Seroatlas · Human Serome Atlas

MAP3K5

Mitogen-activated protein kinase kinase kinase 5

Also known as: ASK1, M3K5_HUMAN, MAPKKK5, MEKK5

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

Protein identityUniProt · HPA

UniProt accession: Q99683
Gene: MAP3K5
Ensembl: ENSG00000197442
Chromosome: 6
Canonical length: 1374 aa
Protein class: Enzymes, Plasma proteins, Predicted intracellular proteins
Subcellular location: Cytosol
Quaternary structure: Homodimer

OverviewNCBI Gene

Mitogen-activated protein kinase (MAPK) signaling cascades include MAPK or extracellular signal-regulated kinase (ERK), MAPK kinase (MKK or MEK), and MAPK kinase kinase (MAPKKK or MEKK). MAPKK kinase/MEKK phosphorylates and activates its downstream protein kinase, MAPK kinase/MEK, which in turn activates MAPK. The kinases of these signaling cascades are highly conserved, and homologs exist in yeast, Drosophila, and mammalian cells. MAPKKK5 contains 1,374 amino acids with all 11 kinase subdomains. Northern blot analysis shows that MAPKKK5 transcript is abundantly expressed in human heart and pancreas. The MAPKKK5 protein phosphorylates and activates MKK4 (aliases SERK1, MAPKK4) in vitro, and activates c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) during transient expression in COS and 293 cells; MAPKKK5 does not activate MAPK/ERK. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

1374 residues, UniProt reviewed canonical sequence.

>Q99683|MAP3K5
     1  MSTEADEGIT FSVPPFAPSG FCTIPEGGIC RRGGAAAVGE GEEHQLPPPP PGSFWNVESA
    61  AAPGIGCPAA TSSSSATRGR GSSVGGGSRR TTVAYVINEA SQGQLVVAES EALQSLREAC
   121  ETVGATLETL HFGKLDFGET TVLDRFYNAD IAVVEMSDAF RQPSLFYHLG VRESFSMANN
   181  IILYCDTNSD SLQSLKEIIC QKNTMCTGNY TFVPYMITPH NKVYCCDSSF MKGLTELMQP
   241  NFELLLGPIC LPLVDRFIQL LKVAQASSSQ YFRESILNDI RKARNLYTGK ELAAELARIR
   301  QRVDNIEVLT ADIVINLLLS YRDIQDYDSI VKLVETLEKL PTFDLASHHH VKFHYAFALN
   361  RRNLPGDRAK ALDIMIPMVQ SEGQVASDMY CLVGRIYKDM FLDSNFTDTE SRDHGASWFK
   421  KAFESEPTLQ SGINYAVLLL AAGHQFESSF ELRKVGVKLS SLLGKKGNLE KLQSYWEVGF
   481  FLGASVLAND HMRVIQASEK LFKLKTPAWY LKSIVETILI YKHFVKLTTE QPVAKQELVD
   541  FWMDFLVEAT KTDVTVVRFP VLILEPTKIY QPSYLSINNE VEEKTISIWH VLPDDKKGIH
   601  EWNFSASSVR GVSISKFEER CCFLYVLHNS DDFQIYFCTE LHCKKFFEMV NTITEEKGRS
   661  TEEGDCESDL LEYDYEYDEN GDRVVLGKGT YGIVYAGRDL SNQVRIAIKE IPERDSRYSQ
   721  PLHEEIALHK HLKHKNIVQY LGSFSENGFI KIFMEQVPGG SLSALLRSKW GPLKDNEQTI
   781  GFYTKQILEG LKYLHDNQIV HRDIKGDNVL INTYSGVLKI SDFGTSKRLA GINPCTETFT
   841  GTLQYMAPEI IDKGPRGYGK AADIWSLGCT IIEMATGKPP FYELGEPQAA MFKVGMFKVH
   901  PEIPESMSAE AKAFILKCFE PDPDKRACAN DLLVDEFLKV SSKKKKTQPK LSALSAGSNE
   961  YLRSISLPVP VLVEDTSSSS EYGSVSPDTE LKVDPFSFKT RAKSCGERDV KGIRTLFLGI
  1021  PDENFEDHSA PPSPEEKDSG FFMLRKDSER RATLHRILTE DQDKIVRNLM ESLAQGAEEP
  1081  KLKWEHITTL IASLREFVRS TDRKIIATTL SKLKLELDFD SHGISQVQVV LFGFQDAVNK
  1141  VLRNHNIKPH WMFALDSIIR KAVQTAITIL VPELRPHFSL ASESDTADQE DLDVEDDHEE
  1201  QPSNQTVRRP QAVIEDAVAT SGVSTLSSTV SHDSQSAHRS LNVQLGRMKI ETNRLLEELV
  1261  RKEKELQALL HRAIEEKDQE IKHLKLKSQP IEIPELPVFH LNSSGTNTED SELTDWLRVN
  1321  GADEDTISRF LAEDYTLLDV LYYVTRDDLK CLRLRGGMLC TLWKAIIDFR NKQT

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MAP3K5 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: 83 nTPM

Expression across tissuesHPA

Tissue

adrenal gland: 83 nTPM
ovary: 46 nTPM
pancreas: 29 nTPM
basal ganglia: 23 nTPM
blood vessel: 22 nTPM
cerebellum: 18 nTPM

Single-cell type

adrenal cortex cells: 2,393 nCPM
pituicytes/fscs: 1,412 nCPM
neutrophils: 1,382 nCPM
prostatic glandular cells: 895 nCPM
microglia: 723 nCPM
astrocytes: 680 nCPM

Immune cell

neutrophil: 5.2 nTPM
T-reg: 4.6 nTPM
basophil: 3.5 nTPM
MAIT T-cell: 2.9 nTPM
memory CD4 T-cell: 2.5 nTPM
NK-cell: 2.3 nTPM

Brain region

hypothalamus: 53 nTPM
basal ganglia: 50 nTPM
thalamus: 47 nTPM
amygdala: 46 nTPM
cerebellum: 46 nTPM
midbrain: 46 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): 0.34
gnomAD pLI: 0.52
gnomAD missense Z: 3.28
DepMap mean gene effect: 0.15
DepMap dependency class: none

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

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of MAP3K5 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 MAP3K5 as an antibody target. Whether an autoantibody or antibody against MAP3K5 could matter depends on whether native MAP3K5 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

MAP3K5 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 MAP3K5 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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