Q63932 (MP2K2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Dual specificity mitogen-activated protein kinase kinase 2
Short name=MAP kinase kinase 2
Short name=MAPKK 2
EC=2.7.12.2

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

Gene names

Name:	Map2k2
Synonyms:	Mek2, Mkk2, Prkmk2

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	401 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.6
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Inhibited by serine/threonine phosphatase 2A.
Subunit structure	Interacts with MORG1. Interacts with SGK1 By similarity. Ref.5 Ref.6
Tissue specificity	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.
Post-translational modification	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. Ref.6
Sequence similarities	Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase Tyrosine-protein kinase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	positive regulation of cell motility Inferred from direct assay. Source: BHF-UCL
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein complex scaffold Inferred from direct assay. Source: BHF-UCL protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW protein tyrosine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 401	401	Dual specificity mitogen-activated protein kinase kinase 2		PRO_0000086373
Regions
	Domain	72 – 370	299	Protein kinase
	Nucleotide binding	78 – 86	9	ATP By similarity
	Compositional bias	266 – 316	51	Pro-rich
Sites
	Active site	194	1	Proton acceptor By similarity
	Binding site	101	1	ATP
	Site	10 – 11	2	Cleavage; by anthrax lethal factor By similarity
Amino acid modifications
	Modified residue	1	1	N-acetylmethionine By similarity
	Modified residue	23	1	Phosphoserine By similarity
	Modified residue	222	1	Phosphoserine; by RAF By similarity
	Modified residue	226	1	Phosphoserine; by RAF By similarity
	Modified residue	293	1	Phosphoserine By similarity
	Modified residue	295	1	Phosphoserine By similarity
	Modified residue	395	1	Phosphothreonine By similarity
	Modified residue	397	1	Phosphothreonine By similarity
Experimental info
	Mutagenesis	101	1	K → M: Inactivation.
	Sequence conflict	96	1	L → F in AAC60678. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q63932 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: F00CD807E86F5B26	FASTA	401	44,402
	10 20 30 40 50 60 MLARRKPVLP ALTINPTIAE GPSPTSEGAS EANLVDLQKK LEELDLDEQQ RKRLEAFLTQ 70 80 90 100 110 120 KAKVGELKDD DFERISELGA GNGGVVTKAR HRPSGLIMAR KLIHLEIKPA VRNQIIRELQ 130 140 150 160 170 180 VLHECNSPYI VGFYGAFYSD GEISICMEHM DGGSLDQVLK EAKRIPEDIL GKVSIAVLRG 190 200 210 220 230 240 LAYLREKHQI MHRDVKPSNI LVNSRGEIKL CDFGVSGQLI DSMANSFVGT RSYMSPERLQ 250 260 270 280 290 300 GTHYSVQSDI WSMGLSLVEL AIGRYPIPPP DAKELEASFG RPVVDGADGE PHSVSPRPRP 310 320 330 340 350 360 PGRPISVGHG MDSRPAMAIF ELLDYIVNEP PPKLPSGVFS SDFQEFVNKC LIKNPAERAD 370 380 390 400 LKLLMNHAFI KRSEGEEVDF AGWLCRTLRL KQPSTPTRTA V

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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(1993) [PubMed: 8297798] [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(2005) [PubMed: 16141072] [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 (JUL-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(1992) [PubMed: 1381507] [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(2004) [PubMed: 15118098] [Abstract] Cited for: INTERACTION WITH MORG1.
[6]	"A Mek1-Mek2 heterodimer determines the strength and duration of the Erk signal." Catalanotti F., Reyes G., Jesenberger V., Galabova-Kovacs G., de Matos Simoes R., Carugo O., Baccarini M. Nat. Struct. Mol. Biol. 16:294-303(2009) [PubMed: 19219045] [Abstract] Cited for: INTERACTION WITH MAP2K1/MEK1, PHOSPHORYLATION BY MAP2K1/MEK1, FUNCTION IN ERK SIGNALING.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	S68267 mRNA. Translation: AAC60678.1. AK009392 mRNA. Translation: BAB26261.1. AK080574 mRNA. Translation: BAC37945.1. CH466553 Genomic DNA. Translation: EDL31456.1.
IPI	IPI00135708.
RefSeq	NP_075627.2. NM_023138.4.
UniGene	Mm.275436.
3D structure databases
ProteinModelPortal	Q63932.
SMR	Q63932. Positions 60-393.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-454N.
IntAct	Q63932. 3 interactions.
MINT	MINT-1518275.
STRING	Q63932.
PTM databases
PhosphoSite	Q63932.
Proteomic databases
PRIDE	Q63932.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000143517; ENSMUSP00000121111; ENSMUSG00000035027.
GeneID	26396.
KEGG	mmu:26396.
Organism-specific databases
CTD	5605.
MGI	MGI:1346867. Map2k2.
Phylogenomic databases
GeneTree	ENSGT00570000078767.
HOGENOM	HBG755340.
HOVERGEN	HBG108518.
InParanoid	Q63932.
OrthoDB	EOG4SF965.
PhylomeDB	Q63932.
Enzyme and pathway databases
BRENDA	2.7.12.2. 3474.
Gene expression databases
ArrayExpress	Q63932.
Bgee	Q63932.
CleanEx	MM_MAP2K2.
Genevestigator	Q63932.
GermOnline	ENSMUSG00000035027. Mus musculus.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_kinase-like_dom. IPR008271. Ser/Thr_kinase_AS. IPR002290. Ser/Thr_kinase_dom. [Graphical view]
KO	K04369.
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SMART	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. 1 hit. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

MP2K2_MOUSE

Accession

Primary (citable) accession number: Q63932
Secondary accession number(s): Q9D7B0

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	July 27, 2011
Last modified:	December 14, 2011
This is version 100 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program