M3K7_BOVIN
ID M3K7_BOVIN Reviewed; 579 AA.
AC A2VDU3;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 20-MAR-2007, sequence version 1.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Mitogen-activated protein kinase kinase kinase 7;
DE EC=2.7.11.25 {ECO:0000250|UniProtKB:O43318};
GN Name=MAP3K7;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Ascending colon;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Serine/threonine kinase which acts as an essential component
CC of the MAP kinase signal transduction pathway. Plays an important role
CC in the cascades of cellular responses evoked by changes in the
CC environment. Mediates signal transduction of TRAF6, various cytokines
CC including interleukin-1 (IL-1), transforming growth factor-beta (TGFB),
CC TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR),
CC tumor necrosis factor receptor CD40 and B-cell receptor (BCR).
CC Ceramides are also able to activate MAP3K7/TAK1. Once activated, acts
CC as an upstream activator of the MKK/JNK signal transduction cascade and
CC the p38 MAPK signal transduction cascade through the phosphorylation
CC and activation of several MAP kinase kinases like MAP2K1/MEK1,
CC MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate
CC p38 MAPKs, c-jun N-terminal kinases (JNKs) and I-kappa-B kinase complex
CC (IKK). Both p38 MAPK and JNK pathways control the transcription factors
CC activator protein-1 (AP-1), while nuclear factor-kappa B is activated
CC by IKK. MAP3K7 activates also IKBKB and MAPK8/JNK1 in response to TRAF6
CC signaling and mediates BMP2-induced apoptosis. In osmotic stress
CC signaling, plays a major role in the activation of MAPK8/JNK1, but not
CC that of NF-kappa-B (By similarity). Promotes TRIM5 capsid-specific
CC restriction activity (By similarity). Phosphorylates RIPK1 at 'Ser-321'
CC which positively regulates RIPK1 interaction with RIPK3 to promote
CC necroptosis but negatively regulates RIPK1 kinase activity and its
CC interaction with FADD to mediate apoptosis (By similarity).
CC {ECO:0000250|UniProtKB:O43318, ECO:0000250|UniProtKB:Q62073}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.25;
CC Evidence={ECO:0000250|UniProtKB:O43318};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.25; Evidence={ECO:0000250|UniProtKB:O43318};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Activated by pro-inflammatory cytokines and in
CC response to physical and chemical stresses, including osmotic stress,
CC oxidative stress, arsenic and ultraviolet light irradiation. Activated
CC by 'Lys-63'-linked polyubiquitination and by autophosphorylation.
CC Association with TAB1/MAP3K7IP1 and TAB2/MAP3K7IP2 promotes activation
CC through autophosphorylation, whereas PPM1B/PP2CB, PP2A and PPP6C
CC dephosphorylation leads to inactivation (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Can form homodimer. Binds both upstream activators and
CC downstream substrates in multimolecular complexes. Interacts with
CC TAB1/MAP3K7IP1, TAB2/MAP3K7IP2 and TAB3/MAP3K7IP3. Identified in the
CC TRIKA2 complex composed of MAP3K7/TAK1, TAB1/MAP3K7IP1 and
CC TAB2/MAP3K7IP2. Interacts with PPM1L and PPM1B/PP2CB. Interaction with
CC PP2A and PPP6C leads to its repressed activity. Interacts with TRAF6
CC and TAB1/MAP3K7IP1; during IL-1 signaling. Interacts with TAOK1 and
CC TAOK2; interaction with TAOK2 interferes with MAP3K7 interaction with
CC IKKA, thus preventing NF-kappa-B activation. Interacts with DYNC2I2
CC (via WD domains). Interacts with CYLD and RBCK1. Interacts with TGFBR1;
CC induces MAP3K7/TAK1 activation by TRAF6. Interacts with MAPK8IP1 and
CC SMAD6. Interacts with isoform 1 of VRK2. Interacts with DAB2; the
CC interaction is induced by TGF-beta stimulation and may mediate TGF-beta
CC stimulated JNK activation. Interacts with TRIM5. Part of a complex
CC containing ITCH, NDFIP1 and MAP3K7. Interacts with IFIT5; the
CC interaction synergizes the recruitment of IKK to MAP3K7 and enhances
CC IKK phosphorylation. Interacts with PLEKHM1 (via N- and C-terminus).
CC Found in a complex with SH3RF1, RAC2, MAP2K7/MKK7, MAPK8IP1/JIP1,
CC MAPK8/JNK1 and MAPK9/JNK2. Interacts with SASH1 (By similarity).
