Human Gene MAP3K7 (ENST00000369329.8) from GENCODE V43
  Description: Homo sapiens mitogen-activated protein kinase kinase kinase 7 (MAP3K7), transcript variant B, mRNA. (from RefSeq NM_145331)
RefSeq Summary (NM_145331): The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase mediates the signaling transduction induced by TGF beta and morphogenetic protein (BMP), and controls a variety of cell functions including transcription regulation and apoptosis. In response to IL-1, this protein forms a kinase complex including TRAF6, MAP3K7P1/TAB1 and MAP3K7P2/TAB2; this complex is required for the activation of nuclear factor kappa B. This kinase can also activate MAPK8/JNK, MAP2K4/MKK4, and thus plays a role in the cell response to environmental stresses. Four alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008].
Gencode Transcript: ENST00000369329.8
Gencode Gene: ENSG00000135341.19
Transcript (Including UTRs)
   Position: hg38 chr6:90,513,579-90,587,072 Size: 73,494 Total Exon Count: 17 Strand: -
Coding Region
   Position: hg38 chr6:90,516,501-90,586,883 Size: 70,383 Coding Exon Count: 17 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-02-17 13:02:02

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr6:90,513,579-90,587,072)mRNA (may differ from genome)Protein (606 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
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-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Mitogen-activated protein kinase kinase kinase 7; EC=; AltName: Full=Transforming growth factor-beta-activated kinase 1; Short=TGF-beta-activated kinase 1;
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 signal transduction of TRAF6, various cytokines including interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR). Ceramides are also able to activate MAP3K7/TAK1. 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 MAP2K1/MEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs, c-jun N-terminal kinases (JNKs) and I-kappa-B kinase complex (IKK). Both p38 MAPK and JNK pathways control the transcription factors activator protein-1 (AP-1), while nuclear factor-kappa B is activated by IKK. MAP3K7 activates also IKBKB and MAPK8/JNK1 in response to TRAF6 signaling and mediates BMP2- induced apoptosis. In osmotic stress signaling, plays a major role in the activation of MAPK8/JNK1, but not that of NF-kappa-B.
CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
COFACTOR: Magnesium.
ENZYME REGULATION: Activated by proinflammatory cytokines and in response to physical and chemical stresses, including osmotic stress, oxidative stress, arsenic and ultraviolet light irradiation. Activated by 'Lys-63'-linked polyubiquitination and by autophosphorylation. Association with TAB1/MAP3K7IP1 and TAB2/MAP3K7IP2 promotes activation through autophosphorylation, whereas PPM1B/PP2CB, PP2A and PPP6C dephosphorylation leads to inactivation.
SUBUNIT: Binds both upstream activators and downstream substrates in multimolecular complexes. Interacts with TAB1/MAP3K7IP1, TAB2/MAP3K7IP2 and TAB3/MAP3K7IP3. Identified in the TRIKA2 complex composed of MAP3K7/TAK1, TAB1/MAP3K7IP1 and TAB2/MAP3K7IP2. Interacts with PPM1L and PPM1B/PP2CB. Interaction with PP2A and PPP6C leads to its repressed activity. Interacts with TRAF6 and TAB1/MAP3K7IP1; during IL-1 signaling. Interacts with TAOK1 and TAOK2; interaction with TAOK2 interferes with MAP3K7 interaction with IKKA, thus preventing NF-kappa-B activation. Interacts with WDR34 (via WD domains). Interacts with CYLD and RBCK1. Interacts with TGFBR1; induces MAP3K7/TAK1 activation by TRAF6. Interacts with MAPK8IP1 and SMAD6 (By similarity). Interacts with isoform 1 of VRK2. Interacts with DAB2; the interaction is induced by TGF-beta stimulation and may mediate TGF-beta stimulated JNK activation.
INTERACTION: Q9UQF2:MAPK8IP1; NbExp=10; IntAct=EBI-358684, EBI-78404; P40763:STAT3; NbExp=4; IntAct=EBI-358684, EBI-518675; Q9NYJ8:TAB2; NbExp=2; IntAct=EBI-358684, EBI-358708;
SUBCELLULAR LOCATION: Cytoplasm. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Note=Although the majority of MAP3K7/TAK1 is found in the cytosol, when complexed with TAB1/MAP3K7IP1 and TAB2/MAP3K7IP2, it is also localized at the cell membrane.
TISSUE SPECIFICITY: Isoform 1A is the most abundant in ovary, skeletal muscle, spleen and blood mononuclear cells. Isoform 1B is highly expressed in brain, kidney and small intestine. Isoform 1C is the major form in prostate. Isoform 1D is the less abundant form.
PTM: Association with TAB1/MAP3K7IP1 promotes autophosphorylation at Ser-192 and subsequent activation. Association with TAB2/MAP3K7IP2, itself associated with free unanchored Lys-63 polyubiquitin chain, promotes autophosphorylation and subsequent activation of MAP3K7. Dephosphorylation at Ser-192 by PPM1B/PP2CB and at Thr-187 by PP2A and PPP6C leads to inactivation.
PTM: Ubiquitinated, leading to proteasomal degradation (By similarity). Requires 'Lys-63'-linked polyubiquitination for autophosphorylation and subsequent activation. 'Lys-63'-linked ubiquitination does not lead to proteasomal degradation. Deubiquitinated by CYLD, a protease that selectively cleaves 'Lys- 63'-linked ubiquitin chains. Deubiquitinated by Y.enterocolitica YopP.
SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.
SIMILARITY: Contains 1 protein kinase domain.

