Mus musculus Protein: Mapk1
Summary
InnateDB Protein IDBP-137676.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol Mapk1
Protein Name mitogen-activated protein kinase 1
Synonyms 9030612K14Rik; AA407128; AU018647; C78273; ERK; Erk2; MAPK2; p41mapk; p42mapk; Prkm1; PRKM2;
Species Mus musculus
Ensembl Protein ENSMUSP00000023462
InnateDB Gene IDBG-137672 (Mapk1)
Protein Structure
UniProt Annotation
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 (By similarity). {ECO:0000250}.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 (By similarity). {ECO:0000250}.
Subcellular Localization Cytoplasm, cytoskeleton, spindle {ECO:0000250}. Nucleus. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250}. Cytoplasm. Note=Associated with the spindle during prometaphase and metaphase (By similarity). PEA15-binding and phosphorylated DAPK1 promote its cytoplasmic retention. Phosphorylation at Ser-244 and Ser-246 as well as autophosphorylation at Thr-188 promote nuclear localization (By similarity). {ECO:0000250}.
Disease Associations
Tissue Specificity Widely expressed.
Comments
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 109 experimentally validated interaction(s) in this database.
They are also associated with 176 interaction(s) predicted by orthology.
Experimentally validated
Total 109 [view]
Protein-Protein 107 [view]
Protein-DNA 0
Protein-RNA 0
DNA-DNA 2 [view]
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 176 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0001784 phosphotyrosine binding
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0004707 MAP kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0008134 transcription factor binding
GO:0008353 RNA polymerase II carboxy-terminal domain kinase activity
GO:0016301 kinase activity
GO:0016772 transferase activity, transferring phosphorus-containing groups
GO:0019902 phosphatase binding
GO:0031435 mitogen-activated protein kinase kinase kinase binding
Biological Process
GO:0000165 MAPK cascade
GO:0000189 MAPK import into nucleus
GO:0006351 transcription, DNA-templated
GO:0006468 protein phosphorylation
GO:0006915 apoptotic process
GO:0006974 cellular response to DNA damage stimulus
GO:0007049 cell cycle
GO:0008284 positive regulation of cell proliferation
GO:0009636 response to toxic substance
GO:0009887 organ morphogenesis
GO:0010800 positive regulation of peptidyl-threonine phosphorylation
GO:0018105 peptidyl-serine phosphorylation
GO:0018107 peptidyl-threonine phosphorylation
GO:0019233 sensory perception of pain
GO:0019858 cytosine metabolic process
GO:0030335 positive regulation of cell migration
GO:0031647 regulation of protein stability
GO:0031663 lipopolysaccharide-mediated signaling pathway
GO:0032496 response to lipopolysaccharide
GO:0032872 regulation of stress-activated MAPK cascade
GO:0033598 mammary gland epithelial cell proliferation
GO:0038127 ERBB signaling pathway
GO:0043330 response to exogenous dsRNA
GO:0043627 response to estrogen
GO:0045087 innate immune response (InnateDB)
GO:0045596 negative regulation of cell differentiation
GO:0045727 positive regulation of translation
GO:0045893 positive regulation of transcription, DNA-templated
GO:0050852 T cell receptor signaling pathway
GO:0050853 B cell receptor signaling pathway
GO:0051090 regulation of sequence-specific DNA binding transcription factor activity
GO:0051493 regulation of cytoskeleton organization
GO:0060716 labyrinthine layer blood vessel development
GO:0070371 ERK1 and ERK2 cascade
GO:0070849 response to epidermal growth factor
GO:0072584 caveolin-mediated endocytosis
GO:0090170 regulation of Golgi inheritance
GO:0097011 cellular response to granulocyte macrophage colony-stimulating factor stimulus
GO:2000641 regulation of early endosome to late endosome transport
Cellular Component
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005769 early endosome
GO:0005770 late endosome
GO:0005794 Golgi apparatus
GO:0005815 microtubule organizing center
GO:0005829 cytosol
GO:0005856 cytoskeleton
GO:0005901 caveola
GO:0005925 focal adhesion
GO:0031143 pseudopodium
GO:0032839 dendrite cytoplasm
GO:0043204 perikaryon
GO:0043234 protein complex
GO:0072686 mitotic spindle
Protein Structure and Domains
PDB ID MGI:1346858
InterPro IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine- /dual specificity protein kinase, catalytic domain
IPR008349 Mitogen-activated protein (MAP) kinase, ERK1/2
IPR008350 Mitogen-activated protein (MAP) kinase, ERK3/4
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain
PFAM PF00069
PF07714
PRINTS PR00109
PR01770
PR01771
PIRSF
SMART SM00220
SM00219
TIGRFAMs
Post-translational Modifications
Modification
Cross-References
SwissProt P63085
PhosphoSite PhosphoSite-P63085
TrEMBL
UniProt Splice Variant
Entrez Gene 26413
UniGene Mm.196581
RefSeq
MGI ID
MGI Symbol Mapk1
OMIM
CCDS CCDS27992
HPRD
IMGT
EMBL AK035386 AK048127 AK087925 AK132241 BC058258 D10939 X58712
GenPept AAH58258 BAA01733 BAC29053 BAC33251 BAC40044 BAE21053 CAA41548