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MAP3K5 Gene

protein-coding   GIFtS: 69
GCID: GC06M136878

Mitogen-Activated Protein Kinase Kinase Kinase 5


(Previous symbol: MEKK5)
Microbiology & Infectious Diseases Congress
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(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Mitogen-Activated Protein Kinase Kinase Kinase 51 2     MAPK/ERK Kinase Kinase 52 3
MEKK51 2 3 5     MEK Kinase 52 3
ASK12 3 5     MEKK 52 3
MAPKKK52 3 5     EC 2.7.11.253 8
Apoptosis Signal Regulating Kinase 11 2     MAP/ERK Kinase Kinase 52
Apoptosis Signal-Regulating Kinase 12 3     EC 2.7.118
ASK-12 3     

External Ids:    HGNC: 68571   Entrez Gene: 42172   Ensembl: ENSG000001974427   OMIM: 6024485   UniProtKB: Q996833   

Export aliases for MAP3K5 gene to outside databases

Previous GC identifers: GC06M136500 GC06M136725 GC06M136858 GC06M136919 GC06M134442


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for MAP3K5 Gene:
Mitogen-activated protein kinase (MAPK) signaling cascades include MAPK or extracellular signal-regulated kinase
(ERK), MAPK kinase (MKK or MEK), and MAPK kinase kinase (MAPKKK or MEKK). MAPKK kinase/MEKK phosphorylates and
activates its downstream protein kinase, MAPK kinase/MEK, which in turn activates MAPK. The kinases of these
signaling cascades are highly conserved, and homologs exist in yeast, Drosophila, and mammalian cells. MAPKKK5
contains 1,374 amino acids with all 11 kinase subdomains. Northern blot analysis shows that MAPKKK5 transcript is
abundantly expressed in human heart and pancreas. The MAPKKK5 protein phosphorylates and activates MKK4 (aliases
SERK1, MAPKK4) in vitro, and activates c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK)
during transient expression in COS and 293 cells; MAPKKK5 does not activate MAPK/ERK. (provided by RefSeq, Jul
2008)

GeneCards Summary for MAP3K5 Gene:
MAP3K5 (mitogen-activated protein kinase kinase kinase 5) is a protein-coding gene. Diseases associated with MAP3K5 include japanese encephalitis, and prostate adenocarcinoma. GO annotations related to this gene include protein kinase binding and protein homodimerization activity. An important paralog of this gene is MAP3K1.

UniProtKB/Swiss-Prot: M3K5_HUMAN, Q99683
Function: Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction
pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment.
Mediates signaling for determination of cell fate such as differentiation and survival. Plays a crucial role in
the apoptosis signal transduction pathway through mitochondria-dependent caspase activation. MAP3K5/ASK1 is
required for the innate immune response, which is essential for host defense against a wide range of pathogens.
Mediates signal transduction of various stressors like oxidative stress as well as by receptor-mediated
inflammatory signals, such as the tumor necrosis factor (TNF) or lipopolysaccharide (LPS). Once activated, acts
as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade
through the phosphorylation and activation of several MAP kinase kinases like MAP2K4/SEK1, MAP2K3/MKK3,
MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs). Both
p38 MAPK and JNKs control the transcription factors activator protein-1 (AP-1)

summary for MAP3K5 Gene:
Apoptosis signal-regulating kinase 1 (ASK1, MAP3K5) is a member of the MAPKKK family. It activates JNK and
p38 pathways in response to a variety of signals, including calcium and GPCR signaling, and endoplasmic
reticulum stress.

