MAP3K8

Functionⁱ

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.8 Publications

Miscellaneous

Can be converted to an oncogenic protein by proviral activation, leading to a C-terminally truncated protein with transforming activity.

Catalytic activityⁱ

ATP + a protein = ADP + a phosphoprotein.

Cofactorⁱ

Mg²⁺

Sites

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Binding siteⁱ	167	ATPPROSITE-ProRule annotation		1
Active siteⁱ	253	Proton acceptorPROSITE-ProRule annotation		1

Regions

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Nucleotide bindingⁱ	144 – 152	ATPPROSITE-ProRule annotation		9

GO - Molecular functionⁱ

ATP binding Source: UniProtKB-KW
magnesium ion binding Source: InterPro
MAP kinase kinase kinase activity Source: Reactome
protein serine/threonine kinase activity
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

activation of protein kinase activity
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
cell cycle Source: UniProtKB-KW
interleukin-1-mediated signaling pathway Source: Reactome
protein phosphorylation
Source: ProtInc
Traceable author statementⁱ
- 2072910
signal transduction by protein phosphorylation
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
stress-activated MAPK cascade Source: Reactome
stress-activated protein kinase signaling cascade
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
T cell costimulation Source: Reactome

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Kinase, Serine/threonine-protein kinase, Transferase
Biological process	Cell cycle, Immunity
Ligand	ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

Reactomeⁱ	R-HSA-389357 CD28 dependent PI3K/Akt signaling R-HSA-5684264 MAP3K8 (TPL2)-dependent MAPK1/3 activation
SignaLinkⁱ	P41279
SIGNORⁱ	P41279

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Mitogen-activated protein kinase kinase kinase 8 (EC:2.7.11.25) Alternative name(s): Cancer Osaka thyroid oncogene Proto-oncogene c-Cot Serine/threonine-protein kinase cot Tumor progression locus 2 Short name: TPL-2
Gene namesⁱ	Name:MAP3K8 Synonyms:COT, ESTF
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 10

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000107968.9
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:6860 MAP3K8
MIMⁱ	191195 gene
neXtProtⁱ	NX_P41279

Keywords - Cellular componentⁱ

Cytoplasm

Pathology & Biotechⁱ

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	62	S → A: Decreased IL1-stimulated activity. Loss of IL1-stimulated phosphorylation of T-290 and MEK phosphorylation activity; when associated with A-400. 1 Publication	1
Mutagenesisⁱ	167	K → R: Loss of catalytic activity. 1 Publication	1
Mutagenesisⁱ	270	D → A: Loss of catalytic activity. 1 Publication	1
Mutagenesisⁱ	290	T → A: Loss of MEK phosphorylation activity and almost abolished autophosphorylation activity. Loss of IL1-stimulated MEK phosphorylation activity but not of IL1-stimulated autophosphorylation activity. No effect on KSR2 binding. 2 Publications	1
Mutagenesisⁱ	290	T → D: Impaired MEK phosphorylation and autophosphorylation activities. No effect on KSR2 binding. 2 Publications	1
Mutagenesisⁱ	290	T → E: Loss of MEK phosphorylation activity and almost abolished autophosphorylation activity. No effect on KSR2 binding. 2 Publications	1
Mutagenesisⁱ	400	S → A: Slightly decreased IL1-stimulated MEK phosphorylation activity. Loss of IL1-stimulated phosphorylation of T-290 and MEK phosphorylation activity; when associated with A-62. 1 Publication	1

Keywords - Diseaseⁱ

Proto-oncogene

Organism-specific databases

DisGeNET More...DisGeNETⁱ	1326
MalaCards human disease database More...MalaCardsⁱ	MAP3K8
Open Targets More...OpenTargetsⁱ	ENSG00000107968
PharmGKBⁱ	PA30606

Chemistry databases

ChEMBLⁱ	CHEMBL4899
IUPHAR/BPS Guide to PHARMACOLOGY More...GuidetoPHARMACOLOGYⁱ	2083

Polymorphism and mutation databases

BioMutaⁱ	MAP3K8
DMDMⁱ	50403742

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000024350	1 – 467	Mitogen-activated protein kinase kinase kinase 8Add BLAST		467

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Modified residueⁱ	62	Phosphoserine; by autocatalysis1 Publication	1
Modified residueⁱ	80	Phosphothreonine1 Publication	1
Modified residueⁱ	141	PhosphoserineCombined sources	1
Modified residueⁱ	290	Phosphothreonine3 Publications	1
Modified residueⁱ	400	Phosphoserine3 Publications	1
Modified residueⁱ	443	Phosphoserine1 Publication	1

Post-translational modificationⁱ

Autophosphorylated. Isoform 1 undergoes phosphorylation mainly on Ser residues, and isoform 2 on both Ser and Thr residues. Thr-290 is autophosphorylated (PubMed:19754427) and/or transphosphorylated (PubMed:15466476); 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. Ser-400 is autophosphorylated (PubMed:19754427) and/or transphosphorylated by IKBKB (PubMed:22988300); the phosphorylation is required for LPS-stimulated activation of the MAPK/ERK pathway in macrophages.5 Publications

Keywords - PTMⁱ

Phosphoprotein

Proteomic databases

MaxQB - The MaxQuant DataBase More...MaxQBⁱ	P41279
PaxDbⁱ	P41279
PeptideAtlas More...PeptideAtlasⁱ	P41279
PRIDEⁱ	P41279
ProteomicsDBⁱ	55458 55459 [P41279-2]

PTM databases

iPTMnetⁱ	P41279
PhosphoSitePlusⁱ	P41279

Expressionⁱ

Tissue specificityⁱ

Expressed in several normal tissues and human tumor-derived cell lines.

Developmental stageⁱ

Isoform 1 is activated specifically during the S and G2/M phases of the cell cycle.

Inductionⁱ

Up-regulated by IL12 in T-lymphocytes. Up-regulated in subcutaneous adipose tissue of obese individuals.2 Publications

Gene expression databases

Bgeeⁱ	ENSG00000107968 Expressed in 192 organ(s), highest expression level in omental fat pad
CleanExⁱ	HS_MAP3K8
ExpressionAtlasⁱ	P41279 baseline and differential
Genevisibleⁱ	P41279 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	CAB005120 HPA017962

HPAⁱ

CAB005120
HPA017962

Interactionⁱ

Subunit structureⁱ

Forms a ternary complex with NFKB1/p105 and TNIP2. Interacts with NFKB1; the interaction increases the stability of MAP3K8 but inhibits its MEK phosphorylation activity, whereas loss of interaction following LPS stimulation leads to its degradation. Interacts with CD40 and TRAF6; the interaction is required for ERK activation. Interacts with KSR2; the interaction inhibits ERK and NF-kappa-B activation.5 Publications

Binary interactionsⁱ

With	Entry	#Exp.	IntAct
HSP90AB1	P08238	2	EBI-354900,EBI-352572
NFKB1	P19838	13	EBI-354900,EBI-300010
NFKB2	Q00653	2	EBI-354900,EBI-307326
PIN1	Q13526	8	EBI-354900,EBI-714158
TNIP2	Q8NFZ5	10	EBI-354900,EBI-359372

Protein-protein interaction databases

BioGridⁱ	107719, 21 interactors
CORUMⁱ	P41279
Database of interacting proteins More...DIPⁱ	DIP-27534N
IntActⁱ	P41279, 14 interactors
Molecular INTeraction database More...MINTⁱ	P41279
STRINGⁱ	9606.ENSP00000263056

