ID MK15_HUMAN Reviewed; 544 AA. AC Q8TD08; Q2TCF9; Q8N362; DT 18-APR-2006, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2002, sequence version 1. DT 24-JAN-2024, entry version 169. DE RecName: Full=Mitogen-activated protein kinase 15 {ECO:0000305}; DE Short=MAP kinase 15; DE Short=MAPK 15; DE EC=2.7.11.24; DE AltName: Full=Extracellular signal-regulated kinase 7; DE Short=ERK-7; DE AltName: Full=Extracellular signal-regulated kinase 8; DE Short=ERK-8; GN Name=MAPK15 {ECO:0000312|HGNC:HGNC:24667}; GN Synonyms=ERK7 {ECO:0000250|UniProtKB:Q9Z2A6}, ERK8 GN {ECO:0000303|PubMed:11875070, ECO:0000303|PubMed:16484222}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INTERACTION RP WITH CSK, MUTAGENESIS OF LYS-42; THR-175 AND TYR-177, PHOSPHORYLATION AT RP THR-175 AND TYR-177, CHARACTERIZATION, FUNCTION, AND ACTIVITY REGULATION. RC TISSUE=Testis; RX PubMed=11875070; DOI=10.1074/jbc.m112483200; RA Abe M.K., Saelzler M.P., Espinosa R. III, Kahle K.T., Hershenson M.B., RA Le Beau M.M., Rosner M.R.; RT "ERK8, a new member of the mitogen-activated protein kinase family."; RL J. Biol. Chem. 277:16733-16743(2002). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, FUNCTION, AND RP INTERACTION WITH ABL1 AND RET. RC TISSUE=Medulla oblongata; RX PubMed=16484222; DOI=10.1074/jbc.m513397200; RA Iavarone C., Acunzo M., Carlomagno F., Catania A., Melillo R.M., RA Carlomagno S.M., Santoro M., Chiariello M.; RT "Activation of the Erk8 mitogen-activated protein (MAP) kinase by RET/PTC3, RT a constitutively active form of the RET proto-oncogene."; RL J. Biol. Chem. 281:10567-10576(2006). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP INTERACTION WITH TGFB1I1. RX PubMed=16624805; DOI=10.1074/jbc.m512418200; RA Saelzler M.P., Spackman C.C., Liu Y., Martinez L.C., Harris J.P., Abe M.K.; RT "ERK8 down-regulates transactivation of the glucocorticoid receptor through RT Hic-5."; RL J. Biol. Chem. 281:16821-16832(2006). RN [5] RP FUNCTION, PHOSPHORYLATION AT THR-175 AND TYR-177, MUTAGENESIS OF LYS-42; RP ASP-155; THR-175 AND TYR-177, AND ACTIVITY REGULATION. RX PubMed=16336213; DOI=10.1042/bj20051288; RA Klevernic I.V., Stafford M.J., Morrice N., Peggie M., Morton S., Cohen P.; RT "Characterization of the reversible phosphorylation and activation of RT ERK8."; RL Biochem. J. 394:365-373(2006). RN [6] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [7] RP PHOSPHORYLATION AT THR-175 AND TYR-177, FUNCTION, MUTAGENESIS OF ASP-155, RP UBIQUITINATION, AND ACTIVITY REGULATION. RX PubMed=19166846; DOI=10.1016/j.febslet.2009.01.011; RA Klevernic I.V., Martin N.M., Cohen P.; RT "Regulation of the activity and expression of ERK8 by DNA damage."; RL FEBS Lett. 583:680-684(2009). RN [8] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=20638370; DOI=10.1016/j.bbrc.2010.07.029; RA Erster O., Seger R., Liscovitch M.; RT "Ligand interaction scan (LIScan) in the study of ERK8."; RL Biochem. Biophys. Res. Commun. 399:37-41(2010). RN [9] RP INTERACTION WITH PCNA, FUNCTION, AND MUTAGENESIS OF GLN-300; PRO-390 AND RP PRO-398. RX PubMed=20733054; DOI=10.1083/jcb.201002124; RA Groehler A.L., Lannigan D.A.; RT "A chromatin-bound kinase, ERK8, protects genomic integrity by inhibiting RT HDM2-mediated degradation of the DNA clamp PCNA."; RL J. Cell Biol. 190:575-586(2010). RN [10] RP FUNCTION. RX PubMed=21847093; DOI=10.1038/emboj.2011.253; RA Zacharogianni M., Kondylis V., Tang Y., Farhan H., Xanthakis D., Fuchs F., RA Boutros M., Rabouille C.; RT "ERK7 is a negative regulator of protein secretion in response to amino- RT acid starvation by modulating Sec16 membrane association."; RL EMBO J. 30:3684-3700(2011). RN [11] RP INTERACTION WITH ESRRA, SUBCELLULAR LOCATION, MUTAGENESIS OF RP 265-LEU--LEU-269 AND 281-LEU--LEU-285, REGION, AND FUNCTION. RX PubMed=21190936; DOI=10.1074/jbc.m110.179523; RA Rossi M., Colecchia D., Iavarone C., Strambi A., Piccioni F., RA Verrotti di Pianella A., Chiariello M.; RT "Extracellular signal-regulated kinase 8 (ERK8) controls estrogen-related RT receptor alpha (ERRalpha) cellular localization and inhibits its RT transcriptional activity."; RL J. Biol. Chem. 286:8507-8522(2011). RN [12] RP INTERACTION WITH GABARAP; MAP1LC3B AND GABARAPL1, SUBCELLULAR LOCATION, RP REGION, MUTAGENESIS OF ASP-155 AND 340-TYR--ILE-343, AND FUNCTION. RX PubMed=22948227; DOI=10.4161/auto.21857; RA Colecchia D., Strambi A., Sanzone S., Iavarone C., Rossi M., Dall'Armi C., RA Piccioni F., Verrotti di Pianella A., Chiariello M.; RT "MAPK15/ERK8 stimulates autophagy by interacting with LC3 and GABARAP RT proteins."; RL Autophagy 8:1724-1740(2012). RN [13] RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF THR-175 AND TYR-177. RX PubMed=24618899; DOI=10.7554/elife.01828; RA Chia J., Tham K.M., Gill D.J., Bard-Chapeau E.A., Bard F.A.; RT "ERK8 is a negative regulator of O-GalNAc glycosylation and cell RT migration."; RL Elife 3:E01828-E01828(2014). RN [14] RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-449, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Colon carcinoma; RX PubMed=24129315; DOI=10.1074/mcp.o113.027870; RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M., RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V., RA Bedford M.T., Comb M.J.; RT "Immunoaffinity enrichment and mass spectrometry analysis of protein RT methylation."; RL Mol. Cell. Proteomics 13:372-387(2014). RN [15] RP FUNCTION. RX PubMed=26595526; DOI=10.18632/oncotarget.6363; RA Liwak-Muir U., Dobson C.C., Naing T., Wylie Q., Chehade L., Baird S.D., RA Chakraborty P.K., Holcik M.; RT "ERK8 is a novel HuR kinase that regulates tumour suppressor PDCD4 through RT a miR-21 dependent mechanism."; RL Oncotarget 7:1439-1450(2016). RN [16] RP SUBCELLULAR LOCATION, FUNCTION, AND MUTAGENESIS OF LYS-42. RX PubMed=29021280; DOI=10.1534/genetics.117.300383; RA Kazatskaya A., Kuhns S., Lambacher N.J., Kennedy J.E., Brear A.G., RA McManus G.J., Sengupta P., Blacque O.E.; RT "Primary Cilium Formation and Ciliary Protein Trafficking Is Regulated by RT the Atypical MAP Kinase MAPK15 in Caenorhabditis elegans and Human Cells."; RL Genetics 207:1423-1440(2017). RN [17] RP FUNCTION, AND MUTAGENESIS OF LYS-42 AND ARG-59. RX PubMed=28842414; DOI=10.1523/jneurosci.1582-17.2017; RA Bermingham D.P., Hardaway J.A., Refai O., Marks C.R., Snider S.L., RA Sturgeon S.M., Spencer W.C., Colbran R.J., Miller D.M. III, Blakely R.D.; RT "The Atypical MAP Kinase SWIP-13/ERK8 Regulates Dopamine Transporters RT through a Rho-Dependent Mechanism."; RL J. Neurosci. 