CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-000284
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Dual specificity mitogen-activated protein kinase kinase 7 
Protein Synonyms/Alias
 MAP kinase kinase 7; MAPKK 7; JNK-activating kinase 2; MAPK/ERK kinase 7; MEK 7; Stress-activated protein kinase kinase 4; SAPK kinase 4; SAPKK-4; SAPKK4; c-Jun N-terminal kinase kinase 2; JNK kinase 2; JNKK 2 
Gene Name
 MAP2K7 
Gene Synonyms/Alias
 JNKK2; MEK7; MKK7; PRKMK7; SKK4 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
9AASSLEQKLSRLEAKubiquitination[1, 2]
95ESIEIDQKLQEIMKQubiquitination[2]
288GVIHRDVKPSNILLDubiquitination[2]
301LDERGQIKLCDFGISubiquitination[2]
369QFPYKNCKTDFEVLTubiquitination[2]
416RKRPKYNKLLEHSFIubiquitination[3]
443WFKDVMAKTESPRTSubiquitination[2]
Reference
 [1] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789] 
Functional Description
 Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K4/MKK4, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4/MKK4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The monophosphorylation of JNKs on the Thr residue is sufficient to increase JNK activity indicating that MAP2K7/MKK7 is important to trigger JNK activity, while the additional phosphorylation of the Tyr residue by MAP2K4/MKK4 ensures optimal JNK activation. Has a specific role in JNK signal transduction pathway activated by proinflammatory cytokines. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. 
Sequence Annotation
 DOMAIN 120 380 Protein kinase.
 NP_BIND 126 134 ATP (By similarity).
 REGION 37 57 D domain (By similarity).
 REGION 377 400 DVD domain.
 ACT_SITE 243 243 Proton acceptor (By similarity).
 BINDING 149 149 ATP (By similarity).
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 271 271 Phosphoserine; by MAP3K (By similarity).
 MOD_RES 275 275 Phosphothreonine; by MAP3K (By  
Keyword
 3D-structure; Acetylation; Alternative splicing; Apoptosis; ATP-binding; Coiled coil; Complete proteome; Cytoplasm; Kinase; Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Stress response; Transferase; Tyrosine-protein kinase. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 419 AA 
Protein Sequence
MAASSLEQKL SRLEAKLKQE NREARRRIDL NLDISPQRPR PTLQLPLAND GGSRSPSSES 60
SPQHPTPPAR PRHMLGLPST LFTPRSMESI EIDQKLQEIM KQTGYLTIGG QVPPSLWRGE 120
GGGPARLDPS WERQWGAGGG GRAPGTLQPS LSSQRYQAEI NDLENLGEMG SGTCGQVWKM 180
RFRKTGHVIA VKQMRRSGNK EENKRILMDL DVVLKSHDCP YIVQCFGTFI TNTDVFIAME 240
LMGTCAEKLK KRMQGPIPER ILGKMTVAIV KALYYLKEKH GVIHRDVKPS NILLDERGQI 300
KLCDFGISGR LVDSKAKTRS AGCAAYMAPE RIDPPDPTKP DYDIRADVWS LGISLVELAT 360
GQFPYKNCKT DFEVLTKVLQ EEPPLLPGHM GFSGDFQSFV KDCLTKDHRK RPKYNKLLEH 420
SFIKRYETLE VDVASWFKDV MAKTESPRTS GVLSQPHLPF FR 462 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005634; C:nucleus; ISS:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0008545; F:JUN kinase kinase activity; IEA:Compara.
 GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
 GO:0004708; F:MAP kinase kinase activity; IDA:UniProtKB.
 GO:0019903; F:protein phosphatase binding; ISS:BHF-UCL.
 GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
 GO:0004713; F:protein tyrosine kinase activity; IEA:UniProtKB-KW.
 GO:0007257; P:activation of JUN kinase activity; ISS:BHF-UCL.
 GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome.
 GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Compara.
 GO:0034166; P:toll-like receptor 10 signaling pathway; TAS:Reactome.
 GO:0034134; P:toll-like receptor 2 signaling pathway; TAS:Reactome.
 GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome.
 GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
 GO:0034146; P:toll-like receptor 5 signaling pathway; TAS:Reactome.
 GO:0034162; P:toll-like receptor 9 signaling pathway; TAS:Reactome.
 GO:0038123; P:toll-like receptor TLR1:TLR2 signaling pathway; TAS:Reactome.
 GO:0038124; P:toll-like receptor TLR6:TLR2 signaling pathway; TAS:Reactome.
 GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome. 
Interpro
 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR002290; Ser/Thr_dual-sp_kinase_dom.
 IPR008271; Ser/Thr_kinase_AS. 
Pfam
 PF00069; Pkinase 
SMART
 SM00220; S_TKc 
PROSITE
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 
PRINTS