UniProtKB - P01111 (RASN_HUMAN)
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Protein
GTPase NRas
Gene
NRAS
Organism
Homo sapiens (Human)
Status
Functioni
Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
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.
Enzyme regulationi
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).
Regions
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Nucleotide bindingi | 10 – 18 | GTP1 Publication | 9 | |
| Nucleotide bindingi | 29 – 30 | GTP1 Publication | 2 | |
| Nucleotide bindingi | 57 – 61 | GTPSequence analysis | 5 | |
| Nucleotide bindingi | 116 – 119 | GTP1 Publication | 4 |
GO - Molecular functioni
- GTPase activity Source: InterPro
- GTP binding Source: UniProtKB-KW
- protein-containing complex binding Source: MGI
GO - Biological processi
- MAPK cascade Source: Reactome
- neutrophil degranulation Source: Reactome
- positive regulation of endothelial cell proliferation Source: BHF-UCL
- Ras protein signal transduction Source: Reactome
- stimulatory C-type lectin receptor signaling pathway Source: Reactome
Keywordsi
| Ligand | GTP-binding, Nucleotide-binding |
Enzyme and pathway databases
| Reactomei | R-HSA-112412 SOS-mediated signalling R-HSA-1169092 Activation of RAS in B cells R-HSA-1236382 Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants R-HSA-1250196 SHC1 events in ERBB2 signaling R-HSA-1250347 SHC1 events in ERBB4 signaling R-HSA-1433557 Signaling by SCF-KIT R-HSA-167044 Signalling to RAS R-HSA-171007 p38MAPK events R-HSA-179812 GRB2 events in EGFR signaling R-HSA-180336 SHC1 events in EGFR signaling R-HSA-186763 Downstream signal transduction R-HSA-1963640 GRB2 events in ERBB2 signaling R-HSA-210993 Tie2 Signaling R-HSA-2179392 EGFR Transactivation by Gastrin R-HSA-2424491 DAP12 signaling R-HSA-2428933 SHC-related events triggered by IGF1R R-HSA-2871796 FCERI mediated MAPK activation R-HSA-375165 NCAM signaling for neurite out-growth R-HSA-5218921 VEGFR2 mediated cell proliferation R-HSA-5621575 CD209 (DC-SIGN) signaling R-HSA-5637810 Constitutive Signaling by EGFRvIII R-HSA-5654688 SHC-mediated cascade:FGFR1 R-HSA-5654693 FRS-mediated FGFR1 signaling R-HSA-5654699 SHC-mediated cascade:FGFR2 R-HSA-5654700 FRS-mediated FGFR2 signaling R-HSA-5654704 SHC-mediated cascade:FGFR3 R-HSA-5654706 FRS-mediated FGFR3 signaling R-HSA-5654712 FRS-mediated FGFR4 signaling R-HSA-5654719 SHC-mediated cascade:FGFR4 R-HSA-5655253 Signaling by FGFR2 in disease R-HSA-5655291 Signaling by FGFR4 in disease R-HSA-5655302 Signaling by FGFR1 in disease R-HSA-5658442 Regulation of RAS by GAPs R-HSA-5673000 RAF activation R-HSA-5673001 RAF/MAP kinase cascade R-HSA-5674135 MAP2K and MAPK activation R-HSA-5675221 Negative regulation of MAPK pathway R-HSA-6798695 Neutrophil degranulation R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants R-HSA-6802948 Signaling by high-kinase activity BRAF mutants R-HSA-6802949 Signaling by RAS mutants R-HSA-6802952 Signaling by BRAF and RAF fusions R-HSA-6802953 RAS signaling downstream of NF1 loss-of-function variants R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF R-HSA-74751 Insulin receptor signalling cascade R-HSA-8849471 PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases R-HSA-8851805 MET activates RAS signaling R-HSA-8853334 Signaling by FGFR3 fusions in cancer R-HSA-8853338 Signaling by FGFR3 point mutants in cancer R-HSA-9026519 Activated NTRK2 signals through RAS R-HSA-9028731 Activated NTRK2 signals through FRS2 and FRS3 |
| SignaLinki | P01111 |
| SIGNORi | P01111 |
Names & Taxonomyi
| Protein namesi | Recommended name: GTPase NRasAlternative name(s): Transforming protein N-Ras |
| Gene namesi | Name:NRAS Synonyms:HRAS1 |
| Organismi | Homo sapiens (Human) |
| Taxonomic identifieri | 9606 [NCBI] |
| Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
| Proteomesi |
|
Organism-specific databases
| EuPathDBi | HostDB:ENSG00000213281.4 |
| HGNCi | HGNC:7989 NRAS |
| MIMi | 164790 gene |
| neXtProti | NX_P01111 |
Pathology & Biotechi
Involvement in diseasei
Leukemia, juvenile myelomonocytic (JMML)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:607785Noonan syndrome 6 (NS6)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:613224| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_063085 | 50 | T → I in NS6; hypermorphic mutation. 1 PublicationCorresponds to variant dbSNP:rs267606921EnsemblClinVar. | 1 | |
| Natural variantiVAR_063086 | 60 | G → E in NS6; hypermorphic mutation. 1 PublicationCorresponds to variant dbSNP:rs267606920EnsemblClinVar. | 1 |
RAS-associated autoimmune leukoproliferative disorder (RALD)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder of apoptosis, characterized by chronic accumulation of non-malignant lymphocytes, defective lymphocyte apoptosis, and an increased risk for the development of hematologic malignancies.
See also OMIM:614470Melanocytic nevus syndrome, congenital (CMNS)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA syndrome characterized by congenital pigmentary skin lesions which can occur at any site and can cover most of the body surface. These lesions may or may not be hairy. Congenital melanocytic nevi are associated with neuromelanosis (the presence of melanin-producing cells within the brain parenchyma or leptomeninges). Less commonly they are associated with malignant melanoma in childhood, both in the skin and the central nervous system. CMNS patients also tend to have a characteristic facial appearance, including wide or prominent forehead, periorbital fullness, small short nose with narrow nasal bridge, round face, full cheeks, prominent premaxilla, and everted lower lip.
See also OMIM:137550| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_006847 | 61 | Q → R in CMNS, NCMS, KNEN and NMTC2; also found in lung carcinoma cell and melanoma. 5 PublicationsCorresponds to variant dbSNP:rs11554290EnsemblClinVar. | 1 |
Melanosis, neurocutaneous (NCMS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare congenital disease characterized by the presence of giant or multiple melanocytic nevi on the skin, foci of melanin-producing cells within the brain parenchyma, and infiltration of leptomeninges by abnormal melanin deposits. Neurologic abnormalities include seizures, hydrocephalus, arachnoid cysts, tumors, and syringomyelia. Some patients may develop malignant melanoma.
See also OMIM:249400Keratinocytic non-epidermolytic nevus (KNEN)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionEpidermal nevi of the common, non-organoid and non-epidermolytic type are benign skin lesions and may vary in their extent from a single (usually linear) lesion to widespread and systematized involvement. They may be present at birth or develop early during childhood.
See also OMIM:162900| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_071130 | 34 | P → L in KNEN. 1 PublicationCorresponds to variant dbSNP:rs397514553EnsemblClinVar. | 1 |
Thyroid cancer, non-medullary, 2 (NMTC2)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA form of non-medullary thyroid cancer (NMTC), a cancer characterized by tumors originating from the thyroid follicular cells. NMTCs represent approximately 95% of all cases of thyroid cancer and are classified into papillary, follicular, Hurthle cell, and anaplastic neoplasms.
See also OMIM:188470Mutagenesis
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Mutagenesisi | 164 | R → A: Loss of GTP-binding activity. | 1 | |
| Mutagenesisi | 181 | C → S: Loss of plasma membrane localization. 1 Publication | 1 |
Keywords - Diseasei
Disease mutation, Proto-oncogeneOrganism-specific databases
| DisGeNETi | 4893 |
| GeneReviewsi | NRAS |
| MalaCardsi | NRAS |
| MIMi | 137550 phenotype 162900 phenotype 188470 phenotype 249400 phenotype 607785 phenotype 613224 phenotype 614470 phenotype |
| OpenTargetsi | ENSG00000213281 |
| Orphaneti | 86834 Juvenile myelomonocytic leukemia 626 Large congenital melanocytic nevus 648 Noonan syndrome 268114 RAS-associated autoimmune leukoproliferative disease |
| PharmGKBi | PA31768 |
Chemistry databases
| ChEMBLi | CHEMBL2079845 |
| GuidetoPHARMACOLOGYi | 2823 |
Polymorphism and mutation databases
| BioMutai | NRAS |
| DMDMi | 131883 |
PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| ChainiPRO_0000043006 | 1 – 186 | GTPase NRasAdd BLAST | 186 | |
| PropeptideiPRO_0000043007 | 187 – 189 | Removed in mature formBy similarity | 3 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Lipidationi | 181 | S-palmitoyl cysteine3 Publications | 1 | |
| Modified residuei | 186 | Cysteine methyl esterBy similarity | 1 | |
| Lipidationi | 186 | S-farnesyl cysteine1 Publication | 1 |
Post-translational modificationi
Palmitoylated by the ZDHHC9-GOLGA7 complex (PubMed:16000296). Depalmitoylated by ABHD17A, ABHD17B and ABHD17C (PubMed:26701913). A continuous cycle of de- and re-palmitoylation regulates rapid exchange between plasma membrane and Golgi (PubMed:16000296, PubMed:15705808, PubMed:2661017, PubMed:26701913).4 Publications
Acetylation at Lys-104 prevents interaction with guanine nucleotide exchange factors (GEFs).By similarity
Keywords - PTMi
Acetylation, Lipoprotein, Methylation, Palmitate, PrenylationProteomic databases
| EPDi | P01111 |
| PaxDbi | P01111 |
| PeptideAtlasi | P01111 |
| PRIDEi | P01111 |
| ProteomicsDBi | 51320 |
2D gel databases
| OGPi | P01111 |
PTM databases
| iPTMneti | P01111 |
| PhosphoSitePlusi | P01111 |
| SwissPalmi | P01111 |
Expressioni
Gene expression databases
| Bgeei | ENSG00000213281 |
| CleanExi | HS_NRAS |
| ExpressionAtlasi | P01111 baseline and differential |
| Genevisiblei | P01111 HS |
Organism-specific databases
| HPAi | CAB010157 HPA049830 |
Interactioni
Subunit structurei
Interacts (active GTP-bound form preferentially) with RGS14 (By similarity). Interacts (active GTP-bound form) with RASSF7.By similarity1 Publication
Binary interactionsi
Protein-protein interaction databases
| BioGridi | 110952, 44 interactors |
| DIPi | DIP-1058N |
| ELMi | P01111 |
| IntActi | P01111, 42 interactors |
| MINTi | P01111 |
| STRINGi | 9606.ENSP00000358548 |
Chemistry databases
| BindingDBi | P01111 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Beta strandi | 2 – 9 | Combined sources | 8 | |
| Helixi | 16 – 25 | Combined sources | 10 | |
| Beta strandi | 38 – 46 | Combined sources | 9 | |
| Beta strandi | 49 – 57 | Combined sources | 9 | |
| Helixi | 62 – 64 | Combined sources | 3 | |
| Helixi | 65 – 71 | Combined sources | 7 | |
| Turni | 72 – 74 | Combined sources | 3 | |
| Beta strandi | 76 – 83 | Combined sources | 8 | |
| Helixi | 87 – 104 | Combined sources | 18 | |
| Beta strandi | 111 – 116 | Combined sources | 6 | |
| Helixi | 127 – 137 | Combined sources | 11 | |
| Beta strandi | 141 – 143 | Combined sources | 3 | |
| Turni | 146 – 148 | Combined sources | 3 | |
| Helixi | 152 – 166 | Combined sources | 15 |
3D structure databases
| ProteinModelPortali | P01111 |
| SMRi | P01111 |
| ModBasei | Search... |
| MobiDBi | Search... |
Miscellaneous databases
| EvolutionaryTracei | P01111 |
Family & Domainsi
Region
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Regioni | 166 – 185 | Hypervariable regionAdd BLAST | 20 |
Motif
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Motifi | 32 – 40 | Effector region | 9 |
Sequence similaritiesi
Phylogenomic databases
| eggNOGi | KOG0395 Eukaryota COG1100 LUCA |
| GeneTreei | ENSGT00860000133672 |
| HOGENOMi | HOG000233973 |
| HOVERGENi | HBG009351 |
| InParanoidi | P01111 |
| KOi | K07828 |
| OMAi | TIEXEQI |
| OrthoDBi | EOG091G0UAU |
| PhylomeDBi | P01111 |
| TreeFami | TF312796 |
Family and domain databases
| InterProi | View protein in InterPro IPR027417 P-loop_NTPase IPR005225 Small_GTP-bd_dom IPR001806 Small_GTPase IPR020849 Small_GTPase_Ras-type |
| PANTHERi | PTHR24070 PTHR24070, 1 hit |
| Pfami | View protein in Pfam PF00071 Ras, 1 hit |
| SUPFAMi | SSF52540 SSF52540, 1 hit |
| TIGRFAMsi | TIGR00231 small_GTP, 1 hit |
| PROSITEi | View protein in PROSITE PS51421 RAS, 1 hit |
Sequencei
Sequence statusi: Complete.
Sequence processingi: The displayed sequence is further processed into a mature form.
P01111-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MTEYKLVVVG AGGVGKSALT IQLIQNHFVD EYDPTIEDSY RKQVVIDGET
60 70 80 90 100
CLLDILDTAG QEEYSAMRDQ YMRTGEGFLC VFAINNSKSF ADINLYREQI
110 120 130 140 150
KRVKDSDDVP MVLVGNKCDL PTRTVDTKQA HELAKSYGIP FIETSAKTRQ
160 170 180
GVEDAFYTLV REIRQYRMKK LNSSDDGTQG CMGLPCVVM
Natural variant
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_021194 | 12 | G → C in leukemia. 1 PublicationCorresponds to variant dbSNP:rs121913250EnsemblClinVar. | 1 | |
| Natural variantiVAR_071129 | 12 | G → D in KNEN and JMML. 2 PublicationsCorresponds to variant dbSNP:rs121913237EnsemblClinVar. | 1 | |
| Natural variantiVAR_063084 | 13 | G → D in RALD and JMML. 2 PublicationsCorresponds to variant dbSNP:rs121434596EnsemblClinVar. | 1 | |
| Natural variantiVAR_006845 | 13 | G → R in CMNS and colorectal cancer; somatic mutation. 2 PublicationsCorresponds to variant dbSNP:rs121434595EnsemblClinVar. | 1 | |
| Natural variantiVAR_071130 | 34 | P → L in KNEN. 1 PublicationCorresponds to variant dbSNP:rs397514553EnsemblClinVar. | 1 | |
| Natural variantiVAR_063085 | 50 | T → I in NS6; hypermorphic mutation. 1 PublicationCorresponds to variant dbSNP:rs267606921EnsemblClinVar. | 1 | |
| Natural variantiVAR_063086 | 60 | G → E in NS6; hypermorphic mutation. 1 PublicationCorresponds to variant dbSNP:rs267606920EnsemblClinVar. | 1 | |
| Natural variantiVAR_006846 | 61 | Q → K in CMNS and NCMS; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs121913254EnsemblClinVar. | 1 | |
| Natural variantiVAR_006847 | 61 | Q → R in CMNS, NCMS, KNEN and NMTC2; also found in lung carcinoma cell and melanoma. 5 PublicationsCorresponds to variant dbSNP:rs11554290EnsemblClinVar. | 1 |
Sequence databases
| Select the link destinations: EMBLi GenBanki DDBJi Links Updated | 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 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 |
| CCDSi | CCDS877.1 |
| PIRi | A90839 TVHURA I38149 |
| RefSeqi | NP_002515.1, NM_002524.4 |
| UniGenei | Hs.486502 |
Genome annotation databases
| Ensembli | ENST00000369535; ENSP00000358548; ENSG00000213281 |
| GeneIDi | 4893 |
| KEGGi | hsa:4893 |
Similar proteinsi
Entry informationi
| Entry namei | RASN_HUMAN | |
| Accessioni | P01111Primary (citable) accession number: P01111 Secondary accession number(s): Q14971, Q15104, Q15282 | |
| Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 21, 1986 |
| Last sequence update: | July 21, 1986 | |
| Last modified: | July 18, 2018 | |
| This is version 214 of the entry and version 1 of the sequence. See complete history. | ||
| Entry statusi | 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. | |
Miscellaneousi
Keywords - Technical termi
3D-structure, Complete proteome, Reference proteomeDocuments
- Human chromosome 1
Human chromosome 1: 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
