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Protein

Mitogen-activated protein kinase kinase kinase 11

Gene

Map3k11

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Enzyme regulationi

Homodimerization via the leucine zipper domains is required for autophosphorylation and subsequent activation (By similarity). Interacts with MAP2K7/MKK4 (By similarity). Interacts with MAP2K7/MKK7.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei145 – 1451ATPPROSITE-ProRule annotation
Active sitei242 – 2421Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi124 – 1329ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: RGD
  • JUN kinase kinase kinase activity Source: RGD
  • MAP kinase kinase kinase activity Source: RGD
  • mitogen-activated protein kinase kinase binding Source: RGD
  • protein serine/threonine kinase activity Source: RGD
  • Rac GTPase binding Source: RGD

GO - Biological processi

  • activation of JNKK activity Source: RGD
  • activation of JUN kinase activity Source: Ensembl
  • cell death Source: RGD
  • cell proliferation Source: Ensembl
  • JNK cascade Source: RGD
  • microtubule-based process Source: Ensembl
  • positive regulation of apoptotic process Source: RGD
  • positive regulation of neuron apoptotic process Source: RGD
  • protein autophosphorylation Source: RGD
  • protein phosphorylation Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-RNO-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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi1359261. Map3k11.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 850850Mitogen-activated protein kinase kinase kinase 11PRO_0000277829Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei11 – 111PhosphoserineBy similarity
Modified residuei35 – 351PhosphoserineBy similarity
Modified residuei278 – 2781Phosphothreonine; by autocatalysisBy similarity
Modified residuei282 – 2821Phosphoserine; by autocatalysis and MAP4K1By similarity
Modified residuei395 – 3951PhosphoserineBy similarity
Modified residuei508 – 5081PhosphoserineCombined sources
Modified residuei525 – 5251PhosphoserineCombined sources
Modified residuei549 – 5491PhosphoserineBy similarity
Modified residuei556 – 5561PhosphoserineBy similarity
Modified residuei557 – 5571PhosphoserineBy similarity
Modified residuei655 – 6551PhosphoserineBy similarity
Modified residuei712 – 7121PhosphothreonineBy similarity
Modified residuei728 – 7281PhosphoserineBy similarity
Modified residuei731 – 7311PhosphoserineBy similarity
Modified residuei743 – 7431PhosphoserineBy similarity
Modified residuei751 – 7511PhosphoserineBy similarity
Modified residuei761 – 7611PhosphoserineCombined sources
Modified residuei773 – 7731PhosphoserineBy similarity
Modified residuei792 – 7921PhosphoserineBy similarity
Modified residuei796 – 7961PhosphoserineBy similarity
Modified residuei818 – 8181PhosphoserineBy similarity

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

PaxDbiQ66HA1.
PRIDEiQ66HA1.

PTM databases

iPTMnetiQ66HA1.
PhosphoSiteiQ66HA1.

Expressioni

Gene expression databases

BgeeiENSRNOG00000020773.
GenevisibleiQ66HA1. RN.

Interactioni

Subunit structurei

Homodimer; undergoes dimerization during activation.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Grik2P422602EBI-4279420,EBI-7809795

GO - Molecular functioni

  • mitogen-activated protein kinase kinase binding Source: RGD
  • Rac GTPase binding Source: RGD

Protein-protein interaction databases

BioGridi259295. 1 interaction.
IntActiQ66HA1. 2 interactions.
STRINGi10116.ENSRNOP00000028185.

Structurei

3D structure databases

ProteinModelPortaliQ66HA1.
SMRiQ66HA1. Positions 43-102.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini42 – 10665SH3PROSITE-ProRule annotationAdd
BLAST
Domaini118 – 380263Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni404 – 42522Leucine-zipper 1Add
BLAST
Regioni439 – 46022Leucine-zipper 2Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi18 – 2912Poly-GlyAdd
BLAST
Compositional biasi473 – 4764Poly-Arg
Compositional biasi600 – 823224Pro-richAdd
BLAST

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 SH3 domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, SH3 domain

Phylogenomic databases

eggNOGiKOG0192. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118807.
HOGENOMiHOG000060081.
HOVERGENiHBG067662.
InParanoidiQ66HA1.
KOiK04419.
OMAiPPPCEVA.
OrthoDBiEOG091G0JNI.
PhylomeDBiQ66HA1.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR001452. SH3_domain.
[Graphical view]
PfamiPF07714. Pkinase_Tyr. 1 hit.
PF14604. SH3_9. 1 hit.
[Graphical view]
PRINTSiPR00452. SH3DOMAIN.
PR00109. TYRKINASE.
SMARTiSM00220. S_TKc. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q66HA1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEPLKNLFLK SPLGSWNGSG SGGGGGSGGV 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 FRAIQLEPAE SGQTWGRQSP
560 570 580 590 600
RRLDDSSNGE RRACWAWGPS SPKPGEAQNG RRRSRMDEAT WYLDSDDSSP
610 620 630 640 650
LGSPSTPPAL NGNPPRPSPE PEEPRRSGPT ERGNSSGTPK LIQRALLRGT
660 670 680 690 700
ALLASLGLGR DLQPPGGLSR ERGESPTAPP PAQMASPCPP DLPSTPLIHL
710 720 730 740 750
SQATPDARGP LTPAPLLLDL GVSSGQPSAK SPRREETRGR TVSPPPGISR
760 770 780 790 800
SAPGTPGTPR SPPLGLISRP RPSPLRNRID PWSFVSAGPR PSPLPSPQPA
810 820 830 840 850
PRRAPWTLFP DSDPFWDSPP ANPFRGGSQD CRTQTKDVGA QAPWAPEAGP
Length:850
Mass (Da):93,109
Last modified:October 11, 2004 - v1
Checksum:i81ECA45841BDB379
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC081952 mRNA. Translation: AAH81952.1.
AY240868 mRNA. Translation: AAO91627.1.
RefSeqiNP_001013168.1. NM_001013150.1.
UniGeneiRn.28235.

Genome annotation databases

EnsembliENSRNOT00000028185; ENSRNOP00000028185; ENSRNOG00000020773.
GeneIDi309168.
KEGGirno:309168.
UCSCiRGD:1359261. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC081952 mRNA. Translation: AAH81952.1.
AY240868 mRNA. Translation: AAO91627.1.
RefSeqiNP_001013168.1. NM_001013150.1.
UniGeneiRn.28235.

3D structure databases

ProteinModelPortaliQ66HA1.
SMRiQ66HA1. Positions 43-102.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi259295. 1 interaction.
IntActiQ66HA1. 2 interactions.
STRINGi10116.ENSRNOP00000028185.

PTM databases

iPTMnetiQ66HA1.
PhosphoSiteiQ66HA1.

Proteomic databases

PaxDbiQ66HA1.
PRIDEiQ66HA1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000028185; ENSRNOP00000028185; ENSRNOG00000020773.
GeneIDi309168.
KEGGirno:309168.
UCSCiRGD:1359261. rat.

Organism-specific databases

CTDi4296.
RGDi1359261. Map3k11.

Phylogenomic databases

eggNOGiKOG0192. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118807.
HOGENOMiHOG000060081.
HOVERGENiHBG067662.
InParanoidiQ66HA1.
KOiK04419.
OMAiPPPCEVA.
OrthoDBiEOG091G0JNI.
PhylomeDBiQ66HA1.

Enzyme and pathway databases

ReactomeiR-RNO-5673000. RAF activation.

Miscellaneous databases

PROiQ66HA1.

Gene expression databases

BgeeiENSRNOG00000020773.
GenevisibleiQ66HA1. RN.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR001452. SH3_domain.
[Graphical view]
PfamiPF07714. Pkinase_Tyr. 1 hit.
PF14604. SH3_9. 1 hit.
[Graphical view]
PRINTSiPR00452. SH3DOMAIN.
PR00109. TYRKINASE.
SMARTiSM00220. S_TKc. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiM3K11_RAT
AccessioniPrimary (citable) accession number: Q66HA1
Secondary accession number(s): Q80YF1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: October 11, 2004
Last modified: September 7, 2016
This is version 113 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.