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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

MAP3K5 Gene

protein-coding   GIFtS: 66
GCID: GC06M136919

mitogen-activated protein kinase kinase kinase 5


(Previous symbol: MEKK5)
 Explore 44 diseases affiliated with
MAP3K5 via
MalaCards
our new
 Human Malady Compendium 
Biological research products
for MAP3K5    

Aliases
for MAP3K5 gene

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, and/or 10fRNAdb)
About This Section
Aliases
Mitogen-Activated Protein Kinase Kinase Kinase 51 2     MEK Kinase 52 3
ASK11 2 3 5     MEKK 52 3
MAPKKK51 2 3 5     EC 2.7.11.253 8
MEKK51 2 3 5     Apoptosis Signal Regulating Kinase 12
Apoptosis Signal-Regulating Kinase 12 3     MAP/ERK Kinase Kinase 52
ASK-12 3     EC 2.7.118
MAPK/ERK Kinase Kinase 52 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 GC06M134442


Summaries
for MAP3K5 gene

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section
Entrez Gene summary for MAP3K5:
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)

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:
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)


Genomic Views
for MAP3K5 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 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000006.11  NC_018917.1  NT_025741.15  
Regulatory elements:
   SABiosciences 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 plasmid: MAP3K5 promoter sequence
   Search SABiosciences Chromatin IP Primers for MAP3K5

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays 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 GC06M136919:  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

Proteins
for MAP3K5 gene

(According to 1UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to 2PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, 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 Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section
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
Subcellular location: 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
2 PDB 3D structures from and Proteopedia for MAP3K5:
2CLQ (3D)        3VW6 (3D)    
Secondary accessions: Q5THN3 Q99461

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

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
  • View modification sites using PhosphoSitePlus2
  • View neXtProt modification sites for NX_Q99683

    • 4/6 DME Specific Peptides for MAP3K5 (Q99683) (see all 6)
     VPGGSLS  LGKKGNL  NLLLSYRD  LFGFQDAVN 

    MAP3K5 Protein expression data from MOPED and PaxDb:    About this image 
    Estimated protein expression log10 (pmol).

    REFSEQ proteins: NP_005914.1  
    ENSEMBL proteins: 
     ENSP00000351908   ENSP00000348104  

    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: MAP3K5
    OriGene Protein Over-expression Lysate: 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 ProSpec Recombinant Proteins
    Uscn Proteins for MAP3K5

    Gene Ontology (GO): 1 cellular component term (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005783endoplasmic reticulum IEA--


    MAP3K5 for ontologies           About GeneDecksing



    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 (see all 8): MAP3K5
    OriGene Custom Antibody Services for MAP3K5 
    GenScript Custom Superior Antibodies Services for MAP3K5
    Novus Biologicals MAP3K5 Antibodies
    Abcam antibodies for MAP3K5 
    Uscn Antibodies for MAP3K5
    ThermoFisher Antibody for MAP3K5

    Assay Products for MAP3K5: 
    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Immunoassay Development
    Browse OriGene Fluorogenic Cell Assay Kits
    Browse R&D Systems for biochemical assays
    GenScript Custom Assay Services for MAP3K5
    Browse Enzo Life Sciences for kits & assays
    Uscn ELISAs and CLIAs for MAP3K5

    Protein Domains /
    Families
    for MAP3K5 gene

    (According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    MAP3K5 for domains           About GeneDecksing

    5/7 InterPro domains/families (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


    Function
    for MAP3K5 gene

    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
    About This Section
    Function Summary:

         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)
    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

    miRNA
    Products:            		 OriGene 3'-UTR Clone: MAP3K5
    Browse MicroRNA Expression Plasmids
    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat MAP3K5
    8/34 QIAGEN miScript miRNA 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 plasmid: MAP3K5 3' UTR sequence
    Inhib. RNA
    Products:            		Browse for Gene Knock-down Tools from EMD Millipore
    OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for MAP3K5 (see all 4)
    OriGene shRNA RFP: MAP3K5
    OriGene siRNA: MAP3K5
    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat MAP3K5

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

    Clone
    Products:             		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
    OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for MAP3K5 (see all 2)
    OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for MAP3K5 (see all 2)
    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
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    Search LifeMap BioReagents cell lines for MAP3K5

    In Situ Assay
    Products:       
         		Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for MAP3K5

    Gene Ontology (GO): 5/10 molecular function terms (GO ID links to tree view) (see all 10):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000287magnesium ion binding IDA17210579
    GO:0004672protein kinase activity IDA--
    GO:0004709MAP kinase kinase kinase activity IDA17210579
    GO:0005515protein binding IPI12813029
    GO:0005524ATP binding IDA17210579


    MAP3K5 for ontologies           About GeneDecksing


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

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

    MAP3K5 for phenotypes           About GeneDecksing


    Pathways & Interactions
    for MAP3K5 gene

    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, 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 Mar 2013 via Entrez Gene).
    About This Section

    Unified GeneCards pathways - 5/45 super-pathways (see all 45) About this table 
    See pathways by source

    Super-pathwaycontained gene-specific pathways
    1TWEAK Pathway
    		HIV-1 Nef- Negative effector of Fas and TNF-alpha0.42
    		Apoptosis through Death Receptors0.32
    		TNF Signaling0.40
    		Fas Signaling0.29
    		Apoptotic Pathways Triggered By HIV10.37
    2Development HGF signaling pathway
    		Apoptosis and survival_Anti-apoptotic action of membrane-bound ESR10.24
    		Apoptosis and survival_Anti-apoptotic action of nuclear ESR1 and ESR20.15
    		Apoptosis and survival Anti-apoptotic action of membrane-bound ESR10.24
    		Apoptosis and survival Anti-apoptotic action of nuclear ESR1 and ESR20.15
    		Neurotrophin signaling pathway0.20
    34-1BB Pathway
    		4-1BB Pathway1.00
    		TNFR2 Pathway0.29
    		CD27 Pathway0.48
    4Signal transduction_JNK pathway
    		Signal transduction_JNK pathway1.00
    		Signal transduction JNK pathway0.98
    5Development Angiotensin signaling via beta-Arrestin
    		Development Angiotensin signaling via beta-Arrestin1.00
    		Development_Angiotensin signaling via beta-Arrestin0.96

    Pathway sources
    See GeneCards unified pathways
    Show all pathways

    5/7 EMD Millipore Pathways for MAP3K5 (see all 7)
        Development Angiotensin signaling via beta-Arrestin
    Apoptosis and survival Anti-apoptotic action of membrane-bound ESR1
    Apoptosis and survival FAS signaling cascades
    Signal transduction JNK pathway
    Apoptosis and survival Lymphotoxin-beta receptor signaling

    5/43 Downloadable PowerPoint Slides of QIAGEN 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

    5/7 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

    5/10 BioSystems Pathways for MAP3K5 (see all 10) 
        p38 MAPK Signaling Pathway
    MAPK signaling pathway
    Apoptosis Modulation and Signaling
    Insulin Signaling
    Integrated Pancreatic Cancer Pathway


    4         Kegg Pathways  (Kegg details for MAP3K5):
        MAPK signaling pathway
    Protein processing in endoplasmic reticulum
    Neurotrophin signaling pathway
    Amyotrophic lateral sclerosis (ALS)


    MAP3K5 for pathways           About GeneDecksing

    Interactions:

        SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for MAP3K5

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

    5/126 Interacting proteins for MAP3K5 (Q996831, 2, 3 ENSP000003519084) via UniProtKB, MINT, STRING, and/or I2D (see all 126)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    SMN1Q166372, 3, ENSP000003700834MINT-8152355 MINT-8152318 MINT-8152311 MINT-8152341 I2D: score=2 STRING: ENSP00000370083
    ARRB1P494072, 3, ENSP000003771414MINT-7263254 MINT-7263304 MINT-7263231 I2D: score=2 STRING: ENSP00000377141
    PPP3R1P630982, 3, ENSP000002343104MINT-8223296 MINT-8223355 I2D: score=3 STRING: ENSP00000234310
    MAP3K2Q9Y2U52, 3, ENSP000003434634MINT-18083 MINT-18082 I2D: score=2 STRING: ENSP00000343463
    SMN2Q166372, 3, ENSP000003701194MINT-8152355 MINT-8152318 MINT-8152311 MINT-8152341 I2D: score=2 STRING: ENSP00000370119
    About this table

