Reviewed, UniProtKB/Swiss-Prot P01112 (RASH_HUMAN)

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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. 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

Ontologies

Keywords
Cellular component	Cell membrane Golgi apparatus Membrane
Disease	Disease mutation Proto-oncogene
Ligand	GTP-binding Nucleotide-binding
PTM	Acetylation Lipoprotein Methylation Palmitate Prenylation S-nitrosylation
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	Ras protein signal transduction Inferred from Experiment. Source: Reactome cell surface receptor linked signal transduction Traceable author statement. Source: ProtInc chemotaxis Traceable author statement. Source: ProtInc organ morphogenesis Traceable author statement. Source: ProtInc
Cellular component	Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from Experiment. Source: Reactome
Molecular function	GTP binding Inferred from electronic annotation. Source: UniProtKB-KW protein C-terminus binding Ref.29 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BRAP	Q7Z569	3	EBI-350145,EBI-349900
byr2	P28829	1	EBI-350145,EBI-1032333	From a different organism.
Pik3ca	P42337	1	EBI-350145,EBI-641748	From a different organism.
PIK3CG	P48736	1	EBI-350145,EBI-1030384
Rabac1	Q9Z0S9	2	EBI-350145,EBI-476965	From a different organism.
RAF1	P04049	5	EBI-350145,EBI-365996
Rapgef4	Q9EQZ6	2	EBI-350145,EBI-772212	From a different organism.
RASA1	P20936	1	EBI-350145,EBI-1026476
RASSF1	Q9NS23-2	2	EBI-350145,EBI-438698
RASSF5	Q8WWW0	1	EBI-350145,EBI-367390
Rassf5	Q5EBH1-2	2	EBI-350145,EBI-960547	From a different organism.
RGL1	Q9NZL6	1	EBI-350145,EBI-365926
RIN1	Q13671	2	EBI-350145,EBI-366017
RIN1	Q13671-1	1	EBI-350145,EBI-366030
SOS1	Q07889	1	EBI-350145,EBI-297487

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 186

186

GTPase HRas

PRO_0000042996

Initiator methionine

1

1

Removed; alternate Ref.10

Chain

2 – 186

185

GTPase HRas, N-terminally processed

PRO_0000326476

Propeptide

187 – 189

3

Removed in mature form

PRO_0000042997

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 HRas; alternate Ref.10

Modified residue

2

1

N-acetylthreonine; in GTPase HRas, N-terminally processed Ref.10

Modified residue

118

1

S-nitrosocysteine

Modified residue

186

1

Cysteine methyl ester Ref.17

Lipidation

181

1

S-palmitoyl cysteine Ref.22 Ref.16 Ref.17 Ref.21

Lipidation

184

1

S-palmitoyl cysteine Ref.22 Ref.16 Ref.17 Ref.21

Lipidation

186

1

S-farnesyl cysteine

Natural variations

Natural variant

12

1

G → A in Costello syndrome.

VAR_026106

Natural variant

12

1

G → C in Costello syndrome.

VAR_045975

Natural variant

12

1

G → E in Costello syndrome.

VAR_045976

Natural variant

12

1

G → S in Costello syndrome, OSCC and CMEMS.

VAR_006837

Natural variant

12

1

G → 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 variant

13

1

G → C in Costello syndrome.

VAR_026107

Natural variant

13

1

G → D in Costello syndrome.

VAR_026108

Natural variant

22

1

Q → K in CMEMS. Ref.41

VAR_045977

Natural variant

58

1

T → I in Costello syndrome.

VAR_045978

Natural variant

61

1

Q → K in follicular thyroid carcinoma samples; somatic mutation; increases transformation of cultured cell lines. Ref.36 Ref.33

VAR_045979

Natural variant

61

1

Q → 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 variant

63

1

E → K in CMEMS. Ref.41

VAR_045980

Natural variant

117

1

K → R in Costello syndrome.

VAR_045981

Natural variant

146

1

A → T in Costello syndrome.

VAR_045982

Natural variant

146

1

A → V in Costello syndrome.

VAR_045983

Experimental info

Mutagenesis

17

1

S → N: Dominant negative. Prevents PLCE1 EGF-induced recruitment to plasma membrane. Ref.15 Ref.19

Mutagenesis

26

1

N → G: Loss of interaction with PLCE1; when associated with V-12. Ref.15 Ref.19

Mutagenesis

29

1

V → A: No effect on interaction with PLCE1; when associated with V-12. Ref.15 Ref.19

Mutagenesis

32

1

Y → F: Loss of interaction and recruitment to plasma membrane of PLCE1; when associated with V-12. Ref.15 Ref.19

Mutagenesis

34

1

P → G: No effect on interaction with PLCE1; when associated with V-12. Ref.15 Ref.19

Mutagenesis

35

1

T → S: Loss of interaction with PLCE1; when associated with V-12. Ref.15 Ref.19

Mutagenesis

37

1

E → G: No effect on interaction with PLCE1; when associated with V-12. Ref.15 Ref.19

Mutagenesis

38

1

D → N: No effect on interaction with PLCE1; when associated with V-12. Ref.15 Ref.19

Mutagenesis

39

1

S → C: No effect on interaction with PLCE1; when associated with V-12. Ref.15 Ref.19

Mutagenesis

59

1

A → T: Loss of GTPase activity and creation of an autophosphorylation site. Ref.15

Mutagenesis

61

1

Q → I: Moderately increased transformation of cultured cell lines. Ref.33 Ref.15

Mutagenesis

61

1

Q → V: Strongly increased transformation of cultured cell lines. Ref.33 Ref.15

Mutagenesis

83

1

A → T: GTP-binding activity reduced by factor of 30. Ref.15 Ref.14

Mutagenesis

118

1

C → S: Abolishes S-nitrosylation. No stimulation of guanine nucleotide exchange. Ref.18 Ref.32 Ref.15

Mutagenesis

119

1

D → N: Loss of GTP-binding activity. Ref.15 Ref.14

Mutagenesis

144

1

T → I: GTP-binding activity reduced by factor of 25. Ref.15 Ref.14

Mutagenesis

164 – 165

2

RQ → AV: Loss of GTP-binding activity. Ref.15

Mutagenesis

181

1

C → S: Exclusively localized in Golgi. Non-specifically localized on all endomembranes; when associated with S-184. Ref.22 Ref.17 Ref.15

Mutagenesis

184

1

C → S: Mainly localized in Golgi. Non-specifically localized on all endomembranes; when associated with S-181. Ref.22 Ref.17 Ref.15

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

189

Helix Strand Turn

Details...

Beta strand

2 – 11

10

Helix

16 – 25

10

Beta strand

36 – 46

11

Beta strand

49 – 58

10

Helix

62 – 64

3

Helix

65 – 74

10

Beta strand

76 – 83

8

Helix

87 – 91

5

Helix

93 – 104

12

Beta strand

111 – 116

6

Helix

127 – 137

11

Beta strand

141 – 143

3

Turn

146 – 148

3

Helix

152 – 164

13

Sequences

	Sequence		Length	Mass (Da)
	P01112-1 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: EE6DC2D933E2856A	FASTA	189	21,298
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

IPI

IPI00000006.

PIR

TVHUH. A93299.

RefSeq

NP_001123914.1.
NP_005334.1.

