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Protein

GTPase HRas

Gene

Hras

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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 – 178GTPBy similarity
Nucleotide bindingi57 – 615GTPBy similarity
Nucleotide bindingi116 – 1194GTPBy similarity

GO - Molecular functioni

  1. GTP binding Source: MGI
  2. protein C-terminus binding Source: MGI

GO - Biological processi

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

Keywords - Ligandi

GTP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_188185. DAP12 signaling.
REACT_188528. GRB2 events in ERBB2 signaling.
REACT_188530. FCERI mediated MAPK activation.
REACT_188574. SHC1 events in ERBB2 signaling.
REACT_188578. Signaling by SCF-KIT.
REACT_188580. SHC1 events in ERBB4 signaling.
REACT_196455. Signaling by FGFR mutants.
REACT_198244. Ras activation uopn Ca2+ infux through NMDA receptor.
REACT_198350. EGFR Transactivation by Gastrin.
REACT_199122. Activation of RAS in B cells.
REACT_199123. Signaling by constitutively active EGFR.
REACT_207601. p38MAPK events.
REACT_210793. Interleukin receptor SHC signaling.
REACT_211860. Tie2 Signaling.
REACT_230639. Downstream signal transduction.
REACT_234357. FRS2-mediated cascade.
REACT_237640. RAF activation.
REACT_237796. NCAM signaling for neurite out-growth.
REACT_239466. SHC-mediated signalling.
REACT_239722. Signalling to RAS.
REACT_241824. SOS-mediated signalling.
REACT_245086. VEGFR2 mediated cell proliferation.
REACT_245103. GRB2 events in EGFR signaling.
REACT_247566. MEK activation.
REACT_257146. RAF phosphorylates MEK.
REACT_257656. EPHB-mediated forward signaling.
REACT_260286. SHC1 events in EGFR signaling.
REACT_94437. 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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 7

Organism-specific databases

MGIiMGI:96224. Hras.

Subcellular locationi

Cell membrane By similarity. 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. The active GTP-bound form is localized most strongly to membranes than the inactive GDP-bound form (By similarity).By similarity

GO - Cellular componenti

  1. Golgi apparatus Source: UniProtKB
  2. Golgi membrane Source: UniProtKB-SubCell
  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
Mutagenesisi61 – 611Q → R: Found in chemically induced liver tumors. 1 Publication

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 186186GTPase HRasPRO_0000042998Add
BLAST
Initiator methioninei1 – 11Removed; alternateBy similarity
Chaini2 – 186185GTPase HRas, N-terminally processedPRO_0000326478Add
BLAST
Propeptidei187 – 1893Removed in mature formBy similarityPRO_0000042999

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 esterBy similarity
Lipidationi186 – 1861S-farnesyl cysteineBy similarity

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

MaxQBiQ61411.
PaxDbiQ61411.
PRIDEiQ61411.

PTM databases

PhosphoSiteiQ61411.

Expressioni

Gene expression databases

BgeeiQ61411.
CleanExiMM_HRAS1.
ExpressionAtlasiQ61411. baseline and differential.
GenevestigatoriQ61411.

Interactioni

Subunit structurei

Forms a signaling complex with RASGRP1 and DGKZ. In its GTP-bound form interacts with PLCE1. Interacts with TBC1D10C and RASSF5. Interacts with PDE6D. Interacts with IKZF3. 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 GNB2L1. Interacts with RAPGEF2 (By similarity). Interacts with RGL3. Interacts with HSPD1. 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 similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Rassf5Q5EBH12EBI-400273,EBI-960530

Protein-protein interaction databases

BioGridi200416. 15 interactions.
DIPiDIP-29361N.
IntActiQ61411. 9 interactions.
MINTiMINT-1215825.

Structurei

3D structure databases

ProteinModelPortaliQ61411.
SMRiQ61411. 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.
GeneTreeiENSGT00780000121849.
HOGENOMiHOG000233973.
HOVERGENiHBG009351.
InParanoidiQ61411.
KOiK02833.
OMAiDSGPGCM.
OrthoDBiEOG7QVM41.
TreeFamiTF312796.

