MAPK3
entrez
5595
canonical
uniprot
P27361
canonical
ensembl
ENSG00000102882
resolver
ensp
ENSP00000263025
resolver
ensp
ENSP00000327293
resolver
ensp
ENSP00000378625
resolver
genesymbol
MAPK3
resolver
genesymbol_syn
ERK1
resolver
genesymbol_syn
PRKM3
resolver
hgnc
HGNC:6877
resolver
uniprot
A8CZ58
resolver
uniprot
B0LPG3
resolver
uniprot
L7RXH5
resolver
uniprot
Q8NHX1
resolver
uniprot
Q9BWJ1
resolver
uniprot_entry
L7RXH5_HUMAN
resolver
uniprot_entry
MK03_HUMAN
resolver
uniprot_entry
Q9BWJ1_HUMAN
resolver
uniprot_sec
A8CZ58
resolver
uniprot_sec
B0LPG3
resolver
uniprot_sec
Q8NHX1
resolver
activity_regulation
ACTIVITY REGULATION: Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on Thr-202 and Tyr-204 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. Dephosphorylated and inactivated by DUSP3, DUSP6 and DUSP9. {ECO:0000269|PubMed:12356731, ECO:0000269|PubMed:19060905}.
uniprot
proteins
amino_acid_sequence
MAAAAAQGGGGGEPRRTEGVGPGVPGEVEMVKGQPFDVGPRYTQLQYIGEGAYGMVSSAYDHVRKTRVAIKKISPFEHQTYCQRTLREIQILLRFRHENVIGIRDILRASTLEAMRDVYIVQDLMETDLYKLLKSQQLSNDHICYFLYQILRGLKYIHSANVLHRDLKPSNLLINTTCDLKICDFGLARIADPEHDHTGFLTEYVATRWYRAPEIMLNSKGYTKSIDIWSVGCILAEMLSNRPIFPGKHYLDQLNHILGILGSPSQEDLNCIINMKARNYLQSLPSKTKVAWAKLFPKSDSKALDLLDRMLTFNPNKRITVEEALAHPYLEQYYDPTDEPVAEEPFTFAMELDDLPKERLKELIFQETARFQPGVLEAP
uniprot
proteins
ec_number
2.7.11.24
uniprot
proteins
function
FUNCTION: Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway (PubMed:34497368). 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 also plays 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, DEPTOR, FRS2 or GRB10) (PubMed:35216969). 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. Phosphorylates GJA1 at 'Ser-279' and 'Ser-282' resulting in an increase in GJA1 ubiquitination and ultimately lysosomal degradation (By similarity). {ECO:0000250|UniProtKB:P21708, ECO:0000269|PubMed:10393181, ECO:0000269|PubMed:10617468, ECO:0000269|PubMed:12110590, ECO:0000269|PubMed:12356731, ECO:0000269|PubMed:12974390, ECO:0000269|PubMed:15788397, ECO:0000269|PubMed:15952796, ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:34497368, ECO:0000269|PubMed:35216969, ECO:0000269|PubMed:8325880, ECO:0000269|PubMed:9155018, ECO:0000269|PubMed:9480836}.
uniprot
proteins
mass_dalton
43136
uniprot
proteins
mutagenesis
MUTAGEN 168; /note="K->R: Complete loss of ubiquitination by TRIM15; when associated with R-302."; /evidence="ECO:0000269|PubMed:34497368"; MUTAGEN 302; /note="K->R: Complete loss of ubiquitination by TRIM15; when associated with R-168."; /evidence="ECO:0000269|PubMed:34497368
uniprot
proteins
post_translational_modification
PTM: Phosphorylated upon KIT and FLT3 signaling (By similarity). Dually phosphorylated on Thr-202 and Tyr-204, which activates the enzyme. Ligand-activated ALK induces tyrosine phosphorylation. Dephosphorylated by PTPRJ at Tyr-204. {ECO:0000250, ECO:0000269|PubMed:17274988, ECO:0000269|PubMed:18983981, ECO:0000269|PubMed:19060905, ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:19494114}.; PTM: Ubiquitinated by TRIM15 via 'Lys-63'-linked ubiquitination; leading to activation. Deubiquitinated by CYLD. {ECO:0000269|PubMed:34497368}.
uniprot
proteins
protein_family
CMGC Ser/Thr protein kinase family
uniprot
proteins
protein_family
MAP kinase subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
pubmed
10224087
uniprot
proteins
pubmed
10393181
uniprot
proteins
pubmed
10521408
uniprot
proteins
pubmed
10617468
uniprot
proteins
pubmed
10747973
uniprot
proteins
pubmed
11912194
uniprot
proteins
pubmed
12110590
uniprot
proteins
pubmed
12356731
uniprot
proteins
pubmed
12974390
uniprot
proteins
pubmed
1319925
uniprot
proteins
pubmed
1540184
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15526160
uniprot
proteins
pubmed
15616553
uniprot
proteins
pubmed
15616583
uniprot
proteins
pubmed
15788397
uniprot
proteins
pubmed
15952796
uniprot
proteins
pubmed
16393692
uniprot
proteins
pubmed
16581800
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17274988
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
18296648
uniprot
proteins
pubmed
18435604
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
18794356
uniprot
proteins
pubmed
18983981
uniprot
proteins
pubmed
19060905
uniprot
proteins
pubmed
19265199
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19447520
uniprot
proteins
pubmed
19494114
uniprot
proteins
pubmed
19565474
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21779493
uniprot
proteins
pubmed
22223895
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24825908
uniprot
proteins
pubmed
32051553
uniprot
proteins
pubmed
34497368
uniprot
proteins
pubmed
35216969
uniprot
proteins
pubmed
35939714
uniprot
proteins
pubmed
7687743
uniprot
proteins
pubmed
8325880
uniprot
proteins
pubmed
8794306
uniprot
proteins
pubmed
9155018
uniprot
proteins
pubmed
9480836
uniprot
proteins
sequence_length
379
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P21708}. Nucleus. Membrane, caveola {ECO:0000250|UniProtKB:P21708}. Cell junction, focal adhesion {ECO:0000250|UniProtKB:Q63844}. Note=Autophosphorylation at Thr-207 promotes nuclear localization (PubMed:19060905). PEA15-binding redirects the biological outcome of MAPK3 kinase-signaling by sequestering MAPK3 into the cytoplasm (By similarity). {ECO:0000250|UniProtKB:Q63844, ECO:0000269|PubMed:19060905}.
uniprot
proteins