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Protein

Mitogen-activated protein kinase kinase kinase 7

Gene

MAP3K7

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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). Promotes TRIM5 capsid-specific restriction activity (By similarity).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Enzyme regulationi

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).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei63ATPPROSITE-ProRule annotation1
Active sitei156Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi42 – 50ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Stress response, Transcription, Transcription regulation

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-BTA-168638. NOD1/2 Signaling Pathway.
R-BTA-202424. Downstream TCR signaling.
R-BTA-2871837. FCERI mediated NF-kB activation.
R-BTA-4086398. Ca2+ pathway.
R-BTA-445989. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
R-BTA-446652. Interleukin-1 signaling.
R-BTA-450302. activated TAK1 mediates p38 MAPK activation.
R-BTA-450321. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
R-BTA-5357956. TNFR1-induced NFkappaB signaling pathway.
R-BTA-5607764. CLEC7A (Dectin-1) signaling.
R-BTA-5689880. Ub-specific processing proteases.
R-BTA-937042. IRAK2 mediated activation of TAK1 complex.
R-BTA-975163. IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation.

Names & Taxonomyi

Protein namesi
Recommended name:
Mitogen-activated protein kinase kinase kinase 7 (EC:2.7.11.25)
Gene namesi
Name:MAP3K7
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 9

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003142841 – 579Mitogen-activated protein kinase kinase kinase 7Add BLAST579

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki72Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei184Phosphothreonine; by autocatalysisBy similarity1
Modified residuei187Phosphothreonine; by autocatalysisBy similarity1
Modified residuei192Phosphoserine; by autocatalysisBy similarity1
Modified residuei367PhosphoserineBy similarity1
Modified residuei389PhosphoserineBy similarity1
Modified residuei412PhosphoserineBy similarity1
Modified residuei428PhosphoserineBy similarity1

Post-translational modificationi

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).By similarity
'Lys-48'-linked polyubiquitination at Lys-72 is induced by TNFalpha, and leads to proteasomal degradation. 'Lys-63'-linked polyubiquitination at Lys-158 by TRIM8 does not lead to proteasomal degradation but contributes to autophosphorylation and activation. Deubiquitinated by CYLD, a protease that selectively cleaves 'Lys-63'-linked ubiquitin chains (By similarity).By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiA2VDU3.
PRIDEiA2VDU3.

Expressioni

Gene expression databases

BgeeiENSBTAG00000002625.

Interactioni

Subunit structurei

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). Interacts with TRIM5 (By similarity).By similarity

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000003401.

Structurei

3D structure databases

ProteinModelPortaliA2VDU3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini36 – 291Protein kinasePROSITE-ProRule annotationAdd BLAST256

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 300Interaction with MAPK8IP1By similarityAdd BLAST300

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi8 – 14Poly-Ser7

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0192. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118807.
HOGENOMiHOG000231735.
HOVERGENiHBG003485.
InParanoidiA2VDU3.
KOiK04427.
OMAiPARSHPW.
OrthoDBiEOG091G03QO.
TreeFamiTF105116.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR017421. MAPKKK7.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR26392:SF74. PTHR26392:SF74. 1 hit.
PfamiPF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSiPR00109. TYRKINASE.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

A2VDU3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSTASAASSS SSSSAGEMIE APSQVLNFEE IDYKEIEVEE VVGRGAFGVV
60 70 80 90 100
CKAKWRAKDV AIKQIESESE RKAFIVELRQ LSRVNHPNIV KLYGACLNPV
110 120 130 140 150
CLVMEYAEGG SLYNVLHGAE PLPYYTAAHA MSWCLQCSQG VAYLHSMQPK
160 170 180 190 200
ALIHRDLKPP NLLLVAGGTV LKICDFGTAC DIQTHMTNNK GSAAWMAPEV
210 220 230 240 250
FEGSNYSEKC DVFSWGIILW EVITRRKPFD EIGGPAFRIM WAVHNGTRPP
260 270 280 290 300
LIKNLPKPIE SLMTRCWSKD PSQRPSMEEI VKIMTHLMRY FPGADEPLQY
310 320 330 340 350
PCQYSDEGQS NSATSTGSFM DITSTNTSNK SDTNMEQVPA TNDTIKRLES
360 370 380 390 400
KLLKNQAKQQ SESGRLSLGA SRGSSVESLP PTSEGKRMSA DMSEIEARIA
410 420 430 440 450
ATTGNGQPRR RSIQDLTVTG TDPGQVSSRS SSPSVRMITT SGPTSEKPAR
460 470 480 490 500
SHPWTPDDST DTNGSDNSIP MAYLTLDHQL QPLAPCPNSK ESMAVFEQHC
510 520 530 540 550
KMAQEYMKVQ TEIALLLQRK QELVAELDQD EKDQQNTSRL VQEHKKLLDE
560 570
NKSLSTYYQQ CKKQLEVIRS QQQKRQGTS
Length:579
Mass (Da):64,216
Last modified:March 20, 2007 - v1
Checksum:iB987EE4700AE63E4
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC133404 mRNA. Translation: AAI33405.1.
RefSeqiNP_001075064.1. NM_001081595.1.
XP_005210930.1. XM_005210873.3.
UniGeneiBt.102295.

Genome annotation databases

EnsembliENSBTAT00000003401; ENSBTAP00000003401; ENSBTAG00000002625.
GeneIDi529146.
KEGGibta:529146.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC133404 mRNA. Translation: AAI33405.1.
RefSeqiNP_001075064.1. NM_001081595.1.
XP_005210930.1. XM_005210873.3.
UniGeneiBt.102295.

3D structure databases

ProteinModelPortaliA2VDU3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000003401.

Proteomic databases

PaxDbiA2VDU3.
PRIDEiA2VDU3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000003401; ENSBTAP00000003401; ENSBTAG00000002625.
GeneIDi529146.
KEGGibta:529146.

Organism-specific databases

CTDi6885.

Phylogenomic databases

eggNOGiKOG0192. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118807.
HOGENOMiHOG000231735.
HOVERGENiHBG003485.
InParanoidiA2VDU3.
KOiK04427.
OMAiPARSHPW.
OrthoDBiEOG091G03QO.
TreeFamiTF105116.

Enzyme and pathway databases

ReactomeiR-BTA-168638. NOD1/2 Signaling Pathway.
R-BTA-202424. Downstream TCR signaling.
R-BTA-2871837. FCERI mediated NF-kB activation.
R-BTA-4086398. Ca2+ pathway.
R-BTA-445989. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
R-BTA-446652. Interleukin-1 signaling.
R-BTA-450302. activated TAK1 mediates p38 MAPK activation.
R-BTA-450321. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
R-BTA-5357956. TNFR1-induced NFkappaB signaling pathway.
R-BTA-5607764. CLEC7A (Dectin-1) signaling.
R-BTA-5689880. Ub-specific processing proteases.
R-BTA-937042. IRAK2 mediated activation of TAK1 complex.
R-BTA-975163. IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation.

Gene expression databases

BgeeiENSBTAG00000002625.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR017421. MAPKKK7.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR26392:SF74. PTHR26392:SF74. 1 hit.
PfamiPF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSiPR00109. TYRKINASE.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiM3K7_BOVIN
AccessioniPrimary (citable) accession number: A2VDU3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: March 20, 2007
Last modified: October 5, 2016
This is version 88 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.