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 fa... See more...

Aliases for MAP3K12 Gene

Aliases for MAP3K12 Gene

  • Mitogen-Activated Protein Kinase Kinase Kinase 12 2 3 4 5
  • DLK 2 3 4
  • MUK 2 3 4
  • Dual Leucine Zipper Bearing Kinase 3 4
  • Dual Leucine Zipper Kinase DLK 2 3
  • MAPK-Upstream Kinase 3 4
  • Mixed Lineage Kinase 3 4
  • EC 2.7.11.25 4 50
  • MEKK12 2 3
  • ZPKP1 2 3
  • ZPK 3 4
  • Leucine Zipper Protein Kinase 3
  • Leucine-Zipper Protein Kinase 4
  • Protein Kinase MUK 3
  • EC 2.7.11 50
  • MAP3K12 5

External Ids for MAP3K12 Gene

Previous HGNC Symbols for MAP3K12 Gene

  • ZPK

Previous GeneCards Identifiers for MAP3K12 Gene

  • GC12M053870
  • GC12M053986
  • GC12M053591
  • GC12M052160
  • GC12M050914

Summaries for MAP3K12 Gene

Entrez Gene Summary for MAP3K12 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]

GeneCards Summary for MAP3K12 Gene

MAP3K12 (Mitogen-Activated Protein Kinase Kinase Kinase 12) is a Protein Coding gene. Diseases associated with MAP3K12 include Tinea Unguium and Tinea Barbae. Among its related pathways are MAPK signaling pathway and Regulation of p38-alpha and p38-beta. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and protein kinase activity. An important paralog of this gene is MAP3K13.

UniProtKB/Swiss-Prot Summary for MAP3K12 Gene

  • Part of a non-canonical MAPK signaling pathway (PubMed:28111074). Activated by APOE, enhances the AP-1-mediated transcription of APP, via a MAP kinase signal transduction pathway composed of MAP2K7 and MAPK1/ERK2 and MAPK3/ERK1 (PubMed:28111074). May be an activator of the JNK/SAPK pathway.

Gene Wiki entry for MAP3K12 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for MAP3K12 Gene

Genomics for MAP3K12 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for MAP3K12 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around MAP3K12 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for MAP3K12

Top Transcription factor binding sites by QIAGEN in the MAP3K12 gene promoter:
  • AP-1
  • Sp1

Genomic Locations for MAP3K12 Gene

Latest Assembly
chr12:53,479,669-53,501,205
(GRCh38/hg38)
Size:
21,537 bases
Orientation:
Minus strand

Previous Assembly
chr12:53,873,453-53,893,242
(GRCh37/hg19 by Entrez Gene)
Size:
19,790 bases
Orientation:
Minus strand

chr12:53,874,274-53,893,847
(GRCh37/hg19 by Ensembl)
Size:
19,574 bases
Orientation:
Minus strand

Genomic View for MAP3K12 Gene

Genes around MAP3K12 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MAP3K12 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MAP3K12 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MAP3K12 Gene

Proteins for MAP3K12 Gene

  • Protein details for MAP3K12 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q12852-M3K12_HUMAN
    Recommended name:
    Mitogen-activated protein kinase kinase kinase 12
    Protein Accession:
    Q12852
    Secondary Accessions:
    • B3KSS9
    • G3V1Y2
    • Q86VQ5
    • Q8WY25

    Protein attributes for MAP3K12 Gene

    Size:
    859 amino acids
    Molecular mass:
    93219 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Homodimer (By similarity). Interacts with MBIP (PubMed:10801814).

    Three dimensional structures from OCA and Proteopedia for MAP3K12 Gene

    Alternative splice isoforms for MAP3K12 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MAP3K12 Gene

Selected DME Specific Peptides for MAP3K12 Gene

Q12852:
  • RRREELRHALDIREHYERKLERANNLYMEL
  • HLDIASADVL
  • GMNYLHLHKIIHRDLKSPN
  • HRDLKSPN
  • KISDFGTSK
  • RNRPSFRQ
  • STFSSEN
  • LWELLTGE
  • GQLYEVLRAGR
  • TPQETYFKSQAEWREEVK
  • WMAPEVI
  • CPDGFKIL
  • IGKAYST
  • GFLEGLFGCLRPVW
  • VKISDFGTSKELSDKSTKMSFAGTVAW
  • GSGAQGAVFLG
  • WEVPFEEI
  • HFEKIKSEGTC
  • ETDIKHLRKLKHPNII

Post-translational modifications for MAP3K12 Gene

  • Autophosphorylated on Ser/Thr. Phosphorylated in cytosol under basal conditions and dephosphorylated when membrane-associated (By similarity).
  • The activity of MAP3K12 can be regulated through its proteasomal degradation. APOE, through a receptor-mediated mechanism, activates MAP3K12 by preventing its proteasomal degradation.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Domains & Families for MAP3K12 Gene

Gene Families for MAP3K12 Gene

Suggested Antigen Peptide Sequences for MAP3K12 Gene

GenScript: Design optimal peptide antigens:
  • Mixed lineage kinase (M3K12_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q12852

UniProtKB/Swiss-Prot:

