Mitogen-activated protein kinase kinase kinase 2

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Q61083 (M3K2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 106. History...

Clusters with 100%, 90%, 50% identity |

Documents (3) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Mitogen-activated protein kinase kinase kinase 2
EC=2.7.11.25

Alternative name(s):
MAPK/ERK kinase kinase 2
Short name=MEK kinase 2
Short name=MEKK 2

Gene names

Name:	Map3k2
Synonyms:	Mekk2

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 › Mus

Protein attributes

Sequence length	619 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Component of a protein kinase signal transduction cascade. Regulates the JNK and ERK5 pathways by phosphorylating and activating MAP2K5 and MAP2K7. Plays a role in caveolae kiss-and-run dynamics By similarity. Ref.3
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium.
Enzyme regulation	Activated by phosphorylation on Thr-524 By similarity. Interacts with PKN2; the interaction activates PKN2 kinase activity in a MAP3K2-independent kinase activity.
Subunit structure	Self-associates By similarity. Binds both upstream activators and downstream substrates in multimolecular complexes. Interacts (via the kinase catalytic domain) with STK38 By similarity. Ref.2 Ref.4
Subcellular location	Cytoplasm. Nucleus. Note: Upon EGF stimulation, translocates into the nucleus.
Post-translational modification	Autophosphorylated. Ref.3 Ref.5 Ref.6
Sequence similarities	Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily. Contains 1 OPR domain. Contains 1 protein kinase domain.
Sequence caution	The sequence AAB03536.1 differs from that shown. Reason: Frameshift at positions 20 and 53.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW MAP kinase kinase kinase activity Inferred from electronic annotation. Source: EC metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction Ref.4. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Map2k5	Q9WVS7	4	EBI-446134,EBI-446144

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 619

619

Mitogen-activated protein kinase kinase kinase 2

PRO_0000086244

Regions

Domain

43 – 122

OPR

Domain

356 – 616

261

Protein kinase

Nucleotide binding

362 – 370

ATP By similarity

Sites

Active site

483

Proton acceptor By similarity

Binding site

385

ATP By similarity

Amino acid modifications

Modified residue

Phosphoserine By similarity

Modified residue

153

Phosphoserine Ref.6

Modified residue

163

Phosphoserine By similarity

Modified residue

164

Phosphoserine By similarity

Modified residue

239

Phosphoserine By similarity

Modified residue

293

Phosphothreonine By similarity

Modified residue

294

Phosphoserine By similarity

Modified residue

297

Phosphoserine By similarity

Modified residue

300

Phosphoserine By similarity

Modified residue

302

Phosphoserine By similarity

Modified residue

304

Phosphothreonine Ref.5

Modified residue

309

Phosphoserine By similarity

Modified residue

310

Phosphothreonine By similarity

Modified residue

312

Phosphoserine By similarity

Modified residue

314

Phosphoserine By similarity

Modified residue

315

Phosphoserine By similarity

Modified residue

331

Phosphoserine Ref.5

Modified residue

337

Phosphothreonine By similarity

Modified residue

344

Phosphoserine By similarity

Modified residue

347

Phosphoserine By similarity

Modified residue

349

Phosphoserine By similarity

Modified residue

514

Phosphoserine By similarity

Modified residue

524

Phosphothreonine By similarity

Experimental info

Mutagenesis

571

F → A: No effect on autophosphorylation. Fails to induce activation of the AP-1 transcription factor, MAPK7 or MAPK8. Ref.3

Mutagenesis

573

I → A: Loss of autophosphorylation. Fails to induce activation of the AP-1 transcription factor, MAPK7 or MAPK8. Ref.3

Mutagenesis

575

T → A: Loss of autophosphorylation and fails to induce activation of the AP-1 transcription factor, MAPK7 or MAPK8; when associated with A-575 and A-576. Ref.3

Mutagenesis

576

Q → A: Loss of autophosphorylation and fails to induce activation of the AP-1 transcription factor, MAPK7 or MAPK8; when associated with A-574 and A-576. Ref.3

Mutagenesis

577

P → A: Loss of autophosphorylation and fails to induce activation of the AP-1 transcription factor, MAPK7 or MAPK8; when associated with A-575 and A-576. Ref.3

Mutagenesis

580

P → A: Loss of autophosphorylation. Ref.3

Mutagenesis

582

L → A: No effect on autophosphorylation and AP-1 transcription factor, MAPK7 or MAPK8 activity. Fails to induce activation and loss of autophosphorylation; when associated with A-582. Ref.3

Mutagenesis

583

P → A: No effect on autophosphorylation and AP-1 transcription factor, MAPK7 or MAPK8 activity. Fails to induce activation and loss of autophosphorylation; when associated with A-581. Ref.3

Mutagenesis

586

V → A: No effect on AP-1 transcription factor activity. Ref.3

Sequences

Sequence

Length

Mass (Da)

Tools

Q61083 [UniParc].

Last modified March 29, 2005. Version 2.
Checksum: 711DA492F18999B6
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FASTA

619

69,574

        10         20         30         40         50         60 
MDDQQALNSI MQDLAVLHKA SRPALSLQET RKAKPSSPKK QNDVRVKFEH RGEKRILQVT 

        70         80         90        100        110        120 
RPVKLEDLRS KSKIAFGQSM DLHYTNNELV IPLTTQDDLD KAVELLDRSI HMKSLKILLV 

       130        140        150        160        170        180 
VNGSTQATNL EPSPSPEDLN NTPLGAERKK RLSVVGPPNR DRSSPPPGYI PDILHQIARN 

       190        200        210        220        230        240 
GSFTSINSEG EFIPESMDQM LDPLSLSSPE NSGSGSCPSL DSPLDGESYP KSRMPRAQSY 

       250        260        270        280        290        300 
PDNHQEFTDY DNPIFEKFGK GGTYPRRYHV SYHHQEYNDG RKTFPRARRT QGTSFRSPVS 

       310        320        330        340        350        360 
FSPTDHSLST SSGSSVFTPE YDDSRIRRRG SDIDNPTLTV TDISPPSRSP RAPTNWRLGK 

       370        380        390        400        410        420 
LLGQGAFGRV YLCYDVDTGR ELAVKQVQFN PESPETSKEV NALECEIQLL KNLLHERIVQ 

       430        440        450        460        470        480 
YYGCLRDPQE KTLSIFMELS PGGSIKDQLK AYGALTENVT RKYTRQILEG VHYLHSNMIV 

       490        500        510        520        530        540 
HRDIKGANIL RDSTGNIKLG DFGASKRLQT ICLSGTGMKS VTGTPYWMSP EVISGEGYGR 

       550        560        570        580        590        600 
KADIWSVACT VVEMLTEKPP WAEFEAMAAI FKIATQPTNP KLPPHVSDYT RDFLKRIFVE 

       610 
AKLRPSAEEL LRHMFVHYH

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of mitogen-activated protein/ERK kinase kinases (MEKK) 2 and 3. Regulation of sequential phosphorylation pathways involving mitogen-activated protein kinase and c-Jun kinase." Blank J.L., Gerwins P., Elliott E.M., Sather S., Johnson G.L. J. Biol. Chem. 271:5361-5368(1996) [PubMed: 8621389] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"MEK kinase 2 binds and activates protein kinase C-related kinase 2. Bifurcation of kinase regulatory pathways at the level of an MAPK kinase kinase." Sun W., Vincent S., Settleman J., Johnson G.L. J. Biol. Chem. 275:24421-24428(2000) [PubMed: 10818102] [Abstract] Cited for: INTERACTION WITH PKN2.
[3]	"Mutations in protein kinase subdomain X differentially affect MEKK2 and MEKK1 activity." Huang J., Tu Z., Lee F.S. Biochem. Biophys. Res. Commun. 303:532-540(2003) [PubMed: 12659851] [Abstract] Cited for: FUNCTION, AUTOPHOSPHORYLATION, MUTAGENESIS OF PHE-571; ISO-573; THR-575; GLN-576; PRO-577; PRO-580; LEU-582; PRO-583 AND VAL-586.
[4]	"PB1 domains of MEKK2 and MEKK3 interact with the MEK5 PB1 domain for activation of the ERK5 pathway." Nakamura K., Johnson G.L. J. Biol. Chem. 278:36989-36992(2003) [PubMed: 12912994] [Abstract] Cited for: INTERACTION WITH MAP2K5.
[5]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed: 17242355] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-304 AND SER-331, MASS SPECTROMETRY. Tissue: Liver.
[6]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed: 19367708] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-153, MASS SPECTROMETRY. Tissue: Melanoma.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U43186 mRNA. Translation: AAB03536.1. Frameshift.
IPI	IPI00117088.
UniGene	Mm.211762.
3D structure databases
ProteinModelPortal	Q61083.
SMR	Q61083. Positions 36-122, 354-617.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q61083. 1 interaction.
STRING	Q61083.
PTM databases
PhosphoSite	Q61083.
Proteomic databases
PRIDE	Q61083.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
UCSC	uc008ejd.2. mouse.
Organism-specific databases
MGI	MGI:1346873. Map3k2.
Phylogenomic databases
eggNOG	roNOG14449.
GeneTree	ENSGT00600000084293.
HOGENOM	HBG446160.
HOVERGEN	HBG006303.
InParanoid	Q61083.
OrthoDB	EOG4R7V9F.
Enzyme and pathway databases
BRENDA	2.7.12.2. 3474.
Gene expression databases
ArrayExpress	Q61083.
Bgee	Q61083.
CleanEx	MM_MAP3K2.
Genevestigator	Q61083.
GermOnline	ENSMUSG00000024383. Mus musculus.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000270. OPR_PB1. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_kinase-like_dom. IPR002290. Ser/Thr_kinase_dom. [Graphical view]
Pfam	PF00564. PB1. 1 hit. PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00666. PB1. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. False negative. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

M3K2_MOUSE

Accession

Primary (citable) accession number: Q61083

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	March 29, 2005
Last modified:	January 25, 2012
This is version 106 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents