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P01116 (RASK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 175. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
GTPase KRas
Alternative name(s):
K-Ras 2
Ki-Ras
c-K-ras
c-Ki-ras

Cleaved into the following chain:

  1. GTPase KRas, N-terminally processed
Gene names
Name:KRAS
Synonyms:KRAS2, RASK2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length189 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.

Enzyme regulation

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).

Subunit structure

Interacts with PHLPP. Interacts (active GTP-bound form preferentially) with RGS14 By similarity.

Subcellular location

Cell membrane; Lipid-anchor; Cytoplasmic side.

Post-translational modification

Acetylation at Lys-104 prevents interaction with guanine nucleotide exchange factors (GEFs). Ref.17 Ref.20

Involvement in disease

Leukemia, acute myelogenous (AML) [MIM:601626]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.25

Leukemia, juvenile myelomonocytic (JMML) [MIM:607785]: An 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.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Noonan syndrome 3 (NS3) [MIM:609942]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.28 Ref.31 Ref.33 Ref.34 Ref.35 Ref.36

Gastric cancer (GASC) [MIM:613659]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.14 Ref.24 Ref.26

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. Ref.23

Cardiofaciocutaneous syndrome 2 (CFC2) [MIM:615278]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.30 Ref.31 Ref.34 Ref.36 Ref.37

KRAS mutations are involved in cancer development.

Sequence similarities

Belongs to the small GTPase superfamily. Ras family.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseCardiomyopathy
Deafness
Disease mutation
Ectodermal dysplasia
Mental retardation
Proto-oncogene
   LigandGTP-binding
Nucleotide-binding
   PTMAcetylation
Lipoprotein
Methylation
Palmitate
Prenylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processFc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

GTP catabolic process

Inferred from electronic annotation. Source: InterPro

MAPK cascade

Traceable author statement. Source: Reactome

Ras protein signal transduction

Traceable author statement. Source: Reactome

activation of MAPKK activity

Traceable author statement. Source: Reactome

axon guidance

Traceable author statement. Source: Reactome

blood coagulation

Traceable author statement. Source: Reactome

cytokine-mediated signaling pathway

Inferred from electronic annotation. Source: Ensembl

epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

fibroblast growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

innate immune response

Traceable author statement. Source: Reactome

insulin receptor signaling pathway

Traceable author statement. Source: Reactome

leukocyte migration

Traceable author statement. Source: Reactome

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

positive regulation of MAP kinase activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of NF-kappaB transcription factor activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of gene expression

Inferred from mutant phenotype PubMed 22065586. Source: BHF-UCL

positive regulation of nitric-oxide synthase activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein phosphorylation

Inferred from mutant phenotype PubMed 22065586. Source: BHF-UCL

response to glucocorticoid

Inferred from electronic annotation. Source: Ensembl

response to mineralocorticoid

Inferred from electronic annotation. Source: Ensembl

small GTPase mediated signal transduction

Traceable author statement. Source: Reactome

social behavior

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentmembrane raft

Inferred from electronic annotation. Source: Ensembl

mitochondrion

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionGDP binding

Inferred from electronic annotation. Source: Ensembl

GMP binding

Inferred from electronic annotation. Source: Ensembl

GTP binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein complex binding

Inferred from direct assay PubMed 23209302. Source: MGI

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

FntaQ046312EBI-367427,EBI-602447From a different organism.
RAF1P040492EBI-367427,EBI-365996
RASSF2P507492EBI-367415,EBI-960081

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Isoforms differ in the C-terminal region which is encoded by two alternative exons (IVA and IVB).
Isoform 2A (identifier: P01116-1)

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.
Isoform 2B (identifier: P01116-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 186186GTPase KRas
PRO_0000082641
Initiator methionine11Removed; alternate Ref.17
Chain2 – 186185GTPase KRas, N-terminally processed
PRO_0000326480
Propeptide187 – 1893Removed in mature form
PRO_0000281291

Regions

Nucleotide binding10 – 178GTP
Nucleotide binding57 – 615GTP
Nucleotide binding116 – 1194GTP
Region166 – 18520Hypervariable region
Motif32 – 409Effector region

Amino acid modifications

Modified residue11N-acetylmethionine; in GTPase KRas; alternate Ref.17
Modified residue21N-acetylthreonine; in GTPase KRas, N-terminally processed Ref.17
Modified residue1041N6-acetyllysine Ref.20
Modified residue1861Cysteine methyl ester By similarity
Lipidation1801S-palmitoyl cysteine By similarity
Lipidation1861S-farnesyl cysteine By similarity

Natural variations

Alternative sequence151 – 1533RVE → GVD in isoform 2B.
VSP_011140
Alternative sequence165 – 18925QYRLK…KCIIM → KHKEKMSKDGKKKKKKSKTK CVIM in isoform 2B.
VSP_011141
Natural variant51K → E in NS3. Ref.33
VAR_065144
Natural variant51K → 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. Ref.26 Ref.34 Ref.36
VAR_064849
Natural variant101G → GG in one individual with 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. Ref.25
VAR_034601
Natural variant121G → A in a colorectal cancer sample; somatic mutation. Ref.32
VAR_036305
Natural variant121G → C in lung carcinoma; somatic mutation. Ref.12 Ref.29
VAR_006839
Natural variant121G → D in pancreatic carcinoma, GASC and lung carcinoma; somatic mutation. Ref.23 Ref.24 Ref.29 Ref.32
VAR_016026
Natural variant121G → R in lung cancer and bladder cancer; somatic mutation. Ref.15
VAR_016027
Natural variant121G → S in lung carcinoma and GASC; somatic mutation. Ref.24 Ref.29 Ref.32
VAR_016028
Natural variant121G → V in lung carcinoma, pancreatic carcinoma, colon cancer and GASC; somatic mutation, constitutively activated. Ref.4 Ref.14 Ref.20 Ref.23 Ref.26 Ref.29 Ref.32
VAR_006840
Natural variant131G → D in a breast carcinoma cell line and GASC; somatic mutation. Ref.21 Ref.26 Ref.32
VAR_016029
Natural variant131G → R in pylocytic astrocytoma; somatic mutation; increase activation of the Ras pathway. Ref.27
VAR_065145
Natural variant141V → 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. Ref.31 Ref.34 Ref.36
VAR_026109
Natural variant221Q → 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. Ref.34 Ref.36
VAR_064850
Natural variant221Q → R in NS3; impairs GTPase-activating protein stimulated GTP hydrolysis with unaffected intrinsic functions and a virtually functional effector interaction. Ref.34 Ref.36
VAR_064851
Natural variant341P → L in NS3; characterized by a defective GTPase-activating protein sensitivity and a strongly reduced interaction with effectors. Ref.34 Ref.36
VAR_064852
Natural variant341P → Q in NS3. Ref.34
VAR_064853
Natural variant341P → R in CFC2; characterized by a defective GTPase-activating protein sensitivity and a strongly reduced interaction with effectors. Ref.31 Ref.36
VAR_026110
Natural variant361I → M in NS3. Ref.34
VAR_064854
Natural variant581T → 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. Ref.31 Ref.35 Ref.36
VAR_026111
Natural variant591A → T in bladder cancer and GASC; somatic mutation. Ref.22 Ref.26
VAR_016030
Natural variant601G → R in CFC2; characterized by a defective GTPase-activating protein sensitivity and a strongly reduced interaction with effectors. Ref.30 Ref.36
VAR_026112
Natural variant601G → S in NS3. Ref.35
VAR_065146
Natural variant611Q → H in lung carcinoma. Ref.7 Ref.11 Ref.29
Corresponds to variant rs17851045 [ dbSNP | Ensembl ].
VAR_006841
Natural variant611Q → R in a colorectal cancer sample; somatic mutation. Ref.32
VAR_036306
Natural variant711Y → H in CFC2. Ref.37
VAR_069784
Natural variant1171K → N in a colorectal cancer sample; somatic mutation. Ref.32
VAR_036307
Natural variant1461A → T in a colorectal cancer sample; somatic mutation. Ref.32
VAR_036308
Natural variant1471K → E in CFC2. Ref.37
VAR_069785
Isoform 2B:
Natural variant1521V → G in NS3.
Natural variant1531D → V in CFC2 and NS3, exhibits only minor alterations in its in vitro biochemical behavior compared to wild-type protein.
Natural variant1561F → I in NS3/CFC2.
Natural variant1561F → 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.