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]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q61411-1) [UniParc]FASTAAdd to Basket

Also known as: p21, H-Ras4A

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« 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
Isoform 2 (identifier: Q61411-2) [UniParc]FASTAAdd to Basket

Also known as: p19, H-RasIDX

The sequence of this isoform differs from the canonical sequence as follows:
     152-189: VEDAFYTLVREIRQHKLRKLNPPDESGPGCMSCKCVLS → SRSGSSSGTLWDPPSPGTHVTQRPSSWRGGCLLYTSP

Show »
Length:188
Mass (Da):20,880
Checksum:iBD42AE50A77341FF
GO

Sequence cautioni

The sequence AAH61885.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti55 – 551I → Y in CAA90306. (PubMed:8922043)Curated
Isoform 2 (identifier: Q61411-2)
Sequence conflicti163 – 1631D → G in CAD24593. (PubMed:14500341)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei152 – 18938VEDAF…KCVLS → SRSGSSSGTLWDPPSPGTHV TQRPSSWRGGCLLYTSP in isoform 2. 1 PublicationVSP_041598Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z50013 Genomic DNA. Translation: CAA90306.1.
AY373386 mRNA. Translation: AAQ81319.1.
AC108908 Genomic DNA. No translation available.
CH466531 Genomic DNA. Translation: EDL18008.1.
CH466531 Genomic DNA. Translation: EDL18009.1.
BC061885 mRNA. Translation: AAH61885.1. Different initiation.
S74119 Genomic DNA. Translation: AAP21090.1.
AJ437023 mRNA. Translation: CAD24593.1.
CCDSiCCDS22003.1. [Q61411-1]
CCDS52439.1. [Q61411-2]
PIRiS57718.
RefSeqiNP_001123915.1. NM_001130443.1. [Q61411-1]
NP_001123916.1. NM_001130444.1. [Q61411-2]
NP_032310.2. NM_008284.2. [Q61411-1]
UniGeneiMm.334313.

Genome annotation databases

EnsembliENSMUST00000026572; ENSMUSP00000026572; ENSMUSG00000025499. [Q61411-1]
ENSMUST00000097957; ENSMUSP00000095570; ENSMUSG00000025499. [Q61411-1]
ENSMUST00000168550; ENSMUSP00000132110; ENSMUSG00000025499. [Q61411-2]
GeneIDi15461.
KEGGimmu:15461.
UCSCiuc009kju.2. mouse. [Q61411-1]
uc009kjv.2. mouse. [Q61411-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z50013 Genomic DNA. Translation: CAA90306.1.
AY373386 mRNA. Translation: AAQ81319.1.
AC108908 Genomic DNA. No translation available.
CH466531 Genomic DNA. Translation: EDL18008.1.
CH466531 Genomic DNA. Translation: EDL18009.1.
BC061885 mRNA. Translation: AAH61885.1. Different initiation.
S74119 Genomic DNA. Translation: AAP21090.1.
AJ437023 mRNA. Translation: CAD24593.1.
CCDSiCCDS22003.1. [Q61411-1]
CCDS52439.1. [Q61411-2]
PIRiS57718.
RefSeqiNP_001123915.1. NM_001130443.1. [Q61411-1]
NP_001123916.1. NM_001130444.1. [Q61411-2]
NP_032310.2. NM_008284.2. [Q61411-1]
UniGeneiMm.334313.

3D structure databases

ProteinModelPortaliQ61411.
SMRiQ61411. Positions 1-166.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200416. 15 interactions.
DIPiDIP-29361N.
IntActiQ61411. 9 interactions.
MINTiMINT-1215825.

Chemistry

BindingDBiQ61411.

PTM databases

PhosphoSiteiQ61411.

Proteomic databases

MaxQBiQ61411.
PaxDbiQ61411.
PRIDEiQ61411.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000026572; ENSMUSP00000026572; ENSMUSG00000025499. [Q61411-1]
ENSMUST00000097957; ENSMUSP00000095570; ENSMUSG00000025499. [Q61411-1]
ENSMUST00000168550; ENSMUSP00000132110; ENSMUSG00000025499. [Q61411-2]
GeneIDi15461.
KEGGimmu:15461.
UCSCiuc009kju.2. mouse. [Q61411-1]
uc009kjv.2. mouse. [Q61411-2]

Organism-specific databases

CTDi3265.
MGIiMGI:96224. Hras.