Chemistry databases

BindingDBⁱ

P41279

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Beta strandⁱ	75 – 78	Combined sources	4
Helixⁱ	81 – 92	Combined sources	12
Beta strandⁱ	106 – 109	Combined sources	4
Beta strandⁱ	117 – 119	Combined sources	3
Turnⁱ	124 – 126	Combined sources	3
Beta strandⁱ	127 – 130	Combined sources	4
Helixⁱ	135 – 137	Combined sources	3
Beta strandⁱ	138 – 145	Combined sources	8
Beta strandⁱ	148 – 157	Combined sources	10
Turnⁱ	158 – 160	Combined sources	3
Beta strandⁱ	163 – 170	Combined sources	8
Helixⁱ	171 – 173	Combined sources	3
Helixⁱ	177 – 184	Combined sources	8
Beta strandⁱ	193 – 199	Combined sources	7
Beta strandⁱ	202 – 207	Combined sources	6
Helixⁱ	215 – 222	Combined sources	8
Helixⁱ	227 – 246	Combined sources	20
Helixⁱ	256 – 258	Combined sources	3
Beta strandⁱ	259 – 261	Combined sources	3
Beta strandⁱ	266 – 268	Combined sources	3
Beta strandⁱ	278 – 282	Combined sources	5
Helixⁱ	291 – 293	Combined sources	3
Helixⁱ	296 – 300	Combined sources	5
Helixⁱ	307 – 322	Combined sources	16
Turnⁱ	326 – 330	Combined sources	5
Helixⁱ	340 – 346	Combined sources	7
Helixⁱ	350 – 352	Combined sources	3
Beta strandⁱ	355 – 357	Combined sources	3
Helixⁱ	359 – 368	Combined sources	10
Turnⁱ	373 – 375	Combined sources	3
Helixⁱ	379 – 382	Combined sources	4
Helixⁱ	386 – 388	Combined sources	3

Show more details

3D structure databases

ProteinModelPortalⁱ	P41279
SMRⁱ	P41279
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	138 – 388	Protein kinasePROSITE-ProRule annotationAdd BLAST		251

Sequence similaritiesⁱ

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.Curated

Phylogenomic databases

eggNOGⁱ	KOG0201 Eukaryota ENOG410XP9G LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00800000124036
HOGENOMⁱ	HOG000285978
HOVERGENⁱ	HBG006306
InParanoidⁱ	P41279
KEGG Orthology (KO) More...KOⁱ	K04415
OMAⁱ	EGGSVME
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0682
PhylomeDBⁱ	P41279
TreeFamⁱ	TF105117

Family and domain databases

InterProⁱ	View protein in InterPro IPR011009 Kinase-like_dom_sf IPR017424 MAPKKK8 IPR000719 Prot_kinase_dom IPR008271 Ser/Thr_kinase_AS
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00069 Pkinase, 1 hit
PIRSFⁱ	PIRSF038171 MAPKKK8, 1 hit
SMARTⁱ	View protein in SMART SM00220 S_TKc, 1 hit
SUPFAMⁱ	SSF56112 SSF56112, 1 hit
PROSITEⁱ	View protein in PROSITE PS50011 PROTEIN_KINASE_DOM, 1 hit PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (2+)ⁱ

Sequence statusⁱ: Complete.

This entry describes 2 isoformsⁱ produced by alternative initiation. Align Add to basket

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show all Align All

Isoform 1 (identifier: P41279-1) [UniParc]FASTA Add to basket

Also known as: 58 kDa

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEYMSTGSDN KEEIDLLIKH LNVSDVIDIM ENLYASEEPA VYEPSLMTMC 
        60         70         80         90        100
QDSNQNDERS KSLLLSGQEV PWLSSVRYGT VEDLLAFANH ISNTAKHFYG 
       110        120        130        140        150
QRPQESGILL NMVITPQNGR YQIDSDVLLI PWKLTYRNIG SDFIPRGAFG 
       160        170        180        190        200
KVYLAQDIKT KKRMACKLIP VDQFKPSDVE IQACFRHENI AELYGAVLWG 
       210        220        230        240        250
ETVHLFMEAG EGGSVLEKLE SCGPMREFEI IWVTKHVLKG LDFLHSKKVI 
       260        270        280        290        300
HHDIKPSNIV FMSTKAVLVD FGLSVQMTED VYFPKDLRGT EIYMSPEVIL 
       310        320        330        340        350
CRGHSTKADI YSLGATLIHM QTGTPPWVKR YPRSAYPSYL YIIHKQAPPL 
       360        370        380        390        400
EDIADDCSPG MRELIEASLE RNPNHRPRAA DLLKHEALNP PREDQPRCQS 
       410        420        430        440        450
LDSALLERKR LLSRKELELP ENIADSSCTG STEESEMLKR QRSLYIDLGA 
       460 
LAGYFNLVRG PPTLEYG

Length:467

Mass (Da):52,925

Last modified:July 19, 2004 - v2

Checksum:ⁱ7728969EA3E4E8EC

GO

Isoform 2 (identifier: P41279-2) [UniParc]FASTA Add to basket

Also known as: 52 kDa

The sequence of this isoform differs from the canonical sequence as follows:
1-29: Missing.

