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Reviewed, UniProtKB/Swiss-Prot P01112 (RASH_HUMAN)

Last modified June 16, 2009. Version 130. Feed History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    GTPase HRas
Alternative name(s):
    Transforming protein p21
    p21ras
    H-Ras-1
    c-H-ras
    Ha-Ras
Cleaved into the following chain:
    1- Recommended name:
            GTPase HRas, N-terminally processed
Gene names
Name: HRAS
Synonyms: HRAS1
OrganismHomo sapiens (Human)
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. Ref.18 Ref.32

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

In its GTP-bound form interacts with PLCE1. Interacts with TBC1D10C. Interacts with RGL3 By similarity. Forms a signaling complex with RASGRP1 and DGKZ. Interacts with RASSF5.

Subcellular location

Cell membrane; Lipid-anchor; Cytoplasmic side. Golgi apparatus membrane; Lipid-anchor. Note: Shuttles between the plasma membrane and the Golgi apparatus. Ref.22

Post-translational modification

Palmitoylated by the ZDHHC9-GOLGA7 complex. A continuous cycle of de- and re-palmitoylation regulates rapid exchange between plasma membrane and Golgi. Ref.22 Ref.16 Ref.17 Ref.21

S-nitrosylated; critical for redox regulation. Important for stimulating guanine nucleotide exchange. No structural perturbation on nitrosylation.

Involvement in disease

Defects in HRAS are the cause of Costello syndrome [MIM:218040]; also known as faciocutaneoskeletal syndrome. Costello syndrome is a rare condition characterized by prenatally increased growth, postnatal growth deficiency, mental retardation, distinctive facial appearance, cardiovascular abnormalities (typically pulmonic stenosis, hypertrophic cardiomyopathy and/or atrial tachycardia), tumor predisposition, skin and musculoskeletal abnormalities.

Defects in HRAS are the cause of congenital myopathy with excess of muscle spindles (CMEMS) [MIM:218040]. CMEMS is a variant of Costello syndrome. Ref.41

Defects in HRAS may be a cause of susceptibility to Hurthle cell thyroid carcinoma [MIM:607464]; also known as Hurthle cell thyroid neoplasia. Hurthle cell thyroid carcinoma accounts for approximately 3% of all thyroid cancers. Although they are classified as variants of follicular neoplasms, they are more often multifocal and somewhat more aggressive and are less likely to take up iodine than are other follicular neoplasms. Ref.36

Mutations which change positions 12, 13 or 61 activate the potential of HRAS to transform cultured cells and are implicated in a variety of human tumors.

Defects in HRAS are a cause of bladder cancer [MIM:109800].

Defects in HRAS are the cause of oral squamous cell carcinoma (OSCC). Ref.35

Sequence similarities

Belongs to the small GTPase superfamily. Ras family.

Mass spectrometry

Molecular mass is 6.223±2 Da from positions 112 - 166. Determined by ESI. Ref.18

Molecular mass is 6.253±2 Da from positions 112 - 166. Determined by ESI. Includes one nitric oxide molecule. Ref.18

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 186186GTPase HRas
PRO_0000042996
Initiator methionine11Removed; alternate Ref.10
Chain2 – 186185GTPase HRas, N-terminally processed
PRO_0000326476
Propeptide187 – 1893Removed in mature form
PRO_0000042997

Regions

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

Amino acid modifications

Modified residue11N-acetylmethionine; in GTPase HRas; alternate Ref.10
Modified residue21N-acetylthreonine; in GTPase HRas, N-terminally processed Ref.10
Modified residue1181S-nitrosocysteine
Modified residue1861Cysteine methyl ester Ref.17
Lipidation1811S-palmitoyl cysteine Ref.22 Ref.16 Ref.17 Ref.21
Lipidation1841S-palmitoyl cysteine Ref.22 Ref.16 Ref.17 Ref.21
Lipidation1861S-farnesyl cysteine

Natural variations

Natural variant121G → A in Costello syndrome.
VAR_026106
Natural variant121G → C in Costello syndrome.
VAR_045975
Natural variant121G → E in Costello syndrome.
VAR_045976
Natural variant121G → S in Costello syndrome, OSCC and CMEMS.
VAR_006837
Natural variant121G → V in Costello syndrome, bladder carcinoma and CMEMS; constitutively activated; interacts and recruits PLCE1 to plasma membrane; loss of interaction with and recruitment to plasma membrane of PLCE1 when associated with F-32; loss of interaction with PLCE1 when associated with G-26, F-32 and S-35; no effect on interaction with PLCE1 when associated with A-29, G-34, G-37, N-38 and C-39.
VAR_006836
Natural variant131G → C in Costello syndrome.
VAR_026107
Natural variant131G → D in Costello syndrome.
VAR_026108
Natural variant221Q → K in CMEMS. Ref.41
VAR_045977
Natural variant581T → I in Costello syndrome.
VAR_045978
Natural variant611Q → K in follicular thyroid carcinoma samples; somatic mutation; increases transformation of cultured cell lines. Ref.36 Ref.33
VAR_045979
Natural variant611Q → L in melanoma; strongly reduced GTP hydrolysis in the presence of RAF1; increases transformation of cultured cell lines. Ref.36 Ref.33
VAR_006838
Natural variant631E → K in CMEMS. Ref.41
VAR_045980
Natural variant1171K → R in Costello syndrome.
VAR_045981
Natural variant1461A → T in Costello syndrome.
VAR_045982
Natural variant1461A → V in Costello syndrome.
VAR_045983

Experimental info

Mutagenesis171S → N: Dominant negative. Prevents PLCE1 EGF-induced recruitment to plasma membrane. Ref.15 Ref.19
Mutagenesis261N → G: Loss of interaction with PLCE1; when associated with V-12. Ref.15 Ref.19
Mutagenesis291V → A: No effect on interaction with PLCE1; when associated with V-12. Ref.15 Ref.19
Mutagenesis321Y → F: Loss of interaction and recruitment to plasma membrane of PLCE1; when associated with V-12. Ref.15 Ref.19
Mutagenesis341P → G: No effect on interaction with PLCE1; when associated with V-12. Ref.15 Ref.19
Mutagenesis351T → S: Loss of interaction with PLCE1; when associated with V-12. Ref.15 Ref.19
Mutagenesis371E → G: No effect on interaction with PLCE1; when associated with V-12. Ref.15 Ref.19
Mutagenesis381D → N: No effect on interaction with PLCE1; when associated with V-12. Ref.15 Ref.19
Mutagenesis391S → C: No effect on interaction with PLCE1; when associated with V-12. Ref.15 Ref.19
Mutagenesis591A → T: Loss of GTPase activity and creation of an autophosphorylation site. Ref.15
Mutagenesis611Q → I: Moderately increased transformation of cultured cell lines. Ref.33 Ref.15
Mutagenesis611Q → V: Strongly increased transformation of cultured cell lines. Ref.33 Ref.15
Mutagenesis831A → T: GTP-binding activity reduced by factor of 30. Ref.15 Ref.14
Mutagenesis1181C → S: Abolishes S-nitrosylation. No stimulation of guanine nucleotide exchange. Ref.18 Ref.32 Ref.15
Mutagenesis1191D → N: Loss of GTP-binding activity. Ref.15 Ref.14
Mutagenesis1441T → I: GTP-binding activity reduced by factor of 25. Ref.15 Ref.14
Mutagenesis164 – 1652RQ → AV: Loss of GTP-binding activity. Ref.15
Mutagenesis1811C → S: Exclusively localized in Golgi. Non-specifically localized on all endomembranes; when associated with S-184. Ref.22 Ref.17 Ref.15
Mutagenesis1841C → S: Mainly localized in Golgi. Non-specifically localized on all endomembranes; when associated with S-181. Ref.22 Ref.17 Ref.15

Secondary structure

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

Details...

