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Details on Person UniProt:P27361 MAPK3

Class:Id	ReferenceGeneProduct:59285
_chainChangeLog	initiator methionine:1 added on Fri February 6 2015;chain:2-379 added on Fri February 6 2015;initiator methionine:1 for 59285 removed on Fri Nov 03 2023;initiator methionine: for 59285 added on Fri Nov 03 2023;initiator methionine: for 59285 removed on Fri Aug 15 2025;initiator methionine:1 for 59285 added on Fri Aug 15 2025
_displayName	UniProt:P27361 MAPK3
_timestamp	2026-02-20 22:45:51
chain	initiator methionine:1 chain:2-379
checksum	E6020CE413EC41F7
comment	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).CATALYTIC ACTIVITY L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)CATALYTIC ACTIVITY L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)COFACTOR 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.SUBUNIT Binds both upstream activators and downstream substrates in multimolecular complexes. Found in a complex with at least BRAF, HRAS, MAP2K1/MEK1, MAPK3 and RGS14 (By similarity). Interacts with ADAM15, ARRB2, CANX, DAPK1 (via death domain), HSF4, IER3, MAP2K1/MEK1, MORG1, NISCH, and SGK1. Interacts with PEA15 and MKNK2 (By similarity). MKNK2 isoform 1 binding prevents from dephosphorylation and inactivation (By similarity). Interacts with TPR. Interacts with CDKN2AIP. Interacts with HSF1 (via D domain and preferentially with hyperphosphorylated form); this interaction occurs upon heat shock (PubMed:10747973). Interacts with CAVIN4 (By similarity). Interacts with GIT1; this interaction is necessary for MAPK3 localization to focal adhesions (By similarity). Interacts with ZNF263 (PubMed:32051553). Interacts with EBF4.SUBUNIT (Microbial infection) Binds to HIV-1 Nef through its SH3 domain. This interaction inhibits its tyrosine-kinase activity.INTERACTION 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).ALTERNATIVE PRODUCTS The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.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.PTM Ubiquitinated by TRIM15 via 'Lys-63'-linked ubiquitination; leading to activation. Deubiquitinated by CYLD.SIMILARITY Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.
description	recommendedName: Mitogen-activated protein kinase 3 shortName: MAP kinase 3 shortName: MAPK 3 ecNumber: 2.7.11.24 alternativeName: ERT2 alternativeName: Extracellular signal-regulated kinase 1 shortName: ERK-1 alternativeName: Insulin-stimulated MAP2 kinase alternativeName: MAP kinase isoform p44 shortName: p44-MAPK alternativeName: Microtubule-associated protein 2 kinase alternativeName: p44-ERK1
geneName	MAPK3 ERK1 PRKM3
identifier	P27361
isSequenceChanged	FALSE
keyword	3D-structure Acetylation Alternative splicing Apoptosis ATP-binding Cell cycle Cell junction Cytoplasm Direct protein sequencing Host-virus interaction Kinase Membrane Nucleotide-binding Nucleus Phosphoprotein Proteomics identification Reference proteome Serine/threonine-protein kinase Transferase Ubl conjugation
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20
name	MAPK3
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8993747] ENSEMBL:ENSG00000102882 MAPK3 [Homo sapiens]
secondaryIdentifier	MK03_HUMAN A8CZ58 B0LPG3 Q8NHX1
sequenceLength	379
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:2422446] UniProt:P27361-3 MAPK3 [Homo sapiens] [ReferenceIsoform:8972940] UniProt:P27361-1 MAPK3 [Homo sapiens] [ReferenceIsoform:8972941] UniProt:P27361-2 MAPK3 [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:59284] MAPK3 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:73724] MAPK3 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:109842] p-T202,Y204-MAPK3 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:112359] p-T202,Y204-MAPK3 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:9635775] p-T202-MAPK3 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:9636295] MAPK3 [endoplasmic reticulum lumen] [Homo sapiens]
(referenceSequence)	[ModifiedResidue:109839] O-phospho-L-threonine at 202 [ModifiedResidue:109840] O4'-phospho-L-tyrosine at 204
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No pathways have been reviewed or authored by UniProt:P27361 MAPK3 (59285)