Protein: TRAF3-interacting JNK-activating modulator (Q9Y228)
Organism: Homo sapiens (Human)
Function: Adapter protein that plays essential roles in both innate and adaptive immunity. Plays a crucial role in the regulation of thymocyte development. Mechanistically, mediates TCR-stimulated activation through recruiting MAP2K1/MEK1 to the Golgi and, thereby, facilitating the interaction of MAP2K1/MEK1 with its activator BRAF. Also plays an essential role in regulatory T-cell stability and function by recruiting the serine-threonine phosphatase catalytic subunit (PPP2CA) to the lysosome, thereby facilitating the interaction of PP2Ac with the mTORC1 component RPTOR and restricting glycolytic metabolism. Positively regulates TLR4 signaling activity in macrophage-mediated inflammation by acting as a molecular clamp to facilitate LPS-induced translocation of TLR4 to lipid rafts. In response to viral infection, facilitates the recruitment of TRAF3 to MAVS within mitochondria leading to IRF3 activation and interferon production. However, participates in the maintenance of immune homeostasis and the prevention of overzealous innate immunity by promoting 'Lys-48'- dependent ubiquitination of TBK1
Subcellular location: Cell membrane. Golgi apparatus membrane; Single-pass type IV membrane protein. Lysosome membrane. Mitochondrion outer membrane. Note=Accumulates on the mitochondria after virus infection
Sequence: MISPDPRPSPGLARWAESYEAKCERRQEIRESRRCRPNVTTCRQVGKTLRIQQREQLQRARLQQFFRRRNLELEEKGKAQHPQAREQGPSRRPGQVTVLKEPLSCARRISSPREQVTGTSSEVFPAQHPPPSGICRDLSDHLSSQAGGLPPQDTPIKKPPKHHRGTQTKAEGPTIKNDASQQTNYGVAVLDKEIIQLSDYLKEALQRELVLKQKMVILQDLLSTLIQASDSSWKGQLNEDKLKGKLRSLENQLYTCTQKYSPWGMKKVLLEMEDQKNSYEQKAKESLQKVLEEKMNAEQQLQSTQRSLALAEQKCEEWRSQYEALKEDWRTLGTQHRELESQLHVLQSKLQGADSRDLQMNQALRFLENEHQQLQAKIECLQGDRDLCSLDTQDLQDQLKRSEAEKLTLVTRVQQLQGLLQNQSLQLQEQEKLLTKKDQALPVWSPKSFPNEVEPEGTGKEKDWDLRDQLQKKTLQLQAKEKECRELHSELDNLSDEYLSCLRKLQHCREELNQSQQLPPRRQCGRWLPVLMVVIAAALAVFLANKDNLMI
InterPro domains: - IPR051176: Centrosomal and Immune Signaling Modulators (family) [94-361]
Interaction partners: - FGFR1 oncogene partner 2
- Striatin-interacting protein 1
- Striatin-3
- MOB-like protein phocein
- Suppressor of IKBKE 1
- Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform
- Serine/threonine-protein kinase 25
- Serine/threonine-protein kinase 24
- Programmed cell death protein 10
- Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0048518 (positive regulation of biological process), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0044419 (biological process involved in interspecies interaction between organisms), GO:0002376 (immune system process), GO:0009987 (cellular process), GO:0009605 (response to external stimulus), GO:0042221 (response to chemical), GO:0019222 (regulation of metabolic process), GO:0006955 (immune response), GO:0009607 (response to biotic stimulus), GO:0051240 (positive regulation of multicellular organismal process), GO:0009893 (positive regulation of metabolic process), GO:0051716 (cellular response to stimulus), GO:0051239 (regulation of multicellular organismal process), GO:0006950 (response to stress), GO:0065009 (regulation of molecular function), GO:0051707 (response to other organism), GO:0043207 (response to external biotic stimulus), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0070887 (cellular response to chemical stimulus), GO:0006952 (defense response), GO:0060255 (regulation of macromolecule metabolic process), GO:0001819 (positive regulation of cytokine production), GO:0051098 (regulation of binding), GO:0001817 (regulation of cytokine production), GO:0009615 (response to virus), GO:0010033 (response to organic substance), GO:0045087 (innate immune response), GO:0098542 (defense response to other organism), GO:0034097 (response to cytokine), GO:0140546 (defense response to symbiont), GO:0032481 (positive regulation of type I interferon production), GO:0051607 (defense response to virus), GO:0071310 (cellular response to organic substance), GO:0140374 (antiviral innate immune response), GO:0010628 (positive regulation of gene expression), GO:0043393 (regulation of protein binding), GO:0010468 (regulation of gene expression), GO:0032479 (regulation of type I interferon production), GO:0032727 (positive regulation of interferon-alpha production), GO:0035456 (response to interferon-beta), GO:0035455 (response to interferon-alpha), GO:0032647 (regulation of interferon-alpha production), GO:0032648 (regulation of interferon-beta production), GO:0032728 (positive regulation of interferon-beta production), GO:0071345 (cellular response to cytokine stimulus), GO:0035457 (cellular response to interferon-alpha), GO:0035458 (cellular response to interferon-beta)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0031974 (membrane-enclosed lumen), GO:0005829 (cytosol), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0005654 (nucleoplasm), GO:0031090 (organelle membrane), GO:0043233 (organelle lumen), GO:0005783 (endoplasmic reticulum), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0005788 (endoplasmic reticulum lumen), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0031981 (nuclear lumen), GO:0005634 (nucleus)