CLIP-associating protein 2; cytoplasmic linker-associated protein 2; protein Orbit homolog 2; hOrbit2 (CLASP2 KIAA0627)

Function

• regulation of microtubule dynamics (density, length distribution & stability of interphase microtubles
• microtubule plus-end tracking protein
  • microtubule binding may be influenced by PIK3CA & GSK3B phosphorylation
• promotes stabilization of dynamic microtubules
• role in nucleation of noncentrosomal microtubules originating from the trans-Golgi network
• role in generating polarized microtubule networks in migrating cells towards the leading edge of the cell
• mediates interactions between microtubule plus ends & cell cortex via interactions with ERC1 & PHLDB2
  • these interactions regulated, at least in part, by phosphatidylinositol 3-kinase signaling
• similar stabilizing function at the kinetochore during bipolar alignment of chromosomes on the mitotic spindle
• mediator of ERBB2-dependent stabilization of microtubules at the cell cortex
• phosphorylated by GSK3B
  • phosphorylation by GSK3B may negatively regulate binding to microtubule lattices in lamella
• phosphorylated upon DNA damage, probably by ATM or ATR
• interacts with CLIP2, ERC1, MAPRE3, microtubules, PHLDB2 & RSN
  • interaction with ERC1 may be mediated by PHLDB2
• interacts with MAPRE1
  • probably required for targeting to the growing microtubule plus ends
• interacts with GCC2
  • recruits CLASP2 to Golgi membranes
• interacts with MACF1 (putative)

Structure

• the microtubule tip localization signal (MtLS) motif mediates interaction with MAPRE1 & targeting to the growing microtubule plus ends
• belongs to the CLASP family
• contains 5 HEAT repeats

Compartment

• cytoplasm, cytoskeleton, centrosome
• chromosome, centromere, kinetochore, spindle
• Golgi, trans-Golgi network
• cell membrane. cell projection, ruffle membrane
• localizes to microtubule plus ends
• localizes to centrosomes, kinetochores & the mitotic spindle from prometaphase
• subsequently localizes to the spindle midzone from anaphase & to the midbody from telophase
• in migrating cells, localizes to the plus ends of microtubules within the cell body & to the entire microtubule lattice within the lamella
• localizes to the cell cortex
  • this requires ERC1 & PHLDB2
• the MEMO1-RHOA-DIAPH1 signaling pathway controls localization of the phosophorylated form to the cell membrane

Alternative splicing

• named isoforms=2
• additional isoforms exist

Expression

brain-specific

More general terms

• cytoskeletal protein
• HEAT repeat-containing protein (HEATR)
• phosphoprotein

Additional terms

• corticotropin-like intermediary peptide (CLIP)

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=23122
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:23122
• OMIM: https://mirror.omim.org/entry/605853
• UniProt: http://www.uniprot.org/uniprot/O75122.html