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Protein

MAP kinase-interacting serine/threonine-protein kinase 1

Gene

MKNK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.4 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.2 Publications

Cofactori

Mg2+2 Publications

Enzyme regulationi

Phosphorylated and activated by the p38 kinases and kinases in the Erk pathway.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei78ATPPROSITE-ProRule annotation1 Publication1
Active sitei211Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi55 – 63ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • intracellular signal transduction Source: UniProtKB
  • peptidyl-serine phosphorylation Source: BHF-UCL
  • protein autophosphorylation Source: GO_Central
  • protein phosphorylation Source: UniProtKB
  • regulation of translation Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Translation regulation

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS01318-MONOMER.
ReactomeiR-HSA-1295596. Spry regulation of FGF signaling.
SignaLinkiQ9BUB5.
SIGNORiQ9BUB5.

Names & Taxonomyi

Protein namesi
Recommended name:
MAP kinase-interacting serine/threonine-protein kinase 1 (EC:2.7.11.1)
Alternative name(s):
MAP kinase signal-integrating kinase 1
Short name:
MAPK signal-integrating kinase 1
Short name:
Mnk1
Gene namesi
Name:MKNK1
Synonyms:MNK1
OrganismiHomo sapiens (Human)Imported
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:7110. MKNK1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi78K → M: Loss of kinase activity; when associated with D-232. 1 Publication1
Mutagenesisi232D → A: Loss of kinase activity; when associated with K-78. 1 Publication1
Mutagenesisi250T → A: Loss of kinase activity; when associated with T-255. 1 Publication1
Mutagenesisi255T → A: Loss of kinase activity; when associated with T-250. 1 Publication1
Mutagenesisi385T → D: Constitutively active. 1 Publication1

Organism-specific databases

DisGeNETi8569.
OpenTargetsiENSG00000079277.
PharmGKBiPA30829.

Chemistry databases

ChEMBLiCHEMBL4718.
GuidetoPHARMACOLOGYi2104.

Polymorphism and mutation databases

BioMutaiMKNK1.
DMDMi30316115.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000863341 – 465MAP kinase-interacting serine/threonine-protein kinase 1Add BLAST465

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei39PhosphoserineCombined sources1
Modified residuei221PhosphoserineCombined sources1
Modified residuei226PhosphoserineCombined sources1
Modified residuei250Phosphothreonine1 Publication1
Modified residuei255Phosphothreonine1 Publication1
Modified residuei385PhosphothreonineCombined sources1 Publication1
Modified residuei460PhosphoserineCombined sources1

Post-translational modificationi

Dual phosphorylation of Thr-250 and Thr-255 activates the kinase. Phosphorylation of Thr-385 activates the kinase. MAPK3/ERK1 is one of the kinases which activate MKNK1/MNK1. Phosphorylation by PAK2 leads to a reduced phosphorylation of EIF4G1.4 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9BUB5.
MaxQBiQ9BUB5.
PaxDbiQ9BUB5.
PeptideAtlasiQ9BUB5.
PRIDEiQ9BUB5.

PTM databases

iPTMnetiQ9BUB5.
PhosphoSitePlusiQ9BUB5.

Expressioni

Tissue specificityi

Ubiquitous.1 Publication

Gene expression databases

BgeeiENSG00000079277.
CleanExiHS_MKNK1.
ExpressionAtlasiQ9BUB5. baseline and differential.
GenevisibleiQ9BUB5. HS.

Organism-specific databases

HPAiHPA071293.

Interactioni

Subunit structurei

Interacts with the C-terminal regions of EIF4G1 and EIF4G2. Also binds to dephosphorylated ERK1 and ERK2, and to the p38 kinases.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
MAPK14Q165393EBI-73837,EBI-73946

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114138. 48 interactors.
IntActiQ9BUB5. 40 interactors.
MINTiMINT-85533.
STRINGi9606.ENSP00000361014.

Chemistry databases

BindingDBiQ9BUB5.

Structurei

Secondary structure

1465
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi44 – 46Combined sources3
Beta strandi48 – 57Combined sources10
Beta strandi59 – 68Combined sources10
Turni69 – 71Combined sources3
Beta strandi74 – 81Combined sources8
Helixi87 – 101Combined sources15
Beta strandi110 – 115Combined sources6
Beta strandi117 – 125Combined sources9
Helixi132 – 139Combined sources8
Helixi144 – 163Combined sources20
Helixi214 – 216Combined sources3
Beta strandi217 – 220Combined sources4
Beta strandi227 – 230Combined sources4
Beta strandi271 – 274Combined sources4
Helixi277 – 296Combined sources20
Helixi337 – 340Combined sources4
Helixi345 – 354Combined sources10
Turni359 – 361Combined sources3
Helixi365 – 370Combined sources6
Turni372 – 375Combined sources4
Helixi439 – 441Combined sources3
Helixi443 – 449Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2HW6X-ray2.50A/B37-382[»]
2Y9QX-ray1.55B434-451[»]
ProteinModelPortaliQ9BUB5.
SMRiQ9BUB5.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9BUB5.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini49 – 374Protein kinasePROSITE-ProRule annotationAdd BLAST326

