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Protein

Mitogen-activated protein kinase kinase kinase 11

Gene

Map3k11

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Activates the JUN N-terminal pathway. Required for serum-stimulated cell proliferation and for mitogen and cytokine activation of MAPK14 (p38), MAPK3 (ERK) and MAPK8 (JNK1) through phosphorylation and activation of MAP2K4/MKK4 and MAP2K7/MKK7. Plays a role in mitogen-stimulated phosphorylation and activation of BRAF, but does not phosphorylate BRAF directly. Influences microtubule organization during the cell cycle (By similarity).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Activity regulationi

Homodimerization via the leucine zipper domains is required for autophosphorylation and subsequent activation.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei145ATPPROSITE-ProRule annotation1
Active sitei242Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi124 – 132ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-5673000 RAF activation

Names & Taxonomyi

Protein namesi
Recommended name:
Mitogen-activated protein kinase kinase kinase 11 (EC:2.7.11.25)
Alternative name(s):
Mixed lineage kinase 3
Gene namesi
Name:Map3k11
Synonyms:Mlk3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:1346880 Map3k11

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2434817

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002778281 – 850Mitogen-activated protein kinase kinase kinase 11Add BLAST850

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei11PhosphoserineBy similarity1
Modified residuei35PhosphoserineCombined sources1
Modified residuei278Phosphothreonine; by autocatalysisBy similarity1
Modified residuei282Phosphoserine; by autocatalysis and MAP4K1By similarity1
Modified residuei395PhosphoserineBy similarity1
Modified residuei508PhosphoserineBy similarity1
Modified residuei525PhosphoserineBy similarity1
Modified residuei549PhosphoserineBy similarity1
Modified residuei556PhosphoserineBy similarity1
Modified residuei557PhosphoserineBy similarity1
Modified residuei655PhosphoserineBy similarity1
Modified residuei709PhosphoserineBy similarity1
Modified residuei712PhosphothreonineBy similarity1
Modified residuei728PhosphoserineBy similarity1
Modified residuei731PhosphoserineBy similarity1
Modified residuei743PhosphoserineCombined sources1
Modified residuei751PhosphoserineBy similarity1
Modified residuei761PhosphoserineBy similarity1
Modified residuei773PhosphoserineBy similarity1
Modified residuei792PhosphoserineCombined sources1
Modified residuei796PhosphoserineCombined sources1
Modified residuei818PhosphoserineBy similarity1

Post-translational modificationi

Autophosphorylation on serine and threonine residues within the activation loop plays a role in enzyme activation. Thr-278 is likely to be the main autophosphorylation site. Phosphorylation of Ser-556 and Ser-557 is induced by CDC42 (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ80XI6
PaxDbiQ80XI6
PeptideAtlasiQ80XI6
PRIDEiQ80XI6

PTM databases

iPTMnetiQ80XI6
PhosphoSitePlusiQ80XI6

Expressioni

Gene expression databases

BgeeiENSMUSG00000004054 Expressed in 233 organ(s), highest expression level in external carotid artery
CleanExiMM_MAP3K11
GenevisibleiQ80XI6 MM

Interactioni

Subunit structurei

Homodimer; undergoes dimerization during activation. Interacts with MAP2K4/MKK4 and MAP2K7/MKK7 (By similarity). Found in a complex with SH3RF1, RAC1, MAP2K7/MKK7, MAPK8IP1/JIP1 and MAPK8/JNK1 (PubMed:23963642).By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi204956, 2 interactors
IntActiQ80XI6, 2 interactors
STRINGi10090.ENSMUSP00000004156

Chemistry databases

BindingDBiQ80XI6

Structurei

3D structure databases

ProteinModelPortaliQ80XI6
SMRiQ80XI6
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini42 – 106SH3PROSITE-ProRule annotationAdd BLAST65
Domaini118 – 380Protein kinasePROSITE-ProRule annotationAdd BLAST263

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni404 – 425Leucine-zipper 1Add BLAST22
Regioni439 – 460Leucine-zipper 2Add BLAST22

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi18 – 29Poly-GlyAdd BLAST12
Compositional biasi473 – 476Poly-Arg4
Compositional biasi600 – 823Pro-richAdd BLAST224

Sequence similaritiesi

Keywords - Domaini

Repeat, SH3 domain

Phylogenomic databases

eggNOGiKOG0192 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00900000140790
HOGENOMiHOG000060081
HOVERGENiHBG067662
InParanoidiQ80XI6
KOiK04419
OMAiYANPVWT
OrthoDBiEOG091G0JNI
PhylomeDBiQ80XI6
TreeFamiTF105118

Family and domain databases

CDDicd12059 SH3_MLK1-3, 1 hit
InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR035779 MLK1-3_SH3
IPR016231 MLK1-4
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR008271 Ser/Thr_kinase_AS
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
PfamiView protein in Pfam
PF07714 Pkinase_Tyr, 1 hit
PF14604 SH3_9, 1 hit
PIRSFiPIRSF000556 MAPKKK9_11, 1 hit
PRINTSiPR00452 SH3DOMAIN
PR00109 TYRKINASE
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SM00326 SH3, 1 hit
SUPFAMiSSF50044 SSF50044, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
PS50002 SH3, 1 hit

Sequencei

Sequence statusi: Complete.

