MK15_HUMAN
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 03-AUG-2022, entry version 161.
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},
GN ERK8 {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 phosphorylates 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}.
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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; 30.
DR IntAct; Q8TD08; 39.
DR STRING; 9606.ENSP00000337691; -.
DR BindingDB; Q8TD08; -.
DR ChEMBL; CHEMBL5198; -.
DR DrugBank; DB00945; Acetylsalicylic acid.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB01017; Minocycline.
DR DrugCentral; Q8TD08; -.
DR GuidetoPHARMACOLOGY; 2090; -.
DR iPTMnet; Q8TD08; -.
DR PhosphoSitePlus; Q8TD08; -.
DR BioMuta; MAPK15; -.
DR DMDM; 74760462; -.
DR EPD; Q8TD08; -.
DR jPOST; Q8TD08; -.
DR MassIVE; Q8TD08; -.
DR MaxQB; Q8TD08; -.
DR PaxDb; Q8TD08; -.
DR PeptideAtlas; Q8TD08; -.
DR PRIDE; Q8TD08; -.
DR ProteomicsDB; 74209; -. [Q8TD08-1]
DR ProteomicsDB; 74210; -. [Q8TD08-2]
DR ProteomicsDB; 74211; -. [Q8TD08-3]
DR Antibodypedia; 957; 355 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 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; 741207at2759; -.
DR PhylomeDB; Q8TD08; -.
DR TreeFam; TF105101; -.
DR PathwayCommons; Q8TD08; -.
DR SignaLink; Q8TD08; -.
DR SIGNOR; Q8TD08; -.
DR BioGRID-ORCS; 225689; 30 hits in 1112 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 88 other tissues.
DR Genevisible; Q8TD08; HS.
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:cellular response to DNA damage stimulus; 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 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 Pfam; PF00069; Pkinase; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS01351; MAPK; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
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 MAPK15-
FT 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 Tyr-
FT 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 rescues 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
