MAP3K8
Mitogen-activated protein kinase kinase kinase 8
Also known as: c-COT, COT, EST, ESTF, M3K8_HUMAN, MEKK8, Tpl-2
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P41279
- Gene
- MAP3K8
- Ensembl
- ENSG00000107968
- Chromosome
- 10
- Canonical length
- 467 aa
- Protein class
- Enzymes, Plasma proteins, Predicted intracellular proteins
- Subcellular location
- Cytosol
OverviewNCBI Gene
This gene is an oncogene that encodes a member of the serine/threonine protein kinase family. The encoded protein localizes to the cytoplasm and can activate both the MAP kinase and JNK kinase pathways. This protein was shown to activate IkappaB kinases, and thus induce the nuclear production of NF-kappaB. This protein was also found to promote the production of TNF-alpha and IL-2 during T lymphocyte activation. This gene may also utilize a downstream in-frame translation start codon, and thus produce an isoform containing a shorter N-terminus. The shorter isoform has been shown to display weaker transforming activity. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2011]
Canonical amino-acid sequenceUniProt
467 residues, UniProt reviewed canonical sequence.
>P41279|MAP3K8
1 MEYMSTGSDN KEEIDLLIKH LNVSDVIDIM ENLYASEEPA VYEPSLMTMC QDSNQNDERS
61 KSLLLSGQEV PWLSSVRYGT VEDLLAFANH ISNTAKHFYG QRPQESGILL NMVITPQNGR
121 YQIDSDVLLI PWKLTYRNIG SDFIPRGAFG KVYLAQDIKT KKRMACKLIP VDQFKPSDVE
181 IQACFRHENI AELYGAVLWG ETVHLFMEAG EGGSVLEKLE SCGPMREFEI IWVTKHVLKG
241 LDFLHSKKVI HHDIKPSNIV FMSTKAVLVD FGLSVQMTED VYFPKDLRGT EIYMSPEVIL
301 CRGHSTKADI YSLGATLIHM QTGTPPWVKR YPRSAYPSYL YIIHKQAPPL EDIADDCSPG
361 MRELIEASLE RNPNHRPRAA DLLKHEALNP PREDQPRCQS LDSALLERKR LLSRKELELP
421 ENIADSSCTG STEESEMLKR QRSLYIDLGA LAGYFNLVRG PPTLEYGLocalizationUniProt · AlphaFold · HPA
Whether an antibody against MAP3K8 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.35
- Highest tissue expression
- 313 nTPM
Expression across tissuesHPA
Tissue
- bone marrow: 313 nTPM
- adipose tissue: 65 nTPM
- lung: 62 nTPM
- urinary bladder: 46 nTPM
- placenta: 44 nTPM
- spleen: 40 nTPM
Single-cell type
- monocytes: 842 nCPM
- neutrophils: 683 nCPM
- innate lymphoid cells: 548 nCPM
- urothelial cells: 543 nCPM
- hofbauer cells: 515 nCPM
- endometrial luminal cells: 501 nCPM
Immune cell
- eosinophil: 53 nTPM
- basophil: 46 nTPM
- non-classical monocyte: 39 nTPM
- naive B-cell: 38 nTPM
- neutrophil: 36 nTPM
- plasmacytoid DC: 30 nTPM
Brain region
- choroid plexus: 42 nTPM
- thalamus: 32 nTPM
- hypothalamus: 26 nTPM
- medulla oblongata: 20 nTPM
- spinal cord: 17 nTPM
- pons: 15 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.32
- gnomAD pLI
- 0.97
- gnomAD missense Z
- 2.29
- DepMap mean gene effect
- 0.07
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
Molecular functions
- ATP binding
- magnesium ion binding
- MAP kinase kinase kinase activity
- protein serine kinase activity
- protein serine/threonine kinase activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Protein kinase domain
- Serine/threonine-protein kinase, active site
- Protein kinase-like domain superfamily
- Mitogen-activated protein kinase kinase kinase
- Protein kinase domain
- Mitogen-activated protein (MAP) kinase kinase kinase 8
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of MAP3K8 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads MAP3K8 as an antibody target. Whether an autoantibody or antibody against MAP3K8 could matter depends on whether native MAP3K8 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
MAP3K8 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label MAP3K8 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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