M3K11_MOUSE
ID M3K11_MOUSE Reviewed; 850 AA.
AC Q80XI6; Q8K0M8; Q9JJ15;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 159.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/Ola;
RX PubMed=10894943; DOI=10.1159/000015569;
RA Saridaki A., Ferraz C., Demaille J., Scherer G., Roux A.-F.;
RT "Genomic sequencing reveals the structure of the Kcnk6 and map3k11 genes
RT and their close vicinity to the sipa1 gene on mouse chromosome 19.";
RL Cytogenet. Cell Genet. 89:85-88(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Colon, Eye, and Salivary gland;
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-743, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35; SER-792 AND SER-796, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Kidney, Liver, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP IDENTIFICATION IN A COMPLEX WITH SH3RF1; RAC1; MAPK8; MAPK8IP1 AND MAP2K7.
RX PubMed=23963642; DOI=10.1002/eji.201343635;
RA Cunningham C.A., Knudson K.M., Peng B.J., Teixeiro E., Daniels M.A.;
RT "The POSH/JIP-1 scaffold network regulates TCR-mediated JNK1 signals and
RT effector function in CD8(+) T cells.";
RL Eur. J. Immunol. 43:3361-3371(2013).
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.
CC {ECO:0000250}.
CC -!- SUBUNIT: Homodimer; undergoes dimerization during activation. Interacts
CC with MAP2K4/MKK4 and MAP2K7/MKK7 (By similarity). Found in a complex
CC with SH3RF1, RAC1, MAP2K7/MKK7, MAPK8IP1/JIP1 and MAPK8/JNK1
CC (PubMed:23963642). {ECO:0000250|UniProtKB:Q16584,
CC ECO:0000250|UniProtKB:Q66HA1, ECO:0000269|PubMed:23963642}.
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}.
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DR EMBL; AF155142; AAF73281.1; -; Genomic_DNA.
DR EMBL; BC030928; AAH30928.1; -; mRNA.
DR EMBL; BC047152; AAH47152.1; -; mRNA.
DR EMBL; BC095963; AAH95963.1; -; mRNA.
DR CCDS; CCDS29476.1; -.
DR RefSeq; NP_071295.2; NM_022012.3.
DR RefSeq; XP_006531815.1; XM_006531752.2.
DR AlphaFoldDB; Q80XI6; -.
DR SMR; Q80XI6; -.
DR BioGRID; 204956; 2.
DR IntAct; Q80XI6; 2.
DR STRING; 10090.ENSMUSP00000004156; -.
DR BindingDB; Q80XI6; -.
DR ChEMBL; CHEMBL2434817; -.
DR iPTMnet; Q80XI6; -.
DR PhosphoSitePlus; Q80XI6; -.
DR EPD; Q80XI6; -.
DR jPOST; Q80XI6; -.
DR MaxQB; Q80XI6; -.
DR PaxDb; Q80XI6; -.
DR PeptideAtlas; Q80XI6; -.
DR PRIDE; Q80XI6; -.
DR ProteomicsDB; 292135; -.
DR Antibodypedia; 29871; 317 antibodies from 34 providers.
DR DNASU; 26403; -.
DR Ensembl; ENSMUST00000004156; ENSMUSP00000004156; ENSMUSG00000004054.
DR GeneID; 26403; -.
DR KEGG; mmu:26403; -.
DR UCSC; uc008get.1; mouse.
DR CTD; 4296; -.
DR MGI; MGI:1346880; Map3k11.
DR VEuPathDB; HostDB:ENSMUSG00000004054; -.
DR eggNOG; KOG0192; Eukaryota.
DR GeneTree; ENSGT00940000161064; -.
DR HOGENOM; CLU_000288_7_14_1; -.
DR InParanoid; Q80XI6; -.
DR OMA; WKREIQD; -.
DR OrthoDB; 115270at2759; -.
DR PhylomeDB; Q80XI6; -.
DR TreeFam; TF105118; -.
DR Reactome; R-MMU-5673000; RAF activation.
DR Reactome; R-MMU-9013148; CDC42 GTPase cycle.
DR Reactome; R-MMU-9013408; RHOG GTPase cycle.
DR Reactome; R-MMU-9013424; RHOV GTPase cycle.
DR BioGRID-ORCS; 26403; 3 hits in 75 CRISPR screens.
DR ChiTaRS; Map3k11; mouse.
DR PRO; PR:Q80XI6; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q80XI6; protein.
DR Bgee; ENSMUSG00000004054; Expressed in granulocyte and 211 other tissues.
DR ExpressionAtlas; Q80XI6; baseline and differential.
DR Genevisible; Q80XI6; MM.
DR GO; GO:0005813; C:centrosome; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0005874; C:microtubule; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0004706; F:JUN kinase kinase kinase activity; ISO:MGI.
DR GO; GO:0004709; F:MAP kinase kinase kinase activity; ISO:MGI.
DR GO; GO:0031434; F:mitogen-activated protein kinase kinase binding; ISO:MGI.
DR GO; GO:0031435; F:mitogen-activated protein kinase kinase kinase binding; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:MGI.
DR GO; GO:0031267; F:small GTPase binding; ISO:MGI.
DR GO; GO:0044843; P:cell cycle G1/S phase transition; ISO:MGI.
DR GO; GO:0008219; P:cell death; ISO:MGI.
DR GO; GO:0007254; P:JNK cascade; ISO:MGI.
DR GO; GO:0000165; P:MAPK cascade; ISO:MGI.
DR GO; GO:0007017; P:microtubule-based process; ISO:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0046330; P:positive regulation of JNK cascade; ISO:MGI.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; ISO:MGI.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISO:MGI.
DR GO; GO:0046777; P:protein autophosphorylation; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; ISO:MGI.
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_0000277828"
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 16..35
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 535..644
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 657..850
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 537..552
FT /note="Polar residues"
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 678..694
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 696..710
FT /note="Polar 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:0007744|PubMed:21183079"
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:0000250|UniProtKB:Q16584"
FT MOD_RES 525
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16584"
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 709
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:0007744|PubMed:19144319"
FT MOD_RES 751
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16584"
FT MOD_RES 761
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16584"
FT MOD_RES 773
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16584"
FT MOD_RES 792
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 796
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 818
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16584"
FT CONFLICT 457..458
FT /note="EL -> DV (in Ref. 1; AAF73281)"
FT /evidence="ECO:0000305"
FT CONFLICT 840..841
FT /note="AQ -> CP (in Ref. 1; AAF73281)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 850 AA; 93226 MW; 96DE238A1A0E2564 CRC64;
MEPLKNLFLK SPLGSWNGSG SGGGGGTGGV 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 FRAIQLEPTE
SGQTWGRQSP RRLEDSSNGE RRACWAWGPS SPKPGEAQNG RRRSRMDEAT WYLDSDDSSP
LGSPSTPPAL NGNPPRPSPE PEEPRRAGPT ERGNSSGTPK LIQRALLRGT ALLASLGLGR
DLQPPGGLSR ERGESPTAPP PAQMPSPCPP ELPSTPLIRL SQTTPDAHSS PTPGPLLLDL
GVPSGQPSAK SPRREETRGR TVSPPPGISR SAPGTPGTPR SPPLGLISRP RPSPLRSRID
PWSFVSAGPR PSPLPSPQPA PRRAPWTLFP DSDPFWDSPP ANPFRGGSQD CRTQTKDMGA
QAPWAPEAGP
