Hardly reversible, non-competitive, and potent inhibitor of CPA1, CPA2 and CPA4. May play a role in inflammation. (updated: April 1, 2015)
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.
No sequence conservation computed yet.
Total structural coverage: 100%
No model available.
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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 RH
102943).
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. ...
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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.