Q07174

SS
Gene name
Map3k8 (Cot, Tpl2)
Protein name
Mitogen-activated protein kinase kinase kinase 8
Names
Cancer Osaka thyroid oncogene, Proto-oncogene c-Cot, Serine/threonine-protein kinase cot, Tumor progression locus 2, TPL-2
Species
Drosophila melanogaster (Fruit fly)
KEGG Pathway
mmu:26410
EC number
2.7.11.24: Protein-serine/threonine kinases
Protein Class

Descriptions

MAPK1 encodes Mitogen-activated protein kinase 1, and is involved in diverse cellular responses by phosphorylating cytoplasmic and nuclear proteins. Unlike other MAP kinases, MAPK1 activates via dual phosphorylation of Thr-186 and Tyr-193 within the activation lip, and mutations at Q105 alone were sufficient for autoactivation. Additionally, in the inactive form, L76, Q10 and I87 form a structural unit that restrains intramolecular autophosphorylation by preventing interactions between activation lip residues and the catalytic base (D149) needed for phosphoryl transfer. Mutations at L76, I87 and additionally S153 increased basal specific activity via autophosphorylation of Thr-186 and Tyr-193.

Autoinhibitory domains (AIDs)

425-467 (C-terminal autoinhibitory domain) SS

Target domain

138-388 (Protein kinase domain)

Relief mechanism

PTM, Cleavage

Assay

Accessory elements

269-292 (Activation loop from InterPro)

Target domain

133-388 (Protein kinase domain)

Relief mechanism

Assay

References

Autoinhibited structure

Activated structure

1 structures for Q07174

Entry ID Method Resolution Chain Position Source
AF-Q07174-F1 Predicted AlphaFoldDB

3 variants for Q07174

Variant ID(s) Position Change Description Diseaes Association Provenance
rs218701417 35 A>E No Ensembl
rs258656766 101 R>C No Ensembl
rs29842835 171 I>V No Ensembl

No associated diseases with Q07174

3 regional properties for Q07174

Type Name Position InterPro Accession
domain Protein kinase domain 25 - 312 IPR000719
conserved_site Mitogen-activated protein (MAP) kinase, conserved site 60 - 166 IPR003527
binding_site Protein kinase, ATP binding site 31 - 55 IPR017441

Functions

Description
EC Number 2.7.11.24 Protein-serine/threonine kinases
Subcellular Localization
  • Nucleus
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

1 GO annotations of cellular component

Name Definition
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.

5 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
magnesium ion binding Binding to a magnesium (Mg) ion.
MAP kinase kinase kinase activity Catalysis of the phosphorylation and activation of a MAP kinase kinase; each MAP kinase kinase can be phosphorylated by any of several MAP kinase kinase kinases.
protein serine kinase activity Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate.
protein serine/threonine/tyrosine kinase activity Catalysis of the reactions: ATP + a protein serine = ADP + protein serine phosphate; ATP + a protein threonine = ADP + protein threonine phosphate; and ATP + a protein tyrosine = ADP + protein tyrosine phosphate.

2 GO annotations of biological process

Name Definition
cell cycle The progression of biochemical and morphological phases and events that occur in a cell during successive cell replication or nuclear replication events. Canonically, the cell cycle comprises the replication and segregation of genetic material followed by the division of the cell, but in endocycles or syncytial cells nuclear replication or nuclear division may not be followed by cell division.
immune system process Any process involved in the development or functioning of the immune system, an organismal system for calibrated responses to potential internal or invasive threats.

13 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
P25390 SSK22 Serine/threonine-protein kinase SSK22 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) PR
Q3SWY6 STK25 Serine/threonine-protein kinase 25 Bos taurus (Bovine) PR
O00506 STK25 Serine/threonine-protein kinase 25 Homo sapiens (Human) PR
Q9Y6E0 STK24 Serine/threonine-protein kinase 24 Homo sapiens (Human) PR
Q9P289 STK26 Serine/threonine-protein kinase 26 Homo sapiens (Human) PR
P41279 MAP3K8 Mitogen-activated protein kinase kinase kinase 8 Homo sapiens (Human) EV
Q9Z2W1 Stk25 Serine/threonine-protein kinase 25 Mus musculus (Mouse) PR
Q99JT2 Stk26 Serine/threonine-protein kinase 26 Mus musculus (Mouse) PR
Q99KH8 Stk24 Serine/threonine-protein kinase 24 Mus musculus (Mouse) PR
O08648 Map3k4 Mitogen-activated protein kinase kinase kinase 4 Mus musculus (Mouse) SS
B0LT89 Stk24 Serine/threonine-protein kinase 24 Rattus norvegicus (Rat) PR
Q63562 Map3k8 Mitogen-activated protein kinase kinase kinase 8 Rattus norvegicus (Rat) SS
H2L099 gck-1 Germinal center kinase 1 Caenorhabditis elegans PR
10 20 30 40 50 60
MSVSITKKFY KLDINRTEWE IPDIYQDLQP VGSGAYGQVS KAVVRGTNMH VAIKKLARPF
70 80 90 100 110 120
QSAVHAKRTY RELRLLKHMD HENVIGLLDI FHPHPANGSL ENFQQVYLVT HLMDADLNNI
130 140 150 160 170 180
IRMQHLSDDH VQFLVYQILR GLKYIHSAGV IHRDLKPSNI AVNEDCELRI LDFGLARPTE
190 200 210 220 230 240
NEMTGYVATR WYRAPEIMLN WMHYDQTVDI WSVGCIMAEL ITRRTLFPGT DHIHQLNLIM
250 260 270 280 290 300
EMLGTPPAEF LKKISSESAR SYIQSLPPMK GRSFKNVFKN ANPLAIDLLE KMLELDAEKR
310 320 330 340 350 360
ITAEEALSHP YLEKYAEPSV EQTSPPYDHS FEDMDLPVDK WKELIYKEVT NFKPPPSYAQ
VLKDVK