Acyl-protein thioesterase 1 (LYPLA1)
The protein contains 230 amino acids for an estimated molecular weight of 24670 Da.
Acts as a 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). Has depalmitoylating activity toward KCNMA1 (PubMed:22399288). Could also depalmitoylate ADRB2 (PubMed:27481942). 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). (updated: Oct. 7, 2020)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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| Variant | Description |
|---|---|
| dbSNP:rs11549448 |
Biological Process
Fatty acid metabolic process
MAPK cascade
Negative regulation of Golgi to plasma membrane protein transport
Nitric oxide metabolic process
Protein depalmitoylation
Regulation of nitric-oxide synthase activity
Small molecule metabolic process
The reference OMIM entry for this protein is 605599
Lysophospholipase i; lypla1
Acyl protein thioesterase 1; apt1
CLONING
Lysophospholipids (LysoPLs) are detergent-like intermediates in phospholipid metabolism. Increased LysoPL levels have been detected in a variety of diseases, including atherosclerosis and hyperlipidemia. In some cases, increased levels of LysoPLs are hypothesized to result from a dysfunction of LysoPL-regulating enzymes, including lysophospholipases, which act on biologic membranes to regulate the level of LysoPLs by hydrolysis. In a database search for sequences homologous to mouse Lypla1, Wang et al. (1999) identified human LYPLA1 sequence fragments. They used RT-PCR on normal human brain RNA to amplify a LYPLA1 cDNA encoding a 230-amino acid, 28-kD protein that shares 92% sequence identity with the mouse protein. The catalytic triad of LYPLA1 (ser119, asp174, his208) is conserved between human and mouse, leading Wang et al. (1999) to conclude that the catalytic mechanism is also conserved between these species. Using Northern blot analysis, Wang et al. (1999) detected expression of LYPLA1 at varying levels in diverse tissues including heart, placenta, skeletal muscle, liver, pancreas, kidney, brain, lung, testis, adrenal, salivary gland, trachea, and colon. Expression was also detected in a broad range of fetal tissues. Western blot analysis supported the broad expression of LYPLA1.GENE FUNCTION
Wang et al. (1999) purified a recombinant LYPLA1 protein for kinetic characterization and demonstrated that the catalytic activity of LYPLA1 exhibits saturation kinetics. LYPLA1 hydrolyzes both monomeric and micellar substrates. LYPLA1 appears first to bind nonspecifically to the mixed micellar surface and then specifically to substrate presented on the surface. The activity of LYPLA1 is irreversibly inhibited by methyl arachindonl fluorophosphonate, which the authors thought was likely due to the covalent modification of the enzyme at the active site ser119. No other enzymatic activities were detected. Wang et al. (1999) concluded that LYPLA1 is a lysophospholipid-specific lysophospholipase. In mouse, the NAD-synthesizing enzyme Nmnat2 (608701) is required for axon survival in vitro as well as axon growth and maintenance in vivo; palmitoylation of a central double-cysteine motif in Nmnat2 is required for axonal transport in primary cultured neurons. Using mouse superior cervical ganglia cultures, NSC34 mouse motoneurons, and HEK293 cells, Milde and Coleman (2014) found that several Zdhhc family palmitoyltransferases catalyzed Nmnat2 cysteine palmitoylation and membrane localization. Endogenous Zdhhc17 (607799) appeared to have a predominant role in this reaction. Conversely, the cytosolic thioesterases Apt1 (LYPLA1) and Apt2 (LYPLA2; 616143) were equally active in reducing Nmnat2 palmitoylation. Depalmitoylation was required, but not sufficient, to release Nmnat2 from cell membranes.MAPPING
The International Radiation Hybrid Mapping Consortium mapped the LYPLA1 gene to chromosome 8 (TMAP RH80504). ... More on the omim web site
Oct. 20, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
April 25, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 605599 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed