UniProtKB - P41279 (M3K8_HUMAN)
Mitogen-activated protein kinase kinase kinase 8
MAP3K8
Functioni
Miscellaneous
Caution
Catalytic activityi
Cofactori
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: ProtInc
GO - Biological processi
- cell cycle Source: UniProtKB-KW
- interleukin-1-mediated signaling pathway Source: Reactome
- protein phosphorylation Source: ProtInc
- stress-activated MAPK cascade Source: Reactome
- T cell costimulation Source: Reactome
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
PathwayCommonsi | P41279 |
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 | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000107968.9 |
HGNCi | HGNC:6860, MAP3K8 |
MIMi | 191195, gene |
neXtProti | NX_P41279 |
Subcellular locationi
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
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. 1 Publication | 1 | |
Mutagenesisi | 290 | T → D: Impaired MEK phosphorylation and autophosphorylation activities. No effect on KSR2 binding. 1 Publication | 1 | |
Mutagenesisi | 290 | T → E: Loss of MEK phosphorylation activity and almost abolished autophosphorylation activity. No effect on KSR2 binding. 1 Publication | 1 |
Keywords - Diseasei
Proto-oncogeneOrganism-specific databases
DisGeNETi | 1326 |
MalaCardsi | MAP3K8 |
OpenTargetsi | ENSG00000107968 |
PharmGKBi | PA30606 |
Miscellaneous databases
Pharosi | P41279, Tchem |
Chemistry databases
ChEMBLi | CHEMBL4899 |
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 | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 80 | Phosphothreonine1 Publication | 1 | |
Modified residuei | 141 | PhosphoserineCombined sources | 1 | |
Modified residuei | 290 | Phosphothreonine2 Publications | 1 | |
Modified residuei | 400 | Phosphoserine2 Publications | 1 | |
Modified residuei | 443 | Phosphoserine1 Publication | 1 |
Post-translational modificationi
Keywords - PTMi
PhosphoproteinProteomic databases
CPTACi | CPTAC-858 CPTAC-859 |
jPOSTi | P41279 |
MassIVEi | P41279 |
MaxQBi | P41279 |
PaxDbi | P41279 |
PeptideAtlasi | P41279 |
PRIDEi | P41279 |
ProteomicsDBi | 55458 [P41279-1] 55459 [P41279-2] |
PTM databases
iPTMneti | P41279 |
PhosphoSitePlusi | P41279 |
Expressioni
Tissue specificityi
Developmental stagei
Inductioni
Gene expression databases
Bgeei | ENSG00000107968, Expressed in bone marrow and 205 other tissues |
ExpressionAtlasi | P41279, baseline and differential |
Genevisiblei | P41279, HS |
Organism-specific databases
HPAi | ENSG00000107968, Tissue enhanced (bone) |
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 PublicationsBinary interactionsi
Hide detailsP41279
With | #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, 27 interactors |
CORUMi | P41279 |
DIPi | DIP-27534N |
IntActi | P41279, 14 interactors |
MINTi | P41279 |
STRINGi | 9606.ENSP00000263056 |
Chemistry databases
BindingDBi | P41279 |
Miscellaneous databases
RNActi | P41279, protein |
Structurei
Secondary structure
3D structure databases
SMRi | P41279 |
ModBasei | Search... |
PDBe-KBi | 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
Phylogenomic databases
eggNOGi | KOG0201, Eukaryota |
GeneTreei | ENSGT00940000158806 |
HOGENOMi | CLU_047137_0_0_1 |
InParanoidi | P41279 |
OMAi | MACKLVP |
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 |
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 |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative initiation. AlignAdd to basketThis entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketQ5T854 | Q5T854_HUMAN | Mitogen-activated protein kinase ki... | MAP3K8 | 132 | Annotation score: | ||
Q5T857 | Q5T857_HUMAN | Mitogen-activated protein kinase ki... | MAP3K8 | 255 | Annotation score: | ||
Q5T853 | Q5T853_HUMAN | Mitogen-activated protein kinase ki... | MAP3K8 | 223 | 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 | Graphical view | 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 |
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] |
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] |
Keywords - Coding sequence diversityi
Alternative initiation, PolymorphismSimilar proteinsi
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] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi 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 | [»] | |
SMRi | P41279 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 107719, 27 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
CPTACi | CPTAC-858 CPTAC-859 |
jPOSTi | P41279 |
MassIVEi | P41279 |
MaxQBi | P41279 |
PaxDbi | P41279 |
PeptideAtlasi | P41279 |
PRIDEi | P41279 |
ProteomicsDBi | 55458 [P41279-1] 55459 [P41279-2] |
Protocols and materials databases
Antibodypediai | 2836, 581 antibodies |
DNASUi | 1326 |
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 | ENSG00000107968, Tissue enhanced (bone) |
MalaCardsi | MAP3K8 |
MIMi | 191195, gene |
neXtProti | NX_P41279 |
OpenTargetsi | ENSG00000107968 |
PharmGKBi | PA30606 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0201, Eukaryota |
GeneTreei | ENSGT00940000158806 |
HOGENOMi | CLU_047137_0_0_1 |
InParanoidi | P41279 |
OMAi | MACKLVP |
PhylomeDBi | P41279 |
TreeFami | TF105117 |
Enzyme and pathway databases
PathwayCommonsi | P41279 |
Reactomei | R-HSA-389357, CD28 dependent PI3K/Akt signaling R-HSA-5684264, MAP3K8 (TPL2)-dependent MAPK1/3 activation |
SignaLinki | P41279 |
SIGNORi | P41279 |
Miscellaneous databases
BioGRID-ORCSi | 1326, 5 hits in 875 CRISPR screens |
ChiTaRSi | MAP3K8, human |
GeneWikii | MAP3K8 |
GenomeRNAii | 1326 |
Pharosi | P41279, Tchem |
PROi | PR:P41279 |
RNActi | P41279, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000107968, Expressed in bone marrow and 205 other tissues |
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... |
MobiDBi | Search... |
Entry informationi
Entry namei | M3K8_HUMAN | |
Accessioni | P41279Primary (citable) accession number: P41279 Secondary accession number(s): A8K2Q5 Q9HC81 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 1995 |
Last sequence update: | July 19, 2004 | |
Last modified: | December 2, 2020 | |
This is version 197 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, Reference proteomeDocuments
- 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 - SIMILARITY comments
Index of protein domains and families - Human chromosome 10
Human chromosome 10: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - Human and mouse protein kinases
Human and mouse protein kinases: classification and index