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Q61411

- RASH_MOUSE

UniProt

Q61411 - RASH_MOUSE

Protein

GTPase HRas

Gene

Hras

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. 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 binding Source: IntAct

    GO - Biological processi

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

    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_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

    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

    ArrayExpressiQ61411.
    BgeeiQ61411.
    CleanExiMM_HRAS1.
    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.
    GeneTreeiENSGT00750000117221.
    HOGENOMiHOG000233973.
    HOVERGENiHBG009351.
    KOiK02833.
    OMAiEKSGCCV.
    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

    MTEYKLVVVG AGGVGKSALT IQLIQNHFVD EYDPTIEDSY RKQVVIDGET    50
    CLLDILDTAG QEEYSAMRDQ YMRTGEGFLC VFAINNTKSF EDIHQYREQI 100
    KRVKDSDDVP MVLVGNKCDL AARTVESRQA QDLARSYGIP YIETSAKTRQ 150
    GVEDAFYTLV REIRQHKLRK LNPPDESGPG CMSCKCVLS 189
    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.

    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS22003.1. [Q61411-1 ]
    CCDS52439.1. [Q61411-2 ]
    PIRi S57718.
    RefSeqi NP_001123915.1. NM_001130443.1. [Q61411-1 ]
    NP_001123916.1. NM_001130444.1. [Q61411-2 ]
    NP_032310.2. NM_008284.2. [Q61411-1 ]
    UniGenei Mm.334313.

    3D structure databases

    ProteinModelPortali Q61411.
    SMRi Q61411. Positions 1-166.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 200416. 15 interactions.
    DIPi DIP-29361N.
    IntActi Q61411. 9 interactions.
    MINTi MINT-1215825.

    Chemistry

    BindingDBi Q61411.

    PTM databases

    PhosphoSitei Q61411.

    Proteomic databases

    MaxQBi Q61411.
    PaxDbi Q61411.
    PRIDEi Q61411.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000026572 ; ENSMUSP00000026572 ; ENSMUSG00000025499 . [Q61411-1 ]
    ENSMUST00000097957 ; ENSMUSP00000095570 ; ENSMUSG00000025499 . [Q61411-1 ]
    ENSMUST00000168550 ; ENSMUSP00000132110 ; ENSMUSG00000025499 . [Q61411-2 ]
    GeneIDi 15461.
    KEGGi mmu:15461.
    UCSCi uc009kju.2. mouse. [Q61411-1 ]
    uc009kjv.2. mouse. [Q61411-2 ]

    Organism-specific databases

    CTDi 3265.
    MGIi MGI:96224. Hras.

    Phylogenomic databases

    eggNOGi COG1100.
    GeneTreei ENSGT00750000117221.
    HOGENOMi HOG000233973.
    HOVERGENi HBG009351.
    KOi K02833.
    OMAi EKSGCCV.
    OrthoDBi EOG7QVM41.
    TreeFami TF312796.

    Enzyme and pathway databases

    Reactomei REACT_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_94437. SHC-mediated cascade.

    Miscellaneous databases

    ChiTaRSi HRAS. mouse.
    NextBioi 288278.
    PROi Q61411.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q61411.
    Bgeei Q61411.
    CleanExi MM_HRAS1.
    Genevestigatori Q61411.

    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

    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: October 1, 2014
    This is version 133 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