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Protein

GTPase HRas

Gene

Hras

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

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

GO - Biological processi

Keywordsi

LigandGTP-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 upon Ca2+ influx 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:96224 Hras

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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_00003264781 – 186GTPase HRasAdd BLAST186
Initiator methionineiRemoved; alternateBy similarity
ChainiPRO_00000429982 – 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, 17 interactors
ComplexPortaliCPX-413 GTPase Hras - Son of sevenless homolog 1 complex
DIPiDIP-29361N
IntActiQ61411, 11 interactors
MINTiQ61411
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

InterProiView protein in InterPro
IPR027417 P-loop_NTPase
IPR005225 Small_GTP-bd_dom
IPR001806 Small_GTPase
IPR020849 Small_GTPase_Ras-type
PANTHERiPTHR24070 PTHR24070, 1 hit
PfamiView protein in Pfam
PF00071 Ras, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
TIGRFAMsiTIGR00231 small_GTP, 1 hit
PROSITEiView protein in PROSITE
PS51421 RAS, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiRASH_MOUSE
AccessioniPrimary (citable) accession number: Q61411
Secondary accession number(s): F7BIB2
, Q6P716, Q80WD2, Q811B9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 27, 2011
Last modified: June 20, 2018
This is version 171 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

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