ENPP3

ENPP3
Identifiers
Aliases	ENPP3, B10, CD203c, NPP3, PD-IBETA, PDNP3, ectonucleotide pyrophosphatase/phosphodiesterase 3
External IDs	OMIM: 602182; MGI: 2143702; GeneCards: ENPP3
Enzyme activity
Gene location (Human)
Chr.	Chromosome 6 (human)
End	131,747,418 bp
Gene location (Mouse)
Chr.	Chromosome 10 (mouse)
End	24,718,721 bp
RNA expression pattern
	Top expressed in
	jejunal mucosa; ; mucosa of ileum; ; seminal vesicula; ; duodenum; ; mucosa of paranasal sinus; ; bronchial epithelial cell; ; endometrium; ; buccal mucosa cell; ; tibialis anterior muscle; ; olfactory zone of nasal mucosa;
	Top expressed in
	epithelium of small intestine; ; conjunctival fornix; ; intestinal villus; ; duodenum; ; parotid gland; ; lacrimal gland; ; cornea; ; jejunum; ; ciliary body; ; left lobe of liver;
	More reference expression data
	n/a
Gene ontology
Molecular function	nucleoside-triphosphate diphosphatase activity; nucleotide diphosphatase activity; phosphodiesterase I activity; polysaccharide binding; metal ion binding; scavenger receptor activity; NADH pyrophosphatase activity; catalytic activity; nucleic acid binding; hydrolase activity; calcium ion binding; zinc ion binding;
Cellular component	integral component of membrane; membrane; integral component of plasma membrane; extracellular region; perinuclear region of cytoplasm; extracellular exosome; plasma membrane; external side of plasma membrane; apical plasma membrane;
Biological process	nucleoside triphosphate catabolic process; receptor-mediated endocytosis; immune response; phosphate-containing compound metabolic process; metabolism; inorganic diphosphate transport; nucleic acid phosphodiester bond hydrolysis; basophil activation involved in immune response; pyrimidine nucleotide metabolic process; negative regulation of mast cell activation involved in immune response; ATP metabolic process; negative regulation of inflammatory response; negative regulation of mast cell proliferation; vesicle-mediated transport; endocytosis;
	Sources:Amigo / QuickGO
Orthologs
Databases	NCBI: entry; OMA: entry
	5169
	209558
	ENSG00000154269
	ENSMUSG00000019989
	O14638
	Q6DYE8
	NM_005021
	NM_134005; NM_145372
	NP_005012
	NP_598766
	Wikidata
View/Edit Human	View/Edit Mouse

Ectonucleotide pyrophosphatase/phosphodiesterase family member 3 is an enzyme that in humans is encoded by the ENPP3 gene.

Function

The protein encoded by this gene belongs to a series of ectoenzymes that are involved in hydrolysis of extracellular nucleotides. These ectoenzymes possess ATPase and ATP pyrophosphatase activities and are type II transmembrane proteins. Expression of the related rat mRNA has been found in a subset of immature glial cells and in the alimentary tract. The corresponding rat protein has been detected in the pancreas, small intestine, colon, and liver. The human mRNA is expressed in glioma cells, prostate, and uterus. Expression of the human protein has been detected in uterus, basophils, and mast cells.

This protein has also been used in conjunction with CD63 as a marker for activated basophils in the Basophil Activation Test for IgE mediated allergic reactions.

ENPP3 hydrolyzes the immunomodulatory second messenger extracellular cyclic GMP-AMP (cGAMP), a signaling molecule that activates the STING pathway. Along with its paralog ENPP1, ENPP3 helps control extracellular cGAMP levels and accounts for the cGAMP hydrolysis observed when ENPP1 is absent. By limiting the amount of extracellular cGAMP available to activate STING, ENPP3 can dampen immune signaling and function as an innate immune checkpoint.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000154269 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000019989 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Jin-Hua P, Goding JW, Nakamura H, Sano K (October 1997). "Molecular cloning and chromosomal localization of PD-Ibeta (PDNP3), a new member of the human phosphodiesterase I genes". Genomics. 45 (2): 412–415. doi:10.1006/geno.1997.4949. PMID 9344668.
1 2 "Entrez Gene: ENPP3 ectonucleotide pyrophosphatase/phosphodiesterase 3".
↑ McGowan EC, Saini S (February 2013). "Update on the performance and application of basophil activation tests". Current Allergy and Asthma Reports. 13 (1): 101–109. doi:10.1007/s11882-012-0324-x. PMC 4078398. PMID 23188565.
↑ Mardjuki R, Wang S, Carozza J, Zirak B, Subramanyam V, Abhiraman G, et al. (May 2024). "Identification of the extracellular membrane protein ENPP3 as a major cGAMP hydrolase and innate immune checkpoint". Cell Reports. 43 (5) 114209. doi:10.1016/j.celrep.2024.114209. PMC 13268100. PMID 38749434.

