LIPL4_CAEEL
ID LIPL4_CAEEL Reviewed; 411 AA.
AC Q94252; A0A0K3AUZ3;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Lipase lipl-4 {ECO:0000255|PIRNR:PIRNR000862};
DE EC=3.1.1.- {ECO:0000305|PubMed:23392608, ECO:0000305|PubMed:25554789};
DE EC=3.1.1.3 {ECO:0000305|PubMed:21906946, ECO:0000305|PubMed:25554789};
DE AltName: Full=Lipase-like 4 {ECO:0000312|WormBase:K04A8.5a};
DE Flags: Precursor;
GN Name=lipl-4 {ECO:0000312|WormBase:K04A8.5a};
GN ORFNames=K04A8.5 {ECO:0000312|WormBase:K04A8.5a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
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] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=21906946; DOI=10.1016/j.cub.2011.07.042;
RA Lapierre L.R., Gelino S., Melendez A., Hansen M.;
RT "Autophagy and lipid metabolism coordinately modulate life span in
RT germline-less C. elegans.";
RL Curr. Biol. 21:1507-1514(2011).
RN [3] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, AND INDUCTION.
RX PubMed=23392608; DOI=10.1101/gad.205294.112;
RA O'Rourke E.J., Kuballa P., Xavier R., Ruvkun G.;
RT "omega-6 Polyunsaturated fatty acids extend life span through the
RT activation of autophagy.";
RL Genes Dev. 27:429-440(2013).
RN [4] {ECO:0000305}
RP INDUCTION.
RX PubMed=23604316; DOI=10.1038/ncb2741;
RA O'Rourke E.J., Ruvkun G.;
RT "MXL-3 and HLH-30 transcriptionally link lipolysis and autophagy to
RT nutrient availability.";
RL Nat. Cell Biol. 15:668-676(2013).
RN [5] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP SUBCELLULAR LOCATION.
RX PubMed=25554789; DOI=10.1126/science.1258857;
RA Folick A., Oakley H.D., Yu Y., Armstrong E.H., Kumari M., Sanor L.,
RA Moore D.D., Ortlund E.A., Zechner R., Wang M.C.;
RT "Aging. Lysosomal signaling molecules regulate longevity in Caenorhabditis
RT elegans.";
RL Science 347:83-86(2015).
RN [6] {ECO:0000305}
RP DEVELOPMENTAL STAGE.
RX PubMed=28503130; DOI=10.3389/fnmol.2017.00101;
RA Shemesh N., Shai N., Meshnik L., Katalan R., Ben-Zvi A.;
RT "Uncoupling the Trade-Off between Somatic Proteostasis and Reproduction in
RT Caenorhabditis elegans Models of Polyglutamine Diseases.";
RL Front. Mol. Neurosci. 10:101-101(2017).
RN [7] {ECO:0000305}
RP FUNCTION.
RX PubMed=30713071; DOI=10.1016/j.devcel.2018.12.022;
RA Ramachandran P.V., Savini M., Folick A.K., Hu K., Masand R., Graham B.H.,
RA Wang M.C.;
RT "Lysosomal Signaling Promotes Longevity by Adjusting Mitochondrial
RT Activity.";
RL Dev. Cell 48:685-696(2019).
CC -!- FUNCTION: Lysosomal lipase that regulates the metabolism of long-chain
CC fatty acids, primarily in response to nutrient availability
CC (PubMed:21906946, PubMed:23392608, PubMed:25554789, PubMed:30713071).
CC The production of these lipid signaling mediators regulates various
CC processes, including lipolysis, autophagy, mitochondrial beta-
CC oxidation, which in turn control lifespan and adaptation to starvation
CC (PubMed:21906946, PubMed:23392608, PubMed:25554789, PubMed:30713071).
CC In response to fasting, promotes the production of omega-6
CC polyunsaturated fatty acids (PUFAs), which in turn activates autophagy
CC resulting in lifespan extension (PubMed:23392608). Produces
CC oleoylethanolamide (OEA), a ligand for the lysosomal lipid chaperone
CC lbp-8 which translocates into the nucleus where it activates the
CC transcription of genes promoting longevity and activation of
CC mitochondrial beta oxidation (PubMed:25554789, PubMed:30713071).
CC {ECO:0000269|PubMed:21906946, ECO:0000269|PubMed:23392608,
CC ECO:0000269|PubMed:25554789, ECO:0000269|PubMed:30713071}.
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:0000305|PubMed:21906946};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-
CC octadecenoate + di-(9Z)-octadecenoylglycerol + H(+);
CC Xref=Rhea:RHEA:38575, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:53753, ChEBI:CHEBI:75945;
CC Evidence={ECO:0000305|PubMed:25554789};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is acidic. {ECO:0000305|PubMed:25554789};
CC -!- SUBCELLULAR LOCATION: Lysosome lumen {ECO:0000269|PubMed:25554789}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000312|WormBase:K04A8.5a};
CC IsoId=Q94252-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:K04A8.5b};
CC IsoId=Q94252-2; Sequence=VSP_060544;
CC -!- DEVELOPMENTAL STAGE: Expressed in all larval stages. Expression
CC decreases in adults. {ECO:0000269|PubMed:28503130}.
CC -!- INDUCTION: Up-regulated in the intestine by fasting.
CC {ECO:0000269|PubMed:23392608, ECO:0000269|PubMed:23604316}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown has no effect on global
CC lipase activity (PubMed:21906946). In a glp-1 (e2141) mutant background
CC which lacks a germline, reduces the increase in both lipase activity
CC and autophagy (PubMed:21906946). {ECO:0000269|PubMed:21906946}.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. Lipase family.
CC {ECO:0000255|PIRNR:PIRNR000862}.
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DR EMBL; BX284605; CCD68856.1; -; Genomic_DNA.
DR EMBL; BX284605; CTQ86835.1; -; Genomic_DNA.
DR PIR; G89074; G89074.
DR RefSeq; NP_001300136.1; NM_001313207.1. [Q94252-2]
DR RefSeq; NP_504662.1; NM_072261.3. [Q94252-1]
DR AlphaFoldDB; Q94252; -.
DR SMR; Q94252; -.
DR STRING; 6239.K04A8.5; -.
DR ESTHER; caeel-K04A8.5; Acidic_Lipase.
DR MEROPS; S33.B07; -.
DR PaxDb; Q94252; -.
DR EnsemblMetazoa; K04A8.5a.1; K04A8.5a.1; WBGene00019376. [Q94252-1]
DR EnsemblMetazoa; K04A8.5b.1; K04A8.5b.1; WBGene00019376. [Q94252-2]
DR GeneID; 179046; -.
DR KEGG; cel:CELE_K04A8.5; -.
DR UCSC; K04A8.5; c. elegans. [Q94252-1]
DR CTD; 179046; -.
DR WormBase; K04A8.5a; CE11708; WBGene00019376; lipl-4. [Q94252-1]
DR WormBase; K04A8.5b; CE50646; WBGene00019376; lipl-4.
DR eggNOG; KOG2624; Eukaryota.
DR HOGENOM; CLU_010974_0_3_1; -.
DR InParanoid; Q94252; -.
DR OMA; YSAYSFH; -.
DR OrthoDB; 651396at2759; -.
DR PhylomeDB; Q94252; -.
DR Reactome; R-CEL-192456; Digestion of dietary lipid.
DR Reactome; R-CEL-6809371; Formation of the cornified envelope.
DR PRO; PR:Q94252; -.
DR Proteomes; UP000001940; Chromosome V.
DR Bgee; WBGene00019376; Expressed in larva and 1 other tissue.
DR GO; GO:0005737; C:cytoplasm; IDA:CACAO.
DR GO; GO:0043202; C:lysosomal lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0004806; F:triglyceride lipase activity; IMP:WormBase.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:WormBase.
DR GO; GO:0042759; P:long-chain fatty acid biosynthetic process; IMP:UniProtKB.
DR GO; GO:0010508; P:positive regulation of autophagy; IDA:CACAO.
DR GO; GO:0016239; P:positive regulation of macroautophagy; IMP:WormBase.
DR GO; GO:0019433; P:triglyceride catabolic process; IMP:WormBase.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR006693; AB_hydrolase_lipase.
DR InterPro; IPR025483; Lipase_euk.
DR Pfam; PF04083; Abhydro_lipase; 1.
DR PIRSF; PIRSF000862; Steryl_ester_lip; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Glycoprotein; Hydrolase; Lipid degradation;
KW Lipid metabolism; Lysosome; Reference proteome; Signal.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..411
FT /note="Lipase lipl-4"
FT /evidence="ECO:0000255"
FT /id="PRO_5004320253"
FT ACT_SITE 177
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PIRSR:PIRSR000862-1"
FT ACT_SITE 352
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PIRSR:PIRSR000862-1"
FT ACT_SITE 384
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PIRSR:PIRSR000862-1"
FT CARBOHYD 51
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 78
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 280
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 335
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT VAR_SEQ 1..157
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_060544"
SQ SEQUENCE 411 AA; 46773 MW; 31EDF03CC7E82B53 CRC64;
MRESISDLMT VMIPLLIILL LSNYSKSVDL EFYLDTPELI KSWGYSVEIY NTTTKDGFIL
ELHRIPYGRE VPTSSDVNNS RPVIFLQHGF LCSSFDWVAN SPHQSAGFVF ADAGFDVWLG
NFRGNTYSRK HVSLNPDKDP KFWDWSWDQI SEYDLPAMIG KALEISGQES LYYTGFSLGT
LTMFAKLSTD PKFSRKIKKY FALAPIGSIK HAHGVFLFLG RHFGKDYEEY VKKHGSDELF
GSSLLFKKIV KYTCGLFDTL EEFCSDITLL FIGTANENWN QTRIPVYLAH TPAGSSSNVM
AHLDQMFSYG GVPTFDMGEE KNLKAYGQKL PPQYNFTGIA DVPIYLFWSD DDWLSTKQDL
EETLFAQLNS QVVQGSFRIE NYNHLHFIWG TNAASQVYNV ITGIILQDDN T
