P01116 (RASK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	189 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
Enzyme regulation	Alternate 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).
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 syndrome characterized by facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears. Other features can include short stature, a short neck with webbing or redundancy of skin, cardiac anomalies, deafness, motor delay and variable intellectual deficits. 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 (CFC syndrome) [MIM:115150]: 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. The inheritance of CFC syndrome is autosomal dominant. Note: The disease is caused by mutations affecting the gene represented in this entry. KRAS mutations are involved in cancer development.
Sequence similarities	Belongs to the small GTPase superfamily. Ras family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Cardiomyopathy Deafness Disease mutation Proto-oncogene
Ligand	GTP-binding Nucleotide-binding
PTM	Acetylation Lipoprotein Methylation Palmitate Prenylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	MAPK cascade Traceable author statement. Source: Reactome Ras protein signal transduction Traceable author statement. Source: Reactome actin cytoskeleton organization Inferred from electronic annotation. Source: Compara 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: Compara 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 negative regulation of neuron apoptotic process Inferred from electronic annotation. Source: Compara neurotrophin TRK receptor signaling pathway Traceable author statement. Source: Reactome positive regulation of MAP kinase activity Inferred from electronic annotation. Source: Compara positive regulation of NF-kappaB transcription factor activity Inferred from electronic annotation. Source: Compara positive regulation of Rac protein signal transduction Inferred from electronic annotation. Source: Compara positive regulation of cell proliferation Inferred from electronic annotation. Source: Compara 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: Compara regulation of long-term neuronal synaptic plasticity Inferred from electronic annotation. Source: Compara regulation of synaptic transmission, GABAergic Inferred from electronic annotation. Source: Compara response to glucocorticoid stimulus Inferred from electronic annotation. Source: Compara response to mineralocorticoid stimulus Inferred from electronic annotation. Source: Compara social behavior Inferred from electronic annotation. Source: Compara striated muscle cell differentiation Inferred from electronic annotation. Source: Compara visual learning Inferred from electronic annotation. Source: Compara
Cellular_component	membrane raft Inferred from electronic annotation. Source: Compara mitochondrion Inferred from electronic annotation. Source: Compara plasma membrane Traceable author statement. Source: Reactome
Molecular_function	GDP binding Inferred from electronic annotation. Source: Compara GMP binding Inferred from electronic annotation. Source: Compara GTP binding Inferred from electronic annotation. Source: UniProtKB-KW GTPase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Fnta	Q04631	2	EBI-367427,EBI-602447	From a different organism.
RAF1	P04049	2	EBI-367427,EBI-365996
RASSF2	P50749	2	EBI-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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 186

186

GTPase KRas

PRO_0000082641

Initiator methionine

1

1

Removed; alternate Ref.17

Chain

2 – 186

185

GTPase KRas, N-terminally processed

PRO_0000326480

Propeptide

187 – 189

3

Removed in mature form

PRO_0000281291

Regions

Nucleotide binding

10 – 17

8

GTP

Nucleotide binding

57 – 61

5

GTP

Nucleotide binding

116 – 119

4

GTP

Region

166 – 185

20

Hypervariable region

Motif

32 – 40

9

Effector region

Amino acid modifications

Modified residue

1

1

N-acetylmethionine; in GTPase KRas; alternate Ref.17

Modified residue

2

1

N-acetylthreonine; in GTPase KRas, N-terminally processed Ref.17

Modified residue

104

1

N6-acetyllysine Ref.20

Modified residue

186

1

Cysteine methyl ester

Lipidation

180

1

S-palmitoyl cysteine

Lipidation

186

1

S-farnesyl cysteine

Natural variations

Alternative sequence

151 – 153

3

RVE → GVD in isoform 2B.

VSP_011140

Alternative sequence

165 – 189

25

QYRLK…KCIIM → KHKEKMSKDGKKKKKKSKTK CVIM in isoform 2B.

