Seroatlas · Human Serome Atlas

MAP3K3

Mitogen-activated protein kinase kinase kinase 3

Also known as: M3K3_HUMAN, MAPKKK3, MEKK3

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
Q99759
Gene
MAP3K3
Ensembl
ENSG00000198909
Chromosome
17
Canonical length
626 aa
Protein class
Cancer-related genes, Enzymes, Plasma proteins, Predicted intracellular proteins
Subcellular location
Nucleoplasm

OverviewNCBI Gene

This gene product is a 626-amino acid polypeptide that is 96.5% identical to mouse Mekk3. Its catalytic domain is closely related to those of several other kinases, including mouse Mekk2, tobacco NPK, and yeast Ste11. Northern blot analysis revealed a 4.6-kb transcript that appears to be ubiquitously expressed. This protein directly regulates the stress-activated protein kinase (SAPK) and extracellular signal-regulated protein kinase (ERK) pathways by activating SEK and MEK1/2 respectively; it does not regulate the p38 pathway. In cotransfection assays, it enhanced transcription from a nuclear factor kappa-B (NFKB)-dependent reporter gene, consistent with a role in the SAPK pathway. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

626 residues, UniProt reviewed canonical sequence.

>Q99759|MAP3K3
     1  MDEQEALNSI MNDLVALQMN RRHRMPGYET MKNKDTGHSN RQSDVRIKFE HNGERRIIAF
    61  SRPVKYEDVE HKVTTVFGQP LDLHYMNNEL SILLKNQDDL DKAIDILDRS SSMKSLRILL
   121  LSQDRNHNSS SPHSGVSRQV RIKASQSAGD INTIYQPPEP RSRHLSVSSQ NPGRSSPPPG
   181  YVPERQQHIA RQGSYTSINS EGEFIPETSE QCMLDPLSSA ENSLSGSCQS LDRSADSPSF
   241  RKSRMSRAQS FPDNRQEYSD RETQLYDKGV KGGTYPRRYH VSVHHKDYSD GRRTFPRIRR
   301  HQGNLFTLVP SSRSLSTNGE NMGLAVQYLD PRGRLRSADS ENALSVQERN VPTKSPSAPI
   361  NWRRGKLLGQ GAFGRVYLCY DVDTGRELAS KQVQFDPDSP ETSKEVSALE CEIQLLKNLQ
   421  HERIVQYYGC LRDRAEKTLT IFMEYMPGGS VKDQLKAYGA LTESVTRKYT RQILEGMSYL
   481  HSNMIVHRDI KGANILRDSA GNVKLGDFGA SKRLQTICMS GTGMRSVTGT PYWMSPEVIS
   541  GEGYGRKADV WSLGCTVVEM LTEKPPWAEY EAMAAIFKIA TQPTNPQLPS HISEHGRDFL
   601  RRIFVEARQR PSAEELLTHH FAQLMY

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MAP3K3 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)
0.44
Highest tissue expression
38 nTPM

Expression across tissuesHPA

Tissue

  • heart muscle: 38 nTPM
  • spleen: 32 nTPM
  • blood vessel: 31 nTPM
  • bone marrow: 30 nTPM
  • tongue: 28 nTPM
  • adipose tissue: 28 nTPM

Single-cell type

  • neutrophils: 558 nCPM
  • monocytes: 166 nCPM
  • kupffer cells: 156 nCPM
  • microglia: 154 nCPM
  • neutrophil progenitors: 141 nCPM
  • retinal ganglion cells: 131 nCPM

Immune cell

  • neutrophil: 25 nTPM
  • eosinophil: 15 nTPM
  • basophil: 15 nTPM
  • non-classical monocyte: 13 nTPM
  • intermediate monocyte: 12 nTPM
  • classical monocyte: 11 nTPM

Brain region

  • medulla oblongata: 27 nTPM
  • cerebellum: 25 nTPM
  • choroid plexus: 24 nTPM
  • white matter: 24 nTPM
  • pons: 24 nTPM
  • spinal cord: 24 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MAP3K3.

Disease | AllUniProt

Conditions MAP3K3 is implicated in, by any mechanism.

  • Cerebral cavernous malformations 5 (CCM5) MIM:621032

Disease | GeneticClinVar

1 pathogenic / likely-pathogenic of 125 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

  • Verrucous hemangioma
  • CEREBRAL CAVERNOUS MALFORMATIONS 5, SOMATIC

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)
0.3
gnomAD pLI
0.99
gnomAD missense Z
2.04
DepMap mean gene effect
-0.19
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

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of MAP3K3 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 MAP3K3 as an antibody target. Whether an autoantibody or antibody against MAP3K3 could matter depends on whether native MAP3K3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

MAP3K3 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 MAP3K3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/MAP3K3. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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