Experimental info

Mutagenesis1641R → A: Loss of GTP-binding activity.

Secondary structure

.............................. 189
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 2A (K-Ras4A) [UniParc].

Last modified July 21, 1986. Version 1.
Checksum: 973547B2E11C2C81

FASTA18921,656
        10         20         30         40         50         60 
MTEYKLVVVG AGGVGKSALT IQLIQNHFVD EYDPTIEDSY RKQVVIDGET CLLDILDTAG 

        70         80         90        100        110        120 
QEEYSAMRDQ YMRTGEGFLC VFAINNTKSF EDIHHYREQI KRVKDSEDVP MVLVGNKCDL 

       130        140        150        160        170        180 
PSRTVDTKQA QDLARSYGIP FIETSAKTRQ RVEDAFYTLV REIRQYRLKK ISKEEKTPGC 


VKIKKCIIM 

« Hide

Isoform 2B (K-Ras4B) [UniParc] [UniParc].

Checksum: B1B6D189BB259861
Show »

FASTA18821,425

References

« Hide 'large scale' references
[1]"Structure and organization of the human Ki-ras proto-oncogene and a related processed pseudogene."
McGrath J.P., Capon D.J., Smith D.H., Chen E.Y., Seeburg P.H., Goeddel D.V., Levinson A.D.
Nature 304:501-506(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 2A AND 2B).
[2]"Structure of the Ki-ras gene of the human lung carcinoma cell line Calu-1."
Shimizu K., Birnbaum D., Ruley M.A., Fasano O., Suard Y., Edlund L., Taparowsky E., Goldfarb M., Wigler M.
Nature 304:497-500(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 2A AND 2B).
Tissue: Lung carcinoma.
[3]"Activation of Ki-ras2 gene in human colon and lung carcinomas by two different point mutations."
Capon D.J., Seeburg P.H., McGrath J.P., Hayflick J.S., Edman U., Levinson A.D., Goeddel D.V.
Nature 304:507-513(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 2A AND 2B).
Tissue: Colon carcinoma and Lung.
[4]"Human colon carcinoma Ki-ras2 oncogene and its corresponding proto-oncogene."
McCoy M.S., Bargmann C.I., Weinberg R.A.
Mol. Cell. Biol. 4:1577-1582(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 2A AND 2B), VARIANT COLON CANCER VAL-12.
Tissue: Colon carcinoma.
[5]"The c-K-ras gene and human cancer (review)."
Kahn S., Yamamoto F., Almoguera C., Winter E., Forrester K., Jordano J., Perucho M.
Anticancer Res. 7:639-652(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2B).
[6]"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
Puhl H.L. III, Ikeda S.R., Aronstam R.S.
Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2B).
Tissue: Brain.
[7]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2B), VARIANT LUNG CARCINOMA HIS-61.
[8]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2B).
Tissue: Testis.
[9]SeattleSNPs variation discovery resource
Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[10]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]"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), VARIANT LUNG CARCINOMA HIS-61.
Tissue: Lung carcinoma.
[12]"Isolation of transforming sequences of two human lung carcinomas: structural and functional analysis of the activated c-K-ras oncogenes."
Nakano H., Yamamoto F., Neville C., Evans D., Mizuno T., Perucho M.
Proc. Natl. Acad. Sci. U.S.A. 81:71-75(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-37, VARIANT LUNG CARCINOMA CYS-12.
Tissue: Lung carcinoma.
[13]"Activation of the c-K-ras oncogene in a human pancreas carcinoma."
Hirai H., Okabe T., Anraku Y., Fujisawa M., Urabe A., Takaku F.
Biochem. Biophys. Res. Commun. 127:168-174(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-96.
Tissue: Pancreatic carcinoma.
[14]"Activated c-Ha-ras oncogene with a guanine to thymine transversion at the twelfth codon in a human stomach cancer cell line."
Deng G., Lu Y., Chen S., Miao J., Lu G., Li H., Cai H., Xu X., Zheng E., Liu P.
Cancer Res. 47:3195-3198(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-37, VARIANT GASC VAL-12.
[15]"Malignant activation of a K-ras oncogene in lung carcinoma but not in normal tissue of the same patient."
Santos E., Martin-Zanca D., Reddy P.E., Pierotti M.A., Porta G., Barbacid M.
Science 223:661-664(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-36, VARIANT BLADDER/LUNG CANCER ARG-12.
Tissue: Lung carcinoma.
[16]"Essential region for transforming activity of human c-Ha-ras-1."
Sekiya T., Tokunaga A., Fushimi M.
Jpn. J. Cancer Res. 76:787-791(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-37.
[17]Bienvenut W.V., Calvo F., Kolch W.
Submitted (FEB-2008) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 1-41; 43-147 AND 150-161, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT MET-1 AND THR-2, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Cervix carcinoma.
[18]"Activation of a human c-K-ras oncogene."
Yamamoto F., Perucho M.
Nucleic Acids Res. 12:8873-8885(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 38-96.
Tissue: Lung carcinoma.
[19]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[20]"Regulation of RAS oncogenicity by acetylation."
Yang M.H., Nickerson S., Kim E.T., Liot C., Laurent G., Spang R., Philips M.R., Shan Y., Shaw D.E., Bar-Sagi D., Haigis M.C., Haigis K.M.
Proc. Natl. Acad. Sci. U.S.A. 109:10843-10848(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION AT LYS-104, VARIANT VAL-12.
[21]"The human c-Kirsten ras gene is activated by a novel mutation in codon 13 in the breast carcinoma cell line MDA-MB231."
Kozma S.C., Bogaard M.E., Buser K., Saurer S.M., Bos J.L., Groner B., Hynes N.E.
Nucleic Acids Res. 15:5963-5971(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BREAST CANCER ASP-13.
[22]"Detection of a rare point mutation in Ki-ras of a human bladder cancer xenograft by polymerase chain reaction and direct sequencing."
Grimmond S.M., Raghavan D., Russell P.J.
Urol. Res. 20:121-126(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BLADDER CANCER THR-59.
[23]"Detection of point mutations in the Kirsten-ras oncogene provides evidence for the multicentricity of pancreatic carcinoma."
Motojima K., Urano T., Nagata Y., Shiku H., Tsurifune T., Kanematsu T.
Ann. Surg. 217:138-143(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PANCREATIC CARCINOMA ASP-12 AND VAL-12.
[24]"Clinicopathologic significance of the K-ras gene codon 12 point mutation in stomach cancer. An analysis of 140 cases."
Lee K.H., Lee J.S., Suh C., Kim S.W., Kim S.B., Lee J.H., Lee M.S., Park M.Y., Sun H.S., Kim S.H.
Cancer 75:2794-2801(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GASC SER-12 AND ASP-12.
[25]"Biochemical characterization of a novel KRAS insertion mutation from a human leukemia."
Bollag G., Adler F., elMasry N., McCabe P.C., Conner E. Jr., Thompson P., McCormick F., Shannon K.
J. Biol. Chem. 271:32491-32494(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN AML, VARIANT GLY-10 INS, CHARACTERIZATION OF VARIANT GLY-10 INS.
[26]"BRAF and KRAS mutations in stomach cancer."
Lee S.H., Lee J.W., Soung Y.H., Kim H.S., Park W.S., Kim S.Y., Lee J.H., Park J.Y., Cho Y.G., Kim C.J., Nam S.W., Kim S.H., Lee J.Y., Yoo N.J.
Oncogene 22:6942-6945(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GASC ASN-5; VAL-12; ASP-13 AND THR-59.
[27]"RAS pathway activation and an oncogenic RAS mutation in sporadic pilocytic astrocytoma."
Sharma M.K., Zehnbauer B.A., Watson M.A., Gutmann D.H.
Neurology 65:1335-1336(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PYLOCYTIC ASTROCYTOMA ARG-13.
[28]"Germline missense mutations affecting KRAS Isoform B are associated with a severe Noonan syndrome phenotype."
Carta C., Pantaleoni F., Bocchinfuso G., Stella L., Vasta I., Sarkozy A., Digilio C., Palleschi A., Pizzuti A., Grammatico P., Zampino G., Dallapiccola B., Gelb B.D., Tartaglia M.
