MAP3K1
Mitogen-activated protein kinase kinase kinase 1
Also known as: M3K1_HUMAN, MAPKKK1, MEKK, MEKK1
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q13233
- Gene
- MAP3K1
- Ensembl
- ENSG00000095015
- Chromosome
- 5
- Canonical length
- 1512 aa
- Protein class
- Cancer-related genes, Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Predicted membrane proteins
- Subcellular location
- Cytosol
OverviewNCBI Gene
The protein encoded by this gene is a serine/threonine kinase and is part of some signal transduction cascades, including the ERK and JNK kinase pathways as well as the NF-kappa-B pathway. The encoded protein is activated by autophosphorylation and requires magnesium as a cofactor in phosphorylating other proteins. This protein has E3 ligase activity conferred by a plant homeodomain (PHD) in its N-terminus and phospho-kinase activity conferred by a kinase domain in its C-terminus. [provided by RefSeq, Mar 2012]
Canonical amino-acid sequenceUniProt
1512 residues, UniProt reviewed canonical sequence.
>Q13233|MAP3K1
1 MAAAAGNRAS SSGFPGARAT SPEAGGGGGA LKASSAPAAA AGLLREAGSG GRERADWRRR
61 QLRKVRSVEL DQLPEQPLFL AASPPASSTS PSPEPADAAG SGTGFQPVAV PPPHGAASRG
121 GAHLTESVAA PDSGASSPAA AEPGEKRAPA AEPSPAAAPA GREMENKETL KGLHKMDDRP
181 EERMIREKLK ATCMPAWKHE WLERRNRRGP VVVKPIPVKG DGSEMNHLAA ESPGEVQASA
241 ASPASKGRRS PSPGNSPSGR TVKSESPGVR RKRVSPVPFQ SGRITPPRRA PSPDGFSPYS
301 PEETNRRVNK VMRARLYLLQ QIGPNSFLIG GDSPDNKYRV FIGPQNCSCA RGTFCIHLLF
361 VMLRVFQLEP SDPMLWRKTL KNFEVESLFQ KYHSRRSSRI KAPSRNTIQK FVSRMSNSHT
421 LSSSSTSTSS SENSIKDEEE QMCPICLLGM LDEESLTVCE DGCRNKLHHH CMSIWAEECR
481 RNREPLICPL CRSKWRSHDF YSHELSSPVD SPSSLRAAQQ QTVQQQPLAG SRRNQESNFN
541 LTHYGTQQIP PAYKDLAEPW IQVFGMELVG CLFSRNWNVR EMALRRLSHD VSGALLLANG
601 ESTGNSGGSS GSSPSGGATS GSSQTSISGD VVEACCSVLS MVCADPVYKV YVAALKTLRA
661 MLVYTPCHSL AERIKLQRLL QPVVDTILVK CADANSRTSQ LSISTLLELC KGQAGELAVG
721 REILKAGSIG IGGVDYVLNC ILGNQTESNN WQELLGRLCL IDRLLLEFPA EFYPHIVSTD
781 VSQAEPVEIR YKKLLSLLTF ALQSIDNSHS MVGKLSRRIY LSSARMVTTV PHVFSKLLEM
841 LSVSSSTHFT RMRRRLMAIA DEVEIAEAIQ LGVEDTLDGQ QDSFLQASVP NNYLETTENS
901 SPECTVHLEK TGKGLCATKL SASSEDISER LASISVGPSS STTTTTTTTE QPKPMVQTKG
961 RPHSQCLNSS PLSHHSQLMF PALSTPSSST PSVPAGTATD VSKHRLQGFI PCRIPSASPQ
1021 TQRKFSLQFH RNCPENKDSD KLSPVFTQSR PLPSSNIHRP KPSRPTPGNT SKQGDPSKNS
1081 MTLDLNSSSK CDDSFGCSSN SSNAVIPSDE TVFTPVEEKC RLDVNTELNS SIEDLLEASM
1141 PSSDTTVTFK SEVAVLSPEK AENDDTYKDD VNHNQKCKEK MEAEEEEALA IAMAMSASQD
1201 ALPIVPQLQV ENGEDIIIIQ QDTPETLPGH TKAKQPYRED TEWLKGQQIG LGAFSSCYQA
1261 QDVGTGTLMA VKQVTYVRNT SSEQEEVVEA LREEIRMMSH LNHPNIIRML GATCEKSNYN
1321 LFIEWMAGGS VAHLLSKYGA FKESVVINYT EQLLRGLSYL HENQIIHRDV KGANLLIDST
1381 GQRLRIADFG AAARLASKGT GAGEFQGQLL GTIAFMAPEV LRGQQYGRSC DVWSVGCAII
1441 EMACAKPPWN AEKHSNHLAL IFKIASATTA PSIPSHLSPG LRDVALRCLE LQPQDRPPSR
1501 ELLKHPVFRT TWLocalizationUniProt · AlphaFold · HPA
Whether an antibody against MAP3K1 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
- 25 nTPM
Expression across tissuesHPA
Tissue
- retina: 25 nTPM
- bone marrow: 23 nTPM
- tonsil: 23 nTPM
- spleen: 19 nTPM
- breast: 19 nTPM
- skin: 19 nTPM
Single-cell type
- neutrophils: 415 nCPM
- b-cells: 303 nCPM
- oligodendrocyte progenitor cells: 255 nCPM
- monocytes: 246 nCPM
- sertoli cells: 233 nCPM
- loop of henle epithelial cells: 217 nCPM
Immune cell
- basophil: 6.3 nTPM
- non-classical monocyte: 4.9 nTPM
- intermediate monocyte: 4.5 nTPM
- memory B-cell: 4 nTPM
- T-reg: 3.8 nTPM
- naive B-cell: 3.4 nTPM
Brain region
- choroid plexus: 17 nTPM
- cerebellum: 12 nTPM
- medulla oblongata: 12 nTPM
- spinal cord: 12 nTPM
- white matter: 12 nTPM
- thalamus: 11 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about MAP3K1.
Disease | AllUniProt
Conditions MAP3K1 is implicated in, by any mechanism.
- 46,XY sex reversal 6 (SRXY6) MIM:613762
Disease | GeneticClinVar
18 pathogenic / likely-pathogenic of 470 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- 46,XY sex reversal 6
- Ovarian neoplasm
- MAP3K1-related disorder
- Inborn genetic diseases
- See cases
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)
- 0.21
- gnomAD pLI
- 1
- gnomAD missense Z
- 1.67
- DepMap mean gene effect
- -0.16
- 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
- Fc-epsilon receptor signaling pathway
- protein phosphorylation
Molecular functions
- ATP binding
- MAP kinase kinase kinase activity
- protein kinase activity
- protein kinase binding
- protein serine kinase activity
- protein serine/threonine kinase activity
- ubiquitin protein ligase activity
- zinc ion binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Protein kinase domain
- Zinc finger, RING-type
- Zinc finger, SWIM-type
- Serine/threonine-protein kinase, active site
- Protein kinase-like domain superfamily
- Armadillo-like helical
- Zinc finger, RING/FYVE/PHD-type
- Armadillo-type fold
- Protein kinase, ATP binding site
- Mitogen-activated protein kinase kinase kinase
- Protein kinase domain
- SWIM zinc finger
- Centrosomal protein CEP104, TOG domain
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of MAP3K1 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 MAP3K1 as an antibody target. Whether an autoantibody or antibody against MAP3K1 could matter depends on whether native MAP3K1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
MAP3K1 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 MAP3K1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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