dbPTM

M3K7_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	M3K7_MOUSE
UniProt AC	Q62073
Protein Name	Mitogen-activated protein kinase kinase kinase 7
Gene Name	Map3k7
Organism	Mus musculus (Mouse).
Sequence Length	579
Subcellular Localization	Cytoplasm. Cell membrane Peripheral membrane protein Cytoplasmic side. Although the majority of MAP3K7/TAK1 is found in the cytosol, when complexed with TAB1/MAP3K7IP1 and TAB2/MAP3K7IP2, it is also localized at the cell membrane..
Protein 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 (By similarity)..
Protein Sequence	MSTASAASSSSSSSASEMIEAPSQVLNFEEIDYKEIEVEEVVGRGAFGVVCKAKWRAKDVAIKQIESESERKAFIVELRQLSRVNHPNIVKLYGACLNPVCLVMEYAEGGSLYNVLHGAEPLPYYTAAHAMSWCLQCSQGVAYLHSMQPKALIHRDLKPPNLLLVAGGTVLKICDFGTACDIQTHMTNNKGSAAWMAPEVFEGSNYSEKCDVFSWGIILWEVITRRKPFDEIGGPAFRIMWAVHNGTRPPLIKNLPKPIESLMTRCWSKDPSQRPSMEEIVKIMTHLMRYFPGADEPLQYPCQYSDEGQSNSATSTGSFMDIASTNTSNKSDTNMEQVPATNDTIKRLESKLLKNQAKQQSESGRLSLGASRGSSVESLPPTSEGKRMSADMSEIEARIVATAGNGQPRRRSIQDLTVTGTEPGQVSSRSSSPSVRMITTSGPTSEKPARSHPWTPDDSTDTNGSDNSIPMAYLTLDHQLQPLAPCPNSKESMAVFEQHCKMAQEYMKVQTEIALLLQRKQELVAELDQDEKDQQNTSRLVQEHKKLLDENKSLSTYYQQCKKQLEVIRSQQQKRQGTS

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
184	Phosphorylation	GTACDIQTHMTNNKG CCCCEEEHHCCCCCC	17.59	18202101
187	Phosphorylation	CDIQTHMTNNKGSAA CEEEHHCCCCCCCCE	28.21	18202101
192	Phosphorylation	HMTNNKGSAAWMAPE HCCCCCCCCEEECCC	19.20	10702308
331	Phosphorylation	STNTSNKSDTNMEQV CCCCCCCCCCCHHHC	54.65	25338131
361	Phosphorylation	KNQAKQQSESGRLSL HHHHHHHCCCCCCCC	31.10	29514104
363	Phosphorylation	QAKQQSESGRLSLGA HHHHHCCCCCCCCCC	34.16	29514104
367	Phosphorylation	QSESGRLSLGASRGS HCCCCCCCCCCCCCC	24.32	24899341
371	Phosphorylation	GRLSLGASRGSSVES CCCCCCCCCCCCCCC	35.06	28066266
374	Phosphorylation	SLGASRGSSVESLPP CCCCCCCCCCCCCCC	30.05	30635358
375	Phosphorylation	LGASRGSSVESLPPT CCCCCCCCCCCCCCC	32.50	29899451
378	Phosphorylation	SRGSSVESLPPTSEG CCCCCCCCCCCCCCC	43.98	27149854
388	Oxidation	PTSEGKRMSADMSEI CCCCCCCCCCCHHHH	4.39	17242355
389	Phosphorylation	TSEGKRMSADMSEIE CCCCCCCCCCHHHHH	25.75	25521595
392	Oxidation	GKRMSADMSEIEARI CCCCCCCHHHHHHHH	3.76	17242355
393	Phosphorylation	KRMSADMSEIEARIV CCCCCCHHHHHHHHH	35.65	22324799
412	Phosphorylation	NGQPRRRSIQDLTVT CCCCCCCCCEEEEEE	23.84	27087446
417	Phosphorylation	RRSIQDLTVTGTEPG CCCCEEEEEECCCCC	25.06	27742792
419	Phosphorylation	SIQDLTVTGTEPGQV CCEEEEEECCCCCCC	32.90	25168779
421	Phosphorylation	QDLTVTGTEPGQVSS EEEEEECCCCCCCCC	29.64	25619855
427	Phosphorylation	GTEPGQVSSRSSSPS CCCCCCCCCCCCCCC	16.49	26824392
427	O-linked_Glycosylation	GTEPGQVSSRSSSPS CCCCCCCCCCCCCCC	16.49	6375885
428	Phosphorylation	TEPGQVSSRSSSPSV CCCCCCCCCCCCCCE	37.01	27087446
430	Phosphorylation	PGQVSSRSSSPSVRM CCCCCCCCCCCCEEE	36.80	26160508
431	Phosphorylation	GQVSSRSSSPSVRMI CCCCCCCCCCCEEEE	45.20	27087446
432	Phosphorylation	QVSSRSSSPSVRMIT CCCCCCCCCCEEEEE	23.57	27087446
434	Phosphorylation	SSRSSSPSVRMITTS CCCCCCCCEEEEECC	25.05	26160508
439	Phosphorylation	SPSVRMITTSGPTSE CCCEEEEECCCCCCC	12.93	22807455
441	Phosphorylation	SVRMITTSGPTSEKP CEEEEECCCCCCCCC	33.84	22807455
445	Phosphorylation	ITTSGPTSEKPARSH EECCCCCCCCCCCCC	46.91	29514104
465	Phosphorylation	DSTDTNGSDNSIPMA CCCCCCCCCCCCEEE	35.37	-
563	Ubiquitination	TYYQQCKKQLEVIRS HHHHHHHHHHHHHHH	68.68	-