37:9288-9304(2017). CC -!- FUNCTION: Atypical MAPK protein that regulates several process such as CC autophagy, ciliogenesis, protein trafficking/secretion and genome CC integrity, in a kinase activity-dependent manner (PubMed:22948227, CC PubMed:24618899, PubMed:29021280, PubMed:21847093, PubMed:20733054). CC Controls both, basal and starvation-induced autophagy throught its CC interaction with GABARAP, MAP1LC3B and GABARAPL1 leading to CC autophagosome formation, SQSTM1 degradation and reduced MAP1LC3B CC inhibitory phosphorylation (PubMed:22948227). Regulates primary cilium CC formation and the localization of ciliary proteins involved in cilium CC structure, transport, and signaling (PubMed:29021280). Prevents the CC relocation of the sugar-adding enzymes from the Golgi to the CC endoplasmic reticulum, thereby restricting the production of sugar- CC coated proteins (PubMed:24618899). Upon amino-acid starvation, mediates CC transitional endoplasmic reticulum site disassembly and inhibition of CC secretion (PubMed:21847093). Binds to chromatin leading to MAPK15 CC activation and interaction with PCNA, that which protects genomic CC integrity by inhibiting MDM2-mediated degradation of PCNA CC (PubMed:20733054). Regulates DA transporter (DAT) activity and protein CC expression via activation of RhoA (PubMed:28842414). In response to CC H(2)O(2) treatment phosphorylates ELAVL1, thus preventing it from CC binding to the PDCD4 3'UTR and rendering the PDCD4 mRNA accessible to CC miR-21 and leading to its degradation and loss of protein expression CC (PubMed:26595526). Also functions in a kinase activity-independent CC manner as a negative regulator of growth (By similarity). CC Phosphorylates in vitro FOS and MBP (PubMed:11875070, PubMed:16484222, CC PubMed:20638370, PubMed:19166846). During oocyte maturation, plays a CC key role in the microtubule organization and meiotic cell cycle CC progression in oocytes, fertilized eggs, and early embryos (By CC similarity). Interacts with ESRRA promoting its re-localization from CC the nucleus to the cytoplasm and then prevents its transcriptional CC activity (PubMed:21190936). {ECO:0000250|UniProtKB:Q80Y86, CC ECO:0000250|UniProtKB:Q9Z2A6, ECO:0000269|PubMed:11875070, CC ECO:0000269|PubMed:16484222, ECO:0000269|PubMed:19166846, CC ECO:0000269|PubMed:20638370, ECO:0000269|PubMed:20733054, CC ECO:0000269|PubMed:21190936, ECO:0000269|PubMed:21847093, CC ECO:0000269|PubMed:22948227, ECO:0000269|PubMed:24618899, CC ECO:0000269|PubMed:26595526, ECO:0000269|PubMed:28842414, CC ECO:0000269|PubMed:29021280}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.24; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; CC EC=2.7.11.24; CC -!