Skip Header

Contribute Send feedback
Read comments (?) or add your own

A2VDU3 (M3K7_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Last modified December 14, 2011. Version 48. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Mitogen-activated protein kinase kinase kinase 7
EC=2.7.11.25
Gene names
Name:MAP3K7
OrganismBos taurus (Bovine)
Taxonomic identifier9913 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

Protein attributes

Sequence length579 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

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 By similarity.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium By similarity.

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 By similarity.

Subunit structure

Binds both upstream activators and downstream substrates in multimolecular complexes. Interacts with TAB1/MAP3K7IP1, TAB2/MAP3K7IP2 and TAB3/MAP3K7IP3 By similarity. Identified in the TRIKA2 complex composed of MAP3K7/TAK1, TAB1/MAP3K7IP1 and TAB2/MAP3K7IP2 By similarity. Interacts with PPM1L and PPM1B/PP2CB By similarity. 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 By similarity. Interacts with WDR34 (via WD domains) By similarity. Interacts with CYLD and RBCK1 By similarity. Interacts with TGFBR1; induces MAP3K7/TAK1 activation by TRAF6 By similarity. Interacts with MAPK8IP1 and SMAD6 By similarity. Interacts with isoform 1 of VRK2 By similarity.

Subcellular location

Cytoplasm By similarity. Cell membrane; Peripheral membrane protein; Cytoplasmic side By similarity. 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 By similarity.

Post-translational modification

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 By similarity.

Ubiquitinated, leading to proteasomal degradation. 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 By similarity.

Sequence similarities

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.

Contains 1 protein kinase domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 579579Mitogen-activated protein kinase kinase kinase 7
PRO_0000314284

Regions

Domain36 – 291256Protein kinase
Nucleotide binding42 – 509ATP By similarity
Region1 – 300300Interaction with MAPK8IP1 By similarity
Compositional bias8 – 147Poly-Ser

Sites

Active site1561Proton acceptor By similarity
Binding site631ATP By similarity

Amino acid modifications

Modified residue1841Phosphothreonine; by autocatalysis By similarity
Modified residue1871Phosphothreonine; by autocatalysis By similarity
Modified residue1921Phosphoserine; by autocatalysis By similarity
Modified residue3891Phosphoserine By similarity
Modified residue4121Phosphoserine By similarity
Modified residue4171Phosphothreonine By similarity
Modified residue4281Phosphoserine By similarity

Sequences

Sequence LengthMass (Da)Tools
A2VDU3 [UniParc].

Last modified March 20, 2007. Version 1.
Checksum: B987EE4700AE63E4

FASTA57964,216
        10         20         30         40         50         60 
MSTASAASSS SSSSAGEMIE APSQVLNFEE IDYKEIEVEE VVGRGAFGVV CKAKWRAKDV 

        70         80         90        100        110        120 
AIKQIESESE RKAFIVELRQ LSRVNHPNIV KLYGACLNPV CLVMEYAEGG SLYNVLHGAE 

       130        140        150        160        170        180 
PLPYYTAAHA MSWCLQCSQG VAYLHSMQPK ALIHRDLKPP NLLLVAGGTV LKICDFGTAC 

       190        200        210        220        230        240 
DIQTHMTNNK GSAAWMAPEV FEGSNYSEKC DVFSWGIILW EVITRRKPFD EIGGPAFRIM 

       250        260        270        280        290        300 
WAVHNGTRPP LIKNLPKPIE SLMTRCWSKD PSQRPSMEEI VKIMTHLMRY FPGADEPLQY 

       310        320        330        340        350        360 
PCQYSDEGQS NSATSTGSFM DITSTNTSNK SDTNMEQVPA TNDTIKRLES KLLKNQAKQQ 

       370        380        390        400        410        420 
SESGRLSLGA SRGSSVESLP PTSEGKRMSA DMSEIEARIA ATTGNGQPRR RSIQDLTVTG 

       430        440        450        460        470        480 
TDPGQVSSRS SSPSVRMITT SGPTSEKPAR SHPWTPDDST DTNGSDNSIP MAYLTLDHQL 

       490        500        510        520        530        540 
QPLAPCPNSK ESMAVFEQHC KMAQEYMKVQ TEIALLLQRK QELVAELDQD EKDQQNTSRL 

       550        560        570 
VQEHKKLLDE NKSLSTYYQQ CKKQLEVIRS QQQKRQGTS

« Hide

References

[1]NIH - Mammalian Gene Collection (MGC) project
Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: Hereford.
Tissue: Ascending colon.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		BC133404 mRNA. Translation: AAI33405.1.
IPIIPI00708123.
RefSeqNP_001075064.1. NM_001081595.1.
UniGeneBt.102295.

3D structure databases

ProteinModelPortalA2VDU3.
SMRA2VDU3. Positions 31-305.
ModBaseSearch...

Protein-protein interaction databases

STRINGA2VDU3.

Proteomic databases

PRIDEA2VDU3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSBTAT00000003401; ENSBTAP00000003401; ENSBTAG00000002625.
GeneID529146.
KEGGbta:529146.

Organism-specific databases

CTD6885.

Phylogenomic databases

eggNOGmaNOG08783.
GeneTreeENSGT00600000084194.
HOVERGENHBG003485.
InParanoidA2VDU3.
OrthoDBEOG4BRWKD.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR017421. MAPKKK7.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
KOK04427.
PfamPF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFPIRSF038168. MAPKKK7. 1 hit.
PRINTSPR00109. TYRKINASE.
SUPFAMSSF56112. Kinase_like. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameM3K7_BOVIN
AccessionPrimary (citable) accession number: A2VDU3
Entry history
Integrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: March 20, 2007
Last modified: December 14, 2011
This is version 48 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents