R-RNO-167044. Signalling to RAS.
R-RNO-171007. p38MAPK events.
R-RNO-179812. GRB2 events in EGFR signaling.
R-RNO-180336. SHC1 events in EGFR signaling.
R-RNO-186763. Downstream signal transduction.
R-RNO-1963640. GRB2 events in ERBB2 signaling.
R-RNO-210993. Tie2 Signaling.
R-RNO-2179392. EGFR Transactivation by Gastrin.
R-RNO-2424491. DAP12 signaling.
R-RNO-2428933. SHC-related events triggered by IGF1R.
R-RNO-2871796. FCERI mediated MAPK activation.
R-RNO-375165. NCAM signaling for neurite out-growth.
R-RNO-5218921. VEGFR2 mediated cell proliferation.
R-RNO-5621575. CD209 (DC-SIGN) signaling.
R-RNO-5654688. SHC-mediated cascade:FGFR1.
R-RNO-5654693. FRS-mediated FGFR1 signaling.
R-RNO-5654699. SHC-mediated cascade:FGFR2.
R-RNO-5654700. FRS-mediated FGFR2 signaling.
R-RNO-5654704. SHC-mediated cascade:FGFR3.
R-RNO-5654706. FRS-mediated FGFR3 signaling.
R-RNO-5654712. FRS-mediated FGFR4 signaling.
R-RNO-5654719. SHC-mediated cascade:FGFR4.
R-RNO-5658442. Regulation of RAS by GAPs.
R-RNO-5673000. RAF activation.
R-RNO-5673001. RAF/MAP kinase cascade.
R-RNO-5674135. MAP2K and MAPK activation.
R-RNO-5675221. Negative regulation of MAPK pathway.
R-RNO-74751. Insulin receptor signalling cascade.
R-RNO-8849471. PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases.
R-RNO-8851805. MET activates RAS signaling.

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 4

Organism-specific databases

RGDi2981. Kras.

Subcellular locationi

  • Cell membrane By similarity; Lipid-anchor By similarity; Cytoplasmic side By similarity
  • Cytoplasmcytosol By similarity

GO - Cellular componenti

  • cytosol Source: UniProtKB-SubCell
  • extrinsic component of cytoplasmic side of plasma membrane Source: UniProtKB
  • focal adhesion Source: Ensembl
  • membrane raft Source: RGD
  • mitochondrion Source: RGD
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000826441 – 186GTPase KRasAdd BLAST186
Initiator methionineiRemoved; alternateBy similarity
ChainiPRO_00003264832 – 186GTPase KRas, N-terminally processedAdd BLAST185
PropeptideiPRO_0000281294187 – 189Removed in mature formBy similarity3

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei2N-acetylthreonine; in GTPase KRas, N-terminally processedBy similarity1
Modified residuei104N6-acetyllysineBy similarity1
Modified residuei118S-nitrosocysteineBy similarity1
Lipidationi180S-palmitoyl cysteineBy similarity1
Modified residuei186Cysteine methyl ester; in isoform 2ABy similarity1
Lipidationi186S-farnesyl cysteine; in isoform 2ABy similarity1

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

PaxDbiP08644.
PRIDEiP08644.

PTM databases

iPTMnetiP08644.
PhosphoSitePlusiP08644.

Expressioni

Gene expression databases

BgeeiENSRNOG00000009338.
ExpressionAtlasiP08644. baseline and differential.
GenevisibleiP08644. RN.

Interactioni

Subunit structurei

Interacts with SOS1 (By similarity). Interacts (when farnesylated) with PDE6D; this promotes dissociation from the cell membrane (By similarity). Interacts with PHLPP. Interacts (active GTP-bound form preferentially) with RGS14.By similarity2 Publications

GO - Molecular functioni

  • LRR domain binding Source: RGD

Protein-protein interaction databases

BioGridi246680. 9 interactors.
STRINGi10116.ENSRNOP00000012588.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1N4SX-ray2.60M/N/O/P/Q/R185-188[»]
ProteinModelPortaliP08644.
SMRiP08644.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni166 – 185Hypervariable regionAdd BLAST20

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi32 – 40Effector region9

Sequence similaritiesi

Belongs to the small GTPase superfamily. Ras family.Curated

Phylogenomic databases

eggNOGiKOG0395. Eukaryota.
COG1100. LUCA.
GeneTreeiENSGT00860000133672.
HOGENOMiHOG000233973.
HOVERGENiHBG009351.
InParanoidiP08644.
KOiK07827.
OMAiKKSRTRC.
OrthoDBiEOG091G0UAU.
PhylomeDBiP08644.
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]
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: P08644-1) [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:July 19, 2004 - v3
Checksum:i97345422E01D2C81
GO
Isoform 2B (identifier: P08644-2) [UniParc] [UniParc]FASTAAdd to basket

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

Show »
Length:188
Mass (Da):21,495
Checksum:iB0A55318AD158F51
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti12G → C in AAA42011 (PubMed:3023884).Curated1
Sequence conflicti47D → H in AAA42011 (PubMed:3023884).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_011144151 – 153RVE → GVD in isoform 2B. 1 Publication3
Alternative sequenceiVSP_011145165 – 189QYRLK…KCVIM → KHKEKMSKDGKKKKKKSRTR CIVM in isoform 2B. 1 PublicationAdd BLAST25

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U09793 mRNA. Translation: AAB60458.1.
AABR03032592 Genomic DNA. No translation available.
M12260, M12259 Genomic DNA. Translation: AAA42011.1.
M54870 Genomic DNA. Translation: AAA40937.1.
M16970 Genomic DNA. Translation: AAA41494.1.
PIRiI58402.
RefSeqiNP_113703.1. NM_031515.3. [P08644-2]
XP_008761576.1. XM_008763354.2. [P08644-2]
XP_017447931.1. XM_017592442.1. [P08644-1]
XP_017447932.1. XM_017592443.1. [P08644-1]
UniGeneiRn.24554.