Phylogenomic databases

eggNOGiCOG1100.
GeneTreeiENSGT00780000121849.
HOGENOMiHOG000233973.
HOVERGENiHBG009351.
InParanoidiQ61411.
KOiK02833.
OMAiDSGPGCM.
OrthoDBiEOG7QVM41.
TreeFamiTF312796.

Enzyme and pathway databases

ReactomeiREACT_188185. DAP12 signaling.
REACT_188528. GRB2 events in ERBB2 signaling.
REACT_188530. FCERI mediated MAPK activation.
REACT_188574. SHC1 events in ERBB2 signaling.
REACT_188578. Signaling by SCF-KIT.
REACT_188580. SHC1 events in ERBB4 signaling.
REACT_196455. Signaling by FGFR mutants.
REACT_198244. Ras activation uopn Ca2+ infux through NMDA receptor.
REACT_198350. EGFR Transactivation by Gastrin.
REACT_199122. Activation of RAS in B cells.
REACT_199123. Signaling by constitutively active EGFR.
REACT_207601. p38MAPK events.
REACT_210793. Interleukin receptor SHC signaling.
REACT_211860. Tie2 Signaling.
REACT_230639. Downstream signal transduction.
REACT_234357. FRS2-mediated cascade.
REACT_237640. RAF activation.
REACT_237796. NCAM signaling for neurite out-growth.
REACT_239466. SHC-mediated signalling.
REACT_239722. Signalling to RAS.
REACT_241824. SOS-mediated signalling.
REACT_245086. VEGFR2 mediated cell proliferation.
REACT_245103. GRB2 events in EGFR signaling.
REACT_247566. MEK activation.
REACT_257146. RAF phosphorylates MEK.
REACT_257656. EPHB-mediated forward signaling.
REACT_260286. SHC1 events in EGFR signaling.
REACT_94437. SHC-mediated cascade.

Miscellaneous databases

NextBioi288278.
PROiQ61411.
SOURCEiSearch...

Gene expression databases

BgeeiQ61411.
CleanExiMM_HRAS1.
ExpressionAtlasiQ61411. baseline and differential.
GenevestigatoriQ61411.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Nucleotide sequence of c-H-ras-1 gene from B6C3F1 mice."
    Przybojewska B., Plucienniczak G.
    Acta Biochim. Pol. 43:575-578(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: C57BL/6 X C3H.
    Tissue: Liver.
  2. Lin L., Fu D.
    Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Strain: BALB/c.
    Tissue: Keratinocyte.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "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] (ISOFORM 1).
    Tissue: Olfactory epithelium.
  6. "Spontaneous mutation at codon 61 of the Ha-ras gene in the nascent liver of B6C3F1, C3H/He and C57BL/6 mice."
    Moulds B.A., Goodman J.I.
    Mutat. Res. 311:1-7(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 59-75, MUTAGENESIS OF GLN-61.
  7. Lubec G., Kang S.U.
    Submitted (APR-2007) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 136-147, IDENTIFICATION BY MASS SPECTROMETRY.
    Strain: C57BL/6.
    Tissue: Brain.
  8. "Alternative splicing of the human proto-oncogene c-H-ras renders a new Ras family protein that trafficks to cytoplasm and nucleus."
    Guil S., de La Iglesia N., Fernandez-Larrea J., Cifuentes D., Ferrer J.C., Guinovart J.J., Bach-Elias M.
    Cancer Res. 63:5178-5187(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 151-189 (ISOFORM 2), ALTERNATIVE SPLICING.
    Strain: NIH/3T3.
  9. "An interaction between p21ras and heat shock protein hsp60, a chaperonin."
    Ikawa S., Weinberg R.A.
    Proc. Natl. Acad. Sci. U.S.A. 89:2012-2016(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HSPD1.
  10. "A novel RalGEF-like protein, RGL3, as a candidate effector for rit and Ras."
    Shao H., Andres D.A.
    J. Biol. Chem. 275:26914-26924(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH RGL3.
  11. Cited for: INTERACTION WITH PIK3CG.

Entry informationi

Entry nameiRASH_MOUSE
AccessioniPrimary (citable) accession number: Q61411
Secondary accession number(s): F7BIB2
, Q6P716, Q80WD2, Q811B9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 27, 2011
Last modified: February 4, 2015
This is version 137 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

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.