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MAPK1 (mitogen-activated protein kinase 1)

Written2010-01Seda Tuncay, Sreeparna Banerjee
Department of Biological Sciences, Middle East Technical University, Ankara 06531, Turkey

(Note : for Links provided by Atlas : click)

Identity

Other namesEC 2.7.11.24
ERK
ERK-2
ERK2
ERT1
MAPK2
P42MAPK
PRKM1
PRKM2
p38
p40
p41
p41mapk
p42-MAPK
HGNC (Hugo) MAPK1
LocusID (NCBI) 5594
Atlas_Id 41288
Location 22q11.21  [Link to chromosome band 22q11]
Location_base_pair Starts at 22113947 and ends at 22221970 bp from pter ( according to hg19-Feb_2009)  [Mapping MAPK1.png]
Local_order According to NCBI Map Viewer, genes flanking ERK2 (MAPK1) in centromere to telomere direction on 22q11.2; 22q11.21 are:
centromere
- PPIL2, peptidylprolyl isomerase (cyclophilin)-like 2, Location: 22q11.21
- YPEL1, yippee-like 1 (Drosophila), Location: 22q11.2
- MAPK1, 22q11.22
- PPM1F, protein phosphatase 1F (PP2C domain containing), Location: 22q11.22
- LOC100286925, hypothetical protein LOC100286925, Location: 22q11.22
- LOC100286894, hypothetical protein LOC100286894, Location: 22q11.22
telomere
Fusion genes
(updated 2016)
CRKL (22q11.21) / MAPK1 (22q11.21)HIVEP1 (6p24.1) / MAPK1 (22q11.21)MAPK1 (22q11.21) / ARHGEF7 (13q34)
MAPK1 (22q11.21) / ATP1A1 (1p13.1)MAPK1 (22q11.21) / CASP1 (11q22.3)MAPK1 (22q11.21) / CLIP2 (7q11.23)
MAPK1 (22q11.21) / GPR107 (9q34.11)MAPK1 (22q11.21) / KCNJ4 (22q13.1)MAPK1 (22q11.21) / MAPK1 (22q11.21)
MAPK1 (22q11.21) / METTL21B (12q14.1)MAPK1 (22q11.21) / PACS1 (11q13.1)MAPK1 (22q11.21) / RFT1 (3p21.1)
MAPK1 (22q11.21) / TOP3B (22q11.22)MAPK1 (22q11.21) / ZNF638 (2p13.2)SERPINB5 (18q21.33) / MAPK1 (22q11.21)

DNA/RNA

 
  Diagram of the ERK2 (MAPK1) gene (isoform 1). Exons are represented by open boxes (in scale). Exons 1 to 8 are from the 5' to 3' direction.
Description According to Entrez Gene ERK2 (MAPK1) gene maps to NC_000022.10 and spans a region of 98.64 kb. According to Spidey mRNA-to-genomic alignment program ERK2 (MAPK1) variant 1 has 8 exons, the sizes being 119, 183, 190, 117, 115, 132, 110, 117 bps (mRNA coordinates).
Transcription Two alternatively spliced transcript variants encoding the same protein, but differing in the UTRs, have been reported for this gene.
Pseudogene No pseudogenes have been reported for ERK2 (MAPK1).

Protein

Note ERK2 (MAPK1) is identified by the specific TEY (Thr-Glu-Tyr) sequence in the activation loop. ERK2 (MAPK1) is activated by dual phosphorylation of tyrosine (Tyr185) and threonine (Thr183) residues which is required for complete activation of the protein. Activated ERK2 (MAPK1) migrates into the nucleus and phosphorylates transcription factors.
Description ERK2 (MAPK1) is a 41 kDa protein consisting of 360 amino acids. ERK2 (MAPK1) protein is 85% identical to ERK1 (MAPK3) (another MAP kinase family member) and the two proteins have even higher, levels of similarity in their substrate binding regions. ERK2 (MAPK1) possess an acidic patch on the surface-exposed loop L16 of the kinase opposite to its catalytic cleft, which acts as a MAP kinase conserved docking motif (CD site; residues 310-325) which can also be found on activators (MAPKK), inhibitors (PTP-SL (PTPRR) and dual specificity phosphatases) and substrates (ELK-1).
Expression Ubiquitously expressed with varying levels in different tissues.
Localisation Subcellular location of ERK2 (MAPK1) protein is the cytoplasm, and the nucleus. Upon activation by dual phosphorylation on its Tyr and Thr residues by upstream kinases, ERK2 (MAPK1) is translocated into the nucleus from cytoplasm where it phosphorylates its nuclear targets.
Function Being one of the most studied cytoplasmic signaling pathways, the ERK pathway is activated via GTP-loading of RAS at the plasma membrane and sequential activation of a series of protein kinases. Activated RAS recruits the RAF family of kinases such as RAF1 to the plasma membrane which in turn acts as a MAPKKK and activates MAP kinase/ERK kinase 1 and 2 (MEK1 (MAP2K1) and MEK2 (MAP2K2)) by serine phosphorylation. MEK1/2 catalyze the phosphorylation of ERK1 (MAPK3) and ERK2 (MAPK1). Activated ERK1/2 (MAPK3/1) phosphorylates many different substrates involved in various cellular responses from cytoskeletal changes to gene transcription.
It has been shown that activation of ERK1/2 (MAPK3/1) is crucial for cyclin D1 induction, providing a molecular link between ERK signaling and cell cycle control as cyclin D1 gene is essential for G1 to S-phase progression.
In response to Angiotensin II, ERK1/2 (MAPK3/1) regulates cell proliferation by either one of two signaling pathways which are heterotrimeric G protein/PKC zeta-dependent signaling and SRC/YES1/FYN signaling. ERK1/2 (MAPK3/1) phosphorylates specific transcription factors ELK-1 (leading to c-FOS transcriptional activity) following its translocation into the nucleus due to heterotrimeric G protein/PKC zeta-dependent signaling. Due to its phosphorylation in the cytoplasm by SRC/YES1/FYN signaling, ERK1/2 complexes with RSK2 (RPS6KA), which in turn becomes activated and translocates into the nucleus to modulate c-FOS transcription and c-FOS protein activity.
The ERK pathway has been found to be responsible for the phosphorylation of BCL2 that contributes to cell survival, the suppression of the apoptotic effect of BAD, the up-regulation of the antiapoptotic protein MCL-1. Moreover, it has been also shown that ERK1/2 is one of the regulators of TP53 protein accumulation and activation during the DNA damage response.
ERK1/2 induces expression of PAI-1 (plasminogen activator type-1 inhibitor) which is closely associated with dynamic changes in cellular morphology and shape-altering physiologic processes.
CIITA is a critical transcription factor for the initiation of the expression of MHC class II genes and their subsequent induction of the immune response. Studies have indicated that ERK1/2 (MAPK3/1) negatively regulates CIITA by blocking expression of the CIITA gene and/or by phosphorylating CIITA at residues including serine 288, resulting in the loss of CIITA transactivation potential by enabling it to interact with CRM1 (XPO1) which causes export of CIITA protein from the nucleus.
Homology - P. troglodytes, mitogen-activated protein kinase 1, MAPK1
- C. lupus familiaris, mitogen-activated protein kinase 1, MAPK1
- B. taurus, mitogen-activated protein kinase 1, MAPK1
- M. musculus, mitogen-activated protein kinase 1, MAPK1
- R. norvegicus, mitogen-activated protein kinase 1, MAPK1
- G. gallus, mitogen-activated protein kinase 1, MAPK1
- D. rerio, mitogen-activated protein kinase 1, MAPK1
- D. melanogaster, rl, rolled
- A. gambiae, AgaP_AGAP009207, AGAP009207-PA
- C. elegans, mpk-1, MAP Kinase
- S. cerevisiae, KSS1, Kss1p
- K. lactis, KLLA0A02497g, hypothetical protein
- E. gossypii, AGOS_ACL191C, ACL191Cp
- A. thaliana, ATMPK2, ATMPK2 (ARABIDOPSIS THALIANA MITOGE...)
- A. thaliana, ATMPK1, ATMPK1 (MITOGEN-ACTIVATED PROTEIN K...)
- O. sativa, Os02g0148100, hypothetical protein
- O. sativa, Os06g0699400, hypothetical protein
- P. falciparum, PF11_0147, mitogen-activated protein kinase 2

Implicated in

Note
Entity Various diseases
Disease Although ERK1-/- mice are not embryonic lethal, ERK2-/- mice are. Thus, the ERK2 protein appears to be essential for viability; although dysregulation of the gene/protein expression has been implicated in a number of diseases. Specifically,ERK2 was found to be activated (phosphorylated) in the presence of aspirin triggered lipoxin (ATL-1), a molecule needed for the resolution of inflammation. The activated ERK2 resulted in the survival of mononuclear phagocytes which then exhibit nonphlogistic activities. Additionally, ERK2, but not ERK1, was shown to be constitutively activated by BCR/ABL1 in chronic myelogenous leukemia and implicated in the acquired resistance to imatinib mesylate.
Oncogenesis Elevated and constitutive activation of ERK1/2 has been detected in a large number of human tumors; including colon, kidney, gastric, prostate, breast, non-small cell lung cancer, bladder, chondrosarcomas and glioblastoma multiforme which show especially high frequencies of kinase activation. The reason for constitutive activation of the ERK pathway in the majority of tumor cells seems to be due to a disorder in RAF, RAS, EGFR or other upstream signaling molecules. In addition, several studies have shown that the ERK-MAPK pathway can directly promote cell motility and the migration of tumor cells.
  
Entity Gastric cancer
Note Epidermal growth factor (EGF) and urokinase plasminogen activator receptor (uPAR (PLAUR)) are elevated in human gastric cancers and it has been shown that uPAR expression is induced by EGF via ERK1/2 as well as AP-1 (JUN) and NF-kB signaling pathways which in turn, stimulates cell invasiveness in human gastric cancer AGS cells.
  
