Reviewed, UniProtKB/Swiss-Prot Q60700 (M3K12_MOUSE)

Names and origin

Protein names

Recommended name:
    Mitogen-activated protein kinase kinase kinase 12
    EC=2.7.11.25
Alternative name(s):
    Mixed lineage kinase
    Leucine-zipper protein kinase
      Short name=ZPK
    Dual leucine zipper bearing kinase
      Short name=DLK
    MAPK-upstream kinase
      Short name=MUK

Gene names

Name:	Map3k12
Synonyms:	Zpk

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	888 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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 By similarity.
Subcellular location	Cytoplasm. Membrane; Peripheral membrane protein.
Tissue specificity	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.
Domain	Interacts with MBIP through the leucine-zipper motif By similarity.
Post-translational modification	Autophosphorylated on Ser/Thr. Phosphorylated in cytosol under basal conditions and dephosphorylated when membrane-associated. 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
Domain	Repeat
Ligand	ATP-binding Magnesium Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	histone phosphorylation Ref.5 Inferred from direct assay. Source: UniProtKB peptidyl-serine phosphorylation Ref.1 Ref.5 Inferred from direct assay. Source: UniProtKB peptidyl-threonine phosphorylation Ref.1 Ref.5 Inferred from direct assay. Source: UniProtKB protein amino acid autophosphorylation Ref.1 Ref.5 Inferred from direct assay. Source: UniProtKB
Cellular component	axon part Inferred from direct assay. Source: MGI cytosol Ref.5 Inferred from direct assay. Source: UniProtKB extrinsic to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell growth cone Inferred from direct assay. Source: MGI plasma membrane Ref.5 Inferred from direct assay. 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: UniProtKB-KW protein homodimerization activity Ref.5 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 888	888	Mitogen-activated protein kinase kinase kinase 12		PRO_0000086262
Regions
	Domain	158 – 399	242	Protein kinase
	Domain	423 – 444	22	Leucine-zipper 1 Potential
	Domain	476 – 497	22	Leucine-zipper 2 Potential
	Nucleotide binding	164 – 172	9	ATP By similarity
	Compositional bias	56 – 62	7	Poly-Gly
	Compositional bias	668 – 671	4	Poly-Pro
	Compositional bias	698 – 701	4	Poly-Pro
	Compositional bias	753 – 764	12	Glu-rich (acidic)
Sites
	Active site	269	1	Proton acceptor By similarity
	Binding site	185	1	ATP
Experimental info
	Mutagenesis	185	1	K → A: Loss of catalytic activity. Ref.5
	Mutagenesis	192	1	E → A: No change. Ref.5
	Sequence conflict	18	1	V → A in AAB17123. Ref.2
	Sequence conflict	28 – 29	2	KL → NV in AAB17123. Ref.2
	Sequence conflict	218	1	C → S in BAC26658. Ref.3
	Sequence conflict	382	1	S → T in AAB17123. Ref.2
	Sequence conflict	392	1	Q → K in BAC28689. Ref.3
	Sequence conflict	494 – 495	2	EQ → DE in AAB17123. Ref.2
	Sequence conflict	517	1	N → D in AAB17123. Ref.2
	Sequence conflict	794	1	E → G in AAB17123. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q60700-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: CFECF1D34F889ABB	FASTA	888	96,084
