UniProtKB - Q9HBH9 (MKNK2_HUMAN)
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Protein
MAP kinase-interacting serine/threonine-protein kinase 2
Gene
MKNK2
Organism
Homo sapiens (Human)
Status
Functioni
Serine/threonine-protein kinase that phosphorylates SFPQ/PSF, HNRNPA1 and EIF4E. May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap. Required for mediating PP2A-inhibition-induced EIF4E phosphorylation. Triggers EIF4E shuttling from cytoplasm to nucleus. Isoform 1 displays a high basal kinase activity, but isoform 2 exhibits a very low kinase activity. Acts as a mediator of the suppressive effects of IFNgamma on hematopoiesis. Negative regulator for signals that control generation of arsenic trioxide As2O3-dependent apoptosis and anti-leukemic responses. Involved in anti-apoptotic signaling in response to serum withdrawal.9 Publications
Catalytic activityi
ATP + a protein = ADP + a phosphoprotein.1 Publication
Cofactori
Protein has several cofactor binding sites:Enzyme regulationi
Inhibited by CGP57380 and staurosporine. Activated by phosphorylation in a negative-feedback regulatory manner in response to chemotherapy (e.g. cytarabine) and thus impairs the generation of antileukemic responses.6 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 113 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 205 | Proton acceptorPROSITE-ProRule annotation | 1 | |
Binding sitei | 209 | Staurosporine1 Publication | 1 | |
Metal bindingi | 299 | Zinc2 Publications | 1 | |
Metal bindingi | 311 | Zinc2 Publications | 1 | |
Metal bindingi | 314 | Zinc2 Publications | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 90 – 98 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB
- calcium-dependent protein serine/threonine kinase activity Source: GO_Central
- calmodulin binding Source: GO_Central
- calmodulin-dependent protein kinase activity Source: GO_Central
- metal ion binding Source: UniProtKB-KW
- protein serine/threonine kinase activity Source: UniProtKB
GO - Biological processi
- cell surface receptor signaling pathway Source: ProtInc
- cellular response to arsenic-containing substance Source: UniProtKB
- extrinsic apoptotic signaling pathway in absence of ligand Source: Ensembl
- hemopoiesis Source: UniProtKB
- intracellular signal transduction Source: UniProtKB
- peptidyl-serine phosphorylation Source: GO_Central
- protein autophosphorylation Source: GO_Central
- protein phosphorylation Source: UniProtKB
- regulation of translation Source: UniProtKB-KW
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Biological process | Apoptosis, Translation regulation |
Ligand | ATP-binding, Magnesium, Metal-binding, Nucleotide-binding, Zinc |
Enzyme and pathway databases
SignaLinki | Q9HBH9. |
SIGNORi | Q9HBH9. |
Names & Taxonomyi
Protein namesi | Recommended name: MAP kinase-interacting serine/threonine-protein kinase 2 (EC:2.7.11.1)Alternative name(s): MAP kinase signal-integrating kinase 2 Short name: MAPK signal-integrating kinase 2 Short name: Mnk2 |
Gene namesi | Name:MKNK2 Synonyms:GPRK7, MNK2 |
Organismi | Homo sapiens (Human)Imported |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000099875.14. |
HGNCi | HGNC:7111. MKNK2. |
MIMi | 605069. gene. |
neXtProti | NX_Q9HBH9. |
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 228 | D → G: Reduced phosphorylation. 1 Publication | 1 | |
Mutagenesisi | 244 | T → A: Loss of kinase activity; when associated with T-249. 1 Publication | 1 | |
Mutagenesisi | 249 | T → A: Loss of kinase activity; when associated with T-244. 1 Publication | 1 | |
Mutagenesisi | 379 | T → D: Constitutively active. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 2872. |
OpenTargetsi | ENSG00000099875. |
PharmGKBi | PA30830. |
Chemistry databases
ChEMBLi | CHEMBL4204. |
GuidetoPHARMACOLOGYi | 2105. |
Polymorphism and mutation databases
BioMutai | MKNK2. |
DMDMi | 90102033. |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000086336 | 1 – 465 | MAP kinase-interacting serine/threonine-protein kinase 2Add BLAST | 465 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 74 | PhosphoserineBy similarity | 1 | |
Modified residuei | 244 | Phosphothreonine1 Publication | 1 | |
Modified residuei | 249 | Phosphothreonine1 Publication | 1 | |
Modified residuei | 379 | Phosphothreonine1 Publication | 1 | |
Modified residuei | 437 | PhosphoserineBy similarity | 1 | |
Modified residuei | 440 | PhosphoserineBy similarity | 1 | |