Genome annotation databases

EnsembliENSRNOT00000012588; ENSRNOP00000012588; ENSRNOG00000009338. [P08644-1]
ENSRNOT00000012887; ENSRNOP00000012887; ENSRNOG00000009338. [P08644-2]
GeneIDi24525.
KEGGirno:24525.
UCSCiRGD:2981. rat. [P08644-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U09793 mRNA. Translation: AAB60458.1.
AABR03032592 Genomic DNA. No translation available.
M12260, M12259 Genomic DNA. Translation: AAA42011.1.
M54870 Genomic DNA. Translation: AAA40937.1.
M16970 Genomic DNA. Translation: AAA41494.1.
PIRiI58402.
RefSeqiNP_113703.1. NM_031515.3. [P08644-2]
XP_008761576.1. XM_008763354.2. [P08644-2]
XP_017447931.1. XM_017592442.1. [P08644-1]
XP_017447932.1. XM_017592443.1. [P08644-1]
UniGeneiRn.24554.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1N4SX-ray2.60M/N/O/P/Q/R185-188[»]
ProteinModelPortaliP08644.
SMRiP08644.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi246680. 9 interactors.
STRINGi10116.ENSRNOP00000012588.

PTM databases

iPTMnetiP08644.
PhosphoSitePlusiP08644.

Proteomic databases

PaxDbiP08644.
PRIDEiP08644.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000012588; ENSRNOP00000012588; ENSRNOG00000009338. [P08644-1]
ENSRNOT00000012887; ENSRNOP00000012887; ENSRNOG00000009338. [P08644-2]
GeneIDi24525.
KEGGirno:24525.
UCSCiRGD:2981. rat. [P08644-1]

Organism-specific databases

CTDi3845.
RGDi2981. Kras.

Phylogenomic databases

eggNOGiKOG0395. Eukaryota.
COG1100. LUCA.
GeneTreeiENSGT00860000133672.
HOGENOMiHOG000233973.
HOVERGENiHBG009351.
InParanoidiP08644.
KOiK07827.
OMAiKKSRTRC.
OrthoDBiEOG091G0UAU.
PhylomeDBiP08644.
TreeFamiTF312796.

Enzyme and pathway databases

ReactomeiR-RNO-112412. SOS-mediated signalling.
R-RNO-1169092. Activation of RAS in B cells.
R-RNO-1250347. SHC1 events in ERBB4 signaling.
R-RNO-1433557. Signaling by SCF-KIT.
R-RNO-167044. Signalling to RAS.
R-RNO-171007. p38MAPK events.
R-RNO-179812. GRB2 events in EGFR signaling.
R-RNO-180336. SHC1 events in EGFR signaling.
R-RNO-186763. Downstream signal transduction.
R-RNO-1963640. GRB2 events in ERBB2 signaling.
R-RNO-210993. Tie2 Signaling.
R-RNO-2179392. EGFR Transactivation by Gastrin.
R-RNO-2424491. DAP12 signaling.
R-RNO-2428933. SHC-related events triggered by IGF1R.
R-RNO-2871796. FCERI mediated MAPK activation.
R-RNO-375165. NCAM signaling for neurite out-growth.
R-RNO-5218921. VEGFR2 mediated cell proliferation.
R-RNO-5621575. CD209 (DC-SIGN) signaling.
R-RNO-5654688. SHC-mediated cascade:FGFR1.
R-RNO-5654693. FRS-mediated FGFR1 signaling.
R-RNO-5654699. SHC-mediated cascade:FGFR2.
R-RNO-5654700. FRS-mediated FGFR2 signaling.
R-RNO-5654704. SHC-mediated cascade:FGFR3.
R-RNO-5654706. FRS-mediated FGFR3 signaling.
R-RNO-5654712. FRS-mediated FGFR4 signaling.
R-RNO-5654719. SHC-mediated cascade:FGFR4.
R-RNO-5658442. Regulation of RAS by GAPs.
R-RNO-5673000. RAF activation.
R-RNO-5673001. RAF/MAP kinase cascade.
R-RNO-5674135. MAP2K and MAPK activation.
R-RNO-5675221. Negative regulation of MAPK pathway.
R-RNO-74751. Insulin receptor signalling cascade.
R-RNO-8849471. PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases.
R-RNO-8851805. MET activates RAS signaling.

Miscellaneous databases

PROiP08644.

Gene expression databases

BgeeiENSRNOG00000009338.
ExpressionAtlasiP08644. baseline and differential.
GenevisibleiP08644. RN.

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]
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiPS51421. RAS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRASK_RAT
AccessioniPrimary (citable) accession number: P08644
Secondary accession number(s): P46203, P97914
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: July 19, 2004
Last modified: November 30, 2016
This is version 162 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

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 one 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.