UniProtKB - Q12852 (M3K12_HUMAN)
Protein
Mitogen-activated protein kinase kinase kinase 12
Gene
MAP3K12
Organism
Homo sapiens (Human)
Status
Functioni
Part of a non-canonical MAPK signaling pathway (PubMed:28111074). Activated by APOE, enhances the AP-1-mediated transcription of APP, via a MAP kinase signal transduction pathway composed of MAP2K7 and MAPK1/ERK2 and MAPK3/ERK1 (PubMed:28111074). May be an activator of the JNK/SAPK pathway.1 Publication
Catalytic activityi
Cofactori
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 152 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 236 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 131 – 139 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- JUN kinase kinase kinase activity Source: ARUK-UCL
- 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
- activation of JNKK activity Source: ARUK-UCL
- activation of JUN kinase activity Source: ARUK-UCL
- 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
- positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
- positive regulation of transcription, DNA-templated Source: UniProtKB
- protein autophosphorylation Source: UniProtKB
- protein phosphorylation Source: UniProtKB
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Ligand | ATP-binding, Magnesium, Nucleotide-binding |
Enzyme and pathway databases
SignaLinki | Q12852 |
SIGNORi | Q12852 |
Names & Taxonomyi
Protein namesi | Recommended name: Mitogen-activated protein kinase kinase kinase 12 (EC:2.7.11.25By similarity)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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:6851 MAP3K12 |
MIMi | 600447 gene |
neXtProti | NX_Q12852 |
Subcellular locationi
Plasma membrane
- Cell membrane By similarity
Other locations
- Cytoplasm By similarity
Note: Behaves essentially as an integral membrane protein.By similarity
Cytosol
- cytosol Source: UniProtKB
Plasma Membrane
- plasma membrane Source: UniProtKB
Other locations
- cytoplasm Source: ProtInc
- growth cone Source: Ensembl
- membrane Source: UniProtKB
Keywords - Cellular componenti
Cell membrane, Cytoplasm, MembranePathology & Biotechi
Organism-specific databases
DisGeNETi | 7786 |
OpenTargetsi | ENSG00000139625 |
PharmGKBi | PA30595 |
Miscellaneous databases
Pharosi | Q12852 |
Chemistry databases
ChEMBLi | CHEMBL1908389 |
DrugBanki | DB12010 Fostamatinib |
DrugCentrali | Q12852 |
GuidetoPHARMACOLOGYi | 2072 |
Polymorphism and mutation databases
BioMutai | MAP3K12 |
DMDMi | 116242624 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000086261 | 1 – 859 | Mitogen-activated protein kinase kinase kinase 12Add BLAST | 859 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 37 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 43 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 607 | PhosphoserineBy similarity | 1 | |
Modified residuei | 695 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Autophosphorylated on Ser/Thr. Phosphorylated in cytosol under basal conditions and dephosphorylated when membrane-associated (By similarity).By similarity
The activity of MAP3K12 can be regulated through its proteasomal degradation. APOE, through a receptor-mediated mechanism, activates MAP3K12 by preventing its proteasomal degradation.1 Publication
Keywords - PTMi
PhosphoproteinProteomic databases
jPOSTi | Q12852 |
MassIVEi | Q12852 |
PaxDbi | Q12852 |
PeptideAtlasi | Q12852 |
PRIDEi | Q12852 |
ProteomicsDBi | 32474 58985 [Q12852-1] |
PTM databases
iPTMneti | Q12852 |
PhosphoSitePlusi | Q12852 |
Expressioni
Tissue specificityi
Highly expressed in brain and kidney.1 Publication
Gene expression databases
Bgeei | ENSG00000139625 Expressed in 212 organ(s), highest expression level in right hemisphere of cerebellum |
ExpressionAtlasi | Q12852 baseline and differential |
