MAP2K3 mitogen-activated protein kinase kinase 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: MAP2K3provided by HGNC
Official Full Name: mitogen-activated protein kinase kinase 3provided by HGNC
Primary source: HGNC:HGNC:6843
See related: Ensembl:ENSG00000034152 MIM:602315; AllianceGenome:HGNC:6843
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: MEK3; MKK3; MAPKK3; PRKMK3; SAPKK2; SAPKK-2
Summary: The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase is activated by mitogenic and environmental stress, and participates in the MAP kinase-mediated signaling cascade. It phosphorylates and thus activates MAPK14/p38-MAPK. This kinase can be activated by insulin, and is necessary for the expression of glucose transporter. Expression of RAS oncogene is found to result in the accumulation of the active form of this kinase, which thus leads to the constitutive activation of MAPK14, and confers oncogenic transformation of primary cells. The inhibition of this kinase is involved in the pathogenesis of Yersina pseudotuberculosis. Multiple alternatively spliced transcript variants that encode distinct isoforms have been reported for this gene. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in bone marrow (RPKM 62.9), gall bladder (RPKM 18.4) and 23 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 17p11.2

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (21284711..21315240)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (21233580..21264159)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (21188023..21218552)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Activated MKK3/MYC crosstalk impairs dabrafenib response in BRAFV600E colorectal cancer leading to resistance.
Title: Activated MKK3/MYC crosstalk impairs dabrafenib response in BRAFV600E colorectal cancer leading to resistance.
Identification of MAP Kinase Kinase 3 as a protein target of myricetin in non-small cell lung cancer cells.
Title: Identification of MAP Kinase Kinase 3 as a protein target of myricetin in non-small cell lung cancer cells.
The miR-19b-3p-MAP2K3-STAT3 feedback loop regulates cell proliferation and invasion in esophageal squamous cell carcinoma.
Title: The miR-19b-3p-MAP2K3-STAT3 feedback loop regulates cell proliferation and invasion in esophageal squamous cell carcinoma.
Quadruple and Truncated MEK3 Mutants Identified from Acute Lymphoblastic Leukemia Promote Degradation and Enhance Proliferation.
Title: Quadruple and Truncated MEK3 Mutants Identified from Acute Lymphoblastic Leukemia Promote Degradation and Enhance Proliferation.
TIPE-mediated up-regulation of MMP-9 promotes colorectal cancer invasion and metastasis through MKK-3/p38/NF-kappaB pro-oncogenic signaling pathway.
Title: TIPE-mediated up-regulation of MMP-9 promotes colorectal cancer invasion and metastasis through MKK-3/p38/NF-κB pro-oncogenic signaling pathway.
Whole-Exome Sequencing Reveals Novel Variations in Patients with Familial Von Hippel-Lindau Syndrome.
Title: Whole-Exome Sequencing Reveals Novel Variations in Patients with Familial Von Hippel-Lindau Syndrome.
The MKK-Dependent Phosphorylation of p38alpha Is Augmented by Arginine Methylation on Arg49/Arg149 during Erythroid Differentiation.
Title: The MKK-Dependent Phosphorylation of p38α Is Augmented by Arginine Methylation on Arg49/Arg149 during Erythroid Differentiation.
Genome-wide RNA interference screening reveals a COPI-MAP2K3 pathway required for YAP regulation.
Title: Genome-wide RNA interference screening reveals a COPI-MAP2K3 pathway required for YAP regulation.
MKK3 sustains cell proliferation and survival through p38DELTA MAPK activation in colorectal cancer.
Title: MKK3 sustains cell proliferation and survival through p38DELTA MAPK activation in colorectal cancer.
Expression of human MKK3 in Drosophila is able to initiate JNK-mediated cell migration, cooperates with oncogenic Ras to trigger tumor invasion, and rescue loss-of-lic induced thorax closure defect.
Title: MKK3 modulates JNK-dependent cell migration and invasion.

Submit: New GeneRIF Correction See all GeneRIFs (47)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	The interaction of HIV-1 Tat with cellular transcription factors CDK9 and Sp1 is required for Tat activation of MAP2K3-, MAP2K6-, and IRF7-mediated luciferase transcription	PubMed
	tat	SiRNA-mediated inhibition of MAP2K6 and MAP2K3 reduces HIV-1 Tat-induced modulation of interferon (IFN)-stimulated genes	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D17S624 (e-PCR)
- UniSTS:72492

MAP2K3_360 (e-PCR)
- UniSTS:277467

RH69047 (e-PCR)
- UniSTS:90080

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables MAP kinase kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables MAP kinase kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables MAP kinase kinase activity	TAS Traceable Author Statement more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein tyrosine kinase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in MAPK cascade	IBA Inferred from Biological aspect of Ancestor more info
involved_in cardiac muscle contraction	IEA Inferred from Electronic Annotation more info
involved_in cellular response to lipopolysaccharide	IEA Inferred from Electronic Annotation more info
involved_in cellular response to sorbitol	IEA Inferred from Electronic Annotation more info
involved_in cellular response to vascular endothelial growth factor stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular senescence	TAS Traceable Author Statement more info
involved_in heart development	IEA Inferred from Electronic Annotation more info
involved_in inflammatory response	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of hippo signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in p38MAPK cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in p38MAPK cascade	TAS Traceable Author Statement more info
involved_in positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of MAPK cascade	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of blood vessel endothelial cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of nitric-oxide synthase biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of protein kinase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in protein phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in regulation of cytokine production	IEA Inferred from Electronic Annotation more info
involved_in response to ischemia	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in stress-activated protein kinase signaling cascade	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	TAS Traceable Author Statement more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in membrane	HDA more info	PubMed
located_in nucleoplasm	TAS Traceable Author Statement more info

General protein information

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Preferred Names: dual specificity mitogen-activated protein kinase kinase 3

Names: MAP kinase kinase 3; MAPK/ERK kinase 3; MAPKK 3; MEK 3; SAPK kinase 2; stress-activated protein kinase kinase 2

NP_001303261.1

EC 2.7.12.2

NP_002747.2

EC 2.7.12.2

NP_659731.1

EC 2.7.12.2

XP_011522260.1

EC 2.7.12.2

XP_011522261.1

EC 2.7.12.2

XP_016880346.2

EC 2.7.12.2

XP_016880348.1

EC 2.7.12.2

XP_047292364.1

EC 2.7.12.2

XP_047292365.1

EC 2.7.12.2

XP_054172654.1

EC 2.7.12.2

XP_054172655.1

EC 2.7.12.2

XP_054172656.1

EC 2.7.12.2

XP_054172657.1

EC 2.7.12.2

XP_054172658.1

EC 2.7.12.2

XP_054172659.1

EC 2.7.12.2

NCBI Reference Sequences (RefSeq)

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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_028256.2 RefSeqGene

Range

5056..35577

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001316332.2 → NP_001303261.1 dual specificity mitogen-activated protein kinase kinase 3 isoform A

Status: REVIEWED

Description

Transcript Variant: This variant (D) contains an alternate 5' exon compared to variant B. This difference results in a distinct 5' UTR and causes translation initiation at a downstream start codon compared to variant B. The resulting isoform (A) is shorter at the N-terminus compared to isoform B. Variants A and D both encode the same isoform (A).

Source sequence(s)

AC087294, AI758302, AK093838, DA131175

Consensus CDS

CCDS11218.1

UniProtKB/TrEMBL

Q53EZ9, Q6FHG1

Conserved Domains (1) summary

cd06617
Location:33 → 315

PKc_MKK3_6; Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6
NM_002756.4 → NP_002747.2 dual specificity mitogen-activated protein kinase kinase 3 isoform A

See identical proteins and their annotated locations for NP_002747.2

Status: REVIEWED

Description

Transcript Variant: This variant (A) represents use of an alternate promoter and 5' UTR and uses a downstream start codon compared to variant B. The resulting isoform (A) is shorter at the N-terminus compared to isoform B. Variants A and D both encode the same isoform (A).

