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Protein

Dual specificity mitogen-activated protein kinase kinase 2

Gene

Map2k2

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

Functioni

Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. Activates the ERK1 and ERK2 MAP kinases.1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Inhibited by serine/threonine phosphatase 2A.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei10 – 112Cleavage; by anthrax lethal factorBy similarity
Binding sitei101 – 1011ATP
Active sitei194 – 1941Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi78 – 869ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. MAP kinase kinase activity Source: MGI
  3. PDZ domain binding Source: MGI
  4. protein complex scaffold Source: BHF-UCL
  5. protein serine/threonine/tyrosine kinase activity Source: UniProtKB
  6. protein serine/threonine kinase activator activity Source: MGI
  7. protein serine/threonine kinase activity Source: UniProtKB-KW
  8. protein tyrosine kinase activity Source: UniProtKB-KW
  9. scaffold protein binding Source: MGI

GO - Biological processi

  1. activation of MAPK activity Source: UniProtKB
  2. epithelial cell proliferation involved in lung morphogenesis Source: MGI
  3. ERK1 and ERK2 cascade Source: MGI
  4. lung morphogenesis Source: MGI
  5. peptidyl-serine autophosphorylation Source: MGI
  6. positive regulation of axonogenesis Source: MGI
  7. positive regulation of cell motility Source: BHF-UCL
  8. positive regulation of protein serine/threonine kinase activity Source: MGI
  9. regulation of axon regeneration Source: MGI
  10. regulation of early endosome to late endosome transport Source: UniProtKB
  11. regulation of Golgi inheritance Source: UniProtKB
  12. regulation of stress-activated MAPK cascade Source: UniProtKB
  13. trachea formation Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.12.2. 3474.
ReactomeiREACT_275935. RAF phosphorylates MEK.
REACT_309034. MEK activation.
REACT_341193. Signaling by FGFR.
REACT_353300. ERK2 activation.
REACT_353319. Signal transduction by L1.

Names & Taxonomyi

Protein namesi
Recommended name:
Dual specificity mitogen-activated protein kinase kinase 2 (EC:2.7.12.2)
Short name:
MAP kinase kinase 2
Short name:
MAPKK 2
Alternative name(s):
ERK activator kinase 2
MAPK/ERK kinase 2
Short name:
MEK 2
Gene namesi
Name:Map2k2
Synonyms:Mek2, Mkk2, Prkmk2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1346867. Map2k2.

Subcellular locationi

GO - Cellular componenti

  1. cell-cell junction Source: MGI
  2. cell cortex Source: Ensembl
  3. cytoplasm Source: MGI
  4. cytoplasmic side of plasma membrane Source: MGI
  5. cytosol Source: UniProtKB
  6. early endosome Source: UniProtKB
  7. endoplasmic reticulum Source: MGI
  8. focal adhesion Source: UniProtKB
  9. Golgi apparatus Source: UniProtKB
  10. late endosome Source: UniProtKB
  11. microtubule Source: MGI
  12. mitochondrion Source: UniProtKB
  13. nucleus Source: UniProtKB
  14. perinuclear region of cytoplasm Source: MGI
  15. peroxisomal membrane Source: MGI
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi101 – 1011K → M: Inactivation. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 401401Dual specificity mitogen-activated protein kinase kinase 2PRO_0000086373Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineBy similarity
Modified residuei23 – 231PhosphoserineBy similarity
Modified residuei222 – 2221Phosphoserine; by RAFBy similarity
Modified residuei226 – 2261Phosphoserine; by RAFBy similarity
Modified residuei293 – 2931PhosphoserineBy similarity
Modified residuei295 – 2951PhosphoserineBy similarity
Modified residuei395 – 3951PhosphothreonineBy similarity
Modified residuei397 – 3971PhosphothreonineBy similarity

Post-translational modificationi

Phosphorylation on Ser/Thr by MAP kinase kinase kinases (RAF or MEKK1) regulates positively the kinase activity. Phosphorylated by MAP2K1/MEK1. Low levels of autophosphorylation have been observed.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ63932.
PaxDbiQ63932.
PRIDEiQ63932.

PTM databases

PhosphoSiteiQ63932.

Expressioni

Tissue specificityi

Expressed in adult intestine, kidney, liver, lung, pancreas, spleen, thymus, and at high levels in the neonatal brain. Lower expression is found in adult brain and heart.

Gene expression databases

BgeeiQ63932.
CleanExiMM_MAP2K2.
ExpressionAtlasiQ63932. baseline and differential.
GenevestigatoriQ63932.

Interactioni

Subunit structurei

Interacts with MORG1. Interacts with SGK1 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
ARHGAP8P85298-45EBI-397724,EBI-9523517From a different organism.
PIN1Q1352612EBI-397724,EBI-714158From a different organism.
Rgs12Q8CGE93EBI-397724,EBI-7340552

Protein-protein interaction databases

BioGridi204950. 5 interactions.
DIPiDIP-454N.
IntActiQ63932. 9 interactions.
MINTiMINT-1518275.
STRINGi10090.ENSMUSP00000121111.

Structurei

3D structure databases

SMRiQ63932. Positions 60-393.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini72 – 370299Protein kinasePROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi266 – 31651Pro-richAdd
BLAST

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000119199.
HOGENOMiHOG000234206.
HOVERGENiHBG108518.
InParanoidiQ63932.
KOiK04369.
OMAiEGASEAH.
OrthoDBiEOG7HF1KZ.
TreeFamiTF105137.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q63932-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLARRKPVLP ALTINPTIAE GPSPTSEGAS EANLVDLQKK LEELDLDEQQ
60 70 80 90 100
RKRLEAFLTQ KAKVGELKDD DFERISELGA GNGGVVTKAR HRPSGLIMAR
110 120 130 140 150
KLIHLEIKPA VRNQIIRELQ VLHECNSPYI VGFYGAFYSD GEISICMEHM
160 170 180 190 200
DGGSLDQVLK EAKRIPEDIL GKVSIAVLRG LAYLREKHQI MHRDVKPSNI
210 220 230 240 250
LVNSRGEIKL CDFGVSGQLI DSMANSFVGT RSYMSPERLQ GTHYSVQSDI
260 270 280 290 300
WSMGLSLVEL AIGRYPIPPP DAKELEASFG RPVVDGADGE PHSVSPRPRP
310 320 330 340 350
PGRPISVGHG MDSRPAMAIF ELLDYIVNEP PPKLPSGVFS SDFQEFVNKC
360 370 380 390 400
LIKNPAERAD LKLLMNHAFI KRSEGEEVDF AGWLCRTLRL KQPSTPTRTA

V
Length:401
Mass (Da):44,402
Last modified:July 27, 2011 - v2
Checksum:iF00CD807E86F5B26
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti96 – 961L → F in AAC60678 (PubMed:8297798).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S68267 mRNA. Translation: AAC60678.1.
AK009392 mRNA. Translation: BAB26261.1.
AK080574 mRNA. Translation: BAC37945.1.
CH466553 Genomic DNA. Translation: EDL31456.1.
CCDSiCCDS24044.1.
RefSeqiNP_075627.2. NM_023138.4.
UniGeneiMm.275436.

Genome annotation databases

EnsembliENSMUST00000143517; ENSMUSP00000121111; ENSMUSG00000035027.
GeneIDi26396.
KEGGimmu:26396.
UCSCiuc007gfx.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S68267 mRNA. Translation: AAC60678.1.
AK009392 mRNA. Translation: BAB26261.1.
AK080574 mRNA. Translation: BAC37945.1.
CH466553 Genomic DNA. Translation: EDL31456.1.
CCDSiCCDS24044.1.
RefSeqiNP_075627.2. NM_023138.4.
UniGeneiMm.275436.

3D structure databases

SMRiQ63932. Positions 60-393.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204950. 5 interactions.
DIPiDIP-454N.
IntActiQ63932. 9 interactions.
MINTiMINT-1518275.
STRINGi10090.ENSMUSP00000121111.

PTM databases

PhosphoSiteiQ63932.

Proteomic databases

MaxQBiQ63932.
PaxDbiQ63932.
PRIDEiQ63932.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000143517; ENSMUSP00000121111; ENSMUSG00000035027.
GeneIDi26396.
KEGGimmu:26396.
UCSCiuc007gfx.2. mouse.

Organism-specific databases

CTDi5605.
MGIiMGI:1346867. Map2k2.

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000119199.
HOGENOMiHOG000234206.
HOVERGENiHBG108518.
InParanoidiQ63932.
KOiK04369.
OMAiEGASEAH.
OrthoDBiEOG7HF1KZ.
TreeFamiTF105137.

Enzyme and pathway databases

BRENDAi2.7.12.2. 3474.
ReactomeiREACT_275935. RAF phosphorylates MEK.
REACT_309034. MEK activation.
REACT_341193. Signaling by FGFR.
REACT_353300. ERK2 activation.
REACT_353319. Signal transduction by L1.

Miscellaneous databases

ChiTaRSiMap2k2. mouse.
NextBioi304343.
PROiQ63932.
SOURCEiSearch...

Gene expression databases

BgeeiQ63932.
CleanExiMM_MAP2K2.
ExpressionAtlasiQ63932. baseline and differential.
GenevestigatoriQ63932.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "MEK2 is a kinase related to MEK1 and is differentially expressed in murine tissues."
    Brott B.K., Alessandrini A., Largaespada D.A., Copeland N.G., Jenkins N.A., Crews C.M., Erikson R.L.
    Cell Growth Differ. 4:921-929(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS.
    Strain: BALB/c.
    Tissue: Neonatal brain.
  2. "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(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Cerebellum and Tongue.
  3. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "Purification of a murine protein-tyrosine/threonine kinase that phosphorylates and activates the Erk-1 gene product: relationship to the fission yeast byr1 gene product."
    Crews C.M., Erikson R.L.
    Proc. Natl. Acad. Sci. U.S.A. 89:8205-8209(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 118-140 AND 210-238.
    Tissue: T-cell.
  5. "Modular construction of a signaling scaffold: MORG1 interacts with components of the ERK cascade and links ERK signaling to specific agonists."
    Vomastek T., Schaeffer H.-J., Tarcsafalvi A., Smolkin M.E., Bissonette E.A., Weber M.J.
    Proc. Natl. Acad. Sci. U.S.A. 101:6981-6986(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MORG1.
  6. Cited for: INTERACTION WITH MAP2K1/MEK1, PHOSPHORYLATION BY MAP2K1/MEK1, FUNCTION IN ERK SIGNALING.

Entry informationi

Entry nameiMP2K2_MOUSE
AccessioniPrimary (citable) accession number: Q63932
Secondary accession number(s): Q9D7B0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 27, 2011
Last modified: April 1, 2015
This is version 131 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, Direct protein sequencing, 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

External Data

Dasty 3

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 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.