MK15_MOUSE
ID MK15_MOUSE Reviewed; 549 AA.
AC Q80Y86;
DT 18-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 151.
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|MGI:MGI:2652894};
GN Synonyms=Erk7 {ECO:0000303|PubMed:25823377},
GN Erk8 {ECO:0000303|PubMed:23351492};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Olfactory epithelium;
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 [2]
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-176 AND TYR-178, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=23351492; DOI=10.1017/s1431927612013918;
RA Yang S.W., Huang H., Gao C., Chen L., Qi S.T., Lin F., Wang J.X., Hou Y.,
RA Xing F.Q., Sun Q.Y.;
RT "The distribution and possible role of ERK8 in mouse oocyte meiotic
RT maturation and early embryo cleavage.";
RL Microsc. Microanal. 19:190-200(2013).
RN [5]
RP INTERACTION WITH DVL2, AND FUNCTION.
RX PubMed=25823377; DOI=10.1038/ncomms7666;
RA Miyatake K., Kusakabe M., Takahashi C., Nishida E.;
RT "ERK7 regulates ciliogenesis by phosphorylating the actin regulator CapZIP
RT in cooperation with Dishevelled.";
RL Nat. Commun. 6:6666-6666(2015).
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 (By similarity)
CC (PubMed:25823377). Controls both, basal and starvation-induced
CC autophagy throught its interaction with GABARAP, MAP1LC3B and GABARAPL1
CC leading to autophagosome formation, SQSTM1 degradation and reduced
CC MAP1LC3B inhibitory phosphorylation. Regulates primary cilium formation
CC and the localization of ciliary proteins involved in cilium structure,
CC transport, and signaling. Prevents the relocation of the sugar-adding
CC enzymes from the Golgi to the endoplasmic reticulum, thereby
CC restricting the production of sugar-coated proteins. Upon amino-acid
CC starvation, mediates transitional endoplasmic reticulum site
CC disassembly and inhibition of secretion. Binds to chromatin leading to
CC MAPK15 activation and interaction with PCNA, that which protects
CC genomic integrity by inhibiting MDM2-mediated degradation of PCNA.
CC Regulates DA transporter (DAT) activity and protein expression via
CC activation of RhoA. In response to H(2)O(2) treatment phosphorylates
CC ELAVL1, thus preventing it from binding to the PDCD4 3'UTR and
CC rendering the PDCD4 mRNA accessible to miR-21 and leading to its
CC degradation and loss of protein expression (By similarity). Also
CC functions in a kinase activity-independent manner as a negative
CC regulator of growth (By similarity). Phosphorylates in vitro FOS and
CC MBP (By similarity). During oocyte maturation, plays a key role in the
CC microtubule organization and meiotic cell cycle progression in oocytes,
CC fertilized eggs, and early embryos (PubMed:23351492). Interacts with
CC ESRRA promoting its re-localization from the nucleus to the cytoplasm
CC and then prevents its transcriptional activity (By similarity).
CC {ECO:0000250|UniProtKB:Q8TD08, ECO:0000250|UniProtKB:Q9Z2A6,
CC ECO:0000269|PubMed:23351492, ECO:0000269|PubMed:25823377}.
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 (By similarity). Inhibited by dual specificity
CC phosphatases, such as DUSP1 (By similarity). Phosphorylation and
CC activation in response to DNA damaging agents, serum stimulation.
CC Constitutively activated when phosphorylated on Tyr-178. Activity
CC depends on the relative rates of MAPK15 autophosphorylation and
CC dephosphorylation by PTPN1 (By similarity).
CC {ECO:0000250|UniProtKB:Q8TD08, ECO:0000250|UniProtKB:Q9Z2A6}.
CC -!- SUBUNIT: Interacts with TGFB1I1 (PubMed:16624805). Interacts with
CC CSK/c-Src, ABL1 and RET. Interacts with GABARAP, MAP1LC3B and
CC GABARAPL1; controls, in a kinase-dependent fashion, both basal and
CC starvation-induced autophagy. Interacts with ESRRA; promotes re-
CC localization of ESRRA to the cytoplasm through a XPO1-dependent
CC mechanism then inhibits ESRRA transcriptional activity. Interacts with
CC PCNA; the interaction is chromatin binding- and kinase activity-
CC dependent and prevents MDM2-mediated PCNA destruction by inhibiting the
CC association of PCNA with MDM2 (By similarity). Interacts with DVL2
CC (PubMed:25823377). Interacts with CLIC3; MAPK15 does not phosphorylates
CC CLIC3 (By similarity). {ECO:0000250|UniProtKB:Q8TD08,
CC ECO:0000250|UniProtKB:Q9Z2A6, ECO:0000269|PubMed:16624805,
CC ECO:0000269|PubMed:25823377}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body
CC {ECO:0000250|UniProtKB:Q8TD08}. Cell junction, tight junction
CC {ECO:0000250|UniProtKB:Q8TD08}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome, centriole
CC {ECO:0000250|UniProtKB:Q8TD08}. Cytoplasmic vesicle, autophagosome
CC {ECO:0000250|UniProtKB:Q8TD08}. Golgi apparatus
CC {ECO:0000250|UniProtKB:Q8TD08}. Nucleus {ECO:0000250|UniProtKB:Q8TD08}.
