Q63562

SS
Gene name
Map3k8 (Tpl2)
Protein name
Mitogen-activated protein kinase kinase kinase 8
Names
EC 2.7.11.25 , Tumor progression locus 2 , TPL-2
Species
Homo sapiens (Human)
KEGG Pathway
rno:116596
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 Q63562

Entry ID Method Resolution Chain Position Source
AF-Q63562-F1 Predicted AlphaFoldDB

No variants for Q63562

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q63562

No associated diseases with Q63562

3 regional properties for Q63562

Type Name Position InterPro Accession
domain Protein kinase domain 20 - 316 IPR000719
active_site Serine/threonine-protein kinase, active site 148 - 160 IPR008271
binding_site Protein kinase, ATP binding site 26 - 50 IPR017441

Functions

Description
EC Number 2.7.11.24 Protein-serine/threonine kinases
Subcellular Localization
  • Cytoplasm
  • 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 kinase activity Catalysis of the phosphorylation of an amino acid residue in a protein, usually according to the reaction
protein serine kinase activity Catalysis of the reactions

5 GO annotations of biological process

Name Definition
cardiac ventricle development The process whose specific outcome is the progression of a cardiac ventricle over time, from its formation to the mature structure. A cardiac ventricle receives blood from a cardiac atrium and pumps it out of the heart.
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.
gap junction-mediated intercellular transport The movement of substances between cells via gap junctions. A gap junction is a fine cytoplasmic channel, found in animal cells, that connects the cytoplasm of one cell to that of an adjacent cell, allowing ions and other molecules to pass freely between the two cells.
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.
phosphorylation The process of introducing a phosphate group into a molecule, usually with the formation of a phosphoric ester, a phosphoric anhydride or a phosphoric amide.

12 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
Q07174 Map3k8 Mitogen-activated protein kinase kinase kinase 8 Mus musculus (Mouse) SS
B0LT89 Stk24 Serine/threonine-protein kinase 24 Rattus norvegicus (Rat) PR
H2L099 gck-1 Germinal center kinase 1 Caenorhabditis elegans PR
10 20 30 40 50 60
MSGPRAGFYR QELNKTVWEV PQRLQGLRPV GSGAYGSVCS AYDARLRQKV AVKKLSRPFQ
70 80 90 100 110 120
SLIHARRTYR ELRLLKHLKH ENVIGLLDVF TPATSIEDFS EVYLVTTLMG ADLNNIVKCQ
130 140 150 160 170 180
ALSDEHVQFL VYQLLRGLKY IHSAGIIHRD LKPSNVAVNE DCELRILDFG LARQADEEMT
190 200 210 220 230 240
GYVATRWYRA PEIMLNWMHY NQTVDIWSVG CIMAELLQGK ALFPGSDYID QLKRIMEVVG
250 260 270 280 290 300
TPSPEVLAKI SSEHARTYIQ SLPPMPQKDL SSIFRGANPL AIDLLGRMLV LDSDQRVSAA
310 320 330 340 350 360
EALAHAYFSQ YHDPEDEPEA EPYDESVEAK ERTLEEWKEL TYQEVLSFKP PEPPKPPGSL
EIEQ