VSP_011141

Natural variant

5

1

K → E in NS3. Ref.33

VAR_065144

Natural variant

5

1

K → 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 variant

10

1

G → 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 variant

12

1

G → A in a colorectal cancer sample; somatic mutation. Ref.32

VAR_036305

Natural variant

12

1

G → C in lung carcinoma; somatic mutation. Ref.12 Ref.29

VAR_006839

Natural variant

12

1

G → D in pancreatic carcinoma, GASC and lung carcinoma; somatic mutation. Ref.23 Ref.24 Ref.29 Ref.32

VAR_016026

Natural variant

12

1

G → R in lung cancer and bladder cancer; somatic mutation. Ref.15

VAR_016027

Natural variant

12

1

G → S in lung carcinoma and GASC; somatic mutation. Ref.24 Ref.29 Ref.32

VAR_016028

Natural variant

12

1

G → 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 variant

13

1

G → D in a breast carcinoma cell line and GASC; somatic mutation. Ref.21 Ref.26 Ref.32

VAR_016029

Natural variant

13

1

G → R in pylocytic astrocytoma; somatic mutation; increase activation of the Ras pathway. Ref.27

VAR_065145

Natural variant

14

1

V → 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 variant

22

1

Q → E in CFC 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. Ref.34 Ref.36

VAR_064850

Natural variant

22

1

Q → 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 variant

34

1

P → 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 variant

34

1

P → Q in NS3. Ref.34

VAR_064853

Natural variant

34

1

P → R in CFC syndrome; characterized by a defective GTPase-activating protein sensitivity and a strongly reduced interaction with effectors. Ref.31 Ref.36

VAR_026110

Natural variant

36

1

I → M in NS3. Ref.34

VAR_064854

Natural variant

58

1

T → 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 variant

59

1

A → T in bladder cancer and GASC; somatic mutation. Ref.22 Ref.26

VAR_016030

Natural variant

60

1

G → R in CFC syndrome; characterized by a defective GTPase-activating protein sensitivity and a strongly reduced interaction with effectors. Ref.30 Ref.36

VAR_026112

Natural variant

60

1

G → S in NS3. Ref.35

VAR_065146

Natural variant

61

1

Q → H in lung carcinoma. Ref.7 Ref.11 Ref.29
Corresponds to variant rs17851045 [ dbSNP | Ensembl ].

VAR_006841

Natural variant

61

1

Q → R in a colorectal cancer sample; somatic mutation. Ref.32

VAR_036306

Natural variant

117

1

K → N in a colorectal cancer sample; somatic mutation. Ref.32

VAR_036307

Natural variant

146

1

A → T in a colorectal cancer sample; somatic mutation. Ref.32

VAR_036308

Isoform 2B:

Natural variant

152

1

V → G in NS3.

Natural variant

153

1

D → V in CFC syndrome and NS3, exhibits only minor alterations in its in vitro biochemical behavior compared to wild-type protein.

Natural variant

156

1

F → I in NS3/CFC syndrome.

Natural variant

156

1

F → 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

Mutagenesis

164

1

R → A: Loss of GTP-binding activity.

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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.

.

.

.

.

189

Helix Strand Turn

Details...

Beta strand

3 – 9

7

Helix

16 – 25

10

Beta strand

38 – 46

9

Beta strand

49 – 57

9

Helix

65 – 74

10

Beta strand

76 – 83

8

Helix

87 – 104

18

Beta strand

111 – 116

6

Beta strand

120 – 122

3

Helix

127 – 137

11

Beta strand

141 – 143

3

Turn

146 – 148

3

Helix

152 – 164

13

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2A (K-Ras4A) [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 973547B2E11C2C81	FASTA	189	21,656
	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
	Isoform 2B (K-Ras4B) [UniParc] [UniParc]. Checksum: B1B6D189BB259861	FASTA	188	21,425
	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 GVDDAFYTLV REIRKHKEKM SKDGKKKKKK SKTKCVIM

References

	« Hide 'large scale' referencesShow '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. , 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. , 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, 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. , 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 CFC SYNDROME 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 CFC SYNDROME 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. , 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 CFC SYNDROME GLU-22, VARIANT NS3/CFC SYNDROME 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 CFC SYNDROME GLU-22; ARG-34 AND ARG-60, CHARACTERIZATION OF VARIANTS ASN-5 AND LEU-156 (ISOFORM 2).
+	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 , 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.

IPI

IPI00423568.
IPI00423570.

PIR

TVHUK. A93311.
TVHU2K. B93311.

RefSeq

NP_004976.2. NM_004985.3.
NP_203524.1. NM_033360.2.

