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Q9BUB5 (MKNK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:MKNK1
Synonyms:MNK1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length465 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.2 Ref.3 Ref.7

Catalytic activity

ATP + a protein = ADP + a phosphoprotein. Ref.1 Ref.2

Cofactor

Magnesium. Ref.1 Ref.2

Enzyme regulation

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

Subunit structure

Interacts with the C-terminal regions of EIF4G1 and EIF4G2. Also binds to dephosphorylated ERK1 and ERK2, and to the p38 kinases. Ref.7 UniProtKB O08605

Subcellular location

Isoform 2: Cytoplasm.

Isoform 3: Cytoplasm. Nucleus Ref.3.

Tissue specificity

Ubiquitous. Ref.3

Post-translational modification

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.

Sequence similarities

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.

Contains 1 protein kinase domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MAPK14Q165393EBI-73837,EBI-73946

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 Ref.2 (identifier: Q9BUB5-1)

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.
Isoform 2 Ref.1 (identifier: Q9BUB5-2)

Also known as: MNK1a;

The sequence of this isoform differs from the canonical sequence as follows:
     165-205: Missing.
Isoform 3 (identifier: Q9BUB5-3)

Also known as: MNK1b;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 465465MAP kinase-interacting serine/threonine-protein kinase 1
PRO_0000086334

Regions

Domain49 – 374326Protein kinase
Nucleotide binding55 – 639ATP By similarity UniProtKB P49137

Sites

Active site2111Proton acceptor By similarity UniProtKB P49137
Binding site781ATP Ref.2

Amino acid modifications

Modified residue391Phosphoserine; by PAK2 By similarity
Modified residue2501Phosphothreonine Ref.2
Modified residue2551Phosphothreonine Ref.2
Modified residue3851Phosphothreonine Ref.2
Modified residue4601Phosphoserine Ref.9

Natural variations

Alternative sequence165 – 20541Missing in isoform 2 and isoform 3.
VSP_007352
Alternative sequence377 – 46589QAPEK…PPTAL → EQQHNGPDALRS in isoform 3.
VSP_017515
Natural variant491K → Q. Ref.10
Corresponds to variant rs56351860 [ dbSNP | Ensembl ].
VAR_040801
Natural variant1581L → V. Ref.10
Corresponds to variant rs56408722 [ dbSNP | Ensembl ].
VAR_040802
Natural variant3081D → N. Ref.10
Corresponds to variant rs55791614 [ dbSNP | Ensembl ].
VAR_040803
Natural variant4461R → Q. Ref.10
Corresponds to variant rs34881418 [ dbSNP | Ensembl ].
VAR_040804

Experimental info

Mutagenesis781K → M: Loss of kinase activity; when associated with D-232. Ref.2
Mutagenesis2321D → A: Loss of kinase activity; when associated with K-78. Ref.2
Mutagenesis2501T → A: Loss of kinase activity; when associated with T-255. Ref.2
Mutagenesis2551T → A: Loss of kinase activity; when associated with T-250. Ref.2
Mutagenesis3851T → D: Constitutively active. Ref.2

Secondary structure

........................................... 465
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 1, 2001. Version 1.
Checksum: CAE225C35DCB2B43

FASTA46551,342
        10         20         30         40         50         60 
MVSSQKLEKP IEMGSSEPLP IADGDRRRKK KRRGRATDSL PGKFEDMYKL TSELLGEGAY 

        70         80         90        100        110        120 
AKVQGAVSLQ NGKEYAVKII EKQAGHSRSR VFREVETLYQ CQGNKNILEL IEFFEDDTRF 

       130        140        150        160        170        180 
YLVFEKLQGG SILAHIQKQK HFNEREASRV VRDVAAALDF LHTKDKVSLC HLGWSAMAPS 

       190        200        210        220        230        240 
GLTAAPTSLG SSDPPTSASQ VAGTTGIAHR DLKPENILCE SPEKVSPVKI CDFDLGSGMK 

       250        260        270        280        290        300 
LNNSCTPITT PELTTPCGSA EYMAPEVVEV FTDQATFYDK RCDLWSLGVV LYIMLSGYPP 

       310        320        330        340        350        360 
FVGHCGADCG WDRGEVCRVC QNKLFESIQE GKYEFPDKDW AHISSEAKDL ISKLLVRDAK 

       370        380        390        400        410        420 
QRLSAAQVLQ HPWVQGQAPE KGLPTPQVLQ RNSSTMDLTL FAAEAIALNR QLSQHEENEL 

       430        440        450        460 
AEEPEALADG LCSMKLSPPC KSRLARRRAL AQAGRGEDRS PPTAL 

« Hide

Isoform 2 (MNK1a) [UniParc].

Checksum: DB39E49EC0BED990
Show »

FASTA42447,402
Isoform 3 (MNK1b) [UniParc].

Checksum: 1CCA03B12D39641F
Show »

FASTA34739,104

References

« Hide 'large scale' references
[1]"MNK1, a new MAP kinase-activated protein kinase, isolated by a novel expression screening method for identifying protein kinase substrates."
Fukunaga R., Hunter T.
EMBO J. 16:1921-1933(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, PHOSPHORYLATION BY MAPK3/ERK1, ENZYME REGULATION.
Tissue: Cervix carcinoma.
[2]"Negative regulation of protein translation by mitogen-activated protein kinase-interacting kinases 1 and 2."
Knauf U., Tschopp C., Gram H.
Mol. Cell. Biol. 21:5500-5511(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, PHOSPHORYLATION AT THR-250; THR-255 AND THR-385, MUTAGENESIS OF LYS-78; ASP-232; THR-250; THR-255 AND THR-385.
Tissue: T-cell.
[3]"Identification and molecular characterization of Mnk1b, a splice variant of human MAP kinase-interacting kinase Mnk1."
O'Loghlen A., Gonzalez V.M., Pineiro D., Perez-Morgado M.I., Salinas M., Martin M.E.
Exp. Cell Res. 299:343-355(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, TISSUE SPECIFICITY, PHOSPHORYLATION, SUBCELLULAR LOCATION.
[4]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Placenta.
[7]"Human eukaryotic translation initiation factor 4G (eIF4G) recruits mnk1 to phosphorylate eIF4E."
Pyronnet S., Imataka H., Gingras A.-C., Fukunaga R., Hunter T., Sonenberg N.
EMBO J. 18:270-279(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH EIF4G1 AND EIF4G2.
[8]"Phosphorylation of Mnk1 by caspase-activated Pak2/gamma-PAK inhibits phosphorylation and interaction of eIF4G with Mnk."
Orton K.C., Ling J., Waskiewicz A.J., Cooper J.A., Merrick W.C., Korneeva N.L., Rhoads R.E., Sonenberg N., Traugh J.A.
J. Biol. Chem. 279:38649-38657(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY PAK2.
[9]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-460, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLN-49; VAL-158; ASN-308 AND GLN-446.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001129025.1. NM_001135553.2.
NP_003675.2. NM_003684.5.
NP_945324.1. NM_198973.3.
UniGeneHs.371594.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2HW6X-ray2.50A/B37-382[»]
2Y9QX-ray1.55B434-451[»]
ProteinModelPortalQ9BUB5.
SMRQ9BUB5. Positions 39-407.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114138. 24 interactions.
IntActQ9BUB5. 16 interactions.
MINTMINT-85533.
STRING9606.ENSP00000361014.

Chemistry

BindingDBQ9BUB5.
ChEMBLCHEMBL4718.
GuidetoPHARMACOLOGY2104.

PTM databases

PhosphoSiteQ9BUB5.

Polymorphism databases

DMDM30316115.

Proteomic databases

PaxDbQ9BUB5.
PRIDEQ9BUB5.

Protocols and materials databases

DNASU8569.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000341183; ENSP00000339573; ENSG00000079277. [Q9BUB5-3]
ENST00000371945; ENSP00000361013; ENSG00000079277. [Q9BUB5-2]
ENST00000371946; ENSP00000361014; ENSG00000079277. [Q9BUB5-1]
ENST00000428112; ENSP00000411135; ENSG00000079277. [Q9BUB5-3]
GeneID8569.
KEGGhsa:8569.
UCSCuc001cqb.4. human. [Q9BUB5-1]
uc001cqc.4. human. [Q9BUB5-2]
uc009vyi.4. human. [Q9BUB5-3]

Organism-specific databases

CTD8569.
GeneCardsGC01M047023.
HGNCHGNC:7110. MKNK1.
MIM606724. gene.
neXtProtNX_Q9BUB5.
PharmGKBPA30829.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOVERGENHBG106949.
InParanoidQ9BUB5.
KOK04372.
OMAASFYDKR.
PhylomeDBQ9BUB5.
TreeFamTF314050.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
SignaLinkQ9BUB5.

Gene expression databases

ArrayExpressQ9BUB5.
BgeeQ9BUB5.
CleanExHS_MKNK1.
GenevestigatorQ9BUB5.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 2 hits.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9BUB5.
GeneWikiMKNK1.
GenomeRNAi8569.
NextBio32143.
PROQ9BUB5.
SOURCESearch...

Entry information

Entry nameMKNK1_HUMAN
AccessionPrimary (citable) accession number: Q9BUB5
Secondary accession number(s): D3DQ20 expand/collapse secondary AC list , D3DQ21, O00312, Q5TC06, Q5TC07, Q6V0N6
Entry history
Integrated into UniProtKB/Swiss-Prot: April 30, 2003
Last sequence update: June 1, 2001
Last modified: April 16, 2014
This is version 131 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM