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Protein

GTPase KRas

Gene

KRAS

Organism
Homo sapiens (Human)
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. 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
  • protein complex binding Source: MGI

GO - Biological processi

Complete GO annotation...

Keywords - Ligandi

GTP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000133703-MONOMER.
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.
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

HGNCiHGNC:6407. KRAS.

Subcellular locationi

GO - Cellular componenti

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

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
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01602612G → D in pancreatic carcinoma; GASC; lung carcinoma and JMML; somatic mutation. 5 PublicationsCorresponds to variant rs121913529dbSNPEnsembl.1
Natural variantiVAR_01602812G → S in lung carcinoma; GASC and JMML; somatic mutation. 4 PublicationsCorresponds to variant rs121913530dbSNPEnsembl.1
Natural variantiVAR_01602913G → D in a breast carcinoma cell line; GASC and JMML; somatic mutation. 4 PublicationsCorresponds to variant rs112445441dbSNPEnsembl.1
Noonan syndrome 3 (NS3)5 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 rs193929331dbSNPEnsembl.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 rs104894365dbSNPEnsembl.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 rs727503110dbSNPEnsembl.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 rs104894366dbSNPEnsembl.1
Natural variantiVAR_06485334P → Q in NS3. 1
Natural variantiVAR_06485436I → M in NS3. Corresponds to variant rs727503109dbSNPEnsembl.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 rs104894364dbSNPEnsembl.1
Natural variantiVAR_06514660G → S in NS3. 1 PublicationCorresponds to variant rs104894359dbSNPEnsembl.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
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 rs104894361dbSNPEnsembl.1
Natural variantiVAR_01602612G → D in pancreatic carcinoma; GASC; lung carcinoma and JMML; somatic mutation. 5 PublicationsCorresponds to variant rs121913529dbSNPEnsembl.1
Natural variantiVAR_01602812G → S in lung carcinoma; GASC and JMML; somatic mutation. 4 PublicationsCorresponds to variant rs121913530dbSNPEnsembl.1
Natural variantiVAR_00684012G → V in lung carcinoma, pancreatic carcinoma, colon cancer and GASC; somatic mutation, constitutively activated, stimulates transcription activation of tumor suppressor genes in non-transformed fibroblasts. 8 PublicationsCorresponds to variant rs121913529dbSNPEnsembl.1
Natural variantiVAR_01602913G → D in a breast carcinoma cell line; GASC and JMML; somatic mutation. 4 PublicationsCorresponds to variant rs112445441dbSNPEnsembl.1
Natural variantiVAR_01603059A → T in bladder cancer and GASC; somatic mutation. 2 PublicationsCorresponds to variant rs121913528dbSNPEnsembl.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.

Cardiofaciocutaneous syndrome 2 (CFC2)4 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 rs104894366dbSNPEnsembl.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 rs104894359dbSNPEnsembl.1
Natural variantiVAR_06978471Y → H in CFC2. 1 PublicationCorresponds to variant rs387907205dbSNPEnsembl.1
Natural variantiVAR_069785147K → E in CFC2. 1 PublicationCorresponds to variant rs387907206dbSNPEnsembl.1
Isoform 2B (identifier: P01116-2)
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

KRAS mutations are involved in cancer development.

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.
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.
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
Modified residuei118S-nitrosocysteineBy similarity1
Lipidationi180S-palmitoyl cysteineBy similarity1
Modified residuei186Cysteine methyl esterBy similarity1
Lipidationi186S-farnesyl cysteineCurated1

Post-translational modificationi

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

Keywords - PTMi

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

Proteomic databases

EPDiP01116.
MaxQBiP01116.
PaxDbiP01116.
PeptideAtlasiP01116.
PRIDEiP01116.

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

WithEntry#Exp.IntActNotes
ARAFQ96II53EBI-367415,EBI-9383168
FntaQ046312EBI-367427,EBI-602447From a different organism.
RAF1P040492EBI-367427,EBI-365996
RASSF2P507492EBI-367415,EBI-960081

