BioPAX pathway converted from "Nuclear DUSPs dephosphorylate MAPKs" in the Reactome database.LEFT-TO-RIGHT3.1.3Nuclear DUSPs dephosphorylate MAPKsMAPKs are inactivated by dephosphorylation of the activation loop T and Y residues by dual-specificity MAPK phosphatases (DUSPs) (reviewed in Roskoski, 2012b). Class 1 DUSPs, including DUSP 1, 2, 4 and 5 are nuclear and are generally activated by the same extracellular stimuli that promote MAPK signaling, establishing a negative feedback loop. DUSP5 is specific for MAPK3 and 1, while the other class 1 enzymes have broad specificity. Nuclear MAPKs may also be inactivated by nuclear forms of class III DUSPs, including DUSP8, 10 and 16, although the preferred substrate of these enzymes are the p38 and JNK MAP kinases (reviewed in Bermudez et al, 2010; Kondoh and Nishida, 2007).Authored: Rothfels, Karen, 2015-02-15Reviewed: Roskoski, Robert Jr, 2015-04-28Edited: Rothfels, Karen, 2015-02-15H2OwaterReactome DB_ID: 29356cytosolGENE ONTOLOGYGO:0005829water [ChEBI:15377]waterChEBICHEBI:15377Reactome Database ID Release 7029356Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29356ReactomeR-ALL-293564Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29356.4Reactomehttp://www.reactome.orgConverted from EntitySet in Reactomep-T,Y MAPK monomers and dimersReactome DB_ID: 5674341Converted from EntitySet in Reactomep-T,Y MAPK dimersPhospho-ERK dimerReactome DB_ID: 198701phospho-ERK-1 dimerp-T202, Y204 MAPK3 dimerReactome DB_ID: 109845nucleoplasmGENE ONTOLOGYGO:0005654p-T202,Y204-MAPK3p-T202,Y204-ERK-1Mitogen-activated protein kinase 3(phosphorylated)Extracellular signal-regulated kinase 1(phosphorylated)Insulin-stimulated MAP2 kinaseMAP kinase 1 phosphorylatedp-T202,Y204-MAPK 1p44-ERK1phosphorylatedERT2 phosphorylatedMAP kinase isoform p44(phosphorylated)Microtubule- associated protein-2 kinaseReactome DB_ID: 112359UniProt:P27361 MAPK3MAPK3ERK1PRKM3FUNCTION 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, 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.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.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).SUBUNIT (Microbial infection) Binds to HIV-1 Nef through its SH3 domain. This interaction inhibits its tyrosine-kinase activity.DOMAIN 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.SIMILARITY Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.Homo sapiensNCBI Taxonomy9606UniProtP27361202EQUALO-phospho-L-threonineMODMOD:00047204EQUALO4'-phospho-L-tyrosineMODMOD:000482EQUAL379EQUALReactome Database ID Release 70112359Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=112359ReactomeR-HSA-1123591Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-112359.12Reactome Database ID Release 70109845Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109845ReactomeR-HSA-1098451Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-109845.1phospho-ERK-2 dimerp-Y185,Y187 MAPK1 dimerReactome DB_ID: 109856p42-MAPKp-T185,Y187-MAPK1p-T185,Y187-ERK-2Mitogen-activated protein kinase 1 phosphorylatedExtracellular signal-regulated kinase 2 phosphorylatedMitogen-activated protein kinase 2MAP kinase 2 phosphorylatedMAPK2 phosphorylatedERT1phosphorylatedReactome DB_ID: 112354UniProt:P28482 MAPK1MAPK1ERK2PRKM1PRKM2FUNCTION 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. Mediates phosphorylation of TPR in respons to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation. Phosphorylates CDK2AP2 (By similarity).FUNCTION 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.ACTIVITY REGULATION 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 DUSP1, DUSP3, DUSP6 and DUSP9. Inactivated by pyrimidylpyrrole inhibitors.SUBUNIT Binds both upstream activators and downstream substrates in multimolecular complexes. This interaction inhibits its tyrosine-kinase activity. Interacts with ADAM15, ARHGEF2, ARRB2, DAPK1 (via death domain), HSF4, IER3, IPO7, DUSP6, NISCH, SGK1, and isoform 1 of NEK2. Interacts (phosphorylated form) with CAV2 ('Tyr-19'-phosphorylated form); the interaction, promoted by insulin, leads to nuclear location and MAPK1 activation. Interacts with MORG1, PEA15 and MKNK2 (By similarity). MKNK2 isoform 1 binding prevents from dephosphorylation and inactivation (By similarity). Interacts with DCC (By similarity). The phosphorylated form interacts with PML (isoform PML-4). Interacts with STYX. Interacts with CDK2AP2. Interacts with CAVIN4 (By similarity). Interacts with DUSP7; the interaction enhances DUSP7 phosphatase activity (PubMed:9788880).SUBUNIT (Microbial infection) Interacts with HIV-1 Nef through its SH3 domain.DOMAIN 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-185 and Tyr-187, which activates the enzyme. Undergoes regulatory phosphorylation on additional residues such as Ser-246 and Ser-248 in the kinase insert domain (KID) These phosphorylations, which