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Mitogen-activated protein kinase kinase kinase 7 (EC 2 7 11 25)

 M3K7_BOVIN              Reviewed;         579 AA.
A2VDU3;
15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
20-MAR-2007, sequence version 1.
08-MAY-2019, entry version 109.
RecName: Full=Mitogen-activated protein kinase kinase kinase 7;
EC=2.7.11.25 {ECO:0000250|UniProtKB:O43318};
Name=MAP3K7;
Bos taurus (Bovine).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Laurasiatheria; Cetartiodactyla; Ruminantia;
Pecora; Bovidae; Bovinae; Bos.
NCBI_TaxID=9913;
[1]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
STRAIN=Hereford; TISSUE=Ascending colon;
NIH - Mammalian Gene Collection (MGC) project;
Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
-!- 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). Promotes TRIM5 capsid-specific restriction activity
(By similarity). {ECO:0000250}.
-!- CATALYTIC ACTIVITY:
Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999,
ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216;
EC=2.7.11.25; Evidence={ECO:0000250|UniProtKB:O43318};
-!- CATALYTIC ACTIVITY:
Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
EC=2.7.11.25; Evidence={ECO:0000250|UniProtKB:O43318};
-!- COFACTOR:
Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
-!- ACTIVITY 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). {ECO:0000250}.
-!- SUBUNIT: Can form homodimer. 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. 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. Interacts with TRIM5. Part of a complex
containing ITCH, NDFIP1 and MAP3K7. Interacts with IFIT5; the
interaction synergizes the recruitment of IKK to MAP3K7 and
enhances IKK phosphorylation. Interacts with PLEKHM1 (via N- and
C-terminus). Found in a complex with SH3RF1, RAC2, MAP2K7/MKK7,
MAPK8IP1/JIP1, MAPK8/JNK1 and MAPK9/JNK2.
{ECO:0000250|UniProtKB:O43318, ECO:0000250|UniProtKB:Q62073}.
-!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
{ECO:0000250}; Peripheral membrane protein {ECO:0000250};
Cytoplasmic side {ECO:0000250}. 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. {ECO:0000250}.
-!- 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 (By
similarity). {ECO:0000250}.
-!- PTM: 'Lys-48'-linked polyubiquitination at Lys-72 is induced by
TNFalpha, and leads to proteasomal degradation. Undergoes 'Lys-
48'-linked polyubiquitination catalyzed by ITCH. '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.
{ECO:0000250|UniProtKB:O43318, ECO:0000250|UniProtKB:Q62073}.
-!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
protein kinase family. MAP kinase kinase kinase subfamily.
{ECO:0000305}.
-----------------------------------------------------------------------
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EMBL; BC133404; AAI33405.1; -; mRNA.
RefSeq; NP_001075064.1; NM_001081595.1.
RefSeq; XP_005210930.1; XM_005210873.3.
SMR; A2VDU3; -.
STRING; 9913.ENSBTAP00000003401; -.
PaxDb; A2VDU3; -.
PRIDE; A2VDU3; -.
Ensembl; ENSBTAT00000003401; ENSBTAP00000003401; ENSBTAG00000002625.
GeneID; 529146; -.
KEGG; bta:529146; -.
CTD; 6885; -.
VGNC; VGNC:31200; MAP3K7.
eggNOG; KOG0192; Eukaryota.
eggNOG; COG0515; LUCA.
GeneTree; ENSGT00940000157785; -.
HOGENOM; HOG000231735; -.
InParanoid; A2VDU3; -.
KO; K04427; -.
OMA; IGTESSQ; -.
OrthoDB; 635654at2759; -.
TreeFam; TF105116; -.
Reactome; R-BTA-168638; NOD1/2 Signaling Pathway.
Reactome; R-BTA-202424; Downstream TCR signaling.
Reactome; R-BTA-2871837; FCERI mediated NF-kB activation.
Reactome; R-BTA-4086398; Ca2+ pathway.
Reactome; R-BTA-445989; TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
Reactome; R-BTA-5357956; TNFR1-induced NFkappaB signaling pathway.
Reactome; R-BTA-5607764; CLEC7A (Dectin-1) signaling.
Reactome; R-BTA-5689880; Ub-specific processing proteases.
Reactome; R-BTA-9020702; Interleukin-1 signaling.
Reactome; R-BTA-937042; IRAK2 mediated activation of TAK1 complex.
Reactome; R-BTA-937072; TRAF6-mediated induction of TAK1 complex within TLR4 complex.
Reactome; R-BTA-975163; IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation.
Proteomes; UP000009136; Chromosome 9.
Bgee; ENSBTAG00000002625; Expressed in 10 organ(s), highest expression level in spleen.
GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
GO; GO:0004709; F:MAP kinase kinase kinase activity; ISS:UniProtKB.
GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
GO; GO:0007252; P:I-kappaB phosphorylation; ISS:UniProtKB.
GO; GO:0007254; P:JNK cascade; ISS:UniProtKB.
GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IBA:GO_Central.
GO; GO:0043507; P:positive regulation of JUN kinase activity; ISS:UniProtKB.
InterPro; IPR011009; Kinase-like_dom_sf.
InterPro; IPR017421; MAPKKK7.
InterPro; IPR000719; Prot_kinase_dom.
InterPro; IPR017441; Protein_kinase_ATP_BS.
InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
InterPro; IPR008271; Ser/Thr_kinase_AS.
PANTHER; PTHR46716; PTHR46716; 2.
Pfam; PF07714; Pkinase_Tyr; 1.
PIRSF; PIRSF038168; MAPKKK7; 1.
PRINTS; PR00109; TYRKINASE.
SMART; SM00220; S_TKc; 1.
SUPFAM; SSF56112; SSF56112; 1.
PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
2: Evidence at transcript level;
Apoptosis; ATP-binding; Cell membrane; Complete proteome; Cytoplasm;
Isopeptide bond; Kinase; Magnesium; Membrane; Metal-binding;
Nucleotide-binding; Phosphoprotein; Reference proteome;
Serine/threonine-protein kinase; Stress response; Transcription;
Transcription regulation; Transferase; Ubl conjugation.
CHAIN 1 579 Mitogen-activated protein kinase kinase
kinase 7.
/FTId=PRO_0000314284.
DOMAIN 36 291 Protein kinase. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
NP_BIND 42 50 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
REGION 1 300 Interaction with MAPK8IP1. {ECO:0000250}.
COMPBIAS 8 14 Poly-Ser.
ACT_SITE 156 156 Proton acceptor. {ECO:0000255|PROSITE-
ProRule:PRU00159, ECO:0000255|PROSITE-
ProRule:PRU10027}.
BINDING 63 63 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
MOD_RES 184 184 Phosphothreonine; by autocatalysis.
{ECO:0000250|UniProtKB:O43318}.
MOD_RES 187 187 Phosphothreonine; by autocatalysis.
{ECO:0000250|UniProtKB:O43318}.
MOD_RES 192 192 Phosphoserine; by autocatalysis.
{ECO:0000250|UniProtKB:O43318}.
MOD_RES 367 367 Phosphoserine.
{ECO:0000250|UniProtKB:O43318}.
MOD_RES 389 389 Phosphoserine.
{ECO:0000250|UniProtKB:O43318}.
MOD_RES 412 412 Phosphoserine.
{ECO:0000250|UniProtKB:O43318}.
MOD_RES 428 428 Phosphoserine.
{ECO:0000250|UniProtKB:O43318}.
CROSSLNK 72 72 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in ubiquitin).
{ECO:0000250|UniProtKB:O43318}.
CROSSLNK 158 158 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in ubiquitin).
{ECO:0000250|UniProtKB:Q62073}.
CROSSLNK 209 209 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in ubiquitin).
{ECO:0000250|UniProtKB:Q62073}.
SEQUENCE 579 AA; 64216 MW; B987EE4700AE63E4 CRC64;
MSTASAASSS SSSSAGEMIE APSQVLNFEE IDYKEIEVEE VVGRGAFGVV CKAKWRAKDV
AIKQIESESE RKAFIVELRQ LSRVNHPNIV KLYGACLNPV CLVMEYAEGG SLYNVLHGAE
PLPYYTAAHA MSWCLQCSQG VAYLHSMQPK ALIHRDLKPP NLLLVAGGTV LKICDFGTAC
DIQTHMTNNK GSAAWMAPEV FEGSNYSEKC DVFSWGIILW EVITRRKPFD EIGGPAFRIM
WAVHNGTRPP LIKNLPKPIE SLMTRCWSKD PSQRPSMEEI VKIMTHLMRY FPGADEPLQY
PCQYSDEGQS NSATSTGSFM DITSTNTSNK SDTNMEQVPA TNDTIKRLES KLLKNQAKQQ
SESGRLSLGA SRGSSVESLP PTSEGKRMSA DMSEIEARIA ATTGNGQPRR RSIQDLTVTG
TDPGQVSSRS SSPSVRMITT SGPTSEKPAR SHPWTPDDST DTNGSDNSIP MAYLTLDHQL
QPLAPCPNSK ESMAVFEQHC KMAQEYMKVQ TEIALLLQRK QELVAELDQD EKDQQNTSRL
VQEHKKLLDE NKSLSTYYQQ CKKQLEVIRS QQQKRQGTS


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WP2341: vitamin B1 (thiamin) biosynthesis and salvage pathway
WP32: Translation Factors
WP1653: Galactose metabolism
WP2340: Thiamine (vitamin B1) biosynthesis and salvage
WP1681: Pantothenate and CoA biosynthesis
WP253: Glycolysis
WP1650: Fluorobenzoate degradation
WP2032: TSH signaling pathway
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WP35: G Protein Signaling Pathways
WP1371: G Protein Signaling Pathways
WP1694: Pyrimidine metabolism
WP731: Sterol regulatory element binding protein related
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WP2199: Seed Development
WP1663: Homologous recombination
WP2272: Pathogenic Escherichia coli infection
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Related Genes :
[Map3k7 Tak1] Mitogen-activated protein kinase kinase kinase 7 (EC 2.7.11.25) (Transforming growth factor-beta-activated kinase 1) (TGF-beta-activated kinase 1)
[MAP3K7 TAK1] Mitogen-activated protein kinase kinase kinase 7 (EC 2.7.11.25) (Transforming growth factor-beta-activated kinase 1) (TGF-beta-activated kinase 1)
[dlk-1 F33E2.2] Mitogen-activated protein kinase kinase kinase dlk-1 (EC 2.7.11.25) (DAP kinase-like kinase) (Death-associated protein kinase-like kinase)
[MAPK14 CSBP CSBP1 CSBP2 CSPB1 MXI2 SAPK2A] Mitogen-activated protein kinase 14 (MAP kinase 14) (MAPK 14) (EC 2.7.11.24) (Cytokine suppressive anti-inflammatory drug-binding protein) (CSAID-binding protein) (CSBP) (MAP kinase MXI2) (MAX-interacting protein 2) (Mitogen-activated protein kinase p38 alpha) (MAP kinase p38 alpha) (Stress-activated protein kinase 2a) (SAPK2a)
[Map3k1 Mekk Mekk1] Mitogen-activated protein kinase kinase kinase 1 (EC 2.7.11.25) (MAPK/ERK kinase kinase 1) (MEK kinase 1) (MEKK 1)
[MAP3K20 MLTK ZAK HCCS4] Mitogen-activated protein kinase kinase kinase 20 (EC 2.7.11.25) (Human cervical cancer suppressor gene 4 protein) (HCCS-4) (Leucine zipper- and sterile alpha motif-containing kinase) (MLK-like mitogen-activated protein triple kinase) (Mitogen-activated protein kinase kinase kinase MLT) (Mixed lineage kinase-related kinase) (MLK-related kinase) (MRK) (Sterile alpha motif- and leucine zipper-containing kinase AZK)
[nsy-1 F59A6.1] Mitogen-activated protein kinase kinase kinase nsy-1 (EC 2.7.11.25) (Apoptosis signal-regulating kinase 1) (ASK-1) (Neuronal symmetry kinase 1)
[Map3k1 Mekk Mekk1] Mitogen-activated protein kinase kinase kinase 1 (EC 2.7.11.25) (MAPK/ERK kinase kinase 1) (MEK kinase 1) (MEKK 1)
[MAP3K11 MLK3 PTK1 SPRK] Mitogen-activated protein kinase kinase kinase 11 (EC 2.7.11.25) (Mixed lineage kinase 3) (Src-homology 3 domain-containing proline-rich kinase)
[Map3k2 Mekk2] Mitogen-activated protein kinase kinase kinase 2 (EC 2.7.11.25) (MAPK/ERK kinase kinase 2) (MEK kinase 2) (MEKK 2)
[MAP3K1 MAPKKK1 MEKK MEKK1] Mitogen-activated protein kinase kinase kinase 1 (EC 2.7.11.25) (MAPK/ERK kinase kinase 1) (MEK kinase 1) (MEKK 1)
[Map3k6 Ask2 Mapkkk6 Mekk6] Mitogen-activated protein kinase kinase kinase 6 (EC 2.7.11.25) (Apoptosis signal-regulating kinase 2)
[MAPK11 PRKM11 SAPK2 SAPK2B] Mitogen-activated protein kinase 11 (MAP kinase 11) (MAPK 11) (EC 2.7.11.24) (Mitogen-activated protein kinase p38 beta) (MAP kinase p38 beta) (p38b) (Stress-activated protein kinase 2b) (SAPK2b) (p38-2)
[MAP3K6 ASK2 MAPKKK6 MEKK6] Mitogen-activated protein kinase kinase kinase 6 (EC 2.7.11.25) (Apoptosis signal-regulating kinase 2)
[Map3k7] Mitogen-activated protein kinase kinase kinase 7 (EC 2.7.11.25)
[Mapk14 Crk1 Csbp1 Csbp2] Mitogen-activated protein kinase 14 (MAP kinase 14) (MAPK 14) (EC 2.7.11.24) (CRK1) (Mitogen-activated protein kinase p38 alpha) (MAP kinase p38 alpha)
[MAPK1 ERK2 PRKM1 PRKM2] Mitogen-activated protein kinase 1 (MAP kinase 1) (MAPK 1) (EC 2.7.11.24) (ERT1) (Extracellular signal-regulated kinase 2) (ERK-2) (MAP kinase isoform p42) (p42-MAPK) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2)
[MAP3K5 ASK1 MAPKKK5 MEKK5] Mitogen-activated protein kinase kinase kinase 5 (EC 2.7.11.25) (Apoptosis signal-regulating kinase 1) (ASK-1) (MAPK/ERK kinase kinase 5) (MEK kinase 5) (MEKK 5)
[Mapk12 Sapk3] Mitogen-activated protein kinase 12 (MAP kinase 12) (MAPK 12) (EC 2.7.11.24) (Extracellular signal-regulated kinase 6) (ERK-6) (Mitogen-activated protein kinase p38 gamma) (MAP kinase p38 gamma) (Stress-activated protein kinase 3)
[Mapk1 Erk2 Mapk Prkm1] Mitogen-activated protein kinase 1 (MAP kinase 1) (MAPK 1) (EC 2.7.11.24) (ERT1) (Extracellular signal-regulated kinase 2) (ERK-2) (MAP kinase isoform p42) (p42-MAPK) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2)
[Mapk1 Erk2 Mapk Prkm1] Mitogen-activated protein kinase 1 (MAP kinase 1) (MAPK 1) (EC 2.7.11.24) (ERT1) (Extracellular signal-regulated kinase 2) (ERK-2) (MAP kinase isoform p42) (p42-MAPK) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2)
[Map3k5 Ask1 Mekk5] Mitogen-activated protein kinase kinase kinase 5 (EC 2.7.11.25) (Apoptosis signal-regulating kinase 1) (ASK-1) (MAPK/ERK kinase kinase 5) (MEK kinase 5) (MEKK 5)
[MAPK12 ERK6 SAPK3] Mitogen-activated protein kinase 12 (MAP kinase 12) (MAPK 12) (EC 2.7.11.24) (Extracellular signal-regulated kinase 6) (ERK-6) (Mitogen-activated protein kinase p38 gamma) (MAP kinase p38 gamma) (Stress-activated protein kinase 3)
[MPK4 At4g01370 F2N1.1 F2N1_2-t] Mitogen-activated protein kinase 4 (AtMPK4) (MAP kinase 4) (EC 2.7.11.24)
[MAPK13 PRKM13 SAPK4] Mitogen-activated protein kinase 13 (MAP kinase 13) (MAPK 13) (EC 2.7.11.24) (Mitogen-activated protein kinase p38 delta) (MAP kinase p38 delta) (Stress-activated protein kinase 4)
[Mapk14 Csbp1 Csbp2] Mitogen-activated protein kinase 14 (MAP kinase 14) (MAPK 14) (EC 2.7.11.24) (CRK1) (Mitogen-activated protein kinase p38 alpha) (MAP kinase p38 alpha)
[Mapk13] Mitogen-activated protein kinase 13 (MAP kinase 13) (MAPK 13) (EC 2.7.11.24) (Mitogen-activated protein kinase p38 delta) (MAP kinase p38 delta) (Stress-activated protein kinase 4)
[MAP3K9 MLK1 PRKE1] Mitogen-activated protein kinase kinase kinase 9 (EC 2.7.11.25) (Mixed lineage kinase 1)
[pmk-1 B0218.3] Mitogen-activated protein kinase pmk-1 (EC 2.7.11.24) (Stress-activated protein kinase pmk-1) (p38 MAP kinase 1)
[MAPK1 ERK2 PRKM1] Mitogen-activated protein kinase 1 (MAP kinase 1) (MAPK 1) (EC 2.7.11.24) (ERT1) (Extracellular signal-regulated kinase 2) (ERK-2) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2)

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