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P01111 (RASN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 168. Feed History...

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

Names and origin

Protein namesRecommended name:
GTPase NRas
Alternative name(s):
Transforming protein N-Ras
Gene names
Name:NRAS
Synonyms:HRAS1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

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

General annotation (Comments)

Function

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

Enzyme regulation

Alternates between an inactive form bound to GDP and an active form bound to GTP. Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by a GTPase-activating protein (GAP).

Subunit structure

Interacts (active GTP-bound form preferentially) with RGS14 By similarity. Interacts (active GTP-bound form) with RASSF7. Ref.17

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

Acetylation at Lys-104 prevents interaction with guanine nucleotide exchange factors (GEFs) By similarity.

Involvement in disease

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 6 (NS6) [MIM:613224]: A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.20

Autoimmune lymphoproliferative syndrome 4 (ALPS4) [MIM:614470]: A disorder of apoptosis, characterized by chronic accumulation of non-malignant lymphocytes, defective lymphocyte apoptosis, and an increased risk for the development of hematologic malignancies.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.19

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 componentCell membrane
Golgi apparatus
Membrane
   DiseaseDisease mutation
Proto-oncogene
   LigandGTP-binding
Nucleotide-binding
   PTMAcetylation
Lipoprotein
Methylation
Palmitate
Prenylation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processFc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

GTP catabolic process

Inferred from electronic annotation. Source: InterPro

MAPK cascade

Traceable author statement. Source: Reactome

Ras protein signal transduction

Traceable author statement. Source: Reactome

actin cytoskeleton organization

Inferred from electronic annotation. Source: Ensembl

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

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: Ensembl

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

positive regulation of Rac protein signal transduction

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

regulation of long-term neuronal synaptic plasticity

Inferred from electronic annotation. Source: Ensembl

regulation of synaptic transmission, GABAergic

Inferred from electronic annotation. Source: Ensembl

small GTPase mediated signal transduction

Traceable author statement. Source: Reactome

striated muscle cell differentiation

Inferred from electronic annotation. Source: Ensembl

visual learning

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentGolgi membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

extracellular vesicular exosome

Inferred from direct assay PubMed 20458337. Source: UniProt

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionGTP binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein complex binding

Inferred from direct assay PubMed 23209302. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 186186GTPase NRas
PRO_0000043006
Propeptide187 – 1893Removed in mature form By similarity
PRO_0000043007

Regions

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

Amino acid modifications

Modified residue1861Cysteine methyl ester By similarity
Lipidation1811S-palmitoyl cysteine Ref.13 Ref.14 Ref.15
Lipidation1861S-farnesyl cysteine Ref.13

Natural variations

Natural variant121G → C in leukemia. Ref.8
VAR_021194
Natural variant131G → D in ALPS4. Ref.19
VAR_063084
Natural variant131G → R in colorectal cancer. Ref.18
VAR_006845
Natural variant501T → I in NS6; hypermorphic mutation. Ref.20
VAR_063085
Natural variant601G → E in NS6; hypermorphic mutation. Ref.20
VAR_063086
Natural variant611Q → K in neuroblastoma cell.
VAR_006846
Natural variant611Q → R in lung carcinoma cell and melanoma. Ref.12
Corresponds to variant rs11554290 [ dbSNP | Ensembl ].
VAR_006847

Experimental info

Mutagenesis1641R → A: Loss of GTP-binding activity.

Secondary structure

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

Details...

Sequences

Sequence LengthMass (Da)Tools
P01111 [UniParc].

Last modified July 21, 1986. Version 1.
Checksum: 6898D3F6815B1EC7

FASTA18921,229
        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 

« Hide

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 38-96.
Tissue: Bone marrow.
[12]"Detection 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: PALMITOYLATION, SUBCELLULAR LOCATION.
[16]"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].
[17]"RASSF7 negatively regulates pro-apoptotic JNK signaling by inhibiting the activity of phosphorylated-MKK7."
Takahashi S., Ebihara A., Kajiho H., Kontani K., Nishina H., Katada T.
Cell Death Differ. 18:645-655(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RASSF7.
[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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: VARIANT ALPS4 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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: VARIANTS NS6 ILE-50 AND GLU-60, CHARACTERIZATION OF VARIANTS NS6 ILE-50 AND GLU-60.
+Additional computationally mapped references.

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 expand/collapse EMBL AC list , 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.
PIRTVHURA. A90839.
I38149.
RefSeqNP_002515.1. NM_002524.4.
UniGeneHs.486502.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3CONX-ray1.65A1-172[»]
ProteinModelPortalP01111.
SMRP01111. Positions 1-167.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110952. 18 interactions.
DIPDIP-1058N.
IntActP01111. 7 interactions.
MINTMINT-131535.
STRING9606.ENSP00000358548.

Chemistry

ChEMBLCHEMBL2079845.

PTM databases

PhosphoSiteP01111.

Polymorphism databases

DMDM131883.

2D gel databases

OGPP01111.

Proteomic databases

PaxDbP01111.
PeptideAtlasP01111.
PRIDEP01111.

Protocols and materials databases

DNASU4893.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000369535; ENSP00000358548; ENSG00000213281.
GeneID4893.
KEGGhsa:4893.
UCSCuc009wgu.3. human.

Organism-specific databases

CTD4893.
GeneCardsGC01M115247.
HGNCHGNC:7989. NRAS.
HPACAB010157.
HPA049830.
MIM164790. gene.
607785. phenotype.
613224. phenotype.
614470. phenotype.
neXtProtNX_P01111.
Orphanet3261. Autoimmune lymphoproliferative syndrome.
86834. Juvenile myelomonocytic leukemia.
626. Large congenital melanocytic nevus.
648. Noonan syndrome.
PharmGKBPA31768.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1100.
HOGENOMHOG000233973.
HOVERGENHBG009351.
InParanoidP01111.
KOK07828.
OMARILNEEC.
OrthoDBEOG7QVM41.
PhylomeDBP01111.
TreeFamTF312796.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_604. Hemostasis.
REACT_6900. Immune System.
SignaLinkP01111.

Gene expression databases

ArrayExpressP01111.
BgeeP01111.
CleanExHS_NRAS.
GenevestigatorP01111.

Family and domain databases

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

Other

ChiTaRSNRAS. human.
EvolutionaryTraceP01111.
GeneWikiNeuroblastoma_RAS_viral_oncogene_homolog.
GenomeRNAi4893.
NextBio18835.
PROP01111.
SOURCESearch...

Entry information

Entry nameRASN_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 168 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM