General Information of Binding Target of SBP (BTS) (ID: ST00139)
BTS Name
Mitogen-activated protein kinase 1
Synonyms
MAP kinase 1; MAPK 1; EC 2.7.11.24; ERT1; Extracellular signal-regulated kinase 2; ERK-2; MAP kinase isoform p42; p42-MAPK; Mitogen-activated protein kinase 2; MAP kinase 2; MAPK 2
BTS Type
Protein
Family
Protein kinase superfamily;
CMGC Ser/Thr protein kinase family;
MAP kinase subfamily
Gene Name
MAPK1
Organism
Homo sapiens (Human)
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 response to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation. Phosphorylates CDK2AP2 (By similarity).; 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 ID
P28482
UniProt Entry
MK01_HUMAN
PFam
PF00069
Gene ID
5594
Sequence
MAAAAAAGAGPEMVRGQVFDVGPRYTNLSYIGEGAYGMVCSAYDNVNKVRVAIKKISPFE
HQTYCQRTLREIKILLRFRHENIIGINDIIRAPTIEQMKDVYIVQDLMETDLYKLLKTQH
LSNDHICYFLYQILRGLKYIHSANVLHRDLKPSNLLLNTTCDLKICDFGLARVADPDHDH
TGFLTEYVATRWYRAPEIMLNSKGYTKSIDIWSVGCILAEMLSNRPIFPGKHYLDQLNHI
LGILGSPSQEDLNCIINLKARNYLLSLPHKNKVPWNRLFPNADSKALDLLDKMLTFNPHK
RIEVEQALAHPYLEQYYDPSDEPIAEAPFKFDMELDDLPKEKLKELIFEETARFQPGYRS
Sequence Length
360
Synthetic Binding Protein (SBP) Targeting This BTS
SBP Name Highest Status Mechanism Affinity Application Details Ref
DARPin anti-ERK2 A443D Research Inhibitor N.A. Tools as phosphorylation-specific protein binders of ERK2
SBP Info
[1]
DARPin anti-ERK2 EpEM6 Research Binder Kd: 633 nM Tools for recognizing post-translationally phosphorylated proteins
SBP Info
[2]
DARPin anti-ERK2 EpEM6 Research Binder Kd: 784 nM Tools for recognizing post-translationally phosphorylated proteins
SBP Info
[2]
DARPin anti-ERK2 EpEM7 Research Binder Kd: 25.2 nM Tools for recognizing post-translationally phosphorylated proteins
SBP Info
[2]
DARPin anti-ERK2 EpEM7 Research Binder Kd: 222 nM Tools for recognizing post-translationally phosphorylated proteins
SBP Info
[2]
DARPin anti-ERK2 pE59 Research Binder Kd: 453 nM Tools for recognizing post-translationally phosphorylated proteins
SBP Info
[2]
DARPin anti-ERK2 pE59 Research Binder Kd: >3500 nM Tools for recognizing post-translationally phosphorylated proteins
SBP Info
[2]
DARPin anti-ERK2 pEM1 Research Binder Kd: 87.1 nM Tools for recognizing post-translationally phosphorylated proteins
SBP Info
[2]
DARPin anti-ERK2 pEM1 Research Binder Kd: >3500 nM Tools for recognizing post-translationally phosphorylated proteins
SBP Info
[2]
DARPin anti-ERK2 S380L Research Inhibitor N.A. Tools as phosphorylation-specific protein binders of ERK2
SBP Info
[1]
Monobody anti-Erk-2 F6.2 Research Inhibitor Kd: 12.4 nM Research tool
SBP Info
[3]
Monobody anti-Erk-2 F7.1 Research Inhibitor Kd: 16.2 nM Research tool
SBP Info
[3]
Monobody anti-Erk-2 F7.4 Research Inhibitor Kd: 18.2 nM Research tool
SBP Info
[3]
Monobody anti-Erk-2 F7.8 Research Inhibitor Kd: 1.3 nM Research tool
SBP Info
[3]
Monobody anti-Erk-2 F7.9 Research Inhibitor Kd: 8.4 nM Research tool
SBP Info
[3]
References
1 Molecular Dynamics Simulations in Designing DARPins as Phosphorylation-Specific Protein Binders of ERK2. Molecules. 2021 Jul 27;26(15):4540.
2 A survival selection strategy for engineering synthetic binding proteins that specifically recognize post-translationally phosphorylated proteins. Nat Commun. 2019 Apr 23;10(1):1830.
3 Epitope-guided engineering of monobody binders for in vivo inhibition of Erk-2 signaling. ACS Chem Biol. 2013 Mar 15;8(3):608-16.