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Protein

Mitogen-activated protein kinase kinase kinase 12

Gene

Map3k12

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

May be an activator of the JNK/SAPK pathway. Phosphorylates beta-casein, histone 1 and myelin basic protein in vitro.

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei185ATP1
Active sitei269Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi164 – 172ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • MAP kinase kinase kinase activity Source: UniProtKB-EC
  • protein homodimerization activity Source: UniProtKB
  • protein kinase binding Source: MGI
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  • histone phosphorylation Source: UniProtKB
  • JNK cascade Source: InterPro
  • mitophagy in response to mitochondrial depolarization Source: Ensembl
  • negative regulation of motor neuron apoptotic process Source: MGI
  • peptidyl-serine phosphorylation Source: UniProtKB
  • peptidyl-threonine phosphorylation Source: UniProtKB
  • protein autophosphorylation Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Magnesium, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Mitogen-activated protein kinase kinase kinase 12 (EC:2.7.11.25)
Alternative name(s):
Dual leucine zipper bearing kinase
Short name:
DLK
Leucine-zipper protein kinase
Short name:
ZPK
MAPK-upstream kinase
Short name:
MUK
Mixed lineage kinase
Gene namesi
Name:Map3k12
Synonyms:Zpk
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:1346881. Map3k12.

Subcellular locationi

GO - Cellular componenti

  • axon Source: MGI
  • cytosol Source: UniProtKB
  • growth cone Source: MGI
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi185K → A: Loss of catalytic activity. 1 Publication1
Mutagenesisi192E → A: No change. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000862621 – 888Mitogen-activated protein kinase kinase kinase 12Add BLAST888

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei37PhosphothreonineCombined sources1
Modified residuei43PhosphothreonineCombined sources1
Modified residuei640PhosphoserineCombined sources1
Modified residuei728PhosphoserineCombined sources1

Post-translational modificationi

Autophosphorylated on Ser/Thr. Phosphorylated in cytosol under basal conditions and dephosphorylated when membrane-associated.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ60700.
PRIDEiQ60700.

PTM databases

iPTMnetiQ60700.
PhosphoSitePlusiQ60700.
SwissPalmiQ60700.

Expressioni

Tissue specificityi

Expressed in brain, kidney, lung, heart, testis, gastrointestinal tract, stomach, liver and pancreas. Within the nervous system, predominantly expressed in neurons and enriched in synaptic terminals.

Gene expression databases

BgeeiENSMUSG00000023050.
CleanExiMM_MAP3K12.
ExpressionAtlasiQ60700. baseline and differential.
GenevisibleiQ60700. MM.

Interactioni

Subunit structurei

Interacts with MBIP.By similarity

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB
  • protein kinase binding Source: MGI

Protein-protein interaction databases

BioGridi204957. 6 interactors.
IntActiQ60700. 6 interactors.
MINTiMINT-126821.
STRINGi10090.ENSMUSP00000023812.

Structurei

3D structure databases

ProteinModelPortaliQ60700.
SMRiQ60700.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini158 – 399Protein kinasePROSITE-ProRule annotationAdd BLAST242

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni423 – 444Leucine-zipper 1Add BLAST22
Regioni476 – 497Leucine-zipper 2Add BLAST22

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi56 – 62Poly-Gly7
Compositional biasi668 – 671Poly-Pro4
Compositional biasi698 – 701Poly-Pro4
Compositional biasi753 – 764Glu-rich (acidic)Add BLAST12

