MAP3K12 Gene (Protein Coding)

Mitogen-Activated Protein Kinase Kinase Kinase 12

GCID:: GC12M053479

GIFtS:: 43

Genes Participants

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

Mitogen-Activated Protein Kinase Kinase Kinase 12 ² ³ ⁴ ⁵
Dual Leucine Zipper Bearing Kinase ³ ⁴
Dual Leucine Zipper Kinase DLK ² ³
Mixed Lineage Kinase ³ ⁴
MAPK-Upstream Kinase ³ ⁴
EC 2.7.11.25 ⁴ ⁵²
ZPK ³ ⁴

DLK ³ ⁴
MUK ³ ⁴
Leucine Zipper Protein Kinase ³
Leucine-Zipper Protein Kinase ⁴
Protein Kinase MUK ³
EC 2.7.11 ⁵²
MEKK12 ³
ZPKP1 ³

External Ids for MAP3K12 Gene

HGNC: 6851
Entrez Gene: 7786
Ensembl: ENSG00000139625
OMIM: 600447
UniProtKB: Q12852

Previous HGNC Symbols for MAP3K12 Gene

Previous GeneCards Identifiers for MAP3K12 Gene

GC12M053870
GC12M053986
GC12M053591
GC12M052160
GC12M050914

Search aliases for MAP3K12 gene in PubMed and other databases

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. Among its related pathways are Regulation of p38-alpha and p38-beta and Angiopoietin Like Protein 8 Regulatory Pathway. 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.
- M3K12_HUMAN,Q12852

Gene Wiki entry for MAP3K12 Gene

Additional gene information for MAP3K12 Gene

Search for MAP3K12 at DataMed
Search for MAP3K12 at HumanCyc

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 for MAP3K12 Gene

Promoters and enhancers for MAP3K12 Gene

GeneHancer (GH) Identifier	GH Type	GH Score	GH Sources	Gene Association Score	Total Score	TSS distance (kb)	Number of Genes Away	Size (kb)	Transcription Factor Binding Sites
GH12J053498	Promoter/Enhancer	2.4	EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER	522.1	-0.5	-470	5	HNRNPK ZBTB40 ZNF217 EP300 TCF12 SIN3A USF1 POLR2G SP1 GTF2E2	MAP3K12 TARBP2 ENSG00000270175 lnc-NPFF-4 KRT1 ZNF740 AAAS ATF7 HNRNPA1 CBX5
GH12J053971	Promoter/Enhancer	2.7	VISTA EPDnew FANTOM5 Ensembl ENCODE dbSUPER	39.9	-503.2	-503176	63	HNRNPK ZBTB40 ZNF217 CTCF ZSCAN5C TCF12 NRF1 POLR2G USF1 NCOR1	HOXC8 HOXC4 HOXC11 HOXC9 HOXC6 HOXC10 HOXC5 HNRNPA1 ATF7 ZNF740
GH12J052894	Promoter/Enhancer	2.3	FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER	36.3	+597.2	597208	16.1	LARP7 EP300 HNRNPK ZNF217 CTCF ZSCAN5C TCF12 NRF1 POLR2G USF1	ZNF740 AAAS PCBP2 SP1 MAP3K12 ATF7 CSAD EIF4B ENSG00000257550 TARBP2
GH12J053452	Promoter/Enhancer	2.1	EPDnew Ensembl ENCODE CraniofacialAtlas	28.5	+47.0	47035	3.8	RXRA HNRNPK FOXK2 ZBTB40 ZNF217 EP300 CTCF TCF12 SIN3A NRF1	PCBP2 AAAS TARBP2 NPFF ZNF740 C12orf10 MAP3K12 PRR13 HNRNPA1 CBX5
GH12J054350	Promoter/Enhancer	2.4	FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER	23.5	-855.5	-855455	11.2	ZNF217 EP300 CTCF ZSCAN5C TCF12 SIN3A NRF1 POLR2G SP1 NCOR1	ENSG00000258086 ENSG00000258137 LOC102724050 SP1 PCBP2 CBX5 ATF7 GPR84 ZNF385A MAP3K12

