P01111 (RASN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
GTPase NRas

Alternative name(s):
Transforming protein N-Ras

Gene names

Name:	NRAS
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.
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 (active GTP-bound form preferentially) with RGS14 By similarity.
Subcellular location	Cell membrane; Lipid-anchor; Cytoplasmic side. Golgi apparatus membrane; Lipid-anchor. Note: Shuttles between the plasma membrane and the Golgi apparatus. Ref.15
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.13 Ref.14 Ref.15
Involvement in disease	Defects in NRAS are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:607785]. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia. Defects in NRAS are the cause of Noonan syndrome type 6 (NS6) [MIM:613224]. 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. Ref.20
Miscellaneous	Mutations which change AA 12, 13 or 61 activate the potential of Ras to transform cultured cells and are implicated in a variety of human tumors.
Sequence similarities	Belongs to the small GTPase superfamily. Ras family.

Ontologies

Keywords
Cellular component	Cell membrane Golgi apparatus Membrane
Disease	Disease mutation Proto-oncogene
Ligand	GTP-binding Nucleotide-binding
PTM	Lipoprotein Methylation Palmitate Phosphoprotein Prenylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	Ras protein signal transduction Traceable author statement. Source: Reactome activation of MAPKK activity Traceable author statement. Source: Reactome axon guidance Traceable author statement. Source: Reactome blood coagulation Traceable author statement. Source: Reactome epidermal growth factor receptor signaling pathway Traceable author statement. Source: Reactome insulin receptor signaling pathway Traceable author statement. Source: Reactome leukocyte migration Traceable author statement. Source: Reactome nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome
Cellular component	Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Traceable author statement. Source: Reactome
Molecular function	GTP binding Inferred from electronic annotation. Source: UniProtKB-KW Ral guanyl-nucleotide exchange factor activity Traceable author statement. Source: Reactome
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 186

186

GTPase NRas

PRO_0000043006

Propeptide

187 – 189

3

Removed in mature form By similarity

PRO_0000043007

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

2

1

Phosphothreonine Ref.16

Modified residue

4

1

Phosphotyrosine Ref.16

Modified residue

186

1

Cysteine methyl ester By similarity

Lipidation

181

1

S-palmitoyl cysteine Ref.13 Ref.14 Ref.15

Lipidation

186

1

S-farnesyl cysteine Ref.13

Natural variations

Natural variant

12

1

G → C in leukemia. Ref.8

VAR_021194

Natural variant

13

1

G → D in a patient with an autoimmune lymphoproliferative disorder. Ref.19

VAR_063084

Natural variant

13

1

G → R in colorectal cancer. Ref.18

VAR_006845

Natural variant

50

1

T → I in NS6; hypermorphic mutation. Ref.20

VAR_063085

Natural variant

60

1

G → E in NS6; hypermorphic mutation. Ref.20

VAR_063086

Natural variant

61

1

Q → K in neuroblastoma cell.

VAR_006846

Natural variant

61

1

Q → R in lung carcinoma cell and melanoma. Ref.12
Corresponds to variant rs11554290 [ dbSNP | Ensembl ].

VAR_006847

Experimental info

Mutagenesis

164

1

R → A: Loss of GTP-binding activity.

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

189

Helix Strand Turn

Details...

