Latexin (LXN)
The protein contains 222 amino acids for an estimated molecular weight of 25750 Da.
Hardly reversible, non-competitive, and potent inhibitor of CPA1, CPA2 and CPA4. May play a role in inflammation. (updated: April 1, 2015)
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.
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| Variant | Description |
|---|---|
| dbSNP:rs8455 | |
| dbSNP:rs59718588 |
Biological Process
Detection of temperature stimulus involved in sensory perception of pain
Inflammatory response
Molecular Function
Enzyme inhibitor activity
Heparin binding
Metalloendopeptidase inhibitor activity
The reference OMIM entry for this protein is 609305
Latexin; lxn
Endogenous carboxypeptidase inhibitor; eci
Tissue carboxypeptidase inhibitor; tci
DESCRIPTION
Latexin is a specific inhibitor of zinc-dependent metallocarboxypeptidases (Pallares et al., 2005).CLONING
Normant et al. (1995) cloned rat brain Lxn, which they called Tci. Northern blot analysis of several rat tissues and specific brain regions detected widespread expression of a single transcript, with highest levels in brain, lung, and digestive tract. Pallares et al. (2005) cloned LXN from human brain cDNA libraries. The deduced 222-amino acid protein is an elongated molecule with N- and C-terminal domains that each consist of an alpha helix enveloped by a curved beta sheet. The 2 domains are separated by a connecting segment.GENE FUNCTION
Normant et al. (1995) showed that purified recombinant rat Lxn completely inhibited rat pancreatic Cpa1 (114850) and Cpa2 (600688). Lxn was less potent against other mammalian carboxypeptidases, and it did not inhibit other metallopeptidases or serine proteases. Pallares et al. (2005) found that recombinant human LXN inhibited the mature active form of CPA4 (607635) in a noncompetitive manner. It also showed low specificity, inhibiting several metallocarboxypeptidases containing a characteristic alpha/beta hydrolase fold. The inhibition constant was within the nanomolar range for these substrates. LXN did not inhibit enzymes of other carboxypeptidase classes.BIOCHEMICAL FEATURES
Pallares et al. (2005) described the structure of CPA4 in complex with its endogenous inhibitor, LXN. CPA4 is a compact protein hollowed out in a funnel-like shape, with the active site at the bottom of the funnel. In the CPA4/LXN complex, CPA4 is bound at the top of the funnel by the interface of the N- and C-terminal subdomains of LXN. The complex occludes a large contact surface but makes few contacts.MAPPING
The International Radiation Hybrid Mapping Consortium mapped the LXN gene to chromosome 3 (TMAP RH102943).ANIMAL MODEL
Natural variation in the size of endogenous stem cell populations is important for homeostatic tissue regeneration, stem cell transplantation, aging, and, potentially, organismal longevity. As reviewed by Liang et al. (2007), several groups have demonstrated the extensive variation in hematopoietic stem cell (HSC) number between strains of laboratory mice. Liang et al. (2007) investigated the genetic determinants underlying variation between HSC numbers in C57BL/6 (B6) and DBA/2 (D2) strains. D2 mice, when young, have at least 3 times as many HSCs as B6. In reciprocal chromosome 3 congenic mice, introgressed D2 alleles increased HSC numbers owing to enhanced proliferation and self-renewal and reduced apoptosis, whereas B6 alleles had the opposite effects. Using oligonucleotide arrays, real-time PCR, and protein blocks, Liang et al. (2007) identified latexin (Lxn), a gene whose differential transcription and expression was associated with the allelic differences. Expression was inversely correlated with the number of HSCs; ectopic expression of Lxn using a retroviral vector decreased stem cell population size. They identified clusters of SNPs upstream of the Lxn transcriptional start site, at least 2 of which are associated with potential binding sites with transcription factors regulating stem cells. Thus, promoter polymorphisms representing difference between the B6 and D2 alleles may affect Lxn gene expression and consequently influence the population size of hematopoietic stem cells. ... More on the omim web site
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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 609305 was added.