CPLM-009677

Genbank Nucleotide ID

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

Mus musculus (Mouse)

Position	Peptide	Type	References
149	NVLHRDLKPSNLLLN	acetylation	[1]
149	NVLHRDLKPSNLLLN	ubiquitination	[2]
201	PEIMLNSKGYTKSID	ubiquitination	[2]

[1] Quantitative acetylome analysis reveals the roles of SIRT1 in regulating diverse substrates and cellular pathways.
Chen Y, Zhao W, Yang JS, Cheng Z, Luo H, Lu Z, Tan M, Gu W, Zhao Y.
Mol Cell Proteomics. 2012 Oct;11(10):1048-62. [PMID: 22826441]
[2] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023]

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 (By similarity).

DOMAIN 23 311 Protein kinase.
NP_BIND 29 37 ATP (By similarity).
REGION 103 106 Inhibitor-binding (By similarity).
REGION 151 152 Inhibitor-binding (By similarity).
MOTIF 183 185 TXY.
ACT_SITE 147 147 Proton acceptor (By similarity).
BINDING 52 52 ATP (By similarity).
BINDING 52 52 Inhibitor (By similarity).
BINDING 106 106 Inhibitor; via amide nitrogen and
BINDING 112 112 Inhibitor (By similarity).
BINDING 152 152 Inhibitor (By similarity).
BINDING 164 164 Inhibitor (By similarity).
BINDING 165 165 Inhibitor (By similarity).
MOD_RES 2 2 N-acetylalanine (By similarity).
MOD_RES 27 27 Phosphoserine; by SGK1 (By similarity).
MOD_RES 183 183 Phosphothreonine; by MAP2K1 and MAP2K2.
MOD_RES 185 185 Phosphotyrosine; by MAP2K1 and MAP2K2.
MOD_RES 188 188 Phosphothreonine; by autocatalysis (By
MOD_RES 244 244 Phosphoserine (By similarity).
MOD_RES 246 246 Phosphoserine (By similarity).
MOD_RES 282 282 Phosphoserine (By similarity).

Acetylation; Apoptosis; ATP-binding; Cell cycle; Complete proteome; Cytoplasm; Cytoskeleton; Direct protein sequencing; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; Transferase.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005901; C:caveola; TAS:UniProtKB.
GO:0005856; C:cytoskeleton; 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: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; IDA:UniProtKB.
GO:0005819; C:spindle; IEA:UniProtKB-SubCell.
GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO:0004707; F:MAP kinase activity; IDA:MGI.
GO:0001784; F:phosphotyrosine binding; IMP:MGI.
GO:0008353; F:RNA polymerase II carboxy-terminal domain kinase activity; IDA:UniProtKB.
GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
GO:0050853; P:B cell receptor signaling pathway; IDA:MGI.
GO:0072584; P:caveolin-mediated endocytosis; TAS:UniProtKB.
GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
GO:0019858; P:cytosine metabolic process; IDA:MGI.
GO:0070371; P:ERK1 and ERK2 cascade; IEA:Compara.
GO:0060716; P:labyrinthine layer blood vessel development; IMP:MGI.
GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IDA:MGI.
GO:0033598; P:mammary gland epithelial cell proliferation; IDA:MGI.
GO:0000189; P:MAPK import into nucleus; IEA:Compara.
GO:0045596; P:negative regulation of cell differentiation; IGI:MGI.
GO:0009887; P:organ morphogenesis; IDA:MGI.
GO:0018105; P:peptidyl-serine phosphorylation; IDA:MGI.
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; IEA:Compara.
GO:0045893; P:positive regulation of transcription, DNA-dependent; IEA:Compara.
GO:0045727; P:positive regulation of translation; IEA:Compara.
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; NAS:UniProtKB.
GO:0032872; P:regulation of stress-activated MAPK cascade; TAS:UniProtKB.
GO:0006974; P:response to DNA damage stimulus; IDA:MGI.
GO:0070849; P:response to epidermal growth factor stimulus; ISS:UniProtKB.
GO:0043627; P:response to estrogen stimulus; IEA:Compara.
GO:0043330; P:response to exogenous dsRNA; IDA:MGI.
GO:0009636; P:response to toxic substance; IEA:Compara.
GO:0019233; P:sensory perception of pain; IEA:Compara.
GO:0050852; P:T cell receptor signaling pathway; IDA:MGI.
GO:0006351; P:transcription, DNA-dependent; NAS:UniProtKB.

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.

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

PR01770; ERK1ERK2MAPK.