PLPL2_CAEEL
ID PLPL2_CAEEL Reviewed; 621 AA.
AC Q11186;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 06-JUN-2002, sequence version 2.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Patanin-like phospholipase domain-containing protein atgl-1 {ECO:0000250|UniProtKB:Q96AD5};
DE EC=3.1.1.3 {ECO:0000250|UniProtKB:Q96AD5};
DE AltName: Full=Adipose triglyceride lipase 1 {ECO:0000312|WormBase:C05D11.7a};
GN Name=atgl-1 {ECO:0000312|WormBase:C05D11.7a};
GN ORFNames=C05D11.7 {ECO:0000312|WormBase:C05D11.7a};
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, PHOSPHORYLATION AT SER-303, TISSUE SPECIFICITY, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF SER-303.
RX PubMed=19052547; DOI=10.1038/nature07536;
RA Narbonne P., Roy R.;
RT "Caenorhabditis elegans dauers need LKB1/AMPK to ration lipid reserves and
RT ensure long-term survival.";
RL Nature 457:210-214(2009).
RN [3]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=20176933; DOI=10.1073/pnas.0912308107;
RA Zhang S.O., Box A.C., Xu N., Le Men J., Yu J., Guo F., Trimble R.,
RA Mak H.Y.;
RT "Genetic and dietary regulation of lipid droplet expansion in
RT Caenorhabditis elegans.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:4640-4645(2010).
RN [4]
RP FUNCTION, TISSUE SPECIFICITY, INDUCTION BY SEROTININ, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=24120942; DOI=10.1016/j.cmet.2013.09.007;
RA Noble T., Stieglitz J., Srinivasan S.;
RT "An integrated serotonin and octopamine neuronal circuit directs the
RT release of an endocrine signal to control C. elegans body fat.";
RL Cell Metab. 18:672-684(2013).
RN [5]
RP FUNCTION, INTERACTION WITH LID-1, SUBCELLULAR LOCATION, UBIQUITINATION,
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF SER-303.
RX PubMed=25202121; DOI=10.1128/mcb.00722-14;
RA Lee J.H., Kong J., Jang J.Y., Han J.S., Ji Y., Lee J., Kim J.B.;
RT "Lipid droplet protein LID-1 mediates ATGL-1-dependent lipolysis during
RT fasting in Caenorhabditis elegans.";
RL Mol. Cell. Biol. 34:4165-4176(2014).
RN [6]
RP FUNCTION, INTERACTION WITH CGI-58, AND SUBCELLULAR LOCATION.
RX PubMed=26083785; DOI=10.1371/journal.pgen.1005284;
RA Xie M., Roy R.;
RT "The causative gene in Chanarian Dorfman syndrome regulates lipid droplet
RT homeostasis in C. elegans.";
RL PLoS Genet. 11:E1005284-E1005284(2015).
RN [7]
RP ERRATUM OF PUBMED:26083785.
RX PubMed=28002418; DOI=10.1371/journal.pgen.1006524;
RA Xie M., Roy R.;
RL PLoS Genet. 12:E1006524-E1006524(2016).
RN [8]
RP FUNCTION, INTERACTION WITH PAR-5, SUBCELLULAR LOCATION, PHOSPHORYLATION AT
RP SER-303, TISSUE SPECIFICITY, UBIQUITINATION, DISRUPTION PHENOTYPE, AND
RP MUTAGENESIS OF SER-303.
RX PubMed=26098762; DOI=10.1371/journal.pone.0130480;
RA Xie M., Roy R.;
RT "AMP-activated kinase regulates lipid droplet localization and stability of
RT adipose triglyceride lipase in C. elegans dauer larvae.";
RL PLoS ONE 10:E0130480-E0130480(2015).
RN [9]
RP DISRUPTION PHENOTYPE.
RX PubMed=28128367; DOI=10.1038/ncomms14237;
RA Palamiuc L., Noble T., Witham E., Ratanpal H., Vaughan M., Srinivasan S.;
RT "A tachykinin-like neuroendocrine signalling axis couples central serotonin
RT action and nutrient sensing with peripheral lipid metabolism.";
RL Nat. Commun. 8:14237-14237(2017).
RN [10]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=33078707; DOI=10.7554/elife.58815;
RA Littlejohn N.K., Seban N., Liu C.C., Srinivasan S.;
RT "A feedback loop governs the relationship between lipid metabolism and
RT longevity.";
RL Elife 9:0-0(2020).
CC -!- FUNCTION: Catalyzes the initial step in triglyceride hydrolysis in
CC adipocyte and non-adipocyte lipid droplets (By similarity). Component
CC of a feedback loop involving atfs-1, atgl-1 and hlh-11
CC (PubMed:33078707). Promotes fat oxidation in response to mitochondrial
CC stress (PubMed:33078707). May play a role in the response of the
CC organism to starvation, enhancing hydrolysis of triglycerides and
CC providing free fatty acids to other tissues to be oxidized in
CC situations of energy depletion (PubMed:19052547, PubMed:20176933,
CC PubMed:24120942, PubMed:25202121, PubMed:26083785, PubMed:26098762).