- ACTIVITY REGULATION: Activated by threonine and tyrosine CC phosphorylation (PubMed:11875070, PubMed:16336213, PubMed:19166846). CC Inhibited by dual specificity phosphatases, such as DUSP1 (By CC similarity). Phosphorylation and activation in response to DNA damaging CC agents, serum stimulation (PubMed:11875070, PubMed:16336213, CC PubMed:19166846). Constitutively activated when phosphorylated on Tyr- CC 177. Activity depends on the relative rates of MAPK15 CC autophosphorylation and dephosphorylation by PTPN1 (PubMed:16336213). CC {ECO:0000250|UniProtKB:Q9Z2A6, ECO:0000269|PubMed:11875070, CC ECO:0000269|PubMed:16336213, ECO:0000269|PubMed:19166846}. CC -!- SUBUNIT: Interacts with CSK/c-Src, ABL1, RET and TGFB1I1 CC (PubMed:11875070, PubMed:16484222, PubMed:16624805). Interacts with CC GABARAP, MAP1LC3B and GABARAPL1; controls, in a kinase-dependent CC fashion, both basal and starvation-induced autophagy (PubMed:22948227). CC Interacts with ESRRA; promotes re-localization of ESRRA to the CC cytoplasm through a XPO1-dependent mechanism then inhibits ESRRA CC transcriptional activity (PubMed:21190936). Interacts with PCNA; the CC interaction is chromatin binding- and kinase activity-dependent and CC prevents MDM2-mediated PCNA destruction by inhibiting the association CC of PCNA with MDM2 (PubMed:20733054). Interacts with DVL2 (By CC similarity). Interacts with CLIC3; MAPK15 does not phosphorylate CLIC3 CC (By similarity). {ECO:0000250|UniProtKB:Q80Y86, CC ECO:0000250|UniProtKB:Q9Z2A6, ECO:0000269|PubMed:11875070, CC ECO:0000269|PubMed:16484222, ECO:0000269|PubMed:16624805, CC ECO:0000269|PubMed:20733054, ECO:0000269|PubMed:21190936, CC ECO:0000269|PubMed:22948227}. CC -!- INTERACTION: CC Q8TD08; P24941: CDK2; NbExp=4; IntAct=EBI-1383794, EBI-375096; CC Q8TD08; P08238: HSP90AB1; NbExp=2; IntAct=EBI-1383794, EBI-352572; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body CC {ECO:0000269|PubMed:29021280}. Cell junction, tight junction CC {ECO:0000269|PubMed:29021280}. Cytoplasm, cytoskeleton, microtubule CC organizing center, centrosome, centriole {ECO:0000269|PubMed:29021280}. CC Cytoplasmic vesicle, autophagosome {ECO:0000269|PubMed:22948227}. Golgi CC apparatus {ECO:0000269|PubMed:24618899}. Nucleus CC {ECO:0000269|PubMed:20638370, ECO:0000269|PubMed:21190936}. Cytoplasm CC {ECO:0000269|PubMed:20638370, ECO:0000269|PubMed:21190936}. Cytoplasm, CC cytoskeleton, spindle {ECO:0000250|UniProtKB:Q80Y86}. Note=Co-localizes CC to the cytoplasm only in presence of ESRRA (PubMed:21190936). CC Translocates to the nucleus upon activation (PubMed:20638370). At CC prometaphase I, metaphase I (MI), anaphase I, telophase I, and CC metaphase II (MII) stages, is stably detected at the spindle (By CC similarity). {ECO:0000250|UniProtKB:Q80Y86, CC ECO:0000269|PubMed:20638370, ECO:0000269|PubMed:21190936}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q8TD08-1; Sequence=Displayed; CC Name=2; Synonyms=Erk8 delta; CC IsoId=Q8TD08-2; Sequence=VSP_017919, VSP_017920; CC Name=3; CC IsoId=Q8TD08-3; Sequence=VSP_017918, VSP_017921; CC -!- TISSUE SPECIFICITY: Widely expressed with a maximal expression in lung CC and kidney. {ECO:0000269|PubMed:11875070, ECO:0000269|PubMed:16484222}. CC -!