Q12852 (M3K12_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names 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

Name:	MAP3K12
Synonyms:	ZPK

Organism

Homo sapiens (Human)

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.4
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. Ref.5
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

Keywords
Cellular component	Cytoplasm Membrane
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	ATP-binding Magnesium Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	JNK cascade Inferred from sequence or structural similarity. Source: UniProtKB histone phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB peptidyl-serine phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB peptidyl-threonine phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB protein autophosphorylation Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	cytosol Inferred from sequence or structural similarity. Source: UniProtKB membrane fraction Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW MAP kinase kinase kinase activity Inferred from electronic annotation. Source: EC magnesium ion binding Inferred from electronic annotation. Source: InterPro protein homodimerization activity Inferred from sequence or structural similarity. Source: UniProtKB protein kinase binding Inferred from physical interaction Ref.2. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FRA10AC1	Q70Z53	2	EBI-710223,EBI-710176

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
	Domain	390 – 411	22	Leucine-zipper 1
	Domain	443 – 464	22	Leucine-zipper 2
	Nucleotide binding	131 – 139	9	ATP By similarity
	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
Amino acid modifications
	Modified residue	634	1	Phosphoserine Ref.5
	Modified residue	757	1	Phosphoserine Ref.5
Natural variations
	Natural variant	409	1	E → K in a breast pleomorphic lobular carcinoma sample; somatic mutation. Ref.6		VAR_040705
	Natural variant	628	1	G → R. Ref.6 Corresponds to variant rs34366500 [ dbSNP | Ensembl ].		VAR_040706
	Natural variant	640	1	G → S. Ref.6 Corresponds to variant rs55794887 [ dbSNP | Ensembl ].		VAR_040707
Experimental info
	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

	Sequence		Length	Mass (Da)
	Q12852 [UniParc]. Last modified October 17, 2006. Version 2. Checksum: 1E1BCAD2F6DFCFE8	FASTA	859	93,219
	10 20 30 40 50 60 MACLHETRTP SPSFGGFVST LSEASMRKLD PDTSDCTPEK DLTPTHVLQL HEQDAGGPGG 70 80 90 100 110 120 AAGSPESRAS RVRADEVRLQ CQSGSGFLEG LFGCLRPVWT MIGKAYSTEH KQQQEDLWEV 130 140 150 160 170 180 PFEEILDLQW VGSGAQGAVF LGRFHGEEVA VKKVRDLKET DIKHLRKLKH PNIITFKGVC 190 200 210 220 230 240 TQAPCYCILM EFCAQGQLYE VLRAGRPVTP SLLVDWSMGI AGGMNYLHLH KIIHRDLKSP 250 260 270 280 290 300 NMLITYDDVV KISDFGTSKE LSDKSTKMSF AGTVAWMAPE VIRNEPVSEK VDIWSFGVVL 310 320 330 340 350 360 WELLTGEIPY KDVDSSAIIW GVGSNSLHLP VPSSCPDGFK ILLRQCWNSK PRNRPSFRQI 370 380 390 400 410 420 LLHLDIASAD VLSTPQETYF KSQAEWREEV KLHFEKIKSE GTCLHRLEEE LVMRRREELR 430 440 450 460 470 480 HALDIREHYE RKLERANNLY MELNALMLQL ELKERELLRR EQALERRCPG LLKPHPSRGL 490 500 510 520 530 540 LHGNTMEKLI KKRNVPQKLS PHSKRPDILK TESLLPKLDA ALSGVGLPGC PKGPPSPGRS 550 560 570 580 590 600 RRGKTRHRKA SAKGSCGDLP GLRTAVPPHE PGGPGSPGGL GGGPSAWEAC PPALRGLHHD 610 620 630 640 650 660 LLLRKMSSSS PDLLSAALGS RGRGATGGAG DPGSPPPARG DTPPSEGSAP GSTSPDSPGG 670 680 690 700 710 720 AKGEPPPPVG PGEGVGLLGT GREGTSGRGG SRAGSQHLTP AALLYRAAVT RSQKRGISSE 730 740 750 760 770 780 EEEGEVDSEV ELTSSQRWPQ SLNMRQSLST FSSENPSDGE EGTASEPSPS GTPEVGSTNT 790 800 810 820 830 840 DERPDERSDD MCSQGSEIPL DPPPSEVIPG PEPSSLPIPH QELLRERGPP NSEDSDCDST 850 ELDNSNSVDA LRPPASLPP

References

	« Hide 'large scale' referencesShow '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: 8037767] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. 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: 14697235] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[4]	"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: 10801814] [Abstract] Cited for: INTERACTION WITH MBIP.
[5]	"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: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-634 AND SER-757, MASS SPECTROMETRY.
[6]	"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. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [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. BC050050 mRNA. Translation: AAH50050.1. Sequence problems.
IPI	IPI00292181.
PIR	JC2363.
RefSeq	NP_001180440.1. NM_001193511.1. NP_006292.3. NM_006301.3.
UniGene	Hs.713539.
3D structure databases
ProteinModelPortal	Q12852.
SMR	Q12852. Positions 118-365.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q12852. 7 interactions.
MINT	MINT-1382019.
STRING	Q12852.
PTM databases
PhosphoSite	Q12852.
Polymorphism databases
DMDM	116242624.
Proteomic databases
PRIDE	Q12852.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000267079; ENSP00000267079; ENSG00000139625.
GeneID	7786.
KEGG	hsa:7786.
UCSC	uc001sdm.1. human.
Organism-specific databases
CTD	7786.
GeneCards	GC12M053870.
HGNC	HGNC:6851. MAP3K12.
HPA	HPA039936.
MIM	600447. gene.
neXtProt	NX_Q12852.
PharmGKB	PA30595.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG15264.
GeneTree	ENSGT00600000084040.
HOVERGEN	HBG052383.
InParanoid	Q12852.
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. IPR000719. Prot_kinase_cat_dom. IPR001245. Ser-Thr/Tyr_kinase. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
KO	K04423.
Pfam	PF07714. Pkinase_Tyr. 1 hit. [Graphical view]
PIRSF	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
NextBio	30143.
SOURCE	Search...

Entry information

Entry name

M3K12_HUMAN

Accession

Primary (citable) accession number: Q12852
Secondary accession number(s): Q86VQ5, Q8WY25

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2001
Last sequence update:	October 17, 2006
Last modified:	January 25, 2012
This is version 113 of the entry and version 2 of the sequence. [Complete history]

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.