CC Acts coordinately with lid-1 within the lipolytic cascade to distribute
CC stored energy to tissues (PubMed:25202121). Together with lipid droplet
CC protein cgi-58, regulates lipid reserves as well as lipid droplet size
CC and localization during the dauer phase in response to phosphorylation
CC by ampk (PubMed:19052547, PubMed:26083785, PubMed:26098762). May
CC regulate serotonin-mediated lipolysis in metabolic tissues
CC (PubMed:24120942). {ECO:0000250|UniProtKB:Q96AD5,
CC ECO:0000269|PubMed:19052547, ECO:0000269|PubMed:20176933,
CC ECO:0000269|PubMed:24120942, ECO:0000269|PubMed:25202121,
CC ECO:0000269|PubMed:26083785, ECO:0000269|PubMed:26098762,
CC ECO:0000269|PubMed:33078707}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a triacylglycerol + H2O = a diacylglycerol + a fatty acid +
CC H(+); Xref=Rhea:RHEA:12044, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17855, ChEBI:CHEBI:18035, ChEBI:CHEBI:28868; EC=3.1.1.3;
CC Evidence={ECO:0000250|UniProtKB:Q96AD5};
CC -!- PATHWAY: Glycerolipid metabolism; triacylglycerol degradation.
CC {ECO:0000250|UniProtKB:Q96AD5}.
CC -!- SUBUNIT: Interacts with par-5 (PubMed:26098762). Interacts with lid-1
CC (PubMed:25202121). Interacts with cgi-58 (PubMed:26083785).
CC {ECO:0000269|PubMed:25202121, ECO:0000269|PubMed:26083785,
CC ECO:0000269|PubMed:26098762}.
CC -!- SUBCELLULAR LOCATION: Lipid droplet {ECO:0000269|PubMed:20176933,
CC ECO:0000269|PubMed:25202121, ECO:0000269|PubMed:26083785,
CC ECO:0000269|PubMed:26098762}. Cell membrane {ECO:0000255}; Single-pass
CC type II membrane protein {ECO:0000255}. Cytoplasm
CC {ECO:0000269|PubMed:26098762}. Note=Accumulates in the cytoplasm when
CC phosphorylated and within lipid droplets when unphosphorylated during
CC the dauer phase (PubMed:26098762). Localization on lipid droplets
CC enhanced by interaction with cgi-58 (PubMed:26083785).
CC {ECO:0000269|PubMed:26083785, ECO:0000269|PubMed:26098762}.
CC -!- TISSUE SPECIFICITY: Expressed in the hypodermis (PubMed:19052547,
CC PubMed:26098762). Expressed in the intestine (at protein level)
CC (PubMed:24120942, PubMed:33078707). {ECO:0000269|PubMed:19052547,
CC ECO:0000269|PubMed:24120942, ECO:0000269|PubMed:26098762,
CC ECO:0000269|PubMed:33078707}.
CC -!- INDUCTION: May be induced by serotonin. {ECO:0000269|PubMed:24120942}.
CC -!- PTM: Phosphorylation at Ser-303 by aak-2 results in possible
CC instability and cytoplasmic accumulation during the dauer phase.
CC {ECO:0000269|PubMed:19052547, ECO:0000269|PubMed:26098762}.
CC -!- PTM: Ubiquitinated (PubMed:25202121, PubMed:26098762). Ubiquitination
CC may decrease upon phosphorylation by kin-1 (PubMed:25202121).
CC {ECO:0000269|PubMed:25202121, ECO:0000269|PubMed:26098762}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown reduces stored lipid
CC droplet hydrolysis during fasting resulting in retained/increased lipid
CC droplets and there are also increased lipid droplets in the fed state
CC (PubMed:24120942, PubMed:25202121). Suppresses fasting-induced oxygen
CC consumption (PubMed:25202121). RNAi-mediated knockdown abrogates the
CC increased fat loss and increased oxygen consumption rate observed in
CC the hlh-11 ok2944 mutant (PubMed:33078707). RNAi-mediated knockdown
CC also abrogates the increased fat loss observed following overexpression
CC of flp-7 (PubMed:28128367, PubMed:33078707). Furthermore, RNAi-mediated
CC knockdown reduces the induction of hsp-60, an indicator of
CC mitochondrial stress following overexpression of either flp-7 or hlh-11
CC (PubMed:33078707). RNAi-mediated knockdown in aak-2 mutants improves
CC the survival of dauer larvae (PubMed:19052547). RNAi-mediated knockdown
CC in daf-2 constitutive dauer phase mutants results in enlarged lipid
CC droplets possibly due to an accumulation of unhydrolyzed triglycerides
CC (PubMed:26098762). {ECO:0000269|PubMed:19052547,
CC ECO:0000269|PubMed:24120942, ECO:0000269|PubMed:25202121,
CC ECO:0000269|PubMed:26098762, ECO:0000269|PubMed:28128367,
CC ECO:0000269|PubMed:33078707}.
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DR EMBL; BX284603; CCD63196.1; -; Genomic_DNA.
DR PIR; C88482; C88482.
DR RefSeq; NP_741196.1; NM_171168.5.
DR AlphaFoldDB; Q11186; -.
DR BioGRID; 41128; 3.
DR STRING; 6239.C05D11.7b.1; -.
DR iPTMnet; Q11186; -.
DR PaxDb; Q11186; -.
DR PeptideAtlas; Q11186; -.
DR EnsemblMetazoa; C05D11.7a.1; C05D11.7a.1; WBGene00015484.
DR GeneID; 175910; -.
DR UCSC; C05D11.7a.1; c. elegans.
DR CTD; 175910; -.
DR WormBase; C05D11.7a; CE29663; WBGene00015484; atgl-1.
DR eggNOG; KOG3773; Eukaryota.
DR HOGENOM; CLU_018371_6_1_1; -.
DR InParanoid; Q11186; -.
DR Reactome; R-CEL-1482883; Acyl chain remodeling of DAG and TAG.
DR Reactome; R-CEL-163560; Triglyceride catabolism.
DR Reactome; R-CEL-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-CEL-8957275; Post-translational protein phosphorylation.
DR UniPathway; UPA00256; -.
DR PRO; PR:Q11186; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00015484; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR ExpressionAtlas; Q11186; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005811; C:lipid droplet; IDA:WormBase.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004806; F:triglyceride lipase activity; IBA:GO_Central.
DR GO; GO:0055088; P:lipid homeostasis; IBA:GO_Central.
DR GO; GO:0019433; P:triglyceride catabolic process; IBA:GO_Central.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR033562; PLPL.
DR InterPro; IPR002641; PNPLA_dom.
DR PANTHER; PTHR12406; PTHR12406; 1.
DR Pfam; PF01734; Patatin; 1.
DR SUPFAM; SSF52151; SSF52151; 1.
DR PROSITE; PS51635; PNPLA; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cytoplasm; Hydrolase; Lipid degradation; Lipid droplet;
KW Lipid metabolism; Membrane; Phosphoprotein; Reference proteome;
KW Signal-anchor; Transmembrane; Transmembrane helix; Ubl conjugation.
FT CHAIN 1..621
FT /note="Patanin-like phospholipase domain-containing protein
FT atgl-1"
FT /evidence="ECO:0000305"
FT /id="PRO_0000065148"
FT TOPO_DOM 33..43
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 44..64
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 65..621
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT DOMAIN 13..180
FT /note="PNPLA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT REGION 541..562
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 595..621
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 46..50
FT /note="GXSXG"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT MOTIF 167..169
FT /note="DGA/G"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT COMPBIAS 541..555
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 48
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT ACT_SITE 167
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT MOD_RES 303
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19052547,
FT ECO:0000269|PubMed:25202121, ECO:0000269|PubMed:26098762"
FT MUTAGEN 303
FT /note="S->A: Abolishes phosphorylation by aak-2 and kin-1.
FT Attenuates interaction with lid-1."
FT /evidence="ECO:0000269|PubMed:19052547,
FT ECO:0000269|PubMed:25202121, ECO:0000269|PubMed:26098762"
SQ SEQUENCE 621 AA; 69364 MW; 93BE89A868F684EC CRC64;
MTMINSRPEL MNLSFSGCGF LCVYHAGVAA AIKEYAPELL QNKILGASAG SIVACGLITG
VCISHATSTI LKVVSQARSR TFGPLHPEFN LLGIVRDELE VILPPNAYEM CTGRLVISLT
RWSDHENVII DEYRSNADLI DAIMCSCFIP LYCGITPPKF RGVQYIDGGV SDNQPIYDEH
TVTVSPFSGE SDICPPDWDS GSMLGVDFNG TSIRFTTRNM FRLMACLWPR STDDLSRMCL
QGFGDALRFL TKCGLAPCIR CLTIQTIDAN EPAGRVSSEC FSENDDAKKV THVAVPRMKK
RASANALNSF RTRGESECET CGDSDIPLEE VNIQSFFPSI MKKPFEDAVA AERSVFQYMM
SFRLVRYATT AMGISKFPFD MALAFVKKVH QYLDMVSPPR WIMLKFRGLA DFILGEVEKQ
KSRYTNFSCL VAVAETDSFG SVLASSTMEK EEHKEIELSE DAKKEMILLR ERDRRRKLLK
KAGKITPNNS ENQFDETSVY DVDSFEHVID FTKSHEALYE FHYRDENQVM KTFGLFTDSQ
QRPYSSASQH QHHHTKSLGG TSRLVHVPEE DEDAPLSAVS APAVIFHGGQ EIVELGESDK
DSGLSGIDTK RKVPDEPTTR F