Domaini

Interacts with MBIP through the leucine-zipper motif.By similarity

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG4721. Eukaryota.
ENOG410YKX2. LUCA.
GeneTreeiENSGT00760000118807.
HOGENOMiHOG000113435.
HOVERGENiHBG052383.
InParanoidiQ60700.
KOiK04423.
OMAiNPEDSDC.
OrthoDBiEOG091G0905.
PhylomeDBiQ60700.
TreeFamiTF105119.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR017419. MAP3K12_MAP3K13.
IPR027257. MAPKKK12.
IPR000719. Prot_kinase_dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFiPIRSF500741. MAPKKK12. 1 hit.
PIRSF038165. MAPKKK12_MAPKKK13. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q60700-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MACLHETRTP SPSFGGFVST LSEASMRKLD PDTSDCTPEK DLTPTQCVLR
60 70 80 90 100
DVVPLGGQGG GGPSPSPGGE PPPEPFANSV LQLHEQDTGG PGGATGSPES
110 120 130 140 150
RASRVRADEV RLQCQSGSGF LEGLFGCLRP VWTMIGKAYS TEHKQQQEDL
160 170 180 190 200
WEVPFEEILD LQWVGSGAQG AVFLGRFHGE EVAVKKVRDL KETDIKHLRK
210 220 230 240 250
LKHPNIITFK GVCTQAPCYC ILMEFCAQGQ LYEVLRAGRP VTPSLLVDWS
260 270 280 290 300
MGIAGGMNYL HLHKIIHRDL KSPNMLITYD DVVKISDFGT SKELSDKSTK
310 320 330 340 350
MSFAGTVAWM APEVIRNEPV SEKVDIWSFG VVLWELLTGE IPYKDVDSSA
360 370 380 390 400
IIWGVGSNSL HLPVPSSCPD GFKILLRQCW NSKPRNRPSF RQILLHLDIA
410 420 430 440 450
SADVLSTPQE TYFKSQAEWR EEVKLHFEKI KSEGTCLHRL EEELVMRRRE
460 470 480 490 500
ELRHALDIRE HYERKLERAN NLYMELNALM LQLELKEREL LRREQALERR
510 520 530 540 550
CPGLLKSHPS RGLLHGNTME KLIKKRNVPQ KLSPHSKRPD ILKTESLLPK
560 570 580 590 600
LDAALSGVGL PGCPKGPPSP GRSRRGKTRH RKASAKGSCG DLPGLRAALP
610 620 630 640 650
PHEPGGLGSP GGLGVGPSAW DACPPALRGL HHDLLLRKMS SSSPDLLSAA
660 670 680 690 700
LGARGRGATG GARDPGSPPP PQGDTPPSEG SAPGSTSPDS PGGAKGEPPP
710 720 730 740 750
PVGPGEGVGL LGTGREGTAG RGGNRAGSQH LTPAALLYRA AVTRSQKRGI
760 770 780 790 800
SSEEEEGEVD SEVELPPSQR WPQGPNMRQS LSTFSSENPS DVEEGTASEP
810 820 830 840 850
SPSGTPEVGS TNTDERPDER SDDMCSQGSE IPLDLPTSEV VPEREASSLP
860 870 880
MQHQDGQGPN PEDSDCDSTE LDNSNSIDAL RPPASLPP
Length:888
Mass (Da):96,084
Last modified:November 1, 1996 - v1
Checksum:iCFECF1D34F889ABB
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti18V → A in AAB17123 (PubMed:8769565).Curated1
Sequence conflicti28 – 29KL → NV in AAB17123 (PubMed:8769565).Curated2
Sequence conflicti218C → S in BAC26658 (PubMed:16141072).Curated1
Sequence conflicti382S → T in AAB17123 (PubMed:8769565).Curated1
Sequence conflicti392Q → K in BAC28689 (PubMed:16141072).Curated1
Sequence conflicti494 – 495EQ → DE in AAB17123 (PubMed:8769565).Curated2
Sequence conflicti517N → D in AAB17123 (PubMed:8769565).Curated1
Sequence conflicti794E → G in AAB17123 (PubMed:8769565).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U14636 mRNA. Translation: AAA57280.1.
U23789 mRNA. Translation: AAB17123.1.
AK029882 mRNA. Translation: BAC26658.1.
AK034374 mRNA. Translation: BAC28689.1.
AK081623 mRNA. Translation: BAC38274.1.
AK166435 mRNA. Translation: BAE38775.1.
BC047158 mRNA. Translation: AAH47158.1.
BC057572 mRNA. Translation: AAH57572.1.
CCDSiCCDS27885.1.
PIRiA55318.
RefSeqiNP_001157115.1. NM_001163643.1.
NP_033608.3. NM_009582.4.
XP_017172113.1. XM_017316624.1.
XP_017172114.1. XM_017316625.1.
UniGeneiMm.172897.
Mm.236513.

Genome annotation databases

EnsembliENSMUST00000023812; ENSMUSP00000023812; ENSMUSG00000023050.
ENSMUST00000169377; ENSMUSP00000133209; ENSMUSG00000023050.
ENSMUST00000171565; ENSMUSP00000127629; ENSMUSG00000023050.
GeneIDi26404.
KEGGimmu:26404.
UCSCiuc007xwc.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U14636 mRNA. Translation: AAA57280.1.
U23789 mRNA. Translation: AAB17123.1.
AK029882 mRNA. Translation: BAC26658.1.
AK034374 mRNA. Translation: BAC28689.1.
AK081623 mRNA. Translation: BAC38274.1.
AK166435 mRNA. Translation: BAE38775.1.
BC047158 mRNA. Translation: AAH47158.1.
BC057572 mRNA. Translation: AAH57572.1.
CCDSiCCDS27885.1.
PIRiA55318.
RefSeqiNP_001157115.1. NM_001163643.1.
NP_033608.3. NM_009582.4.
XP_017172113.1. XM_017316624.1.
XP_017172114.1. XM_017316625.1.
UniGeneiMm.172897.
Mm.236513.

3D structure databases

ProteinModelPortaliQ60700.
SMRiQ60700.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204957. 6 interactors.
IntActiQ60700. 6 interactors.
MINTiMINT-126821.
STRINGi10090.ENSMUSP00000023812.

PTM databases

iPTMnetiQ60700.
PhosphoSitePlusiQ60700.
SwissPalmiQ60700.

Proteomic databases

PaxDbiQ60700.
PRIDEiQ60700.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000023812; ENSMUSP00000023812; ENSMUSG00000023050.
ENSMUST00000169377; ENSMUSP00000133209; ENSMUSG00000023050.
ENSMUST00000171565; ENSMUSP00000127629; ENSMUSG00000023050.
GeneIDi26404.
KEGGimmu:26404.
UCSCiuc007xwc.2. mouse.

Organism-specific databases

CTDi7786.
MGIiMGI:1346881. Map3k12.

Phylogenomic databases

eggNOGiKOG4721. Eukaryota.
ENOG410YKX2. LUCA.
GeneTreeiENSGT00760000118807.
HOGENOMiHOG000113435.
HOVERGENiHBG052383.
InParanoidiQ60700.
KOiK04423.
OMAiNPEDSDC.
OrthoDBiEOG091G0905.
PhylomeDBiQ60700.
TreeFamiTF105119.

Miscellaneous databases

PROiQ60700.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000023050.
CleanExiMM_MAP3K12.
ExpressionAtlasiQ60700. baseline and differential.
GenevisibleiQ60700. MM.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR017419. MAP3K12_MAP3K13.
IPR027257. MAPKKK12.
IPR000719. Prot_kinase_dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFiPIRSF500741. MAPKKK12. 1 hit.
PIRSF038165. MAPKKK12_MAPKKK13. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiM3K12_MOUSE
AccessioniPrimary (citable) accession number: Q60700
Secondary accession number(s): P70286
, Q3TLL7, Q8C4N7, Q8CBX3, Q8CDL6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: November 1, 1996
Last modified: November 30, 2016
This is version 157 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. 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.