- DOMAIN: The N-terminal region (1-20) is the minimal region necessary CC for ubiquitination and further proteasomal degradation. {ECO:0000250}. CC -!- DOMAIN: The TXY motif contains the threonine and tyrosine residues CC whose phosphorylation activates the MAP kinases. CC -!- PTM: Autophosphorylated on Thr-175 and Tyr-177; activates the enzyme. CC {ECO:0000269|PubMed:11875070, ECO:0000269|PubMed:16336213, CC ECO:0000269|PubMed:19166846}. CC -!- PTM: Ubiquitinated (PubMed:19166846). Ubiquitination may allow its CC tight kinase activity regulation and rapid turnover. May be CC ubiquitinated by a SCF E3 ligase (By similarity). CC {ECO:0000250|UniProtKB:Q9Z2A6, ECO:0000269|PubMed:19166846}. CC -!- MISCELLANEOUS: [Isoform 2]: Appears not to be a CSK- and RET-dependent CC activated kinase. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr CC protein kinase family. MAP kinase subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY065978; AAL40897.1; -; mRNA. DR EMBL; AY994058; AAY44299.1; -; mRNA. DR EMBL; BC028034; AAH28034.1; -; mRNA. DR CCDS; CCDS6409.2; -. [Q8TD08-1] DR RefSeq; NP_620590.2; NM_139021.2. [Q8TD08-1] DR AlphaFoldDB; Q8TD08; -. DR SMR; Q8TD08; -. DR BioGRID; 128827; 59. DR IntAct; Q8TD08; 39. DR STRING; 9606.ENSP00000337691; -. DR BindingDB; Q8TD08; -. DR ChEMBL; CHEMBL5198; -. DR DrugBank; DB00945; Acetylsalicylic acid. DR DrugBank; DB02587; Colforsin. DR DrugBank; DB12010; Fostamatinib. DR DrugBank; DB01017; Minocycline. DR DrugCentral; Q8TD08; -. DR GuidetoPHARMACOLOGY; 2090; -. DR GlyGen; Q8TD08; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q8TD08; -. DR PhosphoSitePlus; Q8TD08; -. DR BioMuta; MAPK15; -. DR DMDM; 74760462; -. DR CPTAC; non-CPTAC-3022; -. DR CPTAC; non-CPTAC-3023; -. DR EPD; Q8TD08; -. DR jPOST; Q8TD08; -. DR MassIVE; Q8TD08; -. DR MaxQB; Q8TD08; -. DR PaxDb; 9606-ENSP00000337691; -. DR PeptideAtlas; Q8TD08; -. DR ProteomicsDB; 74209; -. [Q8TD08-1] DR ProteomicsDB; 74210; -. [Q8TD08-2] DR ProteomicsDB; 74211; -. [Q8TD08-3] DR Pumba; Q8TD08; -. DR Antibodypedia; 957; 410 antibodies from 31 providers. DR DNASU; 225689; -. DR Ensembl; ENST00000338033.9; ENSP00000337691.4; ENSG00000181085.15. [Q8TD08-1] DR Ensembl; ENST00000395107.8; ENSP00000378539.4; ENSG00000181085.15. [Q8TD08-3] DR Ensembl; ENST00000395108.2; ENSP00000378540.2; ENSG00000181085.15. [Q8TD08-2] DR Ensembl; ENST00000615253.4; ENSP00000483093.1; ENSG00000274205.4. [Q8TD08-1] DR GeneID; 225689; -. DR KEGG; hsa:225689; -. DR MANE-Select; ENST00000338033.9; ENSP00000337691.4; NM_139021.3; NP_620590.2. DR UCSC; uc003yzj.4; human. [Q8TD08-1] DR AGR; HGNC:24667; -. DR CTD; 225689; -. DR DisGeNET; 225689; -. DR GeneCards; MAPK15; -. DR HGNC; HGNC:24667; MAPK15. DR HPA; ENSG00000181085; Tissue enhanced (choroid plexus, fallopian tube). DR MIM; 618616; gene. DR neXtProt; NX_Q8TD08; -. DR OpenTargets; ENSG00000181085; -. DR PharmGKB; PA142671478; -. DR VEuPathDB; HostDB:ENSG00000181085; -. DR eggNOG; KOG0660; Eukaryota. DR GeneTree; ENSGT00940000159758; -. DR HOGENOM; CLU_000288_181_14_1; -. DR InParanoid; Q8TD08; -. DR OMA; PDQEWTR; -. DR OrthoDB; 117891at2759; -. DR PhylomeDB; Q8TD08; -. DR TreeFam; TF105101; -. DR PathwayCommons; Q8TD08; -. DR SignaLink; Q8TD08; -. DR SIGNOR; Q8TD08; -. DR BioGRID-ORCS; 225689; 30 hits in 1195 CRISPR screens. DR GeneWiki; MAPK15; -. DR GenomeRNAi; 225689; -. DR Pharos; Q8TD08; Tchem. DR PRO; PR:Q8TD08; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; Q8TD08; Protein. DR Bgee; ENSG00000181085; Expressed in right uterine tube and 90 other cell types or tissues. DR GO; GO:0005776; C:autophagosome; IDA:UniProtKB. DR GO; GO:0005923; C:bicellular tight junction; IEA:UniProtKB-SubCell. DR GO; GO:0005911; C:cell-cell junction; IDA:UniProtKB. DR GO; GO:0005814; C:centriole; IDA:UniProtKB. DR GO; GO:0036064; C:ciliary basal body; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW. DR GO; GO:0005576; C:extracellular region; NAS:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0072687; C:meiotic spindle; IEA:Ensembl. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB. DR GO; GO:0016301; F:kinase activity; IDA:UniProtKB. DR GO; GO:0004707; F:MAP kinase activity; IDA:UniProtKB. DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central. DR GO; GO:0017124; F:SH3 domain binding; NAS:UniProtKB. DR GO; GO:0006974; P:DNA damage response; IDA:UniProtKB. DR GO; GO:0090494; P:dopamine uptake; IDA:UniProtKB. DR GO; GO:0007029; P:endoplasmic reticulum organization; IMP:UniProtKB. DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central. DR GO; GO:0030336; P:negative regulation of cell migration; IMP:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB. DR GO; GO:1905188; P:positive regulation of metaphase/anaphase transition of meiosis I; IEA:Ensembl. DR GO; GO:1905832; P:positive regulation of spindle assembly; IEA:Ensembl. DR GO; GO:0051973; P:positive regulation of telomerase activity; IDA:BHF-UCL. DR GO; GO:1904355; P:positive regulation of telomere capping; IDA:BHF-UCL. DR GO; GO:0032212; P:positive regulation of telomere maintenance via telomerase; IDA:BHF-UCL. DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB. DR GO; GO:1904491; P:protein localization to ciliary transition zone; IMP:UniProtKB. DR GO; GO:0010506; P:regulation of autophagy; IDA:UniProtKB. DR GO; GO:1902017; P:regulation of cilium assembly; IMP:UniProtKB. DR GO; GO:0003400; P:regulation of COPII vesicle coating; IMP:UniProtKB. DR CDD; cd07852; STKc_MAPK15-like; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR003527; MAP_kinase_CS. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR PANTHER; PTHR24055; MITOGEN-ACTIVATED PROTEIN KINASE; 1. DR PANTHER; PTHR24055:SF79; MITOGEN-ACTIVATED PROTEIN KINASE 15; 1. DR Pfam; PF00069; Pkinase; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS01351; MAPK; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR Genevisible; Q8TD08; HS. PE 1: Evidence at protein level; KW Alternative splicing; ATP-binding; Cell junction; Cell projection; KW Cytoplasm; Cytoplasmic vesicle; Cytoskeleton; Golgi apparatus; Kinase; KW Methylation; Nucleotide-binding; Nucleus; Phosphoprotein; KW Reference proteome; Repeat; Serine/threonine-protein kinase; KW Tight junction; Transferase; Ubl conjugation. FT