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P20171

- RASH_RAT

UniProt

P20171 - RASH_RAT

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Protein

GTPase HRas

Gene

Hras

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

GO - Biological processi

  1. actin cytoskeleton organization Source: Ensembl
  2. apoptotic process Source: RGD
  3. cell cycle arrest Source: Ensembl
  4. cell proliferation Source: Ensembl
  5. cellular senescence Source: Ensembl
  6. endocytosis Source: Ensembl
  7. epithelial tube branching involved in lung morphogenesis Source: Ensembl
  8. GTP catabolic process Source: InterPro
  9. intrinsic apoptotic signaling pathway Source: Ensembl
  10. mitotic cell cycle checkpoint Source: Ensembl
  11. negative regulation of cell differentiation 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. negative regulation of Rho GTPase activity Source: Ensembl
  16. positive regulation of actin cytoskeleton reorganization Source: Ensembl
  17. positive regulation of cell migration Source: Ensembl
  18. positive regulation of DNA replication Source: RGD
  19. positive regulation of epithelial cell proliferation Source: Ensembl
  20. positive regulation of ERK1 and ERK2 cascade Source: RGD
  21. positive regulation of JNK cascade Source: Ensembl
  22. positive regulation of MAP kinase activity Source: Ensembl
  23. positive regulation of miRNA metabolic process Source: Ensembl
  24. positive regulation of Rac GTPase activity Source: Ensembl
  25. positive regulation of Rac protein signal transduction Source: Ensembl
  26. positive regulation of Ras protein signal transduction Source: MGI
  27. positive regulation of ruffle assembly Source: Ensembl
  28. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
  29. positive regulation of wound healing Source: Ensembl
  30. protein heterooligomerization Source: RGD
  31. Ras protein signal transduction Source: RGD
  32. regulation of long-term neuronal synaptic plasticity Source: Ensembl
  33. regulation of synaptic transmission, GABAergic Source: Ensembl
  34. social behavior Source: RGD
  35. striated muscle cell differentiation Source: Ensembl
  36. 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 1 Publication. Cell membrane By similarity; Lipid-anchor By similarity; Cytoplasmic side By similarity. Golgi apparatus By similarity. Golgi apparatus membrane By similarity; 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.By similarity

GO - Cellular componenti

  1. Golgi apparatus Source: UniProtKB
  2. intracellular membrane-bounded organelle Source: RGD
  3. 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 HRasPRO_0000043000Add
BLAST
Initiator methioninei1 – 11Removed; alternateBy similarity
Chaini2 – 186185GTPase HRas, N-terminally processedPRO_0000326479Add
BLAST
Propeptidei187 – 1893Removed in mature formBy similarityPRO_0000043001

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineBy similarity
Modified residuei2 – 21N-acetylthreonine; in GTPase HRas, N-terminally processedBy similarity
Modified residuei118 – 1181S-nitrosocysteineBy similarity
Lipidationi181 – 1811S-palmitoyl cysteineBy similarity
Lipidationi184 – 1841S-(15-deoxy-Delta12,14-prostaglandin J2-9-yl)cysteine; alternateBy similarity
Lipidationi184 – 1841S-palmitoyl cysteine; alternateBy 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).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).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

ExpressionAtlasiP20171. baseline.
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).By similarity

Protein-protein interaction databases

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

Structurei

Secondary structure

1
189
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.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

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

Motif

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

Sequence similaritiesi

Belongs to the small GTPase superfamily. Ras family.Curated

Phylogenomic databases

eggNOGiCOG1100.
GeneTreeiENSGT00760000118909.
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]
PANTHERiPTHR24070. PTHR24070. 1 hit.
PfamiPF00071. Ras. 1 hit.
[Graphical view]
PRINTSiPR00449. RASTRNSFRMNG.
SMARTiSM00173. RAS. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiPS51421. RAS. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P20171-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MTEYKLVVVG AGGVGKSALT IQLIQNHFVD EYDPTIEDSY RKQVVIDGET
60 70 80 90 100
CLLDILDTAG QEEYSAMRDQ YMRTGEGFLC VFAINNTKSF EDIHQYREQI
110 120 130 140 150
KRVKDSDDVP MVLVGNKCDL AARTVESRQA QDLARSYGIP YIETSAKTRQ
160 170 180
GVEDAFYTLV REIRQHKLRK LNPPDESGPG CMSCKCVLS
Length:189
Mass (Da):21,298
Last modified:July 27, 2011 - v2
Checksum:iEE6DC2D933E2856A
GO

Sequence cautioni

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.

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti179 – 1791P → L in AAA42009. (PubMed:3023901)Curated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
PIRiA25229.
RefSeqiNP_001091711.1. NM_001098241.1.
NP_001123913.1. NM_001130441.1.
UniGeneiRn.102180.

Genome annotation databases

EnsembliENSRNOT00000022363; ENSRNOP00000022363; ENSRNOG00000016611.
GeneIDi293621.
KEGGirno:293621.
UCSCiRGD:2827. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
PIRi A25229.
RefSeqi NP_001091711.1. NM_001098241.1.
NP_001123913.1. NM_001130441.1.
UniGenei Rn.102180.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
3V4F X-ray 1.39 A 1-166 [» ]
ProteinModelPortali P20171.
SMRi P20171. Positions 1-166.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 254357. 5 interactions.
IntActi P20171. 1 interaction.
MINTi MINT-4996514.
STRINGi 10116.ENSRNOP00000022363.

Chemistry

BindingDBi P20171.

Proteomic databases

PaxDbi P20171.
PRIDEi P20171.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000022363 ; ENSRNOP00000022363 ; ENSRNOG00000016611 .
GeneIDi 293621.
KEGGi rno:293621.
UCSCi RGD:2827. rat.

Organism-specific databases

CTDi 3265.
RGDi 2827. Hras.

Phylogenomic databases

eggNOGi COG1100.
GeneTreei ENSGT00760000118909.
HOGENOMi HOG000233973.
HOVERGENi HBG009351.
InParanoidi P20171.
KOi K02833.
OMAi GPEPRIS.
OrthoDBi EOG7QVM41.

Enzyme and pathway databases

Reactomei REACT_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.

Miscellaneous databases

NextBioi 636547.

Gene expression databases

ExpressionAtlasi P20171. baseline.
Genevestigatori P20171.

Family and domain databases

Gene3Di 3.40.50.300. 1 hit.
InterProi IPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR020849. Small_GTPase_Ras.
[Graphical view ]
PANTHERi PTHR24070. PTHR24070. 1 hit.
Pfami PF00071. Ras. 1 hit.
[Graphical view ]
PRINTSi PR00449. RASTRNSFRMNG.
SMARTi SM00173. RAS. 1 hit.
[Graphical view ]
SUPFAMi SSF52540. SSF52540. 1 hit.
TIGRFAMsi TIGR00231. small_GTP. 1 hit.
PROSITEi PS51421. RAS. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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.

Entry informationi

Entry nameiRASH_RAT
AccessioniPrimary (citable) accession number: P20171
Secondary accession number(s): Q4KLL6, Q5RJJ8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: July 27, 2011
Last modified: October 29, 2014
This is version 126 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3