- 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 UCSC Golden Path with GeneCards custom track

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

chr12:53,479,669-53,500,136: (GRCh38/hg38)

Size:: 20,468 bases
Orientation:: Minus strand

chr12:53,874,274-53,893,847: (GRCh37/hg19)

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:

12q13.13 by HGNC
12q13.13 by Entrez Gene
12q13.13 by Ensembl

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 — Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for MAP3K12 Gene

NC_000012.12

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
- 5CEN (3D)
- 5CEO (3D)
- 5CEP (3D)
- 5CEQ (3D)
- 5VO1 (3D)
- 5VO2 (3D)
Alternative splice isoforms for MAP3K12 Gene
UniProtKB/Swiss-Prot:
Q12852-1

Q12852-2

neXtProt entry for MAP3K12 Gene

Protein Expression for MAP3K12 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

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).
- Q12852-M3K12_HUMAN
The activity of MAP3K12 can be regulated through its proteasomal degradation. APOE, through a receptor-mediated mechanism, activates MAP3K12 by preventing its proteasomal degradation.
- Q12852-M3K12_HUMAN
Modification sites at PhosphoSitePlus
- Q12852
Modification sites at neXtProt
- NX_Q12852

Other Protein References for MAP3K12 Gene

ENSEMBL proteins:

REFSEQ proteins:

Antibody Products

G Biosciences Immunotag™ MAP3K12 Antibody

Creative Diagnostics Anti-MAP3K12 monoclonal antibody, clone 584DU34.23.6

Creative Biolabs Mouse Anti-MAP3K12 Monoclnal Antibody (3A10)

OriGene Antibodies for MAP3K12
- 73-355
- 73-356
- 75-355
- AP13892PU-N
- TA324095
- TA324096
Custom Antibody Services

Novus Biologicals Antibodies for MAP3K12

Abcam antibodies for MAP3K12
- MAP3K12

Invitrogen Antibodies for MAP3K12 (AFLGC-MAP3K12)

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Santa Cruz Biotechnology (SCBT) Antibodies for MAP3K12
- ZPK (473CT23.12.5)

Browse Sino Biological Antibodies

Protein Products

OriGene Purified Proteins for MAP3K12
- NM_006301
- NM_006301
Search Origene for MassSpec and Protein Over-expression Lysates for MAP3K12
Origene Custom Protein Services for MAP3K12

Novus Biologicals proteins for MAP3K12

Browse ProSpec Recombinant Proteins

antibodies-online: Show 10 available MAP3K12 Proteins ranked by validation data
Compare Top MAP3K12 Proteins

Search for MAP3K12 Proteins at ProSci

Abcam proteins for MAP3K12
- MAP3K12

Assay Products

antibodies-online: Search results for available MAP3K12 related products ranked by validation data

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Domains & Families for MAP3K12 Gene

Gene Families for MAP3K12 Gene

HGNC:

Mitogen-activated protein kinase kinase kinases

IUPHAR :

LZK subfamily

Human Protein Atlas (HPA):

Enzymes
Predicted intracellular proteins

Protein Domains for MAP3K12 Gene

InterPro:

ProtoNet:

Q12852

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.

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.

M3K12_HUMAN,Q12852

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=. ;.

M3K12_HUMAN,Q12852

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=. ;.

M3K12_HUMAN,Q12852

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

MAP3K12

Enzyme Numbers (IUBMB) for MAP3K12 Gene

EC 2.7.11.25 ⁵² ⁴
EC 2.7.11 ⁵²

Phenotypes From GWAS Catalog for MAP3K12 Gene

Gene Ontology (GO) - Molecular Function for MAP3K12 Gene

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0004672	protein kinase activity	IEA,TAS	8637721
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	--
GO:0005515	protein binding	IPI	16169070

Phenotypes for MAP3K12 Gene

MGI mutant phenotypes for MAP3K12:

inferred from 7 alleles

GenomeRNAi human phenotypes for MAP3K12:

