Q5E9X2

EV
Gene name
MAP2K6
Protein name
Dual specificity mitogen-activated protein kinase kinase 6
Names
MAP kinase kinase 6, MAPKK 6, MAPK/ERK kinase 6, MEK 6
Species
Bos taurus (Bovine)
KEGG Pathway
bta:286883
EC number
2.7.12.2: Dual-specificity kinases (those acting on Ser/Thr and Tyr residues)
Protein Class

Descriptions

(Annotation based on sequence homology with P52564). MAP2K6 is Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. The mechanism of autoinhibition of MAP2K6 differents from those observed for MAP2K1/4 regulation. The activation loop consisting of 3 short α-helices (AH1, AH2, AH3), which are significant in forming the autoinhibition state. AH1, AH2 and AH3 stabilizes the MAP2K6 in the inactive conformation by several interactions between themselves and main body of kinase domain. The phospho-AH2 presumably releases the molecular break and triggers a conformational transitions to the flexible states.

Autoinhibitory domains (AIDs)

Accessory elements

196-218 (Activation loop from InterPro)

Target domain

53-314 (Protein kinase domain)

Relief mechanism

Assay

References

Autoinhibited structure

Activated structure

1 structures for Q5E9X2

Entry ID Method Resolution Chain Position Source
AF-Q5E9X2-F1 Predicted AlphaFoldDB

41 variants for Q5E9X2

Variant ID(s) Position Change Description Diseaes Association Provenance
rs470672358 12 G>A No Ensembl
rs463637168 48 V>G No Ensembl
rs441854262 52 D>G No Ensembl
rs474782667 56 I>T No Ensembl
rs483195700 58 E>* No Ensembl
rs451609830 64 Y>S No Ensembl
rs469681892 66 V>A No Ensembl
rs457460103 67 V>G No Ensembl
rs435779822 70 M>R No Ensembl
rs446544195 74 P>A No Ensembl
rs446544195 74 P>S No Ensembl
rs464214714 76 E>D No Ensembl
rs479324672 76 E>G No Ensembl
rs445611134 78 I>N No Ensembl
rs445611134 78 I>S No Ensembl
rs481831884 79 M>I No Ensembl
rs443493724 81 V>G No Ensembl
rs448468354 83 R>P No Ensembl
rs481265427 84 I>S No Ensembl
rs441148475 92 E>Q No Ensembl
rs459152360 105 R>S No Ensembl
rs468896996 135 S>A No Ensembl
rs1117023645 146 K>I No Ensembl
rs446103927 179 D>E No Ensembl
rs482067516 180 V>G No Ensembl
rs41932221 246 T>S No Ensembl
rs481996653 249 E>G No Ensembl
rs445896215 249 E>Q No Ensembl
rs1116681871 251 A>T No Ensembl
rs444518550 258 D>E No Ensembl
rs462158540 262 T>A No Ensembl
rs440368419 262 T>I No Ensembl
rs462158540 262 T>P No Ensembl
rs451877550 270 V>G No Ensembl
rs439810197 273 E>A No Ensembl
rs475801578 278 L>P No Ensembl
rs457426189 290 F>C No Ensembl
rs435276031 291 T>P No Ensembl
rs437033549 329 K>R No Ensembl
rs469978254 332 L>R No Ensembl
rs448221867 333 G>A No Ensembl

No associated diseases with Q5E9X2

3 regional properties for Q5E9X2

Type Name Position InterPro Accession
domain Protein kinase domain 404 - 659 IPR000719
active_site Serine/threonine-protein kinase, active site 521 - 533 IPR008271
binding_site Protein kinase, ATP binding site 410 - 433 IPR017441

Functions

Description
EC Number 2.7.12.2 Dual-specificity kinases (those acting on Ser/Thr and Tyr residues)
Subcellular Localization
  • Nucleus
  • Cytoplasm
  • Cytoplasm, cytoskeleton
  • Binds to microtubules
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

3 GO annotations of cellular component

Name Definition
cytoskeleton A cellular structure that forms the internal framework of eukaryotic and prokaryotic cells. The cytoskeleton includes intermediate filaments, microfilaments, microtubules, the microtrabecular lattice, and other structures characterized by a polymeric filamentous nature and long-range order within the cell. The various elements of the cytoskeleton not only serve in the maintenance of cellular shape but also have roles in other cellular functions, including cellular movement, cell division, endocytosis, and movement of organelles.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
nucleoplasm That part of the nuclear content other than the chromosomes or the nucleolus.

