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    drk downstream of receptor kinase [ Drosophila melanogaster (fruit fly) ]

    Gene ID: 36497, updated on 17-Dec-2024

    Summary

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    Official Symbol
    drkprovided by FlyBase
    Official Full Name
    downstream of receptor kinaseprovided by FlyBase
    Primary source
    FLYBASE:FBgn0004638
    Locus tag
    Dmel_CG6033
    See related
    AllianceGenome:FB:FBgn0004638
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Drosophila melanogaster
    Lineage
    Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota; Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea; Drosophilidae; Drosophila; Sophophora
    Also known as
    24/1; CG6033; crkl; Dmel\CG6033; Drk; DRK; Drk/Grb2; E(sev)2B; Grb-2; Grb/drk; Grb2; GRB2; Grb2/drk; l(2)10626; l(2)k13809; P1112; Su(sev)R1
    Summary
    Enables phosphotyrosine residue binding activity; signaling receptor binding activity; and signaling receptor complex adaptor activity. Involved in several processes, including cell surface receptor protein tyrosine kinase signaling pathway; learning or memory; and open tracheal system development. Located in plasma membrane and presynapse. Part of protein-containing complex. Is expressed in several structures, including embryonic/larval midgut primordium; imaginal disc; mesoderm; synaptic neuropil domain; and synaptic neuropil subdomain. Used to study autosomal recessive nonsyndromic deafness 114. Human ortholog(s) of this gene implicated in autosomal recessive nonsyndromic deafness 114; breast cancer; prostate adenocarcinoma; and prostate cancer. Orthologous to several human genes including GRB2 (growth factor receptor bound protein 2). [provided by Alliance of Genome Resources, Dec 2024]
    Orthologs
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    Genomic context

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    See drk in Genome Data Viewer
    Location:
    50A13-50A13; 2-68 cM
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    Release 6.54 current Release 6 plus ISO1 MT (GCF_000001215.4) 2R NT_033778.4 (13495222..13502841, complement)
    Release 5.57 previous assembly Release 5 (GCF_000001215.2) 2R NT_033778.3 (9382727..9390346, complement)

    Chromosome 2R - NT_033778.4Genomic Context describing neighboring genes Neighboring gene centromere identifier Neighboring gene bb in a boxcar Neighboring gene mars Neighboring gene Myb-interacting protein 120 Neighboring gene mitochondrial translation elongation factor Tu 1 Neighboring gene Vesicular monoamine transporter Neighboring gene uncharacterized protein

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. Backbone 1H and 15N resonance assignments of the N-terminal SH3 domain of drk in folded and unfolded states using enhanced-sensitivity pulsed field gradient NMR techniques. Zhang O, et al. J Biomol NMR, 1994 Nov. PMID 7812156
    2. Characterization of the backbone dynamics of folded and denatured states of an SH3 domain. Farrow NA, et al. Biochemistry, 1997 Mar 4. PMID 9054544
    3. Improved structural characterizations of the drkN SH3 domain unfolded state suggest a compact ensemble with native-like and non-native structure. Marsh JA, et al. J Mol Biol, 2007 Apr 13. PMID 17320108
    4. Paramagnetic relaxation enhancements in unfolded proteins: theory and application to drkN SH3 domain. Xue Y, et al. Protein Sci, 2009 Jul. PMID 19544584, Free PMC Article
    5. Structural comparison of the unstable drkN SH3 domain and a stable mutant. Bezsonova I, et al. Biochemistry, 2005 Nov 29. PMID 16300404

    See all (260) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Structure and Dynamics of Drk-SH2 Domain and Its Site-Specific Interaction with Sev Receptor Tyrosine Kinase.
      Title: Structure and Dynamics of Drk-SH2 Domain and Its Site-Specific Interaction with Sev Receptor Tyrosine Kinase.
    2. Interactions of the N- and C-Terminal SH3 Domains of Drosophila Drk with the Proline-Rich Peptides from Sos and Dos.
      Title: Interactions of the N- and C-Terminal SH3 Domains of Drosophila Drk with the Proline-Rich Peptides from Sos and Dos.
    3. Disordered proteins mitigate the temperature dependence of site-specific binding free energies.
      Title: Disordered proteins mitigate the temperature dependence of site-specific binding free energies.
    4. identifies DRK/DOS/SOS as the upstream Rac GEF complex required for glial responses to axonal injury, and demonstrates a critical requirement for multiple GEFs in efficient glial activation after injury and internalization/degradation of axonal debris
      Title: DRK/DOS/SOS converge with Crk/Mbc/dCed-12 to activate Rac1 during glial engulfment of axonal debris.
    5. Drk plays a negative role in EGFR signaling by enhancing receptor endocytosis through cooperating with the RING domain of D-Cbl.
      Title: D-Cbl binding to Drk leads to dose-dependent down-regulation of EGFR signaling and increases receptor-ligand endocytosis.
    6. size distribution of molecules within an unfolded state of the N-terminal SH3 domain of drk (drkN SH3) has been studied by small-angle X-ray scattering (SAXS) and pulsed-field-gradient NMR (PFG-NMR) methods
      Title: Distribution of molecular size within an unfolded state ensemble using small-angle X-ray scattering and pulse field gradient NMR techniques.
    7. SH3 domain-mediated binding of the Drk protein to Dos is an important step in signaling of Drosophila receptor tyrosine kinases.
      Title: SH3 domain-mediated binding of the Drk protein to Dos is an important step in signaling of Drosophila receptor tyrosine kinases.
    8. Signalling from the pTyr (YB) Neu (ErbB-2) autophosphorylation site was affected by a haplosufficiency in drk (Grb-2), and in genes thought to function downstream of Grb-2: dab, sos, csw (Shp-2), and dos (Gab-1).
      Title: Genetic identification of effectors downstream of Neu (ErbB-2) autophosphorylation sites in a Drosophila model.
    9. residue-specific pK(a) values for a thermodynamically unstable Src homology 3 domain, enabling the calculation of the pH dependence of stability based on simple analytical expressions
      Title: Site-specific contributions to the pH dependence of protein stability.
    10. Structural characterizations of the drkN SH3 domain unfolded state.
      Title: Improved structural characterizations of the drkN SH3 domain unfolded state suggest a compact ensemble with native-like and non-native structure.
    Submit: New GeneRIF Correction See all GeneRIFs (12)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by FlyBase

    Function Evidence Code Pubs
    enables epidermal growth factor receptor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables epidermal growth factor receptor binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables phosphotyrosine residue binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables phosphotyrosine residue binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables sevenless binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables sevenless binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables signaling receptor complex adaptor activity IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in R7 cell fate commitment IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in Ras protein signal transduction IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    involved_in associative learning IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in epidermal growth factor receptor signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in epidermal growth factor receptor signaling pathway IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    involved_in epithelial cell migration, open tracheal system IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in fibroblast growth factor receptor signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in follicle cell of egg chamber development IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in imaginal disc-derived wing morphogenesis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in insulin receptor signaling pathway IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    involved_in olfactory learning IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of ERK1 and ERK2 cascade IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of TORC1 signaling IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of cell size IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of receptor-mediated endocytosis IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in regulation of MAPK cascade IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in sensory perception of sound IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in sevenless signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in sevenless signaling pathway IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in sevenless signaling pathway IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    involved_in short-term memory IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in torso signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in torso signaling pathway IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in torso signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in tracheal outgrowth, open tracheal system IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in vascular endothelial growth factor receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in vascular endothelial growth factor receptor signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    part_of COP9 signalosome IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasm HDA PubMed 
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleoplasm HDA PubMed 
    is_active_in nucleoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in presynapse IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of protein-containing complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    downstream of receptor kinase
    Names
    CG6033-PA
    CG6033-PB
    CG6033-PC
    CG6033-PD
    CG6033-PF
    downstream of receptor kinases
    downstream receptor kinase
    drk-PA
    drk-PB
    drk-PC
    drk-PD
    drk-PF
    enhancer of sevenless-2B

    NCBI Reference Sequences (RefSeq)

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    Genome Annotation

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference assembly

    Genomic

    1. NT_033778.4 Reference assembly

      Range
      13495222..13502841 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_165998.2 → NP_725306.1  downstream of receptor kinase, isoform F [Drosophila melanogaster]

      See identical proteins and their annotated locations for NP_725306.1

      Status: REVIEWED

      UniProtKB/Swiss-Prot
      A4UZF9, Q08012, Q0E989, Q9V6Q5
      Related
      FBpp0086816
      Conserved Domains (3) summary
      cd09941
      Location:56 → 149
      SH2_Grb2_like; Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar proteins
      cd11804
      Location:2 → 53
      SH3_GRB2_like_N; N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins
      cd11805
      Location:156 → 208
      SH3_GRB2_like_C; C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins

    2. NM_057510.4 → NP_476858.1  downstream of receptor kinase, isoform A [Drosophila melanogaster]

      See identical proteins and their annotated locations for NP_476858.1

      Status: REVIEWED

      UniProtKB/Swiss-Prot
      A4UZF9, Q08012, Q0E989, Q9V6Q5
      Related
      FBpp0086815
      Conserved Domains (3) summary
      cd09941
      Location:56 → 149
      SH2_Grb2_like; Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar proteins
      cd11804
      Location:2 → 53
      SH3_GRB2_like_N; N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins
      cd11805
      Location:156 → 208
      SH3_GRB2_like_C; C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins

    3. NM_165996.2 → NP_725304.1  downstream of receptor kinase, isoform D [Drosophila melanogaster]

      See identical proteins and their annotated locations for NP_725304.1

      Status: REVIEWED

      UniProtKB/Swiss-Prot
      A4UZF9, Q08012, Q0E989, Q9V6Q5
      Related
      FBpp0086817
      Conserved Domains (3) summary
      cd09941
      Location:56 → 149
      SH2_Grb2_like; Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar proteins
      cd11804
      Location:2 → 53
      SH3_GRB2_like_N; N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins
      cd11805
      Location:156 → 208
      SH3_GRB2_like_C; C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins

    4. NM_165994.2 → NP_725302.1  downstream of receptor kinase, isoform B [Drosophila melanogaster]

      See identical proteins and their annotated locations for NP_725302.1

      Status: REVIEWED

      UniProtKB/Swiss-Prot
      A4UZF9, Q08012, Q0E989, Q9V6Q5
      Related
      FBpp0086814
      Conserved Domains (3) summary
      cd09941
      Location:56 → 149
      SH2_Grb2_like; Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar proteins
      cd11804
      Location:2 → 53
      SH3_GRB2_like_N; N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins
      cd11805
      Location:156 → 208
      SH3_GRB2_like_C; C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins

    5. NM_165995.2 → NP_725303.1  downstream of receptor kinase, isoform C [Drosophila melanogaster]

      See identical proteins and their annotated locations for NP_725303.1

      Status: REVIEWED

      UniProtKB/Swiss-Prot
      A4UZF9, Q08012, Q0E989, Q9V6Q5
      Related
      FBpp0086813
      Conserved Domains (3) summary
      cd09941
      Location:56 → 149
      SH2_Grb2_like; Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar proteins
      cd11804
      Location:2 → 53
      SH3_GRB2_like_N; N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins
      cd11805
      Location:156 → 208
      SH3_GRB2_like_C; C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q08012.1 Q08012

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