LYPA1_MOUSE
ID LYPA1_MOUSE Reviewed; 230 AA.
AC P97823; Q3TJZ0; Q7TPX1; Q8BWM6;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Acyl-protein thioesterase 1;
DE Short=APT-1;
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:0000250|UniProtKB:O75608};
GN Name=Lypla1; Synonyms=Apt1, Pla1a;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 98-105; 150-162
RP AND 191-201, MUTAGENESIS OF SER-119, FUNCTION, AND ACTIVE SITE.
RC TISSUE=Macrophage;
RX PubMed=9139730; DOI=10.1074/jbc.272.19.12723;
RA Wang A., Deems R.A., Dennis E.A.;
RT "Cloning, expression, and catalytic mechanism of murine lysophospholipase
RT I.";
RL J. Biol. Chem. 272:12723-12729(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Kidney, and Pancreas;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Kidney, and Osteoblast;
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 [4]
RP PROTEIN SEQUENCE OF 136-149.
RC TISSUE=Brain;
RA Lubec G., Yang J.W., Zigmond M.;
RL Submitted (JUL-2007) to UniProtKB.
RN [5]
RP MUTAGENESIS OF ASP-174 AND HIS-208, AND ACTIVE SITE.
RX PubMed=9268342; DOI=10.1074/jbc.272.35.22030;
RA Wang A., Loo R., Chen Z., Dennis E.A.;
RT "Regiospecificity and catalytic triad of lysophospholipase I.";
RL J. Biol. Chem. 272:22030-22036(1997).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-224, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
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 or HRAS (By similarity). Has depalmitoylating activity toward
CC KCNMA1 (By similarity). Could also depalmitoylate ADRB2 (By
CC similarity). Acts as a lysophospholipase hydrolyzing various
CC lysophospholipids including lysophosphatidylcholine (lyso-PC),
CC lysophosphatidylethanolamine (lyso-PE), lysophosphatidylinositol (lyso-
CC PI) and lysophosphatidylserine (lyso-PS)(PubMed:9139730). Has much
CC higher thioesterase activity than lysophospholipase activity (By
CC similarity). Contributes to the production of lysophosphatidic acid
CC (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 (By similarity).
CC {ECO:0000250|UniProtKB:O75608, ECO:0000250|UniProtKB:P70470,
CC ECO:0000269|PubMed:9139730}.
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:0000250|UniProtKB:O75608};
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:0000250|UniProtKB:O75608};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40436;
CC Evidence={ECO:0000250|UniProtKB:O75608};
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:0000250|UniProtKB:O75608};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41721;
CC Evidence={ECO:0000250|UniProtKB:O75608};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:O75608}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O75608}. Cell
CC membrane {ECO:0000250|UniProtKB:O75608}. Nucleus membrane
CC {ECO:0000250|UniProtKB:O75608}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:O75608}. Note=Shows predominantly a cytoplasmic
CC localization with a weak expression in the cell membrane, nuclear
CC membrane and endoplasmic reticulum. {ECO:0000250|UniProtKB:O75608}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P97823-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P97823-2; Sequence=VSP_009197;
CC -!- MISCELLANEOUS: [Isoform 2]: May be due to an intron retention.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. AB hydrolase 2
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC34318.1; Type=Erroneous initiation; Evidence={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; U89352; AAB48627.1; -; mRNA.
DR EMBL; AK002674; BAB22276.1; -; mRNA.
DR EMBL; AK050549; BAC34318.1; ALT_INIT; mRNA.
DR EMBL; AK146874; BAE27497.1; -; mRNA.
DR EMBL; AK167231; BAE39355.1; -; mRNA.
DR EMBL; BC013536; AAH13536.1; -; mRNA.
DR EMBL; BC052848; AAH52848.1; -; mRNA.
DR CCDS; CCDS14806.1; -. [P97823-1]
DR RefSeq; NP_032892.1; NM_008866.2. [P97823-1]
DR AlphaFoldDB; P97823; -.
DR SMR; P97823; -.
DR BioGRID; 202216; 4.
DR STRING; 10090.ENSMUSP00000027036; -.
DR BindingDB; P97823; -.
DR ChEMBL; CHEMBL3259479; -.
DR ESTHER; mouse-lypla1; LYsophospholipase_carboxylesterase.
DR iPTMnet; P97823; -.
DR PhosphoSitePlus; P97823; -.
DR SwissPalm; P97823; -.
DR EPD; P97823; -.
DR jPOST; P97823; -.
DR MaxQB; P97823; -.
DR PaxDb; P97823; -.
DR PeptideAtlas; P97823; -.
DR PRIDE; P97823; -.
DR ProteomicsDB; 252687; -. [P97823-1]
DR ProteomicsDB; 252688; -. [P97823-2]
DR Antibodypedia; 24492; 314 antibodies from 32 providers.
DR DNASU; 18777; -.
DR Ensembl; ENSMUST00000027036; ENSMUSP00000027036; ENSMUSG00000025903. [P97823-1]
DR Ensembl; ENSMUST00000150971; ENSMUSP00000137248; ENSMUSG00000025903. [P97823-2]
DR GeneID; 18777; -.
DR KEGG; mmu:18777; -.
DR UCSC; uc007afh.1; mouse. [P97823-1]
DR CTD; 10434; -.
DR MGI; MGI:1344588; Lypla1.
DR VEuPathDB; HostDB:ENSMUSG00000025903; -.
DR eggNOG; KOG2112; Eukaryota.
DR GeneTree; ENSGT00940000154185; -.
DR HOGENOM; CLU_049413_3_5_1; -.
DR InParanoid; P97823; -.
DR OMA; QPIGGIM; -.
DR OrthoDB; 1373549at2759; -.
DR PhylomeDB; P97823; -.
DR TreeFam; TF314619; -.
DR Reactome; R-MMU-203615; eNOS activation.
DR Reactome; R-MMU-9648002; RAS processing.
DR BioGRID-ORCS; 18777; 5 hits in 74 CRISPR screens.
DR ChiTaRS; Lypla1; mouse.
DR PRO; PR:P97823; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; P97823; protein.
DR Bgee; ENSMUSG00000025903; Expressed in right kidney and 258 other tissues.
DR ExpressionAtlas; P97823; baseline and differential.
DR Genevisible; P97823; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0031965; C:nuclear membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0052689; F:carboxylic ester hydrolase activity; IBA:GO_Central.
DR GO; GO:0016298; F:lipase activity; ISO:MGI.
DR GO; GO:0004622; F:lysophospholipase activity; ISS:UniProtKB.
DR GO; GO:0008474; F:palmitoyl-(protein) hydrolase activity; IDA:UniProtKB.
DR GO; GO:0004620; F:phospholipase activity; ISS: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; IMP:MGI.
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 Acetylation; Alternative splicing; Cell membrane; Cytoplasm;
KW Direct protein sequencing; Endoplasmic reticulum; Fatty acid metabolism;
KW Hydrolase; Lipid metabolism; Membrane; Nucleus; Reference proteome.
FT CHAIN 1..230
FT /note="Acyl-protein thioesterase 1"
FT /id="PRO_0000102268"
FT ACT_SITE 119
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:9139730"
FT ACT_SITE 174
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:9268342"
FT ACT_SITE 208
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:9268342"
FT MOD_RES 224
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT VAR_SEQ 214..230
FT /note="EMMDVKHFIDKLLPPID -> VGVSGSSE (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_009197"
FT MUTAGEN 119
FT /note="S->A: Abolishes lysophospholipase activity."
FT /evidence="ECO:0000269|PubMed:9139730"
FT MUTAGEN 174
FT /note="D->A: Abolishes lysophospholipase activity."
FT /evidence="ECO:0000269|PubMed:9268342"
FT MUTAGEN 208
FT /note="H->A: Abolishes lysophospholipase activity."
FT /evidence="ECO:0000269|PubMed:9268342"
FT CONFLICT 156
FT /note="P -> L (in Ref. 3; AAH52848)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 230 AA; 24688 MW; 89AF2017AEFC9FAC CRC64;
MCGNNMSAPM PAVVPAARKA TAAVIFLHGL GDTGHGWAEA FAGIKSPHIK YICPHAPVMP
VTLNMNMAMP SWFDIVGLSP DSQEDESGIK QAAETVKALI DQEVKNGIPS NRIILGGFSQ
GGALSLYTAL TTQQKLAGVT ALSCWLPLRA SFSQGPINSA NRDISVLQCH GDCDPLVPLM
FGSLTVERLK ALINPANVTF KIYEGMMHSS CQQEMMDVKH FIDKLLPPID