Gene Wiki entry for MAP3K5 (ASK1) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000006.12  NT_025741.16  NC_018917.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the MAP3K5 gene promoter:
         PPAR-gamma1   p53   AP-1   ATF-2   PPAR-gamma2   c-Jun   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidMAP3K5 promoter sequence
   Search Chromatin IP Primers for MAP3K5

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat MAP3K5


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 6q22.33   Ensembl cytogenetic band:  6q23.3   HGNC cytogenetic band: 6q22.33

MAP3K5 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
MAP3K5 gene location

GeneLoc information about chromosome 6         GeneLoc Exon Structure

GeneLoc location for GC06M136878:  view genomic region     (about GC identifiers)

Start:
136,878,185 bp from pter      End:
137,113,656 bp from pter
Size:
235,472 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: M3K5_HUMAN, Q99683 (See protein sequence)
Recommended Name: Mitogen-activated protein kinase kinase kinase 5  
Size: 1374 amino acids; 154537 Da
Cofactor: Magnesium
Subunit: Homodimer when inactive. Binds both upstream activators and downstream substrates in multimolecular
complexes. Associates with and inhibited by HIV-1 Nef. Part of a cytoplasmic complex made of HIPK1, DAB2IP and
MAP3K5 in response to TNF. This complex formation promotes MAP3K5-JNK activation and subsequent apoptosis.
Interacts with SOCS1 which recognizes phosphorylation of Tyr-718 and induces MAP3K5/ASK1 degradation in
endothelial cells. Interacts with the 14-3-3 family proteins such as YWHAB, YWHAE, YWHAQ, YWHAH, YWHAZ and SFN.
Interacts with ARRB2, BIRC2, DAB2IP, IGF1R, MAP3K6/ASK2, PGAM5, PIM1, PPP5C, SOCS1, STUB1, TRAF2, TRAF6 and TXN.
Interacts with ERN1 in a TRAF2-dependent manner. Interacts with calcineurin subunit PPP3R1 and with PPM1L (By
similarity). Interacts (via N-terminus) with RAF1 and this interaction inhibits the proapoptotic function of
MAP3K5. Interacts with DAB2IP (via N-terminus C2 domain); the interaction occurs in a TNF-alpha-dependent manner.
Interacts with DUSP13/DUSP13A; may positively regulate apoptosis
Selected PDB 3D structures from and Proteopedia for MAP3K5 (see all 8):
2CLQ (3D)        3VW6 (3D)        4BF2 (3D)        4BHN (3D)        4BIB (3D)        4BIC (3D)    
Secondary accessions: Q5THN3 Q99461

Explore the universe of human proteins at neXtProt for MAP3K5: NX_Q99683

Explore proteomics data for MAP3K5 at MOPED

Post-translational modifications: 

  • Phosphorylated at Thr-838 through autophosphorylation and by MAP3K6/ASK2 which leads to activation. Thr-838 is
    dephosphorylated by PPP5C. Ser-83 and Ser-1033 are inactivating phosphorylation sites, the former of which is
    phosphorylated by AKT1 and AKT2. Phosphorylated at Ser-966 which induces association of MAP3K5/ASK1 with the
    14-3-3 family proteins and suppresses MAP3K5/ASK1 activity. Calcineurin (CN) dephosphorylates this site. Also
    dephosphorylated and activated by PGAM51
  • Ubiquitinated. Tumor necrosis factor (TNF) induces TNFR2-dependent ubiquitination leading to proteasomal
    degradation1
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for MAP3K5 (Q99683) (see all 6)
     VPGGSLS  LGKKGNL  NLLLSYRD  LFGFQDAVN 


    See MAP3K5 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_005914.1  
    ENSEMBL proteins: 
     ENSP00000351908   ENSP00000348104  
    Reactome Protein details: Q99683

    MAP3K5 Human Recombinant Protein Products:

    EMD Millipore Purified and/or Recombinant MAP3K5 Protein
    R&D Systems Recombinant & Natural Proteins for MAP3K5 (ASK1)
    Enzo Life Sciences proteins for MAP3K5
    OriGene Purified Protein for MAP3K5
    OriGene Protein Over-expression Lysate for MAP3K5
    OriGene MassSpec for MAP3K5
    OriGene Custom Protein Services for MAP3K5
    GenScript Custom Purified and Recombinant Proteins Services for MAP3K5
    Novus Biologicals MAP3K5 Proteins
    Novus Biologicals MAP3K5 Lysates
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Browse Proteins at Cloud-Clone Corp.