UniGene

Hs.37003

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
121P	X-ray	1.54	A	1-166	[»]
1AA9	NMR	-	A	1-171	[»]
1AGP	X-ray	2.30	A	1-166	[»]
1BKD	X-ray	2.80	R	1-166	[»]
1CLU	X-ray	1.70	A	1-166	[»]
1CRP	NMR	-	A	1-166	[»]
1CRQ	NMR	-	A	1-166	[»]
1CRR	NMR	-	A	1-166	[»]
1CTQ	X-ray	1.26	A	1-166	[»]
1GNP	X-ray	2.70	A	1-166	[»]
1GNQ	X-ray	2.50	A	1-166	[»]
1GNR	X-ray	1.85	A	1-166	[»]
1HE8	X-ray	3.00	B	1-166	[»]
1IAQ	X-ray	2.90	A/B/C	1-166	[»]
1IOZ	X-ray	2.00	A	1-171	[»]
1JAH	X-ray	1.80	A	1-166	[»]
1JAI	X-ray	1.80	A	1-166	[»]
1K8R	X-ray	3.00	A	1-166	[»]
1LF0	X-ray	1.70	A	1-166	[»]
1LF5	X-ray	1.70	A	1-166	[»]
1LFD	X-ray	2.10	B/D	1-167	[»]
1NVU	X-ray	2.20	Q/R	1-166	[»]
1NVV	X-ray	2.18	Q	1-166	[»]
			R	1-166	[»]
1NVW	X-ray	2.70	Q/R	1-166	[»]
1NVX	X-ray	3.20	Q/R	1-166	[»]
1P2S	X-ray	2.45	A	1-166	[»]
1P2T	X-ray	2.00	A	1-166	[»]
1P2U	X-ray	2.00	A	1-166	[»]
1P2V	X-ray	2.30	A	1-166	[»]
1PLJ	X-ray	2.80	A	1-166	[»]
1PLK	X-ray	2.80	A	1-166	[»]
1PLL	X-ray	2.80	A	1-166	[»]
1Q21	X-ray	2.20	A	1-171	[»]
1QRA	X-ray	1.60	A	1-166	[»]
1RVD	X-ray	1.90	A	1-166	[»]
1WQ1	X-ray	2.50	R	1-166	[»]
1XCM	X-ray	1.84	A	1-167	[»]
1XD2	X-ray	2.70	A	1-166	[»]
			B	1-166	[»]
1XJ0	X-ray	1.70	A	1-166	[»]
1ZVQ	X-ray	2.00	A	1-166	[»]
1ZW6	X-ray	1.50	A	1-166	[»]
221P	X-ray	2.30	A	1-166	[»]
2C5L	X-ray	1.90	A/B	1-166	[»]
2CE2	X-ray	1.00	X	1-166	[»]
2CL0	X-ray	1.80	X	1-166	[»]
2CL6	X-ray	1.24	X	1-166	[»]
2CL7	X-ray	1.25	X	1-166	[»]
2CLC	X-ray	1.30	X	1-166	[»]
2CLD	X-ray	1.22	X	1-166	[»]
2EVW	X-ray	1.05	X	1-166	[»]
2GDP	model	-	A	1-171	[»]
2Q21	X-ray	2.20	A	1-171	[»]
2QUZ	X-ray	1.49	A	1-166	[»]
2RGA	X-ray	1.90	A	1-166	[»]
2RGB	X-ray	1.35	A	1-166	[»]
2RGC	X-ray	1.60	A	1-166	[»]
2RGD	X-ray	2.00	A	1-166	[»]
2RGE	X-ray	1.40	A	1-166	[»]
2RGG	X-ray	1.45	A	1-166	[»]
2UZI	X-ray	2.00	R	1-166	[»]
2VH5	X-ray	2.70	R	1-166	[»]
3DDC	X-ray	1.80	A	1-166	[»]
421P	X-ray	2.20	A	1-166	[»]
4Q21	X-ray	2.00	A	1-189	[»]
521P	X-ray	2.60	A	1-166	[»]
5P21	X-ray	1.35	A	1-166	[»]
621P	X-ray	2.40	A	1-166	[»]
6Q21	X-ray	1.95	A/B/C/D	1-171	[»]
721P	X-ray	2.00	A	1-166	[»]
821P	X-ray	1.50	A	1-166	[»]

DisProt

DP00153.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:1050N.

IntAct

P01112. 26 interactions.

PTM databases

PhosphoSite

P01112.

Proteomic databases

PRIDE

P01112.

Genome annotation databases

Ensembl

ENSG00000174775. Homo sapiens. [Contig view]

GeneID

3265.

KEGG

hsa:3265.

Organism-specific databases

GeneCards

GC11M000522.

H-InvDB

HIX0009354.

HGNC

HGNC:5173. HRAS.

HPA

CAB002015.

MIM

109800. phenotype.
190020. gene.
218040. phenotype.
607464. phenotype.

Orphanet

3071. Costello syndrome.

PharmGKB

PA29444.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P01112.

OMA

P01112. NCKCVIS.

Enzyme and pathway databases

Pathway_Interaction_DB

a6b1_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.

Reactome

REACT_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

ArrayExpress

P01112.

Bgee

P01112.

CleanEx

HS_HRAS.

GermOnline

ENSG00000174775. Homo sapiens.

Family and domain databases

InterPro

IPR003577. GTPase_Ras.
IPR013753. Ras.
IPR001806. Ras_GTPase.
IPR015592. Ras_Ras_related.
IPR005225. Small_GTP_bd.
[Graphical view]

PANTHER

PTHR11708:SF125. Ras_Ras_related. 1 hit.

Pfam

PF00071. Ras. 1 hit.
[Graphical view]

PRINTS

PR00449. RASTRNSFRMNG.

SMART

SM00173. RAS. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00231. small_GTP. 1 hit.

PROSITE

PS51421. RAS. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00605. Sulindac.

NextBio

12961.

SOURCE

Search...

Entry information

Entry name

RASH_HUMAN

Accession

Primary (citable) accession number: P01112
Secondary accession number(s): B5BUA0 , 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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)