Sequences

Sequence LengthMass (Da)Tools
P01112-1 [UniParc].

Last modified July 21, 1986. Version 1.
Checksum: EE6DC2D933E2856A

FASTA18921,298
        10         20         30         40         50         60 
MTEYKLVVVG AGGVGKSALT IQLIQNHFVD EYDPTIEDSY RKQVVIDGET CLLDILDTAG 

        70         80         90        100        110        120 
QEEYSAMRDQ YMRTGEGFLC VFAINNTKSF EDIHQYREQI KRVKDSDDVP MVLVGNKCDL 

       130        140        150        160        170        180 
AARTVESRQA QDLARSYGIP YIETSAKTRQ GVEDAFYTLV REIRQHKLRK LNPPDESGPG 


CMSCKCVLS 

« Hide

References

« Hide 'large scale' references
[1]"Complete nucleotide sequences of the T24 human bladder carcinoma oncogene and its normal homologue."
Capon D.J., Chen E.Y., Levinson A.D., Seeburg P.H., Goeddel D.V.
Nature 302:33-37(1983) [PubMed: 6298635] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Nucleotide sequence analysis of the T24 human bladder carcinoma oncogene."
Reddy E.P.
Science 220:1061-1063(1983) [PubMed: 6844927] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Molecular cloning and the total nucleotide sequence of the human c-Ha-ras-1 gene activated in a melanoma from a Japanese patient."
Sekiya T., Fushimi M., Hori H., Hirohashi S., Nishimura S., Sugimura T.
Proc. Natl. Acad. Sci. U.S.A. 81:4771-4775(1984) [PubMed: 6087347] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"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].
Tissue: Brain.
[5]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]"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 (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]"Human protein factory for converting the transcriptome into an in vitro-expressed proteome."
Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B. expand/collapse author list , Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., Nomura N.
Nat. Methods 5:1011-1017(2008) [PubMed: 19054851] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[8]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].
[9]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[10]Bienvenut W.V., Calvo F., Kolch W.
Submitted (FEB-2008) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 1-41; 43-117; 129-161 AND 170-185, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT MET-1 AND THR-2, MASS SPECTROMETRY.
Tissue: Cervix carcinoma.
[11]"Mechanism of activation of a human oncogene."
Tabin C.J., Bradley S.M., Bargmann C.I., Weinberg R.A., Papageorge A.G., Scolnick E.M., Dhar R., Lowy D.R., Chang E.H.
Nature 300:143-149(1982) [PubMed: 6290897] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-37.
[12]"Identification of the principal promoter sequence of the c-H-ras transforming oncogene: deletion analysis of the 5'-flanking region by focus formation assay."
Honkawa H., Masahashi W., Hashimoto S., Hashimoto-Gotoh T.
Mol. Cell. Biol. 7:2933-2940(1987) [PubMed: 3670300] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-16.
[13]"Affinity labeling of c-H-ras p21 consensus elements with periodate-oxidized GDP and GTP."
Loew A., Sprinzl M., Faulhammer H.G.
Eur. J. Biochem. 215:473-479(1993) [PubMed: 8393791] [Abstract]
Cited for: PROTEIN SEQUENCE OF 108-117 AND 132-153.
[14]"Isolation of ras GTP-binding mutants using an in situ colony-binding assay."