are probably mediated by more than one kinase, are important for binding of MAPK1/ERK2 to importin-7 (IPO7) and its nuclear translocation. In addition, autophosphorylation of Thr-190 was shown to affect the subcellular localization of MAPK1/ERK2 as well. Ligand-activated ALK induces tyrosine phosphorylation. Dephosphorylated by PTPRJ at Tyr-187. Phosphorylation on Ser-29 by SGK1 results in its activation by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. DUSP3 and DUSP6 dephosphorylate specifically MAPK1/ERK2 and MAPK3/ERK1 whereas DUSP9 dephosphorylates a broader range of MAPKs. Dephosphorylated by DUSP1 at Thr-185 and Tyr-187.PTM ISGylated.SIMILARITY Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.UniProtP28482185EQUAL187EQUAL2EQUAL360EQUALReactome Database ID Release 70112354Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=112354ReactomeR-HSA-1123541Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-112354.12Reactome Database ID Release 70109856Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109856ReactomeR-HSA-1098561Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-109856.1Reactome Database ID Release 70198701Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=198701ReactomeR-HSA-1987011Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-198701.1Converted from EntitySet in Reactomep-T,Y MAPKsReactome DB_ID: 5674338Reactome Database ID Release 705674338Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5674338ReactomeR-HSA-56743381Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5674338.1Reactome Database ID Release 705674341Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5674341ReactomeR-HSA-56743411Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5674341.1Converted from EntitySet in ReactomeMAPK monomers and dimersReactome DB_ID: 5675363ERK2MAPK1Mitogen-activated protein kinase 1 (EC 2.7.1.-) (Extracellular signal- regulated kinase 2) (ERK-2) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2) (p42-MAPK) (ERT1)Mitogen-activated protein kinase 1 Extracellular signal-regulated kinase 2Mitogen-activated protein kinase 2MAP kinase 2MAPK 2p42-MAPKERT1Reactome DB_ID: 1999602EQUAL360EQUALReactome Database ID Release 70199960Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=199960ReactomeR-HSA-1999601Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-199960.1ERK1MAPK3Mitogen-activated protein kinase 3 Extracellular signal-regulated kinase 1ERK-1Insulin-stimulated MAP2 kinaseMAP kinase 1MAPK 1p44-ERK1ERT2p44-MAPKMicrotubule- associated protein-2 kinaseReactome DB_ID: 737242EQUAL379EQUALReactome Database ID Release 7073724Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=73724ReactomeR-HSA-737241Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-73724.1MAPK1 dimerReactome DB_ID: 56753562Reactome Database ID Release 705675356Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5675356ReactomeR-HSA-56753561Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5675356.1MAPK3 dimerReactome DB_ID: 56753592Reactome Database ID Release 705675359Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5675359ReactomeR-HSA-56753591Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5675359.1Reactome Database ID Release 705675363Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5675363ReactomeR-HSA-56753631Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5675363.1PiOrthophosphatephosphate(3-)PhosphateInorganic PhosphateReactome DB_ID: 113550phosphate(3-) [ChEBI:18367]phosphate(3-)ChEBICHEBI:18367Reactome Database ID Release 70113550Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113550ReactomeR-ALL-1135503Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113550.3ACTIVATIONConverted from EntitySet in Reactomenuclear MAPK DUSPsReactome DB_ID: 5675368DUSP5Reactome DB_ID: 5675342UniProt:Q16690 DUSP5DUSP5VH3FUNCTION Dual specificity protein phosphatase; active with phosphotyrosine, phosphoserine and phosphothreonine residues. The highest relative activity is toward ERK1.SIMILARITY Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.UniProtQ166901EQUAL384EQUALReactome Database ID Release 705675342Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5675342ReactomeR-HSA-56753421Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5675342.1DUSP1Dual specificity protein phosphatase 1DUS1_HUMANReactome DB_ID: 203796UniProt:P28562 DUSP1DUSP1CL100MKP1PTPN10VH1FUNCTION Dual specificity phosphatase that dephosphorylates MAP kinase MAPK1/ERK2 on both 'Thr-183' and 'Tyr-185', regulating its activity during the meiotic cell cycle.TISSUE SPECIFICITY Expressed at high levels in the lung, liver placenta and pancreas. Moderate levels seen in the heart and skeletal muscle. Lower levels found in the brain and kidney.INDUCTION By oxidative stress and heat shock.PTM Phosphorylation at Ser-359 and Ser-364 by MAPK1/ERK2 and MAPK3/ERK1 