Animal Models for MAP3K12 Gene

MGI Knock Outs for MAP3K12:

Map3k12 ^{Map3k12<tm1b(EUCOMM)Hmgu>}
Map3k12 ^{Map3k12<tm1Shir>}
Map3k12 ^{Map3k12<tm1.2Adia>}
Map3k12 ^{Map3k12<tm1.1Lewc>}

Animal Model Products

Taconic Biosciences: Generate A Custom CRISPR Mouse Model For Your Study

CRISPR Products

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OriGene CRISPR knockouts for MAP3K12
- KN416463
- KN509729
- GA105314
- GA204949

Search GeneCopoeia for CRISPR/Cas9 clones, lentivirus and AAV products for MAP3K12

genomics-online: gRNA clones - Search for available MAP3K12 gRNA products
Overview of 115 available MAP3K12 gene related products
Recommended
- pCMV-SPORT6
- pExpress-1
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- pBluescriptR
- pCMV-SPORT6.1
- pORF
- pDONR223
- pPM-C-HA
- pPB-N-His
- pPB-C-His
- pPM-C-His
- pPB-His-MBP
- pPB-His-GST

Santa Cruz Biotechnology (SCBT) CRISPR for MAP3K12

miRNA for MAP3K12 Gene

miRTarBase miRNAs that target MAP3K12

miRNA Products

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Inhibitory RNA Products

Origene shrna, sirna, and RNAi products in human, mouse, rat for MAP3K12
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Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MAP3K12

genomics-online: shRNA clones - Search for available MAP3K12 shRNA products
Overview of 115 available MAP3K12 gene related products
Recommended
- pCMV-SPORT6
- pExpress-1
- pCR4-TOPO
- pBluescriptR
- pCMV-SPORT6.1
- pORF
- pDONR223
- pPM-C-HA
- pPB-N-His
- pPB-C-His
- pPM-C-His
- pPB-His-MBP
- pPB-His-GST

Search Santa Cruz Biotechnology (SCBT) for MAP3K12 siRNA/shRNA

Clone Products

Applied Biological Materials (abm): Clones for MAP3K12 - Select products 50% OFF >
* MAP3K12 as ready-to-use vector or virus: ORF | Lenti- | Retro- | Adeno- | AAV- | Protein Vector - Browse All
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OriGene clones in human,rat for MAP3K12
OriGene ORF clones in human,mouse,rat for MAP3K12
- RC216463
- RC231434
- RG216463
- RG231434
- MR211069
- MR217856
- MG211069
- MG217856
- RR200674
- RC216463L1
- RC216463L1V
- RC216463L2
- RC216463L2V
- RC216463L3
- RC216463L3V
- RC216463L4
- RC216463L4V
- RC231434L3
- RC231434L3V
- RC231434L4
- RC231434L4V
- MR211069L3
- MR211069L3V
- MR211069L4
- MR211069L4V
- MR217856L3
- MR217856L3V
- MR217856L4
- MR217856L4V
- RR200674L3
- RR200674L3V
- RR200674L4
- RR200674L4V
Custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling

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Addgene plasmids for MAP3K12

Search GeneCopoeia for ORF cDNA, lentivirus, AAV viral particles and/or promoter clone products for MAP3K12

genomics-online: cdna clones - Search for available MAP3K12 CDNA products
Overview of 115 available MAP3K12 gene related products
Recommended
- pCMV-SPORT6
- pExpress-1
- pCR4-TOPO
- pBluescriptR
- pCMV-SPORT6.1
- pORF
- pDONR223
- pPM-C-HA
- pPB-N-His
- pPB-C-His
- pPM-C-His
- pPB-His-MBP
- pPB-His-GST
orf clones - Search for available MAP3K12 ORF products
Overview of 115 available MAP3K12 gene related products
Recommended
- pCMV-SPORT6
- pExpress-1
- pCR4-TOPO
- pBluescriptR
- pCMV-SPORT6.1
- pORF
- pDONR223
- pPM-C-HA
- pPB-N-His
- pPB-C-His
- pPM-C-His
- pPB-His-MBP
- pPB-His-GST

Cell Line Products

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Horizon Cell Lines 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}.

