UniProt Accession

 MK03_HUMAN; P27361; A8CZ58; B0LPG3; Q8NHX1 

Genbank Protein ID

 X60188; AY033607; DQ399291; EU332853; AC012645; CH471238; CH471238; BC013992; M84490; Z11696 

Genbank Nucleotide ID

 CAA42744.1; AAK52329.1; ABD60302.1; ABY87542.1; EAW79912.1; EAW79915.1; AAH13992.1; AAA36142.1; CAA77754.1 

Protein Name

 Mitogen-activated protein kinase 3 

Protein Synonyms/Alias

 MAP kinase 3; MAPK 3; ERT2; Extracellular signal-regulated kinase 1; ERK-1; Insulin-stimulated MAP2 kinase; MAP kinase isoform p44; p44-MAPK; Microtubule-associated protein 2 kinase; p44-ERK1 

Gene Name

 MAPK3 

Gene Synonyms/Alias

 ERK1; PRKM3 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
32	PGEVEMVKGQPFDVG	ubiquitination	[1]
72	KTRVAIKKISPFEHQ	ubiquitination	[2]
181	INTTCDLKICDFGLA	ubiquitination	[3]
220	PEIMLNSKGYTKSID	ubiquitination	[2]
287	YLQSLPSKTKVAWAK	ubiquitination	[1]
289	QSLPSKTKVAWAKLF	ubiquitination	[1]
294	KTKVAWAKLFPKSDS	ubiquitination	[1, 2, 4, 5, 6]
302	LFPKSDSKALDLLDR	ubiquitination	[1, 2]
317	MLTFNPNKRITVEEA	ubiquitination	[1, 2]
361	DLPKERLKELIFQET	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] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [3] 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]
 [4] 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]
 [5] 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]
 [6] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789] 

Functional Description

 Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. 

Sequence Annotation

 DOMAIN 42 330 Protein kinase.
 NP_BIND 48 56 ATP (By similarity).
 MOTIF 202 204 TXY.
 ACT_SITE 166 166 Proton acceptor (By similarity).
 BINDING 71 71 ATP (By similarity).
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 170 170 Phosphoserine.
 MOD_RES 198 198 Phosphothreonine.
 MOD_RES 202 202 Phosphothreonine; by MAP2K1 and MAP2K2.
 MOD_RES 204 204 Phosphotyrosine; by MAP2K1 and MAP2K2.
 MOD_RES 207 207 Phosphothreonine; by autocatalysis.  

Keyword

 3D-structure; Acetylation; Alternative splicing; Apoptosis; ATP-binding; Cell cycle; Complete proteome; Cytoplasm; Direct protein sequencing; Host-virus interaction; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transferase. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 379 AA 

Protein Sequence

Gene Ontology

 GO:0005901; C:caveola; TAS:UniProtKB.
 GO:0005829; C:cytosol; TAS:UniProtKB.
 GO:0005769; C:early endosome; TAS:UniProtKB.
 GO:0005925; C:focal adhesion; TAS:UniProtKB.
 GO:0005794; C:Golgi apparatus; TAS:UniProtKB.
 GO:0005770; C:late endosome; TAS:UniProtKB.
 GO:0015630; C:microtubule cytoskeleton; IDA:HPA.
 GO:0005739; C:mitochondrion; TAS:UniProtKB.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0031143; C:pseudopodium; IEA:Compara.
 GO:0005524; F:ATP binding; NAS:UniProtKB.
 GO:0004707; F:MAP kinase activity; IDA:UniProtKB.
 GO:0000187; P:activation of MAPK activity; TAS:Reactome.
 GO:0000186; P:activation of MAPKK activity; TAS:Reactome.
 GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
 GO:0007411; P:axon guidance; TAS:Reactome.
 GO:0030509; P:BMP signaling pathway; IMP:BHF-UCL.
 GO:0051216; P:cartilage development; IEA:Compara.
 GO:0072584; P:caveolin-mediated endocytosis; TAS:UniProtKB.
 GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
 GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; 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:0070498; P:interleukin-1-mediated signaling pathway; IMP:BHF-UCL.
 GO:0060397; P:JAK-STAT cascade involved in growth hormone signaling pathway; TAS:Reactome.
 GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IEA:Compara.
 GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome.
 GO:2000657; P:negative regulation of apolipoprotein binding; IEA:Compara.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0009887; P:organ morphogenesis; IEA:Compara.
 GO:0038083; P:peptidyl-tyrosine autophosphorylation; IDA:UniProtKB.
 GO:0030168; P:platelet activation; TAS:Reactome.
 GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:BHF-UCL.
 GO:0035066; P:positive regulation of histone acetylation; IMP:BHF-UCL.
 GO:0033129; P:positive regulation of histone phosphorylation; IMP:BHF-UCL.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IMP:BHF-UCL.
 GO:0007265; P:Ras protein signal transduction; TAS:Reactome.
 GO:0051493; P:regulation of cytoskeleton organization; TAS:UniProtKB.
 GO:2000641; P:regulation of early endosome to late endosome transport; TAS:UniProtKB.
 GO:0090170; P:regulation of Golgi inheritance; TAS:UniProtKB.
 GO:0051090; P:regulation of sequence-specific DNA binding transcription factor activity; TAS:Reactome.
 GO:0032872; P:regulation of stress-activated MAPK cascade; TAS:UniProtKB.
 GO:0006974; P:response to DNA damage stimulus; IEA:Compara.
 GO:0070849; P:response to epidermal growth factor stimulus; IDA:UniProtKB.
 GO:0043330; P:response to exogenous dsRNA; IEA:Compara.
 GO:0019233; P:sensory perception of pain; IEA:Compara.
 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:0006361; P:transcription initiation from RNA polymerase I promoter; TAS:Reactome.
 GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 

Interpro

 IPR011009; Kinase-like_dom.
 IPR003527; MAP_kinase_CS.
 IPR008349; MAPK_ERK1/2.
 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

 PS01351; MAPK
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 

PRINTS

 PR01770; ERK1ERK2MAPK.