ID   MKNK1_MOUSE             Reviewed;         427 AA.
AC   O08605;
DT   30-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT   30-APR-2003, sequence version 2.
DT   27-MAR-2024, entry version 196.
DE   RecName: Full=MAP kinase-interacting serine/threonine-protein kinase 1;
DE            EC=2.7.11.1 {ECO:0000269|PubMed:9155017};
DE   AltName: Full=MAP kinase signal-integrating kinase 1;
DE            Short=MAPK signal-integrating kinase 1;
DE            Short=Mnk1;
GN   Name=Mknk1; Synonyms=Mnk1;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090 {ECO:0000312|EMBL:CAA71965.1};
RN   [1] {ECO:0000305}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Mammary gland;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [2] {ECO:0000305}
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 13-427, FUNCTION, CATALYTIC ACTIVITY,
RP   COFACTOR, INTERACTION WITH MAPK3; MAPK1 AND P38 KINASE, PHOSPHORYLATION AT
RP   THR-209 AND THR-214, AND MUTAGENESIS OF THR-209 AND THR-214.
RC   TISSUE=Embryo;
RX   PubMed=9155017; DOI=10.1093/emboj/16.8.1909;
RA   Waskiewicz A.J., Flynn A., Proud C.G., Cooper J.A.;
RT   "Mitogen-activated protein kinases activate the serine/threonine kinases
RT   Mnk1 and Mnk2.";
RL   EMBO J. 16:1909-1920(1997).
RN   [3]
RP   PHOSPHORYLATION AT THR-34 AND SER-39 BY PAK2.
RX   PubMed=15234964; DOI=10.1074/jbc.m407337200;
RA   Orton K.C., Ling J., Waskiewicz A.J., Cooper J.A., Merrick W.C.,
RA   Korneeva N.L., Rhoads R.E., Sonenberg N., Traugh J.A.;
RT   "Phosphorylation of Mnk1 by caspase-activated Pak2/gamma-PAK inhibits
RT   phosphorylation and interaction of eIF4G with Mnk.";
RL   J. Biol. Chem. 279:38649-38657(2004).
RN   [4]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-180 AND SER-185, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Pancreas, and Spleen;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
CC   -!- FUNCTION: May play a role in the response to environmental stress and
CC       cytokines. Appears to regulate translation by phosphorylating EIF4E,
CC       thus increasing the affinity of this protein for the 7-methylguanosine-
CC       containing mRNA cap. {ECO:0000269|PubMed:9155017}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC         [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC         COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC         Evidence={ECO:0000269|PubMed:9155017};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC         threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC         Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC         EC=2.7.11.1; Evidence={ECO:0000269|PubMed:9155017};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000269|PubMed:9155017};
CC   -!- ACTIVITY REGULATION: Phosphorylated and activated by the p38 kinases
CC       and kinases in the Erk pathway. {ECO:0000269|PubMed:9155017}.
CC   -!- SUBUNIT: Interacts with the C-terminal regions of EIF4G1 and EIF4G2.
CC       Also binds to dephosphorylated ERK1 and ERK2, and to the p38 kinases.
CC       {ECO:0000269|PubMed:9155017}.
CC   -!- TISSUE SPECIFICITY: Ubiquitously expressed in all tissues examined,
CC       with high levels in skeletal muscle. {ECO:0000269|PubMed:9155017}.
CC   -!- PTM: Dual phosphorylation of Thr-209 and Thr-214 activates the kinase.
CC       Phosphorylation of Thr-344 activates the kinase. MAPK3/ERK1 is one of
CC       the kinases which activate MKNK1/MNK1. Phosphorylation by PAK2 leads to
CC       a reduced phosphorylation of EIF4G1 (By similarity). {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC       protein kinase family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAH21369.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; BC021369; AAH21369.1; ALT_INIT; mRNA.
DR   EMBL; Y11091; CAA71965.1; -; mRNA.
DR   RefSeq; NP_001272417.1; NM_001285488.1.
DR   RefSeq; NP_067436.1; NM_021461.5.
DR   AlphaFoldDB; O08605; -.
DR   SMR; O08605; -.
DR   IntAct; O08605; 1.
DR   MINT; O08605; -.
DR   STRING; 10090.ENSMUSP00000102123; -.
DR   ChEMBL; CHEMBL4523120; -.
DR   iPTMnet; O08605; -.
DR   PhosphoSitePlus; O08605; -.
DR   EPD; O08605; -.
DR   MaxQB; O08605; -.
