ID:JIP1_HUMAN DESCRIPTION: RecName: Full=C-Jun-amino-terminal kinase-interacting protein 1; Short=JIP-1; Short=JNK-interacting protein 1; AltName: Full=Islet-brain 1; Short=IB-1; AltName: Full=JNK MAP kinase scaffold protein 1; AltName: Full=Mitogen-activated protein kinase 8-interacting protein 1; 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. Required for JNK activation in response to excitotoxic stress. Cytoplasmic MAPK8IP1 causes inhibition of JNK- regulated activity by retaining JNK in the cytoplasm and inhibiting JNK phosphorylation of c-Jun. May also participate in ApoER2-specific reelin signaling. Directly, or indirectly, regulates GLUT2 gene expression and beta-cell function. Appears to have a role in cell signaling in mature and developing nerve terminals. May function as a regulator of vesicle transport, through interactions with the JNK-signaling components and motor proteins (By similarity). Functions as an anti-apoptotic protein and whose level seems to influence the beta-cell death or survival response. SUBUNIT: Forms homo- or heterooligomeric complexes. Binds specific components of the JNK signaling pathway namely, MAPK8, MAPK9, MAPK10, MAPKK7, MLK2, MLK3, MAP3K12 and MAP3K13. Also binds the proline-rich domain-containing splice variant of apolipoprotein E receptor 2 (ApoER2). Interacts, via the PID domain, with ARHGEF28. Binds the cytoplasmic tails of LRP1 and LRP2 (Megalin). Binds the TPR motif-containing C-terminal of KNS2, then the pre-assembled MAPK8IP1 scaffolding complexes are transported as a cargo of kinesin, to the required subcellular location. Interacts with the cytoplasmic domain of APP. Interacts with DCLK2 (By similarity). Interacts with MAP3K7. Interacts with isoform 1 and isoform 2 of VRK2. INTERACTION: P05067:APP; NbExp=4; IntAct=EBI-78404, EBI-77613; P12023:App (xeno); NbExp=2; IntAct=EBI-78404, EBI-78814; O43318:MAP3K7; NbExp=10; IntAct=EBI-78404, EBI-358684; SUBCELLULAR LOCATION: Cytoplasm (By similarity). Cytoplasm, perinuclear region (By similarity). Nucleus (By similarity). Endoplasmic reticulum membrane. Mitochondrion membrane. Note=Accumulates in cell surface projections. Under certain stress conditions, translocates to the perinuclear region of neurons. In insulin-secreting cells, detected in both the cytoplasm and nucleus (By similarity). TISSUE SPECIFICITY: Highly expressed in brain. Expressed in neurons, localizing to neurite tips in differentiating cells. Also expressed in the pancreas, testis and prostate. Low levels in heart, ovary and small intestine. Decreased levels in pancreatic beta cells sensitize cells to IL-1-beta-induced apoptosis. DOMAIN: The destruction boxes (D-box) may act as recognition signals for degradation via the ubiquitin-proteasome pathway. DOMAIN: A minimal inhibitory domain prevents pancreatic beta cell apoptosis in vitro, and prevents activation of c-jun by MAPK8, MAPK9 and MAPK10. DOMAIN: The SH3 domain mediates homodimerization (By similarity). PTM: Phosphorylated by MAPK8, MAPK9 and MAPK10. Phosphorylation on Thr-103 is also necessary for the dissociation and activation of MAP3K12. Phosphorylated by isoform 1 and isoform 2 of VRK2. PTM: Ubiquitinated. Two preliminary events are required to prime for ubiquitination; phosphorylation and an increased in intracellular calcium concentration. Then, the calcium influx initiates ubiquitination and degradation by the ubiquitin- proteasome pathway. DISEASE: Defects in MAPK8IP1 are a cause of non-insulin-dependent diabetes mellitus (NIDDM) [MIM:125853]. NIDDM is characterized by an autosomal dominant mode of inheritance, onset during adulthood and insulin resistance. MISCELLANEOUS: A chemically synthesized cell-permeable peptide of the minimal inhibitory domain decreases brain lesions in both transient and permanent ischemia. The level of protection is still high when administered 6 or 12 hours after ischemia. SIMILARITY: Belongs to the JIP scaffold family. SIMILARITY: Contains 1 PID domain. SIMILARITY: Contains 1 SH3 domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9UQF2
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0004860 protein kinase inhibitor activity GO:0005078 MAP-kinase scaffold activity GO:0005515 protein binding GO:0008432 JUN kinase binding GO:0019894 kinesin binding GO:0019901 protein kinase binding GO:0031434 mitogen-activated protein kinase kinase binding GO:0031435 mitogen-activated protein kinase kinase kinase binding
Biological Process: GO:0006355 regulation of transcription, DNA-templated GO:0007165 signal transduction GO:0007258 JUN phosphorylation GO:0016192 vesicle-mediated transport GO:0043066 negative regulation of apoptotic process GO:0043410 positive regulation of MAPK cascade GO:0043508 negative regulation of JUN kinase activity GO:0046328 regulation of JNK cascade GO:0046329 negative regulation of JNK cascade GO:2001243 negative regulation of intrinsic apoptotic signaling pathway
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
