M3K1_RAT
ID M3K1_RAT Reviewed; 1493 AA.
AC Q62925;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Mitogen-activated protein kinase kinase kinase 1;
DE EC=2.7.11.25;
DE AltName: Full=MAPK/ERK kinase kinase 1;
DE Short=MEK kinase 1;
DE Short=MEKK 1;
GN Name=Map3k1; Synonyms=Mekk, Mekk1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP ASP-1369.
RC TISSUE=Brain;
RX PubMed=8643568; DOI=10.1073/pnas.93.11.5291;
RA Xu S., Robbins D.J., Christerson L.B., English J.M., Vanderbilt C.A.,
RA Cobb M.H.;
RT "Cloning of rat MEK kinase 1 cDNA reveals an endogenous membrane-associated
RT 195-kDa protein with a large regulatory domain.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:5291-5295(1996).
RN [2]
RP FUNCTION, ACTIVITY REGULATION, OLIGOMERIZATION, PHOSPHORYLATION AT THR-1381
RP AND THR-1393, AND MUTAGENESIS OF ASP-1350; THR-1381 AND THR-1393.
RX PubMed=11784851; DOI=10.1128/mcb.22.3.737-749.2002;
RA Chadee D.N., Yuasa T., Kyriakis J.M.;
RT "Direct activation of mitogen-activated protein kinase kinase kinase MEKK1
RT by the Ste20p homologue GCK and the adapter protein TRAF2.";
RL Mol. Cell. Biol. 22:737-749(2002).
RN [3]
RP INTERACTION WITH GRIPAP1.
RX PubMed=17761173; DOI=10.1016/j.febslet.2007.08.008;
RA Ye B., Yu W.P., Thomas G.M., Huganir R.L.;
RT "GRASP-1 is a neuronal scaffold protein for the JNK signaling pathway.";
RL FEBS Lett. 581:4403-4410(2007).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-137 AND SER-910, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Component of a protein kinase signal transduction cascade
CC (PubMed:11784851). Activates the ERK and JNK kinase pathways by
CC phosphorylation of MAP2K1 and MAP2K4 (PubMed:11784851). May
CC phosphorylate the MAPK8/JNK1 kinase (By similarity). Activates CHUK and
CC IKBKB, the central protein kinases of the NF-kappa-B pathway
CC (PubMed:11784851). {ECO:0000250|UniProtKB:P53349,
CC ECO:0000269|PubMed:11784851}.
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 -!- 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;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- ACTIVITY REGULATION: Activated by autophosphorylation on Thr-1381 and
CC Thr-1393 following oligomerization. {ECO:0000269|PubMed:11784851}.
CC -!- SUBUNIT: Binds both upstream activators and downstream substrates in
CC multimolecular complexes through its N-terminus. Oligomerizes after
CC binding MAP4K2 or TRAF2. Interacts (via the kinase catalytic domain)
CC with STK38 (By similarity). Interacts with GRIPAP1 (PubMed:17761173).
CC {ECO:0000250|UniProtKB:Q13233, ECO:0000269|PubMed:17761173}.
CC -!- INTERACTION:
CC Q62925; Q12933: TRAF2; Xeno; NbExp=2; IntAct=EBI-636664, EBI-355744;
CC Q62925; P61088: UBE2N; Xeno; NbExp=46; IntAct=EBI-636664, EBI-1052908;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:8643568}; Peripheral
CC membrane protein {ECO:0000269|PubMed:8643568}.
CC -!- TISSUE SPECIFICITY: Most highly expressed in spleen, kidney and lung.
CC -!- PTM: Autophosphorylated. {ECO:0000269|PubMed:11784851}.
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; U48596; AAC52596.1; -; mRNA.
DR PIR; T10757; T10757.
DR RefSeq; NP_446339.1; NM_053887.1.
DR AlphaFoldDB; Q62925; -.
DR SMR; Q62925; -.
DR BioGRID; 250551; 1.
DR IntAct; Q62925; 85.
DR MINT; Q62925; -.
DR STRING; 10116.ENSRNOP00000017968; -.
DR iPTMnet; Q62925; -.
DR PhosphoSitePlus; Q62925; -.
DR PaxDb; Q62925; -.
DR PRIDE; Q62925; -.
DR GeneID; 116667; -.
DR KEGG; rno:116667; -.
DR CTD; 4214; -.
DR RGD; 620966; Map3k1.
DR eggNOG; KOG0198; Eukaryota.
DR InParanoid; Q62925; -.
DR OrthoDB; 797346at2759; -.
DR PhylomeDB; Q62925; -.
DR BRENDA; 2.7.12.2; 5301.
DR Reactome; R-RNO-166058; MyD88:MAL(TIRAP) cascade initiated on plasma membrane.
DR Reactome; R-RNO-2871796; FCERI mediated MAPK activation.
DR Reactome; R-RNO-975138; TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation.
DR Reactome; R-RNO-975871; MyD88 cascade initiated on plasma membrane.
DR PRO; PR:Q62925; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0031941; C:filamentous actin; ISO:RGD.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008092; F:cytoskeletal protein binding; ISO:RGD.
DR GO; GO:0008432; F:JUN kinase binding; IPI:RGD.
DR GO; GO:0004706; F:JUN kinase kinase kinase activity; IDA:RGD.
DR GO; GO:0004708; F:MAP kinase kinase activity; ISO:RGD.
DR GO; GO:0004709; F:MAP kinase kinase kinase activity; IDA:RGD.
DR GO; GO:0051019; F:mitogen-activated protein kinase binding; IPI:RGD.
DR GO; GO:0031434; F:mitogen-activated protein kinase kinase binding; IPI:RGD.
DR GO; GO:0004672; F:protein kinase activity; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0046625; F:sphingolipid binding; IPI:RGD.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IMP:RGD.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0008637; P:apoptotic mitochondrial changes; ISO:RGD.
DR GO; GO:0043010; P:camera-type eye development; ISO:RGD.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; ISO:RGD.
DR GO; GO:0003382; P:epithelial cell morphogenesis; ISO:RGD.
DR GO; GO:0061029; P:eyelid development in camera-type eye; ISO:RGD.
DR GO; GO:0007254; P:JNK cascade; ISO:RGD.
DR GO; GO:0000165; P:MAPK cascade; IDA:RGD.
DR GO; GO:0002011; P:morphogenesis of an epithelial sheet; ISO:RGD.
DR GO; GO:0032232; P:negative regulation of actin filament bundle assembly; IDA:RGD.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:RGD.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IMP:RGD.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IDA:RGD.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; IDA:RGD.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IDA:RGD.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:RGD.
DR GO; GO:0050434; P:positive regulation of viral transcription; IDA:RGD.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:RGD.
DR GO; GO:0006468; P:protein phosphorylation; IDA:RGD.
DR GO; GO:0000209; P:protein polyubiquitination; IMP:RGD.
DR GO; GO:0030334; P:regulation of cell migration; ISO:RGD.
DR GO; GO:0006970; P:response to osmotic stress; IMP:RGD.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISO:RGD.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IGI:RGD.
DR GO; GO:0042060; P:wound healing; ISO:RGD.
DR Gene3D; 1.25.10.10; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR007527; Znf_SWIM.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF48371; SSF48371; 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.
DR PROSITE; PS50089; ZF_RING_2; 1.
DR PROSITE; PS50966; ZF_SWIM; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Kinase; Magnesium; Membrane; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q13233"
FT CHAIN 2..1493
FT /note="Mitogen-activated protein kinase kinase kinase 1"
FT /id="PRO_0000086242"
FT DOMAIN 1224..1489
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ZN_FING 328..356
FT /note="SWIM-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00325"
FT ZN_FING 433..482
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 1..171
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 222..295
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 496..524
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 866..910
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 923..955
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 992..1060
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 49..70
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 154..171
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 866..882
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 924..955
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 996..1037
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1350
FT /note="Proton acceptor"
FT BINDING 1230..1238
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 1253
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q13233"
FT MOD_RES 21
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13233"
FT MOD_RES 137
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 265
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13233"
FT MOD_RES 275
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q13233"
FT MOD_RES 282
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13233"
FT MOD_RES 287
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13233"
FT MOD_RES 290
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13233"
FT MOD_RES 497
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13233"
FT MOD_RES 521
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13233"
FT MOD_RES 910
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 999
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13233"
FT MOD_RES 1024
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13233"
FT MOD_RES 1381
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:11784851"
FT MOD_RES 1393
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:11784851"
FT MUTAGEN 1350
FT /note="D->N: Loss of kinase activity and of
FT autophosphorylation activity."
FT /evidence="ECO:0000269|PubMed:11784851"
FT MUTAGEN 1369
FT /note="D->A: Inactivation."
FT /evidence="ECO:0000269|PubMed:8643568"
FT MUTAGEN 1381
FT /note="T->A: Loss of kinase activity and activation by
FT autophosphorylation; when associated with T-1393."
FT /evidence="ECO:0000269|PubMed:11784851"
FT MUTAGEN 1393
FT /note="T->A: Loss of kinase activity and activation by
FT autophosphorylation; when associated with T-1381."
FT /evidence="ECO:0000269|PubMed:11784851"
SQ SEQUENCE 1493 AA; 161315 MW; 8C5F29F866898524 CRC64;
MAAAAGDRAS SSGFPGAAAA SPEAGGGGGA LQGSGAPAAG AGLLRETGSA GRERADWRRQ
QLRKVRSVEL DQLPEQPLFL TASPPCPSTS PSPEPADAAA GASGFQPAAG PPPPGAASRC
GSHSAELAAA RDSGARSPAG AEPPSAAAPS GREMENKETL KGLHKMDDRP EERMIREKLK
ATCMPAWKHE WLERRNRRGP VVVKPIPIKG DGSEMSNLAA ELQGEGQAGS AAPAPKGRRS
PSPGSSPSGR SGKPESPGVR RKRVSPVPFQ SGRITPPRRA PSPDGFSPYS PEETSRRVNK
VMRARLYLLQ QIGPNSFLIG GDSPDNKYRV FIGPQNCSCG RGTFCIHLLF VMLRVFQLEP
SDPMLWRKTL KNFEVESLFQ KYHSRRSSRI KAPSRNTIQK FVSRMSNCHT LSSSSTSTSS
SENSIKDEEE QMCPICLLGM LDEESLTVCE DGCRNKLHHH CMSIWAEECR RNREPLICPL
CRSKWRSHDF YSHELSSPVD SPTSLRGVQQ PSSPQQPVAG SQRRNQESNF NLTHYGTQQI
PPAYKDLAEP WIQAFGMELV GCLFSRNWNV REMALRRLSH DVSGALLLAN GESTGTSGGG
SGGSLSAGAA SGSSQPSISG DVVEAFCSVL SIVCADPVYK VYVAALKTLR AMLVYTPCHS
LAERIKLQRL LRPVVDTILV KCADANSRTS QLSISTLLEL CKGQAGELAV GREILKAGSI
GVGGVDYVLS CILGNQAESN NWQELLGRLC LIDRLLLEIS AEFYPHIVST DVSQAEPVEI
RYKKLLSLLA FALQSIDNSH SMVGKLSRRI YLSSARMVTT VPPLFSKLVT MLSASGSSHF
ARMRRRLMAI ADEVEIAEVI QLGSEDTLDG QQDSSQALAP PRYPESSSLE HTAHVEKTGK
GLKATRLSAS SEDISDRLAG VSVGLPSSAT TEQPKPTVQT KGRPHSQCLN SSPLSPPQLM
FPAISAPCSS APSVPAGSVT DASKHRPRAF VPCKIPSASP QTQRKFSLQF QRTCSENRDS
EKLSPVFTQS RPPPSSNIHR AKASRPVPGS TSKLGDASKN SMTLDLNSAS QCDDSFGSGS
NSGSAVIPSE ETAFTPAEDK CRLDVNPELN SSIEDLLEAS MPSSDTTVTF KSEVAVLSPE
KAESDDTYKD DVNHNQKCKE KMEAEEEEAL AIAMAMSASQ DALPIVPQLQ VENGEDIIII
QQDTPETLPG HTKANEPYRE DTEWLKGQQI GLGAFSSCYQ AQDVGTGTLM AVKQVTYVRN
TSSEQEEVVE ALREEIRMMS HLNHPNIIRM LGATCEKSNY NLFIEWMAGA SVAHLLSKYG
AFKESVVINY TEQLLRGLSY LHENQIIHRD VKGANLLIDS TGQRLRIADF GAAARLASKG
TGAGEFQGQL LGTIAFMAPE VLRGQQYGRS CDVWSVGCAI IEMACAKPPW NAEKHSNHLA
LIFKIASATT APSIPSHLSP GLRDVALRCL ELQPQDRPPS RELLKHPVFR TTW