CHAIN 1..544 FT /note="Mitogen-activated protein kinase 15" FT /id="PRO_0000232637" FT DOMAIN 13..304 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REPEAT 371..375 FT /note="PXXXP motif" FT /evidence="ECO:0000305|PubMed:20733054" FT REPEAT 378..382 FT /note="PXXXP motif" FT /evidence="ECO:0000305|PubMed:20733054" FT REPEAT 386..390 FT /note="PXXXP motif; regulates binding with chromatin and FT interaction with PCNA" FT /evidence="ECO:0000305|PubMed:20733054" FT REPEAT 394..398 FT /note="PXXXP motif; regulates binding with chromatin and FT interaction with PCNA" FT /evidence="ECO:0000305|PubMed:20733054" FT REGION 265..285 FT /note="Necessary to interact with ESRRA, to regulate its FT subcellular localization and to inhibit its transcriptional FT activity" FT /evidence="ECO:0000269|PubMed:21190936" FT REGION 300..373 FT /note="Requires for interaction with GABARAP, MAP1LC3B AND FT GABARAPL1" FT /evidence="ECO:0000269|PubMed:22948227" FT REGION 347..413 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 175..177 FT /note="TXY" FT ACT_SITE 137 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 19..27 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 42 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 175 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:11875070, FT ECO:0000269|PubMed:16336213, ECO:0000269|PubMed:19166846" FT MOD_RES 177 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:11875070, FT ECO:0000269|PubMed:16336213, ECO:0000269|PubMed:19166846" FT MOD_RES 449 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0007744|PubMed:24129315" FT VAR_SEQ 95 FT /note="M -> MGCPPSPPPPTAVRTLSA (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_017918" FT VAR_SEQ 241..254 FT /note="DLLALGSGCRASVL -> GAQTACRSGTGAST (in isoform 2)" FT /evidence="ECO:0000303|PubMed:16484222" FT /id="VSP_017919" FT VAR_SEQ 255..544 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:16484222" FT /id="VSP_017920" FT VAR_SEQ 261..544 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_017921" FT VARIANT 221 FT /note="T -> K (in dbSNP:rs60732298)" FT /id="VAR_061535" FT VARIANT 505 FT /note="S -> P (in dbSNP:rs56038219)" FT /id="VAR_061536" FT MUTAGEN 42 FT /note="K->A: Not phosphorylated at Thr-175 and Tyr-177." FT /evidence="ECO:0000269|PubMed:16336213" FT MUTAGEN 42 FT /note="K->R: Loss of autophosphorylation and activity. Does FT not increase dopamine transporter activity. Impairs kinase FT activity. Does not rescue cilium assembly in FT MAPK15-depleted cells." FT /evidence="ECO:0000269|PubMed:11875070, FT ECO:0000269|PubMed:28842414, ECO:0000269|PubMed:29021280" FT MUTAGEN 59 FT /note="R->Q: Does not increase dopamine transporter FT activity. Impairs kinase activity." FT /evidence="ECO:0000269|PubMed:28842414" FT MUTAGEN 155 FT /note="D->A: Unable to induce the formation of FT autophagosomal structures. Is able to bind to MAP1LC3B and FT to colocalize with this protein to autophagosomal FT structures. Does not induce phosphorylation by methyl FT methanesulfonate. Loas of phosphorylation. Dominant FT negative mutant. Not phosphorylated at Thr-175 and FT Tyr-177." FT /evidence="ECO:0000269|PubMed:16336213, FT ECO:0000269|PubMed:19166846, ECO:0000269|PubMed:22948227" FT MUTAGEN 175 FT /note="T->A: Loss of autophosphorylation and activity. FT Still heavily phosphorylated at Tyr-177. Does not rescues FT inhibition of O-glycosylation in MAPK15-depleted cells; FT when associated with F-177." FT /evidence="ECO:0000269|PubMed:11875070, FT ECO:0000269|PubMed:16336213, ECO:0000269|PubMed:24618899" FT MUTAGEN 177 FT /note="Y->A: Loss of autophosphorylation and activity. FT Heavily phosphorylated at Thr-175." FT /evidence="ECO:0000269|PubMed:11875070, FT ECO:0000269|PubMed:16336213" FT MUTAGEN 177 FT /note="Y->F: Does not rescue inhibition of O-glycosylation FT in MAPK15-depleted cells; when associated with A-175." FT /evidence="ECO:0000269|PubMed:24618899" FT MUTAGEN 265..269 FT /note="LDALL->ADAAA: Markedly decreases interaction with FT ESRRA. Impairs interaction with ESRRA; when associated with FT A-281 and 284-A--A-285. Loses the ability to re-localize FT ESRRA to the cytoplasm. Does not affect subcellular FT location in cytoplasm in presence of ESRRA. Loses the FT ability to repress ESRRA transcriptional activity." FT /evidence="ECO:0000269|PubMed:21190936" FT MUTAGEN 281..285 FT /note="LRRLL->ARRAA: Markedly decreases interaction with FT ESRRA. Impairs interaction with ESRRA; when associated with FT A-265 and 268-A--A-269. Loses the ability to re-localize FT ESRRA to the cytoplasm. Does not affect subcellular FT location in cytoplasm in presence of ESRRA.Loses the FT ability to repress ESRRA transcriptional activity." FT /evidence="ECO:0000269|PubMed:21190936" FT MUTAGEN 300 FT /note="Q->A: Impairs interaction with PCNA. Associates with FT chromatin." FT /evidence="ECO:0000269|PubMed:20733054" FT MUTAGEN 340..343 FT /note="YQMI->AQMA: Impairs interaction with GABARAP and FT MAP1LC3B. Affects subcellular localization in FT autophagosome. Does not induce autophagy." FT /evidence="ECO:0000269|PubMed:22948227" FT MUTAGEN 390 FT /note="P->A: Impairs chromatin binding; when associated FT with A-398. Increases kinase activity; when associated with FT A-398." FT /evidence="ECO:0000269|PubMed:20733054" FT MUTAGEN 398 FT /note="P->A: Impairs chromatin binding; when associated FT with A-390. Increases kinase activity; when associated with FT A-390." FT /evidence="ECO:0000269|PubMed:20733054" FT CONFLICT 113 FT /note="H -> R (in Ref. 2; AAY44299)" FT /evidence="ECO:0000305" SQ SEQUENCE 544 AA; 59832 MW; 758E0E3B9654AAC5 CRC64; MCTVVDPRIV RRYLLRRQLG QGAYGIVWKA VDRRTGEVVA IKKIFDAFRD KTDAQRTFRE ITLLQEFGDH PNIISLLDVI RAENDRDIYL VFEFMDTDLN AVIRKGGLLQ DVHVRSIFYQ LLRATRFLHS GHVVHRDQKP SNVLLDANCT VKLCDFGLAR SLGDLPEGPE DQAVTEYVAT RWYRAPEVLL SSHRYTLGVD MWSLGCILGE MLRGRPLFPG TSTLHQLELI LETIPPPSEE DLLALGSGCR ASVLHQLGSR PRQTLDALLP PDTSPEALDL LRRLLVFAPD KRLSATQALQ HPYVQRFHCP SDEWAREADV RPRAHEGVQL SVPEYRSRVY QMILECGGSS GTSREKGPEG VSPSQAHLHK PRADPQLPSR TPVQGPRPRP QSSPGHDPAE HESPRAAKNV PRQNSAPLLQ TALLGNGERP PGAKEAPPLT LSLVKPSGRG AAPSLTSQAA AQVANQALIR GDWNRGGGVR VASVQQVPPR LPPEARPGRR MFSTSALQGA QGGARALLGG YSQAYGTVCH SALGHLPLLE GHHV //