MAP3K1 mitogen-activated protein kinase kinase kinase 1, E3 ubiquitin protein ligase [Homo sapiens] - Gene

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Summary

Official Symbol: MAP3K1provided by HGNC
Official Full Name: mitogen-activated protein kinase kinase kinase 1, E3 ubiquitin protein ligaseprovided by HGNC
Primary source: HGNC:6848
See related: Ensembl:ENSG00000095015; MIM:600982; Vega:OTTHUMG00000059486
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: MEKK; MEKK1; SRXY6; MEKK 1; MAPKKK1
Summary: 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]

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Genomic context

Location :: 5q11.2

Sequence :: Chromosome: 5; NC_000005.9 (56110900..56191979)

See MAP3K1 in Epigenomics, MapViewer

Chromosome 5 - NC_000005.9 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?

High MEK1 is associated with hepatocellular carcinoma.
Title: Correlation of gene expression of ATP-binding cassette protein and tyrosine kinase signaling pathway in patients with hepatocellular carcinoma.
Novel phosphorylation-dependent ubiquitination of tristetraprolin by mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 1 (MEKK1) and tumor necrosis factor receptor-associated factor 2 (TRAF2)
Title: Novel phosphorylation-dependent ubiquitination of tristetraprolin by mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 1 (MEKK1) and tumor necrosis factor receptor-associated factor 2 (TRAF2).
Apoptosis induced by cytoskeletal disruption requires distinct domains of MEKK1.
Title: Apoptosis induced by cytoskeletal disruption requires distinct domains of MEKK1.
MAP3K1 rs889312 polymorphism is associated with increased risk of breast cancer in BRCA1 mutation carriers
Title: Association between mitogen-activated protein kinase kinase kinase 1 rs889312 polymorphism and breast cancer risk: evidence from 59,977 subjects.
The upstream molecule of the TRAIL-induced MAPK activation is MEKK, as opposed to ASK1, via the mediation of its signal through JNK/p38 in a caspase-8-dependent manner.
Title: MEKK1/MEKK4 are responsible for TRAIL-induced JNK/p38 phosphorylation.
Data show that MEKK-1 plays an integral role in IL-1beta modulation of Caco-2 TJ barrier function by regulating the activation of the canonical NF-kappaB pathway and the MLCK gene.
Title: IL-1beta-induced increase in intestinal epithelial tight junction permeability is mediated by MEKK-1 activation of canonical NF-kappaB pathway.
mutations in MAP3K1 that result in 46,XY DSD with partial or complete gonadal dysgenesis implicate this pathway in normal human sex determination
Title: Mutations in MAP3K1 cause 46,XY disorders of sex development and implicate a common signal transduction pathway in human testis determination.
MAP/ERK kinase kinase 1 (MEKK1) mediates transcriptional repression by interacting with polycystic kidney disease-1 (PKD1) promoter-bound p53 tumor suppressor protein
Title: MAP/ERK kinase kinase 1 (MEKK1) mediates transcriptional repression by interacting with polycystic kidney disease-1 (PKD1) promoter-bound p53 tumor suppressor protein.
Han11 was required to allow coupling of MEKK1 to DYRK1 and HIPK2.
Title: The WD40-repeat protein Han11 functions as a scaffold protein to control HIPK2 and MEKK1 kinase functions.
Meta-analysis of gene-disease association and gene-gene interaction. (HuGE Navigator)
Title: Association between mitogen-activated protein kinase kinase kinase 1 rs889312 polymorphism and breast cancer risk: evidence from 59,977 subjects.

Submit: New GeneRIF Correction See all (56)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

A multistage genome-wide association study in breast cancer identifies two new risk alleles at 1p11.2 and 14q24.1 (RAD51L1).

Genome-wide association study identifies five new breast cancer susceptibility loci.

Genome-wide association study identifies novel breast cancer susceptibility loci.