Beta strand

2 – 9

8

Helix

17 – 25

9

Beta strand

38 – 45

8

Beta strand

50 – 57

8

Beta strand

79 – 81

3

Helix

87 – 104

18

Beta strand

112 – 114

3

Helix

127 – 136

10

Turn

146 – 148

3

Helix

153 – 166

14

Sequences

	Sequence		Length	Mass (Da)
	P01111 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 6898D3F6815B1EC7	FASTA	189	21,229
	10 20 30 40 50 60 MTEYKLVVVG AGGVGKSALT IQLIQNHFVD EYDPTIEDSY RKQVVIDGET CLLDILDTAG 70 80 90 100 110 120 QEEYSAMRDQ YMRTGEGFLC VFAINNSKSF ADINLYREQI KRVKDSDDVP MVLVGNKCDL 130 140 150 160 170 180 PTRTVDTKQA HELAKSYGIP FIETSAKTRQ GVEDAFYTLV REIRQYRMKK LNSSDDGTQG CMGLPCVVM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure and activation of the human N-ras gene." Taparowsky E., Shimizu K., Goldfarb M., Wigler M. Cell 34:581-586(1983) [PubMed: 6616621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Human N-ras: cDNA cloning and gene structure." Hall A., Brown R. Nucleic Acids Res. 13:5255-5268(1985) [PubMed: 2991860] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Mechanism of activation of an N-ras gene in the human fibrosarcoma cell line HT1080." Brown R., Marshall C.J., Pennie S.G., Hall A. EMBO J. 3:1321-1326(1984) [PubMed: 6086315] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Fibrosarcoma.
[4]	"Mechanism of activation of an N-ras oncogene of SW-1271 human lung carcinoma cells." Yuasa Y., Gol R.A., Chang A., Chiu I.-M., Reddy E.P., Tronick S.R., Aaronson S.A. Proc. Natl. Acad. Sci. U.S.A. 81:3670-3674(1984) [PubMed: 6587382] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Lung carcinoma.
[5]	"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.
[6]	NIEHS SNPs program Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]	"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]. Tissue: Kidney.
[8]	"Transforming genes in human leukemia cells." Hirai H., Tanaka S., Azuma M., Anraku Y., Kobayashi Y., Fujisawa M., Okabe T., Urabe A., Takaku F. Blood 66:1371-1378(1985) [PubMed: 2998510] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 1-96, VARIANT CYS-12. Tissue: Leukemia.
[9]	"Transforming genes from familial adenomatous polyposis patient cells detected by a tumorigenicity assay." Yuasa Y., Kamiyama T., Kato M., Iwama T., Ikeuchi T., Tonomura A. Oncogene 5:589-596(1990) [PubMed: 1970154] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 1-29 AND 43-78.
[10]	"Activation of an N-ras gene in acute myeloblastic leukemia through somatic mutation in the first exon." Gambke C., Hall A., Moroni C. Proc. Natl. Acad. Sci. U.S.A. 82:879-882(1985) [PubMed: 3856237] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 38-96.
[11]	"A point mutation at codon 13 of the N-ras oncogene in myelodysplastic syndrome." Hirai H., Kobayashi Y., Mano H., Hagiwara K., Maru Y., Omine M., Mizoguchi H., Nishida J., Takaku F. Nature 327:430-432(1987) [PubMed: 3295562] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 38-96. Tissue: Bone marrow.
[12]	"Delection of a low frequency of activated ras genes in human melanomas using a tumorigenicity assay." Raybaud F., Noguchi T., Marics I., Adelaide J., Planche J., Batoz M., Aubet C., de Lapeyriere O., Birnbaum D. Cancer Res. 48:950-953(1988) [PubMed: 3276402] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 60-96, VARIANT ARG-61.
[13]	"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, ISOPRENYLATION AT CYS-186.
[14]	"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.
[15]	"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, SUBCELLULAR LOCATION.
[16]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-2 AND TYR-4, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[17]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]	"Amino-acid substitution at codon 13 of the N-ras oncogene in rectal cancer in a Japanese patient." Nitta N., Ochiai M., Nagao M., Sugimura T. Jpn. J. Cancer Res. 78:21-26(1987) [PubMed: 3102434] [Abstract] Cited for: VARIANT COLORECTAL CANCER ARG-13.
[19]	"NRAS mutation causes a human autoimmune lymphoproliferative syndrome." Oliveira J.B., Bidere N., Niemela J.E., Zheng L., Sakai K., Nix C.P., Danner R.L., Barb J., Munson P.J., Puck J.M., Dale J., Straus S.E., Fleisher T.A., Lenardo M.J. Proc. Natl. Acad. Sci. U.S.A. 104:8953-8958(2007) [PubMed: 17517660] [Abstract] Cited for: VARIANT ASP-13.
[20]	"A restricted spectrum of NRAS mutations causes Noonan syndrome." Cirstea I.C., Kutsche K., Dvorsky R., Gremer L., Carta C., Horn D., Roberts A.E., Lepri F., Merbitz-Zahradnik T., Konig R., Kratz C.P., Pantaleoni F., Dentici M.L., Joshi V.A., Kucherlapati R.S., Mazzanti L., Mundlos S., Patton M.A. , Silengo M.C., Rossi C., Zampino G., Digilio C., Stuppia L., Seemanova E., Pennacchio L.A., Gelb B.D., Dallapiccola B., Wittinghofer A., Ahmadian M.R., Tartaglia M., Zenker M. Nat. Genet. 42:27-29(2010) [PubMed: 19966803] [Abstract] Cited for: VARIANTS NS6 ILE-50 AND GLU-60, CHARACTERIZATION OF VARIANTS NS6 ILE-50 AND GLU-60.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

NRASbase

NRAS mutation db

NIEHS-SNPs

Wikipedia

RAS proteins entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X02751 mRNA. Translation: CAA26529.1.
X00642 Genomic DNA. Translation: CAA25269.1.
X00643 Genomic DNA. Translation: CAA25270.1.
X00644 Genomic DNA. Translation: CAA25271.1.
X00645 Genomic DNA. Translation: CAA25272.1.
L00043 , L00040, L00041, L00042 Genomic DNA. Translation: AAA60255.1.
AF493919 mRNA. Translation: AAM12633.1.
AY428630 Genomic DNA. Translation: AAQ94397.1.
BC005219 mRNA. Translation: AAH05219.1.
M25898 Genomic DNA. Translation: AAA36548.1.
X53291, X53292 Genomic DNA. Translation: CAA37384.1.
K03211, M10055 Genomic DNA. Translation: AAA36556.1.
X05565 Genomic DNA. Translation: CAA29079.1.
X07440 Genomic DNA. Translation: CAA30320.1.

IPI

IPI00000005.

PIR

TVHURA. A90839.
I38149.

RefSeq

NP_002515.1. NM_002524.4.

UniGene

Hs.486502.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3CON	X-ray	1.65	A	1-172	[»]

ProteinModelPortal

P01111.

SMR

P01111. Positions 1-167.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-1058N.

IntAct

P01111. 6 interactions.

MINT

MINT-131535.

STRING

P01111.

PTM databases

PhosphoSite

P01111.

Polymorphism databases

DMDM

131883.

2D gel databases

OGP

P01111.

Proteomic databases

PeptideAtlas

P01111.

PRIDE

P01111.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000369535; ENSP00000358548; ENSG00000213281.

GeneID

4893.

KEGG

hsa:4893.

UCSC

uc009wgu.1. human.

Organism-specific databases

CTD

4893.

GeneCards

GC01M115247.

HGNC

HGNC:7989. NRAS.

HPA

CAB010157.

MIM

164790. gene.
607785. phenotype.
613224. phenotype.

neXtProt

NX_P01111.

Orphanet

3261. Autoimmune lymphoproliferative syndrome.
648. Noonan syndrome.

PharmGKB

PA31768.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HBG745225.

HOVERGEN

HBG009351.

InParanoid

P01111.

OMA

DIGTYRE.

OrthoDB

EOG4BRWMX.

PhylomeDB

P01111.

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_604. Hemostasis.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P01111.

Bgee

P01111.

CleanEx

HS_NRAS.

Genevestigator

P01111.

GermOnline

ENSG00000009307. Homo sapiens.

Family and domain databases

InterPro

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

KO

K07828.

PANTHER

PTHR24070. PTHR24070. 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

NextBio

18835.

SOURCE

Search...

Entry information

Entry name

RASN_HUMAN

Accession

Primary (citable) accession number: P01111
Secondary accession number(s): Q14971, Q15104, Q15282

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	January 25, 2012
This is version 145 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.