Glutathione S-transferase LANCL1 (LANCL1)
The protein contains 399 amino acids for an estimated molecular weight of 45283 Da.
Functions as glutathione transferase. Catalyzes conjugation of the glutathione (GSH) to artificial substrates 1-chloro-2,4-dinitrobenzene (CDNB) and p-nitrophenyl acetate. Mitigates neuronal oxidative stress during normal postnatal development and in response to oxidative stresses probably through GSH antioxidant defense mechanism (By similarity). May play a role in EPS8 signaling. Binds glutathione (PubMed:19528316). (updated: Jan. 16, 2019)
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.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- 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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- 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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Biological Process
Carbohydrate metabolic process
G protein-coupled receptor signaling pathway
Regulation of neuron apoptotic process
Regulation of oxidative stress-induced neuron death
Cellular Component
Cytoplasm
Extracellular exosome
Integral component of plasma membrane
Nucleus
Plasma membrane
The reference OMIM entry for this protein is 604155
Lanc-like 1; lancl1
Lanthionine-synthetase component c-like 1 g protein-coupled receptor
G protein-coupled receptor 69a; gpr69a
CLONING
By affinity chromatography of solubilized human erythrocyte membrane proteins, Mayer et al. (1998) identified p40, a 40-kD protein that interacts with the C-terminus of the membrane protein stomatin (133090). They used the sequence of p40 peptides to identify partial cDNAs in an EST database, and then cloned cDNAs corresponding to the entire coding region using a PCR strategy. The predicted 399-amino acid protein contains the characteristic features of G protein-coupled receptors (GPCRs), including 7 transmembrane domains. Northern blot analysis revealed that p40 is expressed as a major 4.8-kb mRNA and as a minor 1.9-kb mRNA in all tissues. Dot blot experiments indicated that the highest levels of expression were in brain, spinal cord, testis, pituitary gland, and kidney. Using in situ hybridization to monkey tissues, Mayer et al. (1998) determined that p40 is expressed at high levels in neurons of the brain and spinal cord, in thymocytes, megakaryocytes, and macrophages. Bauer et al. (2000) determined that LANCL1 is not an integral membrane protein, but rather a weakly associated peripheral membrane protein, and is not a GPCR. They found that LANCL1 contains 7 highly conserved hydrophobic repeats and may play a role in peptide modification. Western blot analysis showed that LANCL1 is mainly expressed in brain, testis, ovary, and kidney.GENE FUNCTION
Zhang et al. (2009) showed that LANCL1 exhibited Zn(2+)-dependent glutathione binding. LANCL1 also bound the SH3 domain of mouse Eps8 (600206), but not other SH3-containing proteins. The interaction between LANCL1 and Eps8 did not require either of the PxxP motifs of LANCL1, but it was inhibited by glutathione. Overexpression of LANCL1 in rat PC12 cells had no effect on NGF (see 162030)-induced neurite outgrowth, but overexpression of an LANCL1 mutant defective in Eps8 binding inhibited NGF-induced neurite outgrowth by 50%.BIOCHEMICAL FEATURES
Zhang et al. (2009) reported the crystal structure of LANCL1, which consists of 2 concentric alpha-helical barrels made up of 7 helices each. A GxxG-containing bulge that mediates Zn(2+) binding is located at the N terminus of each of the 7 inner helices. LANCL1 had a similar structure when cocrystalized with glutathione. In addition to Zn(2+)-mediated binding, there were extensive interactions between LANCL1 and glutathione.GENE STRUCTURE
Mayer et al. (2001) determined that the human and mouse LANCL1 genes span 45 kb and 38 kb, respectively, each comprising 10 exons.MAPPING
The International Radiation Hybrid Mapping Consortium mapped the LANCL1 gene to 2q33-q35 (TMAP WI-13674). By FISH, Mayer et al. (2001) mapped the LANCL1 gene to 2q34 and the mouse homolog to a region of conserved synteny at chromosome 1C2-C5. ... More on the omim web site
May 12, 2019: Protein entry updated
Automatic update: model status changed
Jan. 21, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
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
Oct. 27, 2017: Protein entry updated
Automatic update: model status changed
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 604155 was added.
Feb. 25, 2016: Protein entry updated
Automatic update: model status changed
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed