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    MAP3K2 mitogen-activated protein kinase kinase kinase 2 [ Homo sapiens (human) ]

    Gene ID: 10746, updated on 5-Mar-2024

    Summary

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    Official Symbol
    MAP3K2provided by HGNC
    Official Full Name
    mitogen-activated protein kinase kinase kinase 2provided by HGNC
    Primary source
    HGNC:HGNC:6854
    See related
    Ensembl:ENSG00000169967 MIM:609487; AllianceGenome:HGNC:6854
    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
    MEKK2; MEKK2B
    Summary
    The protein encoded by this gene is a member of serine/threonine protein kinase family. This kinase preferentially activates other kinases involved in the MAP kinase signaling pathway. This kinase has been shown to directly phosphorylate and activate Ikappa B kinases, and thus plays a role in NF-kappa B signaling pathway. This kinase has also been found to bind and activate protein kinase C-related kinase 2, which suggests its involvement in a regulated signaling process. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in bone marrow (RPKM 11.2), thyroid (RPKM 10.3) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    2q14.3
    Exon count:
    19
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (127298668..127388465, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (127733893..127823745, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (128056244..128146041, complement)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene MPRA-validated peak3852 silencer Neighboring gene WBP11 pseudogene 2 Neighboring gene ERCC excision repair 3, TFIIH core complex helicase subunit Neighboring gene RNA, U6 small nuclear 1147, pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:128109563-128110062 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr2:128111582-128112160 Neighboring gene uncharacterized LOC124906074 Neighboring gene MPRA-validated peak3853 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11931 Neighboring gene MAP3K2 divergent transcript Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:128158054-128158766 Neighboring gene translation initiation factor IF-2-like Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11932 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16486 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16487 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:128172964-128173726 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16488 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:128180062-128180860 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:128180861-128181657 Neighboring gene microRNA 4783 Neighboring gene protein C, inactivator of coagulation factors Va and VIIIa

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • 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

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    Related articles in PubMed

    1. Structural basis for antigen recognition by methylated lysine-specific antibodies. Ishii M, et al. J Biol Chem, 2021 Jan-Jun. PMID 33303630, Free PMC Article
    2. Discovery and characterization of an iminocoumarin scaffold as an inhibitor of MEKK2 (MAP3K2). Ahmad S, et al. Biochem Biophys Res Commun, 2018 Jan 29. PMID 29309787, Free PMC Article
    3. Structure-Based Design of a Novel SMYD3 Inhibitor that Bridges the SAM-and MEKK2-Binding Pockets. Van Aller GS, et al. Structure, 2016 May 3. PMID 27066749
    4. EBV microRNA BART 18-5p targets MAP3K2 to facilitate persistence in vivo by inhibiting viral replication in B cells. Qiu J, et al. Proc Natl Acad Sci U S A, 2014 Jul 29. PMID 25012295, Free PMC Article
    5. MEKK2 regulates focal adhesion stability and motility in invasive breast cancer cells. Mirza AA, et al. Biochim Biophys Acta, 2014 May. PMID 24491810, Free PMC Article

    See all (94) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Regulation of a Novel CircTRRAP/miR-761/MAP3K2 CeRNA Cascade in Inflammation, Apoptosis, and Oxidative Stress in Human AC16 Cardiomyocytes under Hypoxia Conditions.
      Title: Regulation of a Novel CircTRRAP/miR-761/MAP3K2 CeRNA Cascade in Inflammation, Apoptosis, and Oxidative Stress in Human AC16 Cardiomyocytes under Hypoxia Conditions.
    2. CircHSPG2 knockdown attenuates hypoxia-induced apoptosis, inflammation, and oxidative stress in human AC16 cardiomyocytes by regulating the miR-1184/MAP3K2 axis.
      Title: CircHSPG2 knockdown attenuates hypoxia-induced apoptosis, inflammation, and oxidative stress in human AC16 cardiomyocytes by regulating the miR-1184/MAP3K2 axis.
    3. CircRNA circBACH1 facilitates hepatitis B virus replication and hepatoma development by regulating the miR-200a-3p/MAP3K2 axis.
      Title: CircRNA circBACH1 facilitates hepatitis B virus replication and hepatoma development by regulating the miR-200a-3p/MAP3K2 axis.
    4. miRNA-338-3p inhibits the migration, invasion and proliferation of human lung adenocarcinoma cells by targeting MAP3K2.
      Title: miRNA-338-3p inhibits the migration, invasion and proliferation of human lung adenocarcinoma cells by targeting MAP3K2.
    5. miR36133p/MAP3K2/p38/caspase3 pathway regulates the heatstressinduced apoptosis of endothelial cells.
      Title: miR‑3613‑3p/MAP3K2/p38/caspase‑3 pathway regulates the heat‑stress‑induced apoptosis of endothelial cells.
    6. Mass-spectrometry-based proteomic correlates of grade and stage reveal pathways and kinases associated with aggressive human cancers.
      Title: Mass-spectrometry-based proteomic correlates of grade and stage reveal pathways and kinases associated with aggressive human cancers.
    7. Structural basis for antigen recognition by methylated lysine-specific antibodies.
      Title: Structural basis for antigen recognition by methylated lysine-specific antibodies.
    8. MIR205HG acts as a ceRNA to expedite cell proliferation and progression in lung squamous cell carcinoma via targeting miR-299-3p/MAP3K2 axis.
      Title: MIR205HG acts as a ceRNA to expedite cell proliferation and progression in lung squamous cell carcinoma via targeting miR-299-3p/MAP3K2 axis.
    9. MEKK2 mediates aberrant ERK activation in neurofibromatosis type I.
      Title: MEKK2 mediates aberrant ERK activation in neurofibromatosis type I.
    10. circ-PITX1 exerted as a competing endogenous RNA (ceRNA) in glioblastoma by sponging miR-379-5p to elevate MAP3K2 expression
      Title: Circular RNA circ-PITX1 promotes the progression of glioblastoma by acting as a competing endogenous RNA to regulate miR-379-5p/MAP3K2 axis.
    Submit: New GeneRIF Correction See all GeneRIFs (35)

