MAP3K12
Mitogen-activated protein kinase kinase kinase 12
Also known as: DLK, M3K12_HUMAN, MEKK12, MUK, ZPK, ZPKP1
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q12852
- Gene
- MAP3K12
- Ensembl
- ENSG00000139625
- Chromosome
- 12
- Canonical length
- 859 aa
- Protein class
- Enzymes, Predicted intracellular proteins, Transporters
- Subcellular location
- Nucleoplasm,Plasma membrane
- Quaternary structure
- Homodimer
OverviewNCBI Gene
This gene encodes a member of the serine/threonine protein kinase family. This kinase contains a leucine-zipper domain and is predominately expressed in neuronal cells. The phosphorylation state of this kinase in synaptic terminals was shown to be regulated by membrane depolarization via calcineurin. This kinase forms heterodimers with leucine zipper containing transcription factors, such as cAMP responsive element binding protein (CREB) and MYC, and thus may play a regulatory role in PKA or retinoic acid induced neuronal differentiation. Alternatively spliced transcript variants encoding different proteins have been described.[provided by RefSeq, Jul 2010]
Canonical amino-acid sequenceUniProt
859 residues, UniProt reviewed canonical sequence.
>Q12852|MAP3K12
1 MACLHETRTP SPSFGGFVST LSEASMRKLD PDTSDCTPEK DLTPTHVLQL HEQDAGGPGG
61 AAGSPESRAS RVRADEVRLQ CQSGSGFLEG LFGCLRPVWT MIGKAYSTEH KQQQEDLWEV
121 PFEEILDLQW VGSGAQGAVF LGRFHGEEVA VKKVRDLKET DIKHLRKLKH PNIITFKGVC
181 TQAPCYCILM EFCAQGQLYE VLRAGRPVTP SLLVDWSMGI AGGMNYLHLH KIIHRDLKSP
241 NMLITYDDVV KISDFGTSKE LSDKSTKMSF AGTVAWMAPE VIRNEPVSEK VDIWSFGVVL
301 WELLTGEIPY KDVDSSAIIW GVGSNSLHLP VPSSCPDGFK ILLRQCWNSK PRNRPSFRQI
361 LLHLDIASAD VLSTPQETYF KSQAEWREEV KLHFEKIKSE GTCLHRLEEE LVMRRREELR
421 HALDIREHYE RKLERANNLY MELNALMLQL ELKERELLRR EQALERRCPG LLKPHPSRGL
481 LHGNTMEKLI KKRNVPQKLS PHSKRPDILK TESLLPKLDA ALSGVGLPGC PKGPPSPGRS
541 RRGKTRHRKA SAKGSCGDLP GLRTAVPPHE PGGPGSPGGL GGGPSAWEAC PPALRGLHHD
601 LLLRKMSSSS PDLLSAALGS RGRGATGGAG DPGSPPPARG DTPPSEGSAP GSTSPDSPGG
661 AKGEPPPPVG PGEGVGLLGT GREGTSGRGG SRAGSQHLTP AALLYRAAVT RSQKRGISSE
721 EEEGEVDSEV ELTSSQRWPQ SLNMRQSLST FSSENPSDGE EGTASEPSPS GTPEVGSTNT
781 DERPDERSDD MCSQGSEIPL DPPPSEVIPG PEPSSLPIPH QELLRERGPP NSEDSDCDST
841 ELDNSNSVDA LRPPASLPPLocalizationUniProt · AlphaFold · HPA
Whether an antibody against MAP3K12 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)
- 0.54
- Highest tissue expression
- 65 nTPM
Expression across tissuesHPA
Tissue
- cerebellum: 65 nTPM
- cerebral cortex: 24 nTPM
- cervix: 20 nTPM
- pituitary gland: 20 nTPM
- endometrium: 19 nTPM
- ovary: 19 nTPM
Single-cell type
- epicardial cells: 116 nCPM
- rod photoreceptor cells: 45 nCPM
- cardiomyocytes: 38 nCPM
- thymocytes: 34 nCPM
- retinal amacrine cells: 34 nCPM
- fibro-adipogenic progenitors: 32 nCPM
Immune cell
- neutrophil: 1 nTPM
- MAIT T-cell: 0.8 nTPM
- memory CD8 T-cell: 0.6 nTPM
- classical monocyte: 0.5 nTPM
- memory CD4 T-cell: 0.5 nTPM
- gdT-cell: 0.4 nTPM
Brain region
- cerebellum: 63 nTPM
- cerebral cortex: 45 nTPM
- white matter: 35 nTPM
- pons: 35 nTPM
- thalamus: 35 nTPM
- hippocampal formation: 34 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)
- 0.07
- gnomAD pLI
- 1
- gnomAD missense Z
- 2.99
- DepMap mean gene effect
- -0.09
- 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
- intracellular signal transduction
- JNK cascade
- negative regulation of motor neuron apoptotic process
- positive regulation of DNA-templated transcription
- positive regulation of ERK1 and ERK2 cascade
- post-translational protein modification
- protein autophosphorylation
- protein phosphorylation
Molecular functions
- ATP binding
- MAP kinase kinase kinase activity
- protein homodimerization activity
- protein kinase activity
- protein kinase binding
- protein serine kinase activity
- protein serine/threonine kinase activator activity
- protein serine/threonine kinase activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Protein kinase domain
- Serine-threonine/tyrosine-protein kinase, catalytic domain
- Serine/threonine-protein kinase, active site
- Protein kinase-like domain superfamily
- Mitogen-activated protein kinase kinase kinase 12/13
- Serine/Threonine Kinases and Pseudokinases
- Protein tyrosine and serine/threonine kinase
- Mitogen-activated protein kinase kinase kinase 12
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of MAP3K12 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 MAP3K12 as an antibody target. Whether an autoantibody or antibody against MAP3K12 could matter depends on whether native MAP3K12 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
MAP3K12 is annotated at the cell surface, where native MAP3K12 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 MAP3K12 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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