Q80XI6-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MEPLKNLFLK SPLGSWNGSG SGGGGGTGGV RPEGSPKATA AYANPVWTAL
60 70 80 90 100
FDYEPNGQDE LALRKGDRVE VLSRDAAISG DEGWWAGQVG GQVGIFPSNY
110 120 130 140 150
VSRGGGPPPC EVASFQELRL EEVIGIGGFG KVYRGSWRGE LVAVKAARQD
160 170 180 190 200
PDEDISVTAE SVRQEARLFA MLAHPNIIAL KAVCLEEPNL CLVMEYAAGG
210 220 230 240 250
PLSRALAGRR VPPHVLVNWA VQIARGMHYL HCEALVPVIH RDLKSNNILL
260 270 280 290 300
LQPIEGDDME HKTLKITDFG LAREWHKTTQ MSAAGTYAWM APEVIKASTF
310 320 330 340 350
SKGSDVWSFG VLLWELLTGE VPYRGIDCLA VAYGVAVNKL TLPIPSTCPE
360 370 380 390 400
PFAQLMADCW AQDPHRRPDF ASILQQLEAL EAQVLREMPR DSFHSMQEGW
410 420 430 440 450
KREIQGLFDE LRAKEKELLS REEELTRAAR EQRSQAEQLR RREHLLAQWE
460 470 480 490 500
LEVFERELTL LLQQVDRERP HVRRRRGTFK RSKLRARDGG ERISMPLDFK
510 520 530 540 550
HRITVQASPG LDRRRNVFEV GAGDSPTFPR FRAIQLEPTE SGQTWGRQSP
560 570 580 590 600
RRLEDSSNGE RRACWAWGPS SPKPGEAQNG RRRSRMDEAT WYLDSDDSSP
610 620 630 640 650
LGSPSTPPAL NGNPPRPSPE PEEPRRAGPT ERGNSSGTPK LIQRALLRGT
660 670 680 690 700
ALLASLGLGR DLQPPGGLSR ERGESPTAPP PAQMPSPCPP ELPSTPLIRL
710 720 730 740 750
SQTTPDAHSS PTPGPLLLDL GVPSGQPSAK SPRREETRGR TVSPPPGISR
760 770 780 790 800
SAPGTPGTPR SPPLGLISRP RPSPLRSRID PWSFVSAGPR PSPLPSPQPA
810 820 830 840 850
PRRAPWTLFP DSDPFWDSPP ANPFRGGSQD CRTQTKDMGA QAPWAPEAGP
Length:850
Mass (Da):93,226
Last modified:June 1, 2003 - v1
Checksum:i96DE238A1A0E2564
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti457 – 458EL → DV in AAF73281 (PubMed:10894943).Curated2
Sequence conflicti840 – 841AQ → CP in AAF73281 (PubMed:10894943).Curated2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF155142 Genomic DNA Translation: AAF73281.1
BC030928 mRNA Translation: AAH30928.1
BC047152 mRNA Translation: AAH47152.1
BC095963 mRNA Translation: AAH95963.1
CCDSiCCDS29476.1
RefSeqiNP_071295.2, NM_022012.3
XP_006531815.1, XM_006531752.2
UniGeneiMm.185026

Genome annotation databases

EnsembliENSMUST00000004156; ENSMUSP00000004156; ENSMUSG00000004054
GeneIDi26403
KEGGimmu:26403
UCSCiuc008get.1 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF155142 Genomic DNA Translation: AAF73281.1
BC030928 mRNA Translation: AAH30928.1
BC047152 mRNA Translation: AAH47152.1
BC095963 mRNA Translation: AAH95963.1
CCDSiCCDS29476.1
RefSeqiNP_071295.2, NM_022012.3
XP_006531815.1, XM_006531752.2
UniGeneiMm.185026

3D structure databases

ProteinModelPortaliQ80XI6
SMRiQ80XI6
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204956, 2 interactors
IntActiQ80XI6, 2 interactors
STRINGi10090.ENSMUSP00000004156

Chemistry databases

BindingDBiQ80XI6
ChEMBLiCHEMBL2434817

PTM databases

iPTMnetiQ80XI6
PhosphoSitePlusiQ80XI6

Proteomic databases

MaxQBiQ80XI6
PaxDbiQ80XI6
PeptideAtlasiQ80XI6
PRIDEiQ80XI6

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000004156; ENSMUSP00000004156; ENSMUSG00000004054
GeneIDi26403
KEGGimmu:26403
UCSCiuc008get.1 mouse

Organism-specific databases

CTDi4296
MGIiMGI:1346880 Map3k11

Phylogenomic databases

eggNOGiKOG0192 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00900000140790
HOGENOMiHOG000060081
HOVERGENiHBG067662
InParanoidiQ80XI6
KOiK04419
OMAiYANPVWT
OrthoDBiEOG091G0JNI
PhylomeDBiQ80XI6
TreeFamiTF105118

Enzyme and pathway databases

ReactomeiR-MMU-5673000 RAF activation

Miscellaneous databases

ChiTaRSiMap3k11 mouse
PROiPR:Q80XI6
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000004054 Expressed in 233 organ(s), highest expression level in external carotid artery
CleanExiMM_MAP3K11
GenevisibleiQ80XI6 MM

Family and domain databases

CDDicd12059 SH3_MLK1-3, 1 hit
InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR035779 MLK1-3_SH3
IPR016231 MLK1-4
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR008271 Ser/Thr_kinase_AS
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
PfamiView protein in Pfam
PF07714 Pkinase_Tyr, 1 hit
PF14604 SH3_9, 1 hit
PIRSFiPIRSF000556 MAPKKK9_11, 1 hit
PRINTSiPR00452 SH3DOMAIN
PR00109 TYRKINASE
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SM00326 SH3, 1 hit
SUPFAMiSSF50044 SSF50044, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
PS50002 SH3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiM3K11_MOUSE
AccessioniPrimary (citable) accession number: Q80XI6
Secondary accession number(s): Q8K0M8, Q9JJ15
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: June 1, 2003
Last modified: September 12, 2018
This is version 139 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  2. SIMILARITY comments
    Index of protein domains and families
  3. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health

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