    MAP3K5 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of MAP3K5
    R&D Systems Antibodies for MAP3K5 (ASK1)
    Cell Signaling Technology (CST) Antibodies for MAP3K5  (ASK1)
    OriGene Antibodies for MAP3K5
    OriGene Custom Antibody Services for MAP3K5
    Novus Biologicals MAP3K5 Antibodies
    Abcam antibodies for MAP3K5
    Browse Antibodies at Cloud-Clone Corp.
    ThermoFisher Antibody for MAP3K5
    LSBio Antibodies in human, mouse, rat for MAP3K5

    MAP3K5 Assay Products:

    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for MAP3K5
    Browse R&D Systems for biochemical assays
    GenScript Custom Assay Services for MAP3K5
    Browse Enzo Life Sciences for kits & assays
    Browse ELISAs at Cloud-Clone Corp.
    Browse CLIAs at Cloud-Clone Corp.


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    MAP3K: Mitogen-activated protein kinase cascade / Kinase kinase kinases

    IUPHAR Guide to PHARMACOLOGY protein family classification: mitogen-activated protein kinase kinase kinase 5
    STE11 family

    Selected InterPro protein domains (see all 7):
     IPR017441 Protein_kinase_ATP_BS
     IPR002290 Ser/Thr_dual-sp_kinase_dom
     IPR011009 Kinase-like_dom
     IPR008271 Ser/Thr_kinase_AS
     IPR025136 DUF4071

    Graphical View of Domain Structure for InterPro Entry Q99683

    ProtoNet protein and cluster: Q99683

    UniProtKB/Swiss-Prot: M3K5_HUMAN, Q99683
    Similarity: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase
    subfamily
    Similarity: Contains 1 protein kinase domain


    MAP3K5 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: M3K5_HUMAN, Q99683
    Function: Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction
    pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment.
    Mediates signaling for determination of cell fate such as differentiation and survival. Plays a crucial role in
    the apoptosis signal transduction pathway through mitochondria-dependent caspase activation. MAP3K5/ASK1 is
    required for the innate immune response, which is essential for host defense against a wide range of pathogens.
    Mediates signal transduction of various stressors like oxidative stress as well as by receptor-mediated
    inflammatory signals, such as the tumor necrosis factor (TNF) or lipopolysaccharide (LPS). Once activated, acts
    as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade
    through the phosphorylation and activation of several MAP kinase kinases like MAP2K4/SEK1, MAP2K3/MKK3,
    MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs). Both
    p38 MAPK and JNKs control the transcription factors activator protein-1 (AP-1)
    Catalytic activity: ATP + a protein = ADP + a phosphoprotein
    Enzyme regulation: Activated by various stressors, including oxidative stress, endoplasmic reticulum stress, and
    calcium overload, as well as by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF)
    and lipopolysaccharide (LPS). Homophilic association of MAP3K5/ASK1 through the C-terminal coiled-coil domains
    and the heteromeric complex formation of MAP3K5/ASK1 with the reduced form of thioredoxin (TXN), constitutes an
    inactive form of the kinase. Upon ROS-induced dissociation of TXN from MAP3K5/ASK1, TRAF2 and TRAF6 are
    reciprocally recruited to MAP3K5/ASK1 and form the active MAP3K5/ASK1 signalosome, in which TRAF2 and TRAF6
    appear to facilitate the active configuration of MAP3K5/ASK1. MAP3K5/ASK1 activity is also regulated through
    several phosphorylation and dephosphorylation events. Thr-838 is an activating phosphorylation site that is
    autophosphorylated and phosphorylated by MAP3K6/ASK2 and dephosphorylated by PPP5C. Ser-83 and Ser-1033 are
    inactivating phosphorylation sites, the former of which is phosphorylated by AKT1 and AKT2. Phosphorylation of
    Ser-966 induces association of MAP3K5/ASK1 with the 14-3-3 family proteins, which suppresses MAP3K5/ASK1
    activity. Calcium/calmodulin-activated protein phosphatase calcineurin (PPP3CA) has been shown to directly
    dephosphorylate this site. SOCS1 binds to ASK1 by recognizing phosphorylation of Tyr-718 and induces MAP3K5/ASK1
    degradation in endothelial cells. Also dephosphorylated and activated by PGAM5. Contains an N-terminal
    autoinhibitory domain
    Induction: By TNF. Inhibited by HIV-1 Nef

         Genatlas biochemistry entry for MAP3K5:
    mitogen activated protein (MAP/ERK) kinase kinase kinase 5

         Enzyme Numbers (IUBMB): EC 2.7.11.251 2 EC 2.7.112

         Gene Ontology (GO): Selected molecular function terms (see all 12):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000287magnesium ion binding IDA17210579
    GO:0004672protein kinase activity IDA--
    GO:0004674protein serine/threonine kinase activity ----
    GO:0004709MAP kinase kinase kinase activity IDA17210579
    GO:0004713protein tyrosine kinase activity ----
         
    MAP3K5 for ontologies           About GeneDecksing


    Phenotypes:
         2 GenomeRNAi human phenotypes for MAP3K5:
     Decreased Salmonella enterica   Increased telomerase activity 

         4 MGI mutant phenotypes (inferred from 1 allele(MGI details for Map3k5):
     cardiovascular system  cellular  homeostasis/metabolism  tumorigenesis 

    MAP3K5 for phenotypes           About GeneDecksing

    Animal Models:
       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for MAP3K5
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for MAP3K5

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for MAP3K5
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for MAP3K5

    miRNA
    Products:
        
    miRTarBase miRNAs that target MAP3K5:
    hsa-mir-769-3p (MIRT039091)

    Block miRNA regulation of human, mouse, rat MAP3K5 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate MAP3K5 (see all 34):
    hsa-miR-582-3p hsa-miR-429 hsa-miR-199a-3p hsa-miR-106a hsa-miR-30d hsa-miR-519a hsa-miR-10b* hsa-miR-30a
    SwitchGear 3'UTR luciferase reporter plasmidMAP3K5 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for MAP3K5
    Predesigned siRNA for gene silencing in human, mouse, rat MAP3K5

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for MAP3K5

    Clone
    Products:
         
    OriGene clones in human, mouse for MAP3K5 (see all 8)
    OriGene ORF clones in mouse, rat for MAP3K5
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: MAP3K5 (NM_005923)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for MAP3K5
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat MAP3K5

    Cell Line
    Products:
         
    GenScript Custom overexpressing Cell Line Services for MAP3K5
    Browse ESI BIO Cell Lines and PureStem Progenitors for MAP3K5 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for MAP3K5


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    M3K5_HUMAN, Q99683: Cytoplasm. Endoplasmic reticulum. Note=Interaction with 14-3-3 proteins alters the
    distribution of MAP3K5/ASK1 and restricts it to the perinuclear endoplasmic reticulum region
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    endoplasmic reticulum5
    cytosol3
    mitochondrion2
    nucleus2
    extracellular1
    peroxisome1

    Gene Ontology (GO): 2 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005783endoplasmic reticulum IEA--
    GO:0005829cytosol TAS--

    MAP3K5 for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for MAP3K5 About   (see all 49)                                                                                              See pathways by source

    SuperPathContained pathways About
    1TWEAK Pathway
    TNF Signaling0.55
    Apoptosis through Death Receptors0.42
    HIV-1 Nef- Negative effector of Fas and TNF-alpha0.46
    Fas Signaling0.35
    Apoptotic Pathways Triggered By HIV10.42
    2Amyotrophic lateral sclerosis (ALS)
    Amyotrophic lateral sclerosis (ALS)0.63
    Amyotrophic lateral sclerosis (ALS)0.63
    3MAPK signaling pathway
    MAPK signaling pathway0.50
    MAPK signaling pathway0.50
    4Development IGF 1 receptor signaling
    Development IGF RI signaling0.49
    Development IGF 1 receptor signaling0.48
    5Development HGF signaling pathway
    Neurotrophin signaling pathway0.36
    Apoptosis and survival Anti apoptotic action of membrane bound ESR10.35

