LACC1
Function
Purine nucleoside enzyme that catalyzes the phosphorolysis of adenosine, guanosine and inosine nucleosides, yielding D-ribose 1-phosphate and the respective free bases, adenine, guanine and hypoxanthine (PubMed:31978345). Also catalyzes the phosphorolysis of S-methyl-5'-thioadenosine into adenine and S-methyl-5-thio-alpha-D-ribose 1-phosphate (PubMed:31978345). Also has adenosine deaminase activity (PubMed:31978345). Acts as a regulator of innate immunity in macrophages by modulating the purine nucleotide metabolism, thereby regulating the metabolic function and bioenergetic state of macrophages (PubMed:31978345). Enables a purine nucleotide cycle between adenosine and inosine monophosphate and adenylosuccinate that prevents cytoplasmic acidification and balances the cytoplasmic-mitochondrial redox interface (PubMed:31978345). The purine nucleotide cycle consumes aspartate and releases fumarate in a manner involving fatty acid oxidation and ATP-citrate lyase activity (PubMed:31978345). Participates in pattern recognition receptor (PRR)-induced cytokines in macrophages: associates with the NOD2-signaling complex and promotes optimal NOD2-induced signaling, cytokine secretion and bacterial clearance (PubMed:28593945, PubMed:31875558). Localizes to the endoplasmic reticulum upon PRR stimulation of macrophages and associates with endoplasmic reticulum-stress sensors, promoting the endoplasmic reticulum unfolded protein response (UPR) (PubMed:31875558). Does not show laccase activity (PubMed:27959965, PubMed:31978345).
Involvement in disease
Juvenile arthritis
JUVAR
A rare, familial form of juvenile arthritis characterized by autosomal recessive inheritance and onset in early childhood of symmetric, chronic joint inflammation. It causes joint swelling, pain, stiffness and restricted joint movement. JUVAR has high clinical variability. Some patients exhibit systemic symptoms, including quotidian fever, erythematous rash, generalized lymphadenopathy, hepatomegaly, and/or splenomegaly. Others display polyarthritis without systemic inflammation.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylated on tyrosine residues.
Sequence Similarities
Belongs to the purine nucleoside phosphorylase YfiH/LACC1 family.
Tissue Specificity
Ubiquitously expressed, with higher expression levels in immune-related tissues such as lymph nodes and spleen (PubMed:27959965). Expressed in both intestinal and peripheral myeloid-derived cells (PubMed:28593945).
Cellular localization
- Cytoplasm
- Nucleus
- Endoplasmic reticulum
- Peroxisome
- Upon stimulation of the pattern-recognition receptor (PRR) NOD2, localizes to the endoplasmic reticulum.
Alternative names
C13orf31, FAMIN, LACC1, Purine nucleoside phosphorylase LACC1, Adenosine deaminase LACC1, Fatty acid metabolism-immunity nexus, Guanosine phosphorylase LACC1, Laccase domain-containing protein 1, S-methyl-5'-thioadenosine phosphorylase LACC1