MP2K7_RAT
ID MP2K7_RAT Reviewed; 419 AA.
AC Q4KSH7;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 02-AUG-2005, sequence version 1.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Dual specificity mitogen-activated protein kinase kinase 7;
DE Short=MAP kinase kinase 7;
DE Short=MAPKK 7;
DE EC=2.7.12.2 {ECO:0000269|PubMed:10051439};
DE AltName: Full=JNK-activating kinase 2;
DE AltName: Full=MAPK/ERK kinase 7;
DE Short=MEK 7;
DE AltName: Full=c-Jun N-terminal kinase kinase 2;
DE Short=JNK kinase 2;
DE Short=JNKK 2;
GN Name=Map2k7 {ECO:0000312|EMBL:AAX61178.1};
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] {ECO:0000312|EMBL:AAX61178.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley {ECO:0000312|EMBL:AAX61178.1};
RA Itoh T., Horiuchi M., Itoh A.;
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000305}
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=10051439; DOI=10.1042/bj3380681;
RA Butterfield L., Zentrich E., Beekman A., Heasley L.E.;
RT "Stress- and cell type-dependent regulation of transfected c-Jun N-terminal
RT kinase and mitogen-activated protein kinase kinase isoforms.";
RL Biochem. J. 338:681-686(1999).
RN [3]
RP PHOSPHORYLATION, AND INTERACTION WITH MAPK8/JNK1; MAPK9/JNK2; MAPK10/JNK3;
RP MAP3K11/MLK3 AND MAP3K5/ASK1.
RX PubMed=14575811; DOI=10.1016/j.lfs.2003.06.025;
RA Zhang Q., Tian H., Fu X., Zhang G.;
RT "Delayed activation and regulation of MKK7 in hippocampal CA1 region
RT following global cerebral ischemia in rats.";
RL Life Sci. 74:37-45(2003).
RN [4]
RP REVIEW ON ACTIVITY REGULATION.
RX PubMed=17496909; DOI=10.1038/sj.onc.1210392;
RA Raman M., Chen W., Cobb M.H.;
RT "Differential regulation and properties of MAPKs.";
RL Oncogene 26:3100-3112(2007).
RN [5]
RP REVIEW ON FUNCTION.
RX PubMed=20801953; DOI=10.1093/jb/mvq098;
RA Asaoka Y., Nishina H.;
RT "Diverse physiological functions of MKK4 and MKK7 during early
RT embryogenesis.";
RL J. Biochem. 148:393-401(2010).
RN [6]
RP REVIEW ON REGULATION, AND REVIEW ON FUNCTION.
RX PubMed=21333379; DOI=10.1016/j.ejcb.2010.11.008;
RA Haeusgen W., Herdegen T., Waetzig V.;
RT "The bottleneck of JNK signaling: molecular and functional characteristics
RT of MKK4 and MKK7.";
RL Eur. J. Cell Biol. 90:536-544(2011).
CC -!- FUNCTION: Dual specificity protein kinase which acts as an essential
CC component of the MAP kinase signal transduction pathway. Essential
CC component of the stress-activated protein kinase/c-Jun N-terminal
CC kinase (SAP/JNK) signaling pathway. With MAP2K4/MKK4, is the one of the
CC only known kinase to directly activate the stress-activated protein
CC kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3.
CC MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation,
CC but they differ in their preference for the phosphorylation site in the
CC Thr-Pro-Tyr motif. MAP2K4/MKK4 shows preference for phosphorylation of
CC the Tyr residue and MAP2K7/MKK7 for the Thr residue. The
CC monophosphorylation of JNKs on the Thr residue is sufficient to
CC increase JNK activity indicating that MAP2K7/MKK7 is important to
CC trigger JNK activity, while the additional phosphorylation of the Tyr
CC residue by MAP2K4/MKK4 ensures optimal JNK activation. Has a specific
CC role in JNK signal transduction pathway activated by pro-inflammatory
CC cytokines. The MKK/JNK signaling pathway is also involved in
CC mitochondrial death signaling pathway, including the release cytochrome
CC c, leading to apoptosis. Part of a non-canonical MAPK signaling
CC pathway, composed of the upstream MAP3K12 kinase and downstream MAP
CC kinases MAPK1/ERK2 and MAPK3/ERK1, that enhances the AP-1-mediated
CC transcription of APP in response to APOE (By similarity).
