• Gene id: 7786

Gene Summary

• Gene Symbol: MAP3K12   Gene   UCSC   Ensembl
• Aliases: DLK, MEKK12, MUK, ZPK, ZPKP1
• Gene name: mitogen-activated protein kinase kinase kinase 12
• Alternate names: mitogen-activated protein kinase kinase kinase 12, MAPK-upstream kinase, dual leucine zipper bearing kinase, dual leucine zipper kinase DLK, leucine zipper protein kinase, mixed lineage kinase, protein kinase MUK,
• Gene location: 12q13.13 (53501204: 53479668)     Exons: 14     NC_000012.12
• Gene summary(Entrez): This gene encodes a member of the serine/threonine protein kinase family. This kinase contains a leucine-zipper domain and is predominately expressed in neuronal cells. The phosphorylation state of this kinase in synaptic terminals was shown to be regulat
• OMIM: 600447

Protein Summary

• Protein general information: Q12852  
  • Name: Mitogen activated protein kinase kinase kinase 12 (EC 2.7.11.25) (Dual leucine zipper bearing kinase) (DLK) (Leucine zipper protein kinase) (ZPK) (MAPK upstream kinase) (MUK) (Mixed lineage kinase)
  • Length: 859  
  • Mass: 93219
  • Tissue specificity: Highly expressed in brain and kidney. {ECO
• Sequence:

  MACLHETRTPSPSFGGFVSTLSEASMRKLDPDTSDCTPEKDLTPTHVLQLHEQDAGGPGGAAGSPESRASRVRAD
  EVRLQCQSGSGFLEGLFGCLRPVWTMIGKAYSTEHKQQQEDLWEVPFEEILDLQWVGSGAQGAVFLGRFHGEEVA
  VKKVRDLKETDIKHLRKLKHPNIITFKGVCTQAPCYCILMEFCAQGQLYEVLRAGRPVTPSLLVDWSMGIAGGMN
  YLHLHKIIHRDLKSPNMLITYDDVVKISDFGTSKELSDKSTKMSFAGTVAWMAPEVIRNEPVSEKVDIWSFGVVL
  WELLTGEIPYKDVDSSAIIWGVGSNSLHLPVPSSCPDGFKILLRQCWNSKPRNRPSFRQILLHLDIASADVLSTP
  QETYFKSQAEWREEVKLHFEKIKSEGTCLHRLEEELVMRRREELRHALDIREHYERKLERANNLYMELNALMLQL
  ELKERELLRREQALERRCPGLLKPHPSRGLLHGNTMEKLIKKRNVPQKLSPHSKRPDILKTESLLPKLDAALSGV
  GLPGCPKGPPSPGRSRRGKTRHRKASAKGSCGDLPGLRTAVPPHEPGGPGSPGGLGGGPSAWEACPPALRGLHHD
  LLLRKMSSSSPDLLSAALGSRGRGATGGAGDPGSPPPARGDTPPSEGSAPGSTSPDSPGGAKGEPPPPVGPGEGV
  GLLGTGREGTSGRGGSRAGSQHLTPAALLYRAAVTRSQKRGISSEEEEGEVDSEVELTSSQRWPQSLNMRQSLST
  FSSENPSDGEEGTASEPSPSGTPEVGSTNTDERPDERSDDMCSQGSEIPLDPPPSEVIPGPEPSSLPIPHQELLR
  ERGPPNSEDSDCDSTELDNSNSVDALRPPASLPP

• Structural information:
  • Protein Domains: (125..36-)
    (/note="Protein-kinase)
    (/evidence="ECO:0000255|PROSITE-ProRule:PRU00159"-)
  • Interpro: IPR011009  IPR017419  IPR027257  IPR000719  IPR001245   IPR008271  
  • Prosite: PS50011 PS00108
  • PDB: 5CEN 5CEO 5CEP 5CEQ 5VO1 5VO2
  • PDBsum: 5CEN 5CEO 5CEP 5CEQ 5VO1 5VO2
  • STRING: ENSP00000448689
• Other Databases: GeneCards:  MAP3K12  Malacards:  MAP3K12

Gene ontology

GO accession	Term name	Evidence code	Go category
GO:0004706	JUN kinase kinase kinase activity	ISS	molecular function
GO:0007257	activation of JUN kinase activity	ISS	biological process
GO:0007256	activation of JNKK activity	ISS	biological process
GO:0018105	peptidyl-serine phosphorylation	ISS	biological process
GO:0007257	activation of JUN kinase activity	IBA	biological process
GO:0004706	JUN kinase kinase kinase activity	IBA	molecular function
GO:0004672	protein kinase activity	IBA	molecular function
GO:0045893	positive regulation of transcription, DNA-templated	IMP	biological process
GO:0070374	positive regulation of ERK1 and ERK2 cascade	IMP	biological process
GO:0004709	MAP kinase kinase kinase activity	IEA	molecular function
GO:0007254	JNK cascade	IEA	biological process
GO:0046777	protein autophosphorylation	IEA	biological process
GO:0000186	activation of MAPKK activity	IEA	biological process
GO:0004672	protein kinase activity	IEA	molecular function
GO:0005524	ATP binding	IEA	molecular function
GO:0006468	protein phosphorylation	IEA	biological process
GO:0005524	ATP binding	IEA	molecular function
GO:0004674	protein serine/threonine kinase activity	IEA	molecular function
GO:0005886	plasma membrane	IEA	cellular component
GO:0016740	transferase activity	IEA	molecular function
GO:0005737	cytoplasm	IEA	cellular component
GO:0016301	kinase activity	IEA	molecular function
GO:0000166	nucleotide binding	IEA	molecular function
GO:0016310	phosphorylation	IEA	biological process
GO:0016020	membrane	IEA	cellular component
GO:0004672	protein kinase activity	TAS	molecular function
GO:0004672	protein kinase activity	TAS	molecular function
GO:0005737	cytoplasm	TAS	cellular component
GO:0005886	plasma membrane	TAS	cellular component
GO:0035556	intracellular signal transduction	TAS	biological process
GO:0007254	JNK cascade	TAS	biological process
GO:0004709	MAP kinase kinase kinase activity	IEA	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:2000672	negative regulation of motor neuron apoptotic process	IEA	biological process
GO:0030426	growth cone	IEA	cellular component
GO:0018107	peptidyl-threonine phosphorylation	IEA	biological process
GO:0006468	protein phosphorylation	IEA	biological process
GO:0005886	plasma membrane	IEA	cellular component
GO:0004706	JUN kinase kinase kinase activity	IEA	molecular function
GO:0004674	protein serine/threonine kinase activity	IEA	molecular function
GO:0046777	protein autophosphorylation	IEA	biological process
GO:0042803	protein homodimerization activity	IEA	molecular function
GO:0030424	axon	IEA	cellular component
GO:0018105	peptidyl-serine phosphorylation	IEA	biological process
GO:0016572	histone phosphorylation	IEA	biological process
GO:0007257	activation of JUN kinase activity	IEA	biological process
GO:0007256	activation of JNKK activity	IEA	biological process
GO:0005829	cytosol	IEA	cellular component
GO:0005886	plasma membrane	IEA	cellular component
GO:0005737	cytoplasm	IEA	cellular component
GO:0006468	protein phosphorylation	IDA	biological process
GO:0046777	protein autophosphorylation	ISS	biological process
GO:0042803	protein homodimerization activity	ISS	molecular function
GO:0007254	JNK cascade	ISS	biological process
GO:0019901	protein kinase binding	IPI	molecular function
GO:0018107	peptidyl-threonine phosphorylation	ISS	biological process
GO:0006468	protein phosphorylation	ISS	biological process
GO:0004674	protein serine/threonine kinase activity	ISS	molecular function
GO:0046777	protein autophosphorylation	ISS	biological process
GO:0018105	peptidyl-serine phosphorylation	ISS	biological process
GO:0016572	histone phosphorylation	ISS	biological process
GO:0005829	cytosol	ISS	cellular component
GO:0016020	membrane	ISS	cellular component
GO:0005886	plasma membrane	ISS	cellular component
GO:0004674	protein serine/threonine kinase activity	ISS	molecular function

KEGG pathways

Pathway id	Pathway name
hsa04010	MAPK signaling pathway

Diseases

Associated diseases	References
Male factor infertility	MIK: 29961538
Teratozoospermia	MIK: 17327269

PubMed references

PMID	Condition	Mutation	Ethnicity	Population details	Infertility_type	Associated_genes
17327269	Teratozoospermia			19 (6 controls, 13 cases)	Male infertility	GSE6872 analyzed by GEO2R (cutoff 1.5 fold)
29961538	Male factor infertility			318 (128 couples presenting with OAT (MF) and 118 maternal age-matched control (no MF) subjects undergoing infertility treatment, 72 surplus cryopreserved blastocysts)	Male infertility	RNA-seq