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P20171

- RASH_RAT

UniProt

P20171 - RASH_RAT

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Protein
GTPase HRas
Gene
Hras, Hras1
Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi10 – 178GTP
Nucleotide bindingi57 – 615GTP
Nucleotide bindingi116 – 1194GTP

GO - Molecular functioni

  1. GTP binding Source: UniProtKB
  2. protein binding Source: UniProtKB
Complete GO annotation...

GO - Biological processi

  1. GTP catabolic process Source: InterPro
  2. Ras protein signal transduction Source: RGD
  3. actin cytoskeleton organization Source: Ensembl
  4. apoptotic process Source: RGD
  5. cell cycle arrest Source: Ensembl
  6. cell proliferation Source: Ensembl
  7. cellular senescence Source: Ensembl
  8. endocytosis Source: Ensembl
  9. intrinsic apoptotic signaling pathway Source: Ensembl
  10. mitotic cell cycle checkpoint Source: Ensembl
  11. negative regulation of Rho GTPase activity Source: Ensembl
  12. negative regulation of cell proliferation Source: Ensembl
  13. negative regulation of gene expression Source: Ensembl
  14. negative regulation of neuron apoptotic process Source: Ensembl
  15. positive regulation of DNA replication Source: RGD
  16. positive regulation of ERK1 and ERK2 cascade Source: RGD
  17. positive regulation of JNK cascade Source: Ensembl
  18. positive regulation of MAP kinase activity Source: Ensembl
  19. positive regulation of Rac GTPase activity Source: Ensembl
  20. positive regulation of Rac protein signal transduction Source: Ensembl
  21. positive regulation of Ras protein signal transduction Source: MGI
  22. positive regulation of actin cytoskeleton reorganization Source: Ensembl
  23. positive regulation of cell migration Source: Ensembl
  24. positive regulation of epithelial cell proliferation Source: Ensembl
  25. positive regulation of miRNA metabolic process Source: Ensembl
  26. positive regulation of ruffle assembly Source: Ensembl
  27. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
  28. positive regulation of wound healing Source: Ensembl
  29. protein heterooligomerization Source: RGD
  30. regulation of long-term neuronal synaptic plasticity Source: Ensembl
  31. regulation of synaptic transmission, GABAergic Source: Ensembl
  32. social behavior Source: RGD
  33. striated muscle cell differentiation Source: Ensembl
  34. visual learning Source: Ensembl
Complete GO annotation...

Keywords - Ligandi

GTP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_195025. Signaling by SCF-KIT.
REACT_195026. SHC1 events in ERBB4 signaling.
REACT_195029. SHC1 events in ERBB2 signaling.
REACT_195202. FCERI mediated MAPK activation.
REACT_195203. GRB2 events in ERBB2 signaling.
REACT_196389. Ras activation uopn Ca2+ infux through NMDA receptor.
REACT_196848. EGFR Transactivation by Gastrin.
REACT_198665. Signaling by FGFR mutants.
REACT_199246. Activation of RAS in B cells.
REACT_199249. Signaling by constitutively active EGFR.
REACT_204559. SOS-mediated signalling.
REACT_206819. Downstream signal transduction.
REACT_212418. DAP12 signaling.
REACT_79133. SHC-mediated cascade.

Names & Taxonomyi

Protein namesi
Recommended name:
GTPase HRas
Alternative name(s):
H-Ras-1
Transforming protein p21
c-H-ras
p21ras
Cleaved into the following chain:
Gene namesi
Name:Hras
Synonyms:Hras1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 1

Organism-specific databases

RGDi2827. Hras.

Subcellular locationi

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.1 Publication

GO - Cellular componenti

  1. Golgi apparatus Source: UniProtKB
  2. Golgi membrane Source: UniProtKB-SubCell
  3. intracellular membrane-bounded organelle Source: RGD
  4. plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi26 – 261N → G: Interacts and partially stimulates PLCE1; when associated with L-61. 1 Publication
Mutagenesisi35 – 351T → S: No interaction and stimulation of PLCE1; when associated with L-61. 1 Publication
Mutagenesisi37 – 371E → G: Reduced interaction and stimulation of PLCE1; when associated with L-61. 1 Publication
Mutagenesisi38 – 381D → N: Reduced interaction and stimulation of PLCE1; when associated with L-61. 1 Publication
Mutagenesisi40 – 401Y → C: No interaction and stimulation of PLCE1; when associated with L-61. 1 Publication
Mutagenesisi61 – 611Q → 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. 1 Publication
Mutagenesisi186 – 1861C → S: Interacts but does not stimulate PLCE1; when associated with L-61. 1 Publication

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 186186GTPase HRas
PRO_0000043000Add
BLAST
Initiator methioninei1 – 11Removed; alternate By similarity
Chaini2 – 186185GTPase HRas, N-terminally processed
PRO_0000326479Add
BLAST
Propeptidei187 – 1893Removed in mature form By similarity
PRO_0000043001

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionine By similarity
Modified residuei2 – 21N-acetylthreonine; in GTPase HRas, N-terminally processed By similarity
Modified residuei118 – 1181S-nitrosocysteine By similarity
Lipidationi181 – 1811S-palmitoyl cysteine By similarity
Lipidationi184 – 1841S-(15-deoxy-Delta12,14-prostaglandin J2-9-yl)cysteine; alternate By similarity
Lipidationi184 – 1841S-palmitoyl cysteine; alternate By similarity
Modified residuei186 – 1861Cysteine methyl ester1 Publication
Lipidationi186 – 1861S-farnesyl cysteine1 Publication

Post-translational modificationi

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.

Keywords - PTMi

Acetylation, Lipoprotein, Methylation, Palmitate, Prenylation, S-nitrosylation

Proteomic databases

PaxDbiP20171.
PRIDEiP20171.

Expressioni

Gene expression databases

GenevestigatoriP20171.

Interactioni

Subunit structurei

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.3 Publications

Protein-protein interaction databases

BioGridi254357. 5 interactions.
IntActiP20171. 1 interaction.
MINTiMINT-4996514.
STRINGi10116.ENSRNOP00000022363.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi2 – 1110
Helixi16 – 2510
Beta strandi36 – 4611
Beta strandi49 – 5810
Helixi62 – 643
Helixi68 – 725
Beta strandi76 – 838
Helixi87 – 915
Helixi93 – 10412
Beta strandi111 – 1166
Helixi127 – 13711
Beta strandi141 – 1433
Turni146 – 1483
Helixi152 – 16312

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3V4FX-ray1.39A1-166[»]
ProteinModelPortaliP20171.
SMRiP20171. Positions 1-166.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni166 – 18520Hypervariable region
Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi32 – 409Effector region

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG1100.
GeneTreeiENSGT00750000117221.
HOGENOMiHOG000233973.
HOVERGENiHBG009351.
InParanoidiP20171.
KOiK02833.
OMAiGPEPRIS.
OrthoDBiEOG7QVM41.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR020849. Small_GTPase_Ras.
[Graphical view]
PANTHERi