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Details on Person UniProt:P53778 MAPK12

Class:Id	ReferenceGeneProduct:69723
_chainChangeLog	chain:1-367 added on Fri February 6 2015
_displayName	UniProt:P53778 MAPK12
_timestamp	2026-02-20 22:01:28
chain	chain:1-367
checksum	EF680401D8E40610
comment	FUNCTION Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK12 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in myoblast differentiation and also in the down-regulation of cyclin D1 in response to hypoxia in adrenal cells suggesting MAPK12 may inhibit cell proliferation while promoting differentiation. Phosphorylates DLG1. Following osmotic shock, MAPK12 in the cell nucleus increases its association with nuclear DLG1, thereby causing dissociation of DLG1-SFPQ complexes. This function is independent of its catalytic activity and could affect mRNA processing and/or gene transcription to aid cell adaptation to osmolarity changes in the environment. Regulates UV-induced checkpoint signaling and repair of UV-induced DNA damage and G2 arrest after gamma-radiation exposure. MAPK12 is involved in the regulation of SLC2A1 expression and basal glucose uptake in L6 myotubes; and negatively regulates SLC2A4 expression and contraction-mediated glucose uptake in adult skeletal muscle. C-Jun (JUN) phosphorylation is stimulated by MAPK14 and inhibited by MAPK12, leading to a distinct AP-1 regulation. MAPK12 is required for the normal kinetochore localization of PLK1, prevents chromosomal instability and supports mitotic cell viability. MAPK12-signaling is also positively regulating the expansion of transient amplifying myogenic precursor cells during muscle growth and regeneration.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 Binds 2 magnesium ions.ACTIVITY REGULATION Activated by phosphorylation on threonine and tyrosine. MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK12 induced by environmental stress, whereas MAP2K6/MKK6 is the major MAPK12 activator in response to TNF.BIOPHYSICOCHEMICAL PROPERTIES Monomer. Interacts with the PDZ domain of the syntrophin SNTA1. Interacts with SH3BP5. Interacts with LIN7C, SCRIB and SYNJ2BP (By similarity). Interacts with PTPN4; this interaction induces the activation of PTPN4 phosphatase activity.INTERACTION Mitochondrial when associated with SH3BP5. In skeletal muscle colocalizes with SNTA1 at the neuromuscular junction and throughout the sarcolemma (By similarity).ALTERNATIVE PRODUCTS Highly expressed in skeletal muscle and heart.INDUCTION Expression of MAPK12 is down-regulation by MAPK14 activation.DOMAIN The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.PTM Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K3/MKK3 and MAP2K6/MKK6, which activates the enzyme.PTM Ubiquitinated. Ubiquitination leads to degradation by the proteasome pathway.DISEASE MAPK is overexpressed in highly metastatic breast cancer cell lines and its expression is preferentially associated with basal-like and metastatic phenotypes of breast tumor samples.SIMILARITY Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.
description	recommendedName: Mitogen-activated protein kinase 12 shortName: MAP kinase 12 shortName: MAPK 12 ecNumber evidence="4"2.7.11.24 alternativeName: Extracellular signal-regulated kinase 6 shortName: ERK-6 alternativeName: Mitogen-activated protein kinase p38 gamma shortName: MAP kinase p38 gamma alternativeName: Stress-activated protein kinase 3
geneName	MAPK12 ERK6 SAPK3
identifier	P53778
isSequenceChanged	FALSE
keyword	3D-structure Alternative splicing ATP-binding Cell cycle Cytoplasm Kinase Magnesium Metal-binding Mitochondrion Nucleotide-binding Nucleus Phosphoprotein Proteomics identification Reference proteome Serine/threonine-protein kinase Stress response Transcription Transcription regulation Transferase Ubl conjugation
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20
name	MAPK12
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8993152] ENSEMBL:ENSG00000188130 MAPK12 [Homo sapiens]
secondaryIdentifier	MK12_HUMAN Q14260 Q6IC53 Q99588 Q99672
sequenceLength	367
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:8966169] UniProt:P53778-1 MAPK12 [Homo sapiens] [ReferenceIsoform:8966170] UniProt:P53778-2 MAPK12 [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:171021] p-T183,Y185-MAPK12 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:171025] MAPK12 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:448833] MAPK12 [nucleoplasm] [Homo sapiens]
(referenceSequence)	[ModifiedResidue:3006594] O-phospho-L-threonine at 185 [ModifiedResidue:3006596] O-phospho-L-threonine at 183
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