Protein: CLIP-associating protein 2 (Cytoplasmic linker-associated protein 2) (Protein Orbit homolog 2) (hOrbit2) (O75122)
Organism: Homo sapiens (Human)
Function: Microtubule plus-end tracking protein that promotes the stabilization of dynamic microtubules. Involved in the nucleation of noncentrosomal microtubules originating from the trans-Golgi network (TGN). Required for the polarization of the cytoplasmic microtubule arrays in migrating cells towards the leading edge of the cell. May act at the cell cortex to enhance the frequency of rescue of depolymerizing microtubules by attaching their plus-ends to cortical platforms composed of ERC1 and PHLDB2. This cortical microtubule stabilizing activity is regulated at least in part by phosphatidylinositol 3-kinase signaling. Also performs a similar stabilizing function at the kinetochore which is essential for the bipolar alignment of chromosomes on the mitotic spindle. Acts as a mediator of ERBB2-dependent stabilization of microtubules at the cell cortex.
Subcellular location: Cytoplasm, cytoskeleton {ECO:0000269|PubMed:15631994, ECO:0000269|PubMed:20937854}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:16914514}. Chromosome, centromere, kinetochore {ECO:0000269|PubMed:16866869, ECO:0000269|PubMed:16914514}. Cytoplasm, cytoskeleton, spindle {ECO:0000269|PubMed:16866869, ECO:0000269|PubMed:16914514}. Golgi apparatus {ECO:0000250|UniProtKB:Q8BRT1}. Golgi apparatus, trans-Golgi network {ECO:0000269|PubMed:17543864}. Cell membrane {ECO:0000269|PubMed:20937854}. Cell projection, ruffle membrane {ECO:0000269|PubMed:20937854}. Cytoplasm, cell cortex {ECO:0000269|PubMed:27410476}. Note=Localizes to microtubule plus ends (PubMed:15631994). Localizes to centrosomes, kinetochores and the mitotic spindle from prometaphase. Subsequently localizes to the spindle midzone from anaphase and to the midbody from telophase (PubMed:16866869, PubMed:16914514). In migrating cells localizes to the plus ends of microtubules within the cell body and to the entire microtubule lattice within the lamella. Localizes to the cell cortex and this requires ERC1 and PHLDB2 (PubMed:16824950). Colocalizes with KANK1 at the cell cortex, likely recruited in cortical microtubule stabilization complexes (CMSC) at focal adhesions rims (PubMed:27410476). The MEMO1-RHOA-DIAPH1 signaling pathway controls localization of the phosphorylated form to the cell membrane. {ECO:0000269|PubMed:15631994, ECO:0000269|PubMed:16824950, ECO:0000269|PubMed:16866869, ECO:0000269|PubMed:16914514, ECO:0000269|PubMed:20937854, ECO:0000269|PubMed:27410476}.
Interaction partners:
- CAP-Gly domain-containing linker protein 1
- CAP-Gly domain-containing linker protein 2
- CLK4-associating serine/arginine rich protein
- Microtubule-associated protein RP/EB family member 1
- Nuclear migration protein nudC
- Pleckstrin homology-like domain family B member 2
- Serine/threonine-protein kinase PLK1
- Cell division cycle protein 20 homolog
- GRIP and coiled-coil domain-containing protein 2
- Serine/threonine-protein kinase MARK2
Sequence:
MAMGDDKSFDDEESVDGNRPSSAASAFKVPAPKTSGNPANSARKPGSAGGPKVGGASKEGGAGAVDEDDFIKAFTDVPSIQIYSSRELEETLNKIREILSDDKHDWDQRANALKKIRSLLVAGAAQYDCFFQHLRLLDGALKLSAKDLRSQVVREACITVAHLSTVLGNKFDHGAEAIVPTLFNLVPNSAKVMATSGCAAIRFIIRHTHVPRLIPLITSNCTSKSVPVRRRSFEFLDLLLQEWQTHSLERHAAVLVETIKKGIHDADAEARVEARKTYMGLRNHFPGEAETLYNSLEPSYQKSLQTYLKSSGSVASLPQSDRSSSSSQESLNRPFSSKWSTANPSTVAGRVSAGSSKASSLPGSLQRSRSDIDVNAAAGAKAHHAAGQSVRSGRLGAGALNAGSYASLEDTSDKLDGTASEDGRVRAKLSAPLAGMGNAKADSRGRSRTKMVSQSQPGSRSGSPGRVLTTTALSTVSSGVQRVLVNSASAQKRSKIPRSQGCSREASPSRLSVARSSRIPRPSVSQGCSREASRESSRDTSPVRSFQPLASRHHSRSTGALYAPEVYGASGPGYGISQSSRLSSSVSAMRVLNTGSDVEEAVADALKKPARRRYESYGMHSDDDANSDASSACSERSYSSRNGSIPTYMRQTEDVAEVLNRCASSNWSERKEGLLGLQNLLKNQRTLSRVELKRLCEIFTRMFADPHGKRVFSMFLETLVDFIQVHKDDLQDWLFVLLTQLLKKMGADLLGSVQAKVQKALDVTRESFPNDLQFNILMRFTVDQTQTPSLKVKVAILKYIETLAKQMDPGDFINSSETRLAVSRVITWTTEPKSSDVRKAAQSVLISLFELNTPEFTMLLGALPKTFQDGATKLLHNHLRNTGNGTQSSMGSPLTRPTPRSPANWSSPLTSPTNTSQNTLSPSAFDYDTENMNSEDIYSSLRGVTEAIQNFSFRSQEDMNEPLKRDSKKDDGDSMCGGPGMSDPRAGGDATDSSQTALDNKASLLHSMPTHSSPRSRDYNPYNYSDSISPFNKSALKEAMFDDDADQFPDDLSLDHSDLVAELLKELSNHNERVEERKIALYELMKLTQEESFSVWDEHFKTILLLLLETLGDKEPTIRALALKVLREILRHQPARFKNYAELTVMKTLEAHKDPHKEVVRSAEEAASVLATSISPEQCIKVLCPIIQTADYPINLAAIKMQTKVIERVSKETLNLLLPEIMPGLIQGYDNSESSVRKACVFCLVAVHAVIGDELKPHLSQLTGSKMKLLNLYIKRAQTGSGGADPTTDVSGQS