(data stored in ACNUC8465 zone)

SWISSPROT: 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   11-DEC-2019, entry version 165.
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.
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;
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}.
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   SMR; P36506; -.
DR   BioGrid; 248693; 7.
DR   IntAct; P36506; 1.
DR   STRING; 10116.ENSRNOP00000027272; -.
DR   ChEMBL; CHEMBL3430876; -.
DR   iPTMnet; P36506; -.
DR   PhosphoSitePlus; P36506; -.
DR   jPOST; P36506; -.
DR   PaxDb; P36506; -.
DR   PRIDE; P36506; -.
DR   Ensembl; ENSRNOT00000027272; ENSRNOP00000027272; ENSRNOG00000020005.
DR   GeneID; 58960; -.
DR   KEGG; rno:58960; -.
DR   UCSC; RGD:61888; rat.
DR   CTD; 5605; -.
DR   RGD; 61888; Map2k2.
DR   eggNOG; KOG0581; Eukaryota.
DR   eggNOG; ENOG410XQ5A; LUCA.
DR   GeneTree; ENSGT00940000153487; -.
DR   HOGENOM; HOG000234206; -.
DR   InParanoid; P36506; -.
DR   KO; K04369; -.
DR   OMA; EAWASTF; -.
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 10 organ(s), highest expression level in skeletal muscle tissue.
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: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:0043539; F:protein serine/threonine kinase activator activity; ISO:RGD.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
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:0000187; P:activation of MAPK activity; IBA:GO_Central.
DR   GO; GO:0032147; P:activation of protein kinase activity; IBA:GO_Central.
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: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 production of miRNAs involved in gene silencing by miRNA; 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:0043497; P:regulation of protein heterodimerization activity; ISO:RGD.
DR   GO; GO:0032872; P:regulation of stress-activated MAPK cascade; TAS:UniProtKB.
DR   GO; GO:0023014; P:signal transduction by protein phosphorylation; IBA:GO_Central.
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;
DR   PRODOM; P36506.
DR   SWISS-2DPAGE; P36506.
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   NP_BIND         78..86
FT                   /note="ATP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   COMPBIAS        266..315
FT                   /note="Pro-rich"
FT   ACT_SITE        194
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10027"
FT   BINDING         101
FT                   /note="ATP"
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
//

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