reduces its rate of degradation.SIMILARITY Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.UniProtP285621EQUAL367EQUALReactome Database ID Release 70203796Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=203796ReactomeR-HSA-2037961Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-203796.1DUSP2Reactome DB_ID: 5675340UniProt:Q05923 DUSP2DUSP2PAC1FUNCTION Regulates mitogenic signal transduction by dephosphorylating both Thr and Tyr residues on MAP kinases ERK1 and ERK2.TISSUE SPECIFICITY Expressed in hematopoietic tissues.INDUCTION By mitogens.SIMILARITY Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.UniProtQ059231EQUAL314EQUALReactome Database ID Release 705675340Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5675340ReactomeR-HSA-56753401Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5675340.1DUSP4Dual specificity protein phosphatase 4DUS4_HUMANReactome DB_ID: 203794UniProt:Q13115 DUSP4DUSP4MKP2VH2FUNCTION Regulates mitogenic signal transduction by dephosphorylating both Thr and Tyr residues on MAP kinases ERK1 and ERK2.SUBUNIT Hollow spherical complex composed of 24 subunits with pseudooctahedral symmetry, has a tetramer as the basic unit.PTM Phosphorylation in the C-terminus by ERK1/2 inhibits proteasomal degradation and stabilizes the protein.SIMILARITY Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.UniProtQ131151EQUAL394EQUALReactome Database ID Release 70203794Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=203794ReactomeR-HSA-2037941Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-203794.1DUSP8Reactome DB_ID: 5675349UniProt:Q13202 DUSP8DUSP8C11orf81VH5FUNCTION Has phosphatase activity with synthetic phosphatase substrates and negatively regulates mitogen-activated protein kinase activity, presumably by catalysing their dephosphorylation. Expected to display protein phosphatase activity toward phosphotyrosine, phosphoserine and phosphothreonine residues.SUBUNIT Monomer.TISSUE SPECIFICITY Abundant in brain, heart and skeletal muscle.SIMILARITY Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.UniProtQ132021EQUAL625EQUALReactome Database ID Release 705675349Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5675349ReactomeR-HSA-56753491Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5675349.1DUSP10Dual specificity protein phosphatase 10DUSA_HUMANReactome DB_ID: 203793UniProt:Q9Y6W6 DUSP10DUSP10MKP5FUNCTION Protein phosphatase involved in the inactivation of MAP kinases. Has a specificity for the MAPK11/MAPK12/MAPK13/MAPK14 subfamily. It preferably dephosphorylates p38.SUBUNIT Monomer. Interacts with MAPK14.TISSUE SPECIFICITY Expressed in keratinocytes (at protein level) (PubMed:29043977). Detected in brain (PubMed:16806267).SIMILARITY Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.UniProtQ9Y6W61EQUAL482EQUALReactome Database ID Release 70203793Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=203793ReactomeR-HSA-2037931Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-203793.1DUSP16Reactome DB_ID: 5675337UniProt:Q9BY84 DUSP16DUSP16KIAA1700MKP7FUNCTION Dual specificity protein phosphatase involved in the inactivation of MAP kinases. Dephosphorylates MAPK10 bound to ARRB2.SUBUNIT Interacts with ARRB2.PTM Phosphorylated at Ser-446 by MAPK1/ERK2, which prevents its degradation, and thereby stabilizes it and blocks JNK MAPK activity.PTM (Microbial infection) Acetylated at Lys-55 by the M.tuberculosis Eis protein; this leads to the inhibition of JNK-dependent autophagy, phagosome maturation, and ROS (reactive oxygen species) generation for enhanced intracellular survival of M.tuberculosis.SIMILARITY Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.UniProtQ9BY841EQUAL665EQUALReactome Database ID Release 705675337Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5675337ReactomeR-HSA-56753371Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5675337.1Reactome Database ID Release 705675368Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5675368ReactomeR-HSA-56753681Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5675368.1GENE ONTOLOGYGO:0008138gene ontology term for cellular functionMIMI:0355Same Catalyst ActivityReactome Database ID Release 705675372Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5675372Reactome Database ID Release 705675373Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5675373ReactomeR-HSA-56753731Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5675373.117208316Pubmed2007Regulation of MAP kinases by MAP kinase phosphatasesKondoh, KunioNishida, EBiochim. Biophys. Acta 1773:1227-3720463170Pubmed2010The dual-specificity MAP kinase phosphatases: critical roles in development and cancerBermudez, OPagès, GGimond, CAm. J. Physiol., Cell Physiol. 299:C189-20222569528Pubmed2012ERK1/2 MAP kinases: structure, function, and regulationRoskoski, Robert JrPharmacol. Res. 66:105-43