ENPP3
Ectonucleotide pyrophosphatase/phosphodiesterase family member 3
Also known as: B10, CD203c, ENPP3_HUMAN, gp130RB13-6, PD-IBETA, PDNP3
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- O14638
- Gene
- ENPP3
- Ensembl
- ENSG00000154269
- Chromosome
- 6
- Canonical length
- 875 aa
- Protein class
- CD markers, Enzymes, Metabolic proteins, Predicted intracellular proteins, Predicted secreted proteins
- Secretome location
- Secreted - unknown location
- Quaternary structure
- Homodimer
OverviewNCBI Gene
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. Two transcript variants, one protein coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Oct 2015]
Canonical amino-acid sequenceUniProt
875 residues, UniProt reviewed canonical sequence.
>O14638|ENPP3
1 MESTLTLATE QPVKKNTLKK YKIACIVLLA LLVIMSLGLG LGLGLRKLEK QGSCRKKCFD
61 ASFRGLENCR CDVACKDRGD CCWDFEDTCV ESTRIWMCNK FRCGETRLEA SLCSCSDDCL
121 QRKDCCADYK SVCQGETSWL EENCDTAQQS QCPEGFDLPP VILFSMDGFR AEYLYTWDTL
181 MPNINKLKTC GIHSKYMRAM YPTKTFPNHY TIVTGLYPES HGIIDNNMYD VNLNKNFSLS
241 SKEQNNPAWW HGQPMWLTAM YQGLKAATYF WPGSEVAING SFPSIYMPYN GSVPFEERIS
301 TLLKWLDLPK AERPRFYTMY FEEPDSSGHA GGPVSARVIK ALQVVDHAFG MLMEGLKQRN
361 LHNCVNIILL ADHGMDQTYC NKMEYMTDYF PRINFFYMYE GPAPRIRAHN IPHDFFSFNS
421 EEIVRNLSCR KPDQHFKPYL TPDLPKRLHY AKNVRIDKVH LFVDQQWLAV RSKSNTNCGG
481 GNHGYNNEFR SMEAIFLAHG PSFKEKTEVE PFENIEVYNL MCDLLRIQPA PNNGTHGSLN
541 HLLKVPFYEP SHAEEVSKFS VCGFANPLPT ESLDCFCPHL QNSTQLEQVN QMLNLTQEEI
601 TATVKVNLPF GRPRVLQKNV DHCLLYHREY VSGFGKAMRM PMWSSYTVPQ LGDTSPLPPT
661 VPDCLRADVR VPPSESQKCS FYLADKNITH GFLYPPASNR TSDSQYDALI TSNLVPMYEE
721 FRKMWDYFHS VLLIKHATER NGVNVVSGPI FDYNYDGHFD APDEITKHLA NTDVPIPTHY
781 FVVLTSCKNK SHTPENCPGW LDVLPFIIPH RPTNVESCPE GKPEALWVEE RFTAHIARVR
841 DVELLTGLDF YQDKVQPVSE ILQLKTYLPT FETTILocalizationUniProt · AlphaFold · HPA
Whether an antibody against ENPP3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 1
- Mean surface accessibility (rSASA)
- 0.22
- Highest tissue expression
- 42 nTPM
Expression across tissuesHPA
Tissue
- small intestine: 42 nTPM
- cervix: 30 nTPM
- salivary gland: 17 nTPM
- duodenum: 15 nTPM
- seminal vesicle: 15 nTPM
- kidney: 9.4 nTPM
Single-cell type
- endometrial luminal cells: 934 nCPM
- mast cells: 394 nCPM
- endometrial glandular cells: 376 nCPM
- medullary thymic epithelial cells: 190 nCPM
- enterocytes: 169 nCPM
- lacrimal acinar cells: 157 nCPM
Immune cell
- basophil: 31 nTPM
- NK-cell: 0.3 nTPM
- MAIT T-cell: 0.2 nTPM
- classical monocyte: 0 nTPM
- eosinophil: 0 nTPM
- gdT-cell: 0 nTPM
Brain region
- cerebellum: 1.7 nTPM
- midbrain: 1 nTPM
- thalamus: 0.9 nTPM
- hypothalamus: 0.8 nTPM
- medulla oblongata: 0.8 nTPM
- pons: 0.8 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 1.02
- gnomAD pLI
- 0
- gnomAD missense Z
- 0.07
- DepMap mean gene effect
- -0.08
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- ATP metabolic process
- basophil activation involved in immune response
- negative regulation of cGAS/STING signaling pathway
- negative regulation of inflammatory response
- negative regulation of mast cell activation involved in immune response
- negative regulation of mast cell proliferation
- nucleoside triphosphate catabolic process
- phosphate ion homeostasis
- phosphate-containing compound metabolic process
- pyrimidine nucleotide metabolic process
Molecular functions
- ATP diphosphatase activity
- bis(5'-adenosyl)-pentaphosphatase activity
- bis(5'-adenosyl)-triphosphatase activity
- bis(5'-nucleosyl)-tetraphosphatase (asymmetrical) activity
- calcium ion binding
- cyclic-GMP-AMP hydrolase activity
- GTP diphosphatase activity
- nucleic acid binding
- nucleoside triphosphate diphosphatase activity
- phosphodiesterase I activity
- UTP diphosphatase activity
- zinc ion binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Somatomedin B domain
- DNA/RNA non-specific endonuclease/pyrophosphatase/phosphodiesterase domain
- Type I phosphodiesterase/nucleotide pyrophosphatase/phosphate transferase
- Alkaline-phosphatase-like, core domain superfamily
- ENPP1-3/EXOG-like, endonuclease/phosphodiesterase domain
- Somatomedin B-like domain superfamily
- His-Me finger superfamily
- DNA/RNA non-specific endonuclease superfamily
- Somatomedin B domain
- Type I phosphodiesterase / nucleotide pyrophosphatase
KeywordsUniProt
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads ENPP3 as an antibody target. Whether an autoantibody or antibody against ENPP3 could matter depends on whether native ENPP3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
ENPP3 is annotated at the cell surface, where native ENPP3 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label ENPP3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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