Nomenclature
Short Name:
SMG1
Full Name:
Serine/threonine-protein kinase SMG1
Alias:
- ATX
- KIAA0421
- Lambda/iota protein kinase C-interacting protein
- LIP
Classification
Type:
Protein-serine/threonine kinase
Group:
Atypical
Family:
PIKK
SubFamily:
SMG1
Structure
Mol. Mass (Da):
410,261
# Amino Acids:
3657
# mRNA Isoforms:
4
mRNA Isoforms:
410,501 Da (3661 AA; Q96Q15); 395,382 Da (3521 AA; Q96Q15-2); 340,674 Da (3031 AA; Q96Q15-3); 269,425 Da (2392 AA; Q96Q15-4)
4D Structure:
Component of a post-splicing multiprotein NMD complex with UPF1/RENT1, UPF2/RENT2, EST1A (SMG5/7a), EST1B/SMG5 and UPF3 (UPF3A or UPF3B). Component of the SMG1C complex, at least composed of SMG1, SMG8 and SMG9. The SMG1C complex is then recruited on premature translation termination codons (PTCs) to form the ribosome:SURF complex, at least composed of ERF1, ERF3 (ERF3A or ERF3B), EEF2, UPF1/RENT1, SMG1, SMG8 and SMG9. Interacts with PRKCI. Interacts with TELO2 and TTI1. Interacts with RUVBL1 and RUVBL2. Interacts with POLR2E.
1D Structure:
Subfamily Alignment
Domain Distribution:
| Start | End | Domain |
|---|---|---|
| 189 | 209 | Coiled-coil |
| 1813 | 1848 | HEAT |
| 1973 | 1999 | Coiled-coil |
| 2146 | 2474 | PI3Kc |
| 3625 | 3657 | FATC |
| 1127 | 1862 | FAT |
Kinexus Products
Click on entries below for direct links to relevant products from Kinexus for this protein kinase.
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Post-translation Modifications
For detailed information on phosphorylation of this kinase go to PhosphoNET
Acetylated:
K169 (N6), K173, K1287, K1513, K1516, K2138, K2139, K2148.
Serine phosphorylated:
S34, S94, S103, S115, S140, S142, S144, S147, S708, S753, S1007, S1218, S1221, S1638, S1897, S1903, S1906, S1907, S1910, S1917, S2087, S2149, S2255, S2537, S2955, S3544, S3556, S3570, S3572, S3576.
Threonine phosphorylated:
T15, T19, T32, T157, T252, T256, T258, T262, T896, T1006, T1047, T1527, T1660, T1789, T2239, T2776, T3181, T3546, T3550, T3569, T3573, T3577.
Tyrosine phosphorylated:
Y40, Y44, Y143, Y252, Y253, Y257, Y549, Y995, Y998, Y1519, Y2150, Y2152, Y2193, Y2218, Y2253, Y2254, Y2536, Y2713.
Ubiquitinated:
K529, K537, K598, K608, K1232, K1989.
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:
26
1219
22
1298
0.4
19
15
28
82
3892
17
3565
26
1253
102
2629
19
907
24
759
2
111
51
158
9
440
37
400
38
1819
51
2743
9
410
10
427
13
618
115
1731
56
2670
37
5782
16
767
175
1961
81
3846
28
4454
0.2
9
14
8
49
2328
36
3867
1
49
15
47
10
488
358
2580
50
2381
26
3351
22
1059
89
2485
21
1000
84
849
23
1111
36
1814
79
3787
38
7311
100
4769
25
7016
43
2034
28
3071
74
3550
36
6068
39
1862
72
2479
56
2680
31
4254
38
1833
27
2939
56
2690
27
3787
1.4
66
28
53
27
1304
18
902
60
2848
38
5933
5
224
68
607
19
903
57
841
39
1856
44
3227
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
99.5
99.6
100
-
-
98
-
-
99
-
-
98
96.8
97.6
99
-
-
-
97.5
98.8
98
-
-
97
-
-
-
94.7
97.5
-
93.3
97.3
93.5
-
-
86
73.3
85.6
74
-
-
-
25.2
43.7
27
33.1
53.3
-
-
-
31
33.9
53.8
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
Regulation
Activation:
NA
Inhibition:
Inhibited by caffeine, LY294002 and wortmannin.
Synthesis:
NA
Degradation:
NA
Known Downstream Substrates
For further details on these substrates click on the Substrate Short Name or UniProt ID. Phosphosite Location is hyperlinked to PhosphoNET
predictions.
Based on in vitro and/or in vivo phosphorylation data
| Substrate Short Name | UniProt ID (Human) | Phosphosite Location | Phosphosite Sequence | Effect of Phosphorylation |
|---|
Disease Linkage
General Disease Association:
Muscle, and neuronal disorders
Specific Diseases (Non-cancerous):
Ullrich congenital muscular dystrophy (UCMD)
Comments:
Ullrich Congenital Muscular Dystrophy (UCMD) is a rare neuronal and muscular disorder affecting skeletal muscles. UCMD is characterized by an impaired ability to walk, joint stiffness, and hypermobility (large range of motion in wrist and ankle joints).
Gene Expression in Cancers:
TranscriptoNET (www.transcriptonet.ca) analysis with mRNA expression data retrieved from the National Center for Biotechnology Information's Gene Expression Omnibus (GEO) database, which was normalized against 60 abundantly and commonly found proteins, indicated altered expression for this protein kinase as shown here as the percent change from normal tissue controls (%CFC) as supported with the Student T-test in the following types of human cancers: Clear cell renal cell carcinomas (cRCC) stage I (%CFC= +2397, p<0.001); Prostate cancer - primary (%CFC= +202, p<0.0001); and Vulvar intraepithelial neoplasia (%CFC= +67, p<0.089); The COSMIC website notes an up-regulated expression score for SMG1 in diverse human cancers of 398, which is 0.9-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 81 for this protein kinase in human cancers was 1.4-fold of the average score of 60 for the human protein kinases.
Mutagenesis Experiments:
Insertional mutagenesis studies in mice support a role for this protein kinase in mouse cancer oncogenesis. The phosphotransferase activity of SMG1 can be inhibited with a D2335A mutation.
Mutation Rate in All Cancers:
Percent mutation rates per 100 amino acids length in human cancers: 0.04 % in 25652 diverse cancer specimens. This rate is -46 % lower 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: 0.15 % in 1270 large intestine cancers tested; 0.13 % in 603 endometrium cancers tested; 0.13 % in 589 stomach cancers tested; 0.11 % in 273 cervix cancers tested; 0.08 % in 864 skin cancers tested; 0.07 % in 1956 lung cancers tested; 0.06 % in 710 oesophagus cancers tested; 0.05 % in 548 urinary tract cancers tested; 0.05 % in 1512 liver cancers tested; 0.05 % in 1448 kidney cancers tested; 0.05 % in 1023 upper aerodigestive tract cancers tested; 0.04 % in 1546 breast cancers tested; 0.03 % in 891 ovary cancers tested; 0.02 % in 382 soft tissue cancers tested; 0.02 % in 238 bone cancers tested; 0.02 % in 1467 pancreas cancers tested; 0.01 % in 939 prostate cancers tested; 0.01 % in 558 thyroid cancers tested; 0.01 % in 441 autonomic ganglia cancers tested; 0.01 % in 2079 central nervous system cancers tested; 0.01 % in 2009 haematopoietic and lymphoid cancers tested.
Frequency of Mutated Sites:
Most frequent mutations with the number of reports indicated in brackets: E733E (6); E733G (2).
Comments:
Ten deletions, 4 insertions and no complex mutations are noted on the COSMIC website.