UniProt Accession

 MP2K2_HUMAN; P36507 

Genbank Protein ID

 L11285; BC000471; BC018645 

Genbank Nucleotide ID

 AAH00471.1; AAH18645.1 

Protein Name

 Dual specificity mitogen-activated protein kinase kinase 2 

Protein Synonyms/Alias

 MAP kinase kinase 2; MAPKK 2; ERK activator kinase 2; MAPK/ERK kinase 2; MEK 2 

Gene Name

 MAP2K2 

Gene Synonyms/Alias

 MEK2; MKK2; PRKMK2 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
6	**MLARRKPVLPALT	ubiquitination	[1]
40	NLVDLQKKLEELELD	ubiquitination	[1, 2]
51	LELDEQQKKRLEAFL	ubiquitination	[1, 2]
61	LEAFLTQKAKVGELK	ubiquitination	[1, 3]
63	AFLTQKAKVGELKDD	ubiquitination	[1, 4]
68	KAKVGELKDDDFERI	ubiquitination	[2]
88	GNGGVVTKVQHRPSG	ubiquitination	[1, 4]
101	SGLIMARKLIHLEIK	ubiquitination	[1]
108	KLIHLEIKPAIRNQI	sumoylation	[5]
108	KLIHLEIKPAIRNQI	ubiquitination	[1, 2, 6, 7, 8]
196	QIMHRDVKPSNILVN	ubiquitination	[1, 2]
209	VNSRGEIKLCDFGVS	ubiquitination	[2]
352	FVNKCLIKNPAERAD	ubiquitination	[1]
361	PAERADLKMLTNHTF	ubiquitination	[1]
370	LTNHTFIKRSEVEEV	ubiquitination	[1]

Reference

 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [3] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [4] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [5] Oncogenic Ras abrogates MEK SUMOylation that suppresses the ERK pathway and cell transformation.
 Kubota Y, O'Grady P, Saito H, Takekawa M.
 Nat Cell Biol. 2011 Mar;13(3):282-91. [PMID: 21336309]
 [6] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [7] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
 [8] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965] 

Functional Description

 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 (By similarity). 

Sequence Annotation

 DOMAIN 72 369 Protein kinase.
 NP_BIND 78 86 ATP (By similarity).
 ACT_SITE 194 194 Proton acceptor (By similarity).
 BINDING 101 101 ATP (By similarity).
 MOD_RES 1 1 N-acetylmethionine.
 MOD_RES 222 222 O-acetylserine; by Yersinia yopJ;
 MOD_RES 222 222 Phosphoserine; by RAF; alternate.
 MOD_RES 226 226 O-acetylserine; by Yersinia yopJ;
 MOD_RES 226 226 Phosphoserine; alternate.
 MOD_RES 293 293 Phosphoserine.
 MOD_RES 295 295 Phosphoserine.
 MOD_RES 394 394 Phosphothreonine.
 MOD_RES 396 396 Phosphothreonine.  

Keyword

 3D-structure; Acetylation; ATP-binding; Complete proteome; Direct protein sequencing; Disease mutation; Kinase; Nucleotide-binding; Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; Transferase; Tyrosine-protein kinase. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 400 AA 

Protein Sequence

Gene Ontology

 GO:0005938; C:cell cortex; IEA:Compara.
 GO:0005911; C:cell-cell junction; IDA:UniProtKB.
 GO:0005829; C:cytosol; TAS:UniProtKB.
 GO:0005769; C:early endosome; TAS:UniProtKB.
 GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
 GO:0005576; C:extracellular region; NAS:UniProtKB.
 GO:0005925; C:focal adhesion; TAS:UniProtKB.
 GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
 GO:0009898; C:internal side of plasma membrane; IDA:UniProtKB.
 GO:0005770; C:late endosome; TAS:UniProtKB.
 GO:0005874; C:microtubule; IDA:UniProtKB.
 GO:0005739; C:mitochondrion; TAS:UniProtKB.
 GO:0005634; C:nucleus; TAS:UniProtKB.
 GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
 GO:0005778; C:peroxisomal membrane; IDA:UniProtKB.
 GO:0005524; F:ATP binding; NAS:UniProtKB.
 GO:0004708; F:MAP kinase kinase activity; IDA:UniProtKB.
 GO:0030165; F:PDZ domain binding; IDA:UniProtKB.
 GO:0043539; F:protein serine/threonine kinase activator activity; IDA:UniProtKB.
 GO:0004674; F:protein serine/threonine kinase activity; NAS:UniProtKB.
 GO:0004713; F:protein tyrosine kinase activity; IEA:UniProtKB-KW.
 GO:0000186; P:activation of MAPKK activity; TAS:Reactome.
 GO:0007411; P:axon guidance; TAS:Reactome.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0070371; P:ERK1 and ERK2 cascade; TAS:Reactome.
 GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0008286; P:insulin receptor signaling pathway; TAS:Reactome.
 GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0036289; P:peptidyl-serine autophosphorylation; IDA:UniProtKB.
 GO:2000147; P:positive regulation of cell motility; IEA:Compara.
 GO:0007265; P:Ras protein signal transduction; TAS:Reactome.
 GO:2000641; P:regulation of early endosome to late endosome transport; TAS:UniProtKB.
 GO:0090170; P:regulation of Golgi inheritance; TAS:UniProtKB.
 GO:0032872; P:regulation of stress-activated MAPK cascade; TAS:UniProtKB.
 GO:0051403; P:stress-activated MAPK cascade; TAS:Reactome.
 GO:0034166; P:toll-like receptor 10 signaling pathway; TAS:Reactome.
 GO:0034134; P:toll-like receptor 2 signaling pathway; TAS:Reactome.
 GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome.
 GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
 GO:0034146; P:toll-like receptor 5 signaling pathway; TAS:Reactome.
 GO:0034162; P:toll-like receptor 9 signaling pathway; TAS:Reactome.
 GO:0038123; P:toll-like receptor TLR1:TLR2 signaling pathway; TAS:Reactome.
 GO:0038124; P:toll-like receptor TLR6:TLR2 signaling pathway; TAS:Reactome.
 GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome. 

Interpro

 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR002290; Ser/Thr_dual-sp_kinase_dom.
 IPR008271; Ser/Thr_kinase_AS. 

Pfam

 PF00069; Pkinase 

SMART

 SM00220; S_TKc 

PROSITE

 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 

PRINTS