UniGene

Hs.37003.
Hs.505033.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1D8D	X-ray	2.00	P	169-173	[»]
1D8E	X-ray	3.00	P	169-173	[»]
1KZO	X-ray	2.20	C	169-173	[»]
1KZP	X-ray	2.10	C	169-173	[»]
3GFT	X-ray	2.27	A/B/C/D/E/F	1-164	[»]
4DSN	X-ray	2.03	A	2-164	[»]
4DSO	X-ray	1.85	A	2-164	[»]
4EPR	X-ray	2.00	A	1-164	[»]
4EPT	X-ray	2.00	A	1-164	[»]
4EPV	X-ray	1.35	A	1-164	[»]
4EPW	X-ray	1.70	A	1-164	[»]
4EPX	X-ray	1.76	A	1-164	[»]
4EPY	X-ray	1.80	A	1-164	[»]

ProteinModelPortal

P01116.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-33951N.

IntAct

P01116. 14 interactions.

MINT

MINT-131580.

STRING

9606.ENSP00000256078.

PTM databases

PhosphoSite

P01116.

Polymorphism databases

DMDM

131875.

Proteomic databases

PaxDb

P01116.

PeptideAtlas

P01116.

PRIDE

P01116.

Protocols and materials databases

DNASU

3845.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000256078; ENSP00000256078; ENSG00000133703.
ENST00000311936; ENSP00000308495; ENSG00000133703.

GeneID

3845.

KEGG

hsa:3845.

UCSC

uc001rgp.1. human.
uc001rgq.1. human.

Organism-specific databases

CTD

3845.

GeneCards

GC12M025358.

HGNC

HGNC:6407. KRAS.

MIM

115150. phenotype.
190070. gene.
601626. phenotype.
607785. phenotype.
609942. phenotype.
613659. phenotype.

neXtProt

NX_P01116.

Orphanet

1340. Cardiofaciocutaneous syndrome.
3071. Costello syndrome.
1333. Familial pancreatic carcinoma.
86834. Juvenile myelomonocytic leukemia.
2612. Linear nevus sebaceus syndrome.
648. Noonan syndrome.

PharmGKB

PA30196.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1100.

HOGENOM

HOG000233973.

HOVERGEN

HBG009351.

InParanoid

P01116.

KO

K07827.

OMA

MSKEGKK.

OrthoDB

EOG4BRWMX.

PhylomeDB

P01116.

Enzyme and pathway databases

Pathway_Interaction_DB

pi3kcipathway. Class I PI3K signaling events.
cd8tcrdownstreampathway. Downstream signaling in naive CD8+ T cells.
ephbfwdpathway. EPHB forward signaling.
il2_1pathway. IL2-mediated signaling events.
trkrpathway. Neurotrophic factor-mediated Trk receptor signaling.
er_nongenomic_pathway. Plasma membrane estrogen receptor signaling.
tcrraspathway. Ras signaling in the CD4+ TCR pathway.
tcrpathway. TCR signaling in naive CD4+ T cells.
cd8tcrpathway. TCR signaling in naive CD8+ T cells.
pi3kplctrkpathway. Trk receptor signaling mediated by PI3K and PLC-gamma.
mapktrkpathway. Trk receptor signaling mediated by the MAPK pathway.

Reactome

REACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_604. Hemostasis.
REACT_6900. Immune System.

SignaLink

P01116.

Gene expression databases

ArrayExpress

P01116.

Bgee

P01116.

CleanEx

HS_KRAS.

Genevestigator

P01116.

GermOnline

ENSG00000133703. Homo sapiens.

Family and domain databases

InterPro

IPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR020849. Small_GTPase_Ras.
[Graphical view]

PANTHER

PTHR24070. PTHR24070. 1 hit.

Pfam

PF00071. Ras. 1 hit.
[Graphical view]

PRINTS

PR00449. RASTRNSFRMNG.

SMART

SM00173. RAS. 1 hit.
[Graphical view]

SUPFAM

SSF52540. SSF52540. 1 hit.

TIGRFAMs

TIGR00231. small_GTP. 1 hit.

PROSITE

PS51421. RAS. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

KRAS. human.

EvolutionaryTrace

P01116.

GenomeRNAi

3845.

NextBio

15131.

SOURCE

Search...

Entry information

Entry name

RASK_HUMAN

Accession

Primary (citable) accession number: P01116
Secondary accession number(s): A8K8Z5 , B0LPF9, P01118, Q96D10

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	May 29, 2013
This is version 165 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.