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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)DescriptionActionsGraphical viewLength
Nucleotide bindingi10 – 17GTPBy similarity8
Nucleotide bindingi57 – 61GTPBy similarity5
Nucleotide bindingi116 – 119GTPBy similarity4

GO - Molecular functioni

  • GTPase activity Source: MGI
  • GTP binding Source: MGI
  • protein C-terminus binding Source: MGI

GO - Biological processi

Complete GO annotation...

Keywords - Ligandi

GTP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-1169092. Activation of RAS in B cells.
R-MMU-1250347. SHC1 events in ERBB4 signaling.
R-MMU-1433557. Signaling by SCF-KIT.
R-MMU-171007. p38MAPK events.
R-MMU-179812. GRB2 events in EGFR signaling.
R-MMU-180336. SHC1 events in EGFR signaling.
R-MMU-186763. Downstream signal transduction.
R-MMU-1963640. GRB2 events in ERBB2 signaling.
R-MMU-210993. Tie2 Signaling.
R-MMU-2179392. EGFR Transactivation by Gastrin.
R-MMU-2424491. DAP12 signaling.
R-MMU-2871796. FCERI mediated MAPK activation.
R-MMU-375165. NCAM signaling for neurite out-growth.
R-MMU-3928662. EPHB-mediated forward signaling.
R-MMU-442982. Ras activation uopn Ca2+ infux through NMDA receptor.
R-MMU-5218921. VEGFR2 mediated cell proliferation.
R-MMU-5621575. CD209 (DC-SIGN) signaling.
R-MMU-5654688. SHC-mediated cascade:FGFR1.
R-MMU-5654693. FRS-mediated FGFR1 signaling.
R-MMU-5654699. SHC-mediated cascade:FGFR2.
R-MMU-5654700. FRS-mediated FGFR2 signaling.
R-MMU-5654704. SHC-mediated cascade:FGFR3.
R-MMU-5654706. FRS-mediated FGFR3 signaling.
R-MMU-5654712. FRS-mediated FGFR4 signaling.
R-MMU-5654719. SHC-mediated cascade:FGFR4.
R-MMU-5658442. Regulation of RAS by GAPs.
R-MMU-5673000. RAF activation.
R-MMU-5673001. RAF/MAP kinase cascade.
R-MMU-5674135. MAP2K and MAPK activation.
R-MMU-5675221. Negative regulation of MAPK pathway.
R-MMU-8849471. PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases.
R-MMU-8851805. MET activates RAS signaling.

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
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:96224. Hras.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi61Q → R: Found in chemically induced liver tumors. 1 Publication1

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000429981 – 186GTPase HRasAdd BLAST186
Initiator methionineiRemoved; alternateBy similarity
ChainiPRO_00003264782 – 186GTPase HRas, N-terminally processedAdd BLAST185
PropeptideiPRO_0000042999187 – 189Removed in mature formBy similarity3

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei2N-acetylthreonine; in GTPase HRas, N-terminally processedBy similarity1
Modified residuei118S-nitrosocysteineBy similarity1
Lipidationi181S-palmitoyl cysteineBy similarity1
Lipidationi184S-(15-deoxy-Delta12,14-prostaglandin J2-9-yl)cysteine; alternateBy similarity1
Lipidationi184S-palmitoyl cysteine; alternateBy similarity1
Modified residuei186Cysteine methyl esterBy similarity1
Lipidationi186S-farnesyl cysteineBy similarity1

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.By similarity
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

EPDiQ61411.
PaxDbiQ61411.
PeptideAtlasiQ61411.
PRIDEiQ61411.

PTM databases

iPTMnetiQ61411.
PhosphoSitePlusiQ61411.
SwissPalmiQ61411.

Expressioni

Gene expression databases

BgeeiENSMUSG00000025499.
CleanExiMM_HRAS1.
ExpressionAtlasiQ61411. baseline and differential.
GenevisibleiQ61411. MM.

Interactioni

Subunit structurei

Forms a signaling complex with RASGRP1 and DGKZ (By similarity). In its GTP-bound form interacts with PLCE1 (By similarity). Interacts with TBC1D10C and RASSF5 (By similarity). Interacts with PDE6D (By similarity). Interacts with IKZF3 (By similarity). Found in a complex with at least BRAF, HRAS, MAP2K1, MAPK3 and RGS14 (By similarity). Interacts (active GTP-bound form) with RGS14 (via RBD 1 domain) (By similarity). Interacts with RACK1 (By similarity). Interacts with RAPGEF2 (By similarity). Interacts with RGL3 (PubMed:10869344). Interacts with HSPD1 (PubMed:1347942). 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 (PubMed:19906996). Interacts (in GTP-bound form) with Oog1 (PubMed:16580637).By similarity4 Publications

Binary interactionsi

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi200416. 15 interactors.
DIPiDIP-29361N.
IntActiQ61411. 9 interactors.
MINTiMINT-1215825.
STRINGi10090.ENSMUSP00000026572.