Bühring HJ, Streble A, Valent P (April 2004). "The basophil-specific ectoenzyme E-NPP3 (CD203c) as a marker for cell activation and allergy diagnosis". International Archives of Allergy and Immunology. 133 (4): 317–329. doi:10.1159/000077351. PMID 15031605. S2CID 12238348.
Andoh K, Piao JH, Terashima K, Nakamura H, Sano K (September 1999). "Genomic structure and promoter analysis of the ecto-phosphodiesterase I gene (PDNP3) expressed in glial cells". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1446 (3): 213–224. doi:10.1016/s0167-4781(99)00090-1. PMID 10524196.
Bühring HJ, Seiffert M, Giesert C, Marxer A, Kanz L, Valent P, et al. (May 2001). "The basophil activation marker defined by antibody 97A6 is identical to the ectonucleotide pyrophosphatase/phosphodiesterase 3". Blood. 97 (10): 3303–3305. doi:10.1182/blood.V97.10.3303. PMID 11342463.
Yano Y, Hayashi Y, Sano K, Shinmaru H, Kuroda Y, Yokozaki H, et al. (November 2003). "Expression and localization of ecto-nucleotide pyrophosphatase/phosphodiesterase I-3 (E-NPP3/CD203c/PD-I beta/B10/gp130RB13-6) in human colon carcinoma". International Journal of Molecular Medicine. 12 (5): 763–766. doi:10.3892/ijmm.12.5.763. PMID 14533006.
Yano Y, Hayashi Y, Sano K, Nagano H, Nakaji M, Seo Y, et al. (April 2004). "Expression and localization of ecto-nucleotide pyrophosphatase/phosphodiesterase I-1 (E-NPP1/PC-1) and -3 (E-NPP3/CD203c/PD-Ibeta/B10/gp130(RB13-6)) in inflammatory and neoplastic bile duct diseases". Cancer Letters. 207 (2): 139–147. doi:10.1016/j.canlet.2003.11.002. PMID 15072822.
Elbatarny HS, Maurice DH (October 2005). "Leptin-mediated activation of human platelets: involvement of a leptin receptor and phosphodiesterase 3A-containing cellular signaling complex". American Journal of Physiology. Endocrinology and Metabolism. 289 (4): E695–702. doi:10.1152/ajpendo.00125.2005. PMID 15886225.
Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, et al. (January 2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
Ocmant A, Peignois Y, Mulier S, Hanssens L, Michils A, Schandené L (March 2007). "Flow cytometry for basophil activation markers: the measurement of CD203c up-regulation is as reliable as CD63 expression in the diagnosis of cat allergy". Journal of Immunological Methods. 320 (1–2): 40–48. doi:10.1016/j.jim.2006.12.002. PMID 17275019.

This article on a gene on human chromosome 6 is a stub. You can help Wikipedia by adding missing information.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000154269 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000019989 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[Jin-Hua_1997-5] Jin-Hua P, Goding JW, Nakamura H, Sano K (October 1997). "Molecular cloning and chromosomal localization of PD-Ibeta (PDNP3), a new member of the human phosphodiesterase I genes". Genomics. 45 (2): 412–415. doi:10.1006/geno.1997.4949. PMID 9344668.

[entrez-6] 1 2 "Entrez Gene: ENPP3 ectonucleotide pyrophosphatase/phosphodiesterase 3".

[7] McGowan EC, Saini S (February 2013). "Update on the performance and application of basophil activation tests". Current Allergy and Asthma Reports. 13 (1): 101–109. doi:10.1007/s11882-012-0324-x. PMC 4078398. PMID 23188565.

[8] Mardjuki R, Wang S, Carozza J, Zirak B, Subramanyam V, Abhiraman G, et al. (May 2024). "Identification of the extracellular membrane protein ENPP3 as a major cGAMP hydrolase and innate immune checkpoint". Cell Reports. 43 (5) 114209. doi:10.1016/j.celrep.2024.114209. PMC 13268100. PMID 38749434.

ENPP3

Function

References

Further reading