MAP4K2
Mitogen-activated protein kinase kinase kinase kinase 2
Also known as: BL44, GCK, M4K2_HUMAN, RAB8IP
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q12851
- Gene
- MAP4K2
- Ensembl
- ENSG00000168067
- Chromosome
- 11
- Canonical length
- 820 aa
- Protein class
- Enzymes, Plasma proteins, Predicted intracellular proteins
- Subcellular location
- Vesicles
OverviewNCBI Gene
The protein encoded by this gene is a member of the serine/threonine protein kinase family. Although this kinase is found in many tissues, its expression in lymphoid follicles is restricted to the cells of germinal centre, where it may participate in B-cell differentiation. This kinase can be activated by TNF-alpha, and has been shown to specifically activate MAP kinases. This kinase is also found to interact with TNF receptor-associated factor 2 (TRAF2), which is involved in the activation of MAP3K1/MEKK1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]
Canonical amino-acid sequenceUniProt
820 residues, UniProt reviewed canonical sequence.
>Q12851|MAP4K2
1 MALLRDVSLQ DPRDRFELLQ RVGAGTYGDV YKARDTVTSE LAAVKIVKLD PGDDISSLQQ
61 EITILRECRH PNVVAYIGSY LRNDRLWICM EFCGGGSLQE IYHATGPLEE RQIAYVCREA
121 LKGLHHLHSQ GKIHRDIKGA NLLLTLQGDV KLADFGVSGE LTASVAKRRS FIGTPYWMAP
181 EVAAVERKGG YNELCDVWAL GITAIELGEL QPPLFHLHPM RALMLMSKSS FQPPKLRDKT
241 RWTQNFHHFL KLALTKNPKK RPTAEKLLQH PFTTQQLPRA LLTQLLDKAS DPHLGTPSPE
301 DCELETYDMF PDTIHSRGQH GPAERTPSEI QFHQVKFGAP RRKETDPLNE PWEEEWTLLG
361 KEELSGSLLQ SVQEALEERS LTIRSASEFQ ELDSPDDTMG TIKRAPFLGP LPTDPPAEEP
421 LSSPPGTLPP PPSGPNSSPL LPTAWATMKQ REDPERSSCH GLPPTPKVHM GACFSKVFNG
481 CPLRIHAAVT WIHPVTRDQF LVVGAEEGIY TLNLHELHED TLEKLISHRC SWLYCVNNVL
541 LSLSGKSTHI WAHDLPGLFE QRRLQQQVPL SIPTNRLTQR IIPRRFALST KIPDTKGCLQ
601 CRVVRNPYTG ATFLLAALPT SLLLLQWYEP LQKFLLLKNF SSPLPSPAGM LEPLVLDGKE
661 LPQVCVGAEG PEGPGCRVLF HVLPLEAGLT PDILIPPEGI PGSAQQVIQV DRDTILVSFE
721 RCVRIVNMQG EPTATLAPEL TFDFPIETVV CLQDSVLAFW SHGMQGRSLD TNEVTQEITD
781 ETRIFRVLGA HRDIILESIP TDNPEAHSNL YILTGHQSTYLocalizationUniProt · AlphaFold · HPA
Whether an antibody against MAP4K2 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
- Cell surface
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.31
- Highest tissue expression
- 18 nTPM
Expression across tissuesHPA
Tissue
- cerebellum: 18 nTPM
- lymph node: 17 nTPM
- spleen: 16 nTPM
- bone marrow: 15 nTPM
- tonsil: 13 nTPM
- cerebral cortex: 11 nTPM
Single-cell type
- platelets: 86 nCPM
- lymphatic endothelial cells: 75 nCPM
- late spermatids: 55 nCPM
- hematopoietic stem cells: 45 nCPM
- early spermatids: 43 nCPM
- b-cells: 40 nCPM
Immune cell
- non-classical monocyte: 16 nTPM
- intermediate monocyte: 13 nTPM
- memory B-cell: 9.9 nTPM
- T-reg: 9.5 nTPM
- neutrophil: 8 nTPM
- naive CD4 T-cell: 7.7 nTPM
Brain region
- cerebral cortex: 21 nTPM
- thalamus: 20 nTPM
- cerebellum: 20 nTPM
- amygdala: 19 nTPM
- white matter: 18 nTPM
- midbrain: 17 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)
- 0.69
- gnomAD pLI
- 0
- gnomAD missense Z
- 1.6
- DepMap mean gene effect
- -0.17
- 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
- immune response
- innate immune response
- intracellular signal transduction
- JNK cascade
- positive regulation of JNK cascade
- positive regulation of JUN kinase activity
- protein phosphorylation
- vesicle targeting
Molecular functions
- ATP binding
- MAP kinase kinase kinase kinase activity
- mitogen-activated protein kinase kinase kinase binding
- protein serine kinase activity
- protein serine/threonine kinase activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of MAP4K2 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 MAP4K2 as an antibody target. Whether an autoantibody or antibody against MAP4K2 could matter depends on whether native MAP4K2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
MAP4K2 is annotated at the cell surface, where native MAP4K2 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label MAP4K2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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