GO - Molecular functioni

  • protein complex binding Source: MGI

Protein-protein interaction databases

BioGridi110043. 444 interactors.
DIPiDIP-33951N.
IntActiP01116. 67 interactors.
MINTiMINT-131580.
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 strandi38 – 46Combined sources9
Beta strandi49 – 57Combined sources9
Helixi60 – 62Combined sources3
Helixi65 – 74Combined sources10
Beta strandi76 – 83Combined sources8
Helixi87 – 91Combined sources5
Helixi93 – 104Combined sources12
Beta strandi111 – 116Combined sources6
Beta strandi120 – 122Combined sources3
Helixi127 – 137Combined sources11
Beta strandi141 – 143Combined sources3
Turni146 – 148Combined sources3
Helixi152 – 164Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1D8DX-ray2.00P178-188[»]
1D8EX-ray3.00P178-188[»]
1KZOX-ray2.20C169-173[»]
1KZPX-ray2.10C169-173[»]
3GFTX-ray2.27A/B/C/D/E/F1-164[»]
4DSNX-ray2.03A2-164[»]
4DSOX-ray1.85A2-164[»]
4EPRX-ray2.00A1-164[»]
4EPTX-ray2.00A1-164[»]
4EPVX-ray1.35A1-164[»]
4EPWX-ray1.70A1-164[»]
4EPXX-ray1.76A1-164[»]
4EPYX-ray1.80A1-164[»]
4L8GX-ray1.52A1-169[»]
4LDJX-ray1.15A1-164[»]
4LPKX-ray1.50A/B1-169[»]
4LRWX-ray2.15A/B1-169[»]
4LUCX-ray1.29A/B1-169[»]
4LV6X-ray1.50A/B1-169[»]
4LYFX-ray1.57A/B/C1-169[»]
4LYHX-ray1.37A/B/C1-169[»]
4LYJX-ray1.93A1-169[»]
4M1OX-ray1.57A/B/C1-169[»]
4M1SX-ray1.55A/B/C1-169[»]
4M1TX-ray1.70A/B/C1-169[»]
4M1WX-ray1.58A/B/C1-169[»]
4M1YX-ray1.49A/B/C1-169[»]
4M21X-ray1.94A/B/C1-169[»]
4M22X-ray2.09A/B/C1-169[»]
4NMMX-ray1.89A1-164[»]
4OBEX-ray1.24A/B1-164[»]
4PZYX-ray1.88A/B1-164[»]
4PZZX-ray1.40A1-164[»]
4Q01X-ray1.29A/B1-164[»]
4Q02X-ray1.70A1-164[»]
4Q03X-ray1.20A1-164[»]
4QL3X-ray1.04A1-11[»]
A13-164[»]
4TQ9X-ray1.49A/B1-164[»]
4TQAX-ray1.13A/B1-164[»]
4WA7X-ray1.99A1-164[»]
5F2EX-ray1.40A1-169[»]
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.
OMAiRRYNREM.
OrthoDBiEOG091G0UAU.
PhylomeDBiP01116.
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: 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 rs193929331dbSNPEnsembl.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 rs104894361dbSNPEnsembl.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 rs121913529dbSNPEnsembl.1
Natural variantiVAR_00683912G → C in lung carcinoma; somatic mutation. 2 PublicationsCorresponds to variant rs121913530dbSNPEnsembl.1
Natural variantiVAR_01602612G → D in pancreatic carcinoma; GASC; lung carcinoma and JMML; somatic mutation. 5 PublicationsCorresponds to variant rs121913529dbSNPEnsembl.1
Natural variantiVAR_01602712G → R in lung cancer and bladder cancer; somatic mutation. 1 PublicationCorresponds to variant rs121913530dbSNPEnsembl.1
Natural variantiVAR_01602812G → S in lung carcinoma; GASC and JMML; somatic mutation. 4 PublicationsCorresponds to variant rs121913530dbSNPEnsembl.1
Natural variantiVAR_00684012G → V in lung carcinoma, pancreatic carcinoma, colon cancer and GASC; somatic mutation, constitutively activated, stimulates transcription activation of tumor suppressor genes in non-transformed fibroblasts. 8 PublicationsCorresponds to variant rs121913529dbSNPEnsembl.1
Natural variantiVAR_01602913G → D in a breast carcinoma cell line; GASC and JMML; somatic mutation. 4 PublicationsCorresponds to variant rs112445441dbSNPEnsembl.1
Natural variantiVAR_06514513G → R in pylocytic astrocytoma; somatic mutation; increase activation of the Ras pathway. 1 PublicationCorresponds to variant rs121913535dbSNPEnsembl.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 rs104894365dbSNPEnsembl.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 rs727503110dbSNPEnsembl.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 rs104894366dbSNPEnsembl.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 rs104894366dbSNPEnsembl.1
Natural variantiVAR_06485436I → M in NS3. Corresponds to variant rs727503109dbSNPEnsembl.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 rs104894364dbSNPEnsembl.1
Natural variantiVAR_01603059A → T in bladder cancer and GASC; somatic mutation. 2 PublicationsCorresponds to variant rs121913528dbSNPEnsembl.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 rs104894359dbSNPEnsembl.1
Natural variantiVAR_06514660G → S in NS3. 1 PublicationCorresponds to variant rs104894359dbSNPEnsembl.1
Natural variantiVAR_00684161Q → H in lung carcinoma. 3 PublicationsCorresponds to variant rs17851045dbSNPEnsembl.1
Natural variantiVAR_03630661Q → R in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant rs121913240dbSNPEnsembl.1
Natural variantiVAR_06978471Y → H in CFC2. 1 PublicationCorresponds to variant rs387907205dbSNPEnsembl.1
Natural variantiVAR_036307117K → N in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant rs770248150dbSNPEnsembl.1
Natural variantiVAR_036308146A → T in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant rs121913527dbSNPEnsembl.1
Natural variantiVAR_069785147K → E in CFC2. 1 PublicationCorresponds to variant rs387907206dbSNPEnsembl.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