M3K12_HUMAN :
  • Interacts with MBIP through the leucine-zipper motif.
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.
Domain:
  • Interacts with MBIP through the leucine-zipper motif.
Family:
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.
genes like me logo Genes that share domains with MAP3K12: view

Function for MAP3K12 Gene

Molecular function for MAP3K12 Gene

UniProtKB/Swiss-Prot Function:
Part of a non-canonical MAPK signaling pathway (PubMed:28111074). Activated by APOE, enhances the AP-1-mediated transcription of APP, via a MAP kinase signal transduction pathway composed of MAP2K7 and MAPK1/ERK2 and MAPK3/ERK1 (PubMed:28111074). May be an activator of the JNK/SAPK pathway.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.25; Evidence={ECO:0000250|UniProtKB:Q60700};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.25; Evidence={ECO:0000250|UniProtKB:Q60700};.
GENATLAS Biochemistry:
mitogen activated protein (MAP/ERK) kinase kinase kinase 12,expressed in brain,interacting with the GTP bound form of RAC and CDC42,regulators of JNK pathway

Enzyme Numbers (IUBMB) for MAP3K12 Gene

Phenotypes From GWAS Catalog for MAP3K12 Gene

Gene Ontology (GO) - Molecular Function for MAP3K12 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0004672 protein kinase activity IEA,IBA 21873635
GO:0004674 protein serine/threonine kinase activity ISS 9353328
GO:0004706 JUN kinase kinase kinase activity IBA,ISS --
GO:0004709 MAP kinase kinase kinase activity IEA --
genes like me logo Genes that share ontologies with MAP3K12: view
genes like me logo Genes that share phenotypes with MAP3K12: view

Animal Models for MAP3K12 Gene

MGI Knock Outs for MAP3K12:

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MAP3K12

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for MAP3K12 Gene

Localization for MAP3K12 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MAP3K12 Gene

Cytoplasm. Cell membrane. Note=Behaves essentially as an integral membrane protein. {ECO:0000250 UniProtKB:Q60700}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for MAP3K12 gene
Compartment Confidence
cytosol 5
plasma membrane 4
nucleus 3
extracellular 2
cytoskeleton 2
mitochondrion 2
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (2)
  • Plasma membrane (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for MAP3K12 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm TAS 8663324
GO:0005829 cytosol ISS --
GO:0005886 plasma membrane TAS,ISS --
GO:0016020 membrane ISS 9353328
GO:0030424 axon IEA --
genes like me logo Genes that share ontologies with MAP3K12: view

Pathways & Interactions for MAP3K12 Gene

PathCards logo

SuperPathways for MAP3K12 Gene

genes like me logo Genes that share pathways with MAP3K12: view

Pathways by source for MAP3K12 Gene

1 GeneGo (Thomson Reuters) pathway for MAP3K12 Gene
  • Signal transduction_JNK pathway
5 Qiagen pathways for MAP3K12 Gene
  • MAPK Family Pathway
  • NFAT and Cardiac Hypertrophy
  • PACAP Signaling
  • TNFR2 Pathway
  • WNT Signaling

SIGNOR curated interactions for MAP3K12 Gene

Activates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for MAP3K12 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000186 activation of MAPKK activity IEA --
GO:0006468 protein phosphorylation IEA,ISS --
GO:0007254 JNK cascade TAS,ISS 9353328
GO:0007256 activation of JNKK activity ISS --
GO:0007257 activation of JUN kinase activity ISS --
genes like me logo Genes that share ontologies with MAP3K12: view

Drugs & Compounds for MAP3K12 Gene

(10) Drugs for MAP3K12 Gene - From: DrugBank, ApexBio, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
fostamatinib Approved, Investigational Pharma Target, inhibitor Kinase Inhibitors 0
Magnesium Approved, Experimental, Investigational Pharma 0
ATP Investigational Nutra 0
URMC-099 Pharma 0

(2) Additional Compounds for MAP3K12 Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • 5'-Adenylphosphoric acid
  • Adenosine 5'-diphosphate
  • ADENOSINE-5'-diphosphATE
  • H3ADP
  • 5'-Adenylphosphate
58-64-0

(1) ApexBio Compounds for MAP3K12 Gene

Compound Action Cas Number
URMC-099 1229582-33-5
genes like me logo Genes that share compounds with MAP3K12: view

Drug products for research

Transcripts for MAP3K12 Gene

mRNA/cDNA for MAP3K12 Gene

2 REFSEQ mRNAs :
6 NCBI additional mRNA sequence :
11 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MAP3K12

Alternative Splicing Database (ASD) splice patterns (SP) for MAP3K12 Gene

ExUns: 1a · 1b ^ 2 ^ 3a · 3b ^ 4a · 4b · 4c ^ 5 ^ 6 ^ 7a · 7b ^ 8a · 8b ^ 9 ^ 10 ^ 11 ^ 12a · 12b ^ 13a · 13b ^ 14 ^ 15 ^ 16
SP1: - - - - -
SP2: - - -
SP3: - - - -
SP4: - - -
SP5:
SP6: -
SP7:
SP8:

Relevant External Links for MAP3K12 Gene

GeneLoc Exon Structure for
MAP3K12

Expression for MAP3K12 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for MAP3K12 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for MAP3K12 Gene

This gene is overexpressed in Brain - Cerebellum (x4.4).

Protein differential expression in normal tissues from HIPED for MAP3K12 Gene

This gene is overexpressed in Cervix (50.6) and Plasma (10.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for MAP3K12 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for MAP3K12

SOURCE GeneReport for Unigene cluster for MAP3K12 Gene:

Hs.713539

mRNA Expression by UniProt/SwissProt for MAP3K12 Gene:

Q12852-M3K12_HUMAN
Tissue specificity: Highly expressed in brain and kidney.

Evidence on tissue expression from TISSUES for MAP3K12 Gene

  • Nervous system(3)
  • Skin(2)
genes like me logo Genes that share expression patterns with MAP3K12: view

Primer products for research

No data available for Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for MAP3K12 Gene

Orthologs for MAP3K12 Gene

This gene was present in the common ancestor of animals.

Orthologs for MAP3K12 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia MAP3K12 29 30
  • 99.77 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia MAP3K12 29 30
  • 92.36 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia MAP3K12 29 30
  • 91.37 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Map3k12 29 16 30
  • 90.69 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Map3k12 29
  • 90.17 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia MAP3K12 30
  • 78 (a)
OneToOne
Chicken
(Gallus gallus)
Aves MAP3K12 30
  • 86 (a)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia MAP3K12 30
  • 76 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia map3k12 29
  • 67.55 (n)
Zebrafish
(Danio rerio)
Actinopterygii map3k12 29
  • 71.59 (n)
MAP3K12 30
  • 64 (a)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta CG8789 31
  • 60 (a)
wnd 30
  • 32 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea dlk-1 30
  • 27 (a)
OneToMany
Species where no ortholog for MAP3K12 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Oppossum (Monodelphis domestica)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for MAP3K12 Gene

ENSEMBL:
Gene Tree for MAP3K12 (if available)
TreeFam:
Gene Tree for MAP3K12 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for MAP3K12: view image
Alliance of Genome Resources:
Additional Orthologs for MAP3K12

Paralogs for MAP3K12 Gene

(9) SIMAP similar genes for MAP3K12 Gene using alignment to 3 proteins:

  • M3K12_HUMAN
  • F8VUG4_HUMAN
  • H3BMF0_HUMAN
genes like me logo Genes that share paralogs with MAP3K12: view

Variants for MAP3K12 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for MAP3K12 Gene

SNP ID Clinical significance and condition Chr 12 pos Variation AA Info Type
rs55794887 Benign: not provided 53,482,786(-) C/Tp.Gly640Ser
NM_001193511.2(MAP3K12):c.2017G>A (p.Gly673Ser)
MISSENSE
VAR_040705 A breast pleomorphic lobular carcinoma sample p.Glu409Lys
rs34366500 -- p.Gly628Arg

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for MAP3K12 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for MAP3K12 Gene

Variant ID Type Subtype PubMed ID
esv1293318 CNV deletion 17803354
esv2289574 CNV deletion 18987734
esv2745906 CNV deletion 23290073
esv2745908 CNV deletion 23290073
esv992595 CNV deletion 20482838
nsv714 CNV insertion 18451855

Variation tolerance for MAP3K12 Gene

Residual Variation Intolerance Score: 6.51% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.70; 46.25% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MAP3K12 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
MAP3K12
Leiden Open Variation Database (LOVD)
MAP3K12

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MAP3K12 Gene

Disorders for MAP3K12 Gene

MalaCards: The human disease database

(2) MalaCards diseases for MAP3K12 Gene - From: COP

Disorder Aliases PubMed IDs
tinea unguium
  • cellulitis and abscess
tinea barbae
  • dermatophytosis of beard
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for MAP3K12

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with MAP3K12: view

No data available for UniProtKB/Swiss-Prot and Genatlas for MAP3K12 Gene

Publications for MAP3K12 Gene

  1. Cloning of a novel putative protein kinase having a leucine zipper domain from human brain. (PMID: 8037767) Reddy UR … Pleasure D (Biochemical and biophysical research communications 1994) 2 3 4 22
  2. SP3 acts as a positive regulator on the core promoter of human ZPK gene. (PMID: 14697235) Itoh A … Itoh T (Biochemical and biophysical research communications 2004) 3 4 22
  3. ApoE2, ApoE3, and ApoE4 Differentially Stimulate APP Transcription and Aβ Secretion. (PMID: 28111074) Huang YA … Südhof TC (Cell 2017) 3 4
  4. The small heat-shock protein Hsp27 undergoes ERK-dependent phosphorylation and redistribution to the cytoskeleton in response to dual leucine zipper-bearing kinase expression. (PMID: 19675578) Robitaille H … Germain L (The Journal of investigative dermatology 2010) 3 22
  5. Genetic variation in MicroRNA genes and risk of oral premalignant lesions. (PMID: 19851984) Clague J … Wu X (Molecular carcinogenesis 2010) 3 40

Products for MAP3K12 Gene