« Hide

        10         20         30         40         50
MENLYASEEP AVYEPSLMTM CQDSNQNDER SKSLLLSGQE VPWLSSVRYG 
        60         70         80         90        100
TVEDLLAFAN HISNTAKHFY GQRPQESGIL LNMVITPQNG RYQIDSDVLL 
       110        120        130        140        150
IPWKLTYRNI GSDFIPRGAF GKVYLAQDIK TKKRMACKLI PVDQFKPSDV 
       160        170        180        190        200
EIQACFRHEN IAELYGAVLW GETVHLFMEA GEGGSVLEKL ESCGPMREFE 
       210        220        230        240        250
IIWVTKHVLK GLDFLHSKKV IHHDIKPSNI VFMSTKAVLV DFGLSVQMTE 
       260        270        280        290        300
DVYFPKDLRG TEIYMSPEVI LCRGHSTKAD IYSLGATLIH MQTGTPPWVK 
       310        320        330        340        350
RYPRSAYPSY LYIIHKQAPP LEDIADDCSP GMRELIEASL ERNPNHRPRA 
       360        370        380        390        400
ADLLKHEALN PPREDQPRCQ SLDSALLERK RLLSRKELEL PENIADSSCT 
       410        420        430 
GSTEESEMLK RQRSLYIDLG ALAGYFNLVR GPPTLEYG

Show »

Length:438

Mass (Da):49,620

Checksum:ⁱ2121FEF4658882FD

GO

Computationally mapped potential isoform sequencesⁱ

There are 3 potential isoforms mapped to this entry.BLAST Align Show all Add to basket

Entry	Entry name	Protein names	Gene names	Length	Annotation

Q5T857	Q5T857_HUMAN	Mitogen-activated protein kinase ki... Mitogen-activated protein kinase kinase kinase 8	MAP3K8	255	Annotation score:
Q5T853	Q5T853_HUMAN	Mitogen-activated protein kinase ki... Mitogen-activated protein kinase kinase kinase 8	MAP3K8	223	Annotation score:
Q5T854	Q5T854_HUMAN	Mitogen-activated protein kinase ki... Mitogen-activated protein kinase kinase kinase 8	MAP3K8	132	Annotation score:

Experimental Info

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Sequence conflictⁱ	399	Q → T in BAA03387 (PubMed:2072910).Curated		1
Sequence conflictⁱ	399	Q → T no nucleotide entry (PubMed:8226782).Curated		1

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_051638	214	S → F. Corresponds to variant dbSNP:rs3087944Ensembl.	1
Natural variantⁱVAR_006198	398 – 415	CQSLD…LLSRK → GHQVIHEGSSTNDPNNSC in oncogenic form. Add BLAST	18
Natural variantⁱVAR_006199	416 – 467	Missing in oncogenic form. Add BLAST	52

Alternative sequence

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Alternative sequenceⁱVSP_018843	1 – 29	Missing in isoform 2. 1 PublicationAdd BLAST		29

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	D14497 mRNA Translation: BAA03387.1 Z14138 mRNA Translation: CAA78512.1 AK290320 mRNA Translation: BAF83009.1 AY309013 Genomic DNA Translation: AAP45053.1 AL161651 Genomic DNA No translation available. CH471072 Genomic DNA Translation: EAW86004.1 CH471072 Genomic DNA Translation: EAW86005.1 CH471072 Genomic DNA Translation: EAW86006.1 CH471072 Genomic DNA Translation: EAW86007.1 BC104833 mRNA Translation: AAI04834.1 BC113566 mRNA Translation: AAI13567.1 AF133211 Genomic DNA Translation: AAG13454.1
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS7166.1 [P41279-1]
PIRⁱ	A48713
NCBI Reference Sequences More...RefSeqⁱ	NP_001231063.1, NM_001244134.1 [P41279-1] NP_001307890.1, NM_001320961.1 [P41279-1] NP_005195.2, NM_005204.3 [P41279-1] XP_016871196.1, XM_017015707.1 XP_016871197.1, XM_017015708.1 [P41279-1] XP_016871198.1, XM_017015709.1 [P41279-1] XP_016871199.1, XM_017015710.1 [P41279-1]
UniGeneⁱ	Hs.432453 Hs.663033 Hs.731448

Genome annotation databases

Ensemblⁱ	ENST00000263056; ENSP00000263056; ENSG00000107968 [P41279-1] ENST00000375321; ENSP00000364470; ENSG00000107968 [P41279-1] ENST00000542547; ENSP00000443610; ENSG00000107968 [P41279-1]
GeneIDⁱ	1326
KEGGⁱ	hsa:1326
UCSC genome browser More...UCSCⁱ	uc001ivi.3 human [P41279-1]

Keywords - Coding sequence diversityⁱ

Alternative initiation, Polymorphism

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
P41279	Isoform 2 of Mitogen-activated protein kinase kinase kinase 8		HUMAN		438	UniRef100_P41279
UPI0007DC5358		HUMAN		304

Protein	Similar proteins		Species	Score	Length	Source
P41279	Mitogen-activated protein kinase kinase kinase 8		RAT		467	UniRef90_P41279
Mitogen-activated protein kinase kinase kinase 8		MOUSE		467
Isoform 2 of Mitogen-activated protein kinase kinase kinase 8		HUMAN		438
Uncharacterized protein		MACNE		572
Uncharacterized protein		PAPAN		572
+94

Protein	Similar proteins		Species	Score	Length	Source
P41279	Mitogen-activated protein kinase kinase kinase 8		RAT		467	UniRef50_P41279
Mitogen-activated protein kinase kinase kinase 8		MOUSE		467
Isoform 2 of Mitogen-activated protein kinase kinase kinase 8		HUMAN		438
Uncharacterized protein		PAPAN		572
Uncharacterized protein		MACNE		572
+301

Cross-referencesⁱ

Web resourcesⁱ

SeattleSNPs

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	D14497 mRNA Translation: BAA03387.1 Z14138 mRNA Translation: CAA78512.1 AK290320 mRNA Translation: BAF83009.1 AY309013 Genomic DNA Translation: AAP45053.1 AL161651 Genomic DNA No translation available. CH471072 Genomic DNA Translation: EAW86004.1 CH471072 Genomic DNA Translation: EAW86005.1 CH471072 Genomic DNA Translation: EAW86006.1 CH471072 Genomic DNA Translation: EAW86007.1 BC104833 mRNA Translation: AAI04834.1 BC113566 mRNA Translation: AAI13567.1 AF133211 Genomic DNA Translation: AAG13454.1
CCDSⁱ	CCDS7166.1 [P41279-1]
PIRⁱ	A48713
RefSeqⁱ	NP_001231063.1, NM_001244134.1 [P41279-1] NP_001307890.1, NM_001320961.1 [P41279-1] NP_005195.2, NM_005204.3 [P41279-1] XP_016871196.1, XM_017015707.1 XP_016871197.1, XM_017015708.1 [P41279-1] XP_016871198.1, XM_017015709.1 [P41279-1] XP_016871199.1, XM_017015710.1 [P41279-1]
UniGeneⁱ	Hs.432453 Hs.663033 Hs.731448

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	4Y83	X-ray	2.89	A/B/C	66-395	[»]
	4Y85	X-ray	2.33	A/B/C	66-395	[»]
	5IU2	X-ray	2.70	A/B	66-395	[»]
ProteinModelPortalⁱ	P41279
SMRⁱ	P41279
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	107719, 21 interactors
CORUMⁱ	P41279
DIPⁱ	DIP-27534N
IntActⁱ	P41279, 14 interactors
MINTⁱ	P41279
STRINGⁱ	9606.ENSP00000263056

Chemistry databases

BindingDBⁱ	P41279
ChEMBLⁱ	CHEMBL4899
GuidetoPHARMACOLOGYⁱ	2083

PTM databases

iPTMnetⁱ	P41279
PhosphoSitePlusⁱ	P41279

Polymorphism and mutation databases

BioMutaⁱ	MAP3K8
DMDMⁱ	50403742

Proteomic databases

MaxQBⁱ	P41279
PaxDbⁱ	P41279
PeptideAtlasⁱ	P41279
PRIDEⁱ	P41279
ProteomicsDBⁱ	55458 55459 [P41279-2]

Protocols and materials databases

The DNASU plasmid repository More...DNASUⁱ	1326
Structural Biology Knowledgebase	Search...

