MAPK1 - Mitogen-activated protein kinase 1 - human protein (Function)
 
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MAPK1 »  Mitogen-activated protein kinase 1   [ EC 2.7.11.24 ]  (MAPK 1)
 
Protein also known as:  Extracellular signal-regulated kinase 2 (ERK-2).
Gene name:  MAPK1
Entry whose protein(s) existence is based on evidence at protein level
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1 1206 2
GENE REF ISO

Function

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Overview 
Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity.  
1
  • UniProtKB
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.  
1
  • UniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524] silver  
1
  • Ortholog Compara
DNA bindingdefinition[GO:0003677]  
1
  • UniProtKB KW
MAP kinase activitydefinition[GO:0004707]  
1
  • EC 2 GO
Mitogen-activated protein kinase kinase kinase bindingdefinition[GO:0031435] silver  
1
  • Ortholog Compara
Phosphatase bindingdefinition[GO:0019902]  
1
  • UniProtKB
Phosphotyrosine bindingdefinition[GO:0001784] silver  
1
  • Ortholog Compara
Protein bindingdefinition[GO:0005515]  
26
  • IntAct
  • UniProtKB
Protein serine/threonine kinase activitydefinition[GO:0004674]  
2
  • UniProtKB
  • BHF-UCL
RNA polymerase II carboxy-terminal domain kinase activitydefinition[GO:0008353]  
1
  • Ortholog Curator
Transcription factor bindingdefinition[GO:0008134] silver  
1
  • Ortholog Compara
GO biological process 
Apoptotic processdefinition[GO:0006915]  
1
  • UniProtKB KW
B cell receptor signaling pathwaydefinition[GO:0050853] silver  
1
  • Ortholog Compara
Caveolin-mediated endocytosisdefinition[GO:0072584]  
1
  • UniProtKB
Cell cycledefinition[GO:0007049]  
1
  • UniProtKB KW
Cellular response to DNA damage stimulusdefinition[GO:0006974] silver  
1
  • Ortholog Compara
Cellular response to granulocyte macrophage colony-stimulating factor stimulusdefinition[GO:0097011] silver  
1
  • Ortholog Compara
Chemotaxisdefinition[GO:0006935]  
1
  • PINC
Cytosine metabolic processdefinition[GO:0019858] silver  
1
  • Ortholog Compara
ERBB signaling pathwaydefinition[GO:0038127]  
1
  • UniProtKB
ERK1 and ERK2 cascadedefinition[GO:0070371]  
1
  • UniProtKB
Labyrinthine layer blood vessel developmentdefinition[GO:0060716] silver  
1
  • Ortholog Compara
Lipopolysaccharide-mediated signaling pathwaydefinition[GO:0031663] silver  
1
  • Ortholog Compara
Long-term synaptic potentiationdefinition[GO:0060291] silver  
1
  • Ortholog Compara
Lung morphogenesisdefinition[GO:0060425] silver  
1
  • Ortholog Compara
Mammary gland epithelial cell proliferationdefinition[GO:0033598] silver  
1
  • Ortholog Compara
MAPK import into nucleusdefinition[GO:0000189] silver  
1
  • Ortholog Compara
Negative regulation of cell differentiationdefinition[GO:0045596] silver  
1
  • Ortholog Compara
Peptidyl-serine phosphorylationdefinition[GO:0018105]  
1
  • BHF-UCL
Peptidyl-threonine phosphorylationdefinition[GO:0018107]  
1
  • Ortholog Curator
Positive regulation of cell migrationdefinition[GO:0030335] silver  
1
  • Ortholog Compara
Positive regulation of cell proliferationdefinition[GO:0008284] silver  
1
  • Ortholog Compara
Positive regulation of peptidyl-threonine phosphorylationdefinition[GO:0010800]  
1
  • UniProtKB
Positive regulation of telomerase activitydefinition[GO:0051973]  
1
  • BHF-UCL
Positive regulation of telomere cappingdefinition[GO:1904355]  
1
  • BHF-UCL
Positive regulation of telomere maintenance via telomerasedefinition[GO:0032212]  
1
  • BHF-UCL
Positive regulation of transcription, DNA-templateddefinition[GO:0045893] silver  
1
  • Ortholog Compara
Positive regulation of translationdefinition[GO:0045727] silver  
1
  • Ortholog Compara
Protein phosphorylationdefinition[GO:0006468]  
1
  • UniProtKB
Regulation of cytoskeleton organizationdefinition[GO:0051493]  
1
  • UniProtKB
Regulation of early endosome to late endosome transportdefinition[GO:2000641]  
1
  • UniProtKB
Regulation of Golgi inheritancedefinition[GO:0090170]  
1
  • UniProtKB
Regulation of protein stabilitydefinition[GO:0031647]  
1
  • Ortholog Curator
Regulation of stress-activated MAPK cascadedefinition[GO:0032872]  
1
  • UniProtKB
Response to epidermal growth factordefinition[GO:0070849]  
1
  • UniProtKB
Response to estrogendefinition[GO:0043627] silver  
1
  • Ortholog Compara
Response to exogenous dsRNAdefinition[GO:0043330] silver  
1
  • Ortholog Compara
Response to stressdefinition[GO:0006950]  
1
  • PINC
Response to toxic substancedefinition[GO:0009636] silver  
1
  • Ortholog Compara
Sensory perception of paindefinition[GO:0019233] silver  
1
  • Ortholog Compara
Signal transductiondefinition[GO:0007165]  
1
  • PINC
T cell receptor signaling pathwaydefinition[GO:0050852] silver  
1
  • Ortholog Compara
Trachea formationdefinition[GO:0060440] silver  
1
  • Ortholog Compara
Transcription, DNA-templateddefinition[GO:0006351]  
1
  • UniProtKB KW
Viral processdefinition[GO:0016032]  
1
  • UniProtKB KW
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.24: ATP + a protein ADP + a phosphoprotein.  
1
  • UniProtKB
It requires the following cofactor
 Mg(2+)  
1
  • UniProtKB
It is regulated in the following manner
Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on Thr-185 and Tyr-187 in response to external stimuli like insulin or NGF. Both phosphorylations are required for activity. This phosphorylation causes dramatic conformational changes, which enable full activation and interaction of MAPK1/ERK2 with its substrates. Phosphorylation on Ser-29 by SGK1 results in its activation by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. Dephosphorylated and inactivated by DUSP3, DUSP6 and DUSP9. Inactivated by pyrimidylpyrrole inhibitors.  
3
  • UniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Acute myeloid leukemia  hsa05221+5594  
Adherens junction  hsa04520+5594  
Aldosterone-regulated sodium reabsorption  hsa04960+5594  
Alzheimer's disease  hsa05010+5594  
Axon guidance  hsa04360+5594  
B cell receptor signaling pathway  hsa04662+5594  
Bladder cancer  hsa05219+5594  
Chagas disease (American trypanosomiasis)  hsa05142+5594  
Chemokine signaling pathway  hsa04062+5594  
Cholinergic synapse  hsa04725+5594  
Chronic myeloid leukemia  hsa05220+5594  
Colorectal cancer  hsa05210+5594  
Dorso-ventral axis formation  hsa04320+5594  
Endometrial cancer  hsa05213+5594  
ErbB signaling pathway  hsa04012+5594  
Fc epsilon RI signaling pathway  hsa04664+5594  
Fc gamma R-mediated phagocytosis  hsa04666+5594  
Focal adhesion  hsa04510+5594  
Gap junction  hsa04540+5594  
Glioma  hsa05214+5594  
Glutamatergic synapse  hsa04724+5594  
GnRH signaling pathway  hsa04912+5594  
Hepatitis C  hsa05160+5594  
Influenza A  hsa05164+5594  
Insulin signaling pathway  hsa04910+5594  
Leishmaniasis  hsa05140+5594  
Long-term depression  hsa04730+5594  
Long-term potentiation  hsa04720+5594  
MAPK signaling pathway  hsa04010+5594  
Melanogenesis  hsa04916+5594  
Melanoma  hsa05218+5594  
mTOR signaling pathway  hsa04150+5594  
Natural killer cell mediated cytotoxicity  hsa04650+5594  
Neurotrophin signaling pathway  hsa04722+5594  
NOD-like receptor signaling pathway  hsa04621+5594  
Non-small cell lung cancer  hsa05223+5594  
Oocyte meiosis  hsa04114+5594  
Osteoclast differentiation  hsa04380+5594  
Pancreatic cancer  hsa05212+5594  
Pathways in cancer  hsa05200+5594  
Pertussis  hsa05133+5594  
Prion diseases  hsa05020+5594  
Progesterone-mediated oocyte maturation  hsa04914+5594  
Prostate cancer  hsa05215+5594  
Regulation of actin cytoskeleton  hsa04810+5594  
Renal cell carcinoma  hsa05211+5594  
Salmonella infection  hsa05132+5594  
Shigellosis  hsa05131+5594  
T cell receptor signaling pathway  hsa04660+5594  
TGF-beta signaling pathway  hsa04350+5594  
Thyroid cancer  hsa05216+5594  
Toll-like receptor signaling pathway  hsa04620+5594  
Toxoplasmosis  hsa05145+5594  
Type II diabetes mellitus  hsa04930+5594  
Vascular smooth muscle contraction  hsa04270+5594  
VEGF signaling pathway  hsa04370+5594  
According to Reactome, this protein belongs to the following pathways:
Activation of the AP-1 family of transcription factors  R-HSA-450341  
Advanced glycosylation endproduct receptor signaling  R-HSA-879415  
CREB phosphorylation through the activation of Ras  R-HSA-442742  
ERK/MAPK targets  R-HSA-198753  
ERKs are inactivated  R-HSA-202670  
FCERI mediated MAPK activation  R-HSA-2871796  
Gastrin-CREB signalling pathway via PKC and MAPK  R-HSA-881907  
Golgi Cisternae Pericentriolar Stack Reorganization  R-HSA-162658  
Growth hormone receptor signaling  R-HSA-982772  
MAP2K and MAPK activation  R-HSA-5674135  
MAPK1 (ERK2) activation  R-HSA-112411  
NCAM signaling for neurite out-growth  R-HSA-375165  
Negative feedback regulation of MAPK pathway  R-HSA-5674499  
Negative regulation of FGFR1 signaling  R-HSA-5654726  
Negative regulation of FGFR2 signaling  R-HSA-5654727  
Negative regulation of FGFR3 signaling  R-HSA-5654732  
Negative regulation of FGFR4 signaling  R-HSA-5654733  
Negative regulation of MAPK pathway  R-HSA-5675221  
Oncogene Induced Senescence  R-HSA-2559585  
Oxidative Stress Induced Senescence  R-HSA-2559580  
phospho-PLA2 pathway  R-HSA-111995  
RAF-independent MAPK1/3 activation  R-HSA-112409  
RAF/MAP kinase cascade  R-HSA-5673001  
Recycling pathway of L1  R-HSA-437239  
Regulation of actin dynamics for phagocytic cup formation  R-HSA-2029482  
Regulation of HSF1-mediated heat shock response  R-HSA-3371453  
RHO GTPases Activate WASPs and WAVEs  R-HSA-5663213  
RSK activation  R-HSA-444257  
Senescence-Associated Secretory Phenotype (SASP)  R-HSA-2559582  
Signal attenuation  R-HSA-74749  
Signal transduction by L1  R-HSA-445144  
Signaling by FGFR1  R-HSA-5654736  
Signaling by FGFR2  R-HSA-5654738  
Signaling by FGFR3  R-HSA-5654741  
Signaling by FGFR4  R-HSA-5654743  
Thrombin signalling through proteinase activated receptors (PARs)  R-HSA-456926  
 

Keywords

Biological process 
Apoptosis  definition   [KW-0053]
Cell cycle  definition   [KW-0131]
Host-virus interaction  definition   [KW-0945]
Transcription  definition   [KW-0804]
Transcription regulation  definition   [KW-0805]
Molecular function 
Kinase  definition   [KW-0418]
Repressor  definition   [KW-0678]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: MAPK1
GenomeRNAi: 5594
PRO: PR:P28482
Chemistry
GuidetoPHARMACOLOGY: 1495