MAP2K4
Dual specificity mitogen-activated protein kinase kinase 4
Also known as: JNKK1, MEK4, MKK4, MP2K4_HUMAN, PRKMK4, SERK1
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P45985
- Gene
- MAP2K4
- Ensembl
- ENSG00000065559
- Chromosome
- 17
- Canonical length
- 399 aa
- Protein class
- Cancer-related genes, Enzymes, Plasma proteins, Predicted intracellular proteins
- Subcellular location
- Nucleoplasm,Cell Junctions
OverviewNCBI Gene
This gene encodes a member of the mitogen-activated protein kinase (MAPK) family. Members of this family act as an integration point for multiple biochemical signals and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation, and development. They form a three-tiered signaling module composed of MAPKKKs, MAPKKs, and MAPKs. This protein is phosphorylated at serine and threonine residues by MAPKKKs and subsequently phosphorylates downstream MAPK targets at threonine and tyrosine residues. A similar protein in mouse has been reported to play a role in liver organogenesis. A pseudogene of this gene is located on the long arm of chromosome X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
Canonical amino-acid sequenceUniProt
399 residues, UniProt reviewed canonical sequence.
>P45985|MAP2K4
1 MAAPSPSGGG GSGGGSGSGT PGPVGSPAPG HPAVSSMQGK RKALKLNFAN PPFKSTARFT
61 LNPNPTGVQN PHIERLRTHS IESSGKLKIS PEQHWDFTAE DLKDLGEIGR GAYGSVNKMV
121 HKPSGQIMAV KRIRSTVDEK EQKQLLMDLD VVMRSSDCPY IVQFYGALFR EGDCWICMEL
181 MSTSFDKFYK YVYSVLDDVI PEEILGKITL ATVKALNHLK ENLKIIHRDI KPSNILLDRS
241 GNIKLCDFGI SGQLVDSIAK TRDAGCRPYM APERIDPSAS RQGYDVRSDV WSLGITLYEL
301 ATGRFPYPKW NSVFDQLTQV VKGDPPQLSN SEEREFSPSF INFVNLCLTK DESKRPKYKE
361 LLKHPFILMY EERAVEVACY VCKILDQMPA TPSSPMYVDLocalizationUniProt · AlphaFold · HPA
Whether an antibody against MAP2K4 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)
- 0.36
- Highest tissue expression
- 42 nTPM
Expression across tissuesHPA
Tissue
- cerebral cortex: 42 nTPM
- hippocampal formation: 29 nTPM
- hypothalamus: 28 nTPM
- tongue: 26 nTPM
- cerebellum: 25 nTPM
- skeletal muscle: 23 nTPM
Single-cell type
- neutrophils: 565 nCPM
- lactotrophs: 297 nCPM
- gonadotrophs: 271 nCPM
- pituicytes/fscs: 264 nCPM
- brain excitatory neurons: 258 nCPM
- sertoli cells: 255 nCPM
Immune cell
- neutrophil: 11 nTPM
- non-classical monocyte: 3.9 nTPM
- NK-cell: 2.8 nTPM
- naive B-cell: 2.7 nTPM
- naive CD8 T-cell: 2.4 nTPM
- gdT-cell: 2.2 nTPM
Brain region
- cerebral cortex: 78 nTPM
- hippocampal formation: 68 nTPM
- pons: 63 nTPM
- basal ganglia: 61 nTPM
- white matter: 60 nTPM
- hypothalamus: 60 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)
- 0.22
- gnomAD pLI
- 1
- gnomAD missense Z
- 3.23
- DepMap mean gene effect
- 0.08
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- cellular response to mechanical stimulus
- cellular senescence
- Fc-epsilon receptor signaling pathway
- intrinsic apoptotic signaling pathway in response to hydrogen peroxide
- JNK cascade
- MAPK cascade
- negative regulation of motor neuron apoptotic process
- response to wounding
- signal transduction
- smooth muscle cell apoptotic process
Molecular functions
- ATP binding
- JUN kinase kinase activity
- MAP kinase kinase activity
- molecular adaptor activity
- protein kinase activity
- protein serine kinase activity
- protein serine/threonine kinase activity
- protein tyrosine kinase activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of MAP2K4 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 MAP2K4 as an antibody target. Whether an autoantibody or antibody against MAP2K4 could matter depends on whether native MAP2K4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
MAP2K4 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 MAP2K4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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