MAP3K12 mitogen-activated protein kinase kinase kinase 12 [Homo sapiens] - Gene

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Summary

Official Symbol: MAP3K12provided by HGNC
Official Full Name: mitogen-activated protein kinase kinase kinase 12provided by HGNC
Primary source: HGNC:6851
See related: Ensembl:ENSG00000139625; HPRD:02709; MIM:600447; Vega:OTTHUMG00000169854
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: DLK; MUK; ZPK; ZPKP1; MEKK12
Summary: 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]

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Genomic context

Location :: 12q13

Sequence :: Chromosome: 12; NC_000012.11 (53874276..53893444, complement)

See MAP3K12 in Epigenomics, MapViewer

Chromosome 12 - NC_000012.11 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

these findings indicate that DLK participates in cell proliferation and/or survival, at least in part, by modulating the expression of cell cycle regulatory proteins.
Title: Loss of DLK expression in WI-38 human diploid fibroblasts induces a senescent-like proliferation arrest.
The results confirm the significance of apoptosis deregulation in CLL, and suggest a possible relationship between ZIPK expression and the clinical course of the disease.
Title: Assessment of the pathway of apoptosis involving PAR-4, DAXX and ZIPK proteins in CLL patients and its relationship with the principal prognostic factors.
the DLK-ERK signaling pathway may act as a regulator of the interaction that occurs between Hsp27 and the cytoskeleton during the formation of the cornified cell envelope, a process conferring to the skin its crucial barrier function
Title: The small heat-shock protein Hsp27 undergoes ERK-dependent phosphorylation and redistribution to the cytoskeleton in response to dual leucine zipper-bearing kinase expression.
Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
Title: Genetic variation in MicroRNA genes and risk of oral premalignant lesions.
Observational study of gene-disease association. (HuGE Navigator)
Title: The variant rs1867277 in FOXE1 gene confers thyroid cancer susceptibility through the recruitment of USF1/USF2 transcription factors.
Src-dependent tyrosine phosphorylation recombinant human DLK was important for regulation of its activity. DLK may have a role in PDGF signaling.
Title: The mixed-lineage kinase DLK undergoes Src-dependent tyrosine phosphorylation and activation in cells exposed to vanadate or platelet-derived growth factor (PDGF).
DAPK-ZIPK-L13a axis forms a unique regulatory module that first represses, then repermits inflammatory gene expression.
Title: DAPK-ZIPK-L13a axis constitutes a negative-feedback module regulating inflammatory gene expression.
for the selective expression of ZPK gene, cell-specific negative regulatory element(s) which locate outside of the core promoter region repress the potent basic promoter activity
Title: SP3 acts as a positive regulator on the core promoter of human ZPK gene.
DLK is a signaling molecule implicated in the regulation of keratinocyte terminal differentiation and cornification
Title: The mitogen-activated protein kinase kinase kinase dual leucine zipper-bearing kinase (DLK) acts as a key regulator of keratinocyte terminal differentiation.
ZIPK is positively regulated by phosphorylation within its kinase domain and contains an inhibitory C-terminal domain that controls enzyme activity.
Title: Regulation of zipper-interacting protein kinase activity in vitro and in vivo by multisite phosphorylation.

Submit: New GeneRIF Correction

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

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Products	Interactant	Other Gene	Source	Pubs	Description
Q12852	Q70Z53	FRA10AC1	HPRD	PubMed
Q12852	P02792	FTL	HPRD	PubMed
Q12852	P45985	MAP2K4	HPRD	PubMed
Q12852	O14733	MAP2K7	HPRD	PubMed
Q12852	Q16584	MAP3K11	HPRD	PubMed
Q12852	Q9NS73	MBIP	HPRD	PubMed
Q12852	Q08116	RGS1	HPRD	PubMed
Q12852	Q02543	RPL18A	HPRD	PubMed
Q12852	SH3 multiple domains 2	SH3RF1	HPRD	PubMed
Q12852	P21980	TGM2	HPRD	PubMed
Q12852	Q15714	TSC22D1	HPRD	PubMed
BioGRID:113566	BioGRID:108276	EGFR	BioGRID	PubMed	Affinity Capture-Western; PCA
BioGRID:113566	BioGRID:108789	FTL	BioGRID	PubMed	Two-hybrid
BioGRID:113566	BioGRID:111595	MAP2K7	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity
BioGRID:113566	BioGRID:111583	MAPK6	BioGRID	PubMed	Two-hybrid
BioGRID:113566	BioGRID:114864	MAPK8IP1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:113566	BioGRID:117086	MAPK8IP2	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:113566	BioGRID:119612	MBIP	BioGRID	PubMed	Affinity Capture-Western; Two-hybrid
BioGRID:113566	BioGRID:111928	RGS1	BioGRID	PubMed	Two-hybrid
BioGRID:113566	BioGRID:114374	TSC22D1	BioGRID	PubMed	Two-hybrid
BioGRID:113566	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
MAP kinase kinase kinase activity	IEA Inferred from Electronic Annotation more info
magnesium ion binding	IEA Inferred from Electronic Annotation more info
nucleotide binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein homodimerization activity	ISS Inferred from Sequence or Structural Similarity more info
protein kinase activity	TAS Traceable Author Statement more info	PubMed
protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
protein serine/threonine kinase activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed

Process	Evidence Code	Pubs
JNK cascade	ISS Inferred from Sequence or Structural Similarity more info	PubMed
histone phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
intracellular protein kinase cascade	TAS Traceable Author Statement more info	PubMed
peptidyl-serine phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
peptidyl-threonine phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
protein autophosphorylation	ISS Inferred from Sequence or Structural Similarity more info	PubMed
protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
protein phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
protein phosphorylation	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
cytoplasm	IEA Inferred from Electronic Annotation more info
cytosol	ISS Inferred from Sequence or Structural Similarity more info
membrane fraction	ISS Inferred from Sequence or Structural Similarity more info	PubMed
plasma membrane	ISS Inferred from Sequence or Structural Similarity more info

General protein information

Preferred Names: mitogen-activated protein kinase kinase kinase 12

Names: mitogen-activated protein kinase kinase kinase 12; protein kinase MUK; MAPK-upstream kinase; mixed lineage kinase; leucine zipper protein kinase; dual leucine zipper kinase DLK; dual leucine zipper bearing kinase

NP_001180440.1

EC 2.7.11.25

NP_006292.3

EC 2.7.11.25

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001193511.1 → NP_001180440.1 mitogen-activated protein kinase kinase kinase 12 isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AC023509, AK094195, BC050050

Consensus CDS

CCDS55831.1

UniProtKB/TrEMBL

B3KSS9

UniProtKB/TrEMBL

G3V1Y2

UniProtKB/Swiss-Prot

Q12852

Related

ENSP00000449038, OTTHUMP00000242301, ENST00000547488, OTTHUMT00000406268

Conserved Domains (2) summary

smart00219
Location:165 – 397
Blast Score: 624

TyrKc; Tyrosine kinase, catalytic domain

cl09925
Location:164 – 398
Blast Score: 557

PKc_like; Protein Kinases, catalytic domain
NM_006301.3 → NP_006292.3 mitogen-activated protein kinase kinase kinase 12 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region compared to variant 1. The resulting protein (isoform 2) is shorter but has the same N- and C-termini compared to isoform 1.

Source sequence(s)

AC023509, AK094195, U07358

Consensus CDS

CCDS8860.1

UniProtKB/TrEMBL

B3KSS9

UniProtKB/Swiss-Prot

Q12852

Related

ENSP00000267079, OTTHUMP00000242300, ENST00000267079, OTTHUMT00000406267

Conserved Domains (2) summary

smart00219
Location:132 – 364
Blast Score: 624

TyrKc; Tyrosine kinase, catalytic domain

cl09925
Location:131 – 365
Blast Score: 557

PKc_like; Protein Kinases, catalytic domain

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000012.11 Reference GRCh37.p5 Primary Assembly

Range

53874276..53893444, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000144.1 Alternate HuRef

Range

50914162..50933025, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC023509.42 (123109..142277)	None
genomic	AF283475.1	AAL67158.1
genomic	CH471054.1	EAW96712.1
		EAW96713.1
		EAW96714.1
		EAW96715.1
		EAW96716.1
mRNA	AB209453.1	BAD92690.1
mRNA	AK094195.1	BAG52841.1
mRNA	AK314530.1	None
mRNA	BC037585.1	None
mRNA	BC050050.1	AAH50050.1
mRNA	U07358.1	AAA67343.1