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Overview

Uniprot IDO75608
Protein NameAcyl-protein thioesterase 1
Gene NameLYPLA1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
105 ALIDQEVKNGIPSNR
190 SLTVEKLKTLVNPAN

Function

Acts as an acyl-protein thioesterase (PubMed:19439193, PubMed:20418879). Hydrolyzes fatty acids from S-acylated cysteine residues in proteins such as trimeric G alpha proteins or HRAS (PubMed:20418879). Acts as a palmitoyl thioesterase that catalyzes depalmitoylation of proteins, such as ADRB2, KCNMA1 and SQSTM1 (PubMed:22399288, PubMed:27481942, PubMed:37802024). Acts as a negative regulator of autophagy by mediating palmitoylation of SQSTM1, decreasing affinity between SQSTM1 and ATG8 proteins and recruitment of ubiquitinated cargo proteins to autophagosomes (PubMed:37802024). Acts as a lysophospholipase and hydrolyzes lysophosphatidylcholine (lyso-PC) (PubMed:19439193). Also hydrolyzes lysophosphatidylethanolamine (lyso-PE), lysophosphatidylinositol (lyso-PI) and lysophosphatidylserine (lyso-PS) (By similarity). Has much higher thioesterase activity than lysophospholipase activity (PubMed:19439193). Contributes to the production of lysophosphatidic acid (LPA) during blood coagulation by recognizing and cleaving plasma phospholipids to generate lysophospholipids which in turn act as substrates for ENPP2 to produce LPA (PubMed:21393252)

Protein Sequence

10 MCGNNMSTPL 20 PAIVPAARKA 30 TAAVIFLHGL 40 GDTGHGWAEA 50 FAGIRSSHIK 60 YICPHAPVRP 70 VTLNMNVAMP 80 SWFDIIGLSP 90 DSQEDESGIK 100 QAAENIKALI 110 DQEVKNGIPS 120 NRIILGGFSQ 130 GGALSLYTAL 140 TTQQKLAGVT 150 ALSCWLPLRA 160 SFPQGPIGGA 170 NRDISILQCH 180 GDCDPLVPLM 190 FGSLTVEKLK 200 TLVNPANVTF 210 KTYEGMMHSS 220 CQQEMMDVKQ 230 FIDKLLPPID

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0005783 endoplasmic reticulum
Cellular Component GO:0070062 extracellular exosome
Cellular Component GO:0005739 mitochondrion
Cellular Component GO:0031965 nuclear membrane
Cellular Component GO:0005886 plasma membrane
Molecular Function GO:0004620 glycerophospholipase activity
Molecular Function GO:0016298 lipase activity
Molecular Function GO:0008474 palmitoyl-(protein) hydrolase activity
Molecular Function GO:0004622 phosphatidylcholine lysophospholipase A1 activity
Biological Process GO:0006631 fatty acid metabolic process
Biological Process GO:0015908 fatty acid transport
Biological Process GO:1905336 negative regulation of aggrephagy
Biological Process GO:0042997 negative regulation of Golgi to plasma membrane protein transport
Biological Process GO:0002084 protein depalmitoylation

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.