CC Interacts with RIPK1 (By similarity). {ECO:0000250|UniProtKB:O43318,
CC ECO:0000250|UniProtKB:Q62073}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}; Cytoplasmic
CC side {ECO:0000250}. Note=Although the majority of MAP3K7/TAK1 is found
CC in the cytosol, when complexed with TAB1/MAP3K7IP1 and TAB2/MAP3K7IP2,
CC it is also localized at the cell membrane. {ECO:0000250}.
CC -!- PTM: Association with TAB1/MAP3K7IP1 promotes autophosphorylation at
CC Ser-192 and subsequent activation. Association with TAB2/MAP3K7IP2,
CC itself associated with free unanchored Lys-63 polyubiquitin chain,
CC promotes autophosphorylation and subsequent activation of MAP3K7.
CC Dephosphorylation at Ser-192 by PPM1B/PP2CB and at Thr-187 by PP2A and
CC PPP6C leads to inactivation (By similarity). {ECO:0000250}.
CC -!- PTM: 'Lys-48'-linked polyubiquitination at Lys-72 is induced by
CC TNFalpha, and leads to proteasomal degradation. Undergoes 'Lys-48'-
CC linked polyubiquitination catalyzed by ITCH. 'Lys-63'-linked
CC polyubiquitination at Lys-158 by TRIM8 does not lead to proteasomal
CC degradation but contributes to autophosphorylation and activation.
CC Deubiquitinated by CYLD, a protease that selectively cleaves 'Lys-63'-
CC linked ubiquitin chains. {ECO:0000250|UniProtKB:O43318,
CC ECO:0000250|UniProtKB:Q62073}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. MAP kinase kinase kinase subfamily.
CC {ECO:0000305}.
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DR EMBL; BC133404; AAI33405.1; -; mRNA.
DR RefSeq; NP_001075064.1; NM_001081595.1.
DR RefSeq; XP_005210930.1; XM_005210873.3.
DR AlphaFoldDB; A2VDU3; -.
DR SMR; A2VDU3; -.
DR STRING; 9913.ENSBTAP00000003401; -.
DR PaxDb; A2VDU3; -.
DR PRIDE; A2VDU3; -.
DR Ensembl; ENSBTAT00000003401; ENSBTAP00000003401; ENSBTAG00000002625.
DR GeneID; 529146; -.
DR KEGG; bta:529146; -.
DR CTD; 6885; -.
DR VEuPathDB; HostDB:ENSBTAG00000002625; -.
DR VGNC; VGNC:31200; MAP3K7.
DR eggNOG; KOG0192; Eukaryota.
DR GeneTree; ENSGT00940000157785; -.
DR HOGENOM; CLU_000288_7_41_1; -.
DR InParanoid; A2VDU3; -.
DR OMA; PARTQCF; -.
DR OrthoDB; 635654at2759; -.
DR TreeFam; TF105116; -.
DR Proteomes; UP000009136; Chromosome 9.
DR Bgee; ENSBTAG00000002625; Expressed in thymus and 106 other tissues.
DR ExpressionAtlas; A2VDU3; baseline.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0004709; F:MAP kinase kinase kinase activity; ISS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007252; P:I-kappaB phosphorylation; ISS:UniProtKB.
DR GO; GO:0007254; P:JNK cascade; ISS:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IBA:GO_Central.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; ISS:UniProtKB.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR017421; MAPKKK7.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR46716; PTHR46716; 2.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PIRSF; PIRSF038168; MAPKKK7; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 2: Evidence at transcript level;
KW Apoptosis; ATP-binding; Cell membrane; Cytoplasm; Isopeptide bond; Kinase;
KW Magnesium; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Stress response;
KW Transcription; Transcription regulation; Transferase; Ubl conjugation.
FT CHAIN 1..579
FT /note="Mitogen-activated protein kinase kinase kinase 7"
FT /id="PRO_0000314284"
FT DOMAIN 36..291
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..300
FT /note="Interaction with MAPK8IP1"
FT /evidence="ECO:0000250"
FT REGION 301..339
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 354..391
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 416..466
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 303..339
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 354..382
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 416..448
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 156
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 42..50
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 63
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 184
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O43318"
FT MOD_RES 187
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O43318"
FT MOD_RES 192
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O43318"
FT MOD_RES 367
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43318"
FT MOD_RES 389
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43318"
FT MOD_RES 412
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43318"
FT MOD_RES 428
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43318"
FT CROSSLNK 72
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:O43318"
FT CROSSLNK 158
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q62073"
FT CROSSLNK 209
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q62073"
SQ 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