8 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
MAP kinase kinase activity Catalysis of the concomitant phosphorylation of threonine (T) and tyrosine (Y) residues in a Thr-Glu-Tyr (TEY) thiolester sequence in a MAP kinase (MAPK) substrate.
phosphatase activator activity Binds to and increases the activity of a phosphatase, an enzyme which catalyzes of the removal of a phosphate group from a substrate molecule.
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 serine kinase activity Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate.
protein serine/threonine kinase activator activity Binds to and increases the activity of a protein serine/threonine kinase.
protein serine/threonine kinase activity Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate, and ATP + protein threonine = ADP + protein threonine phosphate.
protein tyrosine kinase activity Catalysis of the reaction: ATP + a protein tyrosine = ADP + protein tyrosine phosphate.

7 GO annotations of biological process

Name Definition
apoptotic process A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died.
bone development The process whose specific outcome is the progression of bone over time, from its formation to the mature structure. Bone is the hard skeletal connective tissue consisting of both mineral and cellular components.
cardiac muscle contraction Muscle contraction of cardiac muscle tissue.
negative regulation of cold-induced thermogenesis Any process that stops, prevents, or reduces the rate of cold-induced thermogenesis.
osteoblast differentiation The process whereby a relatively unspecialized cell acquires the specialized features of an osteoblast, a mesodermal or neural crest cell that gives rise to bone.
positive regulation of MAP kinase activity Any process that activates or increases the frequency, rate or extent of MAP kinase activity.
stress-activated MAPK cascade The series of molecular signals in which a stress-activated MAP kinase cascade relays a signal; MAP kinase cascades involve at least three protein kinase activities and culminate in the phosphorylation and activation of a MAP kinase.

12 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
P46734 MAP2K3 Dual specificity mitogen-activated protein kinase kinase 3 Homo sapiens (Human) SS
P52564 MAP2K6 Dual specificity mitogen-activated protein kinase kinase 6 Homo sapiens (Human) EV
O14733 MAP2K7 Dual specificity mitogen-activated protein kinase kinase 7 Homo sapiens (Human) PR
P45985 MAP2K4 Dual specificity mitogen-activated protein kinase kinase 4 Homo sapiens (Human) EV
O09110 Map2k3 Dual specificity mitogen-activated protein kinase kinase 3 Mus musculus (Mouse) PR
P70236 Map2k6 Dual specificity mitogen-activated protein kinase kinase 6 Mus musculus (Mouse) EV
Q8CE90 Map2k7 Dual specificity mitogen-activated protein kinase kinase 7 Mus musculus (Mouse) PR
P47809 Map2k4 Dual specificity mitogen-activated protein kinase kinase 4 Mus musculus (Mouse) EV
G5EDF7 sek-1 Dual specificity mitogen-activated protein kinase kinase sek-1 Caenorhabditis elegans PR
G5EDT6 jkk-1 Dual specificity mitogen-activated protein kinase kinase jkk-1 Caenorhabditis elegans PR
Q21307 mek-1 Dual specificity mitogen-activated protein kinase kinase mek-1 Caenorhabditis elegans PR
Q9DGE0 map2k6 Dual specificity mitogen-activated protein kinase kinase 6 Danio rerio (Zebrafish) (Brachydanio rerio) PR
10 20 30 40 50 60
MSQSKGKKRN PGLKIPKEAF EQPQTSSTPP RDLDSKACIS IGNQNFEVKA DDLEPIVELG
70 80 90 100 110 120
RGAYGVVEKM RHVPSEQIMA VKRIRATVNS QEQKRLLMDL DISMRTVDCP FTVTFYGALF
130 140 150 160 170 180
REGDVWICME LMDTSLDKFY KQVIDKGQTI PEDILGKIAV SIVKALEHLH SKLSVIHRDV
190 200 210 220 230 240
KPSNVLINAL GQVKMCDFGI SGYLVDSVAK TIDAGCKPYM APERINPELN QKGYSVKSDI
250 260 270 280 290 300
WSLGITMIEL AILRFPYDSW GTPFQQLKQV VEEPSPQLPA DKFSEEFVDF TSQCLKKNSK
310 320 330
ERPTYPELMQ HPFFTLHESK ATDVASFVKS ILGD