Reactome | UniProt:P53778 MAPK12

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UniProt:P53778 MAPK12 Show undefined attributes

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.
crossReference	[DatabaseIdentifier:12805144] ZINC - FDA approved:MK12_HUMAN [DatabaseIdentifier:12817633] ZINC - World Drugs:MK12_HUMAN [DatabaseIdentifier:12816825] ZINC target:P53778 [DatabaseIdentifier:12813412] ZINC - Substances:MK12_HUMAN [DatabaseIdentifier:12809429] ZINC - Predictions - Purchasable:MK12_HUMAN [DatabaseIdentifier:12806193] ZINC - Investigational:MK12_HUMAN [DatabaseIdentifier:11446967] ENSEMBL:ENSG00000188130 [DatabaseIdentifier:11534578] ENSEMBL:ENSP00000215659 [DatabaseIdentifier:11534577] ENSEMBL:ENSP00000479972 [DatabaseIdentifier:11657276] ENSEMBL:ENST00000622558 [DatabaseIdentifier:11657277] ENSEMBL:ENST00000215659 [DatabaseIdentifier:11779886] Guide to Pharmacology - Targets:1501 [DatabaseIdentifier:11785019] GeneCards:MAPK12 [DatabaseIdentifier:11833109] HMDB Protein:HMDBP01135 [DatabaseIdentifier:11838106] HPA:ENSG00000188130-MAPK12 [DatabaseIdentifier:12122609] OpenTargets:ENSG00000188130 [DatabaseIdentifier:12162937] PDB:7CGA [DatabaseIdentifier:12162935] PDB:1CM8 [DatabaseIdentifier:12143839] PDB:4QUM [DatabaseIdentifier:12162936] PDB:6UNA [DatabaseIdentifier:12241092] PRO:P53778 [DatabaseIdentifier:12282930] Pharos - Targets:P53778 [DatabaseIdentifier:12314185] RefSeq:NP_002960.2 [DatabaseIdentifier:12314186] RefSeq:NP_001290181.1 [DatabaseIdentifier:12803904] ZINC - Biogenic:MK12_HUMAN
databaseName	UniProt
dbId	69723
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
displayName	UniProt:P53778 MAPK12
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:9983091] Weiser, Joel, 2026-02-20
moleculeType	Protein
name	MAPK12
otherIdentifier	11724583_a_at 11742969_a_at 11746262_a_at 11760337_a_at 1556340_PM_at 1556340_at 1556341_PM_s_at 1556341_s_at 16936360 16936397 16936408 206106_PM_at 206106_at 226672_PM_s_at 226672_s_at 3965696 3965698 3965699 3965703 3965704 3965708 3965710 3965712 3965714 3965715 3965716 3965718 3965720 3965723 3965725 3965726 3965729 3965730 3965731 3965733 3965734 3965735 3965736 3965737 3965738 3965739 3965740 3965741 3965742 3965743 3965744 3965745 3965747 3965749 3965750 3965752 3965753 3965754 3965755 3965756 3965757 3965758 3965760 3965761 3965762 3965763 3965764 3965765 3965766 3965767 3965768 3965769 3965770 3965771 3965772 3965773 3965774 3965775 3965776 3965777 3965778 3965779 3965780 3965781 51132_at 6300 8076937 8076962 984_g_at A_23_P29347 A_23_P368740 A_33_P3250055 A_33_P3763846 GE62595 GE80761 GO:0000165 GO:0000166 GO:0000287 GO:0003824 GO:0004672 GO:0004674 GO:0004707 GO:0005515 GO:0005524 GO:0005634 GO:0005654 GO:0005737 GO:0005739 GO:0005829 GO:0006468 GO:0007165 GO:0007517 GO:0016301 GO:0016504 GO:0016740 GO:0030154 GO:0033554 GO:0035556 GO:0042770 GO:0045445 GO:0045786 GO:0046872 GO:0048856 GO:0051149 GO:0051726 GO:0098772 GO:0106310 GO:0140096 HMNXSV003008606 HMNXSV003022701 HMNXSV003031201 HMNXSV003054496 HMNXSV003054897 Hs.26593.0.S1_3p_a_at Hs.55039.0.S2_3p_at Hs.55039.0.S2_3p_x_at Hs2.432642.1.S1_3p_s_at ILMN_1797786 ILMN_2102787 PH_hs_0002346 PH_hs_0020025 PH_hs_0036362 TC22001497.hg TC22001498.hg X79483_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-171025] MAPK12 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-171021] p-T183,Y185-MAPK12 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-448833] MAPK12 [nucleoplasm] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000188130] ENSEMBL:ENSG00000188130 MAPK12 [ReferenceDNASequence:11312537] BioGPS Gene:6300 MAPK12 [ReferenceDNASequence:11397522] COSMIC - genes:MAPK12 MAPK12 [ReferenceDNASequence:11409311] CTD Gene:6300 MAPK12 [ReferenceDNASequence:11434230] dbSNP Gene:6300 MAPK12 [ReferenceDNASequence:11816644] HGNC:6874 MAPK12 [ReferenceDNASequence:11856107] KEGG:hsa:6300 MAPK12 [ReferenceDNASequence:11942326] Monarch:6300 MAPK12 [ReferenceDNASequence:12026419] NCBI Gene:6300 MAPK12 [ReferenceDNASequence:12108205] OMIM:602399 MAPK12 [ReferenceDNASequence:12723219] UCSC:P53778 MAPK12
referenceTranscript	[ReferenceRNASequence:12496249] RefSeq:NM_002969.5 MAPK12 [ReferenceRNASequence:12496250] RefSeq:NM_001303252.3 MAPK12
schemaClass	ReferenceGeneProduct
secondaryIdentifier	MK12_HUMAN Q14260 Q6IC53 Q99588 Q99672
sequenceLength	367
species	[Species:48887] Homo sapiens
stId	uniprot:P53778
url	http://purl.uniprot.org/uniprot/P53778

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-171025] MAPK12 [cytosol] [EntityWithAccessionedSequence:R-HSA-171021] p-T183,Y185-MAPK12 [cytosol] [EntityWithAccessionedSequence:R-HSA-448833] MAPK12 [nucleoplasm]
(referenceSequence)	[ModifiedResidue:3006596] O-phospho-L-threonine at 183 [ModifiedResidue:3006594] O-phospho-L-threonine at 185
(interactor)	[UndirectedInteraction:11199899] UniProt:P15056 <-> UniProt:P53778 (IntAct) [UndirectedInteraction:11213361] UniProt:Q14160 <-> UniProt:P53778 (IntAct) [UndirectedInteraction:11221253] UniProt:Q8IUQ4 <-> UniProt:P53778 (IntAct) [UndirectedInteraction:11260927] UniProt:P53778 <-> UniProt:Q12959 (IntAct) [UndirectedInteraction:11260929] UniProt:P53778 <-> UniProt:O15264 (IntAct) [UndirectedInteraction:11260931] UniProt:P53778 <-> UniProt:Q13884 (IntAct) [UndirectedInteraction:11260933] UniProt:P53778 <-> UniProt:P26045 (IntAct) [UndirectedInteraction:11260935] UniProt:P53778 <-> UniProt:Q15599 (IntAct) [UndirectedInteraction:11260937] UniProt:P53778 <-> UniProt:P05067 (IntAct) [UndirectedInteraction:11260941] UniProt:P53778 <-> UniProt:Q32MK0 (IntAct)

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