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for MAP3K5 (see all 43)
        14-3-3 Induced Apoptosis
    Molecular Mechanisms of Cancer
    Antioxidant Action of Vitamin-C
    G12-G13 in Cellular Signaling
    Interferon Pathway

    2 Cell Signaling Technology (CST) Pathways for MAP3K5
        MAP Kinase Signaling
    Apoptosis and Autophagy

    Selected GeneGo (Thomson Reuters) Pathways for MAP3K5 (see all 7)
        Apoptosis and survival Anti-apoptotic action of membrane-bound ESR1
    Apoptosis and survival Anti-apoptotic action of nuclear ESR1 and ESR2
    Apoptosis and survival FAS signaling cascades
    Signal transduction JNK pathway
    Development Angiotensin signaling via beta-Arrestin

    Selected BioSystems Pathways for MAP3K5 (see all 11)
        MAPK signaling pathway
    Apoptosis Modulation and Signaling
    Insulin Signaling
    p38 MAPK Signaling Pathway
    Amyotrophic lateral sclerosis (ALS)

    1 Reactome Pathway for MAP3K5
        Oxidative Stress Induced Senescence


    Selected Kegg Pathways  (Kegg details for MAP3K5) (see all 6):
        MAPK signaling pathway
    Protein processing in endoplasmic reticulum
    TNF signaling pathway
    Neurotrophin signaling pathway
    Non-alcoholic fatty liver disease (NAFLD)


    MAP3K5 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including MAP3K5: 
              HIV Host Response in human mouse rat
              Apoptosis 384HT in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for MAP3K5

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for MAP3K5 (Q996831, 2, 3 ENSP000003519084) via UniProtKB, MINT, STRING, and/or I2D (see all 150)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    HSPA1AP081073, ENSP000003648024I2D: score=3 STRING: ENSP00000364802
    ENSG00000212866P081073I2D: score=3 
    ENSG00000215328P081073I2D: score=3 
    ENSG00000224501P081073I2D: score=3 
    ENSG00000231555P081073I2D: score=3 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 18):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000165MAPK cascade IDA17210579
    GO:0000186activation of MAPKK activity IDA11959862
    GO:0000187activation of MAPK activity ----
    GO:0001934positive regulation of protein phosphorylation ----
    GO:0002931response to ischemia IEA--

    MAP3K5 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
    About This Section

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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
    4 ApexBio Compounds for MAP3K5     About this table
    CompoundAction CAS #
    FR 180204Selective ERK inhibitor[865362-74-9]
    VX-11epotent, selective, and orally bioavailable inhibitor of ERK[896720-20-0]
    XMD17-109novel, specific ERK-5 inhibitor with an EC50 4.2uM in HEK293 cells[1435488-37-1]
    XMD8-92highly selective ERK5/BMK1 inhibitor[1234480-50-2]

    Compounds for MAP3K5 available from Tocris Bioscience    About this table
    CompoundAction CAS #
    3-MethyladenineClass III PI 3-kinase inhibitor; also inhibits autophagy[5142-23-4]
    CGK 733Induces apoptosis in prematurely senescent cells[905973-89-9]
    Mdivi 1Dynamin inhibitor; attenuates mitochondrial division and apoptosis[338967-87-6]
    Chloroquine diphosphateAntimalarial; inhibits apoptosis and autophagy[50-63-5]
    Necrostatin-1RIPK1 inhibitor; inhibits necroptosis[4311-88-0]

    3 HMDB Compounds for MAP3K5    About this table
    CompoundSynonyms CAS #PubMed Ids
    ADPadenosindiphosphorsaeure (see all 8)58-64-0--
    Adenosine triphosphate5'-(tetrahydrogen triphosphate) Adenosine (see all 24)56-65-5--
    MagnesiumMagnesium (see all 2)7439-95-4--

    Selected Novoseek inferred chemical compound relationships for MAP3K5 gene (see all 30)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    sp 600125 69.8 3 19405983 (1), 20200402 (1), 19735704 (1)
    sb 203580 64.9 7 12968034 (1), 20112989 (1)
    oxygen 52.3 36 16644673 (2), 17724081 (2), 9651337 (1), 16515547 (1) (see all 23)
    n acetylcysteine 48.6 14 19405983 (2), 9651337 (1), 12244106 (1), 20112989 (1) (see all 9)
    h2o2 46.4 35 17456047 (4), 11920685 (3), 14668614 (3), 18501712 (3) (see all 13)
    serine 35.2 23 16644673 (2), 15598880 (1), 17504983 (1), 15094778 (1) (see all 12)
    threonine 34.8 15 15598880 (1), 17504983 (1), 20364819 (1), 15094778 (1) (see all 9)
    ebselen 32 1 14713291 (1)
    ly294002 29.9 4 15782121 (2), 18054391 (1), 12869527 (1)
    nadph 28.9 5 17015265 (2), 18155167 (1), 18028450 (1)

    1 PharmGKB related drug/compound annotation for MAP3K5 gene    About this table
    Drug/compound PharmGKB Annotation
    hydroxyureaCA  



    MAP3K5 for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for MAP3K5 gene: 
    NM_005923.3  

    Unigene Cluster for MAP3K5:

    Mitogen-activated protein kinase kinase kinase 5
    Hs.186486  [show with all ESTs]
    Unigene Representative Sequence: U67156
    3 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000359015(uc011edj.2 uc003qhc.3 uc011edk.1 uc010kgw.1)
    ENST00000463140 ENST00000355845
    Congresses - knowledge worth sharing:
    European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

    miRNA
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    Additional mRNA sequence: 

    AB209093.1 AK293953.1 AK294507.1 AK310942.1 BC054503.2 BC088829.1 D84476.2 U67156.1 

    9 DOTS entries:

    DT.451805  DT.100722589  DT.100751512  DT.121322417  DT.91702811  DT.92009713  DT.121322370  DT.91700170 
    DT.95109734 

    Selected AceView cDNA sequences (see all 106):

    BG926856 AA235088 AW104096 BQ188173 AL133790 BF914042 AI827010 AW664529 
    NM_005923 BM798051 AW955152 AW052036 AI042050 AA651664 AA323321 BM718016 
    BG402936 BC054503 AW662187 BM981228 BQ894240 AA854544 BM990052 AA973986 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    MAP3K5 expression in normal human tissues (normalized intensities)      MAP3K5 embryonic expression: see
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: CTTGAACTGT
    MAP3K5 Expression
    About this image


    MAP3K5 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 8) fully expand
     
     Neural Tube (Nervous System)    fully expand to see all 2 entries
             Mesencephalic Floor Plate
     
     Skeletal Muscle (Muscoskeletal System)    fully expand to see all 2 entries
             Myoblasts Mandibular Arch Muscles
     
     Brain (Nervous System)    fully expand to see all 2 entries
             Cerebral Cortex
     
     Thymus (Hematopoietic System)
             Thymus
     
     Gut Tube (Gastrointestinal Tract)
             Foregut
    MAP3K5 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    MAP3K5 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.186486

    UniProtKB/Swiss-Prot: M3K5_HUMAN, Q99683
    Tissue specificity: Abundantly expressed in heart and pancreas

        Pathway & Disease-focused RT2 Profiler PCR Arrays including MAP3K5: 
              HIV Host Response in human mouse rat
              Apoptosis 384HT in human mouse rat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals and fungi.

    Orthologs for MAP3K5 gene from Selected species (see all 15)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Map3k51 , 5 mitogen-activated protein kinase kinase kinase 51, 5 86.78(n)1
    94.9(a)1
      10 (9.35 cM)5
    264081  NM_008580.41  NP_032606.41 
     199344725 
    chicken
    (Gallus gallus)
    Aves MAP3K51 mitogen-activated protein kinase kinase kinase 5 81.29(n)
    88.83(a)
      421688  XM_419725.4  XP_419725.3 
    lizard
    (Anolis carolinensis)
    Reptilia MAP3K56
    mitogen-activated protein kinase kinase kinase 5
    87(a)
    1 ↔ 1
    GL343200.1(2224819-2299508)
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.305422 Xenopus laevis transcribed sequence with weak similarity more 74.6(n)    48025123 
    zebrafish
    (Danio rerio)
    Actinopterygii map3k51 mitogen-activated protein kinase kinase kinase 5 68.35(n)
    73.85(a)
      555703  NM_001161750.1  NP_001155222.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta Pk92B3 protein amino acid phosphorylation
    receptor signaling more
    48(a)   3 92B4   --
    worm
    (Caenorhabditis elegans)
    Secernentea nsy-13 Protein kinase 44(a)   II(5022901-5029673)   --
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes STE116
    Signal transducing MEK kinase involved in pheromon...
    22(a)
    1 → many
    XII(849866-852019) YLR362W


    ENSEMBL Gene Tree for MAP3K5 (if available)
    TreeFam Gene Tree for MAP3K5 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for MAP3K5 gene
    MAP3K12  MAP3K32  MAP3K152  MAP3K82  MAP3K22  MAP3K192  MAP3K62  
    12 SIMAP similar genes for MAP3K5 using alignment to 2 protein entries:     M3K5_HUMAN (see all proteins):
    MAP3K15    MAP3K6    MAP3K2    MARK4    MST094    PRKY
    STK11    CDK4    RPS6KA2    PAK4    NEK7    NUAK1

    MAP3K5 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for MAP3K5 (see all 4529)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 6 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs58803001,2
    C--136877782(+) TCCTC-/TTTTTT 1 -- ds50010--------
    rs1831774281,2
    --136878431(+) ATATAC/TCATAG 1 -- ds50010--------
    rs23277401,2
    C,F,A--136878593(+) TCACCG/ACAATC 1 -- ds50018Minor allele frequency- A:0.12NA WA EA 498
    rs1859675061,2
    --136878609(+) CTCCCA/GGGCTC 1 -- ds50010--------
    rs1162428731,2
    F--136878619(+) CAAGCG/AATCCT 1 -- ds50011Minor allele frequency- A:0.01WA 118
    rs125269071,2
    C,H--136878672(+) CACCAT/AGCCTA 1 -- ds50015Minor allele frequency- A:0.03NS EA 540
    rs1474974311,2
    --136878734(+) TTACCA/CTCTTT 1 -- ds50010--------
    rs1904787981,2
    --136878745(+) CTTAAA/TCCTCT 1 -- ds50010--------
    rs347059391,2
    C--136878752(+) GTCTG-/T/TTTT
            
    TTTTT
    2 -- ut31 cds10--------
    rs43512801,2
    C,F,A,H--136878772(+) ACCTGA/GATGTC 1 -- ds500127Minor allele frequency- G:0.30NS EA NA WA CSA 2821

    HapMap Linkage Disequilibrium report for MAP3K5 (136878185 - 137113656 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 1 variation for MAP3K5:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv464064CNV Loss19166990

    Locus Specific Mutation Databases (LSDB): MAP3K5

    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing MAP3K5
    DNA2.0 Custom Variant and Variant Library Synthesis for MAP3K5

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 602448    OMIM disorders: --

    Selected diseases for MAP3K5 (see all 48):    About MalaCards
    japanese encephalitis    prostate adenocarcinoma    histiocytoma    fibrous histiocytoma
    hyperglycemia    atopy    encephalitis    thalassemia
    brain injury    osteosarcoma    retinoblastoma    amyotrophic lateral sclerosis
    fatty liver disease    lateral sclerosis    ischemia    prostatitis
    atherosclerosis    adenocarcinoma    lung adenocarcinoma    ovarian cancer


    MAP3K5 for disorders           About GeneDecksing


    Congresses - knowledge worth sharing:
    Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

    Selected Novoseek inferred disease relationships for MAP3K5 gene (see all 22)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    necrosis 50.3 35 9651337 (1), 12591926 (1), 19799997 (1), 12819028 (1) (see all 19)
    tumors 30.6 36 15034865 (2), 9651337 (1), 19799997 (1), 16787350 (1) (see all 20)
    neurodegenerative diseases 25.1 5 19456270 (3), 16472116 (1), 20364819 (1)
    shock 13.9 15 12077134 (5), 12391142 (4), 16038411 (2)
    cardiac hypertrophy 12.7 3 18759454 (1), 16987025 (1), 15824197 (1)
    cancer 9.56 2 17034356 (1), 18380010 (1)
    prostatic adenocarcinoma 6.98 2 12968034 (1)
    cell damage 3.95 1 16195372 (1)
    virus infection 0 2 16764692 (2)
    ischemia 0 1 19052195 (1)

    Genetic Association Database (GAD): MAP3K5
    Human Genome Epidemiology (HuGE) Navigator: MAP3K5 (8 documents)

    Export disorders for MAP3K5 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for MAP3K5 gene, integrated from 10 sources (see all 395):
    (articles sorted by number of sources associating them with MAP3K5)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. AIP1 mediates TNF-alpha-induced ASK1 activation by facilitating dissociation of ASK1 from its inhibitor 14-3-3. (PubMed id 12813029)1, 2, 9 Zhang R.... Min W. (J. Clin. Invest. 2003)
    2. Regulation of apoptosis signal-regulating kinase 1 by protein phosphatase 2Cepsilon. (PubMed id 17456047)1, 2, 9 Saito J....Tamura S. (Biochem. J. 2007)
    3. Thioredoxin and TRAF family proteins regulate reactive oxygen species-dependent activation of ASK1 through reciprocal modulation of the N-terminal homophilic interaction of ASK1. (PubMed id 17724081)1, 2, 9 Fujino G.... Ichijo H. (Mol. Cell. Biol. 2007)
    4. C-terminus of heat shock protein 70-interacting protein facilitates degradation of apoptosis signal-regulating kinase 1 and inhibits apoptosis signal-regulating kinase 1-dependent apoptosis. (PubMed id 16038411)1, 2, 9 Hwang J.R.... Patterson C. (Cell Stress Chaperones 2005)
    5. Apoptosis signal-regulating kinase (ASK) 2 functions as a mitogen- activated protein kinase kinase kinase in a heteromeric complex with ASK1. (PubMed id 17210579)1, 2, 9 Takeda K.... Ichijo H. (J. Biol. Chem. 2007)
    6. Variants in ASK1 are associated with skeletal muscle ASK1 expression, in vivo insulin resistance, and type 2 diabetes in Pima Indians. (PubMed id 20185809)1, 4, 9 Bian L....Bogardus C. (Diabetes 2010)
    7. Activation of apoptosis signal-regulating kinase 1 by the stress- induced activating phosphorylation of pre-formed oligomer. (PubMed id 11920685)1, 2, 9 Tobiume K.... Ichijo H. (J. Cell. Physiol. 2002)
    8. Interaction of apoptosis signal-regulating kinase 1 with isoforms of 14-3-3 proteins. (PubMed id 15023544)1, 2, 9 Subramanian R.R.... Fu H. (Exp. Cell Res. 2004)
    9. Mammalian thioredoxin is a direct inhibitor of apoptosis signal- regulating kinase (ASK) 1. (PubMed id 9564042)1, 2, 9 Saitoh M.... Ichijo H. (EMBO J. 1998)
    10. Apoptosis signal-regulating kinase 1 in stress and immune response. (PubMed id 17883330)1, 2, 9 Takeda K.... Ichijo H. (Annu. Rev. Pharmacol. Toxicol. 2008)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 4217 HGNC: 6857 AceView: MAP3K5 Ensembl:ENSG00000197442 euGenes: HUgn4217
    ECgene: MAP3K5 Kegg: 4217 H-InvDB: MAP3K5

    (According to HUGE)
    About This Section

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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for MAP3K5 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for MAP3K5 Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section

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    Patent Information for MAP3K5 gene:
    Search GeneIP for patents involving MAP3K5

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript, and ESI BIO, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
    Advanced Cell Diagnostics, Animal models from inGenious Targeting Laboratory, genOway)
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