Q8K4K2
SS
Gene name |
Trib3 (Nipk, Trb3) |
Protein name |
Tribbles homolog 3 |
Names |
TRB-3 , Neuronal cell death-inducible putative kinase |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:228775 |
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 |
333-343 (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 Q8K4K2
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-Q8K4K2-F1 | Predicted | AlphaFoldDB |
19 variants for Q8K4K2
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3388602701 | 5 | P>H | No | EVA | |
| rs13469360 | 24 | N>S | No | EVA | |
| rs13469359 | 28 | K>E | No | EVA | |
| rs213918455 | 37 | D>N | No | EVA | |
| rs244760360 | 46 | S>N | No | EVA | |
| rs3388590833 | 58 | L>F | No | EVA | |
| rs228486627 | 66 | T>S | No | EVA | |
| rs3388603416 | 136 | F>L | No | EVA | |
| rs3388601269 | 154 | I>F | No | EVA | |
| rs252650715 | 164 | R>Q | No | EVA | |
| rs3388592660 | 200 | L>M | No | EVA | |
| rs3388585950 | 200 | L>RDG* | No | EVA | |
| rs3412841335 | 202 | N>S | No | EVA | |
| rs3388601219 | 204 | E>G | No | EVA | |
| rs223317466 | 277 | T>I | No | EVA | |
| rs3388601452 | 299 | E>K | No | EVA | |
| rs3388603335 | 303 | R>* | No | EVA | |
| rs3388601382 | 314 | W>L | No | EVA | |
| rs3388592394 | 349 | E>K | No | EVA |
No associated diseases with Q8K4K2
5 regional properties for Q8K4K2
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | Dbl homology (DH) domain | 235 - 432 | IPR000219 |
| domain | Pleckstrin homology domain | 472 - 573 | IPR001849 |
| domain | Protein kinase C-like, phorbol ester/diacylglycerol-binding domain | 39 - 86 | IPR002219 |
| domain | ARHGEF2, PH domain | 470 - 585 | IPR037806 |
| domain | ARHGEF1-like, PH domain | 463 - 570 | IPR041020 |
2 GO annotations of cellular component
| Name | Definition |
|---|---|
| nucleoplasm | That part of the nuclear content other than the chromosomes or the nucleolus. |
| 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. |
8 GO annotations of molecular function
| Name | Definition |
|---|---|
| ATP binding | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. |
| enzyme binding | Binding to an enzyme, a protein with catalytic activity. |
| mitogen-activated protein kinase kinase binding | Binding to a mitogen-activated protein kinase kinase, a protein that can phosphorylate a MAP kinase. |
| protein kinase binding | Binding to a protein kinase, any enzyme that catalyzes the transfer of a phosphate group, usually from ATP, to a protein substrate. |
| protein kinase inhibitor activity | Binds to and stops, prevents or reduces the activity of a protein kinase. |
| transcription corepressor activity | A transcription coregulator activity that represses or decreases the transcription of specific gene sets via binding to a DNA-bound DNA-binding transcription factor, either on its own or as part of a complex. Corepressors often act by altering chromatin structure and modifications. For example, one class of transcription corepressors modifies chromatin structure through covalent modification of histones. A second class remodels the conformation of chromatin in an ATP-dependent fashion. A third class modulates interactions of DNA-bound DNA-binding transcription factors with other transcription coregulators. |
| 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. |
15 GO annotations of biological process
| Name | Definition |
|---|---|
| cellular response to insulin stimulus | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an insulin stimulus. Insulin is a polypeptide hormone produced by the islets of Langerhans of the pancreas in mammals, and by the homologous organs of other organisms. |
| intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress | The series of molecular signals in which an intracellular signal is conveyed to trigger the apoptotic death of a cell. The pathway is induced in response to a stimulus indicating endoplasmic reticulum (ER) stress, and ends when the execution phase of apoptosis is triggered. ER stress usually results from the accumulation of unfolded or misfolded proteins in the ER lumen. |
| negative regulation of DNA-templated transcription | Any process that stops, prevents, or reduces the frequency, rate or extent of cellular DNA-templated transcription. |
| negative regulation of fat cell differentiation | Any process that stops, prevents, or reduces the frequency, rate or extent of adipocyte differentiation. |
| negative regulation of fatty acid biosynthetic process | Any process that stops, prevents, or reduces the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of fatty acids. |
| negative regulation of protein kinase activity | Any process that stops, prevents, or reduces the frequency, rate or extent of protein kinase activity. |
| negative regulation of transcription by RNA polymerase II | Any process that stops, prevents, or reduces the frequency, rate or extent of transcription mediated by RNA polymerase II. |
| 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 protein binding | Any process that activates or increases the frequency, rate or extent of protein binding. |
| positive regulation of protein catabolic process | Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the breakdown of a protein by the destruction of the native, active configuration, with or without the hydrolysis of peptide bonds. |
| positive regulation of ubiquitin-protein transferase activity | Any process that activates, maintains or increases the rate of ubiquitin transferase activity. |
| regulation of autophagy | Any process that modulates the frequency, rate or extent of autophagy. Autophagy is the process in which cells digest parts of their own cytoplasm. |
| regulation of glucose transmembrane transport | Any process that modulates the frequency, rate or extent of glucose transport across a membrane. Glucose transport is the directed movement of the hexose monosaccharide glucose into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. |
| regulation of MAP kinase activity | Any process that modulates the frequency, rate or extent of MAP kinase activity. |
| response to endoplasmic reticulum stress | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stress acting at the endoplasmic reticulum. ER stress usually results from the accumulation of unfolded or misfolded proteins in the ER lumen. |
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 |
| Q5GLH2 | TRIB2 | Tribbles homolog 2 | Bos taurus (Bovine) | SS |
| Q0VCE3 | TRIB3 | Tribbles homolog 3 | 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 |
| Q96RU8 | TRIB1 | Tribbles homolog 1 | Homo sapiens (Human) | EV |
| Q92519 | TRIB2 | Tribbles homolog 2 | Homo sapiens (Human) | SS |
| Q96RU7 | TRIB3 | Tribbles homolog 3 | Homo sapiens (Human) | PR |
| 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 |
| Q8K4K3 | Trib2 | Tribbles homolog 2 | Mus musculus (Mouse) | SS |
| Q8K4K4 | Trib1 | Tribbles homolog 1 | 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 |
| MRATPLAASA | DVSCRKKPLE | FDDNIDAKCP | VLKRVRDEPE | PGPLPSLLPP | SPPPASDLSP |
| 70 | 80 | 90 | 100 | 110 | 120 |
| AVAPATRLGP | YILLEREQGS | CSYRALHCPT | GTEYTCKVYP | ASEAQAVLAP | YARLPTHQHV |
| 130 | 140 | 150 | 160 | 170 | 180 |
| ARPTEVLLGS | RLLYIFFTKT | HGDLHSLVRS | RRGIPESEAA | GLFRQMASAV | AHCHKHGLVL |
| 190 | 200 | 210 | 220 | 230 | 240 |
| RDLKLRRFVF | SNCERTKLVL | ENLEDACVMT | GSDDSLWDKH | ACPAYVGPEI | LSSRPSYSGK |
| 250 | 260 | 270 | 280 | 290 | 300 |
| AADVWSLGVA | LFTMLAGRYP | FHDSEPVLLF | GKIRRGTFAL | PEGLSAPARC | LIRCLLRKEP |
| 310 | 320 | 330 | 340 | 350 | |
| SERLVALGIL | LHPWLREDHG | RVSPPQSDRR | EMDQVVPDGP | QLEEAEEGEV | GLYG |