M3K11_RAT
ID M3K11_RAT Reviewed; 850 AA.
AC Q66HA1; Q80YF1;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Mitogen-activated protein kinase kinase kinase 11;
DE EC=2.7.11.25;
DE AltName: Full=Mixed lineage kinase 3;
GN Name=Map3k11; Synonyms=Mlk3;
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 [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 778-850.
RC STRAIN=Sprague-Dawley;
RX PubMed=14690535; DOI=10.1046/j.1471-4159.2003.02176.x;
RA Ganguly A., Oo T.F., Rzhetskaya M., Pratt R., Yarygina O., Momoi T.,
RA Kholodilov N., Burke R.E.;
RT "CEP11004, a novel inhibitor of the mixed lineage kinases, suppresses
RT apoptotic death in dopamine neurons of the substantia nigra induced by 6-
RT hydroxydopamine.";
RL J. Neurochem. 88:469-480(2004).
RN [3]
RP INTERACTION WITH MAP2K7/MKK7.
RX PubMed=14575811; DOI=10.1016/j.lfs.2003.06.025;
RA Zhang Q., Tian H., Fu X., Zhang G.;
RT "Delayed activation and regulation of MKK7 in hippocampal CA1 region
RT following global cerebral ischemia in rats.";
RL Life Sci. 74:37-45(2003).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-508; SER-525 AND SER-761, 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: Activates the JUN N-terminal pathway. Required for serum-
CC stimulated cell proliferation and for mitogen and cytokine activation
CC of MAPK14 (p38), MAPK3 (ERK) and MAPK8 (JNK1) through phosphorylation
CC and activation of MAP2K4/MKK4 and MAP2K7/MKK7. Plays a role in mitogen-
CC stimulated phosphorylation and activation of BRAF, but does not
CC phosphorylate BRAF directly. Influences microtubule organization during
CC the cell cycle (By similarity). {ECO:0000250}.
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; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Homodimerization via the leucine zipper domains is
CC required for autophosphorylation and subsequent activation (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer; undergoes dimerization during activation. Interacts
CC with MAP2K4/MKK4 (By similarity). Interacts with MAP2K7/MKK7
CC (PubMed:14575811). Found in a complex with SH3RF1, RAC1, MAP2K7/MKK7,
CC MAPK8IP1/JIP1 and MAPK8/JNK1 (By similarity).
CC {ECO:0000250|UniProtKB:Q80XI6, ECO:0000269|PubMed:14575811}.
CC -!- INTERACTION:
CC Q66HA1; P42260: Grik2; NbExp=2; IntAct=EBI-4279420, EBI-7809795;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing
CC center, centrosome. Note=Location is cell cycle dependent.
CC {ECO:0000250}.
CC -!- PTM: Autophosphorylation on serine and threonine residues within the
CC activation loop plays a role in enzyme activation. Thr-278 is likely to
CC be the main autophosphorylation site. Phosphorylation of Ser-556 and
CC Ser-557 is induced by CDC42 (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. MAP kinase kinase kinase subfamily.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BC081952; AAH81952.1; -; mRNA.
DR EMBL; AY240868; AAO91627.1; -; mRNA.
DR RefSeq; NP_001013168.1; NM_001013150.1.
DR AlphaFoldDB; Q66HA1; -.
DR SMR; Q66HA1; -.
DR BioGRID; 259295; 3.
DR IntAct; Q66HA1; 2.
DR MINT; Q66HA1; -.
DR STRING; 10116.ENSRNOP00000028185; -.
DR iPTMnet; Q66HA1; -.
DR PhosphoSitePlus; Q66HA1; -.
DR PaxDb; Q66HA1; -.
DR PRIDE; Q66HA1; -.
DR Ensembl; ENSRNOT00000028185; ENSRNOP00000028185; ENSRNOG00000020773.
DR GeneID; 309168; -.
DR KEGG; rno:309168; -.
DR UCSC; RGD:1359261; rat.
DR CTD; 4296; -.
DR RGD; 1359261; Map3k11.
DR eggNOG; KOG0192; Eukaryota.
DR GeneTree; ENSGT00940000161064; -.
DR HOGENOM; CLU_000288_7_14_1; -.
DR InParanoid; Q66HA1; -.
DR OMA; WKREIQD; -.
DR OrthoDB; 115270at2759; -.
DR PhylomeDB; Q66HA1; -.
DR Reactome; R-RNO-5673000; RAF activation.
DR Reactome; R-RNO-9013148; CDC42 GTPase cycle.
DR Reactome; R-RNO-9013408; RHOG GTPase cycle.
DR Reactome; R-RNO-9013424; RHOV GTPase cycle.
DR PRO; PR:Q66HA1; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000020773; Expressed in jejunum and 19 other tissues.
DR Genevisible; Q66HA1; RN.
DR GO; GO:0005813; C:centrosome; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0005874; C:microtubule; ISO:RGD.
