P63086

Background

Protein Name
Mitogen-activated protein kinase 1
Gene Name
Mapk1
Organism
Rattus norvegicus

Annotations

Function
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). 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).

Mapping Statistics

Site Maximum Consensus Site Population Minimum Consensus Site Population Median Consensus Site Population
EDI 29 2 11.0
MT3 28 2 14.0
PIF 21 3 13.0
ATP 13 1 6.0
DEF 11 2 10.0
DRS 9 2 3.0
AAS 14 4 9.0
DFG 11 2 7.5
LBP 24 1 5.5
PDIG 12 2 3.0

Mapping Results

PDB ID Maximum Consensus Site Population
EDI site MT3 site PIF site ATP site DEF site DRS site AAS site MPP site DFG site LBP site CMP site PDIG site PMP site
Total Druggable Structures per Site 16 12 4 0 0 0 0 0 0 5 0 0 0
3ZUV 13 13 0 6 0 0 0 0 0 0 0 0 0
4XOY 13 0 21 0 0 0 14 0 4 0 0 0 0
4XP2 16 0 0 6 0 4 0 0 10 0 0 0 0
3QYZ 11 16 0 0 0 3 0 0 0 16 0 0 0
4XOZ 14 0 20 1 0 0 0 0 0 5 0 0 0
4XRL 15 16 0 4 0 3 0 0 0 2 0 0 0
2FYS 26 14 0 6 0 9 0 0 0 9 0 0 0
2Z7L 16 28 0 2 0 0 0 0 0 15 0 2 0
4N4S 12 21 0 0 0 4 0 0 0 0 0 0 0
3ERK 0 0 0 0 0 6 0 0 0 24 0 3 0
3R63 29 0 0 0 0 3 0 0 11 14 0 0 0
4GVA 14 14 0 0 0 3 0 0 0 3 0 0 0
4XP3 12 0 15 0 0 0 0 0 0 3 0 0 0
4ERK 9 9 0 4 0 0 0 0 0 17 0 3 0
3C9W 8 17 0 7 0 0 0 0 2 15 0 0 0
2GPH 13 0 0 13 10 0 0 0 0 7 0 0 0
4XRJ 15 0 0 0 0 3 0 0 0 4 0 0 0
4XP0 15 0 0 7 0 6 0 0 2 0 0 0 0
4S33 19 13 0 0 0 4 0 0 0 7 0 2 0
1GOL 13 0 0 0 0 0 0 0 0 15 0 0 0
AFP63086 0 0 0 0 0 0 0 0 0 0 0 0 0
4QYY 16 19 0 6 0 0 0 0 0 2 0 0 0
3O71 16 18 0 2 0 3 0 0 0 9 0 0 0
4S32 17 9 14 0 0 0 0 0 0 2 0 3 0
4GT3 18 23 0 2 0 0 0 0 0 19 0 0 0
3ZU7 18 0 12 8 0 0 0 0 0 8 0 0 0
5HD4 16 20 17 11 0 0 0 0 0 0 0 0 0
4S2Z 16 0 0 0 0 0 0 0 0 7 0 0 0
1ERK 15 14 0 2 0 0 0 0 0 22 0 0 0
4S30 16 0 0 0 0 0 0 0 0 8 0 0 0
2ERK 14 20 0 0 0 0 0 0 0 2 0 0 0
4S34 14 5 0 0 0 3 0 0 9 11 0 0 0
3QYW 15 0 0 0 0 2 0 0 11 0 0 0 0
4GSB 21 18 0 7 0 0 0 0 0 13 0 0 0
4I5H 10 0 0 3 11 0 0 0 6 0 0 12 0
5HD7 16 16 14 11 0 2 0 0 0 0 0 0 0
4XNE 15 0 0 0 0 0 0 0 0 3 0 0 0
4S31 22 0 0 6 0 3 0 0 0 6 0 3 0
5KE0 14 2 17 10 0 2 0 0 0 5 0 0 0