BioPAX pathway converted from "MAPK4,6 translocate to the cytoplasm" in the Reactome database.MAPK4,6 translocate to the cytoplasmMAPK4,6 translocate to the cytoplasmDespite differences in their overall cellular distribution (MAPK6 is found in both the nucleus and the cytosol, while MAPK4 is predominantly found in the cytosol), both MAPK4 and 6 shuttle between the cytosol and the nucleus. Nuclear import of both proteins occurs through an active temperature sensitive pathway, while nuclear export depends on XPO1 (Aberg et al, 2006; Julien et al, 2003). Authored: Rothfels, Karen, 2015-03-30Reviewed: Moens, Ugo, 2015-04-24Reviewed: Seternes, Ole-Morten, 2015-05-05Reviewed: Mathien, Simon, 2015-05-12Reviewed: Meloche, Sylvain, 2015-05-12Reviewed: Soulez, Mathilde, 2015-05-12Edited: Rothfels, Karen, 2015-05-13Converted from EntitySet in ReactomeReactome DB_ID: 56927041nucleoplasmGO0005654MAPK4,6 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityMAPK6 [nucleoplasm]p-S189 MAPK6 [nucleoplasm]p-S186 MAPK4 [nucleoplasm]MAPK4 [nucleoplasm]Reactomehttp://www.reactome.orgHomo sapiensNCBI Taxonomy9606UniProtQ16659UniProtP31152Converted from EntitySet in ReactomeReactome DB_ID: 56927061cytosolGO0005829MAPK4,6 [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityMAPK6 [cytosol]p-S186 MAPK4 [cytosol]MAPK4 [cytosol]p-S189 MAPK6 [cytosol]Reactome Database ID Release 755687109Database 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=5687109ReactomeR-HSA-56871092Reactome 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-5687109.212915405Pubmed2003Nuclear export of ERK3 by a CRM1-dependent mechanism regulates its inhibitory action on cell cycle progressionJulien, CatherineCoulombe, PhilippeMeloche, SylvainJ. Biol. Chem. 278:42615-2416971392Pubmed2006Regulation of MAPK-activated protein kinase 5 activity and subcellular localization by the atypical MAPK ERK4/MAPK4Aberg, EspenPerander, MariaJohansen, BjarneJulien, CatherineMeloche, SylvainKeyse, Stephen MSeternes, Ole-MortenJ. Biol. Chem. 281:35499-510ACTIVATIONReactome Database ID Release 755687133Database 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=5687133ReactomeR-HSA-56871331Reactome 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-5687133.1Reactome DB_ID: 165529UniProt:O14980 XPO1XPO1XPO1CRM1FUNCTION Mediates the nuclear export of cellular proteins (cargos) bearing a leucine-rich nuclear export signal (NES) and of RNAs. In the nucleus, in association with RANBP3, binds cooperatively to the NES on its target protein and to the GTPase RAN in its active GTP-bound form (Ran-GTP). Docking of this complex to the nuclear pore complex (NPC) is mediated through binding to nucleoporins. Upon transit of a nuclear export complex into the cytoplasm, disassembling of the complex and hydrolysis of Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively) cause release of the cargo from the export receptor. The directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Involved in U3 snoRNA transport from Cajal bodies to nucleoli. Binds to late precursor U3 snoRNA bearing a TMG cap.FUNCTION (Microbial infection) Mediates the export of unspliced or incompletely spliced RNAs out of the nucleus from different viruses including HIV-1, HTLV-1 and influenza A. Interacts with, and mediates the nuclear export of HIV-1 Rev and HTLV-1 Rex proteins. Involved in HTLV-1 Rex multimerization.SUBUNIT Found in a U snRNA export complex with PHAX/RNUXA, NCBP1/CBP80, NCBP2/CBP20, RAN, XPO1 and m7G-capped RNA (By similarity). Component of a nuclear export receptor complex composed of KPNB1, RAN, SNUPN and XPO1. Found in a trimeric export complex with SNUPN, RAN and XPO1. Found in a nuclear export complex with RANBP3 and RAN. Found in a 60S ribosomal subunit export complex with NMD3, RAN, XPO1. Interacts with DDX3X, NMD3, NUP42, NUP88, NUP214, RANBP3 and TERT. Interacts with NEMF (via its N-terminus). Interacts with the monomeric form of BIRC5/survivin deacetylated at 'Lys-129'. Interacts with DTNBP1 and SERTAD2; the interactions translocate DTNBP1 and SERTAD2 out of the nucleus. Interacts with ATF2. Interacts with SLC35G1 and STIM1. Interacts with DCAF8. Interacts with CPEB3 (PubMed:22730302). Interacts with HAX1 (PubMed:23164465). Interacts with BOK; translocates to the cytoplasm (PubMed:16302269). Interacts with HSP90AB1 (PubMed:22022502).SUBUNIT (Microbial infection) Interacts with HIV-1 Rev.SUBUNIT (Microbial infection) Interacts with HTLV-1 Rex.SUBUNIT (Microbial infection) Interacts with influenza A nucleoprotein.SUBUNIT (Microbial infection) Interacts with Epstein-Barr virus protein BMLF1.SUBUNIT (Microbial infection) Part of a tetrameric complex composed of CRM1, importin alpha/beta dimer and the Venezuelan equine encephalitis virus (VEEV) capsid; this complex blocks the receptor-mediated transport through the nuclear pore.SUBUNIT (Microbial infection) Interacts with SARS-CoV virus protein ORF9b; this interaction mediates protein ORF9b export out of the nucleus.TISSUE SPECIFICITY Expressed in heart, brain, placenta, lung, liver, skeletal muscle, pancreas, spleen, thymus, prostate, testis, ovary, small intestine, colon and peripheral blood leukocytes. Not expressed in the kidney.MISCELLANEOUS Cellular target of leptomycin B (LMB), a XPO1/CRM1 nuclear export inhibitor.SIMILARITY Belongs to the exportin family.UniProtO14980Chain Coordinates1EQUAL1071EQUAL