Source sequence(s)

AI758302, BC032478, DA987047

Consensus CDS

CCDS11218.1

UniProtKB/TrEMBL

Q53EZ9, Q6FHG1

Related

ENSP00000355081.5, ENST00000361818.9

Conserved Domains (1) summary

cd06617
Location:33 → 315

PKc_MKK3_6; Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6
NM_145109.3 → NP_659731.1 dual specificity mitogen-activated protein kinase kinase 3 isoform B

See identical proteins and their annotated locations for NP_659731.1

Status: REVIEWED

Description

Transcript Variant: This variant (B) encodes the longer isoform (B).

Source sequence(s)

AI758302, BC032478, D87116, DA131175

Consensus CDS

CCDS11217.1

UniProtKB/Swiss-Prot

B3KSK7, P46734, Q99441, Q9UE71, Q9UE72

UniProtKB/TrEMBL

Q53EZ9, Q6FHG1, Q6FI23

Related

ENSP00000345083.4, ENST00000342679.9

Conserved Domains (1) summary

cd06617
Location:62 → 344

PKc_MKK3_6; Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000017.11 Reference GRCh38.p14 Primary Assembly

Range

21284711..21315240

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017024857.3 → XP_016880346.2 dual specificity mitogen-activated protein kinase kinase 3 isoform X1
XM_017024859.2 → XP_016880348.1 dual specificity mitogen-activated protein kinase kinase 3 isoform X5

UniProtKB/TrEMBL

Q53EZ9, Q6FHG1

Conserved Domains (1) summary

cd06617
Location:33 → 315

PKc_MKK3_6; Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6
XM_047436408.1 → XP_047292364.1 dual specificity mitogen-activated protein kinase kinase 3 isoform X3
XM_047436409.1 → XP_047292365.1 dual specificity mitogen-activated protein kinase kinase 3 isoform X4
XM_011523959.3 → XP_011522261.1 dual specificity mitogen-activated protein kinase kinase 3 isoform X5

See identical proteins and their annotated locations for XP_011522261.1

UniProtKB/TrEMBL

Q53EZ9, Q6FHG1

Related

ENSP00000319139.6, ENST00000316920.10

Conserved Domains (1) summary

cd06617
Location:33 → 315

PKc_MKK3_6; Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6
XM_011523958.3 → XP_011522260.1 dual specificity mitogen-activated protein kinase kinase 3 isoform X2

Conserved Domains (2) summary

smart00220
Location:38 → 240

S_TKc; Serine/Threonine protein kinases, catalytic domain

cl21453
Location:33 → 231

PKc_like; Protein Kinases, catalytic domain

Alternate T2T-CHM13v2.0

Genomic

NC_060941.1 Alternate T2T-CHM13v2.0

Range

21233580..21264159

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054316679.1 → XP_054172654.1 dual specificity mitogen-activated protein kinase kinase 3 isoform X1
XM_054316683.1 → XP_054172658.1 dual specificity mitogen-activated protein kinase kinase 3 isoform X5
XM_054316681.1 → XP_054172656.1 dual specificity mitogen-activated protein kinase kinase 3 isoform X3
XM_054316682.1 → XP_054172657.1 dual specificity mitogen-activated protein kinase kinase 3 isoform X4
XM_054316684.1 → XP_054172659.1 dual specificity mitogen-activated protein kinase kinase 3 isoform X5
XM_054316680.1 → XP_054172655.1 dual specificity mitogen-activated protein kinase kinase 3 isoform X2

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_145110.1: Suppressed sequence

Description

NM_145110.1: This RefSeq was temporarily suppressed because currently there are not sufficient data to support this transcript.