CC {ECO:0000250|UniProtKB:Q8CE90, ECO:0000269|PubMed:10051439}.
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:0000269|PubMed:10051439};
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:0000269|PubMed:10051439};
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:0000269|PubMed:10051439};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:10051439};
CC -!- ACTIVITY REGULATION: Activated by phosphorylation by specific MAP
CC kinase kinase kinases such as MAP3K1/MEKK1, MAP3K3/MEKK3, MAP3K11/MLK3
CC and MAP3K12/DLK.
CC -!- SUBUNIT: Interacts with VRK2 (By similarity). Interacts (via its D
CC domain) with its substrates MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3.
CC Interacts (via its DVD domain) with MAP3Ks activators like MAP3K5/ASK1
CC and MAP3K1/MEKK1. Interacts with MAPK8IP1/JIP1, MAPK8IP2/JIP2 and
CC MAPK8IP3/JIP3 scaffold proteins. Interacts with RASSF7, the interaction
CC promotes phosphorylation. Found in a complex with SH3RF1, RAC1,
CC MAP3K11/MLK3, MAPK8IP1/JIP1 and MAPK8/JNK1. Found in a complex with
CC SH3RF1, RAC2, MAP3K7/TAK1, MAPK8IP1/JIP1, MAPK8/JNK1 and MAPK9/JNK2 (By
CC similarity). {ECO:0000250|UniProtKB:O14733,
CC ECO:0000250|UniProtKB:Q8CE90}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q8CE90}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q8CE90}.
CC -!- DOMAIN: The DVD domain (residues 377-400) contains a conserved docking
CC site and is found in the mammalian MAP kinase kinases (MAP2Ks). The DVD
CC sites bind to their specific upstream MAP kinase kinase kinases
CC (MAP3Ks) and are essential for activation.
CC -!- DOMAIN: The D domain (residues 37-57) contains a conserved docking site
CC and is required for the binding to MAPK substrates.
CC -!- PTM: Activated by phosphorylation on Ser-271 and Thr-275 by MAP kinase
CC kinase kinases (MAP3Ks). {ECO:0000269|PubMed:14575811}.
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; AY879265; AAX61178.1; -; mRNA.
DR RefSeq; NP_001020596.1; NM_001025425.1.
DR AlphaFoldDB; Q4KSH7; -.
DR SMR; Q4KSH7; -.
DR STRING; 10116.ENSRNOP00000058535; -.
DR PaxDb; Q4KSH7; -.
DR PeptideAtlas; Q4KSH7; -.
DR PRIDE; Q4KSH7; -.
DR Ensembl; ENSRNOT00000104881; ENSRNOP00000086269; ENSRNOG00000001047.
DR GeneID; 363855; -.
DR KEGG; rno:363855; -.
DR UCSC; RGD:1560043; rat.
DR CTD; 5609; -.
DR RGD; 1560043; Map2k7.
DR eggNOG; KOG0983; Eukaryota.
DR GeneTree; ENSGT00940000158914; -.
DR HOGENOM; CLU_000288_63_23_1; -.
DR InParanoid; Q4KSH7; -.
DR OrthoDB; 688282at2759; -.
DR Reactome; R-RNO-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-RNO-2871796; FCERI mediated MAPK activation.
DR Reactome; R-RNO-450321; JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
DR PRO; PR:Q4KSH7; -.
DR Proteomes; UP000002494; Chromosome 12.
DR Bgee; ENSRNOG00000001047; Expressed in skeletal muscle tissue and 19 other tissues.
DR ExpressionAtlas; Q4KSH7; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005524; F:ATP binding; IDA:RGD.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0008545; F:JUN kinase kinase activity; IDA:RGD.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0004707; F:MAP kinase activity; ISO:RGD.
