Hmdb loader
Identification
HMDB Protein ID HMDBP13345
Secondary Accession Numbers None
Name Purine nucleoside phosphorylase LACC1
Synonyms
  1. Adenosine deaminase LACC1
  2. Fatty acid metabolism-immunity nexus
  3. Guanosine phosphorylase LACC1
  4. Laccase domain-containing protein 1
  5. S-methyl-5'-thioadenosine phosphorylase LACC1
Gene Name LACC1
Protein Type Unknown
Biological Properties
General Function Not Available
Specific 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).
Pathways Not Available
Reactions Not Available
GO Classification
Biological Process
regulation of inflammatory response
inflammatory response
regulation of cellular pH
innate immune response
nucleotide-binding oligomerization domain containing 2 signaling pathway
pattern recognition receptor signaling pathway
positive regulation of cytokine production involved in immune response
regulation of purine nucleotide metabolic process
Cellular Component
endoplasmic reticulum
nucleus
peroxisome
Molecular Function
S-methyl-5-thioadenosine phosphorylase activity
purine-nucleoside phosphorylase activity
copper ion binding
adenosine deaminase activity
guanosine phosphorylase activity
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 430
Molecular Weight 47779.575
Theoretical pI 7.064
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q8IV20
UniProtKB/Swiss-Prot Entry Name LACC1_HUMAN
PDB IDs Not Available
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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  4. Wakil SM, Monies DM, Abouelhoda M, Al-Tassan N, Al-Dusery H, Naim EA, Al-Younes B, Shinwari J, Al-Mohanna FA, Meyer BF, Al-Mayouf S: Association of a mutation in LACC1 with a monogenic form of systemic juvenile idiopathic arthritis. Arthritis Rheumatol. 2015 Jan;67(1):288-95. doi: 10.1002/art.38877. [PubMed:25220867 ]
  5. Cader MZ, Boroviak K, Zhang Q, Assadi G, Kempster SL, Sewell GW, Saveljeva S, Ashcroft JW, Clare S, Mukhopadhyay S, Brown KP, Tschurtschenthaler M, Raine T, Doe B, Chilvers ER, Griffin JL, Kaneider NC, Floto RA, D'Amato M, Bradley A, Wakelam MJ, Dougan G, Kaser A: C13orf31 (FAMIN) is a central regulator of immunometabolic function. Nat Immunol. 2016 Sep;17(9):1046-56. doi: 10.1038/ni.3532. Epub 2016 Aug 1. [PubMed:27478939 ]
  6. Assadi G, Vesterlund L, Bonfiglio F, Mazzurana L, Cordeddu L, Schepis D, Mjosberg J, Ruhrmann S, Fabbri A, Vukojevic V, Percipalle P, Salomons FA, Laurencikiene J, Torkvist L, Halfvarson J, D'Amato M: Functional Analyses of the Crohn's Disease Risk Gene LACC1. PLoS One. 2016 Dec 13;11(12):e0168276. doi: 10.1371/journal.pone.0168276. eCollection 2016. [PubMed:27959965 ]
  7. Lahiri A, Hedl M, Yan J, Abraham C: Human LACC1 increases innate receptor-induced responses and a LACC1 disease-risk variant modulates these outcomes. Nat Commun. 2017 Jun 8;8:15614. doi: 10.1038/ncomms15614. [PubMed:28593945 ]
  8. Karacan I, Ugurlu S, Sahin S, Everest E, Kasapcopur O, Tolun A, Ozdogan H, Turanli ET: LACC1 Gene Defects in Familial Form of Juvenile Arthritis. J Rheumatol. 2018 May;45(5):726-728. doi: 10.3899/jrheum.170834. [PubMed:29717096 ]
  9. Singh A, Suri D, Vignesh P, Anjani G, Jacob P, Girisha KM: LACC1 gene mutation in three sisters with polyarthritis without systemic features. Ann Rheum Dis. 2020 Mar;79(3):425-426. doi: 10.1136/annrheumdis-2019-216263. Epub 2019 Dec 6. [PubMed:31811059 ]
  10. Rabionet R, Remesal A, Mensa-Vilaro A, Murias S, Alcobendas R, Gonzalez-Roca E, Ruiz-Ortiz E, Anton J, Iglesias E, Modesto C, Comas D, Puig A, Drechsel O, Ossowski S, Yague J, Merino R, Estivill X, Arostegui JI: Biallelic loss-of-function LACC1/FAMIN Mutations Presenting as Rheumatoid Factor-Negative Polyarticular Juvenile Idiopathic Arthritis. Sci Rep. 2019 Mar 14;9(1):4579. doi: 10.1038/s41598-019-40874-2. [PubMed:30872671 ]
  11. Cader MZ, de Almeida Rodrigues RP, West JA, Sewell GW, Md-Ibrahim MN, Reikine S, Sirago G, Unger LW, Iglesias-Romero AB, Ramshorn K, Haag LM, Saveljeva S, Ebel JF, Rosenstiel P, Kaneider NC, Lee JC, Lawley TD, Bradley A, Dougan G, Modis Y, Griffin JL, Kaser A: FAMIN Is a Multifunctional Purine Enzyme Enabling the Purine Nucleotide Cycle. Cell. 2020 Jan 23;180(2):278-295.e23. doi: 10.1016/j.cell.2019.12.017. [PubMed:31978345 ]
  12. Huang C, Hedl M, Ranjan K, Abraham C: LACC1 Required for NOD2-Induced, ER Stress-Mediated Innate Immune Outcomes in Human Macrophages and LACC1 Risk Variants Modulate These Outcomes. Cell Rep. 2019 Dec 24;29(13):4525-4539.e4. doi: 10.1016/j.celrep.2019.11.105. [PubMed:31875558 ]