UniProt functional annotation for Q9R237



	UniProt functional annotation for Q9R237

UniProt code: Q9R237.

Organism: Rattus norvegicus (Rat).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.

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 thus inhibiting the 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. Functions as an anti-apoptotic protein and whose level seems to influence the beta-cell death or survival response. Acts as a scaffold protein that coordinates with SH3RF1 in organizing different components of the JNK pathway, including RAC1 or RAC2, MAP3K11/MLK3 or MAP3K7/TAK1, MAP2K7/MKK7, MAPK8/JNK1 and/or MAPK9/JNK2 into a functional multiprotein complex to ensure the effective activation of the JNK signaling pathway. Regulates the activation of MAPK8/JNK1 and differentiation of CD8(+) T-cells. {ECO:0000250|UniProtKB:Q9WVI9, ECO:0000269|PubMed:21076496}.

Subunit: Forms homo- or heterooligomeric complexes (PubMed:16456539). Binds specific components of the JNK signaling pathway namely MAPK8/JNK1, MAPK9/JNK2, MAPK10/JNK3, MAP2K7/MKK7, MAP3K11/MLK3 and DLK1. Also binds the proline-rich domain-containing splice variant of apolipoprotein E receptor 2 (ApoER2). Interacts, via the PID domain, with ARHGEF28 (By similarity). Binds the cytoplasmic tails of LRP1 and LRP2 (Megalin). Binds the TPR motif-containing C-terminal of kinesin light chain, KLC1. Pre-assembled MAPK8IP1 scaffolding complexes are then transported as a cargo of kinesin, to the required subcellular location. Interacts with the cytoplasmic domain of APP (By similarity). Interacts with DCLK2, VRK2 and MAP3K7/TAK1. Found in a complex with SH3RF1, RAC1, MAP3K11/MLK3, MAP2K7/MKK7 and MAPK8/JNK1. Found in a complex with SH3RF1, RAC2, MAP3K7/TAK1, MAP2K7/MKK7, MAPK8/JNK1 and MAPK9/JNK2 (By similarity). Interacts with SH3RF2 (PubMed:22128169). {ECO:0000250|UniProtKB:Q9UQF2, ECO:0000250|UniProtKB:Q9WVI9, ECO:0000269|PubMed:16456539, ECO:0000269|PubMed:21076496, ECO:0000269|PubMed:22128169}.

Subcellular location: Cytoplasm {ECO:0000250}. Cytoplasm, perinuclear region {ECO:0000250}. Nucleus. Endoplasmic reticulum membrane {ECO:0000250}. Mitochondrion membrane {ECO:0000250}. 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.

Tissue specificity: Highly expressed in brain and pancreatic beta- cells. Weaker expression found in kidney.

Domain: The SH3 domain mediates homodimerization.

Ptm: Phosphorylated by MAPK8, MAPK9 and MAPK10. Phosphorylation on Thr- 103 is also necessary for the dissociation and activation of MAP3K12. Phosphorylated by VRK2. Hyperphosphorylated during mitosis following activation of stress-activated and MAP kinases (By similarity). {ECO:0000250}.

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 (By similarity). {ECO:0000250}.

Similarity: Belongs to the JIP scaffold family. {ECO:0000305}.

Sequence caution: Sequence=AAD22543.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=AAD38351.1; Type=Erroneous initiation; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Rattus norvegicus (Rat).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.



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 thus inhibiting the 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. Functions as an anti-apoptotic protein and whose level seems to influence the beta-cell death or survival response. Acts as a scaffold protein that coordinates with SH3RF1 in organizing different components of the JNK pathway, including RAC1 or RAC2, MAP3K11/MLK3 or MAP3K7/TAK1, MAP2K7/MKK7, MAPK8/JNK1 and/or MAPK9/JNK2 into a functional multiprotein complex to ensure the effective activation of the JNK signaling pathway. Regulates the activation of MAPK8/JNK1 and differentiation of CD8(+) T-cells. {ECO:0000250\|UniProtKB:Q9WVI9, ECO:0000269\|PubMed:21076496}.


Subunit:		Forms homo- or heterooligomeric complexes (PubMed:16456539). Binds specific components of the JNK signaling pathway namely MAPK8/JNK1, MAPK9/JNK2, MAPK10/JNK3, MAP2K7/MKK7, MAP3K11/MLK3 and DLK1. Also binds the proline-rich domain-containing splice variant of apolipoprotein E receptor 2 (ApoER2). Interacts, via the PID domain, with ARHGEF28 (By similarity). Binds the cytoplasmic tails of LRP1 and LRP2 (Megalin). Binds the TPR motif-containing C-terminal of kinesin light chain, KLC1. Pre-assembled MAPK8IP1 scaffolding complexes are then transported as a cargo of kinesin, to the required subcellular location. Interacts with the cytoplasmic domain of APP (By similarity). Interacts with DCLK2, VRK2 and MAP3K7/TAK1. Found in a complex with SH3RF1, RAC1, MAP3K11/MLK3, MAP2K7/MKK7 and MAPK8/JNK1. Found in a complex with SH3RF1, RAC2, MAP3K7/TAK1, MAP2K7/MKK7, MAPK8/JNK1 and MAPK9/JNK2 (By similarity). Interacts with SH3RF2 (PubMed:22128169). {ECO:0000250\|UniProtKB:Q9UQF2, ECO:0000250\|UniProtKB:Q9WVI9, ECO:0000269\|PubMed:16456539, ECO:0000269\|PubMed:21076496, ECO:0000269\|PubMed:22128169}.
Subcellular location:		Cytoplasm {ECO:0000250}. Cytoplasm, perinuclear region {ECO:0000250}. Nucleus. Endoplasmic reticulum membrane {ECO:0000250}. Mitochondrion membrane {ECO:0000250}. 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.
Tissue specificity:		Highly expressed in brain and pancreatic beta- cells. Weaker expression found in kidney.
Domain:		The SH3 domain mediates homodimerization.
Ptm:		Phosphorylated by MAPK8, MAPK9 and MAPK10. Phosphorylation on Thr- 103 is also necessary for the dissociation and activation of MAP3K12. Phosphorylated by VRK2. Hyperphosphorylated during mitosis following activation of stress-activated and MAP kinases (By similarity). {ECO:0000250}.
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 (By similarity). {ECO:0000250}.
Similarity:		Belongs to the JIP scaffold family. {ECO:0000305}.
Sequence caution:		Sequence=AAD22543.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=AAD38351.1; Type=Erroneous initiation; Evidence={ECO:0000305};