MP2K2_RAT
ID MP2K2_RAT Reviewed; 400 AA.
AC P36506; A0JN15;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Dual specificity mitogen-activated protein kinase kinase 2;
DE Short=MAP kinase kinase 2;
DE Short=MAPKK 2;
DE EC=2.7.12.2 {ECO:0000250|UniProtKB:P36507};
DE AltName: Full=ERK activator kinase 2;
DE AltName: Full=MAPK/ERK kinase 2;
DE Short=MEK 2;
GN Name=Map2k2; Synonyms=Mek2, Mkk2, Prkmk2;
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 [MRNA].
RX PubMed=8462694; DOI=10.1016/0014-5793(93)80596-m;
RA Otsu M., Terada Y., Okayama H.;
RT "Isolation of two members of the rat MAP kinase kinase gene family.";
RL FEBS Lett. 320:246-250(1993).
RN [2]
RP ERRATUM OF PUBMED:8462694.
RX PubMed=8397117;
RA Otsu M., Terada Y., Okayama H.;
RL FEBS Lett. 331:307-307(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8393135; DOI=10.1128/mcb.13.8.4539-4548.1993;
RA Wu J., Harrison J.K., Dent P., Lynch K.R., Weber M.J., Sturgill T.W.;
RT "Identification and characterization of a new mammalian mitogen-activated
RT protein kinase kinase, MKK2.";
RL Mol. Cell. Biol. 13:4539-4548(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Catalyzes the concomitant phosphorylation of a threonine and
CC a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases.
CC Activates the ERK1 and ERK2 MAP kinases (By similarity). Activates BRAF
CC in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases
CC the inhibitory intramolecular interaction between KSR1 or KSR2 protein
CC kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF
CC dimerization and BRAF activation (By similarity).
CC {ECO:0000250|UniProtKB:P36507, ECO:0000250|UniProtKB:Q63932}.
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=2.7.12.2;
CC Evidence={ECO:0000250|UniProtKB:P36507};
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=2.7.12.2; Evidence={ECO:0000250|UniProtKB:P36507};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.12.2;
CC Evidence={ECO:0000250|UniProtKB:P36507};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000305};
CC -!- SUBUNIT: Interacts with MORG1 (By similarity). Interacts with SGK1 (By
CC similarity). Interacts with KSR1. Interacts with KSR1 and BRAF; the
CC interaction with KSR1 mediates KSR1-BRAF dimerization. Interacts with
CC GLS (By similarity). {ECO:0000250|UniProtKB:P36507,
CC ECO:0000250|UniProtKB:Q63932}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P36507}.
CC Membrane {ECO:0000250|UniProtKB:P36507}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P36507}. Note=Membrane localization is probably
CC regulated by its interaction with KSR1. {ECO:0000250|UniProtKB:P36507}.
CC -!- TISSUE SPECIFICITY: Expressed abundantly in the adult brain and muscle.
CC -!- PTM: MAPKK is itself dependent on Ser/Thr phosphorylation for activity
CC catalyzed by MAP kinase kinase kinases (RAF or MEKK1). Phosphorylated
CC by MAP2K1/MEK1 (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. MAP kinase kinase subfamily. {ECO:0000305}.
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DR EMBL; D14592; BAA03442.1; -; mRNA.
DR EMBL; L14936; AAA41620.1; -; mRNA.
DR EMBL; BC126084; AAI26085.1; -; mRNA.
DR PIR; A48081; A48081.
DR RefSeq; NP_579817.1; NM_133283.1.
DR AlphaFoldDB; P36506; -.
DR SMR; P36506; -.
DR BioGRID; 248693; 7.
DR IntAct; P36506; 1.
DR STRING; 10116.ENSRNOP00000027272; -.
DR BindingDB; P36506; -.
DR ChEMBL; CHEMBL3430876; -.
DR iPTMnet; P36506; -.
DR PhosphoSitePlus; P36506; -.
DR jPOST; P36506; -.
DR PaxDb; P36506; -.
DR PRIDE; P36506; -.
DR GeneID; 58960; -.
DR KEGG; rno:58960; -.
DR UCSC; RGD:61888; rat.
DR CTD; 5605; -.
DR RGD; 61888; Map2k2.
DR VEuPathDB; HostDB:ENSRNOG00000020005; -.
DR eggNOG; KOG0581; Eukaryota.
DR HOGENOM; CLU_000288_63_23_1; -.
DR InParanoid; P36506; -.
DR OMA; IAGWVCK; -.
DR OrthoDB; 688282at2759; -.
DR PhylomeDB; P36506; -.
DR BRENDA; 2.7.12.2; 5301.
DR Reactome; R-RNO-112411; MAPK1 (ERK2) activation.
DR Reactome; R-RNO-170968; Frs2-mediated activation.
DR Reactome; R-RNO-445144; Signal transduction by L1.
DR Reactome; R-RNO-5673000; RAF activation.
DR Reactome; R-RNO-5674135; MAP2K and MAPK activation.
DR Reactome; R-RNO-5674499; Negative feedback regulation of MAPK pathway.
DR PRO; PR:P36506; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Bgee; ENSRNOG00000020005; Expressed in jejunum and 19 other tissues.
DR Genevisible; P36506; RN.
DR GO; GO:0005938; C:cell cortex; IDA:RGD.
DR GO; GO:0005911; C:cell-cell junction; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; ISO:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005769; C:early endosome; TAS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR GO; GO:0005925; C:focal adhesion; TAS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISO:RGD.
DR GO; GO:0005770; C:late endosome; TAS:UniProtKB.
DR GO; GO:0005874; C:microtubule; ISO:RGD.
DR GO; GO:0005739; C:mitochondrion; TAS:UniProtKB.
DR GO; GO:0005634; C:nucleus; TAS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD.
DR GO; GO:0005524; F:ATP binding; IDA:RGD.
DR GO; GO:0004708; F:MAP kinase kinase activity; IDA:RGD.
DR GO; GO:0005078; F:MAP-kinase scaffold activity; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0060090; F:molecular adaptor activity; ISO:RGD.
DR GO; GO:0030165; F:PDZ domain binding; ISO:RGD.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; ISO:RGD.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; TAS:UniProtKB.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0097110; F:scaffold protein binding; ISO:RGD.
DR GO; GO:0060502; P:epithelial cell proliferation involved in lung morphogenesis; ISO:RGD.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; ISO:RGD.
DR GO; GO:0060324; P:face development; ISO:RGD.
DR GO; GO:0007507; P:heart development; ISO:RGD.
DR GO; GO:0060425; P:lung morphogenesis; ISO:RGD.
DR GO; GO:0000165; P:MAPK cascade; IBA:GO_Central.
DR GO; GO:0010629; P:negative regulation of gene expression; IGI:BHF-UCL.
DR GO; GO:0036289; P:peptidyl-serine autophosphorylation; ISO:RGD.
DR GO; GO:0050772; P:positive regulation of axonogenesis; ISO:RGD.
DR GO; GO:2000147; P:positive regulation of cell motility; ISO:RGD.
DR GO; GO:1903800; P:positive regulation of miRNA maturation; ISO:RGD.
DR GO; GO:0071902; P:positive regulation of protein serine/threonine kinase activity; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; IDA:RGD.
DR GO; GO:0048679; P:regulation of axon regeneration; ISO:RGD.
DR GO; GO:2000641; P:regulation of early endosome to late endosome transport; TAS:UniProtKB.
DR GO; GO:0090170; P:regulation of Golgi inheritance; TAS:UniProtKB.
DR GO; GO:0032872; P:regulation of stress-activated MAPK cascade; TAS:UniProtKB.
DR GO; GO:0048538; P:thymus development; ISO:RGD.
DR GO; GO:0030878; P:thyroid gland development; ISO:RGD.
DR GO; GO:0060440; P:trachea formation; ISO:RGD.
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 1: Evidence at protein level;
KW Acetylation; ATP-binding; Cytoplasm; Kinase; Magnesium; Membrane;
KW Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Tyrosine-protein kinase.
FT CHAIN 1..400
FT /note="Dual specificity mitogen-activated protein kinase
FT kinase 2"
FT /id="PRO_0000086374"
FT DOMAIN 72..369
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 282..310
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 194
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 78..86
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 101
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 10..11
FT /note="Cleavage; by anthrax lethal factor"
FT /evidence="ECO:0000250"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P36507"
FT MOD_RES 23
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P36507"
FT MOD_RES 222
FT /note="Phosphoserine; by RAF"
FT /evidence="ECO:0000250|UniProtKB:P36507"
FT MOD_RES 226
FT /note="Phosphoserine; by RAF"
FT /evidence="ECO:0000250|UniProtKB:P36507"
FT MOD_RES 293
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P36507"
FT MOD_RES 295
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P36507"
FT MOD_RES 306
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q02750"
FT MOD_RES 394
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P36507"
FT MOD_RES 396
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P36507"
SQ SEQUENCE 400 AA; 44282 MW; B4E6AB15DEAA82A4 CRC64;
MLARRKPVLP ALTINPTIAE GPSPTSEGAS EAHLVDLQKK LEELDLDEQQ RKRLEAFLTQ
KAKVGELKDD DFERISELGA GNGGVVTKAR HRPSGLIMAR KLIHLEIKPA VRNQIIRELQ
VLHECNSPYI VGFYGAFYSD GEISICMEHM DGGSLDQVLK EAKRIPEDIL GKVSIAVLRG
LAYLREKHQI MHRDVKPSNI LVNSRGEIKL CDFGVSGQLI DSMANSFVGT RSYMSPERLQ
GTHYSVQSDI WSMGLSLVEL AIGRYPIPPP DAKELEASFG RPVVDGADGE PHSVSPRPRP
PGRPISGHGM DSRPAMAIFE LLDYIVNEPP PKLPSGVFSS DFQEFVNKCL IKNPAERADL
KLLTNHAFIK RSEGEDVDFA GWLCRTLRLK QPSTPTRTAV
