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 1953 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.  
25
  • CuratedUniProtKB
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.  
25
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524] silver  
  • IEAOrtholog Compara
DNA bindingdefinition[GO:0003677]  
  • IEAUniProtKB KW
MAP kinase activitydefinition[GO:0004707]  
  • IEAEC 2 GO
Mitogen-activated protein kinase kinase kinase bindingdefinition[GO:0031435] silver  
  • IEAOrtholog Compara
Phosphatase bindingdefinition[GO:0019902]  
1
  • IPIUniProtKB
Phosphotyrosine bindingdefinition[GO:0001784] silver  
  • IEAOrtholog Compara
Protein bindingdefinition[GO:0005515]  
21
  • IPIUniProtKB
  • IPIIntAct
Protein serine/threonine kinase activitydefinition[GO:0004674]  
2
  • IDAUniProtKB
  • IDABHF-UCL
RNA polymerase II carboxy-terminal domain kinase activitydefinition[GO:0008353]  
  • ISSOrtholog Curator
Transcription factor bindingdefinition[GO:0008134] silver  
  • IEAOrtholog Compara
GO biological process 
Apoptotic processdefinition[GO:0006915]  
  • IEAUniProtKB KW
B cell receptor signaling pathwaydefinition[GO:0050853] silver  
  • IEAOrtholog Compara
Caveolin-mediated endocytosisdefinition[GO:0072584]  
1
  • TASUniProtKB
Cell cycledefinition[GO:0007049]  
  • IEAUniProtKB KW
Cellular response to DNA damage stimulusdefinition[GO:0006974] silver  
  • IEAOrtholog Compara
Chemotaxisdefinition[GO:0006935]  
1
  • TASPINC
Cytosine metabolic processdefinition[GO:0019858] silver  
  • IEAOrtholog Compara
ERBB signaling pathwaydefinition[GO:0038127]  
1
  • IDAUniProtKB
ERK1 and ERK2 cascadedefinition[GO:0070371]  
1
  • IDAUniProtKB
Labyrinthine layer blood vessel developmentdefinition[GO:0060716] silver  
  • IEAOrtholog Compara
Lipopolysaccharide-mediated signaling pathwaydefinition[GO:0031663] silver  
  • IEAOrtholog Compara
Mammary gland epithelial cell proliferationdefinition[GO:0033598] silver  
  • IEAOrtholog Compara
MAPK import into nucleusdefinition[GO:0000189] silver  
  • IEAOrtholog Compara
Negative regulation of cell differentiationdefinition[GO:0045596] silver  
  • IEAOrtholog Compara
Organ morphogenesisdefinition[GO:0009887] silver  
  • IEAOrtholog Compara
Peptidyl-serine phosphorylationdefinition[GO:0018105]  
1
  • IDABHF-UCL
Peptidyl-threonine phosphorylationdefinition[GO:0018107]  
  • ISSOrtholog Curator
Positive regulation of cell migrationdefinition[GO:0030335] silver  
  • IEAOrtholog Compara
Positive regulation of cell proliferationdefinition[GO:0008284] silver  
  • IEAOrtholog Compara
Positive regulation of peptidyl-threonine phosphorylationdefinition[GO:0010800]  
1
  • IDAUniProtKB
Positive regulation of transcription, DNA-templateddefinition[GO:0045893] silver  
  • IEAOrtholog Compara
Positive regulation of translationdefinition[GO:0045727] silver  
  • IEAOrtholog Compara
Regulation of cytoskeleton organizationdefinition[GO:0051493]  
1
  • TASUniProtKB
Regulation of early endosome to late endosome transportdefinition[GO:2000641]  
1
  • TASUniProtKB
Regulation of Golgi inheritancedefinition[GO:0090170]  
1
  • TASUniProtKB
Regulation of protein stabilitydefinition[GO:0031647]  
  • ISSOrtholog Curator
Regulation of stress-activated MAPK cascadedefinition[GO:0032872]  
1
  • TASUniProtKB
Response to epidermal growth factordefinition[GO:0070849]  
1
  • IDAUniProtKB
Response to estrogendefinition[GO:0043627] silver  
  • IEAOrtholog Compara
Response to exogenous dsRNAdefinition[GO:0043330] silver  
  • IEAOrtholog Compara
Response to stressdefinition[GO:0006950]  
1
  • TASPINC
Response to toxic substancedefinition[GO:0009636] silver  
  • IEAOrtholog Compara
Sensory perception of paindefinition[GO:0019233] silver  
  • IEAOrtholog Compara
Signal transductiondefinition[GO:0007165]  
1
  • TASPINC
T cell receptor signaling pathwaydefinition[GO:0050852] silver  
  • IEAOrtholog Compara
Transcription, DNA-templateddefinition[GO:0006351]  
  • IEAUniProtKB KW
Viral processdefinition[GO:0016032]  
  • IEAUniProtKB 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.  
  • 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-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.  
2
  • CuratedUniProtKB
 
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  REACT_21326  
Advanced glycosylation endproduct receptor signaling  REACT_25195  
CREB phosphorylation through the activation of Ras  REACT_20568  
ERK/MAPK targets  REACT_12599  
ERK2 activation  REACT_1183  
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  
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  
phospho-PLA2 pathway  REACT_15466  
Recycling pathway of L1  REACT_22365  
Regulation of actin dynamics for phagocytic cup formation  REACT_160086  
Regulation of HSF1-mediated heat shock response  REACT_200780  
RSK activation  REACT_20510  
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  
 

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