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0607. Eukaryota.
ENOG410XQA9. LUCA.
GeneTreeiENSGT00830000128274.
HOVERGENiHBG106949.
InParanoidiQ9BUB5.
KOiK04372.
OMAiILTHIQK.
OrthoDBiEOG091G0G1X.
PhylomeDBiQ9BUB5.
TreeFamiTF314050.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 2 hits.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 11 Publication (identifier: Q9BUB5-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MVSSQKLEKP IEMGSSEPLP IADGDRRRKK KRRGRATDSL PGKFEDMYKL
60 70 80 90 100
TSELLGEGAY AKVQGAVSLQ NGKEYAVKII EKQAGHSRSR VFREVETLYQ
110 120 130 140 150
CQGNKNILEL IEFFEDDTRF YLVFEKLQGG SILAHIQKQK HFNEREASRV
160 170 180 190 200
VRDVAAALDF LHTKDKVSLC HLGWSAMAPS GLTAAPTSLG SSDPPTSASQ
210 220 230 240 250
VAGTTGIAHR DLKPENILCE SPEKVSPVKI CDFDLGSGMK LNNSCTPITT
260 270 280 290 300
PELTTPCGSA EYMAPEVVEV FTDQATFYDK RCDLWSLGVV LYIMLSGYPP
310 320 330 340 350
FVGHCGADCG WDRGEVCRVC QNKLFESIQE GKYEFPDKDW AHISSEAKDL
360 370 380 390 400
ISKLLVRDAK QRLSAAQVLQ HPWVQGQAPE KGLPTPQVLQ RNSSTMDLTL
410 420 430 440 450
FAAEAIALNR QLSQHEENEL AEEPEALADG LCSMKLSPPC KSRLARRRAL
460
AQAGRGEDRS PPTAL
Length:465
Mass (Da):51,342
Last modified:June 1, 2001 - v1
Checksum:iCAE225C35DCB2B43
GO
Isoform 21 Publication (identifier: Q9BUB5-2) [UniParc]FASTAAdd to basket
Also known as: MNK1a

The sequence of this isoform differs from the canonical sequence as follows:
     165-205: Missing.

Show »
Length:424
Mass (Da):47,402
Checksum:iDB39E49EC0BED990
GO
Isoform 3 (identifier: Q9BUB5-3) [UniParc]FASTAAdd to basket
Also known as: MNK1b

The sequence of this isoform differs from the canonical sequence as follows:
     165-205: Missing.
     377-465: QAPEKGLPTP...GEDRSPPTAL → EQQHNGPDALRS

Show »
Length:347
Mass (Da):39,104
Checksum:i1CCA03B12D39641F
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04080149K → Q.1 PublicationCorresponds to variant rs56351860dbSNPEnsembl.1
Natural variantiVAR_040802158L → V.1 PublicationCorresponds to variant rs56408722dbSNPEnsembl.1
Natural variantiVAR_040803308D → N.1 PublicationCorresponds to variant rs55791614dbSNPEnsembl.1
Natural variantiVAR_040804446R → Q.1 PublicationCorresponds to variant rs34881418dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_007352165 – 205Missing in isoform 2 and isoform 3. 2 PublicationsAdd BLAST41
Alternative sequenceiVSP_017515377 – 465QAPEK…PPTAL → EQQHNGPDALRS in isoform 3. 1 PublicationAdd BLAST89

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB000409 mRNA. Translation: BAA19885.1.
AY355461 mRNA. Translation: AAQ84219.1.
AL136373 Genomic DNA. Translation: CAI14764.1.
AL136373 Genomic DNA. Translation: CAI14765.1.
CH471059 Genomic DNA. Translation: EAX06900.1.
CH471059 Genomic DNA. Translation: EAX06902.1.
CH471059 Genomic DNA. Translation: EAX06904.1.
CH471059 Genomic DNA. Translation: EAX06905.1.
BC002755 mRNA. Translation: AAH02755.1.
CCDSiCCDS30705.1. [Q9BUB5-3]
CCDS44134.1. [Q9BUB5-2]
CCDS538.1. [Q9BUB5-1]
RefSeqiNP_001129025.1. NM_001135553.2. [Q9BUB5-2]
NP_003675.2. NM_003684.5. [Q9BUB5-1]
NP_945324.1. NM_198973.3. [Q9BUB5-3]
XP_006711063.1. XM_006711000.1. [Q9BUB5-2]
XP_016858148.1. XM_017002659.1. [Q9BUB5-3]
UniGeneiHs.371594.

Genome annotation databases

EnsembliENST00000371945; ENSP00000361013; ENSG00000079277. [Q9BUB5-2]
ENST00000371946; ENSP00000361014; ENSG00000079277. [Q9BUB5-1]
ENST00000428112; ENSP00000411135; ENSG00000079277. [Q9BUB5-3]
GeneIDi8569.
KEGGihsa:8569.
UCSCiuc001cqb.5. human. [Q9BUB5-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB000409 mRNA. Translation: BAA19885.1.
AY355461 mRNA. Translation: AAQ84219.1.
AL136373 Genomic DNA. Translation: CAI14764.1.
AL136373 Genomic DNA. Translation: CAI14765.1.
CH471059 Genomic DNA. Translation: EAX06900.1.
CH471059 Genomic DNA. Translation: EAX06902.1.
CH471059 Genomic DNA. Translation: EAX06904.1.
CH471059 Genomic DNA. Translation: EAX06905.1.
BC002755 mRNA. Translation: AAH02755.1.
CCDSiCCDS30705.1. [Q9BUB5-3]
CCDS44134.1. [Q9BUB5-2]
CCDS538.1. [Q9BUB5-1]
RefSeqiNP_001129025.1. NM_001135553.2. [Q9BUB5-2]
NP_003675.2. NM_003684.5. [Q9BUB5-1]
NP_945324.1. NM_198973.3. [Q9BUB5-3]
XP_006711063.1. XM_006711000.1. [Q9BUB5-2]
XP_016858148.1. XM_017002659.1. [Q9BUB5-3]
UniGeneiHs.371594.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2HW6X-ray2.50A/B37-382[»]
2Y9QX-ray1.55B434-451[»]
ProteinModelPortaliQ9BUB5.
SMRiQ9BUB5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114138. 48 interactors.
IntActiQ9BUB5. 40 interactors.
MINTiMINT-85533.
STRINGi9606.ENSP00000361014.

Chemistry databases

BindingDBiQ9BUB5.
ChEMBLiCHEMBL4718.
GuidetoPHARMACOLOGYi2104.

PTM databases

iPTMnetiQ9BUB5.
PhosphoSitePlusiQ9BUB5.

Polymorphism and mutation databases

BioMutaiMKNK1.
DMDMi30316115.

Proteomic databases

EPDiQ9BUB5.
MaxQBiQ9BUB5.
PaxDbiQ9BUB5.
PeptideAtlasiQ9BUB5.
PRIDEiQ9BUB5.

Protocols and materials databases

DNASUi8569.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000371945; ENSP00000361013; ENSG00000079277. [Q9BUB5-2]
ENST00000371946; ENSP00000361014; ENSG00000079277. [Q9BUB5-1]
ENST00000428112; ENSP00000411135; ENSG00000079277. [Q9BUB5-3]
GeneIDi8569.
KEGGihsa:8569.
UCSCiuc001cqb.5. human. [Q9BUB5-1]

Organism-specific databases

CTDi8569.
DisGeNETi8569.
GeneCardsiMKNK1.
HGNCiHGNC:7110. MKNK1.
HPAiHPA071293.
MIMi606724. gene.
neXtProtiNX_Q9BUB5.
OpenTargetsiENSG00000079277.
PharmGKBiPA30829.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0607. Eukaryota.
ENOG410XQA9. LUCA.
GeneTreeiENSGT00830000128274.
HOVERGENiHBG106949.
InParanoidiQ9BUB5.
KOiK04372.
OMAiILTHIQK.
OrthoDBiEOG091G0G1X.
PhylomeDBiQ9BUB5.
TreeFamiTF314050.

Enzyme and pathway databases

BioCyciZFISH:HS01318-MONOMER.
ReactomeiR-HSA-1295596. Spry regulation of FGF signaling.
SignaLinkiQ9BUB5.
SIGNORiQ9BUB5.

Miscellaneous databases

EvolutionaryTraceiQ9BUB5.
GeneWikiiMKNK1.
GenomeRNAii8569.
PROiQ9BUB5.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000079277.
CleanExiHS_MKNK1.
ExpressionAtlasiQ9BUB5. baseline and differential.
GenevisibleiQ9BUB5. HS.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 2 hits.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMKNK1_HUMAN
AccessioniPrimary (citable) accession number: Q9BUB5
Secondary accession number(s): D3DQ20
, D3DQ21, O00312, Q5TC06, Q5TC07, Q6V0N6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 30, 2003
Last sequence update: June 1, 2001
Last modified: November 2, 2016
This is version 159 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.