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Protein

GTPase KRas

Gene

KRAS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Ras proteins bind GDP/GTP and possess intrinsic GTPase activity. Plays an important role in the regulation of cell proliferation (PubMed:23698361, PubMed:22711838). 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 (PubMed:24623306).Curated3 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.3 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi10 – 18GTP2 Publications9
Nucleotide bindingi29 – 35GTP2 Publications7
Nucleotide bindingi59 – 60GTP2 Publications2
Nucleotide bindingi116 – 119GTP2 Publications4

GO - Molecular functioni

  • GDP binding Source: Ensembl
  • GMP binding Source: Ensembl
  • GTPase activity Source: Ensembl
  • GTP binding Source: UniProtKB-KW
  • identical protein binding Source: IntAct
  • LRR domain binding Source: Ensembl
  • protein-containing complex binding Source: MGI

GO - Biological processi

Keywordsi

LigandGTP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-112412 SOS-mediated signalling
R-HSA-1169092 Activation of RAS in B cells
R-HSA-1236382 Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants
R-HSA-1250196 SHC1 events in ERBB2 signaling
R-HSA-1250347 SHC1 events in ERBB4 signaling
R-HSA-1433557 Signaling by SCF-KIT
R-HSA-167044 Signalling to RAS
R-HSA-171007 p38MAPK events
R-HSA-179812 GRB2 events in EGFR signaling
R-HSA-180336 SHC1 events in EGFR signaling
R-HSA-186763 Downstream signal transduction
R-HSA-1963640 GRB2 events in ERBB2 signaling
R-HSA-210993 Tie2 Signaling
R-HSA-2179392 EGFR Transactivation by Gastrin
R-HSA-2424491 DAP12 signaling
R-HSA-2428933 SHC-related events triggered by IGF1R
R-HSA-2871796 FCERI mediated MAPK activation
R-HSA-375165 NCAM signaling for neurite out-growth
R-HSA-5218921 VEGFR2 mediated cell proliferation
R-HSA-5621575 CD209 (DC-SIGN) signaling
R-HSA-5637810 Constitutive Signaling by EGFRvIII
R-HSA-5654688 SHC-mediated cascade:FGFR1
R-HSA-5654693 FRS-mediated FGFR1 signaling
R-HSA-5654699 SHC-mediated cascade:FGFR2
R-HSA-5654700 FRS-mediated FGFR2 signaling
R-HSA-5654704 SHC-mediated cascade:FGFR3
R-HSA-5654706 FRS-mediated FGFR3 signaling
R-HSA-5654712 FRS-mediated FGFR4 signaling
R-HSA-5654719 SHC-mediated cascade:FGFR4
R-HSA-5655253 Signaling by FGFR2 in disease
R-HSA-5655291 Signaling by FGFR4 in disease
R-HSA-5655302 Signaling by FGFR1 in disease
R-HSA-5658442 Regulation of RAS by GAPs
R-HSA-5673000 RAF activation
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-5674135 MAP2K and MAPK activation
R-HSA-5675221 Negative regulation of MAPK pathway
R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants
R-HSA-6802948 Signaling by high-kinase activity BRAF mutants
R-HSA-6802949 Signaling by RAS mutants
R-HSA-6802952 Signaling by BRAF and RAF fusions
R-HSA-6802953 RAS signaling downstream of NF1 loss-of-function variants
R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF
R-HSA-74751 Insulin receptor signalling cascade
R-HSA-8849471 PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases
R-HSA-8851805 MET activates RAS signaling
R-HSA-8853334 Signaling by FGFR3 fusions in cancer
R-HSA-8853338 Signaling by FGFR3 point mutants in cancer
R-HSA-8951936 RUNX3 regulates p14-ARF
R-HSA-9026519 Activated NTRK2 signals through RAS
R-HSA-9028731 Activated NTRK2 signals through FRS2 and FRS3
SignaLinkiP01116
SIGNORiP01116

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, RASK2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000133703.11
HGNCiHGNC:6407 KRAS
MIMi190070 gene
neXtProtiNX_P01116

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

Leukemia, acute myelogenous (AML)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes.
See also OMIM:601626
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03460110G → GG in AML; expression in 3T3 cell causes cellular transformation; expression in COS cells activates the Ras-MAPK signaling pathway; lower GTPase activity; faster GDP dissociation rate. 1 Publication1
Leukemia, juvenile myelomonocytic (JMML)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn aggressive pediatric myelodysplastic syndrome/myeloproliferative disorder characterized by malignant transformation in the hematopoietic stem cell compartment with proliferation of differentiated progeny. Patients have splenomegaly, enlarged lymph nodes, rashes, and hemorrhages.
See also OMIM:607785
Noonan syndrome 3 (NS3)6 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells.
See also OMIM:609942
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0651445K → E in NS3. 1 PublicationCorresponds to variant dbSNP:rs193929331EnsemblClinVar.1
Natural variantiVAR_02610914V → I in NS3; affects activity and impairs responsiveness to GTPase activating proteins; characterized by a strong increase of both intrinsic and guanine nucleotide exchanged factor-catalyzed nucleotide exchange leading to an increased level of the activated state. 1 PublicationCorresponds to variant dbSNP:rs104894365EnsemblClinVar.1
Natural variantiVAR_06485122Q → R in NS3; impairs GTPase-activating protein stimulated GTP hydrolysis with unaffected intrinsic functions and a virtually functional effector interaction. Corresponds to variant dbSNP:rs727503110EnsemblClinVar.1
Natural variantiVAR_06485234P → L in NS3; characterized by a defective GTPase-activating protein sensitivity and a strongly reduced interaction with effectors. Corresponds to variant dbSNP:rs104894366EnsemblClinVar.1
Natural variantiVAR_06485334P → Q in NS3. 1
Natural variantiVAR_06485436I → M in NS3. Corresponds to variant dbSNP:rs727503109EnsemblClinVar.1
Natural variantiVAR_02611158T → I in NS3; affects activity and impairs responsiveness to GTPase activating proteins; exhibits only minor alterations in its in vitro biochemical behavior compared to wild-type protein. 2 PublicationsCorresponds to variant dbSNP:rs104894364EnsemblClinVar.1
Natural variantiVAR_06514660G → S in NS3. 1 PublicationCorresponds to variant dbSNP:rs104894359EnsemblClinVar.1
Isoform 2B (identifier: P01116-2)
Natural varianti152V → G in NS3. 1
Gastric cancer (GASC)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease.
See also OMIM:613659
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0648495K → N in GASC; found also in a patient with Costello syndrome; exhibits only minor alterations in its in vitro biochemical behavior compared to wild-type protein. 1 PublicationCorresponds to variant dbSNP:rs104894361EnsemblClinVar.1
Natural variantiVAR_00684012G → V in GASC; also found in lung carcinoma, pancreatic carcinoma and colon cancer; somatic mutation; it is constitutively activated and stimulates transcription activation of tumor suppressor genes in non-transformed fibroblasts. 8 PublicationsCorresponds to variant dbSNP:rs121913529EnsemblClinVar.1
Natural variantiVAR_01603059A → T in GASC; also found in bladder cancer; somatic mutation. 2 PublicationsCorresponds to variant dbSNP:rs121913528EnsemblClinVar.1
Defects in KRAS are a cause of pylocytic astrocytoma (PA). Pylocytic astrocytomas are neoplasms of the brain and spinal cord derived from glial cells which vary from histologically benign forms to highly anaplastic and malignant tumors.1 Publication
Cardiofaciocutaneous syndrome 2 (CFC2)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of cardiofaciocutaneous syndrome, a multiple congenital anomaly disorder characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. CFC2 patients often do not have the skin abnormalities, such as ichthyosis, hyperkeratosis, and hemangioma observed in CFC1.
See also OMIM:615278
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06485022Q → E in CFC2; exhibits an increase in intrinsic and guanine nucleotide exchange factor catalyzed nucleotide exchange in combination with an impaired GTPase-activating protein-stimulated GTP hydrolysis but functional in interaction with effectors. 2 Publications1
Natural variantiVAR_02611034P → R in CFC2; characterized by a defective GTPase-activating protein sensitivity and a strongly reduced interaction with effectors. 2 PublicationsCorresponds to variant dbSNP:rs104894366EnsemblClinVar.1
Natural variantiVAR_02611260G → R in CFC2; characterized by a defective GTPase-activating protein sensitivity and a strongly reduced interaction with effectors. 2 PublicationsCorresponds to variant dbSNP:rs104894359EnsemblClinVar.1
Natural variantiVAR_06978471Y → H in CFC2. 1 PublicationCorresponds to variant dbSNP:rs387907205EnsemblClinVar.1
Natural variantiVAR_069785147K → E in CFC2. 1 PublicationCorresponds to variant dbSNP:rs387907206EnsemblClinVar.1
KRAS mutations are involved in cancer development.9 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi164R → A: Loss of GTP-binding activity. 1

Keywords - Diseasei

Cardiomyopathy, Deafness, Disease mutation, Ectodermal dysplasia, Mental retardation, Proto-oncogene

Organism-specific databases

DisGeNETi3845
GeneReviewsiKRAS
MalaCardsiKRAS
MIMi601626 phenotype
607785 phenotype
609942 phenotype
613659 phenotype
615278 phenotype
OpenTargetsiENSG00000133703
Orphaneti1340 Cardiofaciocutaneous syndrome
1333 Familial pancreatic carcinoma
144 Hereditary nonpolyposis colon cancer
86834 Juvenile myelomonocytic leukemia
2612 Linear nevus sebaceus syndrome
648 Noonan syndrome
251612 Pilocytic astrocytoma
268114 RAS-associated autoimmune leukoproliferative disease
357194 Selection of therapeutic option in colorectal cancer
357191 Selection of therapeutic option in non-small cell lung carcinoma
PharmGKBiPA30196

Chemistry databases

ChEMBLiCHEMBL2189121
DrugBankiDB07780 FARNESYL DIPHOSPHATE
GuidetoPHARMACOLOGYi2824

Polymorphism and mutation databases

BioMutaiKRAS
DMDMi131875

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000826411 – 186GTPase KRasAdd BLAST186
Initiator methionineiRemoved; alternate1 Publication
ChainiPRO_00003264802 – 186GTPase KRas, N-terminally processedAdd BLAST185
PropeptideiPRO_0000281291187 – 189Removed in mature form3

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionine; in GTPase KRas; alternate1 Publication1
Modified residuei2N-acetylthreonine; in GTPase KRas, N-terminally processed1 Publication1
Modified residuei104N6-acetyllysine1 Publication1
Lipidationi180S-palmitoyl cysteineBy similarity1
Modified residuei186Cysteine methyl esterCombined sources1 Publication1
Lipidationi186S-farnesyl cysteineCombined sources1 Publication1

Post-translational modificationi

Acetylation at Lys-104 prevents interaction with guanine nucleotide exchange factors (GEFs).2 Publications

Keywords - PTMi

Acetylation, Lipoprotein, Methylation, Palmitate, Prenylation

Proteomic databases

EPDiP01116
MaxQBiP01116
PaxDbiP01116
PeptideAtlasiP01116
PRIDEiP01116
ProteomicsDBi51323
51324 [P01116-2]
TopDownProteomicsiP01116-2 [P01116-2]

PTM databases

iPTMnetiP01116
PhosphoSitePlusiP01116
SwissPalmiP01116

Expressioni

Gene expression databases

BgeeiENSG00000133703
CleanExiHS_KRAS
ExpressionAtlasiP01116 baseline and differential
GenevisibleiP01116 HS

Organism-specific databases

HPAiHPA049830

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 (PubMed:23698361). Interacts with SOS1 (PubMed:22431598).By similarity2 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • LRR domain binding Source: Ensembl

Protein-protein interaction databases

BioGridi110043, 458 interactors
CORUMiP01116
DIPiDIP-33951N
IntActiP01116, 70 interactors
MINTiP01116
STRINGi9606.ENSP00000256078

Chemistry databases

BindingDBiP01116

Structurei

Secondary structure

1189
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi3 – 9Combined sources7
Helixi16 – 25Combined sources10
Beta strandi27 – 30Combined sources4
Beta strandi38 – 46Combined sources9
Beta strandi49 – 57Combined sources9
Helixi60 – 62Combined sources3
Helixi65 – 74Combined sources10
Beta strandi76 – 83Combined sources8
Helixi87 – 91Combined sources5
Helixi93 – 104Combined sources12
Beta strandi105 – 107Combined sources3
Beta strandi111 – 116Combined sources6
Beta strandi120 – 122Combined sources3
Helixi127 – 137Combined sources11
Beta strandi141 – 143Combined sources3
Turni146 – 148Combined sources3
Helixi152 – 167Combined sources16
Helixi169 – 173Combined sources5
Beta strandi175 – 177Combined sources3
Beta strandi182 – 184Combined sources3

3D structure databases

ProteinModelPortaliP01116
SMRiP01116
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01116

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
InParanoidiP01116
KOiK07827
OMAiQSWAVNM
OrthoDBiEOG091G0UAU
PhylomeDBiP01116
TreeFamiTF312796

Family and domain databases

InterProiView protein in InterPro
IPR027417 P-loop_NTPase
IPR005225 Small_GTP-bd_dom
IPR001806 Small_GTPase
IPR020849 Small_GTPase_Ras-type
PANTHERiPTHR24070 PTHR24070, 1 hit
PfamiView protein in Pfam
PF00071 Ras, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
TIGRFAMsiTIGR00231 small_GTP, 1 hit
PROSITEiView protein in PROSITE
PS51421 RAS, 1 hit