Am. J. Hum. Genet. 79:129-135(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NS3 GLY-152 (ISOSORM 2) AND VAL-153 (ISOFORM 2).
[29]"Distinct epidermal growth factor receptor and KRAS mutation patterns in non-small cell lung cancer patients with different tobacco exposure and clinicopathologic features."
Tam I.Y.S., Chung L.P., Suen W.S., Wang E., Wong M.C.M., Ho K.K., Lam W.K., Chiu S.W., Girard L., Minna J.D., Gazdar A.F., Wong M.P.
Clin. Cancer Res. 12:1647-1653(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LUNG CARCINOMA CYS-12; ASP-12; SER-12; VAL-12 AND HIS-61.
[30]"Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome."
Niihori T., Aoki Y., Narumi Y., Neri G., Cave H., Verloes A., Okamoto N., Hennekam R.C.M., Gillessen-Kaesbach G., Wieczorek D., Kavamura M.I., Kurosawa K., Ohashi H., Wilson L., Heron D., Bonneau D., Corona G., Kaname T. expand/collapse author list , Naritomi K., Baumann C., Matsumoto N., Kato K., Kure S., Matsubara Y.
Nat. Genet. 38:294-296(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CFC2 ARG-60.
[31]"Germline KRAS mutations cause Noonan syndrome."
Schubbert S., Zenker M., Rowe S.L., Boell S., Klein C., Bollag G., van der Burgt I., Musante L., Kalscheuer V., Wehner L.-E., Nguyen H., West B., Zhang K.Y.J., Sistermans E., Rauch A., Niemeyer C.M., Shannon K., Kratz C.P.
Nat. Genet. 38:331-336(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NS3 ILE-14 AND ILE-58, VARIANT CFC2 ARG-34, CHARACTERIZATION OF VARIANTS NS3 ILE-14 AND ILE-58.
[32]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] ALA-12; ASP-12; SER-12; VAL-12; ASP-13; ARG-61; ASN-117 AND THR-146.
[33]"Further evidence of genetic heterogeneity in Costello syndrome: involvement of the KRAS gene."
Bertola D.R., Pereira A.C., Brasil A.S., Albano L.M., Kim C.A., Krieger J.E.
J. Hum. Genet. 52:521-526(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NS3 GLU-5.
[34]"Expansion of the genotypic and phenotypic spectrum in patients with KRAS germline mutations."
Zenker M., Lehmann K., Schulz A.L., Barth H., Hansmann D., Koenig R., Korinthenberg R., Kreiss-Nachtsheim M., Meinecke P., Morlot S., Mundlos S., Quante A.S., Raskin S., Schnabel D., Wehner L.E., Kratz C.P., Horn D., Kutsche K.
J. Med. Genet. 44:131-135(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NS3 ILE-14; ARG-22; LEU-34; GLN-34; MET-36 AND VAL-153 (ISOFORM 2), VARIANT CFC2 GLU-22, VARIANT NS3/CFC2 ILE-156 (ISOFORM 2), VARIANTS ASN-5 AND LEU-156 (ISOFORM 2).
[35]"Craniosynostosis in patients with Noonan syndrome caused by germline KRAS mutations."
Kratz C.P., Zampino G., Kriek M., Kant S.G., Leoni C., Pantaleoni F., Oudesluys-Murphy A.M., Di Rocco C., Kloska S.P., Tartaglia M., Zenker M.
Am. J. Med. Genet. A 149:1036-1040(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NS3 ILE-58 AND SER-60.
[36]"Germline KRAS mutations cause aberrant biochemical and physical properties leading to developmental disorders."
Gremer L., Merbitz-Zahradnik T., Dvorsky R., Cirstea I.C., Kratz C.P., Zenker M., Wittinghofer A., Ahmadian M.R.
Hum. Mutat. 32:33-43(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS NS3 ILE-14; ARG-22; LEU-34; ILE-58 AND VAL-153 (ISOFORM 2), CHARACTERIZATION OF VARIANTS CFC2 GLU-22; ARG-34 AND ARG-60, CHARACTERIZATION OF VARIANTS ASN-5 AND LEU-156 (ISOFORM 2).
[37]"Two novel germline KRAS mutations: expanding the molecular and clinical phenotype."
Stark Z., Gillessen-Kaesbach G., Ryan M.M., Cirstea I.C., Gremer L., Ahmadian M.R., Savarirayan R., Zenker M.
Clin. Genet. 81:590-594(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CFC2 HIS-71 AND GLU-147.
+Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology
GeneReviews
SHMPD

The Singapore human mutation and polymorphism database

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L00049 expand/collapse EMBL AC list , L00045, L00046, L00047 Genomic DNA. Translation: AAB59444.1.
L00048 expand/collapse EMBL AC list , 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.
PIRTVHUK. A93311.
TVHU2K. B93311.
RefSeqNP_004976.2. NM_004985.4.
NP_203524.1. NM_033360.3.
UniGeneHs.37003.
Hs.505033.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1D8DX-ray2.00P169-173[»]
1D8EX-ray3.00P169-173[»]
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[»]
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[»]
ProteinModelPortalP01116.
SMRP01116. Positions 1-166.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110043. 32 interactions.
DIPDIP-33951N.
IntActP01116. 20 interactions.
MINTMINT-131580.
STRING9606.ENSP00000256078.

Chemistry

ChEMBLCHEMBL2189121.

PTM databases

PhosphoSiteP01116.

Polymorphism databases

DMDM131875.

Proteomic databases

PaxDbP01116.
PeptideAtlasP01116.
PRIDEP01116.

Protocols and materials databases

DNASU3845.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000256078; ENSP00000256078; ENSG00000133703. [P01116-1]
ENST00000311936; ENSP00000308495; ENSG00000133703. [P01116-2]
GeneID3845.
KEGGhsa:3845.
UCSCuc001rgp.1. human. [P01116-1]
uc001rgq.1. human. [P01116-2]

Organism-specific databases

CTD3845.
GeneCardsGC12M025358.
HGNCHGNC:6407. KRAS.
MIM190070. gene.
601626. phenotype.
607785. phenotype.
609942. phenotype.
613659. phenotype.
615278. phenotype.
neXtProtNX_P01116.
Orphanet1340. Cardiofaciocutaneous syndrome.
3071. Costello 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.
357194. Selection of therapeutic option in colorectal cancer.
357191. Selection of therapeutic option in non-small cell lung carcinoma.
PharmGKBPA30196.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1100.
HOGENOMHOG000233973.
HOVERGENHBG009351.
InParanoidP01116.
KOK07827.
OMARRYNREM.
OrthoDBEOG7QVM41.
PhylomeDBP01116.
TreeFamTF312796.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_604. Hemostasis.
REACT_6900. Immune System.
SignaLinkP01116.

Gene expression databases

ArrayExpressP01116.
BgeeP01116.
CleanExHS_KRAS.
GenevestigatorP01116.

Family and domain databases

Gene3D3.40.50.300. 1 hit.
InterProIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR020849. Small_GTPase_Ras.
[Graphical view]
PANTHERPTHR24070. PTHR24070. 1 hit.
PfamPF00071. Ras. 1 hit.
[Graphical view]
PRINTSPR00449. RASTRNSFRMNG.
SMARTSM00173. RAS. 1 hit.
[Graphical view]
SUPFAMSSF52540. SSF52540. 1 hit.
TIGRFAMsTIGR00231. small_GTP. 1 hit.
PROSITEPS51421. RAS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSKRAS. human.
EvolutionaryTraceP01116.
GeneWikiKRAS.
GenomeRNAi3845.
NextBio15131.
PROP01116.
SOURCESearch...

Entry information

Entry nameRASK_HUMAN
AccessionPrimary (citable) accession number: P01116
Secondary accession number(s): A8K8Z5 expand/collapse secondary AC list , B0LPF9, P01118, Q96D10
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: April 16, 2014
This is version 175 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM