module: dmel_vcb_ubiquitin_ligase
title: VHL-Elongin B/C-Cul2 ubiquitin ligase in Drosophila melanogaster
label: VCB-Cul2 ubiquitin ligase
module_type: PROTEIN_COMPLEX
description: >-
  The VCB complex consists of the von Hippel-Lindau tumour suppressor protein
  (Vhl) bound to the adaptor heterodimer Elongin B and Elongin C. Together with
  Cul2 and the RING protein Roc1a it forms a cullin-RING E3 ubiquitin ligase
  in which Vhl is the substrate receptor. Its best-known substrates are
  hypoxia-inducible factor alpha subunits (Sima in Drosophila) after prolyl
  hydroxylation in normoxia, so the ligase couples oxygen availability to
  HIF-alpha degradation.
summary: >-
  Cul2-Roc1a cullin-RING ligase with the EloB-EloC adaptor and the
  substrate receptor Vhl.
concepts:
  - {id: GO:0030891, label: VCB complex}
  - {id: GO:0031462, label: Cul2-RING ubiquitin ligase complex}
parts:
  - id: cul2_roc1a_core
    label: Cul2-Roc1a catalytic core
    role: cullin-RING catalytic core
    genes: [Cul2, Roc1a]
    function: {id: GO:0061630, label: ubiquitin protein ligase activity}
  - id: elongin_bc
    label: Elongin B-Elongin C adaptor
    role: BC-box adaptor
    genes: [EloB, EloC]
  - id: vhl_receptor
    label: Vhl substrate receptor
    role: substrate receptor
    genes: [Vhl]
connections:
  - {source: vhl_receptor, target: cul2_roc1a_core, connection_type: PROVIDES_INPUT_FOR, description: Vhl delivers hydroxylated substrates to the catalytic core via Elongin B/C.}
notes: >-
  Strictly the VCB complex is Vhl-EloB-EloC; FlyBase includes Cul2 and Roc1a,
  so the module is the full CRL2-Vhl ligase. EloB and EloC are also subunits
  of the Elongin transcription elongation complex and of other Cul2/Cul5
  ligases.