LYPA1_HUMAN
ID LYPA1_HUMAN Reviewed; 230 AA.
AC O75608; O43202; Q9UQF9;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Acyl-protein thioesterase 1;
DE Short=APT-1;
DE Short=hAPT1;
DE EC=3.1.2.-;
DE AltName: Full=Lysophospholipase 1;
DE AltName: Full=Lysophospholipase I;
DE Short=LPL-I;
DE Short=LysoPLA I;
DE AltName: Full=Palmitoyl-protein hydrolase {ECO:0000305};
DE EC=3.1.2.22 {ECO:0000269|PubMed:22399288};
GN Name=LYPLA1; Synonyms=APT1, LPL1;
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] (ISOFORM 1).
RA Hu G.;
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), X-RAY CRYSTALLOGRAPHY (1.5
RP ANGSTROMS) OF 6-230, SUBUNIT, AND ACTIVE SITE.
RC TISSUE=Testis;
RX PubMed=11080636; DOI=10.1016/s0969-2126(00)00529-3;
RA Devedjiev Y., Dauter Z., Kuznetsov S.R., Jones T.L.Z., Derewenda Z.S.;
RT "Crystal structure of the human acyl protein thioesterase I from a single
RT X-ray data set to 1.5 A.";
RL Structure 8:1137-1146(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for 300
RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor
RT cells.";
RL Genome Res. 10:1546-1560(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow, and Eye;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 127-230 (ISOFORM 1).
RC TISSUE=Brain;
RA Yu W., Sarginson J., Gibbs R.A.;
RL Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP SER-119.
RX PubMed=19439193; DOI=10.1016/j.bbalip.2009.05.001;
RA Hirano T., Kishi M., Sugimoto H., Taguchi R., Obinata H., Ohshima N.,
RA Tatei K., Izumi T.;
RT "Thioesterase activity and subcellular localization of acylprotein
RT thioesterase 1/lysophospholipase 1.";
RL Biochim. Biophys. Acta 1791:797-805(2009).
RN [7]
RP ACTIVITY REGULATION, AND FUNCTION.
RX PubMed=20418879; DOI=10.1038/nchembio.362;
RA Dekker F.J., Rocks O., Vartak N., Menninger S., Hedberg C., Balamurugan R.,
RA Wetzel S., Renner S., Gerauer M., Scholermann B., Rusch M., Kramer J.W.,
RA Rauh D., Coates G.W., Brunsveld L., Bastiaens P.I., Waldmann H.;
RT "Small-molecule inhibition of APT1 affects Ras localization and
RT signaling.";
RL Nat. Chem. Biol. 6:449-456(2010).
RN [8]
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 [9]
RP FUNCTION, CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY.
RX PubMed=21393252; DOI=10.1194/jlr.m013326;
RA Bolen A.L., Naren A.P., Yarlagadda S., Beranova-Giorgianni S., Chen L.,
RA Norman D., Baker D.L., Rowland M.M., Best M.D., Sano T., Tsukahara T.,
RA Liliom K., Igarashi Y., Tigyi G.;
RT "The phospholipase A1 activity of lysophospholipase A-I links platelet
RT activation to LPA production during blood coagulation.";
RL J. Lipid Res. 52:958-970(2011).
RN [10]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=22399288; DOI=10.1074/jbc.m111.335547;
RA Tian L., McClafferty H., Knaus H.G., Ruth P., Shipston M.J.;
RT "Distinct acyl protein transferases and thioesterases control surface
RT expression of calcium-activated potassium channels.";
RL J. Biol. Chem. 287:14718-14725(2012).
RN [11]
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 [12]
RP FUNCTION.
RX PubMed=27481942; DOI=10.1074/jbc.m116.725762;
RA Adachi N., Hess D.T., McLaughlin P., Stamler J.S.;
RT "S-Palmitoylation of a Novel Site in the beta2-Adrenergic Receptor
RT Associated with a Novel Intracellular Itinerary.";
RL J. Biol. Chem. 291:20232-20246(2016).
CC -!- FUNCTION: Acts as a acyl-protein thioesterase (PubMed:19439193,
CC PubMed:20418879). Hydrolyzes fatty acids from S-acylated cysteine
CC residues in proteins such as trimeric G alpha proteins or HRAS
CC (PubMed:20418879). Has depalmitoylating activity toward KCNMA1
CC (PubMed:22399288). Could also depalmitoylate ADRB2 (PubMed:27481942).