Q12852-M3K12_HUMAN

Subcellular locations from

COMPARTMENTS

Compartment	Confidence
cytosol	5
plasma membrane	4
nucleus	3
extracellular	2
cytoskeleton	2
mitochondrion	2
peroxisome	1
endoplasmic reticulum	1
endosome	1
lysosome	1
golgi apparatus	1

Subcellular locations from the

Human Protein Atlas (HPA)

Cell Junctions (2)
Nucleoplasm (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	--

Pathways & Interactions for MAP3K12 Gene

SuperPathways for MAP3K12 Gene

	SuperPathway	Contained pathways
1	MAPK signaling pathway	MAPK signaling pathway .45	MAPK Signaling Pathway .45
2	Angiopoietin Like Protein 8 Regulatory Pathway	Angiopoietin Like Protein 8 Regulatory Pathway .49	Insulin Signaling .49
3	TGF-Beta Pathway	MAPK Family Pathway .60
4	NFAT and Cardiac Hypertrophy	NFAT and Cardiac Hypertrophy .42
5	IL-2 Pathway	PACAP Signaling .37

Pathways by source for MAP3K12 Gene

5 BioSystems pathways for MAP3K12 Gene

1 KEGG pathway for MAP3K12 Gene

MAPK signaling pathway

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

Interacting Proteins for MAP3K12 Gene

STRING Interaction Network Preview (showing top 5 STRING interactants - click image to see top 25)

Selected Interacting proteins: Q12852-M3K12_HUMAN ENSP00000448689 for MAP3K12 Gene via UniProtKB MINT STRING IID

Symbol	External ID(s)	Details
FRA10AC1	Q70Z53 ⁴ ¹²⁷ ENSP00000360488 ²¹	EBI-710223, EBI-710176 STRING: ENSP00000360488 IID: # exp=1
MAPK6	Q16659 ²⁰ ¹²⁷ ENSP00000261845 ²¹	MINT-8261362 STRING: ENSP00000261845 IID: # exp=1 # pred=2
AKT1	ENSP00000451828 ²¹ P31749 ¹²⁷	STRING: ENSP00000451828 IID: # pred=1
CDC42BPB	ENSP00000355237 ²¹ Q9Y5S2 ¹²⁷	STRING: ENSP00000355237 IID: # pred=1
EGFR	ENSP00000275493 ²¹ P00533 ¹²⁷	STRING: ENSP00000275493 IID: # exp=1 # pred=2

GPS-Prot Interaction Network for MAP3K12

;

SIGNOR curated interactions for MAP3K12 Gene

Activates:

MYL12B

Is activated by:

SH3RF1

Is inactivated by:

MAPK8IP1

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	ISS,TAS	9353328
GO:0007256	activation of JNKK activity	ISS	--
GO:0007257	activation of JUN kinase activity	ISS	--

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
fostamatinib	Approved, Investigational	MalaCards Medline Plus	Pharma	Target, inhibitor	Kinase Inhibitors
Magnesium	Approved, Experimental, Investigational	MalaCards Medline Plus	Pharma
ATP	Investigational	MalaCards Medline Plus	Nutra	Agonist, Activator, Full agonist, Antagonist, Pore Blocker, Potentiation
URMC-099		MalaCards Medline Plus	Pharma

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

Name	Synonyms	Role	CAS Number	PubChem IDs	PubMed IDs
ADP	5'-Adenylphosphoric acid Adenosine 5'-diphosphate ADENOSINE-5'-diphosphATE H3ADP 5'-Adenylphosphate	Full agonist, Agonist, Partial agonist, Antagonist, Gating inhibitor	MalaCards Medline Plus	58-64-0	6022

(1) ApexBio Compounds for MAP3K12 Gene

Compound	Action	Cas Number
URMC-099		1229582-33-5

Drug Products

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ApexBio compounds for MAP3K12

Transcripts for MAP3K12 Gene