LYPA2_HUMAN
ID LYPA2_HUMAN Reviewed; 231 AA.
AC O95372; Q7Z4Z2;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Acyl-protein thioesterase 2;
DE Short=APT-2;
DE EC=3.1.2.- {ECO:0000269|PubMed:28826475};
DE AltName: Full=Lysophospholipase II;
DE Short=LPL-II;
DE Short=LysoPLA II;
DE AltName: Full=Palmitoyl-protein hydrolase {ECO:0000305};
DE EC=3.1.2.22 {ECO:0000269|PubMed:28826475};
GN Name=LYPLA2; Synonyms=APT2;
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].
RC TISSUE=Testis;
RA Kuznetsov S.R., Jones T.L.Z.;
RL Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Yue P., Yu L., Tu Q., Ding J.B., Fu S.N., Zhao S.Y.;
RT "Cloning and expression of a novel human cDNA homology to murine
RT lysophospholipase I mRNA.";
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon, and Placenta;
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 [5]
RP FUNCTION IN DEACYLATION OF GAP43.
RX PubMed=21152083; DOI=10.1371/journal.pone.0015045;
RA Tomatis V.M., Trenchi A., Gomez G.A., Daniotti J.L.;
RT "Acyl-protein thioesterase 2 catalyzes the deacylation of peripheral
RT membrane-associated GAP-43.";
RL PLoS ONE 5:E15045-E15045(2010).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, ACTIVITY REGULATION, AND TISSUE SPECIFICITY.
RX PubMed=25301951; DOI=10.1074/jbc.m114.582353;
RA Manna J.D., Wepy J.A., Hsu K.L., Chang J.W., Cravatt B.F., Marnett L.J.;
RT "Identification of the major prostaglandin glycerol ester hydrolase in
RT human cancer cells.";
RL J. Biol. Chem. 289:33741-33753(2014).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, PALMITOYLATION AT CYS-2, AND MUTAGENESIS OF
RP CYS-2 AND SER-122.
RX PubMed=28826475; DOI=10.7554/elife.27826;
RA Abrami L., Dallavilla T., Sandoz P.A., Demir M., Kunz B., Savoglidis G.,
RA Hatzimanikatis V., van der Goot F.G.;
RT "Identification and dynamics of the human ZDHHC16-ZDHHC6 palmitoylation
RT cascade.";
RL Elife 6:0-0(2017).
CC -!- FUNCTION: Acts as a acyl-protein thioesterase hydrolyzing fatty acids
CC from S-acylated cysteine residues in proteins such as trimeric G alpha
CC proteins, GAP43, ZDHHC6 or HRAS (PubMed:21152083, PubMed:28826475).
CC Deacylates GAP43 (PubMed:21152083). Mediates depalmitoylation of ZDHHC6
CC (PubMed:28826475). Has lysophospholipase activity (PubMed:25301951).
CC Hydrolyzes prostaglandin glycerol esters (PG-Gs) in the following order
CC prostaglandin D2-glycerol ester (PGD2-G) > prostaglandin E2 glycerol
CC ester (PGE2-G) > prostaglandin F2-alpha-glycerol ester (PGF2-alpha-G)
CC (PubMed:25301951). Hydrolyzes 1-arachidonoylglycerol but not 2-
CC arachidonoylglycerol or arachidonoylethanolamide (PubMed:25301951).
CC {ECO:0000269|PubMed:21152083, ECO:0000269|PubMed:25301951,
CC ECO:0000269|PubMed:28826475}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + S-hexadecanoyl-L-cysteinyl-[protein] = H(+) +
CC hexadecanoate + L-cysteinyl-[protein]; Xref=Rhea:RHEA:19233,
CC Rhea:RHEA-COMP:10131, Rhea:RHEA-COMP:11032, ChEBI:CHEBI:7896,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29950,
CC ChEBI:CHEBI:74151; EC=3.1.2.22;
CC Evidence={ECO:0000269|PubMed:28826475};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + prostaglandin E2 1-glyceryl ester = glycerol + H(+) +
CC prostaglandin E2; Xref=Rhea:RHEA:48296, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:90230,
CC ChEBI:CHEBI:606564; Evidence={ECO:0000269|PubMed:25301951};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48297;
CC Evidence={ECO:0000305|PubMed:25301951};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-sn-glycero-3-phosphocholine + H2O = H(+) +
CC hexadecanoate + sn-glycerol 3-phosphocholine; Xref=Rhea:RHEA:40435,
CC ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16870, ChEBI:CHEBI:72998;
CC Evidence={ECO:0000269|PubMed:25301951};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40436;
CC Evidence={ECO:0000305|PubMed:25301951};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octadecanoyl-sn-glycero-3-phosphocholine + H2O = H(+) +
CC octadecanoate + sn-glycerol 3-phosphocholine; Xref=Rhea:RHEA:40887,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16870,
