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Protein

Mitogen-activated protein kinase kinase kinase 12

Gene

MAP3K12

Organism
Homo sapiens (Human)
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 sitei152ATPPROSITE-ProRule annotation1
Active sitei236Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi131 – 139ATPPROSITE-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 activity Source: ProtInc
  • protein kinase binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  • histone phosphorylation Source: UniProtKB
  • intracellular signal transduction Source: ProtInc
  • JNK cascade Source: UniProtKB
  • negative regulation of motor neuron apoptotic process Source: Ensembl
  • 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

Enzyme and pathway databases

BioCyciZFISH:HS06639-MONOMER.
SignaLinkiQ12852.
SIGNORiQ12852.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:6851. MAP3K12.

Subcellular locationi

GO - Cellular componenti

  • axon Source: Ensembl
  • cytoplasm Source: ProtInc
  • cytosol Source: UniProtKB
  • growth cone Source: Ensembl
  • membrane Source: UniProtKB
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi7786.
OpenTargetsiENSG00000139625.
PharmGKBiPA30595.

Chemistry databases

ChEMBLiCHEMBL1908389.
GuidetoPHARMACOLOGYi2072.

Polymorphism and mutation databases

BioMutaiMAP3K12.
DMDMi116242624.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000862611 – 859Mitogen-activated protein kinase kinase kinase 12Add BLAST859

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei37PhosphothreonineBy similarity1
Modified residuei43PhosphothreonineBy similarity1
Modified residuei607PhosphoserineBy similarity1
Modified residuei695PhosphoserineBy similarity1

Post-translational modificationi

Autophosphorylated on Ser/Thr. Phosphorylated in cytosol under basal conditions and dephosphorylated when membrane-associated (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ12852.
PaxDbiQ12852.
PeptideAtlasiQ12852.
PRIDEiQ12852.

PTM databases

iPTMnetiQ12852.
PhosphoSitePlusiQ12852.

Expressioni

Tissue specificityi

Highly expressed in brain and kidney.

Gene expression databases

BgeeiENSG00000139625.
CleanExiHS_MAP3K12.
ExpressionAtlasiQ12852. baseline and differential.
GenevisibleiQ12852. HS.

Organism-specific databases

HPAiHPA039936.

Interactioni

Subunit structurei

Interacts with MBIP.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
FRA10AC1Q70Z532EBI-710223,EBI-710176

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi113566. 12 interactors.
IntActiQ12852. 9 interactors.
MINTiMINT-1382019.
STRINGi9606.ENSP00000448689.

Chemistry databases

BindingDBiQ12852.

Structurei

Secondary structure

1859
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi122 – 124Combined sources3
Beta strandi126 – 134Combined sources9
Beta strandi137 – 144Combined sources8
Beta strandi147 – 153Combined sources7
Helixi157 – 160Combined sources4
Helixi163 – 165Combined sources3
Beta strandi176 – 180Combined sources5
Beta strandi187 – 191Combined sources5
Helixi198 – 203Combined sources6
Helixi210 – 229Combined sources20
Helixi239 – 241Combined sources3
Beta strandi242 – 244Combined sources3
Beta strandi250 – 252Combined sources3
Helixi264 – 271Combined sources8
Helixi272 – 276Combined sources5
Helixi279 – 282Combined sources4
Helixi290 – 305Combined sources16
Turni309 – 312Combined sources4
Helixi315 – 323Combined sources9
Helixi337 – 346Combined sources10
Helixi351 – 353Combined sources3
Helixi357 – 372Combined sources16
Helixi376 – 396Combined sources21

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5CENX-ray1.70A115-402[»]
5CEOX-ray2.28A115-402[»]
5CEPX-ray1.99A115-402[»]
5CEQX-ray1.91A115-402[»]
ProteinModelPortaliQ12852.
SMRiQ12852.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini125 – 366Protein kinasePROSITE-ProRule annotationAdd BLAST242

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni390 – 411Leucine-zipper 1Add BLAST22
Regioni443 – 464Leucine-zipper 2Add BLAST22

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi665 – 668Poly-Pro4
Compositional biasi720 – 731Glu-rich (acidic)Add BLAST12

Domaini

Interacts with MBIP through the leucine-zipper motif.

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG4721. Eukaryota.
ENOG410YKX2. LUCA.
GeneTreeiENSGT00760000118807.
HOGENOMiHOG000113435.
HOVERGENiHBG052383.
InParanoidiQ12852.
KOiK04423.
OMAiNPEDSDC.
OrthoDBiEOG091G0905.
PhylomeDBiQ12852.

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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q12852-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MACLHETRTP SPSFGGFVST LSEASMRKLD PDTSDCTPEK DLTPTHVLQL
60 70 80 90 100
HEQDAGGPGG AAGSPESRAS RVRADEVRLQ CQSGSGFLEG LFGCLRPVWT
110 120 130 140 150
MIGKAYSTEH KQQQEDLWEV PFEEILDLQW VGSGAQGAVF LGRFHGEEVA
160 170 180 190 200
VKKVRDLKET DIKHLRKLKH PNIITFKGVC TQAPCYCILM EFCAQGQLYE
210 220 230 240 250
VLRAGRPVTP SLLVDWSMGI AGGMNYLHLH KIIHRDLKSP NMLITYDDVV
260 270 280 290 300
KISDFGTSKE LSDKSTKMSF AGTVAWMAPE VIRNEPVSEK VDIWSFGVVL
310 320 330 340 350
WELLTGEIPY KDVDSSAIIW GVGSNSLHLP VPSSCPDGFK ILLRQCWNSK
360 370 380 390 400
PRNRPSFRQI LLHLDIASAD VLSTPQETYF KSQAEWREEV KLHFEKIKSE
410 420 430 440 450
GTCLHRLEEE LVMRRREELR HALDIREHYE RKLERANNLY MELNALMLQL
460 470 480 490 500
ELKERELLRR EQALERRCPG LLKPHPSRGL LHGNTMEKLI KKRNVPQKLS
510 520 530 540 550
PHSKRPDILK TESLLPKLDA ALSGVGLPGC PKGPPSPGRS RRGKTRHRKA
560 570 580 590 600
SAKGSCGDLP GLRTAVPPHE PGGPGSPGGL GGGPSAWEAC PPALRGLHHD
610 620 630 640 650
LLLRKMSSSS PDLLSAALGS RGRGATGGAG DPGSPPPARG DTPPSEGSAP
660 670 680 690 700
GSTSPDSPGG AKGEPPPPVG PGEGVGLLGT GREGTSGRGG SRAGSQHLTP
710 720 730 740 750
AALLYRAAVT RSQKRGISSE EEEGEVDSEV ELTSSQRWPQ SLNMRQSLST
760 770 780 790 800
FSSENPSDGE EGTASEPSPS GTPEVGSTNT DERPDERSDD MCSQGSEIPL
810 820 830 840 850
DPPPSEVIPG PEPSSLPIPH QELLRERGPP NSEDSDCDST ELDNSNSVDA

LRPPASLPP
Length:859
Mass (Da):93,219
Last modified:October 17, 2006 - v2
Checksum:i1E1BCAD2F6DFCFE8
GO
Isoform 2 (identifier: Q12852-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     46-46: H → QCVLRDVVPLGGQGGGGPSPSPGGEPPPEPFANS

Note: No experimental confirmation available.
Show »
Length:892
Mass (Da):96,322
Checksum:iEA0C10CFE2461876
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti355P → S in BAG52841 (PubMed:14702039).Curated1
Sequence conflicti498K → N in AAA67343 (PubMed:8037767).Curated1
Sequence conflicti504K → Q in AAA67343 (PubMed:8037767).Curated1
Sequence conflicti511T → A in AAA67343 (PubMed:8037767).Curated1
Sequence conflicti533G → A in AAA67343 (PubMed:8037767).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_040705409E → K in a breast pleomorphic lobular carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_040706628G → R.1 PublicationCorresponds to variant rs34366500dbSNPEnsembl.1
Natural variantiVAR_040707640G → S.1 PublicationCorresponds to variant rs55794887dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04464646H → QCVLRDVVPLGGQGGGGPSP SPGGEPPPEPFANS in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U07358 mRNA. Translation: AAA67343.1.
AF283475 Genomic DNA. Translation: AAL67158.1.
AK094195 mRNA. Translation: BAG52841.1.
AC023509 Genomic DNA. No translation available.
CH471054 Genomic DNA. Translation: EAW96715.1.
BC050050 mRNA. Translation: AAH50050.1. Sequence problems.
CCDSiCCDS55831.1. [Q12852-2]
CCDS8860.1. [Q12852-1]
PIRiJC2363.
RefSeqiNP_001180440.1. NM_001193511.1. [Q12852-2]
NP_006292.3. NM_006301.3. [Q12852-1]
XP_005269195.1. XM_005269138.3. [Q12852-2]
XP_006719651.1. XM_006719588.3. [Q12852-2]
XP_011537027.1. XM_011538725.2. [Q12852-2]
XP_016875445.1. XM_017019956.1. [Q12852-1]
UniGeneiHs.713539.

