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Aliases for MAP3K5 Gene

Aliases for MAP3K5 Gene

  • Mitogen-Activated Protein Kinase Kinase Kinase 5 2 3
  • MAPKKK5 3 4 6
  • MEKK5 3 4 6
  • ASK1 3 4 6
  • Apoptosis Signal Regulating Kinase 1 2 3
  • Apoptosis Signal-Regulating Kinase 1 3 4
  • MAPK/ERK Kinase Kinase 5 3 4
  • MEK Kinase 5 3 4
  • EC 2.7.11.25 4 64
  • MEKK 5 3 4
  • ASK-1 3 4
  • MAP/ERK Kinase Kinase 5 3
  • EC 2.7.11 64

External Ids for MAP3K5 Gene

Previous Symbols for MAP3K5 Gene

  • MEKK5

Summaries for MAP3K5 Gene

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. Among its related pathways are MAPK signaling pathway and Development FGFR signaling pathway. GO annotations related to this gene include protein homodimerization activity and protein kinase binding. An important paralog of this gene is MAP3K3.

UniProtKB/Swiss-Prot for MAP3K5 Gene

  • 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).

Tocris 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 Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MAP3K5 Gene

Genomics for MAP3K5 Gene

Genomic Location for MAP3K5 Gene

Start:
136,557,040 bp from pter
End:
136,793,047 bp from pter
Size:
236,008 bases
Orientation:
Minus strand

Genomic View for MAP3K5 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for MAP3K5 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MAP3K5 Gene

Regulatory Elements for MAP3K5 Gene

Proteins for MAP3K5 Gene

  • Protein details for MAP3K5 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q99683-M3K5_HUMAN
    Recommended name:
    Mitogen-activated protein kinase kinase kinase 5
    Protein Accession:
    Q99683
    Secondary Accessions:
    • A6NIA0
    • B4DGB2
    • Q5THN3
    • Q99461

    Protein attributes for MAP3K5 Gene

    Size:
    1374 amino acids
    Molecular mass:
    154537 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • 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.

    Three dimensional structures from OCA and Proteopedia for MAP3K5 Gene

    Alternative splice isoforms for MAP3K5 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MAP3K5 Gene

Proteomics data for MAP3K5 Gene at MOPED

Selected DME Specific Peptides for MAP3K5 Gene

Post-translational modifications for MAP3K5 Gene

  • 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 PGAM5.
  • Ubiquitinated. Tumor necrosis factor (TNF) induces TNFR2-dependent ubiquitination leading to proteasomal degradation.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for MAP3K5 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Domains for MAP3K5 Gene

Gene Families for MAP3K5 Gene

HGNC:
  • MAP3K :Mitogen-activated protein kinase cascade / Kinase kinase kinases
IUPHAR :

UniProtKB/Swiss-Prot:

M3K5_HUMAN
Domain:
  • Contains 1 protein kinase domain.:
    • Q99683
Family:
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.:
    • Q99683
genes like me logo Genes that share domains with MAP3K5: view

Function for MAP3K5 Gene

Molecular function for MAP3K5 Gene

GENATLAS Biochemistry: mitogen activated protein (MAP/ERK) kinase kinase kinase 5
UniProtKB/Swiss-Prot CatalyticActivity: ATP + a protein = ADP + a phosphoprotein
UniProtKB/Swiss-Prot EnzymeRegulation: 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.
UniProtKB/Swiss-Prot 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).
UniProtKB/Swiss-Prot Induction: By TNF. Inhibited by HIV-1 Nef

Enzyme Numbers (IUBMB) for MAP3K5 Gene

Gene Ontology (GO) - Molecular Function for MAP3K5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000287 magnesium ion binding IDA 17210579
GO:0004672 protein kinase activity IDA 21771788
GO:0004709 MAP kinase kinase kinase activity IDA 17210579
GO:0004713 protein tyrosine kinase activity --
GO:0005515 protein binding IPI 11003656
genes like me logo Genes that share ontologies with MAP3K5: view
genes like me logo Genes that share phenotypes with MAP3K5: view

miRNA for MAP3K5 Gene

miRTarBase miRNAs that target MAP3K5

No data available for Animal Models , Transcription Factor Targeting and HOMER Transcription for MAP3K5 Gene

