Protein: C-Jun-amino-terminal kinase-interacting protein 3 (JIP-3) (JNK-interacting protein 3) (JNK MAP kinase scaffold protein 3) (E9PSK7)
Organism: Rattus norvegicus (Rat)
Function: The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module. May function as a regulator of vesicle transport, through interactions with the JNK-signaling components and motor proteins (By similarity). Promotes neuronal axon elongation in a kinesin- and JNK-dependent manner. Activates cofilin at axon tips via local activation of JNK, thereby regulating filopodial dynamics and enhancing axon elongation. Its binding to kinesin heavy chains (KHC), promotes kinesin-1 motility along microtubules and is essential for axon elongation and regeneration. Regulates cortical neuronal migration by mediating NTRK2/TRKB anterograde axonal transport during brain development. Acts as an adapter that bridges the interaction between NTRK2/TRKB and KLC1 and drives NTRK2/TRKB axonal but not dendritic anterograde transport, which is essential for subsequent BDNF-triggered signaling and filopodia formation.
Subcellular location: Cytoplasm {ECO:0000250|UniProtKB:Q9ESN9}. Golgi apparatus {ECO:0000250|UniProtKB:Q9ESN9}. Cytoplasmic vesicle {ECO:0000250|UniProtKB:Q9ESN9}. Cell projection, growth cone {ECO:0000250|UniProtKB:Q9ESN9}. Cell projection, axon {ECO:0000269|PubMed:21775604, ECO:0000269|PubMed:23576431}. Cell projection, dendrite {ECO:0000269|PubMed:21775604}. Cytoplasm, perinuclear region {ECO:0000269|PubMed:21775604}. Note=Localized in the soma and growth cones of differentiated neurites and the Golgi and vesicles of the early secretory compartment of epithelial cells. KIF5A/B/C-mediated transportation to axon tips is essential for its function in enhancing neuronal axon elongation. {ECO:0000250|UniProtKB:Q9ESN9, ECO:0000269|PubMed:23576431}.
Sequence: MMEIQMDEGGGVVVYQDDYCSGSVMSERVSGLAGSIYREFERLIHCYDEEVVKELMPLVVNVLENLDSVLSENQEHEVELELLREDNEQLLTQYEREKALRKQAEEKFIEFEDALEQEKKELQIQVEHYEFQTRQLELKAKNYADQISRLEERESEMKKEYNALHQRHTEMIQTYVEHIERSKMQQVGGGGQTESSLPGRSRKERPTSLNVFPLADGMVRAQMGGKLVPAGDHWHLSDLGQLQSSSSYQCPNDEMSESGQSSAAATPSTTGTKSNTPTSSVPSAAVTPLNESLQPLGDYGSVTKNNKRAREKRNSRNMEVQVTQEMRNVSIGMGSSDEWSDVQDIIDSTPELDVCPETRLDRTGSSPTQGIVNKAFGINTDSLYHELSTAGSEVIGDVDEGADLLGEFSGMGKEVGNLLLENSQLLETKNALNVVKNDLIAKVDQLSGEQEVLKGELEAAKQAKVKLENRIKELEEELKRVKSEAVTARREPREEVEDDKIPMAQRRRFTRVEMARVLMERNQYKERLMELQEAVRWTEMIRASREHPSVQEKKKSTIWQFFSRLFSSSSSPPPAKRSYPSVNIHYKSPTTAGFSQRRNHALCQISAGSRPLEFFPDDDCTSSARREQKREQYRQVREHVRNDDGRLQACGWSLPAKYKQLSPNGGQEDTRMKNVPVPVYCRPLVEKDPSTKLWCAAGVNLSGWKPNEEDSSNGPKPAPGRDPLTCDREGEGEPKSTHPSPEKKKAKEVPEADATSSRVWILTSTLTTSKVVIIDANQPGTVVDQFTVCNAHVLCISSIPAASDSDYPPGDMFLDSDVNPEDSGADGVLAGITLVGCATRCNVPRSNCSSRGDTPVLDKGQGDVAATANGKVNPSQSTEEATEATEVPDPGPSESEATTVRPGPLTEHVFTDPAPTQSSSTQPASENGSESDGSIVQPQVEPSGESSATTSSAAPTMWLGAQNGWLYVHSAVANWKKCLHSIKLKDSVLSLVHVKGRVLVALADGTLAIFHRGEDGQWDLSNYHLMDLGHPHHSIRCMAVVDDRVWCGYKNKVHVIQPKTMQIEKSFDAHPRRESQVRQLAWIGDGVWVSIRLDSTLRLYHAHTHQHLQDVDIEPYVSKMLGTGKLGFSFVRITALLIAGNRLWVGTGNGVVISIPLTETVVLHRGQLLGLRANKTSPTSGEGTRPGGIIHVYGDDSSDKTASSFIPYCSMAQAQLCFHGHRDAVKFFVSVPGNVLATLNGSVLDSPSEGPGPAAPAADAEGQKLKNALVLSGGEGYIDFRIGDGEDDETEEGTGDVNQTKPSLSKAERSHIIVWQVSYTPE
InterPro domains: - IPR032486: JNK-interacting protein, leucine zipper II (domain) [410-479]
- IPR034744: RH2 domain (domain) [506-580]
- IPR015943: WD40/YVTN repeat-like-containing domain superfamily (homologous_superfamily) [934-1179]
- IPR039911: JNK-interacting protein 3/4 (family) [6-1320]
- IPR034743: RH1 domain (domain) [12-100]
- IPR036322: WD40-repeat-containing domain superfamily (homologous_superfamily) [957-1159]
Interaction partners: - Mitogen-activated protein kinase 10
- Dual specificity mitogen-activated protein kinase kinase 7
- Dual specificity mitogen-activated protein kinase kinase 4
- Kinesin light chain
- Kinesin light chain 4
- Mitogen-activated protein kinase 9
- Mitogen-activated protein kinase 8
- Kinesin light chain 1
- Kinesin light chain 3
- Mitogen-activated protein kinase kinase kinase 1
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0098772 (molecular function regulator activity), GO:0005488 (binding), GO:0030234 (enzyme regulator activity), GO:0005515 (protein binding), GO:0140678 (molecular function inhibitor activity), GO:0019899 (enzyme binding), GO:0004857 (enzyme inhibitor activity), GO:0008092 (cytoskeletal protein binding), GO:0019900 (kinase binding), GO:0019894 (kinesin binding), GO:0019901 (protein kinase binding)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0050789 (regulation of biological process), GO:0048519 (negative regulation of biological process), GO:0050793 (regulation of developmental process), GO:0019222 (regulation of metabolic process), GO:0050794 (regulation of cellular process), GO:0045926 (negative regulation of growth), GO:0051093 (negative regulation of developmental process), GO:0048523 (negative regulation of cellular process), GO:0040008 (regulation of growth), GO:0009892 (negative regulation of metabolic process), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:0045596 (negative regulation of cell differentiation), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0048640 (negative regulation of developmental growth), GO:0001558 (regulation of cell growth), GO:0030308 (negative regulation of cell growth), GO:0022603 (regulation of anatomical structure morphogenesis), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0045595 (regulation of cell differentiation), GO:0060255 (regulation of macromolecule metabolic process), GO:0031323 (regulation of cellular metabolic process), GO:0080090 (regulation of primary metabolic process), GO:0051128 (regulation of cellular component organization), GO:0031324 (negative regulation of cellular metabolic process), GO:0048638 (regulation of developmental growth), GO:0045664 (regulation of neuron differentiation), GO:0022604 (regulation of cell morphogenesis), GO:1903859 (regulation of dendrite extension), GO:0051246 (regulation of protein metabolic process), GO:0051248 (negative regulation of protein metabolic process), GO:0010563 (negative regulation of phosphorus metabolic process), GO:0045665 (negative regulation of neuron differentiation), GO:0051174 (regulation of phosphorus metabolic process), GO:0031399 (regulation of protein modification process), GO:0031400 (negative regulation of protein modification process), GO:0045936 (negative regulation of phosphate metabolic process), GO:0019220 (regulation of phosphate metabolic process), GO:0042325 (regulation of phosphorylation), GO:0001933 (negative regulation of protein phosphorylation), GO:0001932 (regulation of protein phosphorylation), GO:0042326 (negative regulation of phosphorylation)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0005829 (cytosol), GO:0098793 (presynapse), GO:0048471 (perinuclear region of cytoplasm), GO:0030054 (cell junction), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0031090 (organelle membrane), GO:0008021 (synaptic vesicle), GO:0031410 (cytoplasmic vesicle), GO:0043229 (intracellular organelle), GO:0045202 (synapse), GO:0030133 (transport vesicle), GO:0043227 (membrane-bounded organelle), GO:0030658 (transport vesicle membrane), GO:0099503 (secretory vesicle), GO:0043231 (intracellular membrane-bounded organelle), GO:0098588 (bounding membrane of organelle), GO:0012506 (vesicle membrane), GO:0070382 (exocytic vesicle), GO:0030672 (synaptic vesicle membrane), GO:0031982 (vesicle), GO:0030659 (cytoplasmic vesicle membrane), GO:0097708 (intracellular vesicle), GO:0099501 (exocytic vesicle membrane)