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

Gene ID: 5606, updated on 9-Dec-2024

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
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Genomic context

See MAP2K3 in Genome Data Viewer
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_000017.11Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:21142166-21142910 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:21143656-21144400 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:21147379-21148121 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:21152353-21152854 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8315 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8316 Neighboring gene N-acetyltransferase domain containing 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:21166079-21166648 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11882 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8317 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8318 Neighboring gene eukaryotic translation initiation factor 1 pseudogene 5 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11883 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:21187095-21187595 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11884 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr17:21190872-21192071 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:21200045-21200584 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:21200745-21201246 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:21201247-21201746 Neighboring gene H3K27ac hESC enhancer GRCh37_chr17:21212475-21212974 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:21215299-21215916 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:21220325-21220834 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:21221172-21221848 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:21221849-21222525 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:21226043-21226716 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:21241499-21242434 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:21246647-21247147 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:21248662-21249219 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:21249895-21250396 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:21250397-21250896 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr17:21260572-21261142 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr17:21261143-21261713 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:21262777-21263487 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:21273483-21274248 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:21274448-21275184 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:21275185-21275920 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:21275921-21276656 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:21276657-21277392 Neighboring gene potassium inwardly rectifying channel subfamily J member 12 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:21300639-21301238 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:21302987-21303964 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:21303965-21304942 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:21307551-21308050 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:21308458-21308958 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:21313097-21314057 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:21314058-21315017 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:21328219-21328718 Neighboring gene uncharacterized LOC124903950

Genomic regions, transcripts, and products

Expression

  • Project title: 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

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

HIV-1 interactions

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

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
 
enables JUN kinase kinase activity 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 histone H2AXY142 kinase activity IEA
Inferred from Electronic Annotation
more info
 
enables histone H3Y41 kinase activity IEA
Inferred from Electronic Annotation
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
 
Process Evidence Code Pubs
involved_in JNK cascade IEA
Inferred from Electronic Annotation
more info
 
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 chromatin remodeling IEA
Inferred from Electronic Annotation
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 protein kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
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 PubMed 
located_in nucleoplasm TAS
Traceable Author Statement
more info
 

General protein information

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
NP_002747.2
NP_659731.1
XP_011522260.1
XP_011522261.1
XP_016880346.2
XP_016880348.1
XP_047292364.1
XP_047292365.1
XP_054172654.1
XP_054172655.1
XP_054172656.1
XP_054172657.1
XP_054172658.1
XP_054172659.1

NCBI Reference Sequences (RefSeq)

NEW Try the new Transcript table

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

  1. NG_028256.2 RefSeqGene

    Range
    5056..35577
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001316332.2NP_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:33315
    PKc_MKK3_6; Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6
  2. NM_002756.4NP_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:33315
    PKc_MKK3_6; Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6
  3. NM_145109.3NP_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:62344
    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

  1. NC_000017.11 Reference GRCh38.p14 Primary Assembly

    Range
    21284711..21315240
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017024857.3XP_016880346.2  dual specificity mitogen-activated protein kinase kinase 3 isoform X1

  2. XM_017024859.2XP_016880348.1  dual specificity mitogen-activated protein kinase kinase 3 isoform X5

    UniProtKB/TrEMBL
    Q53EZ9, Q6FHG1
    Conserved Domains (1) summary
    cd06617
    Location:33315
    PKc_MKK3_6; Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6
  3. XM_047436408.1XP_047292364.1  dual specificity mitogen-activated protein kinase kinase 3 isoform X3

    UniProtKB/TrEMBL
    C7DUW4
  4. XM_047436409.1XP_047292365.1  dual specificity mitogen-activated protein kinase kinase 3 isoform X4

    UniProtKB/TrEMBL
    C7DUW4
  5. XM_011523959.3XP_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:33315
    PKc_MKK3_6; Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6
  6. XM_011523958.3XP_011522260.1  dual specificity mitogen-activated protein kinase kinase 3 isoform X2

    Conserved Domains (2) summary
    smart00220
    Location:38240
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cl21453
    Location:33231
    PKc_like; Protein Kinases, catalytic domain

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060941.1 Alternate T2T-CHM13v2.0

    Range
    21233580..21264159
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054316679.1XP_054172654.1  dual specificity mitogen-activated protein kinase kinase 3 isoform X1

  2. XM_054316683.1XP_054172658.1  dual specificity mitogen-activated protein kinase kinase 3 isoform X5

    UniProtKB/TrEMBL
    Q53EZ9, Q6FHG1
  3. XM_054316681.1XP_054172656.1  dual specificity mitogen-activated protein kinase kinase 3 isoform X3

    UniProtKB/TrEMBL
    C7DUW4
  4. XM_054316682.1XP_054172657.1  dual specificity mitogen-activated protein kinase kinase 3 isoform X4

    UniProtKB/TrEMBL
    C7DUW4
  5. XM_054316684.1XP_054172659.1  dual specificity mitogen-activated protein kinase kinase 3 isoform X5

    UniProtKB/TrEMBL
    Q53EZ9, Q6FHG1
  6. XM_054316680.1XP_054172655.1  dual specificity mitogen-activated protein kinase kinase 3 isoform X2

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. 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.