CPLM-000687

Genbank Nucleotide ID

Mitogen-activated protein kinase kinase kinase 7

Protein Synonyms/Alias

Transforming growth factor-beta-activated kinase 1; TGF-beta-activated kinase 1

Homo sapiens (Human)

Position	Peptide	Type	References
158	ALIHRDLKPPNLLLV	ubiquitination	[1]
209	EGSNYSEKCDVFSWG	ubiquitination	[1]
269	LMTRCWSKDPSQRPS	ubiquitination	[2]
346	PATNDTIKRLESKLL	ubiquitination	[3]
351	TIKRLESKLLKNQAK	ubiquitination	[2]
474	TSGPTSEKPTRSHPW	ubiquitination	[2]
547	IALLLQRKQELVAEL	ubiquitination	[2, 4]
579	KKLLDENKSLSTYYQ	ubiquitination	[2]
590	TYYQQCKKQLEVIRS	ubiquitination	[1, 2, 5, 6]

[1] 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]
[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] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[4] Integrated proteomic analysis of post-translational modifications by serial enrichment.
Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
[5] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
[6] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]

Functional Description

Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signal transduction of TRAF6, various cytokines including interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR). Ceramides are also able to activate MAP3K7/TAK1. Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K1/MEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs, c-jun N-terminal kinases (JNKs) and I-kappa-B kinase complex (IKK). Both p38 MAPK and JNK pathways control the transcription factors activator protein-1 (AP-1), while nuclear factor-kappa B is activated by IKK. MAP3K7 activates also IKBKB and MAPK8/JNK1 in response to TRAF6 signaling and mediates BMP2- induced apoptosis. In osmotic stress signaling, plays a major role in the activation of MAPK8/JNK1, but not that of NF-kappa-B. Promotes TRIM5 capsid-specific restriction activity.

DOMAIN 36 291 Protein kinase.
NP_BIND 42 50 ATP (By similarity).
REGION 1 300 Interaction with MAPK8IP1 (By
ACT_SITE 156 156 Proton acceptor (By similarity).
BINDING 63 63 ATP.
MOD_RES 184 184 Phosphothreonine; by autocatalysis
MOD_RES 187 187 Phosphothreonine; by autocatalysis.
MOD_RES 192 192 Phosphoserine; by autocatalysis.
MOD_RES 389 389 Phosphoserine.
MOD_RES 439 439 Phosphoserine.

3D-structure; Alternative splicing; Apoptosis; ATP-binding; Cell membrane; Complete proteome; Cytoplasm; Kinase; Magnesium; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; Stress response; Transcription; Transcription regulation; Transferase; Ubl conjugation.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005671; C:Ada2/Gcn5/Ada3 transcription activator complex; IDA:BHF-UCL.
GO:0005829; C:cytosol; TAS:Reactome.
GO:0010008; C:endosome membrane; TAS:Reactome.
GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO:0000287; F:magnesium ion binding; IEA:InterPro.
GO:0004708; F:MAP kinase kinase activity; IEA:Compara.
GO:0004709; F:MAP kinase kinase kinase activity; IDA:UniProtKB.
GO:0000187; P:activation of MAPK activity; IDA:UniProtKB.
GO:0007250; P:activation of NF-kappaB-inducing kinase activity; IMP:UniProtKB.
GO:0001525; P:angiogenesis; IEA:Compara.
GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
GO:0043966; P:histone H3 acetylation; IDA:BHF-UCL.
GO:0007252; P:I-kappaB phosphorylation; IDA:UniProtKB.
GO:0045087; P:innate immune response; TAS:Reactome.
GO:0007254; P:JNK cascade; IDA:UniProtKB.
GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome.
GO:0043066; P:negative regulation of apoptotic process; IEA:Compara.
GO:0001841; P:neural tube formation; IEA:Compara.
GO:0070423; P:nucleotide-binding oligomerization domain containing signaling pathway; TAS:Reactome.
GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IMP:UniProtKB.
GO:0032743; P:positive regulation of interleukin-2 production; IMP:UniProtKB.
GO:0046330; P:positive regulation of JNK cascade; IEA:Compara.
GO:0043507; P:positive regulation of JUN kinase activity; IDA:UniProtKB.
GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; TAS:Reactome.
GO:0050870; P:positive regulation of T cell activation; IC:UniProtKB.
GO:0002726; P:positive regulation of T cell cytokine production; IMP:UniProtKB.
GO:0050852; P:T cell receptor signaling pathway; NAS:UniProtKB.
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:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:ProtInc.
GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome.

IPR011009; Kinase-like_dom.
IPR017421; MAPKKK7.
IPR000719; Prot_kinase_cat_dom.
IPR017441; Protein_kinase_ATP_BS.
IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
IPR008271; Ser/Thr_kinase_AS.

PF07714; Pkinase_Tyr

PS00107; PROTEIN_KINASE_ATP
PS50011; PROTEIN_KINASE_DOM
PS00108; PROTEIN_KINASE_ST