CC Cytoplasm {ECO:0000250|UniProtKB:Q8TD08}. Cytoplasm, cytoskeleton,
CC spindle {ECO:0000269|PubMed:23351492}. Note=Co-localizes to the
CC cytoplasm only in presence of ESRRA. Translocates to the nucleus upon
CC activation (By similarity). At prometaphase I, metaphase I (MI),
CC anaphase I, telophase I, and metaphase II (MII) stages, is stably
CC detected at the spindle (PubMed:23351492).
CC {ECO:0000250|UniProtKB:Q8TD08, ECO:0000269|PubMed:23351492}.
CC -!- TISSUE SPECIFICITY: Expressed at all stages of oocyte meiotic
CC maturation. {ECO:0000269|PubMed:23351492}.
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-176 and Tyr-178; activates the enzyme.
CC {ECO:0000250|UniProtKB:Q8TD08}.
CC -!- PTM: Ubiquitinated. Ubiquitination may allow its tight kinase activity
CC regulation and rapid turnover. May be ubiquitinated by a SCF E3 ligase
CC (By similarity). {ECO:0000250|UniProtKB:Q9Z2A6}.
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; BC048082; AAH48082.1; -; mRNA.
DR CCDS; CCDS27558.1; -.
DR RefSeq; NP_808590.1; NM_177922.2.
DR AlphaFoldDB; Q80Y86; -.
DR SMR; Q80Y86; -.
DR BioGRID; 237123; 8.
DR STRING; 10090.ENSMUSP00000087098; -.
DR iPTMnet; Q80Y86; -.
DR PhosphoSitePlus; Q80Y86; -.
DR MaxQB; Q80Y86; -.
DR PaxDb; Q80Y86; -.
DR PRIDE; Q80Y86; -.
DR ProteomicsDB; 291466; -.
DR Antibodypedia; 957; 355 antibodies from 31 providers.
DR DNASU; 332110; -.
DR Ensembl; ENSMUST00000089669; ENSMUSP00000087098; ENSMUSG00000063704.
DR GeneID; 332110; -.
DR KEGG; mmu:332110; -.
DR UCSC; uc007whz.1; mouse.
DR CTD; 225689; -.
DR MGI; MGI:2652894; Mapk15.
DR VEuPathDB; HostDB:ENSMUSG00000063704; -.
DR eggNOG; KOG0660; Eukaryota.
DR GeneTree; ENSGT00940000159758; -.
DR HOGENOM; CLU_000288_181_14_1; -.
DR InParanoid; Q80Y86; -.
DR OMA; PDQEWTR; -.
DR OrthoDB; 741207at2759; -.
DR PhylomeDB; Q80Y86; -.
DR TreeFam; TF105101; -.
DR BioGRID-ORCS; 332110; 2 hits in 75 CRISPR screens.
DR PRO; PR:Q80Y86; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q80Y86; protein.
DR Bgee; ENSMUSG00000063704; Expressed in spermatocyte and 58 other tissues.
DR ExpressionAtlas; Q80Y86; baseline and differential.
DR Genevisible; Q80Y86; MM.
DR GO; GO:0005776; C:autophagosome; ISS:UniProtKB.
DR GO; GO:0005923; C:bicellular tight junction; IEA:UniProtKB-SubCell.
DR GO; GO:0005911; C:cell-cell junction; ISS:UniProtKB.
DR GO; GO:0005814; C:centriole; ISS:UniProtKB.
DR GO; GO:0036064; C:ciliary basal body; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0072687; C:meiotic spindle; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0016301; F:kinase activity; ISS:UniProtKB.
DR GO; GO:0004707; F:MAP kinase activity; ISS:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; ISS: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:0006974; P:cellular response to DNA damage stimulus; ISO:MGI.
DR GO; GO:0090494; P:dopamine uptake; ISS:UniProtKB.
DR GO; GO:0007029; P:endoplasmic reticulum organization; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0030336; P:negative regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0008156; P:negative regulation of DNA replication; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:1905188; P:positive regulation of metaphase/anaphase transition of meiosis I; IMP:UniProtKB.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; ISO:MGI.
DR GO; GO:1905832; P:positive regulation of spindle assembly; IMP:UniProtKB.
DR GO; GO:0051973; P:positive regulation of telomerase activity; ISO:MGI.
DR GO; GO:1904355; P:positive regulation of telomere capping; ISO:MGI.
DR GO; GO:0032212; P:positive regulation of telomere maintenance via telomerase; ISO:MGI.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:1904491; P:protein localization to ciliary transition zone; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; ISO:MGI.
DR GO; GO:0010506; P:regulation of autophagy; ISS:UniProtKB.
DR GO; GO:1902017; P:regulation of cilium assembly; IMP:UniProtKB.
DR GO; GO:0003400; P:regulation of COPII vesicle coating; ISS:UniProtKB.
DR GO; GO:0032355; P:response to estradiol; ISO:MGI.
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 ATP-binding; Cell junction; Cell projection; Cytoplasm;
KW Cytoplasmic vesicle; Cytoskeleton; Golgi apparatus; Kinase; Methylation;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Tight junction; Transferase;
KW Ubl conjugation.
FT CHAIN 1..549
FT /note="Mitogen-activated protein kinase 15"
FT /id="PRO_0000232638"
FT DOMAIN 14..305
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REPEAT 380..384
FT /note="PXXXP motif"
FT /evidence="ECO:0000250|UniProtKB:Q8TD08"
FT REPEAT 387..391
FT /note="PXXXP motif"
FT /evidence="ECO:0000250|UniProtKB:Q8TD08"
FT REPEAT 395..399
FT /note="PXXXP motif; regulates binding with chromatin and
FT interaction with PCNA"
FT /evidence="ECO:0000250|UniProtKB:Q8TD08"
FT REPEAT 403..407
FT /note="PXXXP motif; regulates binding with chromatin and
FT interaction with PCNA"
FT /evidence="ECO:0000250|UniProtKB:Q8TD08"
FT REGION 1..20
FT /note="Ubiquitin-conjugating"
FT REGION 266..286
FT /note="Necessary to interact with ESRRA, to regulate its
FT subcellular localization and to inhibit its transcriptional
FT activity"
FT /evidence="ECO:0000250|UniProtKB:Q8TD08"
FT REGION 301..382
FT /note="Requires for interaction with GABARAP, MAP1LC3B AND
FT GABARAPL1"
FT /evidence="ECO:0000250|UniProtKB:Q8TD08"
FT REGION 370..507
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 176..178
FT /note="TXY"
FT COMPBIAS 394..415
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 425..439
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 441..467
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 138
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 20..28
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 43
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 176
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 178
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 451
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q8TD08"
SQ SEQUENCE 549 AA; 60679 MW; A42181A1EC40C1A6 CRC64;
MCAAEVDRHV AQRYLIKRRL GKGAYGIVWK AMDRRTGEVV AIKKIFDAFR DQIDAQRTFR
EIMLLKEFGG HPNIIRLLDV IPAKNDRDIY LVFESMDTDL NAVIQKGRLL KDIHKRCIFY
QLLRATKFIH SGRVIHRDQK PANVLLDSAC RVKLCDFGLA RSLGDLPEGP GGQALTEYVA
TRWYRAPEVL LSSRWYTPGV DMWSLGCILG EMLRGQPLFP GTSTFHQLEL ILKTIPLPSM
EELQDLGSDY SALILQNLGS RPQQTLDALL PPDTPPEALD LLKRLLAFAP DKRLSAEQAL
QHPYVQRFHC PDREWARESD VRLPVHEGDQ LSAPEYRKRL YQIILEQSGN SRSPREEGLG
VVASRAELRA SPARTQSLKS GVLPQVPAET PARKRGPKPP RSPGHDPEHV EVRRQSSDPL
FQLPPPGRGE RPPGATGQPP SAPSGVKTQV RAMAPSLTSQ AEAQAANQAL IRSDPARGGG
PRAVGARRVP SRLPREAPEP RPGRRMFGIS VSQGAQGAAR AALGGYSQAY GTVCRSALGR
LPLLPGPRA