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
192	S	Phosphorylation	Kinase	MAP3K7	Q62073	GPS
412	S	Phosphorylation	Kinase	PKA-FAMILY	-	GPS

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
63	K	Phosphorylation	-
Association with TAB2/MAP3K7IP2, itself associated with free unanchored Lys-63 polyubiquitin chain, promotes autophosphorylation and subsequent activation of MAP3K7.
63	K	ubiquitylation	-
Association with TAB2/MAP3K7IP2, itself associated with free unanchored Lys-63 polyubiquitin chain, promotes autophosphorylation and subsequent activation of MAP3K7.
72	K	ubiquitylation	16157589
'Lys-48'-linked polyubiquitination at Lys-72 is induced by TNFalpha, and leads to proteasomal degradation.
158	K	Phosphorylation	29291351
'Lys-63'-linked polyubiquitination at Lys-158 by TRIM8 does not lead to proteasomal degradation but contributes to autophosphorylation and activation.
158	K	ubiquitylation	29291351
'Lys-63'-linked polyubiquitination at Lys-158 by TRIM8 does not lead to proteasomal degradation but contributes to autophosphorylation and activation.
187	T	Phosphorylation	-
Dephosphorylation at Thr-187 by PP2A and PPP6C leads to inactivation (By similarity).

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of M3K7_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
TRAF6_HUMAN	TRAF6	physical	10882101
TAB2_HUMAN	TAB2	physical	10882101
MALT1_MOUSE	Malt1	physical	16831874
BCL10_MOUSE	Bcl10	physical	16831874
IRAK1_MOUSE	Irak1	physical	16831874
PELI2_MOUSE	Peli2	physical	16831874
NEMO_MOUSE	Ikbkg	physical	21566132
TAB2_MOUSE	Tab2	physical	19955178
TAB3_MOUSE	Tab3	physical	19955178
BIRC2_MOUSE	Birc2	physical	19898473
BIRC3_MOUSE	Birc3	physical	19898473
TRAF6_MOUSE	Traf6	physical	19898473
MYD88_MOUSE	Myd88	physical	19898473
NEMO_MOUSE	Ikbkg	physical	19898473
UBE2N_MOUSE	Ube2n	physical	19898473
MP2K4_MOUSE	Map2k4	physical	19898473
TRAF6_MOUSE	Traf6	physical	18635759
M3K7_MOUSE	Map3k7	physical	18635759
TRAF6_MOUSE	Traf6	physical	22637723
MP2K6_MOUSE	Map2k6	physical	21606198
TAB2_HUMAN	TAB2	physical	17158449
M3K7_MOUSE	Map3k7	physical	17384642
TAB2_MOUSE	Tab2	physical	17384642
TAB3_MOUSE	Tab3	physical	17384642
TAB1_MOUSE	Tab1	physical	15218018
CAR11_MOUSE	Card11	physical	16301747
SKIL_MOUSE	Skil	physical	17276978
JIP1_MOUSE	Mapk8ip1	physical	17709393
VRK2_MOUSE	Vrk2	physical	17709393
SASH1_MOUSE	Sash1	physical	23776175
TRAF6_MOUSE	Traf6	physical	24558484
TAB1_HUMAN	TAB1	physical	19675569
TAB2_HUMAN	TAB2	physical	19675569
AAPK2_MOUSE	Prkaa2	physical	20615388
AAPK1_MOUSE	Prkaa1	physical	20615388
TAB1_MOUSE	Tab1	physical	29143862

Drug and Disease Associations

Kegg Drug
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of M3K7_MOUSE

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"The phagosomal proteome in interferon-gamma-activated macrophages."; Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,Thibault P.; Immunity 30:143-154(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-389 AND SER-412, ANDMASS SPECTROMETRY.	19144319 [Abstract]
"Large-scale phosphorylation analysis of mouse liver."; Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-412, AND MASSSPECTROMETRY.	17242355 [Abstract]
"Qualitative and quantitative analyses of protein phosphorylation innaive and stimulated mouse synaptosomal preparations."; Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F.,Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D.,Gerrits B., Panse C., Schlapbach R., Mansuy I.M.; Mol. Cell. Proteomics 6:283-293(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-412, AND MASSSPECTROMETRY.	17114649 [Abstract]

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