DR GO; GO:0004708; F:MAP kinase kinase activity; IDA:UniProtKB.
DR GO; GO:0031435; F:mitogen-activated protein kinase kinase kinase binding; IPI:RGD.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0019903; F:protein phosphatase binding; ISO:RGD.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0071347; P:cellular response to interleukin-1; ISO:RGD.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISO:RGD.
DR GO; GO:0072709; P:cellular response to sorbitol; IEP:RGD.
DR GO; GO:0007254; P:JNK cascade; IDA:RGD.
DR GO; GO:0000165; P:MAPK cascade; IBA:GO_Central.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IDA:RGD.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; ISO:RGD.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IMP:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:RGD.
DR GO; GO:0051973; P:positive regulation of telomerase activity; ISO:RGD.
DR GO; GO:1904355; P:positive regulation of telomere capping; ISO:RGD.
DR GO; GO:0032212; P:positive regulation of telomere maintenance via telomerase; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:RGD.
DR GO; GO:2000671; P:regulation of motor neuron apoptotic process; ISO:RGD.
DR GO; GO:0009408; P:response to heat; ISO:RGD.
DR GO; GO:0006970; P:response to osmotic stress; IDA:UniProtKB.
DR GO; GO:0034612; P:response to tumor necrosis factor; ISO:RGD.
DR GO; GO:0009411; P:response to UV; ISO:RGD.
DR GO; GO:0009611; P:response to wounding; ISO:RGD.
DR GO; GO:0051403; P:stress-activated MAPK cascade; IDA:UniProtKB.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
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; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Acetylation; Apoptosis; ATP-binding; Coiled coil; Cytoplasm; Kinase;
KW Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Stress response;
KW Transferase; Tyrosine-protein kinase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:O14733"
FT CHAIN 2..419
FT /note="Dual specificity mitogen-activated protein kinase
FT kinase 7"
FT /id="PRO_0000271407"
FT DOMAIN 120..380
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 18..77
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 37..57
FT /note="D Domain"
FT /evidence="ECO:0000250"
FT REGION 377..400
FT /note="DVD domain"
FT /evidence="ECO:0000250"
FT COILED 2..30
FT /evidence="ECO:0000255"
FT COMPBIAS 18..33
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 243
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q13131,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 126..134
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q13131,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 149
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q13131,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 44..45
FT /note="Cleavage; by anthrax lethal factor"
FT /evidence="ECO:0000250"
FT SITE 76..77
FT /note="Cleavage; by anthrax lethal factor"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:O14733"
FT MOD_RES 271
FT /note="Phosphoserine; by MAP3K"
FT /evidence="ECO:0000250"
FT MOD_RES 275
FT /note="Phosphothreonine; by MAP3K"
FT /evidence="ECO:0000250"
FT MOD_RES 411
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14733"
SQ SEQUENCE 419 AA; 47536 MW; 60405BF7111E294B CRC64;
MAASSLEQKL SRLEAKLKQE NREARRRIDL NLDISPQRPR PTLQLPLAND GGSRSPSSES
SPQHPTPPSR PRHMLGLPST LFTPRSMESI EIDQKLQEIM KQTGYLTIGG QRYQAEINDL
ENLGEMGSGT CGQVWKMRFR KTGHIIAVKQ MRRSGNKEEN KRILMDLDVV LKSHDCPYIV
QCFGTFITNT DVFIAMELMG TCAEKLKKRM QGPIPERILG KMTVAIVKAL YYLKEKHGVI
HRDVKPSNIL LDERGQIKLC DFGISGRLVD SKAKTRSAGC AAYMAPERID PPDPTKPDYD
IRADVWSLGI SLVELATGQF PYKNCKTDFE VLTKVLQEEP PLLPGHMGFS GDFQSFVKDC
LTKDHRKRPK YNKLLEHSFI KHYETLEVDV ASWFKDVMAK TESPRTSGVL SQHHLPFFR