CC Acts as a lysophospholipase and hydrolyzes lysophosphatidylcholine
CC (lyso-PC) (PubMed:19439193). Also hydrolyzes
CC lysophosphatidylethanolamine (lyso-PE), lysophosphatidylinositol (lyso-
CC PI) and lysophosphatidylserine (lyso-PS) (By similarity). Has much
CC higher thioesterase activity than lysophospholipase activity
CC (PubMed:19439193). Contributes to the production of lysophosphatidic
CC acid (LPA) during blood coagulation by recognizing and cleaving plasma
CC phospholipids to generate lysophospholipids which in turn act as
CC substrates for ENPP2 to produce LPA (PubMed:21393252).
CC {ECO:0000250|UniProtKB:P70470, ECO:0000269|PubMed:19439193,
CC ECO:0000269|PubMed:20418879, ECO:0000269|PubMed:21393252,
CC ECO:0000269|PubMed:22399288, ECO:0000269|PubMed:27481942}.
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:22399288};
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:19439193};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40436;
CC Evidence={ECO:0000305|PubMed:19439193};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1-(9Z-octadecenoyl)-2-acyl-sn-glycero-3-phosphocholine + H2O
CC = (9Z)-octadecenoate + a 2-acyl-sn-glycero-3-phosphocholine + H(+);
CC Xref=Rhea:RHEA:41720, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:57875, ChEBI:CHEBI:78421;
CC Evidence={ECO:0000269|PubMed:21393252};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41721;
CC Evidence={ECO:0000305|PubMed:21393252};
CC -!- ACTIVITY REGULATION: Inhibited by palmostatin-B, leading to impair
CC depalmitoylating of Ras. {ECO:0000269|PubMed:20418879}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=27.3 uM for lysophosphatidylcholine for lysophospholipase activity
CC {ECO:0000269|PubMed:19439193};
CC KM=3.49 uM for thioesterase activity {ECO:0000269|PubMed:19439193};
CC Vmax=1.62 umol/min/mg enzyme toward lysophosphatidylcholine for
CC lysophospholipase activity {ECO:0000269|PubMed:19439193};
CC Vmax=27.3 umol/min/mg enzyme for thioesterase activity
CC {ECO:0000269|PubMed:19439193};
CC pH dependence:
CC Optimum pH is 7.4 for the thioesterase activity.
CC {ECO:0000269|PubMed:19439193};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:11080636}.
CC -!- INTERACTION:
CC O75608; Q08379: GOLGA2; NbExp=3; IntAct=EBI-1052185, EBI-618309;
CC O75608; Q5VUG0: SFMBT2; NbExp=3; IntAct=EBI-1052185, EBI-12025260;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19439193}. Cell
CC membrane {ECO:0000269|PubMed:19439193}. Nucleus membrane
CC {ECO:0000269|PubMed:19439193}. Endoplasmic reticulum
CC {ECO:0000269|PubMed:19439193}. Note=Shows predominantly a cytoplasmic
CC localization with a weak expression in the cell membrane, nuclear
CC membrane and endoplasmic reticulum. {ECO:0000269|PubMed:19439193}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O75608-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O75608-2; Sequence=VSP_009196;
CC -!- TISSUE SPECIFICITY: Platelets. {ECO:0000269|PubMed:21393252}.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. AB hydrolase 2
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB88180.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF081281; AAC31610.1; -; mRNA.
DR EMBL; AF291053; AAG10063.1; -; mRNA.
DR EMBL; AF077198; AAD26993.1; -; mRNA.
DR EMBL; AF077199; AAD26994.1; -; mRNA.
DR EMBL; BC008652; AAH08652.1; -; mRNA.
DR EMBL; BC010397; AAH10397.1; -; mRNA.
DR EMBL; AF035293; AAB88180.1; ALT_INIT; mRNA.
DR CCDS; CCDS6157.1; -. [O75608-1]
DR CCDS; CCDS64899.1; -. [O75608-2]
DR RefSeq; NP_001266285.1; NM_001279356.1.
DR RefSeq; NP_001266286.1; NM_001279357.1. [O75608-2]
DR RefSeq; NP_001266287.1; NM_001279358.1.
DR RefSeq; NP_001266288.1; NM_001279359.1.
DR RefSeq; NP_001266289.1; NM_001279360.1.