	10 20 30 40 50 60 MACLHETRTP SPSFGGFVST LSEASMRKLD PDTSDCTPEK DLTPTQCVLR DVVPLGGQGG 70 80 90 100 110 120 GGPSPSPGGE PPPEPFANSV LQLHEQDTGG PGGATGSPES RASRVRADEV RLQCQSGSGF 130 140 150 160 170 180 LEGLFGCLRP VWTMIGKAYS TEHKQQQEDL WEVPFEEILD LQWVGSGAQG AVFLGRFHGE 190 200 210 220 230 240 EVAVKKVRDL KETDIKHLRK LKHPNIITFK GVCTQAPCYC ILMEFCAQGQ LYEVLRAGRP 250 260 270 280 290 300 VTPSLLVDWS MGIAGGMNYL HLHKIIHRDL KSPNMLITYD DVVKISDFGT SKELSDKSTK 310 320 330 340 350 360 MSFAGTVAWM APEVIRNEPV SEKVDIWSFG VVLWELLTGE IPYKDVDSSA IIWGVGSNSL 370 380 390 400 410 420 HLPVPSSCPD GFKILLRQCW NSKPRNRPSF RQILLHLDIA SADVLSTPQE TYFKSQAEWR 430 440 450 460 470 480 EEVKLHFEKI KSEGTCLHRL EEELVMRRRE ELRHALDIRE HYERKLERAN NLYMELNALM 490 500 510 520 530 540 LQLELKEREL LRREQALERR CPGLLKSHPS RGLLHGNTME KLIKKRNVPQ KLSPHSKRPD 550 560 570 580 590 600 ILKTESLLPK LDAALSGVGL PGCPKGPPSP GRSRRGKTRH RKASAKGSCG DLPGLRAALP 610 620 630 640 650 660 PHEPGGLGSP GGLGVGPSAW DACPPALRGL HHDLLLRKMS SSSPDLLSAA LGARGRGATG 670 680 690 700 710 720 GARDPGSPPP PQGDTPPSEG SAPGSTSPDS PGGAKGEPPP PVGPGEGVGL LGTGREGTAG 730 740 750 760 770 780 RGGNRAGSQH LTPAALLYRA AVTRSQKRGI SSEEEEGEVD SEVELPPSQR WPQGPNMRQS 790 800 810 820 830 840 LSTFSSENPS DVEEGTASEP SPSGTPEVGS TNTDERPDER SDDMCSQGSE IPLDLPTSEV 850 860 870 880 VPEREASSLP MQHQDGQGPN PEDSDCDSTE LDNSNSIDAL RPPASLPP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 7983011] [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: 8769565] [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: 16141072] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6. 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: 8663324] [Abstract] Cited for: PHOSPHORYLATION, MUTAGENESIS OF LYS-185 AND GLU-192.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
IPI	IPI00120072.
PIR	A55318.
RefSeq	NP_001157115.1. NP_033608.3.
UniGene	Mm.172897 Mm.236513
3D structure databases
HSSP	HSSP built from PDB template 1VR2 based on UniProtKB P35968.
ModBase	Search...
Protein-protein interaction databases
STRING	Q60700.
PTM databases
PhosphoSite	Q60700.
Proteomic databases
PRIDE	Q60700.
Genome annotation databases
Ensembl	ENSMUST00000023812; ENSMUSP00000023812; ENSMUSG00000023050; Mus musculus. [Genome view]
GeneID	26404.
KEGG	mmu:26404.
UCSC	uc007xwc.1. mouse.
Organism-specific databases
CTD	26404.
MGI	MGI:1346881. Map3k12.
Phylogenomic databases
HOGENOM	Q60700.
HOVERGEN	Q60700.
OMA	TGREGTS.
Enzyme and pathway databases
BRENDA	2.7.11.25. 244.
Gene expression databases
ArrayExpress	Q60700.
Bgee	Q60700.
CleanEx	MM_MAP3K12.
Genevestigator	Q60700.
GermOnline	ENSMUSG00000023050. Mus musculus.
Family and domain databases
InterPro	IPR017419. MAP3K12_MAP3K13. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. IPR001245. Tyr_pkinase. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
PIRSF	PIRSF038165. MAPKKK12_MAPKKK13. 1 hit.
PRINTS	PR00109. TYRKINASE.
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
PROSITE	PS00107. PROTEIN_KINASE_ATP. False negative. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	304373.
SOURCE	Search...

Entry information

Entry name

M3K12_MOUSE

Accession

Primary (citable) accession number: Q60700
Secondary accession number(s): P70286 , Q3TLL7, Q8C4N7, Q8CBX3, Q8CDL6

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2001
Last sequence update:	November 1, 1996
Last modified:	November 3, 2009
This is version 94 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)