MKNK2_RAT
ID MKNK2_RAT Reviewed; 459 AA.
AC Q5U2N4;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 07-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=MAP kinase-interacting serine/threonine-protein kinase 2;
DE EC=2.7.11.1;
DE AltName: Full=MAP kinase signal-integrating kinase 2;
DE Short=MAPK signal-integrating kinase 2;
DE Short=Mnk2;
GN Name=Mknk2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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).
CC -!- FUNCTION: Serine/threonine-protein kinase that phosphorylates SFPQ/PSF,
CC HNRNPA1 and EIF4E. May play a role in the response to environmental
CC stress and cytokines. Appears to regulate translation by
CC phosphorylating EIF4E, thus increasing the affinity of this protein for
CC the 7-methylguanosine-containing mRNA cap. Required for mediating PP2A-
CC inhibition-induced EIF4E phosphorylation. Triggers EIF4E shuttling from
CC cytoplasm to nucleus. Enhances the formation of EIF4F complex in
CC pachytene spermatocytes, thus promoting mRNA translation during
CC spermatogenesis. Displays a high basal kinase activity. Acts as a
CC mediator of the suppressive effects of IFNgamma on hematopoiesis.
CC Negative regulator for signals that control generation of arsenic
CC trioxide As(2)O(3)-dependent apoptosis and anti-leukemic responses.
CC Involved in anti-apoptotic signaling in response to serum withdrawal
CC (By similarity). {ECO:0000250}.
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 -!- 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;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Inhibited by CGP57380 and staurosporine.
CC {ECO:0000250}.
CC -!- SUBUNIT: Monomer. Interacts with the C-terminal regions of EIF4G1 and
CC EIF4G2; this interaction is promoted when MAPK pathways are repressed
CC but repressed upon ERK proteins activation. Also binds to
CC dephosphorylated MAPK3/ERK1 and MAPK1/ER2K. Interaction with
CC phosphorylated MAPK3/ERK1 and MAPK1/ER2K protects it from
CC dephosphorylation and inactivation. Interacts with ESR2 and EIF4E in
CC the nucleus (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus, PML body
CC {ECO:0000250}.
CC -!- PTM: Dual phosphorylation of Thr-244 and Thr-249 activates the kinase.
CC Phosphorylation of Thr-379 activates the kinase. Phosphorylated upon
CC arsenic trioxide As(2)O(3) treatment. Phosphorylated by MAPK1/ERK2,
CC MAPK11 and MAPK14. Dephosphorylated by PP2A (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; BC085941; AAH85941.1; -; mRNA.
DR RefSeq; NP_001011985.1; NM_001011985.1.
DR AlphaFoldDB; Q5U2N4; -.
DR SMR; Q5U2N4; -.
DR STRING; 10116.ENSRNOP00000039672; -.
DR PaxDb; Q5U2N4; -.
DR Ensembl; ENSRNOT00000041106; ENSRNOP00000039672; ENSRNOG00000029028.
DR GeneID; 299618; -.
DR KEGG; rno:299618; -.
DR UCSC; RGD:1305728; rat.
DR CTD; 2872; -.
DR RGD; 1305728; Mknk2.
DR eggNOG; KOG0607; Eukaryota.
DR GeneTree; ENSGT00940000154587; -.
DR HOGENOM; CLU_000288_63_0_1; -.
DR InParanoid; Q5U2N4; -.
DR OMA; NKMTEVT; -.
DR OrthoDB; 608695at2759; -.
DR PhylomeDB; Q5U2N4; -.
DR TreeFam; TF314050; -.
DR PRO; PR:Q5U2N4; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Bgee; ENSRNOG00000029028; Expressed in skeletal muscle tissue and 19 other tissues.
DR Genevisible; Q5U2N4; RN.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0071243; P:cellular response to arsenic-containing substance; ISO:RGD.
DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; ISO:RGD.
DR GO; GO:0030097; P:hemopoiesis; ISO:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; ISO:RGD.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0046777; P:protein autophosphorylation; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; ISO:RGD.
DR GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW.
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 Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 2: Evidence at transcript level;
KW Apoptosis; ATP-binding; Cytoplasm; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Translation regulation; Zinc.
FT CHAIN 1..459
FT /note="MAP kinase-interacting serine/threonine-protein
FT kinase 2"
FT /id="PRO_0000226965"
FT DOMAIN 84..368
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 28..67
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 60..66
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT MOTIF 438..442
FT /note="MAP kinase binding"
FT /evidence="ECO:0000250"
FT ACT_SITE 205
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 90..98
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 113
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 160..162
FT /ligand="staurosporine"
FT /ligand_id="ChEBI:CHEBI:57491"
FT /evidence="ECO:0000250"
FT BINDING 209
FT /ligand="staurosporine"
FT /ligand_id="ChEBI:CHEBI:57491"
FT /evidence="ECO:0000250"
FT BINDING 299
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 311
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 314
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT MOD_RES 74
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CDB0"
FT MOD_RES 244
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9HBH9"
FT MOD_RES 249
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9HBH9"
FT MOD_RES 379
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9HBH9"
FT MOD_RES 431
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CDB0"
FT MOD_RES 434
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CDB0"
FT MOD_RES 446
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9HBH9"
FT MOD_RES 450
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8CDB0"
SQ SEQUENCE 459 AA; 51574 MW; 7D26909FB98AC34D CRC64;
MVQKRTAELQ GFHRSFKGQN PFELAFTLDP AQHGDSDFSP QCEARPDMPS SQPIDIPDAK
KRGRKKKRCR ATDSFSGRFE DVYQLQEDVL GEGAHARVQT CVNLITNQEY AVKIIEKQLG
HIRSRVFREV EMLYQCQGHR NVLELIEFFE EEDRFYLVFE KMRGGSILSH IHRRRHFNEL
EASVVVQDVA SALDFLHNKG IAHRDLKPEN ILCEHPNQVS PVKICDFDLG SGIKLNGDCS
PISTPELLTP CGSAEYMAPE VVEAFSEEAS IYDKRCDLWS LGVILYILLS GYPPFVGHCG
SDCGWDRGEA CPACQNMLFE SIQEGKYEFP DKDWSHISFA AKDLISKLLV RDAKQRLSAA
QVLQHPWVQG CAPENTLPTP LVLQRNSCAK DLTSFAAEAI AMNRQLAQCE EDAGQDQPVL
IRATSRCLQL SPPSQSKLAQ RRQRASLSAT PVVLVGDRV