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: P01116-1) [UniParc]FASTAAdd to basket
Also known as: K-Ras4A

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 QDLARSYGIP FIETSAKTRQ
160 170 180
RVEDAFYTLV REIRQYRLKK ISKEEKTPGC VKIKKCIIM
Length:189
Mass (Da):21,656
Last modified:July 21, 1986 - v1
Checksum:i973547B2E11C2C81
GO
Isoform 2B (identifier: P01116-2) [UniParc] [UniParc]FASTAAdd to basket
Also known as: K-Ras4B

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

Show »
Length:188
Mass (Da):21,425
Checksum:iB1B6D189BB259861
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0651445K → E in NS3. 1 PublicationCorresponds to variant dbSNP:rs193929331EnsemblClinVar.1
Natural variantiVAR_0648495K → N in GASC; found also in a patient with Costello syndrome; exhibits only minor alterations in its in vitro biochemical behavior compared to wild-type protein. 1 PublicationCorresponds to variant dbSNP:rs104894361EnsemblClinVar.1
Natural variantiVAR_03460110G → GG in AML; expression in 3T3 cell causes cellular transformation; expression in COS cells activates the Ras-MAPK signaling pathway; lower GTPase activity; faster GDP dissociation rate. 1 Publication1
Natural variantiVAR_03630512G → A in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs121913529EnsemblClinVar.1
Natural variantiVAR_00683912G → C in lung carcinoma; somatic mutation. 2 PublicationsCorresponds to variant dbSNP:rs121913530EnsemblClinVar.1
Natural variantiVAR_01602612G → D in GASC and JMML; also found in pancreatic carcinoma and lung carcinoma; somatic mutation. 5 PublicationsCorresponds to variant dbSNP:rs121913529EnsemblClinVar.1
Natural variantiVAR_01602712G → R in lung cancer and bladder cancer; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs121913530EnsemblClinVar.1
Natural variantiVAR_01602812G → S in GASC and JMML; also found in lung carcinoma; somatic mutation. 4 PublicationsCorresponds to variant dbSNP:rs121913530EnsemblClinVar.1
Natural variantiVAR_00684012G → V in GASC; also found in lung carcinoma, pancreatic carcinoma and colon cancer; somatic mutation; it is constitutively activated and stimulates transcription activation of tumor suppressor genes in non-transformed fibroblasts. 8 PublicationsCorresponds to variant dbSNP:rs121913529EnsemblClinVar.1
Natural variantiVAR_01602913G → D in GASC and JMML; also found in a breast carcinoma cell line; somatic mutation. 4 PublicationsCorresponds to variant dbSNP:rs112445441EnsemblClinVar.1
Natural variantiVAR_06514513G → R in pylocytic astrocytoma; somatic mutation; increase activation of the Ras pathway. 1 PublicationCorresponds to variant dbSNP:rs121913535EnsemblClinVar.1
Natural variantiVAR_02610914V → I in NS3; affects activity and impairs responsiveness to GTPase activating proteins; characterized by a strong increase of both intrinsic and guanine nucleotide exchanged factor-catalyzed nucleotide exchange leading to an increased level of the activated state. 1 PublicationCorresponds to variant dbSNP:rs104894365EnsemblClinVar.1
Natural variantiVAR_06485022Q → E in CFC2; exhibits an increase in intrinsic and guanine nucleotide exchange factor catalyzed nucleotide exchange in combination with an impaired GTPase-activating protein-stimulated GTP hydrolysis but functional in interaction with effectors. 2 Publications1
Natural variantiVAR_06485122Q → R in NS3; impairs GTPase-activating protein stimulated GTP hydrolysis with unaffected intrinsic functions and a virtually functional effector interaction. Corresponds to variant dbSNP:rs727503110EnsemblClinVar.1
Natural variantiVAR_06485234P → L in NS3; characterized by a defective GTPase-activating protein sensitivity and a strongly reduced interaction with effectors. Corresponds to variant dbSNP:rs104894366EnsemblClinVar.1
Natural variantiVAR_06485334P → Q in NS3. 1
Natural variantiVAR_02611034P → R in CFC2; characterized by a defective GTPase-activating protein sensitivity and a strongly reduced interaction with effectors. 2 PublicationsCorresponds to variant dbSNP:rs104894366EnsemblClinVar.1
Natural variantiVAR_06485436I → M in NS3. Corresponds to variant dbSNP:rs727503109EnsemblClinVar.1
Natural variantiVAR_02611158T → I in NS3; affects activity and impairs responsiveness to GTPase activating proteins; exhibits only minor alterations in its in vitro biochemical behavior compared to wild-type protein. 2 PublicationsCorresponds to variant dbSNP:rs104894364EnsemblClinVar.1
Natural variantiVAR_01603059A → T in GASC; also found in bladder cancer; somatic mutation. 2 PublicationsCorresponds to variant dbSNP:rs121913528EnsemblClinVar.1
Natural variantiVAR_02611260G → R in CFC2; characterized by a defective GTPase-activating protein sensitivity and a strongly reduced interaction with effectors. 2 PublicationsCorresponds to variant dbSNP:rs104894359EnsemblClinVar.1
Natural variantiVAR_06514660G → S in NS3. 1 PublicationCorresponds to variant dbSNP:rs104894359EnsemblClinVar.1
Natural variantiVAR_00684161Q → H in lung carcinoma. 3 PublicationsCorresponds to variant dbSNP:rs17851045EnsemblClinVar.1
Natural variantiVAR_03630661Q → R in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs121913240EnsemblClinVar.1
Natural variantiVAR_06978471Y → H in CFC2. 1 PublicationCorresponds to variant dbSNP:rs387907205EnsemblClinVar.1
Natural variantiVAR_036307117K → N in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs770248150EnsemblClinVar.1
Natural variantiVAR_036308146A → T in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs121913527EnsemblClinVar.1
Natural variantiVAR_069785147K → E in CFC2. 1 PublicationCorresponds to variant dbSNP:rs387907206EnsemblClinVar.1
Isoform 2B (identifier: P01116-2)
Natural varianti152V → G in NS3. 1
Natural varianti153D → V in CFC2 and NS3, exhibits only minor alterations in its in vitro biochemical behavior compared to wild-type protein. 1
Natural varianti156F → I in NS3/CFC2. 1
Natural varianti156F → L Found in a patient with Costello syndrome, exhibits an increase in intrinsic and guanine nucleotide exchange factor catalyzed nucleotide exchange in combination with an impaired GTPase-activating protein-stimulated GTP hydrolysis but functional in interaction with effectors. 1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_011140151 – 153RVE → GVD in isoform 2B. 5 Publications3
Alternative sequenceiVSP_011141165 – 189QYRLK…KCIIM → KHKEKMSKDGKKKKKKSKTK CVIM in isoform 2B. 5 PublicationsAdd BLAST25