Feig L.A., Pan B.-T., Roberts T.M., Cooper G.M.
Proc. Natl. Acad. Sci. U.S.A. 83:4607-4611(1986) [PubMed: 3088563] [Abstract]
Cited for: MUTAGENESIS OF ALA-83; ASP-119 AND THR-144.
[15]"Deletion mutants of Harvey ras p21 protein reveal the absolute requirement of at least two distant regions for GTP-binding and transforming activities."
Lacal J.C., Anderson P.S., Aaronson S.A.
EMBO J. 5:679-687(1986) [PubMed: 3011420] [Abstract]
Cited for: MUTAGENESIS OF 164-ARG-GLN-165.
[16]"All ras proteins are polyisoprenylated but only some are palmitoylated."
Hancock J.F., Magee A.I., Childs J.E., Marshall C.J.
Cell 57:1167-1177(1989) [PubMed: 2661017] [Abstract]
Cited for: PALMITOYLATION AT CYS-181 AND CYS-184.
[17]"Palmitoylation of Ha-Ras facilitates membrane binding, activation of downstream effectors, and meiotic maturation in Xenopus oocytes."
Dudler T., Gelb M.H.
J. Biol. Chem. 271:11541-11547(1996) [PubMed: 8626715] [Abstract]
Cited for: PALMITOYLATION AT CYS-181 AND CYS-184, ISOPRENYLATION AT CYS-186, METHYLATION AT CYS-186, MUTAGENESIS OF CYS-181 AND CYS-184.
[18]"A molecular redox switch on p21(ras). Structural basis for the nitric oxide-p21(ras) interaction."
Lander H.M., Hajjar D.P., Hempstead B.L., Mirza U.A., Chait B.T., Campbell S., Quilliam L.A.
J. Biol. Chem. 272:4323-4326(1997) [PubMed: 9020151] [Abstract]
Cited for: S-NITROSYLATION AT CYS-118, FUNCTION, MASS SPECTROMETRY, MUTAGENESIS OF CYS-118.
[19]"Regulation of a novel human phospholipase C, PLCepsilon, through membrane targeting by Ras."
Song C., Hu C.-D., Masago M., Kariya K., Yamawaki-Kataoka Y., Shibatohge M., Wu D., Satoh T., Kataoka T.
J. Biol. Chem. 276:2752-2757(2001) [PubMed: 11022048] [Abstract]
Cited for: INTERACTION WITH PLCE1, CHARACTERIZATION OF VARIANT VAL-12, MUTAGENESIS OF SER-17; ASN-26; VAL-29; TYR-32; PRO-34; THR-35; GLU-37; ASP-38 AND SER-39.
[20]"Diacylglycerol kinase zeta regulates Ras activation by a novel mechanism."
Topham M.K., Prescott S.M.
J. Cell Biol. 152:1135-1143(2001) [PubMed: 11257115] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH RASGRP1 AND DGKZ.
[21]"DHHC9 and GCP16 constitute a human protein fatty acyltransferase with specificity for H- and N-Ras."
Swarthout J.T., Lobo S., Farh L., Croke M.R., Greentree W.K., Deschenes R.J., Linder M.E.
J. Biol. Chem. 280:31141-31148(2005) [PubMed: 16000296] [Abstract]
Cited for: PALMITOYLATION AT CYS-181 AND CYS-184.
[22]"An acylation cycle regulates localization and activity of palmitoylated Ras isoforms."
Rocks O., Peyker A., Kahms M., Verveer P.J., Koerner C., Lumbierres M., Kuhlmann J., Waldmann H., Wittinghofer A., Bastiaens P.I.H.
Science 307:1746-1752(2005) [PubMed: 15705808] [Abstract]
Cited for: PALMITOYLATION AT CYS-181 AND CYS-184, MUTAGENESIS OF CYS-181 AND CYS-184, SUBCELLULAR LOCATION.
[23]"Feedback inhibition of calcineurin and Ras by a dual inhibitory protein Carabin."
Pan F., Sun L., Kardian D.B., Whartenby K.A., Pardoll D.M., Liu J.O.
Nature 445:433-436(2007) [PubMed: 17230191] [Abstract]
Cited for: INTERACTION WITH TBC1D10C.
[24]"Three-dimensional structure of an oncogene protein: catalytic domain of human c-H-ras p21."
de Vos A.M., Tong L., Milburn M.V., Matias P.M., Jancarik J., Noguchi S., Nishimura S., Miura K., Ohtsuka E., Kim S.-H.
