UniProt Accession

 MK01_HUMAN; P28482 

Genbank Protein ID

 M84489; Z11694; Z11695; AP000555; BC017832 

Genbank Nucleotide ID

 AAA58459.1; CAA77752.1; CAA77753.1; AAH17832.1 

Protein Name

 Mitogen-activated protein kinase 1 

Protein Synonyms/Alias

 MAP kinase 1; MAPK 1; ERT1; Extracellular signal-regulated kinase 2; ERK-2; MAP kinase isoform p42; p42-MAPK; Mitogen-activated protein kinase 2; MAP kinase 2; MAPK 2 

Gene Name

 MAPK1 

Gene Synonyms/Alias

 ERK2; PRKM1; PRKM2 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
55	KVRVAIKKISPFEHQ	ubiquitination	[1]
99	APTIEQMKDVYIVQD	ubiquitination	[2]
151	NVLHRDLKPSNLLLN	ubiquitination	[1]
164	LNTTCDLKICDFGLA	ubiquitination	[1]
203	PEIMLNSKGYTKSID	ubiquitination	[1, 2, 3]
272	LSLPHKNKVPWNRLF	ubiquitination	[1]
285	LFPNADSKALDLLDK	ubiquitination	[1]
292	KALDLLDKMLTFNPH	ubiquitination	[1, 3]
330	PIAEAPFKFDMELDD	ubiquitination	[2]
344	DLPKEKLKELIFEET	ubiquitination	[1, 2]

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] 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] 

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, DCC, 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. Mediates phosphorylation of TPR in respons to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation. 

Sequence Annotation

 DOMAIN 25 313 Protein kinase.
 NP_BIND 31 39 ATP (By similarity).
 DNA_BIND 259 277
 REGION 105 108 Inhibitor-binding.
 REGION 153 154 Inhibitor-binding.
 MOTIF 185 187 TXY.
 MOTIF 318 322 Cytoplasmic retention motif.
 MOTIF 327 333 Nuclear translocation motif.
 ACT_SITE 149 149 Proton acceptor (By similarity).
 BINDING 54 54 ATP (By similarity).
 BINDING 54 54 Inhibitor.
 BINDING 108 108 Inhibitor; via amide nitrogen and
 BINDING 114 114 Inhibitor.
 BINDING 154 154 Inhibitor.
 BINDING 166 166 Inhibitor.
 BINDING 167 167 Inhibitor.
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 29 29 Phosphoserine; by SGK1.
 MOD_RES 185 185 Phosphothreonine; by MAP2K1 and MAP2K2.
 MOD_RES 187 187 Phosphotyrosine; by MAP2K1 and MAP2K2.
 MOD_RES 190 190 Phosphothreonine; by autocatalysis.
 MOD_RES 246 246 Phosphoserine.
 MOD_RES 248 248 Phosphoserine.
 MOD_RES 284 284 Phosphoserine.  

Keyword

 3D-structure; Acetylation; Apoptosis; ATP-binding; Cell cycle; Complete proteome; Cytoplasm; Cytoskeleton; Direct protein sequencing; DNA-binding; Host-virus interaction; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Repressor; Serine/threonine-protein kinase; Transcription; Transcription regulation; Transferase. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 360 AA 

Protein Sequence

Gene Ontology

 GO:0005901; C:caveola; TAS:UniProtKB.
 GO:0005829; C:cytosol; TAS:UniProtKB.
 GO:0032839; C:dendrite cytoplasm; IEA:Compara.
 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:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
 GO:0005739; C:mitochondrion; TAS:UniProtKB.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0043204; C:perikaryon; IEA:Compara.
 GO:0031143; C:pseudopodium; IEA:Compara.
 GO:0005819; C:spindle; IEA:UniProtKB-SubCell.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
 GO:0004707; F:MAP kinase activity; TAS:ProtInc.
 GO:0008353; F:RNA polymerase II carboxy-terminal domain kinase activity; ISS: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:0050853; P:B cell receptor signaling pathway; IEA:Compara.
 GO:0072584; P:caveolin-mediated endocytosis; TAS:UniProtKB.
 GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
 GO:0019858; P:cytosine metabolic process; IEA:Compara.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0070371; P:ERK1 and ERK2 cascade; IDA:UniProtKB.
 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:0006917; P:induction of apoptosis; TAS:ProtInc.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0008286; P:insulin receptor signaling pathway; TAS:Reactome.
 GO:0060397; P:JAK-STAT cascade involved in growth hormone signaling pathway; TAS:Reactome.
 GO:0060716; P:labyrinthine layer blood vessel development; IEA:Compara.
 GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IEA:Compara.
 GO:0033598; P:mammary gland epithelial cell proliferation; IEA:Compara.
 GO:0000189; P:MAPK import into nucleus; IEA:Compara.
 GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome.
 GO:0045596; P:negative regulation of cell differentiation; IEA:Compara.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0009887; P:organ morphogenesis; IEA:Compara.
 GO:0018105; P:peptidyl-serine phosphorylation; IDA:BHF-UCL.
 GO:0030168; P:platelet activation; TAS:Reactome.
 GO:0030335; P:positive regulation of cell migration; IEA:Compara.
 GO:0008284; P:positive regulation of cell proliferation; IEA:Compara.
 GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; IDA:UniProtKB.
 GO:0045893; P:positive regulation of transcription, DNA-dependent; IEA:Compara.
 GO:0045727; P:positive regulation of translation; IEA:Compara.
 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:0043627; P:response to estrogen stimulus; IEA:Compara.
 GO:0043330; P:response to exogenous dsRNA; IEA:Compara.
 GO:0009636; P:response to toxic substance; IEA:Compara.
 GO:0019233; P:sensory perception of pain; IEA:Compara.
 GO:0051403; P:stress-activated MAPK cascade; TAS:Reactome.
 GO:0007268; P:synaptic transmission; TAS:Reactome.
 GO:0050852; P:T cell receptor signaling pathway; IEA:Compara.
 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:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
 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.