DR   PaxDb; 10090-ENSMUSP00000019677; -.
DR   ProteomicsDB; 290256; -.
DR   Pumba; O08605; -.
DR   DNASU; 17346; -.
DR   GeneID; 17346; -.
DR   KEGG; mmu:17346; -.
DR   UCSC; uc008ufl.2; mouse.
DR   AGR; MGI:894316; -.
DR   CTD; 8569; -.
DR   MGI; MGI:894316; Mknk1.
DR   eggNOG; KOG0607; Eukaryota.
DR   InParanoid; O08605; -.
DR   OrthoDB; 2899709at2759; -.
DR   PhylomeDB; O08605; -.
DR   Reactome; R-MMU-1295596; Spry regulation of FGF signaling.
DR   BioGRID-ORCS; 17346; 3 hits in 82 CRISPR screens.
DR   ChiTaRS; Mknk1; mouse.
DR   PRO; PR:O08605; -.
DR   Proteomes; UP000000589; Unplaced.
DR   RNAct; O08605; Protein.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR   GO; GO:0009931; F:calcium-dependent protein serine/threonine kinase activity; IBA:GO_Central.
DR   GO; GO:0005516; F:calmodulin binding; IBA:GO_Central.
DR   GO; GO:0004683; F:calmodulin-dependent protein kinase activity; IBA:GO_Central.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR   GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; IMP:MGI.
DR   GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB.
DR   GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR   GO; GO:0006446; P:regulation of translational initiation; ISO:MGI.
DR   GO; GO:0009651; P:response to salt stress; IDA:UniProtKB.
DR   CDD; cd14174; STKc_Mnk1; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR008271; Ser/Thr_kinase_AS.
DR   PANTHER; PTHR24349:SF114; MAP KINASE-INTERACTING SERINE_THREONINE-PROTEIN KINASE 1; 1.
DR   PANTHER; PTHR24349; SERINE/THREONINE-PROTEIN KINASE; 1.
DR   Pfam; PF00069; Pkinase; 1.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE   1: Evidence at protein level;
KW   ATP-binding; Kinase; Magnesium; Metal-binding; Nucleotide-binding;
KW   Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW   Transferase; Translation regulation.
FT   CHAIN           1..427
FT                   /note="MAP kinase-interacting serine/threonine-protein
FT                   kinase 1"
FT                   /id="PRO_0000086335"
FT   DOMAIN          49..333
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          1..37
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          407..427
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        170
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10027"
FT   BINDING         55..63
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         78
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOD_RES         34
FT                   /note="Phosphothreonine; by PAK2"
FT                   /evidence="ECO:0000269|PubMed:15234964"
FT   MOD_RES         39
FT                   /note="Phosphoserine; by PAK2"
FT                   /evidence="ECO:0000269|PubMed:15234964"
FT   MOD_RES         180
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         185
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         209
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000269|PubMed:9155017"
FT   MOD_RES         214
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000269|PubMed:9155017"
FT   MOD_RES         344
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BUB5"
FT   MUTAGEN         209
FT                   /note="T->A: Loss of kinase activity; when associated with
FT                   T-214."
FT                   /evidence="ECO:0000269|PubMed:9155017"
FT   MUTAGEN         214
FT                   /note="T->A: Loss of kinase activity; when associated with
FT                   T-209."
FT                   /evidence="ECO:0000269|PubMed:9155017"
SQ   SEQUENCE   427 AA;  47915 MW;  7D59A1CBEE4DF68F CRC64;
     MVSSQKLEKP IEMGSSEPLP IVDSDKRRKK KRKTRATDSL PGKFEDVYQL TSELLGEGAY
     AKVQGAVNLQ SGKEYAVKII EKQAGHSRSR VFREVETLYQ CQGNRNILEL IEFFEDDTRF
     YLVFEKLQGG SILAHIQKRK HFNEREASRV VRDVATALDF LHTKGIAHRD LKPENILCES
     PEKVSPVKIC DFDLGSGVKL NNSCTPITTP ELTTPCGSAE YMAPEVVEVF RDEATFYDKR
     CDLWSLGVVL YIMLSGYPPF VGHCGADCGW DRGEVCRMCQ NKLFESIQEG KYEFPDKDWA
     HISNEAKDLI SKLLVRDAKQ RLSAAQVLQH PWVQGQAPER GLPTPQVLQR NSSTMDLTLF
     AAEAIALNRQ LSQHEENELA EEQEALAEGL CSMKLSPPSK SRLARRRALA QAGRSRDANP
     CLTPAGL
//