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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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei185 – 1851ATP
Active sitei269 – 2691Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi164 – 1729ATPPROSITE-ProRule annotation

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: MGI
  • 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)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi185 – 1851K → A: Loss of catalytic activity. 1 Publication
Mutagenesisi192 – 1921E → A: No change. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 888888Mitogen-activated protein kinase kinase kinase 12PRO_0000086262Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei37 – 371PhosphothreonineCombined sources
Modified residuei43 – 431PhosphothreonineCombined sources
Modified residuei640 – 6401PhosphoserineCombined sources
Modified residuei728 – 7281PhosphoserineCombined sources

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

MaxQBiQ60700.
PaxDbiQ60700.
PRIDEiQ60700.

PTM databases

iPTMnetiQ60700.
PhosphoSiteiQ60700.
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

BgeeiQ60700.
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 interactions.
IntActiQ60700. 6 interactions.
MINTiMINT-126821.
STRINGi10090.ENSMUSP00000023812.

Structurei

3D structure databases

ProteinModelPortaliQ60700.
SMRiQ60700. Positions 101-459.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini158 – 399242Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni423 – 44422Leucine-zipper 1Add
BLAST
Regioni476 – 49722Leucine-zipper 2Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi56 – 627Poly-Gly
Compositional biasi668 – 6714Poly-Pro
Compositional biasi698 – 7014Poly-Pro
Compositional biasi753 – 76412Glu-rich (acidic)Add
BLAST

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.
OrthoDBiEOG7B8S3P.
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti18 – 181V → A in AAB17123 (PubMed:8769565).Curated
Sequence conflicti28 – 292KL → NV in AAB17123 (PubMed:8769565).Curated
Sequence conflicti218 – 2181C → S in BAC26658 (PubMed:16141072).Curated
Sequence conflicti382 – 3821S → T in AAB17123 (PubMed:8769565).Curated
Sequence conflicti392 – 3921Q → K in BAC28689 (PubMed:16141072).Curated
Sequence conflicti494 – 4952EQ → DE in AAB17123 (PubMed:8769565).Curated
Sequence conflicti517 – 5171N → D in AAB17123 (PubMed:8769565).Curated
Sequence conflicti794 – 7941E → G in AAB17123 (PubMed:8769565).Curated

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_011243946.1. XM_011245644.1.
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_011243946.1. XM_011245644.1.
UniGeneiMm.172897.
Mm.236513.

3D structure databases

ProteinModelPortaliQ60700.
SMRiQ60700. Positions 101-459.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

PTM databases

iPTMnetiQ60700.
PhosphoSiteiQ60700.
SwissPalmiQ60700.

Proteomic databases

MaxQBiQ60700.
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.
OrthoDBiEOG7B8S3P.
PhylomeDBiQ60700.
TreeFamiTF105119.

Miscellaneous databases

PROiQ60700.
SOURCEiSearch...

Gene expression databases

BgeeiQ60700.
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...

Publicationsi

« Hide 'large scale' publications
  1. "Identification, molecular cloning, and characterization of dual leucine zipper bearing kinase. A novel serine/threonine protein kinase that defines a second subfamily of mixed lineage kinases."
    Holzman L.B., Merritt S.E., Fan G.
    J. Biol. Chem. 269:30808-30817(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: CD-1.
    Tissue: Brain.
  2. "Cell-specific expression of the ZPK gene in adult mouse tissues."
    Blouin R., Beaudoin J., Bergeron P., Nadeau A., Grondin G.
    DNA Cell Biol. 15:631-642(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: ICR X Swiss Webster.
    Tissue: Brain.
  3. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Diencephalon, Embryonic head and Testis.
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Brain and Retina.
  5. "Characterization of dual leucine zipper-bearing kinase, a mixed lineage kinase present in synaptic terminals whose phosphorylation state is regulated by membrane depolarization via calcineurin."
    Mata M., Merritt S.E., Fan G., Yu G.G., Holzman L.B.
    J. Biol. Chem. 271:16888-16896(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION, MUTAGENESIS OF LYS-185 AND GLU-192.
  6. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-37; THR-43; SER-640 AND SER-728, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain.

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: June 8, 2016
This is version 153 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.