Entity Breast cancer
Note In breast cancer patients, ERK1/2 has been found to be heavily phosphorylated on tyrosyl residues and have a 5-10 fold elevated activity compared to benign conditions (fibroadenoma and fibrocystic disease). Localization studies showed that hyperexpressed ERK1/2 mRNA localized to malignant epithelial cells. Furthermore, hyperexpression of ERK1/2 mRNA (5-20 fold) was also observed in metastatic cells within the lymph nodes of breast cancer patients. In addition, in a recent study it was also shown that phosphorylated ERK1/2 levels were significantly high in breast cancer cell lines with high metastatic potential compared to non metastatic breast cancer cell lines. Beta-catenin, cyclin D1, and survivin have been shown to be downstream effectors of pERK1/2, while G1/0 proteins, phospholipase C, and protein kinase C serve as upstream activators of pERK1/2 in those cells.
  
Entity Colorectal cancer
Note Several lines of evidence indicate that overexpression and activation of ERK-MAPK pathway play an important part in progression of colorectal cancer. The constitutive activation of the RAF/MEK/ERK has been shown to be necessary for RAS-induced transformation of HT1080 human colon carcinoma cell line.
  
Entity Non-small-cell lung cancer
Note It has been found that nuclear and cytoplasmic ERK1/2 activation positively correlates with the stage and lymph node metastases in lung cancer. Therefore ERK1/2 is associated with advanced and aggressive NSCLC tumors.
  
Entity Bladder cancer
Note ERK1/2 has been shown to mediate TNF-alpha-induced MMP-9 expression by regulating the binding activity of the transcription factors, NF-kB, AP-1 and SP-1, in urinary bladder cancer HT1376 cells.
  
Entity Glioblastoma multiforme
Note The activation of ERK1/2 has been implicated in different pathobiological processes of GBM which is the most common and malignant brain tumor. The ERK1/2 activation has been linked to EGFR overexpression and hypermethylation of 9p21 locus.
  
Entity Prostate cancer
Note In prostate tumors, the level of activated MAP kinase were found to be increased with increasing Gleason score and tumor stage while nonneoplastic prostate tissue showed little or no staining with activated MAP kinase antiserum.
  
Entity Kidney cancer
Note In a high number of human renal cancers ERK1/2 has been found to be constitutively activated. Moreover, ERK1/2 activation was observed more frequently with high-grade renal cancer cells (RCC) compared to low-grade RCC.
  
Entity Chondrosarcomas
Note Activation of the JNK (MAPK8) and ERK signal transduction pathways have been shown to increase the activity and expression levels of their downstream effectors, transcription factors AP-1 and RUNX2. These transcription factors, in turn, stimulate genes that are involved in chondroblast cell biology, ultimately inducing chondroblastic tumorigenesis.
  
Entity Cardiac hypertrophy
Note It has been implicated that ERK1/2 mediate cardiac hypertrophy, which is a major risk factor for the development of arrhythmias, heart failure and sudden death.
  

Bibliography

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Citation

This paper should be referenced as such :
Tuncay, S ; Banerjee, S
MAPK1 (mitogen-activated protein kinase 1)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(10):986-989.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/MAPK1ID41288ch22q11.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 2 ]
  Lymphomatoid papulosis (LyP) with 6p25.3 rearrangement DUSP22 and IRF4/
t(6;7)(p25.3;q32.3) DUSP22/FRA7H

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 0 ]
  Skin: Melanoma

External links

Nomenclature
HGNC (Hugo)MAPK1   6871
Cards
AtlasMAPK1ID41288ch22q11
Entrez_Gene (NCBI)MAPK1  5594  mitogen-activated protein kinase 1
AliasesERK; ERK-2; ERK2; ERT1; 
MAPK2; P42MAPK; PRKM1; PRKM2; p38; p40; p41; p41mapk; p42-MAPK
GeneCards (Weizmann)MAPK1
Ensembl hg19 (Hinxton)ENSG00000100030 [Gene_View]  chr22:22113947-22221970 [Contig_View]  MAPK1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000100030 [Gene_View]  chr22:22113947-22221970 [Contig_View]  MAPK1 [Vega]
ICGC DataPortalENSG00000100030
TCGA cBioPortalMAPK1
AceView (NCBI)MAPK1
Genatlas (Paris)MAPK1
WikiGenes5594
SOURCE (Princeton)MAPK1
Genomic and cartography
GoldenPath hg19 (UCSC)MAPK1  -     chr22:22113947-22221970 -  22q11.2   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)MAPK1  -     22q11.2   [Description]    (hg38-Dec_2013)
EnsemblMAPK1 - 22q11.2 [CytoView hg19]  MAPK1 - 22q11.2 [CytoView hg38]
Mapping of homologs : NCBIMAPK1 [Mapview hg19]  MAPK1 [Mapview hg38]
OMIM176948   
Gene and transcription
Genbank (Entrez)AI004470 AK055080 AK057143 AK090869 AK295188
RefSeq transcript (Entrez)NM_002745 NM_138957
RefSeq genomic (Entrez)NC_000022 NC_018933 NG_023054 NT_011520 NW_004929430
Consensus coding sequences : CCDS (NCBI)MAPK1
Cluster EST : UnigeneHs.431850 [ NCBI ]
CGAP (NCI)Hs.431850
Alternative Splicing GalleryENSG00000100030
Gene ExpressionMAPK1 [ NCBI-GEO ]   MAPK1 [ EBI - ARRAY_EXPRESS ]   MAPK1 [ SEEK ]   MAPK1 [ MEM ]
Gene Expression Viewer (FireBrowse)MAPK1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5594
GTEX Portal (Tissue expression)MAPK1
Protein : pattern, domain, 3D structure
UniProt/SwissProtP28482 (Uniprot)
NextProtP28482  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP28482
Splice isoforms : SwissVarP28482 (Swissvar)
Catalytic activity : Enzyme2.7.11.24 [ Enzyme-Expasy ]   2.7.11.242.7.11.24 [ IntEnz-EBI ]   2.7.11.24 [ BRENDA ]   2.7.11.24 [ KEGG ]   
PhosPhoSitePlusP28482
Domaine pattern : Prosite (Expaxy)MAPK (PS01351)    PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_ST (PS00108)   
Domains : Interpro (EBI)Kinase-like_dom    MAP_kinase_CS    MAPK_ERK1/2    Prot_kinase_dom    Protein_kinase_ATP_BS    Ser/Thr_dual-sp_kinase    Ser/Thr_kinase_AS   
Domain families : Pfam (Sanger)Pkinase (PF00069)   
Domain families : Pfam (NCBI)pfam00069   
Domain families : Smart (EMBL)S_TKc (SM00220)  
DMDM Disease mutations5594
Blocks (Seattle)MAPK1
PDB (SRS)1PME    1TVO    1WZY    2OJG    2OJI    2OJJ    2Y9Q    3D42    3D44    3I5Z    3I60    3SA0    3TEI    3W55    4FMQ    4FUX    4FUY    4FV0    4FV1    4FV2    4FV3    4FV4    4FV5    4FV6    4FV7    4FV8    4FV9    4G6N    4G6O    4H3P    4H3Q    4IZ5    4IZ7    4IZA    4N0S    4NIF    4O6E    4QP1    4QP2    4QP3    4QP4    4QP6    4QP7    4QP8    4QP9    4QPA    4QTA    4QTE    4XJ0    4ZZM    4ZZN    4ZZO    5BUE    5BUI    5BUJ    5BVD    5BVE    5BVF   
PDB (PDBSum)1PME    1TVO    1WZY    2OJG    2OJI    2OJJ    2Y9Q    3D42    3D44    3I5Z    3I60    3SA0    3TEI    3W55    4FMQ    4FUX    4FUY    4FV0    4FV1    4FV2    4FV3    4FV4    4FV5    4FV6    4FV7    4FV8    4FV9    4G6N    4G6O    4H3P    4H3Q    4IZ5    4IZ7    4IZA    4N0S    4NIF    4O6E    4QP1    4QP2    4QP3    4QP4    4QP6    4QP7    4QP8    4QP9    4QPA    4QTA    4QTE    4XJ0    4ZZM    4ZZN    4ZZO    5BUE    5BUI    5BUJ    5BVD    5BVE    5BVF   
PDB (IMB)1PME    1TVO    1WZY    2OJG    2OJI    2OJJ    2Y9Q    3D42    3D44    3I5Z    3I60    3SA0    3TEI    3W55    4FMQ    4FUX    4FUY    4FV0    4FV1    4FV2    4FV3    4FV4    4FV5    4FV6    4FV7    4FV8    4FV9    4G6N    4G6O    4H3P    4H3Q    4IZ5    4IZ7    4IZA    4N0S    4NIF    4O6E    4QP1    4QP2    4QP3    4QP4    4QP6    4QP7    4QP8    4QP9    4QPA    4QTA    4QTE    4XJ0    4ZZM    4ZZN    4ZZO    5BUE    5BUI    5BUJ    5BVD    5BVE    5BVF   
PDB (RSDB)1PME    1TVO    1WZY    2OJG    2OJI    2OJJ    2Y9Q    3D42    3D44    3I5Z    3I60    3SA0    3TEI    3W55    4FMQ    4FUX    4FUY    4FV0    4FV1    4FV2    4FV3    4FV4    4FV5    4FV6    4FV7    4FV8    4FV9    4G6N    4G6O    4H3P    4H3Q    4IZ5    4IZ7    4IZA    4N0S    4NIF    4O6E    4QP1    4QP2    4QP3    4QP4    4QP6    4QP7    4QP8    4QP9    4QPA    4QTA    4QTE    4XJ0    4ZZM    4ZZN    4ZZO    5BUE    5BUI    5BUJ    5BVD    5BVE    5BVF   
Structural Biology KnowledgeBase1PME    1TVO    1WZY    2OJG    2OJI    2OJJ    2Y9Q    3D42    3D44    3I5Z    3I60    3SA0    3TEI    3W55    4FMQ    4FUX    4FUY    4FV0    4FV1    4FV2    4FV3    4FV4    4FV5    4FV6    4FV7    4FV8    4FV9    4G6N    4G6O    4H3P    4H3Q    4IZ5    4IZ7    4IZA    4N0S    4NIF    4O6E    4QP1    4QP2    4QP3    4QP4    4QP6    4QP7    4QP8    4QP9    4QPA    4QTA    4QTE    4XJ0    4ZZM    4ZZN    4ZZO    5BUE    5BUI    5BUJ    5BVD    5BVE    5BVF   
SCOP (Structural Classification of Proteins)1PME    1TVO    1WZY    2OJG    2OJI    2OJJ    2Y9Q    3D42    3D44    3I5Z    3I60    3SA0    3TEI    3W55    4FMQ    4FUX    4FUY    4FV0    4FV1    4FV2    4FV3    4FV4    4FV5    4FV6    4FV7    4FV8    4FV9    4G6N    4G6O    4H3P    4H3Q    4IZ5    4IZ7    4IZA    4N0S    4NIF    4O6E    4QP1    4QP2    4QP3    4QP4    4QP6    4QP7    4QP8    4QP9    4QPA    4QTA    4QTE    4XJ0    4ZZM    4ZZN    4ZZO    5BUE    5BUI    5BUJ    5BVD    5BVE    5BVF   
CATH (Classification of proteins structures)1PME    1TVO    1WZY    2OJG    2OJI    2OJJ    2Y9Q    3D42    3D44    3I5Z    3I60    3SA0    3TEI    3W55    4FMQ    4FUX    4FUY    4FV0    4FV1    4FV2    4FV3    4FV4    4FV5    4FV6    4FV7    4FV8    4FV9    4G6N    4G6O    4H3P    4H3Q    4IZ5    4IZ7    4IZA    4N0S    4NIF    4O6E    4QP1    4QP2    4QP3    4QP4    4QP6    4QP7    4QP8    4QP9    4QPA    4QTA    4QTE    4XJ0    4ZZM    4ZZN    4ZZO    5BUE    5BUI    5BUJ    5BVD    5BVE    5BVF   
SuperfamilyP28482
Human Protein AtlasENSG00000100030
Peptide AtlasP28482
HPRD01496
IPIIPI00003479   IPI00874012   IPI01015278   
Protein Interaction databases
DIP (DOE-UCLA)P28482
IntAct (EBI)P28482
FunCoupENSG00000100030
BioGRIDMAPK1
STRING (EMBL)MAPK1
ZODIACMAPK1
Ontologies - Pathways
QuickGOP28482
Ontology : AmiGOMAPK cascade  activation of MAPK activity  MAPK import into nucleus  phosphotyrosine binding  DNA binding  protein serine/threonine kinase activity  protein serine/threonine kinase activity  MAP kinase activity  protein binding  ATP binding  nucleus  nucleus  nucleoplasm  nucleoplasm  cytoplasm  cytoplasm  mitochondrion  early endosome  late endosome  Golgi apparatus  microtubule organizing center  cytosol  cytoskeleton  caveola  focal adhesion  transcription, DNA-templated  protein phosphorylation  apoptotic process  chemotaxis  response to stress  cellular response to DNA damage stimulus  cell cycle  signal transduction  synaptic transmission  axon guidance  transcription factor binding  positive regulation of cell proliferation  RNA polymerase II carboxy-terminal domain kinase activity  fibroblast growth factor receptor signaling pathway  response to toxic substance  positive regulation of peptidyl-threonine phosphorylation  regulation of phosphatidylinositol 3-kinase signaling  microtubule cytoskeleton  viral process  kinase activity  peptidyl-serine phosphorylation  peptidyl-threonine phosphorylation  sensory perception of pain  cytosine metabolic process  phosphatase binding  platelet activation  positive regulation of cell migration  axon  thyroid gland development  pseudopodium  mitogen-activated protein kinase kinase kinase binding  regulation of protein stability  lipopolysaccharide-mediated signaling pathway  positive regulation of telomere maintenance via telomerase  dendrite cytoplasm  regulation of stress-activated MAPK cascade  mammary gland epithelial cell proliferation  Fc-epsilon receptor signaling pathway  Fc-gamma receptor signaling pathway involved in phagocytosis  ERBB signaling pathway  outer ear morphogenesis  identical protein binding  perikaryon  protein complex  response to exogenous dsRNA  response to estrogen  negative regulation of cell differentiation  positive regulation of translation  positive regulation of transcription, DNA-templated  thymus development  T cell receptor signaling pathway  B cell receptor signaling pathway  regulation of sequence-specific DNA binding transcription factor activity  regulation of cytoskeleton organization  positive regulation of telomerase activity  Bergmann glial cell differentiation  long-term synaptic potentiation  face development  JAK-STAT cascade involved in growth hormone signaling pathway  lung morphogenesis  trachea formation  labyrinthine layer blood vessel development  cardiac neural crest cell development involved in heart development  extracellular exosome  ERK1 and ERK2 cascade  ERK1 and ERK2 cascade  response to epidermal growth factor  caveolin-mediated endocytosis  mitotic spindle  regulation of Golgi inheritance  cellular response to granulocyte macrophage colony-stimulating factor stimulus  regulation of cellular response to heat  positive regulation of telomere capping  regulation of early endosome to late endosome transport  
Ontology : EGO-EBIMAPK cascade  activation of MAPK activity  MAPK import into nucleus  phosphotyrosine binding  DNA binding  protein serine/threonine kinase activity  protein serine/threonine kinase activity  MAP kinase activity  protein binding  ATP binding  nucleus  nucleus  nucleoplasm  nucleoplasm  cytoplasm  cytoplasm  mitochondrion  early endosome  late endosome  Golgi apparatus  microtubule organizing center  cytosol  cytoskeleton  caveola  focal adhesion  transcription, DNA-templated  protein phosphorylation  apoptotic process  chemotaxis  response to stress  cellular response to DNA damage stimulus  cell cycle  signal transduction  synaptic transmission  axon guidance  transcription factor binding  positive regulation of cell proliferation  RNA polymerase II carboxy-terminal domain kinase activity  fibroblast growth factor receptor signaling pathway  response to toxic substance  positive regulation of peptidyl-threonine phosphorylation  regulation of phosphatidylinositol 3-kinase signaling  microtubule cytoskeleton  viral process  kinase activity  peptidyl-serine phosphorylation  peptidyl-threonine phosphorylation  sensory perception of pain  cytosine metabolic process  phosphatase binding  platelet activation  positive regulation of cell migration  axon  thyroid gland development  pseudopodium  mitogen-activated protein kinase kinase kinase binding  regulation of protein stability  lipopolysaccharide-mediated signaling pathway  positive regulation of telomere maintenance via telomerase  dendrite cytoplasm  regulation of stress-activated MAPK cascade  mammary gland epithelial cell proliferation  Fc-epsilon receptor signaling pathway  Fc-gamma receptor signaling pathway involved in phagocytosis  ERBB signaling pathway  outer ear morphogenesis  identical protein binding  perikaryon  protein complex  response to exogenous dsRNA  response to estrogen  negative regulation of cell differentiation  positive regulation of translation  positive regulation of transcription, DNA-templated  thymus development  T cell receptor signaling pathway  B cell receptor signaling pathway  regulation of sequence-specific DNA binding transcription factor activity  regulation of cytoskeleton organization  positive regulation of telomerase activity  Bergmann glial cell differentiation  long-term synaptic potentiation  face development  JAK-STAT cascade involved in growth hormone signaling pathway  lung morphogenesis  trachea formation  labyrinthine layer blood vessel development  cardiac neural crest cell development involved in heart development  extracellular exosome  ERK1 and ERK2 cascade  ERK1 and ERK2 cascade  response to epidermal growth factor  caveolin-mediated endocytosis  mitotic spindle  regulation of Golgi inheritance  cellular response to granulocyte macrophage colony-stimulating factor stimulus  regulation of cellular response to heat  positive regulation of telomere capping  regulation of early endosome to late endosome transport  
Pathways : BIOCARTAErk and PI-3 Kinase Are Necessary for Collagen Binding in Corneal Epithelia [Genes]    How Progesterone Initiates the Oocyte Maturation [Genes]    Stat3 Signaling Pathway [Genes]    Angiotensin II mediated activation of JNK Pathway via Pyk2 dependent signaling [Genes]    Bioactive Peptide Induced Signaling Pathway [Genes]    Erk1/Erk2 Mapk Signaling pathway [Genes]    Signaling of Hepatocyte Growth Factor Receptor [Genes]    Links between Pyk2 and Map Kinases [Genes]    Trefoil Factors Initiate Mucosal Healing [Genes]    Role of Erk5 in Neuronal Survival [Genes]    Growth Hormone Signaling Pathway [Genes]    Mechanism of Gene Regulation by Peroxisome Proliferators via PPARa(alpha) [Genes]    CCR3 signaling in Eosinophils [Genes]    Influence of Ras and Rho proteins on G1 to S Transition [Genes]    Roles of -arrestin-dependent Recruitment of Src Kinases in GPCR Signaling [Genes]    Phosphorylation of MEK1 by cdk5/p35 down regulates the MAP kinase pathway [Genes]    Ceramide Signaling Pathway [Genes]    Phospholipids as signalling intermediaries [Genes]    Integrin Signaling Pathway [Genes]    NFAT and Hypertrophy of the heart (Transcription in the broken heart) [Genes]    Regulation of Splicing through Sam68 [Genes]    IL-2 Receptor Beta Chain in T cell Activation [Genes]    Cadmium induces DNA synthesis and proliferation in macrophages [Genes]    Role of MAL in Rho-Mediated Activation of SRF [Genes]    Regulation of BAD phosphorylation [Genes]    Transcription factor CREB and its extracellular signals [Genes]    Regulation of eIF4e and p70 S6 Kinase [Genes]    MAPKinase Signaling Pathway [Genes]    Sprouty regulation of tyrosine kinase signals [Genes]    CXCR4 Signaling Pathway [Genes]    fMLP induced chemokine gene expression in HMC-1 cells [Genes]    Multiple antiapoptotic pathways from IGF-1R signaling lead to BAD phosphorylation [Genes]    Keratinocyte Differentiation [Genes]    Aspirin Blocks Signaling Pathway Involved in Platelet Activation [Genes]    Oxidative Stress Induced Gene Expression Via Nrf2 [Genes]    Fc Epsilon Receptor I Signaling in Mast Cells [Genes]    Pelp1 Modulation of Estrogen Receptor Activity [Genes]    Agrin in Postsynaptic Differentiation [Genes]    Role of -arrestins in the activation and targeting of MAP kinases [Genes]    Human Cytomegalovirus and Map Kinase Pathways [Genes]    Role of ERBB2 in Signal Transduction and Oncology [Genes]    PTEN dependent cell cycle arrest and apoptosis [Genes]   
Pathways : KEGGMAPK signaling pathway    ErbB signaling pathway    Ras signaling pathway    Rap1 signaling pathway    Chemokine signaling pathway    HIF-1 signaling pathway    FoxO signaling pathway    Oocyte meiosis    mTOR signaling pathway    PI3K-Akt signaling pathway    Adrenergic signaling in cardiomyocytes    Vascular smooth muscle contraction    Dorso-ventral axis formation    TGF-beta signaling pathway    Axon guidance    VEGF signaling pathway    Osteoclast differentiation    Focal adhesion    Adherens junction    Gap junction    Toll-like receptor signaling pathway    NOD-like receptor signaling pathway    Natural killer cell mediated cytotoxicity    T cell receptor signaling pathway    B cell receptor signaling pathway    Fc epsilon RI signaling pathway    Fc gamma R-mediated phagocytosis    TNF signaling pathway    Circadian entrainment    Long-term potentiation    Neurotrophin signaling pathway    Retrograde endocannabinoid signaling    Glutamatergic synapse    Cholinergic synapse    Serotonergic synapse    Long-term depression    Regulation of actin cytoskeleton    Insulin signaling pathway    GnRH signaling pathway    Progesterone-mediated oocyte maturation    Estrogen signaling pathway    Melanogenesis    Prolactin signaling pathway    Thyroid hormone signaling pathway    Type II diabetes mellitus    Aldosterone-regulated sodium reabsorption    Alzheimer's disease    Prion diseases    Alcoholism    Shigellosis    Salmonella infection    Pertussis    Leishmaniasis    Chagas disease (American trypanosomiasis)    Toxoplasmosis    Tuberculosis    Hepatitis C    Hepatitis B    Influenza A    Pathways in cancer    Viral carcinogenesis    Proteoglycans in cancer    MicroRNAs in cancer    Colorectal cancer    Renal cell carcinoma    Pancreatic cancer    Endometrial cancer    Glioma    Prostate cancer    Thyroid cancer    Melanoma    Bladder cancer    Chronic myeloid leukemia    Acute myeloid leukemia    Non-small cell lung cancer   
REACTOMEP28482 [protein]
REACTOME PathwaysR-HSA-111995 phospho-PLA2 pathway [pathway]
REACTOME PathwaysR-HSA-112411 MAPK1 (ERK2) activation [pathway]
REACTOME PathwaysR-HSA-5654736 Signaling by FGFR1 [pathway]
REACTOME PathwaysR-HSA-162658 Golgi Cisternae Pericentriolar Stack Reorganization [pathway]
REACTOME PathwaysR-HSA-202670 ERKs are inactivated [pathway]
REACTOME PathwaysR-HSA-2871796 FCERI mediated MAPK activation [pathway]
REACTOME PathwaysR-HSA-5654738 Signaling by FGFR2 [pathway]
REACTOME PathwaysR-HSA-437239 Recycling pathway of L1 [pathway]
REACTOME PathwaysR-HSA-442742 CREB phosphorylation through the activation of Ras [pathway]
REACTOME PathwaysR-HSA-2559585 Oncogene Induced Senescence [pathway]
REACTOME PathwaysR-HSA-5675221 Negative regulation of MAPK pathway [pathway]
REACTOME PathwaysR-HSA-5654741 Signaling by FGFR3 [pathway]
REACTOME PathwaysR-HSA-450341 Activation of the AP-1 family of transcription factors [pathway]
REACTOME PathwaysR-HSA-5654743 Signaling by FGFR4 [pathway]
REACTOME PathwaysR-HSA-444257 RSK activation [pathway]
REACTOME PathwaysR-HSA-881907 Gastrin-CREB signalling pathway via PKC and MAPK [pathway]
REACTOME PathwaysR-HSA-112409 RAF-independent MAPK1/3 activation [pathway]
REACTOME PathwaysR-HSA-375165 NCAM signaling for neurite out-growth [pathway]
REACTOME PathwaysR-HSA-879415 Advanced glycosylation endproduct receptor signaling [pathway]
REACTOME PathwaysR-HSA-198753 ERK/MAPK targets [pathway]
REACTOME PathwaysR-HSA-2029482 Regulation of actin dynamics for phagocytic cup formation [pathway]
REACTOME PathwaysR-HSA-5654726 Negative regulation of FGFR1 signaling [pathway]
REACTOME PathwaysR-HSA-202670 ERKs are inactivated [pathway]
REACTOME PathwaysR-HSA-445144 Signal transduction by L1 [pathway]
REACTOME PathwaysR-HSA-5654727 Negative regulation of FGFR2 signaling [pathway]
REACTOME PathwaysR-HSA-5674135 MAP2K and MAPK activation [pathway]
REACTOME PathwaysR-HSA-5673001 RAF/MAP kinase cascade [pathway]
REACTOME PathwaysR-HSA-5663213 RHO GTPases Activate WASPs and WAVEs [pathway]
REACTOME PathwaysR-HSA-2559582 Senescence-Associated Secretory Phenotype (SASP) [pathway]
REACTOME PathwaysR-HSA-3371453 Regulation of HSF1-mediated heat shock response [pathway]
REACTOME PathwaysR-HSA-456926 Thrombin signalling through proteinase activated receptors (PARs) [pathway]
REACTOME PathwaysR-HSA-5654733 Negative regulation of FGFR4 signaling [pathway]
REACTOME PathwaysR-HSA-2559580 Oxidative Stress Induced Senescence [pathway]
REACTOME PathwaysR-HSA-74749 Signal attenuation [pathway]
REACTOME PathwaysR-HSA-198753 ERK/MAPK targets [pathway]
REACTOME PathwaysR-HSA-5654732 Negative regulation of FGFR3 signaling [pathway]
REACTOME PathwaysR-HSA-5674499 Negative feedback regulation of MAPK pathway [pathway]
REACTOME PathwaysR-HSA-982772 Growth hormone receptor signaling [pathway]
NDEx Network
Atlas of Cancer Signalling NetworkMAPK1
Wikipedia pathwaysMAPK1
Orthology - Evolution
OrthoDB5594
GeneTree (enSembl)ENSG00000100030
Phylogenetic Trees/Animal Genes : TreeFamMAPK1
Homologs : HomoloGeneMAPK1
Homology/Alignments : Family Browser (UCSC)MAPK1
Gene fusions - Rearrangements
Fusion : MitelmanCRKL/MAPK1 [22q11.21/22q11.21]  [t(22;22)(q11;q11)]  
Fusion : MitelmanHIVEP1/MAPK1 [6p24.1/22q11.21]  [t(6;22)(p24;q11)]  
Fusion : MitelmanMAPK1/ARHGEF7 [22q11.21/13q34]  [t(13;22)(q34;q11)]  
Fusion : MitelmanMAPK1/KCNJ4 [22q11.21/22q13.1]  [t(22;22)(q11;q13)]  
Fusion : MitelmanMAPK1/METTL21B [22q11.21/12q14.1]  [t(12;22)(q14;q11)]  
Fusion : MitelmanMAPK1/TOP3B [22q11.21/22q11.22]  [t(22;22)(q11;q11)]  
Fusion: TCGAHIVEP1 6p24.1 MAPK1 22q11.21 LUAD
Fusion: TCGAMAPK1 22q11.21 ARHGEF7 13q34 LUAD
Fusion: TCGAMAPK1 22q11.21 KCNJ4 22q13.1 BRCA
Fusion: TCGAMAPK1 22q11.21 TOP3B 22q11.22 LUAD
Polymorphisms : SNP, variants
NCBI Variation ViewerMAPK1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)MAPK1
dbVarMAPK1
ClinVarMAPK1
1000_GenomesMAPK1 
Exome Variant ServerMAPK1
ExAC (Exome Aggregation Consortium)MAPK1 (select the gene name)
Genetic variants : HAPMAP5594
Genomic Variants (DGV)MAPK1 [DGVbeta]
Mutations
ICGC Data PortalMAPK1 
TCGA Data PortalMAPK1 
Broad Tumor PortalMAPK1
OASIS PortalMAPK1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICMAPK1 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch MAPK1
DgiDB (Drug Gene Interaction Database)MAPK1
DoCM (Curated mutations)MAPK1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)MAPK1 (select a term)
intoGenMAPK1
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)22:22113947-22221970  ENSG00000100030
CONAN: Copy Number AnalysisMAPK1 
Mutations and Diseases : HGMDMAPK1
OMIM176948   
MedgenMAPK1
Genetic Testing Registry MAPK1
NextProtP28482 [Medical]
TSGene5594
GENETestsMAPK1
Huge Navigator MAPK1 [HugePedia]
snp3D : Map Gene to Disease5594
BioCentury BCIQMAPK1
ClinGenMAPK1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD5594
Chemical/Pharm GKB GenePA30616
Clinical trialMAPK1
Miscellaneous
canSAR (ICR)MAPK1 (select the gene name)
Probes
Litterature
PubMed499 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineMAPK1
EVEXMAPK1
GoPubMedMAPK1
iHOPMAPK1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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