Nomenclature
Short Name:
ENPP3
Full Name:
Ectonucleotide pyrophosphatase/phosphodiesterase family member 3
Alias:
- PD-Ibeta
- Phosphodiesterase 1 beta
- Phosphodiesterase I/nucleotide pyrophosphatase 3
- CD203c
- PDNP3
Classification
Type:
Protein-serine/threonine kinase
Group:
Atypical
Family:
SubFamily:
NA
Specific Links
Structure
Mol. Mass (Da):
100,124
# Amino Acids:
# mRNA Isoforms:
1
mRNA Isoforms:
100,124 Da (875 AA; O14638)
4D Structure:
1D Structure:
Subfamily Alignment
Domain Distribution:
| Start | End | Domain |
|---|
Post-translation Modifications
For detailed information on phosphorylation of this kinase go to PhosphoNET
N-GlcNAcylated:
N1236, N279, N290, N426, N533, N582, N594, N687, N699, N789.
Threonine phosphorylated:
T205, T689, T846.
Tyrosine phosphorylated:
Y389, Y694, Y755, Y851, Y867.
Distribution
Based on gene microarray analysis from the NCBI
Human Tissue Distribution
% Max Expression:
Mean Expression:
Number of Samples:
Standard Deviation:
% Max Expression:
Mean Expression:
Number of Samples:
Standard Deviation:
44
1168
28
1208
2
40
7
38
3
83
17
87
11
281
105
965
22
570
31
425
0.5
14
58
19
4
95
32
102
26
683
33
1663
16
416
7
277
12
314
78
493
2
63
27
63
19
512
101
461
2
41
30
51
2
46
3
13
1
31
24
43
3
69
17
87
47
1233
41
5030
8
221
21
166
2
55
88
74
13
347
109
267
2
42
23
52
2
47
25
66
2
63
20
63
2
48
21
64
7
172
23
149
16
410
72
486
1
35
30
51
17
436
21
414
5
135
21
94
7
188
42
118
19
503
18
367
100
2628
37
4523
6
163
71
472
29
754
78
646
4
97
48
101
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
99.3
99.6
99
97
98.2
97
-
-
82
-
-
-
80.6
88.4
85
-
-
-
80.6
90.4
81
81.4
90.1
82
-
-
-
69.5
82.5
-
51.4
67
67
20.9
34.6
63
21.3
34.7
-
-
-
-
-
-
-
-
-
-
24.9
42.8
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
42
-
-
-
-
-
-
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
Regulation
Activation:
NA
Inhibition:
NA
Synthesis:
NA
Degradation:
NA
Disease Linkage
General Disease Association:
Gastrointestinal disorders
Specific Diseases (Non-cancerous):
Bile duct disease; SM-AHNMD
Comments:
Normally, ENPP3 is expressed at low levels in the kidney proximal tubules, however is has been found to be overexpressed in several renal neoplasms. Additionally, utilization of an anti-ENPP3 antibody resulted in cell cycle arrest in the G2/M phase and promoted apoptosis. In addition, ENPP3-mediated hydrolysis of nucleotide sugars is predicted to have significant influence on glycosyltransferase activities, thus functioning to regulate the overall glycosylation profile of the cell and various cellular processes. Mutations in this gene have been associated with bile duct disease and SM-AHNMD.Bile duct disease is a general term for a blockage of the duct that drains bile from the gallbladder to the small intestine. This blockage can be due to gall stones, cancer, infection, or internal scar tissue, and can result in liver failure due to bile accumulation. SM-AHNMD, also called systemic mastocytosis with associated clonal, hematologic non-mast cell lineage disease, is a disease affecting the bone marrow and bone with similarities to systemic and non-systemic mastocytosis. Histamine is thought to have a role in the pathology of this disease.
Gene Expression in Cancers:
The COSMIC website notes an up-regulated expression score for ENPP3 in diverse human cancers of 324, which is 0.7-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 0 for this protein kinase in human cancers was 100% lower than the average score of 60 for the human protein kinases.
Mutagenesis Experiments:
Insertional mutagenesis studies in mice have not yet revealed a role for this protein kinase in mouse cancer oncogenesis.
Mutation Rate in All Cancers:
Percent mutation rates per 100 amino acids length in human cancers: 0.08 % in 24525 diverse cancer specimens. This rate is only 13 % higher than the average rate of 0.075 % calculated for human protein kinases in general.
Mutation Rate in Specific Cancers:
Highest percent mutation rates per 100 amino acids length in human cancers: 0.38 % in 864 skin cancers tested; 0.29 % in 273 cervix cancers tested; 0.28 % in 603 endometrium cancers tested; 0.26 % in 1240 large intestine cancers tested; 0.21 % in 555 stomach cancers tested; 0.21 % in 1610 lung cancers tested.
Frequency of Mutated Sites:
Most frequent mutations with the number of reports indicated in brackets: R102C (4); W250* (3).
Comments:
Only 5 deletions, no insertions or complex mutations are noted on the COSMIC website.