module: dmel_wave_regulatory_complex
title: WAVE regulatory complex (SCAR complex) in Drosophila melanogaster
label: WAVE regulatory complex
module_type: PROTEIN_COMPLEX
description: >-
  The WAVE regulatory complex (WRC) is a five-subunit complex that holds the Arp2/3
  activator SCAR (WAVE) in an inactive state until it is recruited and activated at
  the plasma membrane, mainly by the small GTPase Rac. It is built from two
  subcomplexes: a Cyfip (Sra1)-Hem (Nap1) dimer and a trimer of SCAR, Abi and
  HSPC300. Once activated, the C-terminal VCA region of SCAR binds actin and the
  Arp2/3 complex and stimulates branched actin nucleation. In Drosophila the WRC is
  needed for lamellipodia formation, axon growth, myoblast fusion and egg chamber
  development, and loss of one subunit destabilizes the others.
summary: >-
  Five-subunit complex (Cyfip, Hem, SCAR, Abi, HSPC300) that keeps SCAR/WAVE
  inactive until Rac-dependent activation of Arp2/3 nucleation.
concepts:
  - {id: GO:0031209, label: SCAR complex}
parts:
  - id: cyfip_hem_dimer
    label: Cyfip-Hem dimer
    role: Rac-binding regulatory subcomplex
    description: >-
      Cyfip (Sra1 homolog) and Hem (Nap1/Kette homolog) form the large regulatory
      dimer; Cyfip contains the binding site for active Rac and helps hold the SCAR
      VCA region in the inactive state.
    genes: [Cyfip, Hem]
    complex_label: Cyfip-Hem dimer
  - id: scar_abi_hspc300_trimer
    label: SCAR-Abi-HSPC300 trimer
    role: Arp2/3-activating subcomplex
    description: >-
      SCAR carries the VCA region that activates the Arp2/3 complex; Abi and the
      small protein HSPC300 bind the SCAR N-terminus.
    genes: [SCAR, Abi, HSPC300]
    complex_label: SCAR-Abi-HSPC300 trimer
    processes:
      - {id: GO:2000601, label: positive regulation of Arp2/3 complex-mediated actin nucleation}
connections:
  - source: cyfip_hem_dimer
    target: scar_abi_hspc300_trimer
    connection_type: NEGATIVELY_REGULATES
    description: >-
      In the assembled complex the Cyfip-Hem dimer sequesters the SCAR VCA region;
      Rac binding to Cyfip relieves this inhibition.
notes: >-
  The Arp2/3 complex acted on by the WRC is a separate module
  (dmel_arp2_3_complex). Rac GTPases and membrane recruitment factors are
  regulators and are not parts.
group: WRC
function_note: >-
  No molecular function is assigned: the WAVE regulatory complex activates the
  Arp2/3 complex through the VCA domain of SCAR, but the fly subunits carry
  only binding and adaptor terms in GOA.