-  Primer design for this transcript

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-  MalaCards Disease Associations
  MalaCards Gene Search: MAP3K7
Diseases sorted by gene-association score: cardiospondylocarpofacial syndrome* (1588), frontometaphyseal dysplasia 2* (1229), frontometaphyseal dysplasia* (275), narcolepsy (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 10.96 RPKM in Spleen
Total median expression: 354.70 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -112.60189-0.596 Picture PostScript Text
3' UTR -683.002922-0.234 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR011009 - Kinase-like_dom
IPR017421 - MAPKKK7
IPR000719 - Prot_kinase_cat_dom
IPR017441 - Protein_kinase_ATP_BS
IPR001245 - Ser-Thr/Tyr_kinase_cat_dom
IPR008271 - Ser/Thr_kinase_AS

Pfam Domains:
PF07714 - Protein tyrosine kinase

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2EVA - X-ray MuPIT 2YIY - X-ray MuPIT

ModBase Predicted Comparative 3D Structure on O43318
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserNo orthologGenome BrowserGenome BrowserNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGI EnsemblEnsembl  
Protein Sequence Protein SequenceProtein Sequence  
Alignment AlignmentAlignment  

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0000287 magnesium ion binding
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0004709 MAP kinase kinase kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0030971 receptor tyrosine kinase binding
GO:0042802 identical protein binding
GO:0046872 metal ion binding
GO:0097110 scaffold protein binding

Biological Process:
GO:0000186 activation of MAPKK activity
GO:0000187 activation of MAPK activity
GO:0002223 stimulatory C-type lectin receptor signaling pathway
GO:0002726 positive regulation of T cell cytokine production
GO:0002755 MyD88-dependent toll-like receptor signaling pathway
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006468 protein phosphorylation
GO:0006915 apoptotic process
GO:0007165 signal transduction
GO:0007179 transforming growth factor beta receptor signaling pathway
GO:0007223 Wnt signaling pathway, calcium modulating pathway
GO:0007249 I-kappaB kinase/NF-kappaB signaling
GO:0007250 activation of NF-kappaB-inducing kinase activity
GO:0007252 I-kappaB phosphorylation
GO:0007254 JNK cascade
GO:0016032 viral process
GO:0016239 positive regulation of macroautophagy
GO:0016310 phosphorylation
GO:0016579 protein deubiquitination
GO:0032743 positive regulation of interleukin-2 production
GO:0038095 Fc-epsilon receptor signaling pathway
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043276 anoikis
GO:0043507 positive regulation of JUN kinase activity
GO:0043966 histone H3 acetylation
GO:0050852 T cell receptor signaling pathway
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051403 stress-activated MAPK cascade
GO:0070423 nucleotide-binding oligomerization domain containing signaling pathway
GO:0070498 interleukin-1-mediated signaling pathway

Cellular Component:
GO:0005634 nucleus
GO:0005671 Ada2/Gcn5/Ada3 transcription activator complex
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0010008 endosome membrane
GO:0016020 membrane
GO:0008385 IkappaB kinase complex

-  Descriptions from all associated GenBank mRNAs
  AB009356 - Homo sapiens TAK1a mRNA for TGF-beta activated kinase 1a, complete cds.
AB009357 - Homo sapiens TAK1b mRNA for TGF-beta activated kinase 1b, complete cds.
BC017715 - Homo sapiens mitogen-activated protein kinase kinase kinase 7, mRNA (cDNA clone MGC:21263 IMAGE:3906837), complete cds.
AK299268 - Homo sapiens cDNA FLJ55358 complete cds, highly similar to Mitogen-activated protein kinase kinase kinase7 (EC
AF218074 - Homo sapiens TGF beta-activated kinase splice variant d (TAK1) mRNA, complete cds.
AB009358 - Homo sapiens mRNA for TGF-beta activated kinase 1c, complete cds.
AK315774 - Homo sapiens cDNA, FLJ96888, Homo sapiens mitogen-activated protein kinase kinase kinase 7(MAP3K7), transcript variant A, mRNA.
KJ905325 - Synthetic construct Homo sapiens clone ccsbBroadEn_14856 MAP3K7 gene, encodes complete protein.
BT019654 - Homo sapiens mitogen-activated protein kinase kinase kinase 7 mRNA, complete cds.
BT019655 - Homo sapiens mitogen-activated protein kinase kinase kinase 7 mRNA, complete cds.
AB528733 - Synthetic construct DNA, clone: pF1KB9918, Homo sapiens MAP3K7 gene for mitogen-activated protein kinase kinase kinase 7, without stop codon, in Flexi system.
BX648277 - Homo sapiens mRNA; cDNA DKFZp686O13119 (from clone DKFZp686O13119).
JD028398 - Sequence 9422 from Patent EP1572962.
JD021874 - Sequence 2898 from Patent EP1572962.
JD021327 - Sequence 2351 from Patent EP1572962.
JD035436 - Sequence 16460 from Patent EP1572962.
AK055901 - Homo sapiens cDNA FLJ31339 fis, clone MESAN1000032, highly similar to Homo sapiens mRNA for TGF-beta activated kinase 1a.
AL050393 - Homo sapiens mRNA; cDNA DKFZp586F0420 (from clone DKFZp586F0420); partial cds.
JD048444 - Sequence 29468 from Patent EP1572962.
JD190241 - Sequence 171265 from Patent EP1572962.
JD168798 - Sequence 149822 from Patent EP1572962.
JD527847 - Sequence 508871 from Patent EP1572962.
JD102826 - Sequence 83850 from Patent EP1572962.
JD146576 - Sequence 127600 from Patent EP1572962.
JD085253 - Sequence 66277 from Patent EP1572962.
JD486620 - Sequence 467644 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04010 - MAPK signaling pathway
hsa04310 - Wnt signaling pathway
hsa04520 - Adherens junction
hsa04620 - Toll-like receptor signaling pathway
hsa04621 - NOD-like receptor signaling pathway
hsa04622 - RIG-I-like receptor signaling pathway
hsa04660 - T cell receptor signaling pathway
hsa05140 - Leishmaniasis

BioCarta from NCI Cancer Genome Anatomy Project
h_tgfbPathway - TGF beta signaling pathway
h_alkPathway - ALK in cardiac myocytes
h_fasPathway - FAS signaling pathway ( CD95 )
h_nfkbPathway - NF-kB Signaling Pathway
h_tnfr1Pathway - TNFR1 Signaling Pathway
h_wntPathway - WNT Signaling Pathway
h_il1rPathway - Signal transduction through IL1R
h_nthiPathway - NFkB activation by Nontypeable Hemophilus influenzae
h_Par1Pathway - Thrombin signaling and protease-activated receptors
h_mapkPathway - MAPKinase Signaling Pathway
h_p38mapkPathway - p38 MAPK Signaling Pathway
h_tollPathway - Toll-Like Receptor Pathway

Reactome (by CSHL, EBI, and GO)

Protein O43318 (Reactome details) participates in the following event(s):

R-HSA-4332356 CAMK2 binds MAP3K7
R-HSA-446870 Polyubiquitinated TRAF6 binds the TAK1 complex
R-HSA-936960 Activated TRAF6:p-IRAK2 interacts with TAK1 complex
R-HSA-975097 Activated TRAF6:p-IRAK2 interacts with TAK1 complex upon TLR7/8 or 9 stimulation
R-HSA-177690 Activated TLR3:TRIF:K63pUb-TRAF6 recruits TAK1complex
R-HSA-936947 Activated TLR4:TICAM1:K63pUb-TRAF6 recruits TAK1complex
R-HSA-2730861 Recruitment of TAK1 kinase complex to oligo-K63-pUb-TRAF6
R-HSA-5357860 TNF:TNFR1:TRADD:TRAF2:K63polyUb-RIPK1:BIRC2/3 recruits TAK1 complex
R-HSA-5607759 TRIKA2 binds K63polyUb-TRAF6 oligomer
R-HSA-1168641 TAK1 associated with the CBM complex phosphorylates IKKbeta
R-HSA-5696534 USP18 deubiquitinates TAK1:TAB1
R-HSA-688985 K63 polyubiquitinated RIP2 associates with the TAK1 complex
R-HSA-202510 Activation of TAK1-TAB2 complex
R-HSA-847070 Phosphorylated TAK1 dissociates from the TLR3 receptor complex
R-HSA-937075 Phosphorylated TAK1 leaves activated TLR receptor complex
R-HSA-936951 Activation of TAK1 complex bound to activated TLR4 complex
R-HSA-936991 Auto phosphorylation of TAK1 bound to p-IRAK2:pUb oligo-TRAF6: free K63 pUb:TAB1:TAB2/TAB3
R-HSA-177692 Activation of recruited TAK1 within the activated TLR3 complex
R-HSA-975103 Auto phosphorylation of TAK1 bound to p-IRAK2:pUb oligo-TRAF6: free K63 pUb:TAB1:TAB2/TAB3 upon TLR7/8 or 9 activation
R-HSA-727819 TAK1 phosphorylates MKK6
R-HSA-5607732 K63polyUb-TAK1 autophosphorylates
R-HSA-2730876 Phosphorylation of IKK-beta by TAK1
R-HSA-202500 Activation of IKK complex
R-HSA-168184 Activated TAK1 mediates phosphorylation of the IKK Complex
R-HSA-450337 Activated TAK1 phosphorylates MKK4/MKK7
R-HSA-450346 activated human TAK1 phosphorylates MKK3/MKK6
R-HSA-5607742 K63polyUb-p-3T,1S-TAK1 phosphorylates IKK-beta
R-HSA-1169091 Activation of NF-kappaB in B cells
R-HSA-4086398 Ca2+ pathway
R-HSA-9020702 Interleukin-1 signaling
R-HSA-937042 IRAK2 mediated activation of TAK1 complex
R-HSA-975163 IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation
R-HSA-9014325 TICAM1,TRAF6-dependent induction of TAK1 complex
R-HSA-937072 TRAF6-mediated induction of TAK1 complex within TLR4 complex
R-HSA-2871837 FCERI mediated NF-kB activation
R-HSA-5357956 TNFR1-induced NFkappaB signaling pathway
R-HSA-5607764 CLEC7A (Dectin-1) signaling
R-HSA-5689880 Ub-specific processing proteases
R-HSA-168638 NOD1/2 Signaling Pathway
R-HSA-1168372 Downstream signaling events of B Cell Receptor (BCR)
R-HSA-3858494 Beta-catenin independent WNT signaling
R-HSA-202424 Downstream TCR signaling
R-HSA-446652 Interleukin-1 family signaling
R-HSA-166058 MyD88:Mal cascade initiated on plasma membrane
R-HSA-975871 MyD88 cascade initiated on plasma membrane
R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
R-HSA-168164 Toll Like Receptor 3 (TLR3) Cascade
R-HSA-937061 TRIF(TICAM1)-mediated TLR4 signaling
R-HSA-2454202 Fc epsilon receptor (FCERI) signaling
R-HSA-75893 TNF signaling
R-HSA-5621481 C-type lectin receptors (CLRs)
R-HSA-5688426 Deubiquitination
R-HSA-168643 Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
R-HSA-983705 Signaling by the B Cell Receptor (BCR)
R-HSA-195721 Signaling by WNT
R-HSA-202403 TCR signaling
R-HSA-449147 Signaling by Interleukins
R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade
R-HSA-168179 Toll Like Receptor TLR1:TLR2 Cascade
R-HSA-168188 Toll Like Receptor TLR6:TLR2 Cascade
R-HSA-168142 Toll Like Receptor 10 (TLR10) Cascade
R-HSA-168176 Toll Like Receptor 5 (TLR5) Cascade
R-HSA-975155 MyD88 dependent cascade initiated on endosome
R-HSA-168898 Toll-Like Receptors Cascades
R-HSA-166166 MyD88-independent TLR4 cascade
R-HSA-168249 Innate Immune System
R-HSA-73887 Death Receptor Signalling
R-HSA-597592 Post-translational protein modification
R-HSA-1280218 Adaptive Immune System
R-HSA-162582 Signal Transduction
R-HSA-445989 TAK1 activates NFkB by phosphorylation and activation of IKKs complex
R-HSA-450321 JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
R-HSA-450302 activated TAK1 mediates p38 MAPK activation
R-HSA-1280215 Cytokine Signaling in Immune system
R-HSA-181438 Toll Like Receptor 2 (TLR2) Cascade
R-HSA-168138 Toll Like Receptor 9 (TLR9) Cascade
R-HSA-168181 Toll Like Receptor 7/8 (TLR7/8) Cascade
R-HSA-168256 Immune System
R-HSA-392499 Metabolism of proteins
R-HSA-450294 MAP kinase activation
R-HSA-448424 Interleukin-17 signaling

-  Other Names for This Gene
  Alternate Gene Symbols: B2RE27, E1P523, ENST00000369329.1, ENST00000369329.2, ENST00000369329.3, ENST00000369329.4, ENST00000369329.5, ENST00000369329.6, ENST00000369329.7, M3K7_HUMAN, NM_145331, O43317, O43318, O43319, Q5TDN2, Q5TDN3, Q5TDT7, Q9NTR3, Q9NZ70, TAK1, uc003pnz.1, uc003pnz.2, uc003pnz.3, uc003pnz.4
UCSC ID: ENST00000369329.8
RefSeq Accession: NM_145331
Protein: O43318 (aka M3K7_HUMAN)
CCDS: CCDS5027.1, CCDS5028.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.