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L00049
, L00045, L00046, L00047 Genomic DNA Translation: AAB59444.1
L00048
, L00045, L00046, L00047 Genomic DNA Translation: AAB59445.1
M54968 mRNA Translation: AAB41942.1
AF493917 mRNA Translation: AAM12631.1
BT007153 mRNA Translation: AAP35817.1
AK292510 mRNA Translation: BAF85199.1
CH471094 Genomic DNA Translation: EAW96511.1
CH471094 Genomic DNA Translation: EAW96512.1
EU332849 Genomic DNA Translation: ABY87538.1
BC013572 mRNA Translation: AAH13572.1
K01519 Genomic DNA No translation available.
K01520 Genomic DNA No translation available.
M25876 Genomic DNA Translation: AAA35683.1
M34904 Genomic DNA Translation: AAA36149.1
M30539 Genomic DNA Translation: AAA36557.1
X01669 Genomic DNA Translation: CAA25828.1
X02825 Genomic DNA Translation: CAA26593.1
K03210, K03209 Genomic DNA Translation: AAA36554.1
CCDSiCCDS8702.1 [P01116-2]
CCDS8703.1 [P01116-1]
PIRiA93311 TVHUK
B93311 TVHU2K
RefSeqiNP_004976.2, NM_004985.4 [P01116-2]
NP_203524.1, NM_033360.3 [P01116-1]
XP_006719132.1, XM_006719069.3 [P01116-1]
XP_011518955.1, XM_011520653.2 [P01116-2]
UniGeneiHs.37003
Hs.505033

Genome annotation databases

EnsembliENST00000256078; ENSP00000256078; ENSG00000133703 [P01116-1]
ENST00000311936; ENSP00000308495; ENSG00000133703 [P01116-2]
GeneIDi3845
KEGGihsa:3845
UCSCiuc001rgp.3 human [P01116-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiRASK_HUMAN
AccessioniPrimary (citable) accession number: P01116
Secondary accession number(s): A8K8Z5
, B0LPF9, P01118, Q96D10
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: July 18, 2018
This is version 223 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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