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

General

cytoskeletal protein HEAT repeat-containing protein (HEATR) phosphoprotein

Properties

SIZE: entity length = 1294 aa MW = 141 kD COMPARTMENT: cytoplasm golgi MOTIF: Ser phosphorylation site {S8} HEAT repeat {173-208} HEAT repeat {209-245} serine-rich region {310-587} MOTIF: serine residue (SEVERAL) Ser phosphorylation site {S326} Ser phosphorylation site {S327} Ser phosphorylation site {S330} Ser phosphorylation site {S368} Ser phosphorylation site {S370} MAPRE1/MAPRE3 interaction {444-580} Microtubule localization {494-497} Ser phosphorylation site {S507} Microtubule localization {517-520} Ser phosphorylation site {S523} Ser phosphorylation site {S525} Ser phosphorylation site {S529} Ser phosphorylation site {S583} Ser phosphorylation site {S596} HEAT repeat {772-809} RSN interaction {872-1294} MOTIF: Ser phosphorylation site {S994} cortical localization {1017-1294} Ser phosphorylation site {S1029} Ser phosphorylation site {S1053} coiled coil {1055-1084} Ser phosphorylation site {S1057} HEAT repeat {1098-1135} HEAT repeat {1216-1253}

Database Correlations

OMIM 605853 UniProt O75122 Pfam PF12348 Entrez Gene 23122 Kegg hsa:23122

References

UniProt :accession Q7Z460