    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)

    Genotypes

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Screening in Jurkat T-cells with a short-hairpin-RNA (shRNA) library identifies MAP3K2, a member of mitogen-activated protein kinase kinase family (serine/threonine protein kinase), is important for HIV-1 replication PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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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

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables MAP kinase kinase kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein kinase activity IDA
    Inferred from Direct Assay
    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 IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in MAPK cascade IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cellular response to mechanical stimulus IEP
    Inferred from Expression Pattern
    more info
    		 PubMed 
    involved_in intracellular signal transduction IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in phosphorylation IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    mitogen-activated protein kinase kinase kinase 2
    Names
    MAP/ERK kinase kinase 2
    MAPK/ERK kinase kinase 2
    MEK kinase 2
    MEKK 2
    NP_001358839.1
    NP_001358840.1
    NP_006600.3
    XP_047298945.1
    XP_047298946.1
    XP_047298947.1
    XP_054196193.1
    XP_054196194.1

    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.

    mRNA and Protein(s)

    1. NM_001371910.2 → NP_001358839.1  mitogen-activated protein kinase kinase kinase 2

      Status: REVIEWED

      Source sequence(s)
      AC068282, AC110926
      Consensus CDS
      CCDS46404.1
      UniProtKB/Swiss-Prot
      B9EG87, Q53QL9, Q53S75, Q59GZ6, Q8NC32, Q9NYK3, Q9Y2U5
      Related
      ENSP00000507315.1, ENST00000682094.1
      Conserved Domains (2) summary
      cd06405
      Location:44 → 122
      PB1_Mekk2_3; The PB1 domain is present in the two mitogen-activated protein kinase kinases MEKK2 and MEKK3 which are two members of the signaling kinase cascade involved in angiogenesis and early cardiovascular development. The PB1 domain of MEKK2 (and/or MEKK3) ...
      cd06652
      Location:353 → 616
      STKc_MEKK2; Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 2

    2. NM_001371911.1 → NP_001358840.1  mitogen-activated protein kinase kinase kinase 2

      Status: REVIEWED

      Source sequence(s)
      AC068282, AC110926
      Consensus CDS
      CCDS46404.1
      UniProtKB/Swiss-Prot
      B9EG87, Q53QL9, Q53S75, Q59GZ6, Q8NC32, Q9NYK3, Q9Y2U5
      Related
      ENSP00000387246.1, ENST00000409947.5
      Conserved Domains (2) summary
      cd06405
      Location:44 → 122
      PB1_Mekk2_3; The PB1 domain is present in the two mitogen-activated protein kinase kinases MEKK2 and MEKK3 which are two members of the signaling kinase cascade involved in angiogenesis and early cardiovascular development. The PB1 domain of MEKK2 (and/or MEKK3) ...
      cd06652
      Location:353 → 616
      STKc_MEKK2; Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 2

    3. NM_006609.5 → NP_006600.3  mitogen-activated protein kinase kinase kinase 2

      See identical proteins and their annotated locations for NP_006600.3

      Status: REVIEWED

      Source sequence(s)
      AC068282, AC110926
      Consensus CDS
      CCDS46404.1
      UniProtKB/Swiss-Prot
      B9EG87, Q53QL9, Q53S75, Q59GZ6, Q8NC32, Q9NYK3, Q9Y2U5
      Related
      ENSP00000343463.5, ENST00000344908.9
      Conserved Domains (2) summary
      cd06405
      Location:44 → 122
      PB1_Mekk2_3; The PB1 domain is present in the two mitogen-activated protein kinase kinases MEKK2 and MEKK3 which are two members of the signaling kinase cascade involved in angiogenesis and early cardiovascular development. The PB1 domain of MEKK2 (and/or MEKK3) ...
      cd06652
      Location:353 → 616
      STKc_MEKK2; Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 2

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      127298668..127388465 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047442990.1 → XP_047298946.1  mitogen-activated protein kinase kinase kinase 2 isoform X1

      UniProtKB/Swiss-Prot
      B9EG87, Q53QL9, Q53S75, Q59GZ6, Q8NC32, Q9NYK3, Q9Y2U5

    2. XM_047442991.1 → XP_047298947.1  mitogen-activated protein kinase kinase kinase 2 isoform X1

      UniProtKB/Swiss-Prot
      B9EG87, Q53QL9, Q53S75, Q59GZ6, Q8NC32, Q9NYK3, Q9Y2U5

    3. XM_047442989.1 → XP_047298945.1  mitogen-activated protein kinase kinase kinase 2 isoform X1

      UniProtKB/Swiss-Prot
      B9EG87, Q53QL9, Q53S75, Q59GZ6, Q8NC32, Q9NYK3, Q9Y2U5

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      127733893..127823745 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054340218.1 → XP_054196193.1  mitogen-activated protein kinase kinase kinase 2 isoform X1

      UniProtKB/Swiss-Prot
      B9EG87, Q53QL9, Q53S75, Q59GZ6, Q8NC32, Q9NYK3, Q9Y2U5

    2. XM_054340219.1 → XP_054196194.1  mitogen-activated protein kinase kinase kinase 2 isoform X1

      UniProtKB/Swiss-Prot
      B9EG87, Q53QL9, Q53S75, Q59GZ6, Q8NC32, Q9NYK3, Q9Y2U5
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9Y2U5.2 GenPept UniProtKB/Swiss-Prot:Q9Y2U5

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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