Genevisiblei | Q12852 HS |
Organism-specific databases
HPAi | HPA039936 HPA071996 |
Interactioni
Subunit structurei
Binary interactionsi
With | Entry | #Exp. | IntAct | Notes |
---|---|---|---|---|
Q70Z53 | 2 | EBI-710223,EBI-710176 |
GO - Molecular functioni
- protein homodimerization activity Source: UniProtKB
- protein kinase binding Source: UniProtKB
Protein-protein interaction databases
BioGridi | 113566, 13 interactors |
IntActi | Q12852, 9 interactors |
MINTi | Q12852 |
STRINGi | 9606.ENSP00000448689 |
Chemistry databases
BindingDBi | Q12852 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q12852 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 125 – 366 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 242 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 390 – 411 | Leucine-zipper 1Add BLAST | 22 | |
Regioni | 443 – 464 | Leucine-zipper 2Add BLAST | 22 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 665 – 668 | Poly-Pro | 4 | |
Compositional biasi | 720 – 731 | Glu-rich (acidic)Add BLAST | 12 |
Domaini
Interacts with MBIP through the leucine-zipper motif.1 Publication
Sequence similaritiesi
Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.Curated
Keywords - Domaini
RepeatPhylogenomic databases
eggNOGi | KOG4721 Eukaryota ENOG410YKX2 LUCA |
GeneTreei | ENSGT00940000159006 |
HOGENOMi | HOG000113435 |
InParanoidi | Q12852 |
KOi | K04423 |
OMAi | EQGPPNS |
OrthoDBi | 938929at2759 |
PhylomeDBi | Q12852 |
Family and domain databases
InterProi | View protein in InterPro IPR011009 Kinase-like_dom_sf IPR017419 MAP3K12_MAP3K13 IPR027257 MAPKKK12 IPR000719 Prot_kinase_dom IPR001245 Ser-Thr/Tyr_kinase_cat_dom IPR008271 Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF07714 Pkinase_Tyr, 1 hit |
PIRSFi | PIRSF500741 MAPKKK12, 1 hit PIRSF038165 MAPKKK12_MAPKKK13, 1 hit |
PRINTSi | PR00109 TYRKINASE |
SMARTi | View protein in SMART SM00220 S_TKc, 1 hit |
SUPFAMi | SSF56112 SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS50011 PROTEIN_KINASE_DOM, 1 hit PS00108 PROTEIN_KINASE_ST, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q12852-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketF8VUG4 | F8VUG4_HUMAN | Mitogen-activated protein kinase ki... | MAP3K12 | 393 | Annotation score: | ||
H3BMF0 | H3BMF0_HUMAN | Mitogen-activated protein kinase ki... | MAP3K12 | 25 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 355 | P → S in BAG52841 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 498 | K → N in AAA67343 (PubMed:8037767).Curated | 1 | |
Sequence conflicti | 504 | K → Q in AAA67343 (PubMed:8037767).Curated | 1 | |
Sequence conflicti | 511 | T → A in AAA67343 (PubMed:8037767).Curated | 1 | |
Sequence conflicti | 533 | G → A in AAA67343 (PubMed:8037767).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_040705 | 409 | E → K in a breast pleomorphic lobular carcinoma sample; somatic mutation. 1 Publication | 1 | |
Natural variantiVAR_040706 | 628 | G → R1 PublicationCorresponds to variant dbSNP:rs34366500Ensembl. | 1 | |
Natural variantiVAR_040707 | 640 | G → S1 PublicationCorresponds to variant dbSNP:rs55794887Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_044646 | 46 | H → QCVLRDVVPLGGQGGGGPSP SPGGEPPPEPFANS in isoform 2. 1 Publication | 1 |
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. |
CCDSi | CCDS55831.1 [Q12852-2] CCDS8860.1 [Q12852-1] |
PIRi | JC2363 |
RefSeqi | NP_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] |
Genome annotation databases
Ensembli | ENST00000267079; ENSP00000267079; ENSG00000139625 [Q12852-1] ENST00000547035; ENSP00000448689; ENSG00000139625 [Q12852-2] ENST00000547488; ENSP00000449038; ENSG00000139625 [Q12852-2] |
GeneIDi | 7786 |
KEGGi | hsa:7786 |
UCSCi | uc001sdm.3 human [Q12852-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