Localization for MAP3K5 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MAP3K5 Gene

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
Jensen Localization Image for MAP3K5 Gene COMPARTMENTS Subcellular localization image for MAP3K5 gene
Compartment Confidence
endoplasmic reticulum 5
cytosol 3
mitochondrion 2
nucleus 2
extracellular 1
peroxisome 1

Gene Ontology (GO) - Cellular Components for MAP3K5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005783 endoplasmic reticulum --
GO:0005829 cytosol TAS --
GO:1902911 protein kinase complex IDA 15983381
GO:1990604 IRE1-TRAF2-ASK1 complex IDA 12050113
genes like me logo Genes that share ontologies with MAP3K5: view

Pathways for MAP3K5 Gene

genes like me logo Genes that share pathways with MAP3K5: view

Gene Ontology (GO) - Biological Process for MAP3K5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade IDA 17210579
GO:0000186 activation of MAPKK activity IDA 11959862
GO:0000187 activation of MAPK activity --
GO:0001934 positive regulation of protein phosphorylation --
GO:0002931 response to ischemia IEA --
genes like me logo Genes that share ontologies with MAP3K5: view

Compounds for MAP3K5 Gene

(4) ApexBio Compounds for MAP3K5 Gene

Compound Action Cas Number
FR 180204 Selective ERK inhibitor [865362-74-9]
VX-11e potent, selective, and orally bioavailable inhibitor of ERK [896720-20-0]
XMD17-109 novel, specific ERK-5 inhibitor with an EC50 4.2uM in HEK293 cells [1435488-37-1]
XMD8-92 highly selective ERK5/BMK1 inhibitor [1234480-50-2]

(5) Tocris Compounds for MAP3K5 Gene

Compound Action Cas Number
3-Methyladenine Class III PI 3-kinase inhibitor; also inhibits autophagy [5142-23-4]
CGK 733 Induces apoptosis in prematurely senescent cells [905973-89-9]
Chloroquine diphosphate Antimalarial; inhibits apoptosis and autophagy [50-63-5]
Mdivi 1 Dynamin inhibitor; attenuates mitochondrial division and apoptosis [338967-87-6]
Necrostatin-1 RIPK1 inhibitor; inhibits necroptosis [4311-88-0]

(3) HMDB Compounds for MAP3K5 Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
56-65-5
ADP
  • adenosindiphosphorsaeure
58-64-0
Magnesium
  • Magnesium
7439-95-4

(30) Novoseek inferred chemical compound relationships for MAP3K5 Gene

Compound -log(P) Hits PubMed IDs
sp 600125 69.8 3
sb 203580 64.9 2
oxygen 52.3 25
n acetylcysteine 48.6 10
h2o2 46.4 26

(1) PharmGKB related drug/compound annotations for MAP3K5 Gene

Drug/compound Annotation
hydroxyurea CA
genes like me logo Genes that share compounds with MAP3K5: view

Transcripts for MAP3K5 Gene

Unigene Clusters for MAP3K5 Gene

Mitogen-activated protein kinase kinase kinase 5:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for MAP3K5 Gene

No ASD Table

Relevant External Links for MAP3K5 Gene

GeneLoc Exon Structure for
MAP3K5
ECgene alternative splicing isoforms for
MAP3K5

Expression for MAP3K5 Gene

mRNA expression in normal human tissues for MAP3K5 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for MAP3K5 Gene

This gene is overexpressed in Adrenal Gland (5.6).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for MAP3K5 Gene

SOURCE GeneReport for Unigene cluster for MAP3K5 Gene Hs.186486

mRNA Expression by UniProt/SwissProt for MAP3K5 Gene

Q99683-M3K5_HUMAN
Tissue specificity: Abundantly expressed in heart and pancreas
genes like me logo Genes that share expressions with MAP3K5: view

Orthologs for MAP3K5 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for MAP3K5 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia MAP3K5 36
  • 99.61 (n)
  • 99.71 (a)
MAP3K5 37
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia MAP3K5 36
  • 92.26 (n)
  • 95.68 (a)
MAP3K5 37
  • 96 (a)
OneToOne
dog
(Canis familiaris)
Mammalia MAP3K5 36
  • 92.43 (n)
  • 96.63 (a)
MAP3K5 37
  • 97 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Map3k5 36
  • 86.78 (n)
  • 94.9 (a)
Map3k5 16
Map3k5 37
  • 94 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia MAP3K5 37
  • 59 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia MAP3K5 37
  • 93 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Map3k5 36
  • 85.59 (n)
  • 94.17 (a)
chicken
(Gallus gallus)
Aves MAP3K5 36
  • 81.29 (n)
  • 88.83 (a)
MAP3K5 37
  • 89 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia MAP3K5 37
  • 87 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia Xl.30542 36
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100497692 36
  • 72.03 (n)
  • 77 (a)
zebrafish
(Danio rerio)
Actinopterygii map3k5 36
  • 68.35 (n)
  • 73.85 (a)
map3k5 37
  • 72 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta Pk92B 37
  • 39 (a)
OneToMany
Pk92B 38
  • 48 (a)
worm
(Caenorhabditis elegans)
Secernentea nsy-1 37
  • 33 (a)
OneToMany
nsy-1 38
  • 44 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes STE11 37
  • 22 (a)
OneToMany
Species with no ortholog for MAP3K5:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for MAP3K5 Gene

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

Paralogs for MAP3K5 Gene

Paralogs for MAP3K5 Gene

Selected SIMAP similar genes for MAP3K5 Gene using alignment to 2 proteins:

genes like me logo Genes that share paralogs with MAP3K5: view

Variants for MAP3K5 Gene

Sequence variations from dbSNP and Humsavar for MAP3K5 Gene

SNP ID Clin Chr 06 pos Sequence Context AA Info Type MAF
rs11138 -- 136,557,296(-) TCAAT(G/T)ACTGT utr-variant-3-prime
rs11503 -- 136,557,194(-) TTAAG(C/T)TTCTG utr-variant-3-prime
rs720344 -- 136,727,304(-) ATATA(C/G)TGTCT intron-variant
rs720345 -- 136,727,123(-) TTTCA(C/T)CTGTT intron-variant
rs742305 -- 136,616,960(+) tgatc(C/T)gccag intron-variant

Structural Variations from Database of Genomic Variants (DGV) for MAP3K5 Gene

Variant ID Type Subtype PubMed ID
nsv464064 CNV Loss 19166990

Relevant External Links for MAP3K5 Gene

HapMap Linkage Disequilibrium report
MAP3K5
Locus Specific Mutation Databases (LSDB)
MAP3K5

Disorders for MAP3K5 Gene

(22) Novoseek inferred disease relationships for MAP3K5 Gene

Disease -log(P) Hits PubMed IDs
necrosis 50.3 19
tumors 30.6 21
neurodegenerative diseases 25.1 5
shock 13.9 11
cardiac hypertrophy 12.7 3

Relevant External Links for MAP3K5

Genetic Association Database (GAD)
MAP3K5
Human Genome Epidemiology (HuGE) Navigator
MAP3K5
genes like me logo Genes that share disorders with MAP3K5: view

No data available for UniProtKB/Swiss-Prot for MAP3K5 Gene

Publications for MAP3K5 Gene

  1. Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways. (PMID: 8974401) Ichijo H. … Gotoh Y. (Science 1997) 3 4 23
  2. Mammalian thioredoxin is a direct inhibitor of apoptosis signal- regulating kinase (ASK) 1. (PMID: 9564042) Saitoh M. … Ichijo H. (EMBO J. 1998) 3 4 23
  3. ASK1 is essential for JNK/SAPK activation by TRAF2. (PMID: 9774977) Nishitoh H. … Ichijo H. (Mol. Cell 1998) 3 4 23
  4. Suppression of apoptosis signal-regulating kinase 1-induced cell death by 14-3-3 proteins. (PMID: 10411906) Zhang L. … Fu H. (Proc. Natl. Acad. Sci. U.S.A. 1999) 3 4 23
  5. Akt phosphorylates and negatively regulates apoptosis signal- regulating kinase 1. (PMID: 11154276) Kim A.H. … Chao M.V. (Mol. Cell. Biol. 2001) 3 4 23

Products for MAP3K5 Gene

Sources for MAP3K5 Gene

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