DR GO; GO:0005524; F:ATP binding; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0004706; F:JUN kinase kinase kinase activity; IDA:RGD.
DR GO; GO:0004709; F:MAP kinase kinase kinase activity; IDA:RGD.
DR GO; GO:0031434; F:mitogen-activated protein kinase kinase binding; IPI:RGD.
DR GO; GO:0031435; F:mitogen-activated protein kinase kinase kinase binding; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:RGD.
DR GO; GO:0031267; F:small GTPase binding; IPI:RGD.
DR GO; GO:0044843; P:cell cycle G1/S phase transition; ISO:RGD.
DR GO; GO:0008219; P:cell death; IMP:RGD.
DR GO; GO:0007254; P:JNK cascade; IDA:RGD.
DR GO; GO:0000165; P:MAPK cascade; ISO:RGD.
DR GO; GO:0007017; P:microtubule-based process; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; 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; ISO:RGD.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IMP:RGD.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:RGD.
DR GO; GO:0006468; P:protein phosphorylation; IDA:RGD.
DR CDD; cd12059; SH3_MLK1-3; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR035779; MLK1-3_SH3.
DR InterPro; IPR016231; MLK1-4.
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 InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF14604; SH3_9; 1.
DR PIRSF; PIRSF000556; MAPKKK9_11; 1.
DR PRINTS; PR00452; SH3DOMAIN.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00220; S_TKc; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF50044; SSF50044; 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; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cytoplasm; Cytoskeleton; Kinase; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; SH3 domain; Transferase.
FT CHAIN 1..850
FT /note="Mitogen-activated protein kinase kinase kinase 11"
FT /id="PRO_0000277829"
FT DOMAIN 42..106
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 118..380
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 18..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 404..425
FT /note="Leucine-zipper 1"
FT REGION 439..460
FT /note="Leucine-zipper 2"
FT REGION 536..850
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 578..592
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 680..694
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 749..769
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 788..804
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 242
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 124..132
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 145
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 11
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16584"
FT MOD_RES 35
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80XI6"
FT MOD_RES 278
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q16584"
FT MOD_RES 282
FT /note="Phosphoserine; by autocatalysis and MAP4K1"
FT /evidence="ECO:0000250|UniProtKB:Q16584"
FT MOD_RES 395
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16584"
FT MOD_RES 508
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 525
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 549
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16584"
FT MOD_RES 556
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16584"
FT MOD_RES 557
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16584"
FT MOD_RES 655
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16584"
FT MOD_RES 712
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q16584"
FT MOD_RES 728
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16584"
FT MOD_RES 731
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16584"
FT MOD_RES 743
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16584"
FT MOD_RES 751
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16584"
FT MOD_RES 761
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 773
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16584"
FT MOD_RES 792
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16584"
FT MOD_RES 796
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16584"
FT MOD_RES 818
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16584"
SQ SEQUENCE 850 AA; 93109 MW; 81ECA45841BDB379 CRC64;
MEPLKNLFLK SPLGSWNGSG SGGGGGSGGV RPEGSPKATA AYANPVWTAL FDYEPNGQDE
LALRKGDRVE VLSRDAAISG DEGWWAGQVG GQVGIFPSNY VSRGGGPPPC EVASFQELRL
EEVIGIGGFG KVYRGSWRGE LVAVKAARQD PDEDISVTAE SVRQEARLFA MLAHPNIIAL
KAVCLEEPNL CLVMEYAAGG PLSRALAGRR VPPHVLVNWA VQIARGMHYL HCEALVPVIH
RDLKSNNILL LQPIEGDDME HKTLKITDFG LAREWHKTTQ MSAAGTYAWM APEVIKASTF
SKGSDVWSFG VLLWELLTGE VPYRGIDCLA VAYGVAVNKL TLPIPSTCPE PFAQLMADCW
AQDPHRRPDF ASILQQLEAL EAQVLREMPR DSFHSMQEGW KREIQGLFDE LRAKEKELLS
REEELTRAAR EQRSQAEQLR RREHLLAQWE LEVFERELTL LLQQVDRERP HVRRRRGTFK
RSKLRARDGG ERISMPLDFK HRITVQASPG LDRRRNVFEV GAGDSPTFPR FRAIQLEPAE
SGQTWGRQSP RRLDDSSNGE RRACWAWGPS SPKPGEAQNG RRRSRMDEAT WYLDSDDSSP
LGSPSTPPAL NGNPPRPSPE PEEPRRSGPT ERGNSSGTPK LIQRALLRGT ALLASLGLGR
DLQPPGGLSR ERGESPTAPP PAQMASPCPP DLPSTPLIHL SQATPDARGP LTPAPLLLDL
GVSSGQPSAK SPRREETRGR TVSPPPGISR SAPGTPGTPR SPPLGLISRP RPSPLRNRID
PWSFVSAGPR PSPLPSPQPA PRRAPWTLFP DSDPFWDSPP ANPFRGGSQD CRTQTKDVGA
QAPWAPEAGP