Science 239:888-893(1988) [PubMed: 2448879] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
[25]"Structure of the guanine-nucleotide-binding domain of the Ha-ras oncogene product p21 in the triphosphate conformation."
Pai E.F., Kabsch W., Krengel U., Holmes K.C., John J., Wittinghofer A.
Nature 341:209-214(1989) [PubMed: 2476675] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
[26]"Refined crystal structure of the triphosphate conformation of H-ras p21 at 1.35-A resolution: implications for the mechanism of GTP hydrolysis."
Pai E.F., Krengel U., Petsko G.A., Goody R.S., Kabsch W., Wittinghofer A.
EMBO J. 9:2351-2359(1990) [PubMed: 2196171] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS).
[27]"Crystal structures at 2.2-A resolution of the catalytic domains of normal ras protein and an oncogenic mutant complexed with GDP."
Tong L.A., de Vos A.M., Milburn M.V., Kim S.H.
J. Mol. Biol. 217:503-516(1991) [PubMed: 1899707] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
[28]"Solution structure and dynamics of ras p21.GDP determined by heteronuclear three- and four-dimensional NMR spectroscopy."
Kraulis P.J., Domaille P.J., Campbell-Burk S.L., van Aken T., Laue E.D.
Biochemistry 33:3515-3531(1994) [PubMed: 8142349] [Abstract]
Cited for: STRUCTURE BY NMR OF 1-166.
[29]"The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants."
Scheffzek K., Ahmadian M.R., Kabsch W., Wiesmuller L., Lautwein A., Schmitz F., Wittinghofer A.
Science 277:333-338(1997) [PubMed: 9219684] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1-166 IN COMPLEX WITH RASGAP.
[30]"The pre-hydrolysis state of p21(ras) in complex with GTP: new insights into the role of water molecules in the GTP hydrolysis reaction of ras-like proteins."
Scheidig A.J., Burmester C., Goody R.S.
Structure 7:1311-1324(1999) [PubMed: 10574788] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.26 ANGSTROMS).
[31]"The structural basis for the transition from Ras-GTP to Ras-GDP."
Hall B.E., Bar-Sagi D., Nassar N.
Proc. Natl. Acad. Sci. U.S.A. 99:12138-12142(2002) [PubMed: 12213964] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 1-166 IN COMPLEXES WITH GTP ANALOGS.
[32]"Structural and biochemical studies of p21Ras S-nitrosylation and nitric oxide-mediated guanine nucleotide exchange."
Williams J.G., Pappu K., Campbell S.L.
Proc. Natl. Acad. Sci. U.S.A. 100:6376-6381(2003) [PubMed: 12740440] [Abstract]
Cited for: STRUCTURE BY NMR OF 1-166, MASS SPECTROMETRY, S-NITROSYLATION, FUNCTION, MUTAGENESIS OF CYS-118.
[33]"Transformation efficiency of RasQ61 mutants linked to structural features of the switch regions in the presence of Raf."
Buhrman G., Wink G., Mattos C.
Structure 15:1618-1629(2007) [PubMed: 18073111] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 1-166 IN COMPLEXES WITH GTP ANALOG, CHARACTERIZATION OF VARIANTS LEU-61 AND LYS-61, MUTAGENESIS OF GLN-61.
[34]"Novel type of Ras effector interaction established between tumour suppressor NORE1A and Ras switch II."
Stieglitz B., Bee C., Schwarz D., Yildiz O., Moshnikova A., Khokhlatchev A., Herrmann C.
EMBO J. 27:1995-2005(2008) [PubMed: 18596699] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1-166 IN COMPLEX WITH RASSF5.
[35]"The p53 tumor-suppressor gene and ras oncogene mutations in oral squamous-cell carcinoma."
