Q8K4K4
SS
Gene name |
Trib1 (Trb1) |
Protein name |
Tribbles homolog 1 |
Names |
TRB-1 |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:211770 |
EC number |
|
Protein Class |
|
Descriptions
TRIB1 controls the levels of C/EBPs involved in the differentiation of myeloid cells and adipocytes by recruiting the proteins to COP1 ubiquitin ligase. TRIB1 recognizes a conserved stretch within a transactivation domain of C/EBP proteins, and suggests a model by which TRIB1 acts as a dynamic adapter for recruiting C/EBPs to COP1. TRIB1 contains a pseudokinase domain and this pseudokinase interacts with the COP1-binding motif and prevents the recruitment of COP1 ubiquitin ligase.
Autoinhibitory domains (AIDs)
Target domain |
355-360 (COP1-binding motif) |
Relief mechanism |
PTM |
Assay |
|
Accessory elements
No accessory elements
References
- Murphy JM et al. (2015) "Molecular Mechanism of CCAAT-Enhancer Binding Protein Recruitment by the TRIB1 Pseudokinase", Structure (London, England : 1993), 23, 2111-21
- Jamieson SA et al. (2018) "Substrate binding allosterically relieves autoinhibition of the pseudokinase TRIB1", Science signaling, 11,
Autoinhibited structure
Activated structure
1 structures for Q8K4K4
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-Q8K4K4-F1 | Predicted | AlphaFoldDB |
12 variants for Q8K4K4
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs1133164668 | 2 | R>W | No | EVA | |
| rs3551720111 | 86 | P>S | No | EVA | |
| rs3389372038 | 162 | K>E | No | EVA | |
| rs3389343295 | 164 | F>I | No | EVA | |
| rs3389282336 | 167 | M>I | No | EVA | |
| rs3389282407 | 179 | E>D | No | EVA | |
| rs3389359293 | 180 | E>G | No | EVA | |
| rs3389363244 | 183 | A>V | No | EVA | |
| rs3389314210 | 189 | I>N | No | EVA | |
| rs3389343294 | 211 | F>I | No | EVA | |
| rs3389355894 | 259 | T>I | No | EVA | |
| rs3389353302 | 273 | M>L | No | EVA |
No associated diseases with Q8K4K4
2 GO annotations of cellular component
| Name | Definition |
|---|---|
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| nucleus | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. |
5 GO annotations of molecular function
| Name | Definition |
|---|---|
| mitogen-activated protein kinase kinase binding | Binding to a mitogen-activated protein kinase kinase, a protein that can phosphorylate a MAP kinase. |
| protein kinase inhibitor activity | Binds to and stops, prevents or reduces the activity of a protein kinase. |
| RNA polymerase II-specific DNA-binding transcription factor binding | Binding to a sequence-specific DNA binding RNA polymerase II transcription factor, any of the factors that interact selectively and non-covalently with a specific DNA sequence in order to modulate transcription. |
| ubiquitin protein ligase binding | Binding to a ubiquitin protein ligase enzyme, any of the E3 proteins. |
| ubiquitin-protein transferase regulator activity | Binds to and modulates the activity of a ubiquitin-protein transferase, an enzyme that catalyzes the covalent attachment of ubiquitin to lysine in a substrate protein. |
12 GO annotations of biological process
| Name | Definition |
|---|---|
| JNK cascade | An intracellular protein kinase cascade containing at least a JNK (a MAPK), a JNKK (a MAPKK) and a JUN3K (a MAP3K). The cascade can also contain an additional tier |
| negative regulation of DNA-binding transcription factor activity | Any process that stops, prevents, or reduces the frequency, rate or extent of the activity of a transcription factor, any factor involved in the initiation or regulation of transcription. |
| negative regulation of lipopolysaccharide-mediated signaling pathway | Any process that stops, prevents, or reduces the frequency, rate or extent of signaling in response to detection of lipopolysaccharide. |
| negative regulation of neutrophil differentiation | Any process that stops, prevents, or reduces the frequency, rate or extent of neutrophil differentiation. |
| negative regulation of smooth muscle cell migration | Any process that stops, prevents, or reduces the frequency, rate or extent of smooth muscle cell migration. |
| negative regulation of smooth muscle cell proliferation | Any process that stops, prevents or reduces the rate or extent of smooth muscle cell proliferation. |
| positive regulation of eosinophil differentiation | Any process that activates or increases the frequency, rate or extent of eosinophil differentiation. |
| positive regulation of macrophage differentiation | Any process that activates or increases the frequency, rate or extent of macrophage differentiation. |
| positive regulation of proteasomal ubiquitin-dependent protein catabolic process | Any process that activates or increases the frequency, rate or extent of the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of ubiquitin, and mediated by the proteasome. |
| positive regulation of ubiquitin-protein transferase activity | Any process that activates, maintains or increases the rate of ubiquitin transferase activity. |
| regulation of MAP kinase activity | Any process that modulates the frequency, rate or extent of MAP kinase activity. |
| response to lipopolysaccharide | Any process that results in a change in state or activity of an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lipopolysaccharide stimulus; lipopolysaccharide is a major component of the cell wall of gram-negative bacteria. |
65 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| Q02066 | Abscisic acid-inducible protein kinase | Triticum aestivum (Wheat) | PR | |
| Q3SZW1 | TSSK1B | Testis-specific serine/threonine-protein kinase 1 | Bos taurus (Bovine) | PR |
| Q0VCE3 | TRIB3 | Tribbles homolog 3 | Bos taurus (Bovine) | SS |
| Q5GLH2 | TRIB2 | Tribbles homolog 2 | Bos taurus (Bovine) | SS |
| Q28283 | TRIB2 | Tribbles homolog 2 | Canis lupus familiaris (Dog) (Canis familiaris) | SS |
| Q14680 | MELK | Maternal embryonic leucine zipper kinase | Homo sapiens (Human) | EV |
| Q15831 | STK11 | Serine/threonine-protein kinase STK11 | Homo sapiens (Human) | PR |
| Q13131 | PRKAA1 | 5'-AMP-activated protein kinase catalytic subunit alpha-1 | Homo sapiens (Human) | EV |
| Q96RG2 | PASK | PAS domain-containing serine/threonine-protein kinase | Homo sapiens (Human) | EV |
| P54646 | PRKAA2 | 5'-AMP-activated protein kinase catalytic subunit alpha-2 | Homo sapiens (Human) | EV |
| Q9BXA7 | TSSK1B | Testis-specific serine/threonine-protein kinase 1 | Homo sapiens (Human) | PR |
| Q92519 | TRIB2 | Tribbles homolog 2 | Homo sapiens (Human) | SS |
| Q96RU7 | TRIB3 | Tribbles homolog 3 | Homo sapiens (Human) | PR |
| Q96RU8 | TRIB1 | Tribbles homolog 1 | Homo sapiens (Human) | EV |
| Q8BRK8 | Prkaa2 | 5'-AMP-activated protein kinase catalytic subunit alpha-2 | Mus musculus (Mouse) | SS |
| Q61241 | Tssk1b | Testis-specific serine/threonine-protein kinase 1 | Mus musculus (Mouse) | PR |
| Q61846 | Melk | Maternal embryonic leucine zipper kinase | Mus musculus (Mouse) | PR |
| O54863 | Tssk2 | Testis-specific serine/threonine-protein kinase 2 | Mus musculus (Mouse) | PR |
| Q5EG47 | Prkaa1 | 5'-AMP-activated protein kinase catalytic subunit alpha-1 | Mus musculus (Mouse) | SS |
| Q8K4K2 | Trib3 | Tribbles homolog 3 | Mus musculus (Mouse) | SS |
| Q8K4K3 | Trib2 | Tribbles homolog 2 | Mus musculus (Mouse) | SS |
| Q28948 | PRKAA2 | 5'-AMP-activated protein kinase catalytic subunit alpha-2 | Sus scrofa (Pig) | SS |
| Q09137 | Prkaa2 | 5'-AMP-activated protein kinase catalytic subunit alpha-2 | Rattus norvegicus (Rat) | EV |
| P54645 | Prkaa1 | 5'-AMP-activated protein kinase catalytic subunit alpha-1 | Rattus norvegicus (Rat) | EV |
| Q9WTQ6 | Trib3 | Tribbles homolog 3 | Rattus norvegicus (Rat) | SS |
| Q5QNM6 | CIPK13 | Putative CBL-interacting protein kinase 13 | Oryza sativa subsp japonica (Rice) | PR |
| Q5JLQ9 | CIPK30 | CBL-interacting protein kinase 30 | Oryza sativa subsp japonica (Rice) | PR |
| Q5N942 | SAPK4 | Serine/threonine-protein kinase SAPK4 | Oryza sativa subsp japonica (Rice) | PR |
| Q852Q0 | OSK3 | Serine/threonine protein kinase OSK3 | Oryza sativa subsp. japonica (Rice) | SS |
| Q75LR7 | SAPK1 | Serine/threonine-protein kinase SAPK1 | Oryza sativa subsp japonica (Rice) | PR |
| Q75H77 | SAPK10 | Serine/threonine-protein kinase SAPK10 | Oryza sativa subsp japonica (Rice) | PR |
| Q7Y0B9 | SAPK8 | Serine/threonine-protein kinase SAPK8 | Oryza sativa subsp japonica (Rice) | PR |
| Q7XQP4 | SAPK7 | Serine/threonine-protein kinase SAPK7 | Oryza sativa subsp japonica (Rice) | PR |
