Q12852 (M3K12_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 127.
History...
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | 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 names |
| ||||
| Organism | Homo sapiens (Human) [Reference proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo![]() |
Protein attributes
| Sequence length | 859 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | May be an activator of the JNK/SAPK pathway. Phosphorylates beta-casein, histone 1 and myelin basic protein in vitro. |
| Catalytic activity | ATP + a protein = ADP + a phosphoprotein. |
| Cofactor | Magnesium. |
| Subunit structure | Interacts with MBIP. Ref.7 |
| Subcellular location | Cytoplasm By similarity. Membrane; Peripheral membrane protein By similarity. |
| Tissue specificity | Highly expressed in brain and kidney. |
| Domain | Interacts with MBIP through the leucine-zipper motif. |
| Post-translational modification | Autophosphorylated on Ser/Thr. Phosphorylated in cytosol under basal conditions and dephosphorylated when membrane-associated By similarity. |
| Sequence similarities | Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily. Contains 1 protein kinase domain. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| FRA10AC1 | Q70Z53 | 2 | EBI-710223,EBI-710176 |
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q12852-1) 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. | ||||||
| Isoform 2 (identifier: Q12852-2) The sequence of this isoform differs from the canonical sequence as follows: 46-46: H → QCVLRDVVPLGGQGGGGPSPSPGGEPPPEPFANS | ||||||
| Note: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 859 | 859 | Mitogen-activated protein kinase kinase kinase 12 | PRO_0000086261 | |||||
Regions | |||||||||
| Domain | 125 – 366 | 242 | Protein kinase | ||||||
| Nucleotide binding | 131 – 139 | 9 | ATP By similarity | ||||||
| Region | 390 – 411 | 22 | Leucine-zipper 1 | ||||||
| Region | 443 – 464 | 22 | Leucine-zipper 2 | ||||||
| Compositional bias | 665 – 668 | 4 | Poly-Pro | ||||||
| Compositional bias | 720 – 731 | 12 | Glu-rich (acidic) | ||||||
Sites | |||||||||
| Active site | 236 | 1 | Proton acceptor By similarity | ||||||
| Binding site | 152 | 1 | ATP By similarity | ||||||
Natural variations | |||||||||
| Alternative sequence | 46 | 1 | H → QCVLRDVVPLGGQGGGGPSP SPGGEPPPEPFANS in isoform 2. | VSP_044646 | |||||
| Natural variant | 409 | 1 | E → K in a breast pleomorphic lobular carcinoma sample; somatic mutation. Ref.10 | VAR_040705 | |||||
| Natural variant | 628 | 1 | G → R. Ref.10 Corresponds to variant rs34366500 [ dbSNP | Ensembl ]. | VAR_040706 | |||||
| Natural variant | 640 | 1 | G → S. Ref.10 Corresponds to variant rs55794887 [ dbSNP | Ensembl ]. | VAR_040707 | |||||
Experimental info | |||||||||
| Sequence conflict | 355 | 1 | P → S in BAG52841. Ref.3 | ||||||
| Sequence conflict | 498 | 1 | K → N in AAA67343. Ref.1 | ||||||
| Sequence conflict | 504 | 1 | K → Q in AAA67343. Ref.1 | ||||||
| Sequence conflict | 511 | 1 | T → A in AAA67343. Ref.1 | ||||||
| Sequence conflict | 533 | 1 | G → A in AAA67343. Ref.1 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Cloning of a novel putative protein kinase having a leucine zipper domain from human brain." Reddy U.R., Pleasure D. Biochem. Biophys. Res. Commun. 202:613-620(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Teratocarcinoma. |
| [2] | "SP3 acts as a positive regulator on the core promoter of human ZPK gene." Itoh A., Wang Z., Ito Y., Reddy U.R., Itoh T. Biochem. Biophys. Res. Commun. 313:612-618(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [3] | "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). |
| [4] | "The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. Gibbs R.A.Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [5] | Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [6] | "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] (ISOFORM 1). Tissue: Testis. |
| [7] | "MAPK upstream kinase (MUK)-binding inhibitory protein, a negative regulator of MUK/Dual leucine zipper-bearing kinase/leucine zipper protein kinase." Fukuyama K., Yoshida M., Yamashita A., Deyama T., Baba M., Suzuki A., Mohri H., Ikezawa Z., Nakajima H., Hirai S., Ohno S. J. Biol. Chem. 275:21247-21254(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MBIP. |
| [8] | "Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. |
| [9] | "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell. |
| [10] | "Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. Stratton M.R.Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] LYS-409; ARG-628 AND SER-640. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | 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. |
| IPI | IPI00292181. IPI00796081. |
| PIR | JC2363. |
| RefSeq | NP_001180440.1. NM_001193511.1. NP_006292.3. NM_006301.3. |
| UniGene | Hs.713539. |
3D structure databases | |
| ProteinModelPortal | Q12852. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q12852. 8 interactions. |
| MINT | MINT-1382019. |
| STRING | 9606.ENSP00000267079. |
PTM databases | |
| PhosphoSite | Q12852. |
Polymorphism databases | |
| DMDM | 116242624. |
Proteomic databases | |
| PaxDb | Q12852. |
| PRIDE | Q12852. |
Protocols and materials databases | |
| DNASU | 7786. |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000267079; ENSP00000267079; ENSG00000139625. ENST00000547035; ENSP00000448689; ENSG00000139625. ENST00000547488; ENSP00000449038; ENSG00000139625. |
| GeneID | 7786. |
| KEGG | hsa:7786. |
| UCSC | uc001sdm.2. human. |
Organism-specific databases | |
| CTD | 7786. |
| GeneCards | GC12M053870. |
| H-InvDB | HIX0010672. |
| HGNC | HGNC:6851. MAP3K12. |
| HPA | HPA039936. |
| MIM | 600447. gene. |
| neXtProt | NX_Q12852. |
| PharmGKB | PA30595. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | COG0515. |
| HOGENOM | HOG000113435. |
| HOVERGEN | HBG052383. |
| InParanoid | Q12852. |
| KO | K04423. |
| OMA | RSDDMCS. |
| PhylomeDB | Q12852. |
Enzyme and pathway databases | |
| Pathway_Interaction_DB | p38alphabetapathway. Regulation of p38-alpha and p38-beta. |
Gene expression databases | |
| ArrayExpress | Q12852. |
| Bgee | Q12852. |
| CleanEx | HS_MAP3K12. |
| Genevestigator | Q12852. |
| GermOnline | ENSG00000139625. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR011009. Kinase-like_dom. IPR017419. MAP3K12_MAP3K13. IPR027257. MAPKKK12. IPR000719. Prot_kinase_cat_dom. IPR001245. Ser-Thr/Tyr_kinase_cat_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view] |
| Pfam | PF07714. Pkinase_Tyr. 1 hit. [Graphical view] |
| PIRSF | PIRSF500741. MAPKKK12. 1 hit. PIRSF038165. MAPKKK12_MAPKKK13. 1 hit. |
| PRINTS | PR00109. TYRKINASE. |
| SUPFAM | SSF56112. Kinase_like. 1 hit. |
| PROSITE | PS00107. PROTEIN_KINASE_ATP. False negative. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other | |
| BindingDB | Q12852. |
| ChEMBL | CHEMBL1908389. |
| ChiTaRS | MAP3K12. human. |
| GenomeRNAi | 7786. |
| NextBio | 30143. |
| SOURCE | Search... |
Entry information
| Entry name | M3K12_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q12852 Secondary accession number(s): B3KSS9 Q8WY25 | ||||||||
| Entry history |
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| Entry status | 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. | ||||||||
Relevant documents
| Human and mouse protein kinases Human and mouse protein kinases: classification and index |
| 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 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 |
| SIMILARITY comments Index of protein domains and families |

Clusters with