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Products	Interactant	Other Gene	Source	Pubs	Description
AAC97073.1	NP_004570.2	MAP4K2	BIND	PubMed	GCK interacts with, and phsophorylates, MEKK1.
AAC97073.1	NP_002737.1	MAPK3	BIND	PubMed	MEKK1 interacts with ERK1.
Q13233	NP_002746.1	MAP2K1	BIND	PubMed	MEKK1 interacts with MEK1.
Q13233	NP_003001.1	MAP2K4	BIND	PubMed	MEKK1 phosphorylates MEK4.
Q13233	NP_660186.1	MAP2K7	BIND	PubMed	MEKK1 interacts with MEK7.
Q13233	NP_002736.2	MAPK1	BIND	PubMed	MEKK1 interacts with ERK2.
Q13233	NP_002871.1	RAF1	BIND	PubMed	MEKK1 interacts with Raf-1.
XP_042066.8	NC_000011.8	CD82	BIND	PubMed	MAP3K1 (MEKK1) interacts with the CD82 (KAI1) promoter.
XP_042066.8	NP_003001.1	MAP2K4	BIND	PubMed	MKK4 interacts with MEKK1. This interaction was modeled on a demonstrated interaction between human MKK4 and rat MEKK1.
XP_042066.8	NP_660186.1	MAP2K7	BIND	PubMed	MKK7 interacts with MEKK1. This interaction was modeled on a demonstrated interaction between human MKK7 and rat MEKK1.
BioGRID:110378	BioGRID:106739	ALK	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western
BioGRID:110378	BioGRID:113909	AXIN1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110378	BioGRID:116312	CDC37	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110378	BioGRID:115532	DCAF7	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110378	BioGRID:108173	DTX1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:110378	BioGRID:108189	DVL2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110378	BioGRID:108579	FKBP5	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110378	BioGRID:109142	GRB2	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:110378	BioGRID:109556	HSP90AA2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110378	BioGRID:109767	IKBKB	BioGRID	PubMed	Biochemical Activity
BioGRID:110378	BioGRID:111590	MAP2K1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110378	BioGRID:112315	MAP2K4	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110378	BioGRID:111809	MAP4K2	BioGRID	PubMed	Reconstituted Complex
BioGRID:110378	BioGRID:114838	MAP4K4	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110378	BioGRID:111580	MAPK1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110378	BioGRID:111585	MAPK8	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity; Reconstituted Complex
BioGRID:110378	BioGRID:116774	MAPK8IP3	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110378	BioGRID:111831	RAF1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:110378	BioGRID:112075	RPL30	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110378	BioGRID:112044	RPL4	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110378	BioGRID:112121	RPS13	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110378	BioGRID:113038	TRAF2	BioGRID	PubMed	Affinity Capture-Western; Co-fractionation
BioGRID:110378	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western
BioGRID:110378	BioGRID:113169	UBE2D1	BioGRID	PubMed	Two-hybrid
BioGRID:110378	BioGRID:113170	UBE2D2	BioGRID	PubMed	Two-hybrid
BioGRID:110378	BioGRID:113171	UBE2D3	BioGRID	PubMed	Two-hybrid
BioGRID:110378	BioGRID:119641	UBE2D4	BioGRID	PubMed	Two-hybrid
BioGRID:110378	BioGRID:113172	UBE2E1	BioGRID	PubMed	Two-hybrid
BioGRID:110378	BioGRID:113177	UBE2I	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:110378	BioGRID:114672	UBE2L6	BioGRID	PubMed	Two-hybrid
BioGRID:110378	BioGRID:120572	UBE2W	BioGRID	PubMed	Two-hybrid
BioGRID:110378	BioGRID:113363	YWHAE	BioGRID	PubMed	Reconstituted Complex

Function	Evidence Code	Pubs
ATP binding	NAS Non-traceable Author Statement more info
JUN kinase binding	IEA Inferred from Electronic Annotation more info
JUN kinase kinase kinase activity	IEA Inferred from Electronic Annotation more info
MAP kinase kinase kinase activity	NAS Non-traceable Author Statement more info	PubMed
MAPK/ERK kinase kinase activity	IEA Inferred from Electronic Annotation more info
identical protein binding	IEA Inferred from Electronic Annotation more info
metal ion binding	IEA Inferred from Electronic Annotation more info
mitogen-activated protein kinase binding	IEA Inferred from Electronic Annotation more info
mitogen-activated protein kinase kinase 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 kinase activity	IDA Inferred from Direct Assay more info	PubMed
protein kinase activity	TAS Traceable Author Statement more info
protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info
sphingolipid binding	IEA Inferred from Electronic Annotation more info
ubiquitin-protein ligase activity	IEA Inferred from Electronic Annotation more info
zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
MAPK cascade	NAS Non-traceable Author Statement more info	PubMed
MyD88-dependent toll-like receptor signaling pathway	TAS Traceable Author Statement more info
Toll signaling pathway	TAS Traceable Author Statement more info
activation of MAPKK activity	NAS Non-traceable Author Statement more info	PubMed
apoptotic mitochondrial changes	IEA Inferred from Electronic Annotation more info
camera-type eye development	IEA Inferred from Electronic Annotation more info
cellular response to mechanical stimulus	IEP Inferred from Expression Pattern more info	PubMed
innate immune response	TAS Traceable Author Statement more info
negative regulation of actin filament bundle assembly	IEA Inferred from Electronic Annotation more info
peptidyl-serine phosphorylation	IEA Inferred from Electronic Annotation more info
positive regulation of actin filament polymerization	IEA Inferred from Electronic Annotation more info
positive regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
positive regulation of viral transcription	IEA Inferred from Electronic Annotation more info
protein autophosphorylation	IEA Inferred from Electronic Annotation more info
protein oligomerization	IEA Inferred from Electronic Annotation more info
protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
protein phosphorylation	NAS Non-traceable Author Statement more info	PubMed
protein phosphorylation	TAS Traceable Author Statement more info
protein polyubiquitination	IEA Inferred from Electronic Annotation more info
protein ubiquitination involved in ubiquitin-dependent protein catabolic process	IEA Inferred from Electronic Annotation more info
regulation of cell migration	IEA Inferred from Electronic Annotation more info
response to osmotic stress	IEA Inferred from Electronic Annotation more info
toll-like receptor 1 signaling pathway	TAS Traceable Author Statement more info
toll-like receptor 2 signaling pathway	TAS Traceable Author Statement more info
toll-like receptor 4 signaling pathway	TAS Traceable Author Statement more info
toll-like receptor signaling pathway	TAS Traceable Author Statement more info
transforming growth factor beta receptor signaling pathway	IEA Inferred from Electronic Annotation more info
wound healing	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
cytoplasm	IEA Inferred from Electronic Annotation more info
cytoskeleton	IEA Inferred from Electronic Annotation more info
cytosol	TAS Traceable Author Statement more info
membrane fraction	IEA Inferred from Electronic Annotation more info

General protein information

Preferred Names: mitogen-activated protein kinase kinase kinase 1

Names: mitogen-activated protein kinase kinase kinase 1; MEK kinase 1; MAP/ERK kinase kinase 1; MAPK/ERK kinase kinase 1

NP_005912.1

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.

Genomic

NG_031884.1 RefSeqGene

Range

5001..86080

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_005921.1 → NP_005912.1 mitogen-activated protein kinase kinase kinase 1

Status: REVIEWED

Source sequence(s)

AA602425, AC008937, AF042838, BU194120, DA889202

Consensus CDS

CCDS43318.1

UniProtKB/Swiss-Prot

Q13233

Related

ENSP00000382423, OTTHUMP00000065818, ENST00000399503, OTTHUMT00000132309

Conserved Domains (3) summary

cd06630
Location:1242 – 1509
Blast Score: 1335

STKc_MEKK1; Catalytic domain of the Protein Serine/Threonine Kinase, MAP/ERK kinase kinase 1

smart00220
Location:1243 – 1508
Blast Score: 649

S_TKc; Serine/Threonine protein kinases, catalytic domain

cl15348
Location:441 – 494
Blast Score: 105

RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...

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_000005.9 Reference GRCh37.p5 Primary Assembly

Range

56110900..56191979

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000137.1 Alternate HuRef

Range

53082897..53163892

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC008937.7 (37931..119639)	None
genomic	U29671.1	AAB05828.1
mRNA	AA602425.1	None
mRNA	AF042838.1	AAC97073.1
mRNA	AK307828.1	None
mRNA	BU194120.1	None
mRNA	BX537527.1	None
mRNA	DA889202.1	None