Sakai E., Rikimaru K., Ueda M., Matsumoto Y., Ishii N., Enomoto S., Yamamoto H., Tsuchida N.
Int. J. Cancer 52:867-872(1992) [PubMed: 1459726] [Abstract]
Cited for: VARIANT OSCC SER-12.
[36]"RAS point mutations and PAX8-PPAR gamma rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma."
Nikiforova M.N., Lynch R.A., Biddinger P.W., Alexander E.K., Dorn G.W. II, Tallini G., Kroll T.G., Nikiforov Y.E.
J. Clin. Endocrinol. Metab. 88:2318-2326(2003) [PubMed: 12727991] [Abstract]
Cited for: VARIANT LYS-61, INVOLVEMENT IN SUSCEPTIBILITY TO HURTHLE CELL THYROID CARCINOMA.
[37]"Germline mutations in HRAS proto-oncogene cause Costello syndrome."
Aoki Y., Niihori T., Kawame H., Kurosawa K., Ohashi H., Tanaka Y., Filocamo M., Kato K., Suzuki Y., Kure S., Matsubara Y.
Nat. Genet. 37:1038-1040(2005) [PubMed: 16170316] [Abstract]
Cited for: VARIANTS COSTELLO SYNDROME ALA-12; SER-12; VAL-12 AND ASP-13.
[38]"HRAS mutation analysis in Costello syndrome: genotype and phenotype correlation."
Gripp K.W., Lin A.E., Stabley D.L., Nicholson L., Scott C.I. Jr., Doyle D., Aoki Y., Matsubara Y., Zackai E.H., Lapunzina P., Gonzalez-Meneses A., Holbrook J., Agresta C.A., Gonzalez I.L., Sol-Church K.
Am. J. Med. Genet. A 140:1-7(2006) [PubMed: 16329078] [Abstract]
Cited for: VARIANTS COSTELLO SYNDROME ALA-12; SER-12 AND CYS-13.
[39]"Genotype-phenotype correlation in Costello syndrome: HRAS mutation analysis in 43 cases."
Kerr B., Delrue M.-A., Sigaudy S., Perveen R., Marche M., Burgelin I., Stef M., Tang B., Eden O.B., O'Sullivan J., De Sandre-Giovannoli A., Reardon W., Brewer C., Bennett C., Quarell O., M'Cann E., Donnai D., Stewart F. expand/collapse author list , Hennekam R., Cave H., Verloes A., Philip N., Lacombe D., Levy N., Arveiler B., Black G.
J. Med. Genet. 43:401-405(2006) [PubMed: 16443854] [Abstract]
Cited for: VARIANTS COSTELLO SYNDROME SER-12; CYS-12; GLU-12; ALA-12 AND ARG-117.
[40]"Diversity, parental germline origin, and phenotypic spectrum of de novo HRAS missense changes in Costello syndrome."
Zampino G., Pantaleoni F., Carta C., Cobellis G., Vasta I., Neri C., Pogna E.A., De Feo E., Delogu A., Sarkozy A., Atzeri F., Selicorni A., Rauen K.A., Cytrynbaum C.S., Weksberg R., Dallapiccola B., Ballabio A., Gelb B.D., Neri G., Tartaglia M.
Hum. Mutat. 28:265-272(2007) [PubMed: 17054105] [Abstract]
Cited for: VARIANTS COSTELLO SYNDROME SER-12 AND THR-146.
[41]"Myopathy caused by HRAS germline mutations: implications for disturbed myogenic differentiation in the presence of constitutive HRas activation."
van der Burgt I., Kupsky W., Stassou S., Nadroo A., Barroso C., Diem A., Kratz C.P., Dvorsky R., Ahmadian M.R., Zenker M.
J. Med. Genet. 44:459-462(2007) [PubMed: 17412879] [Abstract]
Cited for: VARIANTS CMEMS VAL-12; SER-12; LYS-22 AND LYS-63.
[42]"Costello syndrome associated with novel germline HRAS mutations: an attenuated phenotype?"
Gripp K.W., Innes A.M., Axelrad M.E., Gillan T.L., Parboosingh J.S., Davies C., Leonard N.J., Lapointe M., Doyle D., Catalano S., Nicholson L., Stabley D.L., Sol-Church K.
Am. J. Med. Genet. A 146:683-690(2008) [PubMed: 18247425] [Abstract]
Cited for: VARIANTS COSTELLO SYNDROME ILE-58 AND VAL-146.
+Additional computationally mapped references.