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. |
CCDSi | CCDS55831.1 [Q12852-2] CCDS8860.1 [Q12852-1] |
PIRi | JC2363 |
RefSeqi | NP_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] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5CEN | X-ray | 1.70 | A | 115-402 | [»] | |
5CEO | X-ray | 2.28 | A | 115-402 | [»] | |
5CEP | X-ray | 1.99 | A | 115-402 | [»] | |
5CEQ | X-ray | 1.91 | A | 115-402 | [»] | |
5VO1 | X-ray | 2.45 | A | 115-402 | [»] | |
5VO2 | X-ray | 2.96 | A | 115-402 | [»] | |
SMRi | Q12852 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGridi | 113566, 13 interactors |
IntActi | Q12852, 9 interactors |
MINTi | Q12852 |
STRINGi | 9606.ENSP00000448689 |
Chemistry databases
BindingDBi | Q12852 |
ChEMBLi | CHEMBL1908389 |
DrugBanki | DB12010 Fostamatinib |
DrugCentrali | Q12852 |
GuidetoPHARMACOLOGYi | 2072 |
PTM databases
iPTMneti | Q12852 |
PhosphoSitePlusi | Q12852 |
Polymorphism and mutation databases
BioMutai | MAP3K12 |
DMDMi | 116242624 |
Proteomic databases
jPOSTi | Q12852 |
MassIVEi | Q12852 |
PaxDbi | Q12852 |
PeptideAtlasi | Q12852 |
PRIDEi | Q12852 |
ProteomicsDBi | 32474 58985 [Q12852-1] |
Protocols and materials databases
DNASUi | 7786 |
Genome annotation databases
Ensembli | ENST00000267079; ENSP00000267079; ENSG00000139625 [Q12852-1] ENST00000547035; ENSP00000448689; ENSG00000139625 [Q12852-2] ENST00000547488; ENSP00000449038; ENSG00000139625 [Q12852-2] |
GeneIDi | 7786 |
KEGGi | hsa:7786 |
UCSCi | uc001sdm.3 human [Q12852-1] |
Organism-specific databases
CTDi | 7786 |
DisGeNETi | 7786 |
GeneCardsi | MAP3K12 |
HGNCi | HGNC:6851 MAP3K12 |
HPAi | HPA039936 HPA071996 |
MIMi | 600447 gene |
neXtProti | NX_Q12852 |
OpenTargetsi | ENSG00000139625 |
PharmGKBi | PA30595 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4721 Eukaryota ENOG410YKX2 LUCA |
GeneTreei | ENSGT00940000159006 |
HOGENOMi | HOG000113435 |
InParanoidi | Q12852 |
KOi | K04423 |
OMAi | EQGPPNS |
OrthoDBi | 938929at2759 |
PhylomeDBi | Q12852 |
Enzyme and pathway databases
SignaLinki | Q12852 |
SIGNORi | Q12852 |
Miscellaneous databases
ChiTaRSi | MAP3K12 human |
GeneWikii | MAP3K12 |
GenomeRNAii | 7786 |
Pharosi | Q12852 |
PROi | PR:Q12852 |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000139625 Expressed in 212 organ(s), highest expression level in right hemisphere of cerebellum |
ExpressionAtlasi | Q12852 baseline and differential |
Genevisiblei | Q12852 HS |
Family and domain databases
InterProi | View protein in InterPro IPR011009 Kinase-like_dom_sf IPR017419 MAP3K12_MAP3K13 IPR027257 MAPKKK12 IPR000719 Prot_kinase_dom IPR001245 Ser-Thr/Tyr_kinase_cat_dom IPR008271 Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF07714 Pkinase_Tyr, 1 hit |
PIRSFi | PIRSF500741 MAPKKK12, 1 hit PIRSF038165 MAPKKK12_MAPKKK13, 1 hit |
PRINTSi | PR00109 TYRKINASE |
SMARTi | View protein in SMART SM00220 S_TKc, 1 hit |
SUPFAMi | SSF56112 SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS50011 PROTEIN_KINASE_DOM, 1 hit PS00108 PROTEIN_KINASE_ST, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | M3K12_HUMAN | |
Accessioni | Q12852Primary (citable) accession number: Q12852 Secondary accession number(s): B3KSS9 Q8WY25 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | September 26, 2001 |
Last sequence update: | October 17, 2006 | |
Last modified: | October 16, 2019 | |
This is version 185 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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 proteomeDocuments
- Human chromosome 12
Human chromosome 12: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - Human and mouse protein kinases
Human and mouse protein kinases: classification and index - SIMILARITY comments
Index of protein domains and families - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references