Structurei

3D structure databases

ProteinModelPortaliQ61411.
SMRiQ61411.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni166 – 185Hypervariable regionAdd BLAST20

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi32 – 40Effector region9

Sequence similaritiesi

Belongs to the small GTPase superfamily. Ras family.Curated

Phylogenomic databases

eggNOGiKOG0395. Eukaryota.
COG1100. LUCA.
GeneTreeiENSGT00860000133672.
HOGENOMiHOG000233973.
HOVERGENiHBG009351.
InParanoidiQ61411.
KOiK02833.
OMAiDCMNCKC.
OrthoDBiEOG091G0UAU.
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]
PfamiPF00071. 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. AlignAdd to basket

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 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti55I → Y in CAA90306 (PubMed:8922043).Curated1
Isoform 2 (identifier: Q61411-2)
Sequence conflicti163D → G in CAD24593 (PubMed:14500341).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_041598152 – 189VEDAF…KCVLS → SRSGSSSGTLWDPPSPGTHV TQRPSSWRGGCLLYTSP in isoform 2. 1 PublicationAdd BLAST38

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]
XP_006536222.2. XM_006536159.2. [Q61411-1]
UniGeneiMm.334313.

Genome annotation databases

EnsembliENSMUST00000026572; ENSMUSP00000026572; ENSMUSG00000025499. [Q61411-1]
ENSMUST00000097957; ENSMUSP00000095570; ENSMUSG00000025499. [Q61411-1]
ENSMUST00000124314; ENSMUSP00000147731; ENSMUSG00000025499. [Q61411-2]
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]
XP_006536222.2. XM_006536159.2. [Q61411-1]
UniGeneiMm.334313.

3D structure databases

ProteinModelPortaliQ61411.
SMRiQ61411.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200416. 15 interactors.
DIPiDIP-29361N.
IntActiQ61411. 9 interactors.
MINTiMINT-1215825.
STRINGi10090.ENSMUSP00000026572.

PTM databases

iPTMnetiQ61411.
PhosphoSitePlusiQ61411.
SwissPalmiQ61411.

Proteomic databases

EPDiQ61411.
PaxDbiQ61411.
PeptideAtlasiQ61411.
PRIDEiQ61411.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000026572; ENSMUSP00000026572; ENSMUSG00000025499. [Q61411-1]
ENSMUST00000097957; ENSMUSP00000095570; ENSMUSG00000025499. [Q61411-1]
ENSMUST00000124314; ENSMUSP00000147731; ENSMUSG00000025499. [Q61411-2]
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

eggNOGiKOG0395. Eukaryota.
COG1100. LUCA.
GeneTreeiENSGT00860000133672.
HOGENOMiHOG000233973.
HOVERGENiHBG009351.
InParanoidiQ61411.
KOiK02833.
OMAiDCMNCKC.
OrthoDBiEOG091G0UAU.
TreeFamiTF312796.

Enzyme and pathway databases

ReactomeiR-MMU-1169092. Activation of RAS in B cells.
R-MMU-1250347. SHC1 events in ERBB4 signaling.
R-MMU-1433557. Signaling by SCF-KIT.
R-MMU-171007. p38MAPK events.
R-MMU-179812. GRB2 events in EGFR signaling.
R-MMU-180336. SHC1 events in EGFR signaling.
R-MMU-186763. Downstream signal transduction.
R-MMU-1963640. GRB2 events in ERBB2 signaling.
R-MMU-210993. Tie2 Signaling.
R-MMU-2179392. EGFR Transactivation by Gastrin.
R-MMU-2424491. DAP12 signaling.
R-MMU-2871796. FCERI mediated MAPK activation.
R-MMU-375165. NCAM signaling for neurite out-growth.
R-MMU-3928662. EPHB-mediated forward signaling.
R-MMU-442982. Ras activation uopn Ca2+ infux through NMDA receptor.
R-MMU-5218921. VEGFR2 mediated cell proliferation.
R-MMU-5621575. CD209 (DC-SIGN) signaling.
R-MMU-5654688. SHC-mediated cascade:FGFR1.
R-MMU-5654693. FRS-mediated FGFR1 signaling.
R-MMU-5654699. SHC-mediated cascade:FGFR2.
R-MMU-5654700. FRS-mediated FGFR2 signaling.
R-MMU-5654704. SHC-mediated cascade:FGFR3.
R-MMU-5654706. FRS-mediated FGFR3 signaling.
R-MMU-5654712. FRS-mediated FGFR4 signaling.
R-MMU-5654719. SHC-mediated cascade:FGFR4.
R-MMU-5658442. Regulation of RAS by GAPs.
R-MMU-5673000. RAF activation.
R-MMU-5673001. RAF/MAP kinase cascade.
R-MMU-5674135. MAP2K and MAPK activation.
R-MMU-5675221. Negative regulation of MAPK pathway.
R-MMU-8849471. PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases.
R-MMU-8851805. MET activates RAS signaling.

Miscellaneous databases

PROiQ61411.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000025499.
CleanExiMM_HRAS1.
ExpressionAtlasiQ61411. baseline and differential.
GenevisibleiQ61411. MM.

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]
PfamiPF00071. Ras. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiPS51421. RAS. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: November 30, 2016
This is version 158 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

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 one 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.