Seroatlas · Human Serome Atlas

MAP4K4

Mitogen-activated protein kinase kinase kinase kinase 4

Also known as: FLH21957, HGK, M4K4_HUMAN, NIK

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

Protein identityUniProt · HPA

UniProt accession: O95819
Gene: MAP4K4
Ensembl: ENSG00000071054
Chromosome: 2
Canonical length: 1239 aa
Protein class: Enzymes, Plasma proteins, Predicted intracellular proteins

OverviewNCBI Gene

The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase has been shown to specifically activate MAPK8/JNK. The activation of MAPK8 by this kinase is found to be inhibited by the dominant-negative mutants of MAP3K7/TAK1, MAP2K4/MKK4, and MAP2K7/MKK7, which suggests that this kinase may function through the MAP3K7-MAP2K4-MAP2K7 kinase cascade, and mediate the TNF-alpha signaling pathway. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

1239 residues, UniProt reviewed canonical sequence.

>O95819|MAP4K4
     1  MANDSPAKSL VDIDLSSLRD PAGIFELVEV VGNGTYGQVY KGRHVKTGQL AAIKVMDVTE
    61  DEEEEIKLEI NMLKKYSHHR NIATYYGAFI KKSPPGHDDQ LWLVMEFCGA GSITDLVKNT
   121  KGNTLKEDWI AYISREILRG LAHLHIHHVI HRDIKGQNVL LTENAEVKLV DFGVSAQLDR
   181  TVGRRNTFIG TPYWMAPEVI ACDENPDATY DYRSDLWSCG ITAIEMAEGA PPLCDMHPMR
   241  ALFLIPRNPP PRLKSKKWSK KFFSFIEGCL VKNYMQRPST EQLLKHPFIR DQPNERQVRI
   301  QLKDHIDRTR KKRGEKDETE YEYSGSEEEE EEVPEQEGEP SSIVNVPGES TLRRDFLRLQ
   361  QENKERSEAL RRQQLLQEQQ LREQEEYKRQ LLAERQKRIE QQKEQRRRLE EQQRREREAR
   421  RQQEREQRRR EQEEKRRLEE LERRRKEEEE RRRAEEEKRR VEREQEYIRR QLEEEQRHLE
   481  VLQQQLLQEQ AMLLECRWRE MEEHRQAERL QRQLQQEQAY LLSLQHDHRR PHPQHSQQPP
   541  PPQQERSKPS FHAPEPKAHY EPADRAREVE DRFRKTNHSS PEAQSKQTGR VLEPPVPSRS
   601  ESFSNGNSES VHPALQRPAE PQVPVRTTSR SPVLSRRDSP LQGSGQQNSQ AGQRNSTSIE
   661  PRLLWERVEK LVPRPGSGSS SGSSNSGSQP GSHPGSQSGS GERFRVRSSS KSEGSPSQRL
   721  ENAVKKPEDK KEVFRPLKPA DLTALAKELR AVEDVRPPHK VTDYSSSSEE SGTTDEEDDD
   781  VEQEGADEST SGPEDTRAAS SLNLSNGETE SVKTMIVHDD VESEPAMTPS KEGTLIVRQT
   841  QSASSTLQKH KSSSSFTPFI DPRLLQISPS SGTTVTSVVG FSCDGMRPEA IRQDPTRKGS
   901  VVNVNPTNTR PQSDTPEIRK YKKRFNSEIL CAALWGVNLL VGTESGLMLL DRSGQGKVYP
   961  LINRRRFQQM DVLEGLNVLV TISGKKDKLR VYYLSWLRNK ILHNDPEVEK KQGWTTVGDL
  1021  EGCVHYKVVK YERIKFLVIA LKSSVEVYAW APKPYHKFMA FKSFGELVHK PLLVDLTVEE
  1081  GQRLKVIYGS CAGFHAVDVD SGSVYDIYLP THIQCSIKPH AIIILPNTDG MELLVCYEDE
  1141  GVYVNTYGRI TKDVVLQWGE MPTSVAYIRS NQTMGWGEKA IEIRSVETGH LDGVFMHKRA
  1201  QRLKFLCERN DKVFFASVRS GGSSQVYFMT LGRTSLLSW

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MAP4K4 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): 0.46
Highest tissue expression: 230 nTPM

Expression across tissuesHPA

Tissue

spinal cord: 230 nTPM
midbrain: 189 nTPM
hippocampal formation: 181 nTPM
amygdala: 176 nTPM
basal ganglia: 152 nTPM
hypothalamus: 113 nTPM

Single-cell type

neutrophils: 3,043 nCPM
oligodendrocytes: 1,372 nCPM
microglia: 1,111 nCPM
retinal ganglion cells: 1,055 nCPM
monocytes: 820 nCPM
endometrial luminal cells: 809 nCPM

Immune cell

neutrophil: 12 nTPM
basophil: 9 nTPM
plasmacytoid DC: 5.3 nTPM
naive B-cell: 3.8 nTPM
T-reg: 3.5 nTPM
memory B-cell: 3.2 nTPM

Brain region

white matter: 691 nTPM
thalamus: 479 nTPM
medulla oblongata: 447 nTPM
basal ganglia: 431 nTPM
midbrain: 384 nTPM
amygdala: 364 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MAP4K4.

Disease | GeneticClinVar

14 pathogenic / likely-pathogenic of 294 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Inborn genetic diseases
Cerebral arteriovenous malformation
Renal dysplasia
Imperforate anus
MAP4K4-related neurodevelopmental delay

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): 0.18
gnomAD pLI: 1
gnomAD missense Z: 4.74
DepMap mean gene effect: -0.05
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 MAP4K4 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 MAP4K4 as an antibody target. Whether an autoantibody or antibody against MAP4K4 could matter depends on whether native MAP4K4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

MAP4K4 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 MAP4K4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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