Genome annotation databases

Ensemblⁱ	ENST00000263056; ENSP00000263056; ENSG00000107968 [P41279-1] ENST00000375321; ENSP00000364470; ENSG00000107968 [P41279-1] ENST00000542547; ENSP00000443610; ENSG00000107968 [P41279-1]
GeneIDⁱ	1326
KEGGⁱ	hsa:1326
UCSCⁱ	uc001ivi.3 human [P41279-1]

Organism-specific databases

CTDⁱ	1326
DisGeNETⁱ	1326
EuPathDBⁱ	HostDB:ENSG00000107968.9
GeneCardsⁱ	MAP3K8
HGNCⁱ	HGNC:6860 MAP3K8
HPAⁱ	CAB005120 HPA017962
MalaCardsⁱ	MAP3K8
MIMⁱ	191195 gene
neXtProtⁱ	NX_P41279
OpenTargetsⁱ	ENSG00000107968
PharmGKBⁱ	PA30606
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG0201 Eukaryota ENOG410XP9G LUCA
GeneTreeⁱ	ENSGT00800000124036
HOGENOMⁱ	HOG000285978
HOVERGENⁱ	HBG006306
InParanoidⁱ	P41279
KOⁱ	K04415
OMAⁱ	EGGSVME
OrthoDBⁱ	EOG091G0682
PhylomeDBⁱ	P41279
TreeFamⁱ	TF105117

Enzyme and pathway databases

Reactomeⁱ	R-HSA-389357 CD28 dependent PI3K/Akt signaling R-HSA-5684264 MAP3K8 (TPL2)-dependent MAPK1/3 activation
SignaLinkⁱ	P41279
SIGNORⁱ	P41279

Miscellaneous databases

ChiTaRSⁱ	MAP3K8 human
GeneWikiⁱ	MAP3K8
GenomeRNAiⁱ	1326
Protein Ontology More...PROⁱ	PR:P41279
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000107968 Expressed in 192 organ(s), highest expression level in omental fat pad
CleanExⁱ	HS_MAP3K8
ExpressionAtlasⁱ	P41279 baseline and differential
Genevisibleⁱ	P41279 HS

Family and domain databases

InterProⁱ	View protein in InterPro IPR011009 Kinase-like_dom_sf IPR017424 MAPKKK8 IPR000719 Prot_kinase_dom IPR008271 Ser/Thr_kinase_AS
Pfamⁱ	View protein in Pfam PF00069 Pkinase, 1 hit
PIRSFⁱ	PIRSF038171 MAPKKK8, 1 hit
SMARTⁱ	View protein in SMART SM00220 S_TKc, 1 hit
SUPFAMⁱ	SSF56112 SSF56112, 1 hit
PROSITEⁱ	View protein in PROSITE PS50011 PROTEIN_KINASE_DOM, 1 hit PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	M3K8_HUMAN
Accessionⁱ	P41279Primary (citable) accession number: P41279 Secondary accession number(s): A8K2Q5 , D3DRX1, Q14275, Q5T855, Q9HC81
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
	Last sequence update:	July 19, 2004
	Last modified:	November 7, 2018
	This is version 182 of the entry and version 2 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousⁱ

Keywords - Technical termⁱ

3D-structure, Complete proteome, Reference proteome

Documents

SIMILARITY comments
Index of protein domains and families
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations
Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
PDB cross-references
Index of Protein Data Bank (PDB) cross-references
Human chromosome 10
Human chromosome 10: entries, gene names and cross-references to MIM
Human and mouse protein kinases
Human and mouse protein kinases: classification and index

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UniProtKB - P41279 (M3K8_HUMAN)

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Mitogen-activated protein kinase kinase kinase 8

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Miscellaneous

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Regions

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

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Cytosol

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Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Keywords - Diseasei

Organism-specific databases

Chemistry databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

Protein-protein interaction databases

Chemistry databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

Family and domain databases

Experimental Info

Natural variant

Alternative sequence

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Documents

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Web resourcesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