dbPTM

M3K8_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	M3K8_HUMAN
UniProt AC	P41279
Protein Name	Mitogen-activated protein kinase kinase kinase 8
Gene Name	MAP3K8
Organism	Homo sapiens (Human).
Sequence Length	467
Subcellular Localization	Cytoplasm .
Protein Description	Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the proinflammatory cytokine TNF-alpha (TNF) during immune responses. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. Involved in mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. In vitro, activates MAPK/ERK pathway in response to IL1 in an IRAK1-independent manner, leading to up-regulation of IL8 and CCL4. Transduces CD40 and TNFRSF1A signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. May also play a role in the transduction of TNF signals that activate JNK and NF-kappa-B in some cell types. In adipocytes, activates MAPK/ERK pathway in an IKBKB-dependent manner in response to IL1B and TNF, but not insulin, leading to induction of lipolysis. Plays a role in the cell cycle. Isoform 1 shows some transforming activity, although it is much weaker than that of the activated oncogenic variant..
Protein Sequence	MEYMSTGSDNKEEIDLLIKHLNVSDVIDIMENLYASEEPAVYEPSLMTMCQDSNQNDERSKSLLLSGQEVPWLSSVRYGTVEDLLAFANHISNTAKHFYGQRPQESGILLNMVITPQNGRYQIDSDVLLIPWKLTYRNIGSDFIPRGAFGKVYLAQDIKTKKRMACKLIPVDQFKPSDVEIQACFRHENIAELYGAVLWGETVHLFMEAGEGGSVLEKLESCGPMREFEIIWVTKHVLKGLDFLHSKKVIHHDIKPSNIVFMSTKAVLVDFGLSVQMTEDVYFPKDLRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPWVKRYPRSAYPSYLYIIHKQAPPLEDIADDCSPGMRELIEASLERNPNHRPRAADLLKHEALNPPREDQPRCQSLDSALLERKRLLSRKELELPENIADSSCTGSTEESEMLKRQRSLYIDLGALAGYFNLVRGPPTLEYG

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
5	Phosphorylation	---MEYMSTGSDNKE ---CCCCCCCCCCHH	28.81	27251275
6	Phosphorylation	--MEYMSTGSDNKEE --CCCCCCCCCCHHH	24.95	27251275
8	Phosphorylation	MEYMSTGSDNKEEID CCCCCCCCCCHHHHH	37.79	27251275
62	Phosphorylation	QNDERSKSLLLSGQE CCCHHHHHHHHCCCC	26.04	16806191
74	Phosphorylation	GQEVPWLSSVRYGTV CCCCCCCCCCCCCCH	23.95	24719451
80	Phosphorylation	LSSVRYGTVEDLLAF CCCCCCCCHHHHHHH	16.28	17472361
106	Phosphorylation	YGQRPQESGILLNMV CCCCCCCCCEEEEEE	26.36	28270605
115	Phosphorylation	ILLNMVITPQNGRYQ EEEEEEECCCCCEEE	13.86	28270605
121	Phosphorylation	ITPQNGRYQIDSDVL ECCCCCEEEECCCEE	15.95	28270605
125	Phosphorylation	NGRYQIDSDVLLIPW CCEEEECCCEEEEEE	31.11	16806191
135	Phosphorylation	LLIPWKLTYRNIGSD EEEEEECEECCCCCC	19.39	29514088
136	Phosphorylation	LIPWKLTYRNIGSDF EEEEECEECCCCCCC	16.46	-
141	Phosphorylation	LTYRNIGSDFIPRGA CEECCCCCCCCCCCC	26.08	19664994
153	Phosphorylation	RGAFGKVYLAQDIKT CCCCCCEEEECHHHC	10.37	-
290	Phosphorylation	FPKDLRGTEIYMSPE CCCCCCCCEEEECCE	16.87	15466476
295	Phosphorylation	RGTEIYMSPEVILCR CCCEEEECCEEEEEC	10.84	22210691
334	Phosphorylation	WVKRYPRSAYPSYLY HHHCCCCCCCCCEEE	27.87	16806191
368	Phosphorylation	MRELIEASLERNPNH HHHHHHHHHHHCCCC	20.27	-
400	Phosphorylation	EDQPRCQSLDSALLE CCCCCHHCHHHHHHH	37.46	17472361
413	Phosphorylation	LERKRLLSRKELELP HHHHHHHCHHHHCCC	45.99	12138205
426	Phosphorylation	LPENIADSSCTGSTE CCCCCCCCCCCCCHH	20.49	28348404
427	Phosphorylation	PENIADSSCTGSTEE CCCCCCCCCCCCHHH	19.08	28348404
429	Phosphorylation	NIADSSCTGSTEESE CCCCCCCCCCHHHHH	35.79	28348404
431	Phosphorylation	ADSSCTGSTEESEML CCCCCCCCHHHHHHH	17.94	28348404
432	Phosphorylation	DSSCTGSTEESEMLK CCCCCCCHHHHHHHH	45.15	28348404
443	Phosphorylation	EMLKRQRSLYIDLGA HHHHHHHHEEEEHHH	19.72	15466476

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
400	S	Phosphorylation	Kinase	AKT1	P31749	PSP
400	S	Phosphorylation	Kinase	AKT-FAMILY	-	GPS
400	S	Phosphorylation	Kinase	PKB_GROUP	-	PhosphoELM
413	S	Phosphorylation	Kinase	AKT-FAMILY	-	GPS

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
290	T	Phosphorylation	15466476
Phosphorylated on Thr-290; the phosphorylation is necessary but not sufficient for full kinase activity in vitro and for the dissociation of isoform 1 from NFKB1, leading to its degradation.
400	S	Phosphorylation	17472361
Phosphorylated on Ser-400 by IKBKB; the phosphorylation is required for LPS-stimulated activation of the MAPK/ERK pathway in macrophages.

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 M3K8_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
NFKB1_HUMAN	NFKB1	physical	9950430
NFKB1_HUMAN	NFKB1	physical	14743216
NFKB2_HUMAN	NFKB2	physical	14743216
TF65_HUMAN	RELA	physical	14743216
TNIP2_HUMAN	TNIP2	physical	14743216
KSR2_HUMAN	KSR2	physical	12975377
IKKA_HUMAN	CHUK	physical	10072079
MP2K1_HUMAN	MAP2K1	physical	8631303
MP2K4_HUMAN	MAP2K4	physical	8631303
TRAF2_HUMAN	TRAF2	physical	11932422
AKT1_HUMAN	AKT1	physical	12138205
TNIP2_HUMAN	TNIP2	physical	15169888
NFKB1_HUMAN	NFKB1	physical	15169888
TRAF2_HUMAN	TRAF2	physical	15670770
TRAF6_HUMAN	TRAF6	physical	15670770
TAB2_HUMAN	TAB2	physical	15670770
HS90A_HUMAN	HSP90AA1	physical	22939624
MP2K1_HUMAN	MAP2K1	physical	16291755
NFKB1_HUMAN	NFKB1	physical	21988832
STIP1_HUMAN	STIP1	physical	21988832
NFKB1_HUMAN	NFKB1	physical	25852190
NFKB2_HUMAN	NFKB2	physical	25852190
TF65_HUMAN	RELA	physical	25852190
TNIP2_HUMAN	TNIP2	physical	25852190

Drug and Disease Associations

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

Regulatory Network of M3K8_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"A quantitative atlas of mitotic phosphorylation."; Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,Elledge S.J., Gygi S.P.; Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-141, AND MASSSPECTROMETRY.	18669648 [Abstract]

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