Genome annotation databases

EnsembliENST00000267079; ENSP00000267079; ENSG00000139625. [Q12852-1]
ENST00000547035; ENSP00000448689; ENSG00000139625. [Q12852-2]
ENST00000547488; ENSP00000449038; ENSG00000139625. [Q12852-2]
GeneIDi7786.
KEGGihsa:7786.
UCSCiuc001sdm.3. human. [Q12852-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U07358 mRNA. Translation: AAA67343.1.
AF283475 Genomic DNA. Translation: AAL67158.1.
AK094195 mRNA. Translation: BAG52841.1.
AC023509 Genomic DNA. No translation available.
CH471054 Genomic DNA. Translation: EAW96715.1.
BC050050 mRNA. Translation: AAH50050.1. Sequence problems.
CCDSiCCDS55831.1. [Q12852-2]
CCDS8860.1. [Q12852-1]
PIRiJC2363.
RefSeqiNP_001180440.1. NM_001193511.1. [Q12852-2]
NP_006292.3. NM_006301.3. [Q12852-1]
XP_005269195.1. XM_005269138.3. [Q12852-2]
XP_006719651.1. XM_006719588.3. [Q12852-2]
XP_011537027.1. XM_011538725.2. [Q12852-2]
XP_016875445.1. XM_017019956.1. [Q12852-1]
UniGeneiHs.713539.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5CENX-ray1.70A115-402[»]
5CEOX-ray2.28A115-402[»]
5CEPX-ray1.99A115-402[»]
5CEQX-ray1.91A115-402[»]
ProteinModelPortaliQ12852.
SMRiQ12852.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113566. 12 interactors.
IntActiQ12852. 9 interactors.
MINTiMINT-1382019.
STRINGi9606.ENSP00000448689.

Chemistry databases

BindingDBiQ12852.
ChEMBLiCHEMBL1908389.
GuidetoPHARMACOLOGYi2072.

PTM databases

iPTMnetiQ12852.
PhosphoSitePlusiQ12852.

Polymorphism and mutation databases

BioMutaiMAP3K12.
DMDMi116242624.

Proteomic databases

EPDiQ12852.
PaxDbiQ12852.
PeptideAtlasiQ12852.
PRIDEiQ12852.

Protocols and materials databases

DNASUi7786.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000267079; ENSP00000267079; ENSG00000139625. [Q12852-1]
ENST00000547035; ENSP00000448689; ENSG00000139625. [Q12852-2]
ENST00000547488; ENSP00000449038; ENSG00000139625. [Q12852-2]
GeneIDi7786.
KEGGihsa:7786.
UCSCiuc001sdm.3. human. [Q12852-1]

Organism-specific databases

CTDi7786.
DisGeNETi7786.
GeneCardsiMAP3K12.
H-InvDBHIX0010672.
HGNCiHGNC:6851. MAP3K12.
HPAiHPA039936.
MIMi600447. gene.
neXtProtiNX_Q12852.
OpenTargetsiENSG00000139625.
PharmGKBiPA30595.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4721. Eukaryota.
ENOG410YKX2. LUCA.
GeneTreeiENSGT00760000118807.
HOGENOMiHOG000113435.
HOVERGENiHBG052383.
InParanoidiQ12852.
KOiK04423.
OMAiNPEDSDC.
OrthoDBiEOG091G0905.
PhylomeDBiQ12852.

Enzyme and pathway databases

BioCyciZFISH:HS06639-MONOMER.
SignaLinkiQ12852.
SIGNORiQ12852.

Miscellaneous databases

ChiTaRSiMAP3K12. human.
GeneWikiiMAP3K12.
GenomeRNAii7786.
PROiQ12852.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000139625.
CleanExiHS_MAP3K12.
ExpressionAtlasiQ12852. baseline and differential.
GenevisibleiQ12852. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: Q12852
Secondary accession number(s): B3KSS9
, G3V1Y2, Q86VQ5, Q8WY25
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: October 17, 2006
Last modified: November 2, 2016
This is version 162 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. 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.