P46196 (MK01_BOVIN) Reviewed, UniProtKB/Swiss-Prot
Last modified June 11, 2014. Version 126. History...
Names and origin
|Protein names||Recommended name:|
Mitogen-activated protein kinase 1
Short name=MAP kinase 1
Short name=MAPK 1
Extracellular signal-regulated kinase 2
Mitogen-activated protein kinase 2
Short name=MAP kinase 2
Short name=MAPK 2
|Organism||Bos taurus (Bovine) [Reference proteome]|
|Taxonomic identifier||9913 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos|
|Sequence length||360 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at transcript level|
General annotation (Comments)
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. May play a role in the spindle assembly checkpoint By similarity. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation 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 By similarity.
ATP + a protein = ADP + a phosphoprotein.
Magnesium By similarity.
Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on Thr-185 and Tyr-187 in response to external stimuli like insulin or NGF. Both phosphorylations are required for activity. This phosphorylation causes dramatic conformational changes, which enable full activation and interaction of MAPK1/ERK2 with its substrates. Phosphorylation on Ser-29 by SGK1 results in its activation by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. Dephosphorylated and inactivated by DUSP3, DUSP6 and DUSP9. Inactivated by pyrimidylpyrrole inhibitors By similarity.
Binds both upstream activators and downstream substrates in multimolecular complexes. Interacts with ADAM15, ARHGEF2, ARRB2, DAPK1 (via death domain), HSF4, IER3, IPO7, MKNK2, DUSP6, MORG1, NISCH, PEA15, SGK1, and isoform 1of NEK2 By similarity. Interacts (phosphorylated form) with CAV2 ('Tyr-19'-phosphorylated form); the interaction, promoted by insulin, leads to nuclear location and MAPK1 activation By similarity. MKNK2 isoform 1binding prevents from dephosphorylation and inactivation By similarity. Interacts with DCC By similarity. The phosphorylated form interacts with PML By similarity.
Nucleus By similarity. Cytoplasm › cytoskeleton › microtubule organizing center › centrosome By similarity. Cytoplasm By similarity. Cytoplasm › cytoskeleton › spindle By similarity. Note: PEA15-binding and phosphorylated DAPK1 promote its cytoplasmic retention By similarity. Phosphorylation at Ser-246 and Ser-248 as well as autophosphorylation at Thr-190 promote nuclear localization By similarity. Associated with the spindle during prometaphase and metaphase By similarity.
The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.
Dually phosphorylated on Thr-185 and Tyr-187, which activates the enzyme. Phosphorylated upon FLT3 and KIT signaling By similarity. Phosphorylation on Ser-29 by SGK1 results in its activation by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2 By similarity. Phosphorylation at Ser-246 and Ser-248 as well as autophosphorylation at Thr-190 promote nuclear localization. Ligand-activated ALK induces tyrosine phosphorylation By similarity. Dephosphorylated by PTPRJ at Tyr-187 By similarity.
ISGylated By similarity.
Contains 1 protein kinase domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Initiator methionine||1||1||Removed By similarity|
|Chain||2 – 360||359||Mitogen-activated protein kinase 1||PRO_0000186246|
|Domain||25 – 313||289||Protein kinase|
|Nucleotide binding||31 – 39||9||ATP By similarity|
|Region||105 – 108||4||Inhibitor-binding By similarity|
|Region||153 – 154||2||Inhibitor-binding By similarity|
|Motif||185 – 187||3||TXY|
|Compositional bias||2 – 9||8||Poly-Ala|
|Active site||149||1||Proton acceptor By similarity|
|Binding site||54||1||ATP By similarity|
|Binding site||54||1||Inhibitor By similarity|
|Binding site||108||1||Inhibitor; via amide nitrogen and carbonyl oxygen By similarity|
|Binding site||114||1||Inhibitor By similarity|
|Binding site||154||1||Inhibitor By similarity|
|Binding site||166||1||Inhibitor By similarity|
|Binding site||167||1||Inhibitor By similarity|
Amino acid modifications
|Modified residue||2||1||N-acetylalanine By similarity|
|Modified residue||29||1||Phosphoserine; by SGK1 By similarity|
|Modified residue||185||1||Phosphothreonine; by MAP2K1 and MAP2K2 By similarity|
|Modified residue||187||1||Phosphotyrosine; by MAP2K1 and MAP2K2 By similarity|
|Modified residue||190||1||Phosphothreonine; by autocatalysis By similarity|
|Modified residue||246||1||Phosphoserine By similarity|
|Modified residue||248||1||Phosphoserine By similarity|
|Modified residue||284||1||Phosphoserine By similarity|
|||"Cloning and sequencing of ERK2 from a bovine adrenal medulla cDNA library."|
Ely C.M., Cox M.E., Her J., Parsons S.J.
Submitted (JUL-1992) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Adrenal medulla.
|||NIH - Mammalian Gene Collection (MGC) project|
Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Fetal pons.
|Z14089 mRNA. Translation: CAA78467.1.|
BC133588 mRNA. Translation: AAI33589.2.
|RefSeq||NP_786987.1. NM_175793.2. |
3D structure databases
|SMR||P46196. Positions 8-357. |
Protein-protein interaction databases
Protocols and materials databases
Genome annotation databases
Family and domain databases
|InterPro||IPR011009. Kinase-like_dom. |
|Pfam||PF00069. Pkinase. 1 hit. |
|PRINTS||PR01770. ERK1ERK2MAPK. |
|SMART||SM00220. S_TKc. 1 hit. |
|SUPFAM||SSF56112. SSF56112. 1 hit. |
|PROSITE||PS01351. MAPK. 1 hit. |
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
|Accession||Primary (citable) accession number: P46196|
Secondary accession number(s): A2VE60
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families