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P20171 (RASH_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
GTPase HRas
Alternative name(s):
H-Ras-1
Transforming protein p21
c-H-ras
p21ras

Cleaved into the following chain:

  1. GTPase HRas, N-terminally processed
Gene names
Name:Hras
Synonyms:Hras1
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

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

Forms a signaling complex with RASGRP1 and DGKZ. In its GTP-bound form interacts with PLCE1. Interacts with TBC1D10C. Interacts with RGL3 and RASSF5. Interacts with HSPD1. Interacts with PDE6D. Interacts with IKZF3. Interacts with GNB2L1 By similarity. Found in a complex with at least BRAF, HRAS, MAP2K1, MAPK3 and RGS14. Interacts (active GTP-bound form) with RGS14 (via RBD 1 domain). Interacts with PIK3CG; the interaction is required for membrane recruitment and beta-gamma G protein dimer-dependent activation of the PI3K gamma complex PIK3CG:PIK3R6 By similarity. Interacts with RAPGEF2 By similarity. Ref.5 Ref.6 Ref.7

Subcellular location

Cell membrane. Cell membrane; Lipid-anchor; Cytoplasmic side By similarity. Golgi apparatus By similarity. Golgi apparatus membrane; Lipid-anchor By similarity. Note: Shuttles between the plasma membrane and the Golgi apparatus By similarity. The active GTP-bound form is localized most strongly to membranes than the inactive GDP-bound form. Ref.7

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 By similarity.

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

The covalent modification of cysteine by 15-deoxy-Delta12,14-prostaglandin-J2 is autocatalytic and reversible. It may occur as an alternative to other cysteine modifications, such as S-nitrosylation and S-palmitoylation By similarity.

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

Sequence similarities

Belongs to the small GTPase superfamily. Ras family.

Sequence caution

The sequence AAH86608.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence AAH99130.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Cellular componentCell membrane
Golgi apparatus
Membrane
   DiseaseProto-oncogene
   LigandGTP-binding
Nucleotide-binding
   PTMAcetylation
Lipoprotein
Methylation
Palmitate
Prenylation
S-nitrosylation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processGTP catabolic process

Inferred from electronic annotation. Source: InterPro

Ras protein signal transduction

Inferred from mutant phenotype PubMed 12077341. Source: RGD

actin cytoskeleton organization

Inferred from electronic annotation. Source: Ensembl

apoptotic process

Inferred from mutant phenotype PubMed 14988264. Source: RGD

cell cycle arrest

Inferred from electronic annotation. Source: Ensembl

cell proliferation

Inferred from electronic annotation. Source: Ensembl

cellular senescence

Inferred from electronic annotation. Source: Ensembl

endocytosis

Inferred from electronic annotation. Source: Ensembl

intrinsic apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

mitotic cell cycle checkpoint

Inferred from electronic annotation. Source: Ensembl

negative regulation of Rho GTPase activity

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of gene expression

Inferred from electronic annotation. Source: Ensembl

negative regulation of neuron apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of DNA replication

Inferred from mutant phenotype PubMed 9487126. Source: RGD

positive regulation of ERK1 and ERK2 cascade

Inferred from mutant phenotype PubMed 18163378. Source: RGD

positive regulation of JNK cascade

Inferred from electronic annotation. Source: Ensembl

positive regulation of MAP kinase activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of Rac GTPase activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of Rac protein signal transduction

Inferred from electronic annotation. Source: Ensembl

positive regulation of Ras protein signal transduction

Inferred from mutant phenotype PubMed 19029245. Source: MGI

positive regulation of actin cytoskeleton reorganization

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell migration

Inferred from electronic annotation. Source: Ensembl

positive regulation of epithelial cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of miRNA metabolic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of ruffle assembly

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

positive regulation of wound healing

Inferred from electronic annotation. Source: Ensembl

protein heterooligomerization

Inferred from physical interaction PubMed 15917294. Source: RGD

regulation of long-term neuronal synaptic plasticity

Inferred from electronic annotation. Source: Ensembl

regulation of synaptic transmission, GABAergic

Inferred from electronic annotation. Source: Ensembl

social behavior

Inferred from expression pattern PubMed 19616040. Source: RGD

striated muscle cell differentiation

Inferred from electronic annotation. Source: Ensembl

visual learning

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentGolgi apparatus

Inferred from sequence or structural similarity. Source: UniProtKB

Golgi membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

intracellular membrane-bounded organelle

Inferred from direct assay PubMed 19616040. Source: RGD

plasma membrane

Inferred from direct assay Ref.7. Source: UniProtKB

   Molecular_functionGTP binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 186186GTPase HRas
PRO_0000043000
Initiator methionine11Removed; alternate By similarity
Chain2 – 186185GTPase HRas, N-terminally processed
PRO_0000326479
Propeptide187 – 1893Removed in mature form By similarity
PRO_0000043001

Regions

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

Amino acid modifications

Modified residue11N-acetylmethionine By similarity
Modified residue21N-acetylthreonine; in GTPase HRas, N-terminally processed By similarity
Modified residue1181S-nitrosocysteine By similarity
Modified residue1861Cysteine methyl ester Ref.4
Lipidation1811S-palmitoyl cysteine By similarity
Lipidation1841S-(15-deoxy-Delta12,14-prostaglandin J2-9-yl)cysteine; alternate By similarity
Lipidation1841S-palmitoyl cysteine; alternate By similarity
Lipidation1861S-farnesyl cysteine Ref.4

Experimental info

Mutagenesis261N → G: Interacts and partially stimulates PLCE1; when associated with L-61. Ref.5
Mutagenesis351T → S: No interaction and stimulation of PLCE1; when associated with L-61. Ref.5
Mutagenesis371E → G: Reduced interaction and stimulation of PLCE1; when associated with L-61. Ref.5
Mutagenesis381D → N: Reduced interaction and stimulation of PLCE1; when associated with L-61. Ref.5
Mutagenesis401Y → C: No interaction and stimulation of PLCE1; when associated with L-61. Ref.5
Mutagenesis611Q → L: Constitutively active. Constitutively interacts and stimulates PLCE1 phospholipase activity. Reduced interaction and stimulation of PLCE1; when associated with G-37 and N-38. No interaction and stimulation of PLCE1; when associated with S-35 and C-40. Interacts and partially stimulates PLCE1; when associated with G-26. Interacts but does not stimulate PLCE1; when associated with S-186. Ref.5
Mutagenesis1861C → S: Interacts but does not stimulate PLCE1; when associated with L-61. Ref.5
Sequence conflict1791P → L in AAA42009. Ref.1

Secondary structure

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

Details...

Sequences

Sequence LengthMass (Da)Tools
P20171 [UniParc].

Last modified July 27, 2011. Version 2.
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]"Nucleotide sequence of the two rat cellular rasH genes."
Ruta M., Wolford R., Dhar R., Defeo-Jones D., Ellis R.W., Scolnick E.M.
Mol. Cell. Biol. 6:1706-1710(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"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: Brain and Thymus.
[3]"Nucleotide sequence and characterization of the 5' flanking region of the rat Ha-ras protooncogene."
Damante G., Filetti S., Rapoport B.
Proc. Natl. Acad. Sci. U.S.A. 84:774-778(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-37.
[4]"Posttranslational modification of the Ha-ras oncogene protein: evidence for a third class of protein carboxyl methyltransferases."
Clarke S., Vogel J.P., Deschenes R.J., Stock J.
Proc. Natl. Acad. Sci. U.S.A. 85:4643-4647(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: ISOPRENYLATION AT CYS-186, CLEAVAGE, METHYLATION AT CYS-186.
[5]"Phospholipase C(epsilon): a novel Ras effector."
Kelley G.G., Reks S.E., Ondrako J.M., Smrcka A.V.
EMBO J. 20:743-754(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PLCE1, MUTAGENESIS OF ASN-26; THR-35; GLU-37; ASP-38; TYR-40; GLN-61 AND CYS-186.
[6]"Regulator of G-protein signaling 14 (RGS14) is a selective H-Ras effector."
Willard F.S., Willard M.D., Kimple A.J., Soundararajan M., Oestreich E.A., Li X., Sowa N.A., Kimple R.J., Doyle D.A., Der C.J., Zylka M.J., Snider W.D., Siderovski D.P.
PLoS ONE 4:E4884-E4884(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH BRAF; MAP2K1; MAPK3 AND RGS14, INTERACTION WITH RGS14.
[7]"RGS14 is a multifunctional scaffold that integrates G protein and Ras/Raf MAPkinase signalling pathways."
Shu F.J., Ramineni S., Hepler J.R.
Cell. Signal. 22:366-376(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RGS14, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M13011 Genomic DNA. Translation: AAA42009.1.
BC086608 mRNA. Translation: AAH86608.1. Different initiation.
BC099130 mRNA. Translation: AAH99130.1. Different initiation.
M15188 Genomic DNA. Translation: AAA42008.1.
PIRA25229.
RefSeqNP_001091711.1. NM_001098241.1.
NP_001123913.1. NM_001130441.1.
UniGeneRn.102180.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3V4FX-ray1.39A1-166[»]
ProteinModelPortalP20171.
SMRP20171. Positions 1-166.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid254357. 5 interactions.
IntActP20171. 1 interaction.
MINTMINT-4996514.
STRING10116.ENSRNOP00000022363.

Chemistry

BindingDBP20171.

Proteomic databases

PaxDbP20171.
PRIDEP20171.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000022363; ENSRNOP00000022363; ENSRNOG00000016611.
GeneID293621.
KEGGrno:293621.
UCSCRGD:2827. rat.

Organism-specific databases

CTD3265.
RGD2827. Hras.

Phylogenomic databases

eggNOGCOG1100.
GeneTreeENSGT00750000117221.
HOGENOMHOG000233973.
HOVERGENHBG009351.
InParanoidP20171.
KOK02833.
OMARSSYDEI.
OrthoDBEOG7QVM41.

Gene expression databases

GenevestigatorP20171.

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

NextBio636547.

Entry information

Entry nameRASH_RAT
AccessionPrimary (citable) accession number: P20171
Secondary accession number(s): Q4KLL6, Q5RJJ8
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: July 27, 2011
Last modified: April 16, 2014
This is version 121 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references