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Protein

Mitogen-activated protein kinase kinase kinase 2

Gene

Map3k2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Enzyme regulationi

Activated by phosphorylation on Thr-524 (By similarity). Interacts with PKN2; the interaction activates PKN2 kinase activity in a MAP3K2-independent kinase activity.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei385 – 3851ATPPROSITE-ProRule annotation
Active sitei483 – 4831Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi362 – 3709ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.12.2. 3474.

Names & Taxonomyi

Protein namesi
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 namesi
Name:Map3k2
Synonyms:Mekk2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1346873. Map3k2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi571 – 5711F → A: No effect on autophosphorylation. Fails to induce activation of the AP-1 transcription factor, MAPK7 or MAPK8. 1 Publication
Mutagenesisi573 – 5731I → A: Loss of autophosphorylation. Fails to induce activation of the AP-1 transcription factor, MAPK7 or MAPK8. 1 Publication
Mutagenesisi575 – 5751T → 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. 1 Publication
Mutagenesisi576 – 5761Q → 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. 1 Publication
Mutagenesisi577 – 5771P → 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. 1 Publication
Mutagenesisi580 – 5801P → A: Loss of autophosphorylation. 1 Publication
Mutagenesisi582 – 5821L → 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. 1 Publication
Mutagenesisi583 – 5831P → 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. 1 Publication
Mutagenesisi586 – 5861V → A: No effect on AP-1 transcription factor activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 619619Mitogen-activated protein kinase kinase kinase 2PRO_0000086244Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei26 – 261PhosphoserineBy similarity
Modified residuei153 – 1531PhosphoserineBy similarity
Modified residuei164 – 1641PhosphoserineBy similarity
Modified residuei239 – 2391PhosphoserineCombined sources
Modified residuei297 – 2971PhosphoserineBy similarity
Modified residuei331 – 3311PhosphoserineCombined sources
Modified residuei344 – 3441PhosphoserineCombined sources
Modified residuei349 – 3491PhosphoserineCombined sources

Post-translational modificationi

Ubiquitination by XIAP/BIRC4 does not lead to proteasomal degradation.By similarity
Autophosphorylated.

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ61083.
MaxQBiQ61083.
PaxDbiQ61083.
PRIDEiQ61083.

PTM databases

iPTMnetiQ61083.
PhosphoSiteiQ61083.

Expressioni

Gene expression databases

CleanExiMM_MAP3K2.

Interactioni

Subunit structurei

Self-associates (By similarity). Binds both upstream activators and downstream substrates in multimolecular complexes. Interacts (via the kinase catalytic domain) with STK38 (By similarity). Interacts with XIAP/BIRC4 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Map2k5Q9WVS74EBI-446134,EBI-446144

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ61083. 2 interactions.
MINTiMINT-1531359.
STRINGi10090.ENSMUSP00000094326.

Structurei

3D structure databases

ProteinModelPortaliQ61083.
SMRiQ61083. Positions 1-122, 328-616.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini43 – 12280PB1PROSITE-ProRule annotationAdd
BLAST
Domaini356 – 616261Protein kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 PB1 domain.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0198. Eukaryota.
ENOG410XQGS. LUCA.
HOGENOMiHOG000049130.
HOVERGENiHBG006303.
InParanoidiQ61083.
PhylomeDBiQ61083.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000270. PB1_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
[Graphical view]
PfamiPF00564. PB1. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00666. PB1. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51745. PB1. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q61083-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDDQQALNSI MQDLAVLHKA SRPALSLQET RKAKPSSPKK QNDVRVKFEH
60 70 80 90 100
RGEKRILQVT RPVKLEDLRS KSKIAFGQSM DLHYTNNELV IPLTTQDDLD
110 120 130 140 150
KAVELLDRSI HMKSLKILLV VNGSTQATNL EPSPSPEDLN NTPLGAERKK
160 170 180 190 200
RLSVVGPPNR DRSSPPPGYI PDILHQIARN GSFTSINSEG EFIPESMDQM
210 220 230 240 250
LDPLSLSSPE NSGSGSCPSL DSPLDGESYP KSRMPRAQSY PDNHQEFTDY
260 270 280 290 300
DNPIFEKFGK GGTYPRRYHV SYHHQEYNDG RKTFPRARRT QGTSFRSPVS
310 320 330 340 350
FSPTDHSLST SSGSSVFTPE YDDSRIRRRG SDIDNPTLTV TDISPPSRSP
360 370 380 390 400
RAPTNWRLGK LLGQGAFGRV YLCYDVDTGR ELAVKQVQFN PESPETSKEV
410 420 430 440 450
NALECEIQLL KNLLHERIVQ YYGCLRDPQE KTLSIFMELS PGGSIKDQLK
460 470 480 490 500
AYGALTENVT RKYTRQILEG VHYLHSNMIV HRDIKGANIL RDSTGNIKLG
510 520 530 540 550
DFGASKRLQT ICLSGTGMKS VTGTPYWMSP EVISGEGYGR KADIWSVACT
560 570 580 590 600
VVEMLTEKPP WAEFEAMAAI FKIATQPTNP KLPPHVSDYT RDFLKRIFVE
610
AKLRPSAEEL LRHMFVHYH
Length:619
Mass (Da):69,574
Last modified:March 29, 2005 - v2
Checksum:i711DA492F18999B6
GO

Sequence cautioni

The sequence AAB03536.1 differs from that shown. Reason: Frameshift at positions 20 and 53. Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U43186 mRNA. Translation: AAB03536.1. Frameshift.
CCDSiCCDS29117.1.
UniGeneiMm.211762.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U43186 mRNA. Translation: AAB03536.1. Frameshift.
CCDSiCCDS29117.1.
UniGeneiMm.211762.

3D structure databases

ProteinModelPortaliQ61083.
SMRiQ61083. Positions 1-122, 328-616.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ61083. 2 interactions.
MINTiMINT-1531359.
STRINGi10090.ENSMUSP00000094326.

PTM databases

iPTMnetiQ61083.
PhosphoSiteiQ61083.

Proteomic databases

EPDiQ61083.
MaxQBiQ61083.
PaxDbiQ61083.
PRIDEiQ61083.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

MGIiMGI:1346873. Map3k2.

Phylogenomic databases

eggNOGiKOG0198. Eukaryota.
ENOG410XQGS. LUCA.
HOGENOMiHOG000049130.
HOVERGENiHBG006303.
InParanoidiQ61083.
PhylomeDBiQ61083.

Enzyme and pathway databases

BRENDAi2.7.12.2. 3474.

Miscellaneous databases

ChiTaRSiMap3k2. mouse.
PROiQ61083.
SOURCEiSearch...

Gene expression databases

CleanExiMM_MAP3K2.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000270. PB1_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
[Graphical view]
PfamiPF00564. PB1. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00666. PB1. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51745. PB1. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
    Cited for: FUNCTION, AUTOPHOSPHORYLATION, MUTAGENESIS OF PHE-571; ILE-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] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MAP2K5.
  5. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-331, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  6. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239; SER-331; SER-344 AND SER-349, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain, Kidney, Lung, Pancreas, Spleen and Testis.

Entry informationi

Entry nameiM3K2_MOUSE
AccessioniPrimary (citable) accession number: Q61083
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: March 29, 2005
Last modified: May 11, 2016
This is version 144 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.