DR RefSeq; NP_006321.1; NM_006330.3. [O75608-1]
DR PDB; 1FJ2; X-ray; 1.50 A; A/B=6-230.
DR PDB; 5SYM; X-ray; 1.55 A; A/B=1-230.
DR PDB; 6QGN; X-ray; 2.10 A; A/B/C/D=1-230.
DR PDB; 6QGO; X-ray; 2.60 A; B/C=1-230.
DR PDB; 6QGQ; X-ray; 2.60 A; A/B/C/D=1-230.
DR PDB; 6QGS; X-ray; 2.75 A; A/B/C/D/E/F=1-230.
DR PDBsum; 1FJ2; -.
DR PDBsum; 5SYM; -.
DR PDBsum; 6QGN; -.
DR PDBsum; 6QGO; -.
DR PDBsum; 6QGQ; -.
DR PDBsum; 6QGS; -.
DR AlphaFoldDB; O75608; -.
DR SMR; O75608; -.
DR BioGRID; 115701; 82.
DR IntAct; O75608; 12.
DR STRING; 9606.ENSP00000320043; -.
DR BindingDB; O75608; -.
DR ChEMBL; CHEMBL1681631; -.
DR SwissLipids; SLP:000000734; -.
DR ESTHER; human-LYPLA1; LYsophospholipase_carboxylesterase.
DR MEROPS; S09.941; -.
DR GlyGen; O75608; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O75608; -.
DR PhosphoSitePlus; O75608; -.
DR SwissPalm; O75608; -.
DR BioMuta; LYPLA1; -.
DR OGP; O75608; -.
DR CPTAC; CPTAC-536; -.
DR CPTAC; CPTAC-537; -.
DR EPD; O75608; -.
DR jPOST; O75608; -.
DR MassIVE; O75608; -.
DR MaxQB; O75608; -.
DR PaxDb; O75608; -.
DR PeptideAtlas; O75608; -.
DR PRIDE; O75608; -.
DR ProteomicsDB; 50117; -. [O75608-1]
DR ProteomicsDB; 50118; -. [O75608-2]
DR Antibodypedia; 24492; 314 antibodies from 32 providers.
DR DNASU; 10434; -.
DR Ensembl; ENST00000316963.8; ENSP00000320043.3; ENSG00000120992.18. [O75608-1]
DR Ensembl; ENST00000343231.10; ENSP00000344477.6; ENSG00000120992.18. [O75608-2]
DR GeneID; 10434; -.
DR KEGG; hsa:10434; -.
DR MANE-Select; ENST00000316963.8; ENSP00000320043.3; NM_006330.4; NP_006321.1.
DR UCSC; uc003xrz.5; human. [O75608-1]
DR CTD; 10434; -.
DR DisGeNET; 10434; -.
DR GeneCards; LYPLA1; -.
DR HGNC; HGNC:6737; LYPLA1.
DR HPA; ENSG00000120992; Low tissue specificity.
DR MIM; 605599; gene.
DR neXtProt; NX_O75608; -.
DR OpenTargets; ENSG00000120992; -.
DR PharmGKB; PA30499; -.
DR VEuPathDB; HostDB:ENSG00000120992; -.
DR eggNOG; KOG2112; Eukaryota.
DR GeneTree; ENSGT00940000154185; -.
DR InParanoid; O75608; -.
DR OMA; QPIGGIM; -.
DR PhylomeDB; O75608; -.
DR TreeFam; TF314619; -.
DR BRENDA; 3.1.2.22; 2681.
DR PathwayCommons; O75608; -.
DR Reactome; R-HSA-203615; eNOS activation.
DR Reactome; R-HSA-9648002; RAS processing.
DR SignaLink; O75608; -.
DR BioGRID-ORCS; 10434; 29 hits in 1073 CRISPR screens.
DR ChiTaRS; LYPLA1; human.
DR EvolutionaryTrace; O75608; -.
DR GeneWiki; LYPLA1; -.
DR GenomeRNAi; 10434; -.
DR Pharos; O75608; Tchem.
DR PRO; PR:O75608; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; O75608; protein.
DR Bgee; ENSG00000120992; Expressed in penis and 211 other tissues.
DR ExpressionAtlas; O75608; baseline and differential.
DR Genevisible; O75608; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0052689; F:carboxylic ester hydrolase activity; IBA:GO_Central.
DR GO; GO:0016298; F:lipase activity; IDA:CACAO.
DR GO; GO:0004622; F:lysophospholipase activity; IDA:UniProtKB.
DR GO; GO:0008474; F:palmitoyl-(protein) hydrolase activity; IDA:UniProtKB.
DR GO; GO:0004620; F:phospholipase activity; IDA:UniProtKB.
DR GO; GO:0006631; P:fatty acid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0042997; P:negative regulation of Golgi to plasma membrane protein transport; IEA:Ensembl.
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; Acetylation; Alternative splicing; Cell membrane; Cytoplasm;
KW Endoplasmic reticulum; Fatty acid metabolism; Hydrolase; Lipid metabolism;
KW Membrane; Nucleus; Reference proteome.
FT CHAIN 1..230
FT /note="Acyl-protein thioesterase 1"
FT /id="PRO_0000102267"
FT ACT_SITE 119
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:19439193"
FT ACT_SITE 174
FT /note="Charge relay system"
FT /evidence="ECO:0000305|PubMed:11080636"
FT ACT_SITE 208
FT /note="Charge relay system"
FT /evidence="ECO:0000305|PubMed:11080636"
FT MOD_RES 224
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P97823"
FT VAR_SEQ 57..72
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11042152"
FT /id="VSP_009196"
FT VARIANT 153
FT /note="P -> S (in dbSNP:rs11549448)"
FT /id="VAR_060991"
FT MUTAGEN 119
FT /note="S->A: Loss of thioesterase and lysophospholipase
FT activity."
FT /evidence="ECO:0000269|PubMed:19439193"
FT CONFLICT 127..131
FT /note="YTALT -> SLIRG (in Ref. 5; AAB88180)"
FT /evidence="ECO:0000305"
FT STRAND 12..14
FT /evidence="ECO:0007829|PDB:1FJ2"
FT STRAND 17..19
FT /evidence="ECO:0007829|PDB:5SYM"
FT STRAND 21..27
FT /evidence="ECO:0007829|PDB:1FJ2"
FT STRAND 30..32
FT /evidence="ECO:0007829|PDB:1FJ2"
FT HELIX 34..42
FT /evidence="ECO:0007829|PDB:1FJ2"
FT STRAND 49..53
FT /evidence="ECO:0007829|PDB:1FJ2"
FT STRAND 58..60
FT /evidence="ECO:0007829|PDB:1FJ2"
FT HELIX 62..64
FT /evidence="ECO:0007829|PDB:1FJ2"
FT STRAND 68..70
FT /evidence="ECO:0007829|PDB:1FJ2"
FT HELIX 86..105
FT /evidence="ECO:0007829|PDB:1FJ2"
FT HELIX 110..112
FT /evidence="ECO:0007829|PDB:1FJ2"
FT STRAND 113..118
FT /evidence="ECO:0007829|PDB:1FJ2"
FT HELIX 120..129
FT /evidence="ECO:0007829|PDB:1FJ2"
FT STRAND 137..143
FT /evidence="ECO:0007829|PDB:1FJ2"
FT HELIX 149..151
FT /evidence="ECO:0007829|PDB:1FJ2"
FT TURN 160..163
FT /evidence="ECO:0007829|PDB:1FJ2"
FT STRAND 166..171
FT /evidence="ECO:0007829|PDB:1FJ2"
FT STRAND 175..177
FT /evidence="ECO:0007829|PDB:1FJ2"
FT HELIX 179..192
FT /evidence="ECO:0007829|PDB:1FJ2"
FT HELIX 195..197
FT /evidence="ECO:0007829|PDB:1FJ2"
FT STRAND 198..203
FT /evidence="ECO:0007829|PDB:1FJ2"
FT HELIX 212..225
FT /evidence="ECO:0007829|PDB:1FJ2"
SQ SEQUENCE 230 AA; 24670 MW; 90C0522F765F1AC6 CRC64;
MCGNNMSTPL PAIVPAARKA TAAVIFLHGL GDTGHGWAEA FAGIRSSHIK YICPHAPVRP
VTLNMNVAMP SWFDIIGLSP DSQEDESGIK QAAENIKALI DQEVKNGIPS NRIILGGFSQ
GGALSLYTAL TTQQKLAGVT ALSCWLPLRA SFPQGPIGGA NRDISILQCH GDCDPLVPLM
FGSLTVEKLK TLVNPANVTF KTYEGMMHSS CQQEMMDVKQ FIDKLLPPID