Cross-references

Sequence databases

J00277 Genomic DNA. Translation: AAB02605.1.
AF493916 mRNA. Translation: AAM12630.1.
CR536579 mRNA. Translation: CAG38816.1.
CR542271 mRNA. Translation: CAG47067.1.
BT019421 mRNA. Translation: AAV38228.1.
AB451336 mRNA. Translation: BAG70150.1.
AB451485 mRNA. Translation: BAG70299.1.
CH471158 Genomic DNA. Translation: EAX02337.1.
BC095471 mRNA. Translation: AAH95471.1.
M17232 Genomic DNA. Translation: AAA35685.1.
IPIIPI00000006.
PIRTVHUH. A93299.
RefSeqNP_001123914.1.
NP_005334.1.
UniGeneHs.37003

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
121PX-ray1.54A1-166[»]
1AA9NMR-A1-171[»]
1AGPX-ray2.30A1-166[»]
1BKDX-ray2.80R1-166[»]
1CLUX-ray1.70A1-166[»]
1CRPNMR-A1-166[»]
1CRQNMR-A1-166[»]
1CRRNMR-A1-166[»]
1CTQX-ray1.26A1-166[»]
1GNPX-ray2.70A1-166[»]
1GNQX-ray2.50A1-166[»]
1GNRX-ray1.85A1-166[»]
1HE8X-ray3.00B1-166[»]
1IAQX-ray2.90A/B/C1-166[»]
1IOZX-ray2.00A1-171[»]
1JAHX-ray1.80A1-166[»]
1JAIX-ray1.80A1-166[»]
1K8RX-ray3.00A1-166[»]
1LF0X-ray1.70A1-166[»]
1LF5X-ray1.70A1-166[»]
1LFDX-ray2.10B/D1-167[»]
1NVUX-ray2.20Q/R1-166[»]
1NVVX-ray2.18Q1-166[»]
R1-166[»]
1NVWX-ray2.70Q/R1-166[»]
1NVXX-ray3.20Q/R1-166[»]
1P2SX-ray2.45A1-166[»]
1P2TX-ray2.00A1-166[»]
1P2UX-ray2.00A1-166[»]
1P2VX-ray2.30A1-166[»]
1PLJX-ray2.80A1-166[»]
1PLKX-ray2.80A1-166[»]
1PLLX-ray2.80A1-166[»]
1Q21X-ray2.20A1-171[»]
1QRAX-ray1.60A1-166[»]
1RVDX-ray1.90A1-166[»]
1WQ1X-ray2.50R1-166[»]
1XCMX-ray1.84A1-167[»]
1XD2X-ray2.70A1-166[»]
B1-166[»]
1XJ0X-ray1.70A1-166[»]
1ZVQX-ray2.00A1-166[»]
1ZW6X-ray1.50A1-166[»]
221PX-ray2.30A1-166[»]
2C5LX-ray1.90A/B1-166[»]
2CE2X-ray1.00X1-166[»]
2CL0X-ray1.80X1-166[»]
2CL6X-ray1.24X1-166[»]
2CL7X-ray1.25X1-166[»]
2CLCX-ray1.30X1-166[»]
2CLDX-ray1.22X1-166[»]
2EVWX-ray1.05X1-166[»]
2GDPmodel-A1-171[»]
2Q21X-ray2.20A1-171[»]
2QUZX-ray1.49A1-166[»]
2RGAX-ray1.90A1-166[»]
2RGBX-ray1.35A1-166[»]
2RGCX-ray1.60A1-166[»]
2RGDX-ray2.00A1-166[»]
2RGEX-ray1.40A1-166[»]
2RGGX-ray1.45A1-166[»]
2UZIX-ray2.00R1-166[»]
2VH5X-ray2.70R1-166[»]
3DDCX-ray1.80A1-166[»]
421PX-ray2.20A1-166[»]
4Q21X-ray2.00A1-189[»]
521PX-ray2.60A1-166[»]
5P21X-ray1.35A1-166[»]
621PX-ray2.40A1-166[»]
6Q21X-ray1.95A/B/C/D1-171[»]
721PX-ray2.00A1-166[»]
821PX-ray1.50A1-166[»]
DisProtDP00153.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP:1050N.
IntActP01112. 26 interactions.