    Gene Ontology (GO): 5/15 biological process terms (GO ID links to tree view) (see all 15):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000165MAPK cascade IDA--
    GO:0000186activation of MAPKK activity IDA11959862
    GO:0000187activation of MAPK activity ----
    GO:0006919activation of cysteine-type endopeptidase activity involved in apoptotic process IDA14761963
    GO:0007254JNK cascade IDA--


    MAP3K5 for ontologies           About GeneDecksing



    Drugs & Compounds
    for MAP3K5 gene

    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section

    MAP3K5 for compounds           About GeneDecksing

    Browse Small Molecules at EMD Millipore
    Browse drugs & compounds from Enzo Life Sciences

    Compounds for MAP3K5 available from Tocris Bioscience    About this table
    CompoundAction CAS #
    NQDI 1Inhibitor of apoptosis signal-regulating kinase 1 (ASK1)[175026-96-7]

    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--
    10/30 Novoseek 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)

    Search CenterWatch for drugs/clinical trials and news about MAP3K5 / M3K5 

    Transcripts
    for MAP3K5 gene

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section
    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

    miRNA
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    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
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    Inhib. RNA
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    Additional cDNA 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 

    24/106 AceView cDNA sequences (see all 106):

    AW104096 BF914042 AA651664 AI827010 BG402936 AW955152 AI042050 AA973986 
    CD621373 BE672574 BQ188173 BC054503 AA235088 AL133790 AA854544 BQ894240 
    AW052036 AW662187 BM798051 BM718016 BM981228 NM_005923 BG926856 BM990052 

    GeneLoc Exon Structure


    Expression
    for MAP3K5 gene

    (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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    MAP3K5 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS
    CGAP TAG: CTTGAACTGT

    Microarray
    RNAseq (Illumina Body Map)
    (100×FPKM)½
    SAGE (Serial Analysis of Gene Expression)
    About this image

    MAP3K5 expression in embryonic tissues and stem cells
    Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine    About this table
    2 LifeMap In Vivo Development Anatomical Compartments/Cells 
    Tissue Anatomical Compartment CellCategory (developmental path)
    Extraembryonic MesodermExtraembryonic Capillary PlexusExtraembryonic AngioblastsEndothelium
    BrainMedulla OblongataBrain
    Expression: Positive    Negative     Selective marker
    Experimental details: Curated     Microarrays     In-situ hybridization

    See MAP3K5 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for MAP3K5

    SOURCE GeneReport for Unigene cluster: Hs.186486

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

        SABiosciences Expression via Pathway-Focused PCR Arrays including MAP3K5: 
              HIV Host Response in human mouse rat
              Apoptosis 384HT in human mouse rat

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    In Situ
    Assay Products:     
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    Orthologs
    for MAP3K5 gene

    (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)
    About This Section
    This gene was present in the common ancestor of eukaryotes.

    Orthologs for MAP3K5 gene from 8/19 species (see all 19)    About this table
    Organism Taxonomic
    classification    		 Gene Description Human
    Similarity    		 Orthology
    Type    		 Details
    chicken
    (Gallus gallus)    		 Aves MAP3K51 mitogen-activated protein kinase kinase kinase 5 80.63(n)
    87.94(a)    		   421688  XM_419725.3  XP_419725.2 
    lizard
    (Anolis carolinensis)    		 Reptilia MAP3K56
    		 --
    		 88(a)
    		 1 ↔ 1
    		 GL343200.1(2225112-2298639)
    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 68.2(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)   --
    thale cress
    (Arabidopsis thaliana)    		 eudicotyledons AT2G342906
    AT5G275106
    (see all 26)    		 protein kinase family protein
    (see all 26)    		 32(a)
    28(a)
    (see all 26)    		 possible ortholog
    possible ortholog
    (see all 26)    		 2(14472633-14473430)
    5(9713173-9714078)
    rice
    (Oryza sativa)    		 Liliopsida --
    --
    (see all 11)    		 STE_MEKK_ste11_MAP3K.11 - STE kinases include homo...
    STE_MEKK_ste11_MAP3K.8 - STE kinases include homol...
    (see all 11)    		 39(a)
    23(a)
    (see all 11)    		 possible ortholog
    possible ortholog
    (see all 11)    		 2(32455259-32456963)
    2(12893454-12895429)


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

    Paralogs
    for MAP3K5 gene

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for MAP3K5 gene
    MAP3K12  MAP3K32  MAP3K152  MAP3K192  MAP3K22  MAP3K82  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



    Genomic Variants
    for MAP3K5 gene

    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, UniProtKB, 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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    10/3752 NCBI SNPs in MAP3K5 are shown (see all 3752)     About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance    		Chr 6 posSequence#AA
    Chg    		TypeMore#Allele
    freq    		PopTotal
    sample    		More
    ----------
    rs1831774281,2
    		--136877705(+) ATATAC/TCATAG 1 -- ds50010--------
    rs58803001,2
    		C--136877782(+) TCCTC-/TTTTTT 1 -- ds50010--------
    rs23277401,2
    		C,F,A,--136877867(+) TCACCG/ACAATC 1 -- ds50018Minor allele frequency- A:0.12NA WA EA 498
    rs1859675061,2
    		--136877883(+) CTCCCA/GGGCTC 1 -- ds50010--------
    rs1162428731,2
    		--136877893(+) CAAGCG/AATCCT 1 -- ds50011Minor allele frequency- A:0.01WA 118
    rs125269071,2
    		C,H,--136877946(+) CACCAT/AGCCTA 1 -- ds50015Minor allele frequency- A:0.03NS EA 540
    rs1474974311,2
    		--136878008(+) TTACCA/CTCTTT 1 -- ds50010--------
    rs1904787981,2
    		--136878019(+) CTTAAA/TCCTCT 1 -- ds50010--------
    rs43512801,2
    		C,F,A,H,--136878046(+) ACCTGA/GATGTC 1 -- ds500127Minor allele frequency- G:0.30NS EA NA WA CSA 2821
    rs787444161,2
    		C,F,--136878134(+) CAGATT/CATCTA 1 -- ds50012Minor allele frequency- C:0.03NA EA 240

    HapMap Linkage Disequilibrium report for MAP3K5 (136878185 - 137113656 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
          Database of Genomic Variants (DGV) variations for MAP3K5: --
    Locus Specific Mutation Databases (LSDB): MAP3K5

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    Disorders / Diseases
    for MAP3K5 gene

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section
    MAP3K5 for disorders           About GeneDecksing

    OMIM gene information: 602448    OMIM disorders: --

    20/44 diseases for MAP3K5 (see all 44):    About MalaCards
    amyotrophic lateral sclerosis (als)    fibrous histiocytoma    amyotrophic lateral sclerosis    malignant fibrous histiocytoma
    non-hodgkin lymphoma    lateral sclerosis    japanese encephalitis    histiocytoma
    hodgkin's lymphoma    brain injury    neurodegenerative disease    acute myeloid leukemia
    myeloid leukemia    insulin resistance    encephalitis    renal cell carcinoma
    hyperglycemia    diabetes mellitus    rheumatoid arthritis    osteoarthritis

    10/22 Novoseek 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)

    Human Genome Epidemiology (HuGE) Navigator: MAP3K5 (8 documents)

    Export disorders for MAP3K5 gene to outside databases

    Publications
    for MAP3K5 gene

    (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)
    About This Section

    PubMed articles for MAP3K5 gene, integrated from 9 sources (see all 375):
    (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. (2003)
    2. Regulation of apoptosis signal-regulating kinase 1 by protein phosphatase 2Cepsilon. (PubMed id 17456047)1, 2, 9 Saito J....Tamura S. (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. (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. (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. (2007)
    6. 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. (2002)
    7. 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. (2004)
    8. Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1. (PubMed id 9564042)1, 2, 9 Saitoh M....Ichijo H. (1998)
    9. Apoptosis signal-regulating kinase 1 in stress and immune response. (PubMed id 17883330)1, 2, 9 Takeda K....Ichijo H. (2008)
    10. Negative control of apoptosis signal-regulating kinase 1 through phosphorylation of Ser-1034. (PubMed id 15094778)1, 2, 9 Fujii K.... Fu H. (2004)

    External Searches for MAP3K5 gene

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     ANDOR
    Aliases
    Disorders
    Free Text  
      Query String
    		PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    Genome Databases showing MAP3K5 gene

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

    Other Databases showing MAP3K5 gene

    (According to HUGE)
    About This Section
    		   --

    Specialized Databases showing MAP3K5 gene

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    NameDescription
    PharmGKB entry for MAP3K5 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for MAP3K5 Genetics and Cytogenetics in Oncology and Haematology

    Intellectual Property
    for MAP3K5 gene

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



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    About This Section

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