Modified residuei | 452 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Dual phosphorylation of Thr-244 and Thr-249 activates the kinase. Phosphorylation of Thr-379 activates the kinase. Phosphorylated upon arsenic trioxide As2O3 treatment. Phosphorylated by MAPK1/ERK2, MAPK11 and MAPK14. Dephosphorylated by PP2A.4 Publications
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | Q9HBH9. |
PaxDbi | Q9HBH9. |
PeptideAtlasi | Q9HBH9. |
PRIDEi | Q9HBH9. |
PTM databases
iPTMneti | Q9HBH9. |
PhosphoSitePlusi | Q9HBH9. |
Expressioni
Tissue specificityi
Ubiquitously expressed in all tissues examined. Isoform 2 is expressed at higher levels in the ovary than is isoform 1.1 Publication
Gene expression databases
Bgeei | ENSG00000099875. |
CleanExi | HS_MKNK2. |
ExpressionAtlasi | Q9HBH9. baseline and differential. |
Genevisiblei | Q9HBH9. HS. |
Organism-specific databases
HPAi | CAB037253. HPA021875. HPA053989. |
Interactioni
Subunit structurei
Monomer. Interacts with the C-terminal regions of EIF4G1 and EIF4G2; this interaction is promoted when MAPK pathways are repressed but repressed upon ERK proteins activation. Also binds to dephosphorylated MAPK3/ERK1 and MAPK1/ERK2. Isoform 1 interaction with phosphorylated MAPK3/ERK1 and MAPK1/ERK2 protects it from dephosphorylation and inactivation. Isoform 2 interacts with ESR2 and EIF4E in the nucleus.6 Publications
Binary interactionsi
With | Entry | #Exp. | IntAct | Notes |
---|---|---|---|---|
MAPK14 | Q16539 | 3 | EBI-2864341,EBI-73946 |
GO - Molecular functioni
- calmodulin binding Source: GO_Central
Protein-protein interaction databases
BioGridi | 109130. 39 interactors. |
IntActi | Q9HBH9. 34 interactors. |
STRINGi | 9606.ENSP00000250896. |
Chemistry databases
BindingDBi | Q9HBH9. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more detailsFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Beta strandi | 74 – 76 | Combined sources | 3 | |
Turni | 79 – 81 | Combined sources | 3 | |
Beta strandi | 83 – 85 | Combined sources | 3 | |
Beta strandi | 94 – 102 | Combined sources | 9 | |
Beta strandi | 104 – 106 | Combined sources | 3 | |
Beta strandi | 109 – 116 | Combined sources | 8 | |
Helixi | 123 – 135 | Combined sources | 13 | |
Beta strandi | 145 – 151 | Combined sources | 7 | |
Beta strandi | 154 – 160 | Combined sources | 7 | |
Helixi | 167 – 174 | Combined sources | 8 | |
Helixi | 179 – 198 | Combined sources | 20 | |
Helixi | 208 – 210 | Combined sources | 3 | |
Beta strandi | 211 – 214 | Combined sources | 4 | |
Beta strandi | 216 – 219 | Combined sources | 4 | |
Beta strandi | 221 – 224 | Combined sources | 4 | |
Helixi | 254 – 256 | Combined sources | 3 | |
Helixi | 259 – 264 | Combined sources | 6 | |
Helixi | 267 – 272 | Combined sources | 6 | |
Helixi | 273 – 275 | Combined sources | 3 | |
Helixi | 276 – 290 | Combined sources | 15 | |
Helixi | 312 – 324 | Combined sources | 13 | |
Helixi | 331 – 334 | Combined sources | 4 | |
Helixi | 339 – 348 | Combined sources | 10 | |
Turni | 353 – 355 | Combined sources | 3 | |
Helixi | 359 – 364 | Combined sources | 6 | |
Turni | 366 – 368 | Combined sources | 3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2AC3 | X-ray | 2.10 | A | 72-385 | [»] | |
2AC5 | X-ray | 3.20 | A | 72-385 | [»] | |
2HW7 | X-ray | 2.71 | A | 72-385 | [»] | |
ProteinModelPortali | Q9HBH9. | |||||
SMRi | Q9HBH9. | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q9HBH9. |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 84 – 388 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 305 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 160 – 162 | Staurosporine binding | 3 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 60 – 66 | Nuclear localization signal | 7 | |
Motifi | 444 – 448 | MAP kinase bindingBy similarity | 5 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0607. Eukaryota. ENOG410XQA9. LUCA. |
GeneTreei | ENSGT00900000140876. |
HOVERGENi | HBG106949. |
InParanoidi | Q9HBH9. |
KOi | K04372. |
OMAi | EAIAMNR. |
OrthoDBi | EOG091G0G1X. |
PhylomeDBi | Q9HBH9. |
Family and domain databases
InterProi | View protein in InterPro IPR011009. Kinase-like_dom_sf. IPR000719. Prot_kinase_dom. IPR017441. Protein_kinase_ATP_BS. IPR008271. Ser/Thr_kinase_AS. |
Pfami | View protein in Pfam PF00069. Pkinase. 1 hit. |
SMARTi | View protein in SMART SM00220. S_TKc. 1 hit. |
SUPFAMi | SSF56112. SSF56112. 1 hit. |
PROSITEi | View protein in PROSITE PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. |
s (5)i Sequence
Sequence statusi: Complete.
This entry describes 5 produced by isoformsialternative splicing. AlignAdd to basket
Isoform 11 Publication (identifier: Q9HBH9-1) [UniParc]FASTAAdd to basket
Also known as: 2a1 Publication
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
10 20 30 40 50
MVQKKPAELQ GFHRSFKGQN PFELAFSLDQ PDHGDSDFGL QCSARPDMPA
60 70 80 90 100
SQPIDIPDAK KRGKKKKRGR ATDSFSGRFE DVYQLQEDVL GEGAHARVQT
110 120 130 140 150
CINLITSQEY AVKIIEKQPG HIRSRVFREV EMLYQCQGHR NVLELIEFFE
160 170 180 190 200
EEDRFYLVFE KMRGGSILSH IHKRRHFNEL EASVVVQDVA SALDFLHNKG
210 220 230 240 250
IAHRDLKPEN ILCEHPNQVS PVKICDFDLG SGIKLNGDCS PISTPELLTP
260 270 280 290 300
CGSAEYMAPE VVEAFSEEAS IYDKRCDLWS LGVILYILLS GYPPFVGRCG
310 320 330 340 350
SDCGWDRGEA CPACQNMLFE SIQEGKYEFP DKDWAHISCA AKDLISKLLV
360 370 380 390 400
RDAKQRLSAA QVLQHPWVQG CAPENTLPTP MVLQRNSCAK DLTSFAAEAI
410 420 430 440 450
AMNRQLAQHD EDLAEEEAAG QGQPVLVRAT SRCLQLSPPS QSKLAQRRQR
460
ASLSSAPVVL VGDHA
Isoform 31 Publication (identifier: Q9HBH9-3)
Sequence is not available
Length:–
Mass (Da):–
Isoform 41 Publication (identifier: Q9HBH9-4)
Sequence is not available
Length:–
Mass (Da):–
Isoform 51 Publication (identifier: Q9HBH9-5)
Sequence is not available
Length:–
Mass (Da):–
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 261 | V → L in AAF17226 (Ref. 2) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_051648 | 10 | Q → K. Corresponds to variant dbSNP:rs3746101Ensembl. | 1 | |
Natural variantiVAR_040805 | 73 | D → N1 PublicationCorresponds to variant dbSNP:rs56158214Ensembl. | 1 | |
Natural variantiVAR_051649 | 428 | R → Q. Corresponds to variant dbSNP:rs34475638Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_007353 | 386 – 414 | NSCAK…DEDLA → WDSHFLLPPHPCRIHVRPGG LVRTVTVNE in isoform 2. 3 PublicationsAdd BLAST | 29 | |
Alternative sequenceiVSP_007354 | 415 – 465 | Missing in isoform 2. 3 PublicationsAdd BLAST | 51 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF237775 mRNA. Translation: AAG26336.1. AF237776 mRNA. Translation: AAG26337.1. AF125532 mRNA. Translation: AAF17226.1. BC073140 mRNA. Translation: AAH73140.1. |
CCDSi | CCDS12079.1. [Q9HBH9-2] CCDS12080.1. [Q9HBH9-1] |
RefSeqi | NP_060042.2. NM_017572.3. [Q9HBH9-2] NP_951009.1. NM_199054.2. [Q9HBH9-1] |
UniGenei | Hs.515032. |
Genome annotation databases
Ensembli | ENST00000250896; ENSP00000250896; ENSG00000099875. [Q9HBH9-1] ENST00000309340; ENSP00000309485; ENSG00000099875. [Q9HBH9-2] ENST00000591601; ENSP00000467811; ENSG00000099875. [Q9HBH9-1] |
GeneIDi | 2872. |
KEGGi | hsa:2872. |
UCSCi | uc002lus.3. human. [Q9HBH9-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Entry informationi
Entry namei | MKNK2_HUMAN | |
Accessioni | Q9HBH9Primary (citable) accession number: Q9HBH9 Secondary accession number(s): Q6GPI3 Q9Y2N6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 30, 2003 |
Last sequence update: | March 7, 2006 | |
Last modified: | March 28, 2018 | |
This is version 170 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |