A kinesin like protein involved in Hh signaling that binds to microtubules and tethers Ci in the cytoplasm.

• required for transducing high levels of Hh signalling activity (Wang, 2000, Wang, 2000)

• Repressor of Hh signaling
• cos2^w1 (null) clones have increased Ci levels
• cos2³ mutation partially suppresses fu vein phenotype just like Su(fu)^LP (Preat, 1993)
• fu[I]; cos2⁷ flies look like cos2⁷ flies (Preat, 1993)
• fu[II]; cos2³ die as late pupae and have extreme adult cos2 phenotype (Preat, 1993)

• Ci signaling complex
  • complex is made irrespective of Fu and Cos-2phosphorylation (Robbins, 1997)
  • Complex probably contains Su(fu) ([Monnier, 1998)
• Cos2-Fu
  • Cos-2 co-IP with both Fu and Ci in embryo extracts (Robbins, 1997, Sisson, 1997)
  • Cos-2-Fu-Ci complex associates w/ microtubules in absence of Hh signalling (Robbins, 1997, Sisson, 1997)
  • The C-term domain (aa 421-805) of Fu is necessary and sufficient to bind Cos2 (Ascano, 2002)
  • There appears to be a separate Cos2-Fu species in gel filtration experiments (Ascano, 2002)
• Cos2-Ci
  • forms a complex with Ci via a domain in its C terminus termed the CORD (Wang, 2000),
• Cos-2 binds microtubules in an Hh-sensitive manner (Robbins, 1997)
• IPs from ovarian extracts show that Sxl is in a complex with Fu and Cos2, along with b- and g-tubulin(Vied, 2001)

• Cos2 mRNA levels are uniform throughout discs, however protein levels are higher in the anterior compartment (Sisson, 1997)
  • Perhaps Ci stabilizes Cos2 in a macromolecular complex in anterior cells or Ci heightens translation of COS2 mRNA (Sisson, 1997)

• The N-terminal (residues 1-450) and C-terminal (residues 1050-1201) regions are predicted to form globular structures consisting of alternating alpha helices and beta sheets. The central region (residues 643-990) contains 36 heptad repeats that are predicted to mediate the formation of a stable homodimer through a parallel coiled coil (Sisson, 1997) refs contains additional structural info
• N-term domain similar to motor domains of kinesin superfamily proteins, but unlikely has motor activity

• Cytoplasmic
• Higher protein levels in the A compartment in imaginal discs although there is no difference in mRNA expression (Sisson, 1997)
• Tagged versions of Fu and Cos2 (UAS constructs) can enter the nucleus, but the rate of entry does not change with Hh signaling (Methot, 2000)

• becomes hyperphosphorylated (on serines) in response to Hh activity
• Fused is apparently not directly responsible for the phosphorylation of Cos2, which occurs even when inactivating mutations are present in the kinase domain of Fused (Robbins, 1997)
• Fu phosphorylates Cos2 on S572 and to a lesser extent S931 in a Hh dependent fashion (baculovirus system) (Nybakken, 2002)
• Phosphorylation is delayed by 15-30 minutes, similar to Fu (Robbins, 1997)
  • response delayed relative to the release of the complex from microtubules

• N-term domain of Cos2 is similar to motor domains of kinesin superfamily proteins, but unlikely has motor activity

• Cos2 mutant clones cross the A/P boundary (Wang, 2000)
• In a cos2 Su(fu) double mutant en is ectopically expressed (Wang, 2000)
• Cos2 somatic clones in the anterior compartment of wing discs express high levels of cytoplasmic Ci staining and cause mirror-image duplications of the wing (Sisson, 1997).

• monoclonal antibody: (Ascano, 2002)