MAPK3 - Mitogen-activated protein kinase 3 - human protein (Function)
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MAPK3 »  Mitogen-activated protein kinase 3   [ EC ]  (MAPK 3)
Protein also known as:  Extracellular signal-regulated kinase 1 (ERK-1).
Gene name:  MAPK3
Entry whose protein(s) existence is based on evidence at protein level
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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.  
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
MAP kinase activitydefinition[GO:0004707]  
  • NASUniProtKB
Phosphatase bindingdefinition[GO:0019902]  
  • IPIUniProtKB
Phosphotyrosine bindingdefinition[GO:0001784] silver  
  • IEAOrtholog Compara
Protein bindingdefinition[GO:0005515]  
  • IPIIntAct
  • IPIUniProtKB
GO biological process 
Apoptotic processdefinition[GO:0006915]  
  • IEAUniProtKB KW
BMP signaling pathwaydefinition[GO:0030509]  
Cartilage developmentdefinition[GO:0051216] silver  
  • IEAOrtholog Compara
Caveolin-mediated endocytosisdefinition[GO:0072584]  
  • TASUniProtKB
Cell cycledefinition[GO:0007049]  
  • IEAUniProtKB KW
Cellular response to mechanical stimulusdefinition[GO:0071260]  
  • IEPUniProtKB
DNA damage induced protein phosphorylationdefinition[GO:0006975]  
  • IDAUniProtKB
Interleukin-1-mediated signaling pathwaydefinition[GO:0070498]  
Lipopolysaccharide-mediated signaling pathwaydefinition[GO:0031663] silver  
  • IEAOrtholog Compara
MAPK cascadedefinition[GO:0000165]  
Negative regulation of apolipoprotein bindingdefinition[GO:2000657] silver  
  • IEAOrtholog Compara
Organ morphogenesisdefinition[GO:0009887] silver  
  • IEAOrtholog Compara
Peptidyl-tyrosine autophosphorylationdefinition[GO:0038083]  
  • IDAUniProtKB
  • IDAUniProtKB
Positive regulation of ERK1 and ERK2 cascadedefinition[GO:0070374]  
Positive regulation of histone acetylationdefinition[GO:0035066]  
Positive regulation of histone phosphorylationdefinition[GO:0033129]  
Positive regulation of protein phosphorylationdefinition[GO:0001934]  
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944]  
Protein phosphorylationdefinition[GO:0006468]  
  • IDAUniProtKB
Regulation of cytoskeleton organizationdefinition[GO:0051493]  
  • TASUniProtKB
Regulation of early endosome to late endosome transportdefinition[GO:2000641]  
  • TASUniProtKB
Regulation of Golgi inheritancedefinition[GO:0090170]  
  • TASUniProtKB
Regulation of stress-activated MAPK cascadedefinition[GO:0032872]  
  • TASUniProtKB
Response to epidermal growth factordefinition[GO:0070849]  
  • IDAUniProtKB
Response to exogenous dsRNAdefinition[GO:0043330] silver  
  • IEAOrtholog Compara
Sensory perception of paindefinition[GO:0019233] silver  
  • IEAOrtholog Compara
Viral processdefinition[GO:0016032]  
  • IEAUniProtKB KW
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC ATP + a protein ADP + a phosphoprotein.  
  • CuratedUniProtKB
It requires the following cofactor
Magnesium (By similarity).  
  • CuratedUniProtKB
It is regulated in the following manner
Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on Thr-202 and Tyr-204 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. Dephosphorylated and inactivated by DUSP3, DUSP6 and DUSP9.  
  • CuratedUniProtKB
More information is available from:
According to KEGG, this protein belongs to the following pathways:
Acute myeloid leukemia  hsa05221+5595  
Adherens junction  hsa04520+5595  
Aldosterone-regulated sodium reabsorption  hsa04960+5595  
Alzheimer's disease  hsa05010+5595  
Axon guidance  hsa04360+5595  
B cell receptor signaling pathway  hsa04662+5595  
Bladder cancer  hsa05219+5595  
Chagas disease (American trypanosomiasis)  hsa05142+5595  
Chemokine signaling pathway  hsa04062+5595  
Cholinergic synapse  hsa04725+5595  
Chronic myeloid leukemia  hsa05220+5595  
Colorectal cancer  hsa05210+5595  
Dorso-ventral axis formation  hsa04320+5595  
Endometrial cancer  hsa05213+5595  
ErbB signaling pathway  hsa04012+5595  
Fc epsilon RI signaling pathway  hsa04664+5595  
Fc gamma R-mediated phagocytosis  hsa04666+5595  
Focal adhesion  hsa04510+5595  
Gap junction  hsa04540+5595  
Glioma  hsa05214+5595  
Glutamatergic synapse  hsa04724+5595  
GnRH signaling pathway  hsa04912+5595  
Hepatitis C  hsa05160+5595  
Influenza A  hsa05164+5595  
Insulin signaling pathway  hsa04910+5595  
Leishmaniasis  hsa05140+5595  
Long-term depression  hsa04730+5595  
Long-term potentiation  hsa04720+5595  
MAPK signaling pathway  hsa04010+5595  
Melanogenesis  hsa04916+5595  
Melanoma  hsa05218+5595  
mTOR signaling pathway  hsa04150+5595  
Natural killer cell mediated cytotoxicity  hsa04650+5595  
Neurotrophin signaling pathway  hsa04722+5595  
NOD-like receptor signaling pathway  hsa04621+5595  
Non-small cell lung cancer  hsa05223+5595  
Oocyte meiosis  hsa04114+5595  
Osteoclast differentiation  hsa04380+5595  
Pancreatic cancer  hsa05212+5595  
Pathways in cancer  hsa05200+5595  
Pertussis  hsa05133+5595  
Prion diseases  hsa05020+5595  
Progesterone-mediated oocyte maturation  hsa04914+5595  
Prostate cancer  hsa05215+5595  
Regulation of actin cytoskeleton  hsa04810+5595  
Renal cell carcinoma  hsa05211+5595  
Salmonella infection  hsa05132+5595  
Shigellosis  hsa05131+5595  
T cell receptor signaling pathway  hsa04660+5595  
TGF-beta signaling pathway  hsa04350+5595  
Thyroid cancer  hsa05216+5595  
Toll-like receptor signaling pathway  hsa04620+5595  
Toxoplasmosis  hsa05145+5595  
Type II diabetes mellitus  hsa04930+5595  
Vascular smooth muscle contraction  hsa04270+5595  
VEGF signaling pathway  hsa04370+5595  
According to Reactome, this protein belongs to the following pathways:
Activation of the AP-1 family of transcription factors  REACT_21326  
Advanced glycosylation endproduct receptor signaling  REACT_25195  
ERK/MAPK targets  REACT_12599  
ERK1 activation  REACT_1391  
ERKs are inactivated  REACT_12436  
FCERI mediated MAPK activation  REACT_163701  
Gastrin-CREB signalling pathway via PKC and MAPK  REACT_120966  
Golgi Cisternae Pericentriolar Stack Reorganization  REACT_1100  
Growth hormone receptor signaling  REACT_111133  
ISG15 antiviral mechanism  REACT_115831  
NCAM signaling for neurite out-growth  REACT_18334  
Negative regulation of FGFR signaling  REACT_111184  
Oncogene Induced Senescence  REACT_169325  
Oxidative Stress Induced Senescence  REACT_169436  
Regulation of actin dynamics for phagocytic cup formation  REACT_160086  
Regulation of HSF1-mediated heat shock response  REACT_200780  
RNA Polymerase I Promoter Opening  REACT_2232  
Senescence-Associated Secretory Phenotype (SASP)  REACT_169168  
Signal attenuation  REACT_508  
Signal transduction by L1  REACT_22272  
Signaling by FGFR  REACT_9470  
Thrombin signalling through proteinase activated receptors (PARs)  REACT_21384  


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

Further external links

GeneWiki: MAPK3
GenomeRNAi: 5595
PRO: PR:P27361