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
SHMPD

The Singapore human mutation and polymorphism database

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1D8DX-ray2.00P178-188[»]
1D8EX-ray3.00P178-188[»]
1KZOX-ray2.20C169-173[»]
1KZPX-ray2.10C169-173[»]
3GFTX-ray2.27A/B/C/D/E/F1-164[»]
4DSNX-ray2.03A2-164[»]
4DSOX-ray1.85A2-164[»]
4EPRX-ray2.00A1-164[»]
4EPTX-ray2.00A1-164[»]
4EPVX-ray1.35A1-164[»]
4EPWX-ray1.70A1-164[»]
4EPXX-ray1.76A1-164[»]
4EPYX-ray1.80A1-164[»]
4L8GX-ray1.52A1-169[»]
4LDJX-ray1.15A1-164[»]
4LPKX-ray1.50A/B1-169[»]
4LRWX-ray2.15A/B1-169[»]
4LUCX-ray1.29A/B1-169[»]
4LV6X-ray1.50A/B1-169[»]
4LYFX-ray1.57A/B/C1-169[»]
4LYHX-ray1.37A/B/C1-169[»]
4LYJX-ray1.93A1-169[»]
4M1OX-ray1.57A/B/C1-169[»]
4M1SX-ray1.55A/B/C1-169[»]
4M1TX-ray1.70A/B/C1-169[»]
4M1WX-ray1.58A/B/C1-169[»]
4M1YX-ray1.49A/B/C1-169[»]
4M21X-ray1.94A/B/C1-169[»]
4M22X-ray2.09A/B/C1-169[»]
4NMMX-ray1.89A1-164[»]
4OBEX-ray1.24A/B1-164[»]
4PZYX-ray1.88A/B1-164[»]
4PZZX-ray1.40A1-164[»]
4Q01X-ray1.29A/B1-164[»]
4Q02X-ray1.70A1-164[»]
4Q03X-ray1.20A1-164[»]
4QL3X-ray1.04A1-11[»]
A13-164[»]
4TQ9X-ray1.49A/B1-164[»]
4TQAX-ray1.13A/B1-164[»]
4WA7X-ray1.99A1-164[»]
5F2EX-ray1.40A1-169[»]
ProteinModelPortaliP01116.
SMRiP01116.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110043. 444 interactors.
DIPiDIP-33951N.
IntActiP01116. 67 interactors.
MINTiMINT-131580.
STRINGi9606.ENSP00000256078.

Chemistry databases

BindingDBiP01116.
ChEMBLiCHEMBL2189121.
GuidetoPHARMACOLOGYi2824.

PTM databases

iPTMnetiP01116.
PhosphoSitePlusiP01116.
SwissPalmiP01116.

Polymorphism and mutation databases

BioMutaiKRAS.
DMDMi131875.

Proteomic databases

EPDiP01116.
MaxQBiP01116.
PaxDbiP01116.
PeptideAtlasiP01116.
PRIDEiP01116.

Protocols and materials databases

DNASUi3845.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi3845.
DisGeNETi3845.
GeneCardsiKRAS.
GeneReviewsiKRAS.
HGNCiHGNC:6407. KRAS.
HPAiHPA049830.
MalaCardsiKRAS.
MIMi190070. gene.
601626. phenotype.
607785. phenotype.
609942. phenotype.
613659. phenotype.
615278. phenotype.
neXtProtiNX_P01116.
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.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0395. Eukaryota.
COG1100. LUCA.
GeneTreeiENSGT00860000133672.
HOGENOMiHOG000233973.
HOVERGENiHBG009351.
InParanoidiP01116.
KOiK07827.
OMAiRRYNREM.
OrthoDBiEOG091G0UAU.
PhylomeDBiP01116.
TreeFamiTF312796.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000133703-MONOMER.
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.
SignaLinkiP01116.
SIGNORiP01116.

Miscellaneous databases

ChiTaRSiKRAS. human.
EvolutionaryTraceiP01116.
GeneWikiiKRAS.
GenomeRNAii3845.
PROiP01116.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000133703.
CleanExiHS_KRAS.
ExpressionAtlasiP01116. baseline and differential.
GenevisibleiP01116. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: P01116
Secondary accession number(s): A8K8Z5
, B0LPF9, P01118, Q96D10
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: November 30, 2016
This is version 205 of the entry and version 1 of the sequence. [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

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.