MK15_CAEEL
ID MK15_CAEEL Reviewed; 470 AA.
AC Q11179; G8JY04; Q8T3F7;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 06-JUN-2002, sequence version 2.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Mitogen-activated protein kinase 15 {ECO:0000305};
DE EC=2.7.11.24 {ECO:0000250|UniProtKB:Q17446};
DE AltName: Full=Swimming-induced paralysis protein 13 {ECO:0000303|PubMed:28842414};
DE Short=SWIP-13 {ECO:0000303|PubMed:28842414};
GN Name=mapk-15 {ECO:0000303|PubMed:28745435, ECO:0000312|WormBase:C05D10.2a};
GN Synonyms=swip-13 {ECO:0000303|PubMed:28842414};
GN ORFNames=C05D10.2 {ECO:0000312|WormBase:C05D10.2a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=28745435; DOI=10.1002/cm.21387;
RA Piasecki B.P., Sasani T.A., Lessenger A.T., Huth N., Farrell S.;
RT "MAPK-15 is a ciliary protein required for PKD-2 localization and male
RT mating behavior in Caenorhabditis elegans.";
RL Cytoskeleton 74:390-402(2017).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
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 [4]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF 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).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP AND MUTAGENESIS OF LYS-42; 185-TRP--TYR-470; ASP-203 AND 342-TYR--ILE-345.
RX PubMed=29879119; DOI=10.1371/journal.pgen.1007435;
RA McLachlan I.G., Beets I., de Bono M., Heiman M.G.;
RT "A neuronal MAP kinase constrains growth of a Caenorhabditis elegans
RT sensory dendrite throughout the life of the organism.";
RL PLoS Genet. 14:E1007435-E1007435(2018).
CC -!- FUNCTION: Atypical MAPK protein. Regulates primary cilium formation in
CC sensory neurons and the localization of ciliary proteins involved in
CC cilium structure, transport, and signaling (PubMed:29021280,
CC PubMed:28745435). Acts in dopamine (DA) neurons to support synaptic
CC membrane dat-1 availability via activation of rho-1 thereby sustaining
CC normal levels of DA clearance (PubMed:28842414). Plays a role in male
CC mating behavior, probably in part through regulating the localization
CC of the polycystin pkd-2 (PubMed:28745435). Functions postembryonically
CC in the URX sensory neurons to constrain URX dendrite growth throughout
CC lifetime, probably by restricting expansion of the subcellular sensory
CC compartment at the dendrite ending (PubMed:29879119).
CC {ECO:0000269|PubMed:28745435, ECO:0000269|PubMed:28842414,
CC ECO:0000269|PubMed:29021280, ECO:0000269|PubMed:29879119}.
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 Evidence={ECO:0000250|UniProtKB:Q17446};
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; Evidence={ECO:0000250|UniProtKB:Q17446};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q17446};
CC -!- ACTIVITY REGULATION: Activated by threonine and tyrosine
CC phosphorylation. {ECO:0000250|UniProtKB:Q17446}.
CC -!- SUBCELLULAR LOCATION: Cell projection, dendrite
CC {ECO:0000269|PubMed:29879119}. Note=Enriched localization at the URX
CC dendrite ending. {ECO:0000269|PubMed:29879119}.
CC -!- SUBCELLULAR LOCATION: [Isoform a]: Perikaryon
CC {ECO:0000269|PubMed:28745435}. Cell projection, dendrite
CC {ECO:0000269|PubMed:28745435}. Cell projection, cilium
CC {ECO:0000269|PubMed:28745435, ECO:0000269|PubMed:29021280}. Cell
CC projection, cilium membrane {ECO:0000269|PubMed:28745435}. Cytoplasm,
CC cytoskeleton, cilium axoneme {ECO:0000269|PubMed:29021280}. Cytoplasm,
CC cytoskeleton, cilium basal body {ECO:0000269|PubMed:29021280}. Cell
CC junction {ECO:0000269|PubMed:29021280}.
CC -!- SUBCELLULAR LOCATION: [Isoform c]: Perikaryon
CC {ECO:0000269|PubMed:28745435}. Cell projection, dendrite
CC {ECO:0000269|PubMed:28745435}. Cell projection, cilium
CC {ECO:0000269|PubMed:28745435, ECO:0000269|PubMed:29021280}. Cell
CC projection, cilium membrane {ECO:0000269|PubMed:28745435}. Cytoplasm,
CC cytoskeleton, cilium axoneme {ECO:0000269|PubMed:29021280}. Cytoplasm,
CC cytoskeleton, cilium basal body {ECO:0000269|PubMed:29021280}. Cell
CC junction {ECO:0000269|PubMed:29021280}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=a {ECO:0000312|WormBase:C05D10.2a};
CC IsoId=Q11179-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:C05D10.2b};
CC IsoId=Q11179-2; Sequence=VSP_059128;
CC Name=c {ECO:0000312|WormBase:C05D10.2c};
CC IsoId=Q11179-3; Sequence=VSP_059129, VSP_059130;
CC -!- TISSUE SPECIFICITY: Expressed in the URX neuron and in many other head
CC sensory neurons (PubMed:29879119). Isoform a: Expressed in head and
CC tail ciliated sensory neurons, and in mid-body neurons. Isoform c:
CC Expressed in head and tail ciliated sensory neurons, and in mid-body
CC neurons. {ECO:0000269|PubMed:28745435, ECO:0000269|PubMed:29021280,
CC ECO:0000269|PubMed:29879119}.
CC -!- DEVELOPMENTAL STAGE: Expressed in all larval stages.
CC {ECO:0000269|PubMed:29879119}.
CC -!- DOMAIN: The TXY motif contains the threonine and tyrosine residues
CC whose phosphorylation activates the MAP kinases.
CC {ECO:0000250|UniProtKB:Q17446}.
CC -!- PTM: Dually phosphorylated on Thr-178 and Tyr-180, which activates the
CC enzyme. {ECO:0000250|UniProtKB:Q17446}.
CC -!- DISRUPTION PHENOTYPE: Viable, but males display irregular mating
CC behavior (PubMed:28745435). Ciliary defects in ciliated sensory neurons
CC include impaired extension of dendrites, and abnormal amphid and
CC phasmid sensillum morphology (PubMed:28745435, PubMed:29021280).
CC Homozygotes present the swimming-induced paralysis (Swip) phenotype
CC (PubMed:28842414). {ECO:0000269|PubMed:28745435,
CC ECO:0000269|PubMed:28842414, ECO:0000269|PubMed:29021280}.
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; FO080362; CCD63173.1; -; Genomic_DNA.
DR EMBL; BX284603; CCD63174.1; -; Genomic_DNA.
DR EMBL; BX284603; CCD63175.1; -; Genomic_DNA.
DR PIR; H88473; H88473.
DR RefSeq; NP_741165.1; NM_171144.4. [Q11179-1]
DR RefSeq; NP_741166.1; NM_171145.4.
DR RefSeq; NP_741167.1; NM_171146.3.
DR AlphaFoldDB; Q11179; -.
DR SMR; Q11179; -.
DR BioGRID; 41078; 4.
DR STRING; 6239.C05D10.2a; -.
DR PaxDb; Q11179; -.
DR PeptideAtlas; Q11179; -.
DR EnsemblMetazoa; C05D10.2a.1; C05D10.2a.1; WBGene00015478. [Q11179-1]
DR GeneID; 175857; -.
DR KEGG; cel:CELE_C05D10.2; -.
DR UCSC; C05D10.2c; c. elegans. [Q11179-1]
DR CTD; 175857; -.
DR WormBase; C05D10.2a; CE29020; WBGene00015478; mapk-15. [Q11179-1]
DR WormBase; C05D10.2b; CE30421; WBGene00015478; mapk-15. [Q11179-2]
DR WormBase; C05D10.2c; CE30422; WBGene00015478; mapk-15. [Q11179-3]
DR eggNOG; KOG0660; Eukaryota.
DR GeneTree; ENSGT00940000159758; -.
DR InParanoid; Q11179; -.
DR OMA; PDQEWTR; -.
DR OrthoDB; 741207at2759; -.
DR PhylomeDB; Q11179; -.
DR PRO; PR:Q11179; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00015478; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR GO; GO:0005930; C:axoneme; IDA:UniProtKB.
DR GO; GO:0005911; C:cell-cell junction; IDA:UniProtKB.
DR GO; GO:0036064; C:ciliary basal body; IDA:UniProtKB.
DR GO; GO:0060170; C:ciliary membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004707; F:MAP kinase activity; IBA:GO_Central.
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:0007610; P:behavior; IEA:UniProtKB-KW.
DR GO; GO:0030030; P:cell projection organization; IEA:UniProtKB-KW.
DR GO; GO:0090494; P:dopamine uptake; IDA:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:1904491; P:protein localization to ciliary transition zone; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:1902017; P:regulation of cilium assembly; 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 InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 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.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Behavior; Cell junction; Cell membrane;
KW Cell projection; Cilium biogenesis/degradation; Cytoplasm; Cytoskeleton;
KW Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..470
FT /note="Mitogen-activated protein kinase 15"
FT /evidence="ECO:0000305"
FT /id="PRO_0000186307"
FT DOMAIN 13..306
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 362..445
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 178..180
FT /note="TXY"
FT COMPBIAS 380..414
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 425..440
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 137
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
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 178
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q17446"
FT MOD_RES 180
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q17446"
FT VAR_SEQ 87..470
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_059128"
FT VAR_SEQ 363..367
FT /note="YGEDK -> VVRRR (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_059129"
FT VAR_SEQ 368..470
FT /note="Missing (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_059130"
FT MUTAGEN 42
FT /note="K->A: Causes URX dendrite overgrowth."
FT /evidence="ECO:0000269|PubMed:29879119"
FT MUTAGEN 59
FT /note="R->Q: In vt32; loss of function allele that displays
FT reserpine-sensitive swimming-induced paralysis phenotype."
FT /evidence="ECO:0000269|PubMed:28842414"
FT MUTAGEN 185..470
FT /note="Missing: In hmn5; overgrowth of URX dendrite,
FT extending up to 150% of its normal length, making a U-turn
FT at the nose and looping back in the direction of the cell
FT body rather than ceasing growth at the tip of the nose,
FT with increasing dendrite outgrowth from larval stages to
FT adult animals. Rarely, starved animals exhibit ectopic
FT branching of the URX dendrites."
FT /evidence="ECO:0000269|PubMed:29879119"
FT MUTAGEN 203
FT /note="D->N: In hmn51; causes URX dendrite overgrowth."
FT /evidence="ECO:0000269|PubMed:29879119"
FT MUTAGEN 342..345
FT /note="Missing: Causes URX dendrite overgrowth."
FT /evidence="ECO:0000269|PubMed:29879119"
SQ SEQUENCE 470 AA; 54039 MW; 8908B49D15173DF0 CRC64;
MTDDVDTHIH EKFDLQKRLG KGAYGIVWKA YDKRSRETVA LKKIFDAFRN PTDSQRTFRE
VMFLQEFGKH PNVIKLYNIF RADNDRDIYL AFEFMEADLH NVIKKGSILK DVHKQYIMCQ
LFRAIRFLHS GNVLHRDLKP SNVLLDADCR VKLADFGLAR SLSSLEDYPE GQKMPDLTEY
VATRWYRSPE ILLAAKRYTK GVDMWSLGCI LAEMLIGRAL FPGSSTINQI ERIMNTIAKP
SRADIASIGS HYAASVLEKM PQRPRKPLDL IITQSQTAAI DMVQRLLIFA PQKRLTVEQC
LVHPYVVQFH NPSEEPVLNY EVYPPLPDHI QLSIDDYRDR LYEMIDEKKA SFKRIQHEKI
RPYGEDKSRA PIAQAECSDT DYDTARSLQR TTSMDKNNSS SHDSSSGTLR ERAASAESRT
SKDSNGEMRN GNGNTPSSIK QRRRSVERAR LFANIKPSKI LHPHKLISNY