| Q852Q2 | OSK1 | Serine/threonine protein kinase OSK1 | Oryza sativa subsp. japonica (Rice) | SS |
| Q6ZLP5 | CIPK23 | CBL-interacting protein kinase 23 | Oryza sativa subsp japonica (Rice) | PR |
| Q0D4J7 | SAPK2 | Serine/threonine-protein kinase SAPK2 | Oryza sativa subsp japonica (Rice) | PR |
| Q8LIG4 | CIPK3 | CBL-interacting protein kinase 3 | Oryza sativa subsp japonica (Rice) | PR |
| Q852Q1 | OSK4 | Serine/threonine protein kinase OSK4 | Oryza sativa subsp. japonica (Rice) | SS |
| Q6ERS4 | CIPK16 | CBL-interacting protein kinase 16 | Oryza sativa subsp japonica (Rice) | PR |
| P0C5D6 | SAPK3 | Serine/threonine-protein kinase SAPK3 | Oryza sativa subsp japonica (Rice) | PR |
| Q2RAX3 | CIPK33 | CBL-interacting protein kinase 33 | Oryza sativa subsp japonica (Rice) | PR |
| Q75V57 | SAPK9 | Serine/threonine-protein kinase SAPK9 | Oryza sativa subsp japonica (Rice) | PR |
| Q21017 | kin-29 | Serine/threonine-protein kinase kin-29 | Caenorhabditis elegans | SS |
| P45894 | aak-1 | 5'-AMP-activated protein kinase catalytic subunit alpha-1 | Caenorhabditis elegans | SS |
| Q95ZQ4 | aak-2 | 5'-AMP-activated protein kinase catalytic subunit alpha-2 | Caenorhabditis elegans | SS |
| G5EED4 | nipi-3 | Protein nipi-3 | Caenorhabditis elegans | PR |
| P43291 | SRK2A | Serine/threonine-protein kinase SRK2A | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q93VD3 | CIPK23 | CBL-interacting serine/threonine-protein kinase 23 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q9C958 | SRK2B | Serine/threonine-protein kinase SRK2B | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q9M9E9 | SRK2C | Serine/threonine-protein kinase SRK2C | Arabidopsis thaliana (Mouse-ear cress) | PR |
| O64812 | SRK2J | Serine/threonine-protein kinase SRK2J | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q2V452 | CIPK3 | CBL-interacting serine/threonine-protein kinase 3 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| O22971 | CIPK13 | CBL-interacting serine/threonine-protein kinase 13 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q38997 | KIN10 | SNF1-related protein kinase catalytic subunit alpha KIN10 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| P92958 | KIN11 | SNF1-related protein kinase catalytic subunit alpha KIN11 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q39192 | SRK2D | Serine/threonine-protein kinase SRK2D | Arabidopsis thaliana (Mouse-ear cress) | PR |
| O65554 | CIPK6 | CBL-interacting serine/threonine-protein kinase 6 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q940H6 | SRK2E | Serine/threonine-protein kinase SRK2E | Arabidopsis thaliana (Mouse-ear cress) | PR |
| P43292 | SRK2G | Serine/threonine-protein kinase SRK2G | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q9LDI3 | CIPK24 | CBL-interacting serine/threonine-protein kinase 24 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q9FLZ3 | KIN12 | SNF1-related protein kinase catalytic subunit alpha KIN12 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q9FJ54 | CIPK20 | CBL-interacting serine/threonine-protein kinase 20 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q94CG0 | CIPK21 | CBL-interacting serine/threonine-protein kinase 21 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q9FFP9 | SRK2H | Serine/threonine-protein kinase SRK2H | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q39193 | SRK2I | Serine/threonine-protein kinase SRK2I | Arabidopsis thaliana (Mouse-ear cress) | PR |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MRVGPVRFAL | SGASQPRGPG | LLFPAARGTP | AKRLLDTDDA | GAVAAKCPRL | SECSSPPDYL |
| 70 | 80 | 90 | 100 | 110 | 120 |
| SPPGSPCSPQ | PPPSTQGTGG | SCVSSPGPSR | IADYLLLPLA | EREHVSRALC | IHTGRELRCK |
| 130 | 140 | 150 | 160 | 170 | 180 |
| EFPIKHYQDK | IRPYIQLPSH | SNITGIVEVL | LGESKAYVFF | EKDFGDMHSY | VRSRKRLREE |
| 190 | 200 | 210 | 220 | 230 | 240 |
| EAARLFKQIV | SAVAHCHQSA | IVLGDLKLRK | FVFSTEERTQ | LRLESLEDTH | IIKGEDDALS |
| 250 | 260 | 270 | 280 | 290 | 300 |
| DKHGCPAYVS | PEILNTTGTY | SGKAADVWSL | GVMLYTLLVG | RYPFHDSDPS | ALFSKIRRGQ |
| 310 | 320 | 330 | 340 | 350 | 360 |
| FCIPEHVSPK | ARCLIRSLLR | REPSERLTAP | QILLHPWFEY | VLEPGYVDSE | IGTSDQIVPE |
| 370 | |||||
| YQEDSDISSF | FC |