Nomenclature
Short Name:
ENPP1
Full Name:
Ectonucleotide pyrophosphatase/phosphodiesterase family member 1
Alias:
- EC 3.1.4.1
- EC 3.6.1.9
- Phosphodiesterase I, nucleotide pyrophosphatase 1
- Plasma-cell membrane glycoprotein PC-1
- E-NPP 1
- NPP1
- NPPase
- PC-1
Classification
Type:
Protein-serine/threonine kinase
Group:
Atypical
Family:
SubFamily:
NA
Specific Links
Structure
Mol. Mass (Da):
104924
# Amino Acids:
925
# mRNA Isoforms:
1
mRNA Isoforms:
104,924 Da (925 AA; P22413)
4D Structure:
1D Structure:
3D Image (rendered using PV Viewer):
PDB ID
Subfamily Alignment
Domain Distribution:
| Start | End | Domain |
|---|
Post-translation Modifications
For detailed information on phosphorylation of this kinase go to PhosphoNET
Acetylated:
K62.
Methylated:
R65.
N-GlcNAcylated:
N179, N285, N342, N477, N585, N643, N700, N731, N748.
Threonine phosphorylated:
T256.
Tyrosine phosphorylated:
Y280, Y440.
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:
65
834
44
1100
2
21
18
19
10
127
26
125
23
300
162
1049
48
615
45
543
29
373
100
1252
17
221
55
458
92
1182
64
3033
31
394
17
390
5
63
140
58
19
243
55
332
30
382
239
473
3
38
48
54
4
53
13
61
25
326
49
431
4
46
26
81
6
78
416
688
9
113
36
131
3
44
143
51
27
347
165
345
4
54
46
61
3
34
49
48
7
87
36
84
8
104
37
119
6
77
47
105
100
1288
109
2416
3
36
51
53
15
195
37
179
44
564
37
607
5
61
56
73
24
303
24
301
43
550
46
916
28
365
95
682
45
584
109
527
7
91
61
74
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
97.7
98.9
99
98.3
99.1
98
-
-
87
-
-
-
86
92.4
88
-
-
-
78.9
87.7
81
78.4
87.7
80
-
-
-
49.9
65.7
-
65.4
79.2
67
43.6
59.3
61
21
32.2
57
-
-
-
-
-
-
-
-
-
24
40.4
35
-
-
-
-
-
-
-
-
-
-
-
45
-
-
43
-
-
-
-
-
-
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
Regulation
Activation:
NA
Inhibition:
NA
Synthesis:
NA
Degradation:
NA
Disease Linkage
General Disease Association:
Skin, cardiovascular, bone, muscloskeletal, and metabolic disorders
Specific Diseases (Non-cancerous):
Cole disease; Arterial calcification, Generalized, of Infancy, 1 (GACI1); Obesity; Arterial calcification of infancy (GACI1); Insulin resistance; Ossification of the posterior longitudinal ligament of the spine (OPLL); Rickets; Diabetes mellitus Type 2; Hypophosphatasia; Hypophosphatemic rickets, autosomal recessive 2 (ARHR2); Ankylosis; Calcinosis; Pseudogout; Bile duct disease; Hypophosphatemic rickets, Ar
Comments:
Mutations in ENPP1 are linked to several diabetes mellitus or obesity related diseases. L91P and S287F mutations are associated with ossification of the posterior longitudinal ligament of the spine (OPLL), which is a calcification of the posterior longitudinal ligament of the spinal column, usually at the level of the cervical spine. Several mutations at various positions can attribute to arterial calcification of infancy, generalized, 1 (GACI1), and it is usually fetal within the first 6 months due to refractory heart failure resulted from myocardial ischemia. K173Q mutation is associated with diabetes mellitus, non-insulin-dependent (NIDDM). G266V and Y901S mutations are linked to yypophosphatemic rickets, autosomal recessive, 2 (ARHR2), which is a disorder of proximal renal tubule function and may lead to bone pain, fractures and growth abnormalities.
Gene Expression in Cancers:
The COSMIC website notes an up-regulated expression score for ENPP1 in diverse human cancers of 417, which is 0.9-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 1 for this protein kinase in human cancers was 98% 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 very similar (+ 10% higher) to 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: 0.45 % in 864 skin cancers tested; 0.31 % in 1240 large intestine cancers tested; 0.2 % in 603 endometrium cancers tested; 0.17 % in 1610 lung cancers tested; 0.15 % in 589 stomach cancers tested.
Frequency of Mutated Sites:
Most frequent mutations with the number of reports indicated in brackets: R424Q (5); E845G (4); R404* (3).
Comments:
No deletions, insertions or complex mutations are noted on the COSMIC website.