PTM databases

PhosphoSiteP01112.

Proteomic databases

PRIDEP01112.

Genome annotation databases

EnsemblENSG00000174775. Homo sapiens. [Contig view]
GeneID3265.
KEGGhsa:3265.

Organism-specific databases

GeneCardsGC11M000522.
H-InvDBHIX0009354.
HGNCHGNC:5173. HRAS.
HPACAB002015.
MIM109800. phenotype.
190020. gene.
218040. phenotype.
607464. phenotype.
Orphanet3071. Costello syndrome.
PharmGKBPA29444.
GenAtlasSearch...

Phylogenomic databases

HOVERGENP01112.
OMAP01112. NCKCVIS.

Enzyme and pathway databases

Pathway_Interaction_DBa6b1_a6b4_integrin_pathway. a6b1 and a6b4 Integrin signaling.
bcr_5pathway. BCR signaling pathway.
pi3kcipathway. Class I PI3K signaling events.
cd8tcrdownstreampathway. Downstream signaling in naive CD8+ T cells.
endothelinpathway. Endothelins.
ephbfwdpathway. EPHB forward signaling.
epopathway. EPO signaling pathway.
fcer1pathway. Fc-epsilon receptor I signaling in mast cells.
igf1_pathway. IGF1 pathway.
il2_1pathway. IL2-mediated signaling events.
insulin_pathway. Insulin Pathway.
lysophospholipid_pathway. LPA receptor mediated events.
trkrpathway. Neurotrophic factor-mediated Trk receptor signaling.
pdgfrbpathway. PDGFR-beta signaling pathway.
er_nongenomic_pathway. Plasma membrane estrogen receptor signaling.
tcrraspathway. Ras signaling in the CD4+ TCR pathway.
met_pathway. Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).
kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit).
vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2.
ret_pathway. Signaling events regulated by Ret tyrosine kinase.
syndecan_2_pathway. Syndecan-2-mediated signaling events.
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.
ReactomeREACT_11061. Signalling by NGF.
REACT_498. Signaling by Insulin receptor.
REACT_604. Hemostasis.
REACT_6900. Signaling in Immune system.
REACT_9417. Signaling by EGFR.

Gene expression databases

ArrayExpressP01112.
BgeeP01112.
CleanExHS_HRAS.
GermOnlineENSG00000174775. Homo sapiens.

Family and domain databases

InterProIPR003577. GTPase_Ras.
IPR013753. Ras.
IPR001806. Ras_GTPase.
IPR015592. Ras_Ras_related.
IPR005225. Small_GTP_bd.
[Graphical view]
PANTHERPTHR11708:SF125. Ras_Ras_related. 1 hit.
PfamPF00071. Ras. 1 hit.
[Graphical view]
PRINTSPR00449. RASTRNSFRMNG.
SMARTSM00173. RAS. 1 hit.
[Graphical view]
TIGRFAMsTIGR00231. small_GTP. 1 hit.
PROSITEPS51421. RAS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB00605. Sulindac.
NextBio12961.
SOURCESearch...

Entry information

Entry nameRASH_HUMAN
AccessionPrimary (citable) accession number: P01112
Secondary accession number(s): B5BUA0 expand/collapse secondary AC list , Q14080, Q6FHV9, Q9UCE2
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: June 16, 2009
This is version 130 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents