MAPK1

Gene Information
 
Gene Symbol
MAPK1
 
Aliases
ERK, ERK-2, ERK2, ERT1, MAPK2, P42MAPK, PRKM1, PRKM2, p38, p40, p41, p41mapk, p42-MAPK
 
Entrez Gene ID
 
Gene Name
Mitogen-activated protein kinase 1
 
Chromosomal Location
22q11.21
 
HGNC ID
 
Summary
This gene encodes a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. The activation of this kinase requires its phosphorylation by upstream kinases. Upon activation, this kinase translocates to the nucleus of the stimulated cells, where it phosphorylates nuclear targets. One study also suggests that this protein acts as a transcriptional repressor independent of its kinase activity. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Two alternatively spliced transcript variants encoding the same protein, but differing in the UTRs, have been reported for this gene. (provided by RefSeq, Jan 2014)
 
GeneCards ID
 
UniGene
 
RefSeq mRNA
Protein

Gene Ontology (GO)

GO ID Ontology Definition Evidence Reference
GO:0006935 Biological process Chemotaxis TAS 10706854
GO:0006950 Biological process Response to stress TAS 10958679
GO:0007165 Biological process Signal transduction TAS 1540184
GO:0010800 Biological process Positive regulation of peptidyl-threonine phosphorylation IDA 16314496
GO:0018105 Biological process Peptidyl-serine phosphorylation IDA 15850461
Protein Information
 
Protein Name
MAP kinase 1 , MAP kinase isoform p42 , Mitogen-activated protein kinase 2 , ERK2 , p42-MAPK , ERT1 , Extracellular signal-regulated kinase 2 , extracellular signal-regulated kinase 2 , p41 , PRKM2 , MAPK 1 , p40 , p41mapk , mitogen-activated protein kinase 1, ERK-2 , mitogen-activated protein kinase 2 , MAPK 2 , ERK , PRKM1 , p38 , P42MAPK , MAP kinase 2 , MAPK2 , protein tyrosine kinase ERK2 , EC 2.7.11.24
 
Function
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. 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.
 
UniProt
 
InterPro
 
Pfam
Pfam Accession Pfam ID
PF00069 Pkinase
 
KEGG
MAPK 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, Oxytocin signaling pathway, Type II diabetes mellitus, Aldosterone-regulated sodium reabsorption, Alzheimers 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
 
OMIM

Associated Diseases

Diseases References
Hyperinsulinemia. 21176559
Polycystic ovary syndrome (PCOS) 16505239
   
References
 
Primary:

[Extracellular signal-regulated protein kinase activation in endometrium with polycystic ovary syndrome and its significance].

Song Xue-Ru, Zhang Hui-Ying, Zhang Yan-Fang, Han Yu-Kun, Li Ke-Jun
Department of Obstetrics and Gynecology, General Hospital, Tianjin Medical University, Tianjin 300052, China. songxr63@yahoo.com.cn
Zhonghua Fu Chan Ke Za Zhi. 2010 Oct;45(10):767-71.
 
Supporting Literature:
PubMed ID Associated gene/s Associated condition Genetic Mutation Diagnostic Criteria Association with PCOS Ethnicity Conclusion
(IRS)-1 serine 
 
 
Women with PCOS (n = 20) had six or fewer menses per year and elevated total testosterone and/or non–sex hormone–binding globulin–bound testosterone levels 
Related 
20 PCOS womens and 15 control 
ERK1/2 activation may play a role in feedback of insulin signaling and contribute to resistance to insulin's metabolic actions in PCOS. 
p-ERK1/2 
Hyperinsulinemia. 
 
 
Related 
52 patients as PCOS and 32 non-PCOS  
Endometrium in PCOS group was higher and expression of p-ERK1/2 was significantly increased in group of endometrial hyperplasia and carcinoma compare to control 
Insulin 
phosphorylation of ERK1/2  
 
Rotterdam criteria 
Related 
9 PCOS womes and 7 controls 
The altered response of ERK to insulin in PCOS was the most obvious signalling defect associated with insulin resistance in muscle from these patients. 

 

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