CC ChEBI:CHEBI:25629, ChEBI:CHEBI:73858;
CC Evidence={ECO:0000269|PubMed:25301951};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40888;
CC Evidence={ECO:0000305|PubMed:25301951};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-sn-glycero-3-phosphate + H2O = H(+) +
CC hexadecanoate + sn-glycerol 3-phosphate; Xref=Rhea:RHEA:49092,
CC ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57518, ChEBI:CHEBI:57597;
CC Evidence={ECO:0000269|PubMed:25301951};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49093;
CC Evidence={ECO:0000305|PubMed:25301951};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-sn-glycero-3-phospho-L-serine + H2O = H(+) +
CC hexadecanoate + sn-glycero-3-phospho-L-serine; Xref=Rhea:RHEA:44552,
CC ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:64765, ChEBI:CHEBI:75020;
CC Evidence={ECO:0000269|PubMed:25301951};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44553;
CC Evidence={ECO:0000305|PubMed:25301951};
CC -!- ACTIVITY REGULATION: Inhibited by compound 1 or (5,5-Dioxido-4H-
CC thieno[3,2-c]thiochromen-2-yl)(4-(4-methoxyphenyl)piperazin-1-
CC yl)methanone. {ECO:0000269|PubMed:25301951}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=67 uM for prostaglandin D2-glycerol ester (PGD2-G)
CC {ECO:0000269|PubMed:25301951};
CC KM=13 uM for prostaglandin E2-glycerol ester (PGE2-G)
CC {ECO:0000269|PubMed:25301951};
CC KM=5 uM for prostaglandin F2-alpha-glycerol ester (PGF2-alpha-G)
CC {ECO:0000269|PubMed:25301951};
CC KM=8.3 uM for Lyso-PC (C16:0) {ECO:0000269|PubMed:25301951};
CC KM=7.8 uM for Lyso-PC (C18:0) {ECO:0000269|PubMed:25301951};
CC KM=40.7 uM for Lyso-PC (C18:1) {ECO:0000269|PubMed:25301951};
CC KM=11.1 uM for Lyso-PA (C16:0) {ECO:0000269|PubMed:25301951};
CC KM=13.3 uM for Lyso-PS (C16:0) {ECO:0000269|PubMed:25301951};
CC KM=7.6 uM for 1-arachidonoylglycerol {ECO:0000269|PubMed:25301951};
CC -!- INTERACTION:
CC O95372; Q0VD86: INCA1; NbExp=3; IntAct=EBI-715999, EBI-6509505;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:25301951}.
CC -!- TISSUE SPECIFICITY: Expressed in various breast cancer cell lines.
CC {ECO:0000269|PubMed:25301951}.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. AB hydrolase 2
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAP97210.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF098668; AAC72844.1; -; mRNA.
DR EMBL; AF090423; AAP97210.1; ALT_FRAME; mRNA.
DR EMBL; AL031295; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC017034; AAH17034.1; -; mRNA.
DR EMBL; BC017193; AAH17193.1; -; mRNA.
DR CCDS; CCDS241.1; -.
DR RefSeq; NP_009191.1; NM_007260.2.
DR PDB; 5SYN; X-ray; 1.64 A; A/B/C/D=1-231.
DR PDB; 6BJE; X-ray; 2.70 A; A/B=10-231.
DR PDBsum; 5SYN; -.
DR PDBsum; 6BJE; -.
DR AlphaFoldDB; O95372; -.
DR SMR; O95372; -.
DR BioGRID; 116444; 50.
DR IntAct; O95372; 15.
DR MINT; O95372; -.
DR STRING; 9606.ENSP00000363638; -.
DR BindingDB; O95372; -.
DR ChEMBL; CHEMBL1932891; -.
DR SwissLipids; SLP:000001479; -.
DR ESTHER; human-LYPLA2; LYsophospholipase_carboxylesterase.
DR MEROPS; S09.025; -.
DR iPTMnet; O95372; -.
DR MetOSite; O95372; -.
DR PhosphoSitePlus; O95372; -.
DR SwissPalm; O95372; -.
DR BioMuta; LYPLA2; -.
DR OGP; O95372; -.
DR EPD; O95372; -.
DR jPOST; O95372; -.
DR MassIVE; O95372; -.
DR MaxQB; O95372; -.
DR PaxDb; O95372; -.
DR PeptideAtlas; O95372; -.
DR PRIDE; O95372; -.
DR ProteomicsDB; 50827; -.
DR Antibodypedia; 30196; 176 antibodies from 25 providers.
DR DNASU; 11313; -.
DR Ensembl; ENST00000374514.8; ENSP00000363638.3; ENSG00000011009.11.
DR GeneID; 11313; -.
DR KEGG; hsa:11313; -.
DR MANE-Select; ENST00000374514.8; ENSP00000363638.3; NM_007260.3; NP_009191.1.
DR UCSC; uc001bht.4; human.
DR CTD; 11313; -.
DR DisGeNET; 11313; -.
DR GeneCards; LYPLA2; -.
DR HGNC; HGNC:6738; LYPLA2.
DR HPA; ENSG00000011009; Low tissue specificity.
DR neXtProt; NX_O95372; -.
DR OpenTargets; ENSG00000011009; -.
DR PharmGKB; PA30500; -.
DR VEuPathDB; HostDB:ENSG00000011009; -.
DR eggNOG; KOG2112; Eukaryota.
DR GeneTree; ENSGT00940000156197; -.
DR HOGENOM; CLU_049413_3_5_1; -.
DR InParanoid; O95372; -.
DR OMA; WYDILAM; -.
DR OrthoDB; 1373549at2759; -.
DR PhylomeDB; O95372; -.
DR TreeFam; TF314619; -.
DR PathwayCommons; O95372; -.
DR Reactome; R-HSA-373760; L1CAM interactions.
DR SignaLink; O95372; -.
DR SIGNOR; O95372; -.
DR BioGRID-ORCS; 11313; 11 hits in 1074 CRISPR screens.
DR ChiTaRS; LYPLA2; human.
DR GenomeRNAi; 11313; -.
DR Pharos; O95372; Tchem.
DR PRO; PR:O95372; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O95372; protein.
DR Bgee; ENSG00000011009; Expressed in lower esophagus mucosa and 188 other tissues.
DR ExpressionAtlas; O95372; baseline and differential.
DR Genevisible; O95372; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005795; C:Golgi stack; IEA:Ensembl.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0052689; F:carboxylic ester hydrolase activity; IBA:GO_Central.
DR GO; GO:0004622; F:lysophospholipase activity; IDA:UniProtKB.
DR GO; GO:0008474; F:palmitoyl-(protein) hydrolase activity; IDA:UniProtKB.
DR GO; GO:0046464; P:acylglycerol catabolic process; IDA:UniProtKB.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0006631; P:fatty acid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:1905344; P:prostaglandin catabolic process; IDA:UniProtKB.
DR GO; GO:0002084; P:protein depalmitoylation; IDA:UniProtKB.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR003140; PLipase/COase/thioEstase.
DR Pfam; PF02230; Abhydrolase_2; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Fatty acid metabolism; Hydrolase;
KW Lipid metabolism; Lipoprotein; Palmitate; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..231
FT /note="Acyl-protein thioesterase 2"
FT /id="PRO_0000102271"
FT ACT_SITE 122
FT /note="Charge relay system"
FT /evidence="ECO:0000305|PubMed:28826475"
FT ACT_SITE 176
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:O75608"
FT ACT_SITE 210
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:O75608"
FT MOD_RES 82
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QYL8"
FT LIPID 2
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:28826475"
FT MUTAGEN 2
FT /note="C->A: Abolishes palmitoylation."
FT /evidence="ECO:0000269|PubMed:28826475"
FT MUTAGEN 122
FT /note="S->A: Abolishes ability to mediate depalmitoylation
FT of ZDHHC6."
FT /evidence="ECO:0000269|PubMed:28826475"
FT STRAND 11..17
FT /evidence="ECO:0007829|PDB:5SYN"
FT STRAND 25..30
FT /evidence="ECO:0007829|PDB:5SYN"
FT STRAND 33..35
FT /evidence="ECO:0007829|PDB:6BJE"
FT HELIX 38..45
FT /evidence="ECO:0007829|PDB:5SYN"
FT STRAND 52..57
FT /evidence="ECO:0007829|PDB:5SYN"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:5SYN"
FT HELIX 65..67
FT /evidence="ECO:0007829|PDB:5SYN"
FT STRAND 71..73
FT /evidence="ECO:0007829|PDB:5SYN"
FT HELIX 89..108
FT /evidence="ECO:0007829|PDB:5SYN"
FT HELIX 113..115
FT /evidence="ECO:0007829|PDB:5SYN"
FT STRAND 116..121
FT /evidence="ECO:0007829|PDB:5SYN"
FT HELIX 123..133
FT /evidence="ECO:0007829|PDB:5SYN"
FT STRAND 140..146
FT /evidence="ECO:0007829|PDB:5SYN"
FT HELIX 152..154
FT /evidence="ECO:0007829|PDB:5SYN"
FT TURN 155..158
FT /evidence="ECO:0007829|PDB:5SYN"
FT HELIX 161..165
FT /evidence="ECO:0007829|PDB:5SYN"
FT STRAND 167..173
FT /evidence="ECO:0007829|PDB:5SYN"
FT STRAND 177..179
FT /evidence="ECO:0007829|PDB:5SYN"
FT HELIX 181..192
FT /evidence="ECO:0007829|PDB:5SYN"
FT HELIX 197..199
FT /evidence="ECO:0007829|PDB:5SYN"
FT STRAND 200..205
FT /evidence="ECO:0007829|PDB:5SYN"
FT HELIX 214..227
FT /evidence="ECO:0007829|PDB:5SYN"
SQ SEQUENCE 231 AA; 24737 MW; 813C9C71757C5135 CRC64;
MCGNTMSVPL LTDAATVSGA ERETAAVIFL HGLGDTGHSW ADALSTIRLP HVKYICPHAP
RIPVTLNMKM VMPSWFDLMG LSPDAPEDEA GIKKAAENIK ALIEHEMKNG IPANRIVLGG
FSQGGALSLY TALTCPHPLA GIVALSCWLP LHRAFPQAAN GSAKDLAILQ CHGELDPMVP
VRFGALTAEK LRSVVTPARV QFKTYPGVMH SSCPQEMAAV KEFLEKLLPP V
