Protein: Tribbles homolog 1 (TRB-1) (G-protein-coupled receptor-induced gene 2 protein) (GIG-2) (SKIP1) (Q96RU8)
Organism: Homo sapiens (Human)
Function: Adapter protein involved in protein degradation by interacting with COP1 ubiquitin ligase. The COP1-binding motif is masked by autoinhibitory interactions with the protein kinase domain. Serves to alter COP1 substrate specificity by directing the activity of COP1 toward CEBPA. Binds selectively the recognition sequence of CEBPA. Regulates myeloid cell differentiation by altering the expression of CEBPA in a COP1-dependent manner (By similarity). Controls macrophage, eosinophil and neutrophil differentiation via the COP1-binding domain (By similarity). Interacts with MAPK kinases and regulates activation of MAP kinases, but has no kinase activity.
Sequence: MRVGPVRSAMSGASQPRGPALLFPATRGVPAKRLLDADDAAAVAAKCPRLSECSSPPDYLSPPGSPCSPQPPPAAPGAGGGSGSAPGPSRIADYLLLPLAEREHVSRALCIHTGRELRCKVFPIKHYQDKIRPYIQLPSHSNITGIVEVILGETKAYVFFEKDFGDMHSYVRSRKRLREEEAARLFKQIVSAVAHCHQSAIVLGDLKLRKFVFSTEERTQLRLESLEDTHIMKGEDDALSDKHGCPAYVSPEILNTTGTYSGKAADVWSLGVMLYTLLVGRYPFHDSDPSALFSKIRRGQFCIPEHISPKARCLIRSLLRREPSERLTAPEILLHPWFESVLEPGYIDSEIGTSDQIVPEYQEDSDISSFFC
InterPro domains: - IPR011009: Protein kinase-like domain superfamily (homologous_superfamily) [105-341]
- IPR024105: Tribbles homologue 1, pseudokinase domain (domain) [97-338]
- IPR024104: Pseudokinase tribbles family/serine-threonine-protein kinase 40 (family) [1-372]
- IPR000719: Protein kinase domain (domain) [1-338]
Interaction partners: - Dual specificity mitogen-activated protein kinase kinase 1
- CCAAT/enhancer-binding protein alpha
- RIB43A-like with coiled-coils protein 2
- E3 ubiquitin-protein ligase COP1
- Early growth response protein 1
- Serine/threonine-protein kinase 40
- DET1 homolog
- Fos-related antigen 2
- Protein FosB
- Tribbles homolog 2
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:0050789 (regulation of biological process), GO:0048519 (negative regulation of biological process), GO:0065009 (regulation of molecular function), GO:0019222 (regulation of metabolic process), GO:0009892 (negative regulation of metabolic process), GO:0060255 (regulation of macromolecule metabolic process), GO:0050790 (regulation of catalytic activity), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:0080090 (regulation of primary metabolic process), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0044092 (negative regulation of molecular function), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0043086 (negative regulation of catalytic activity), GO:0051246 (regulation of protein metabolic process), GO:0051336 (regulation of hydrolase activity), GO:0051248 (negative regulation of protein metabolic process), GO:0052547 (regulation of peptidase activity), GO:0045861 (negative regulation of proteolysis), GO:0051346 (negative regulation of hydrolase activity), GO:0030162 (regulation of proteolysis), GO:0010466 (negative regulation of peptidase activity)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005829 (cytosol), GO:0005737 (cytoplasm), GO:0031974 (membrane-enclosed lumen), GO:0005654 (nucleoplasm), GO:0043233 (organelle lumen), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0031981 (nuclear lumen), GO:0005634 (nucleus)