O08605 (MKNK1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	Mknk1
Synonyms:	Mnk1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	427 AA.
Sequence status	Complete.
Protein existence	Evidence 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.2
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. Ref.2
Cofactor	Magnesium. Ref.2
Enzyme regulation	Phosphorylated and activated by the p38 kinases and kinases in the Erk pathway. Ref.2
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.2 UniProtKB Q9BUB5
Tissue specificity	Ubiquitously expressed in all tissues examined, with high levels in skeletal muscle. Ref.2
Post-translational modification	Dual phosphorylation of Thr-209 and Thr-214 activates the kinase. Phosphorylation of Thr-344 activates the kinase. MAPK3/ERK1 is one of the kinases which activate MKNK1/MNK1. Phosphorylation by PAK2 leads to a reduced phosphorylation of EIF4G1 By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. Contains 1 protein kinase domain.
Sequence caution	The sequence AAH21369.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Translation regulation
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	extrinsic apoptotic signaling pathway in absence of ligand Inferred from mutant phenotype PubMed 17903173. Source: MGI intracellular signal transduction Inferred from direct assay Ref.2. Source: UniProtKB peptidyl-serine phosphorylation Inferred from electronic annotation. Source: Ensembl regulation of translation Inferred from electronic annotation. Source: UniProtKB-KW response to salt stress Inferred from direct assay Ref.2. Source: UniProtKB
Molecular_function	ATP binding Inferred from direct assay Ref.2. Source: UniProtKB protein serine/threonine kinase activity Inferred from direct assay Ref.2. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 427	427	MAP kinase-interacting serine/threonine-protein kinase 1		PRO_0000086335
Regions
	Domain	49 – 333	285	Protein kinase
	Nucleotide binding	55 – 63	9	ATP By similarity UniProtKB P49137
Sites
	Active site	170	1	Proton acceptor By similarity UniProtKB P49137
	Binding site	78	1	ATP By similarity UniProtKB Q9BUB5
Amino acid modifications
	Modified residue	34	1	Phosphothreonine; by PAK2 Ref.3
	Modified residue	39	1	Phosphoserine; by PAK2 Ref.3
	Modified residue	209	1	Phosphothreonine Ref.2
	Modified residue	214	1	Phosphothreonine Ref.2
	Modified residue	344	1	Phosphothreonine By similarity UniProtKB Q9BUB5
Experimental info
	Mutagenesis	209	1	T → A: Loss of kinase activity; when associated with T-214. Ref.2
	Mutagenesis	214	1	T → A: Loss of kinase activity; when associated with T-209. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	O08605 [UniParc]. Last modified April 30, 2003. Version 2. Checksum: 7D59A1CBEE4DF68F	FASTA	427	47,915
	10 20 30 40 50 60 MVSSQKLEKP IEMGSSEPLP IVDSDKRRKK KRKTRATDSL PGKFEDVYQL TSELLGEGAY 70 80 90 100 110 120 AKVQGAVNLQ SGKEYAVKII EKQAGHSRSR VFREVETLYQ CQGNRNILEL IEFFEDDTRF 130 140 150 160 170 180 YLVFEKLQGG SILAHIQKRK HFNEREASRV VRDVATALDF LHTKGIAHRD LKPENILCES 190 200 210 220 230 240 PEKVSPVKIC DFDLGSGVKL NNSCTPITTP ELTTPCGSAE YMAPEVVEVF RDEATFYDKR 250 260 270 280 290 300 CDLWSLGVVL YIMLSGYPPF VGHCGADCGW DRGEVCRMCQ NKLFESIQEG KYEFPDKDWA 310 320 330 340 350 360 HISNEAKDLI SKLLVRDAKQ RLSAAQVLQH PWVQGQAPER GLPTPQVLQR NSSTMDLTLF 370 380 390 400 410 420 AAEAIALNRQ LSQHEENELA EEQEALAEGL CSMKLSPPSK SRLARRRALA QAGRSRDANP CLTPAGL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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]. Tissue: Mammary gland.
[2]	"Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2." Waskiewicz A.J., Flynn A., Proud C.G., Cooper J.A. EMBO J. 16:1909-1920(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 13-427, FUNCTION, INTERACTION WITH MAPK3; MAPK1 AND P38 KINASE, PHOSPHORYLATION AT THR-209 AND THR-214, MUTAGENESIS OF THR-209 AND THR-214. Tissue: Embryo.
[3]	"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 AT THR-34 AND SER-39 BY PAK2.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	BC021369 mRNA. Translation: AAH21369.1. Different initiation. Y11091 mRNA. Translation: CAA71965.1.
RefSeq	NP_001272417.1. NM_001285488.1. NP_067436.1. NM_021461.5.
UniGene	Mm.209327.
3D structure databases
ProteinModelPortal	O08605.
SMR	O08605. Positions 39-369.
ModBase	Search...
MobiDB	Search...
Protein-protein interaction databases
IntAct	O08605. 1 interaction.
MINT	MINT-1524139.
PTM databases
PhosphoSite	O08605.
Proteomic databases
PaxDb	O08605.
PRIDE	O08605.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	17346.
KEGG	mmu:17346.
UCSC	uc008ufl.1. mouse.
Organism-specific databases
CTD	8569.
MGI	MGI:894316. Mknk1.
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000231140.
HOVERGEN	HBG106949.
InParanoid	O08605.
KO	K04372.
Gene expression databases
ArrayExpress	O08605.
Bgee	O08605.
CleanEx	MM_MKNK1.
Genevestigator	O08605.
Family and domain databases
InterPro	IPR011009. 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]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. SSF56112. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	MKNK1. mouse.
NextBio	291932.
PRO	O08605.
SOURCE	Search...

Entry information

Entry name

MKNK1_MOUSE

Accession

Primary (citable) accession number: O08605

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 30, 2003
Last sequence update:	April 30, 2003
Last modified:	February 19, 2014
This is version 131 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program