Nomenclature
Short Name:
H11
Full Name:
Protein kinase H11
Alias:
- Alpha crystallin C chain
- HSPB8
- CRYAC
- E2IG1
- E2-induced gene 1 protein
- E2IG1
- HSP22
Classification
Type:
Protein-serine/threonine kinase
Group:
Atypical
Family:
H11
SubFamily:
NA
Structure
Mol. Mass (Da):
21,604
# Amino Acids:
196
# mRNA Isoforms:
1
mRNA Isoforms:
21,604 Da (196 AA; Q9UJY1)
4D Structure:
Monomer. Interacts with HSPB1.
1D Structure:
Subfamily Alignment
Domain Distribution:
| Start | End | Domain |
|---|---|---|
| 93 | 185 | HSP20 |
Post-translation Modifications
For detailed information on phosphorylation of this kinase go to PhosphoNET
Methylated:
R71, R78.
Serine phosphorylated:
S14, S24, S27, S57, S104, S122.
Threonine phosphorylated:
T63, T87.
Tyrosine phosphorylated:
Y118.
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:
54
1198
22
944
4
79
9
48
61
1356
3
474
30
656
75
686
35
784
24
578
11
254
54
465
4
86
25
138
66
1465
27
1327
15
339
10
259
8
170
61
124
3
63
16
61
59
1301
84
822
6
141
14
81
3
77
6
74
4
98
13
87
3
67
12
64
50
1115
82
794
13
283
8
176
75
1656
78
1218
35
783
84
716
67
1485
12
878
15
328
14
185
14
320
4
151
4
89
8
66
13
284
12
225
30
673
48
674
23
514
17
196
15
326
8
127
20
437
8
134
7
148
28
133
14
312
18
217
100
2219
26
4897
25
552
90
919
31
695
52
596
25
545
35
1146
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
66.4
68.4
100
96.9
96.9
98
-
-
96
-
-
95
-
-
94
-
-
-
94.4
96.9
94
95.4
97.5
95
-
-
-
-
-
-
36.2
52
69
63.5
73.4
63
55.6
67.1
62
-
-
-
37.2
54.1
-
-
-
-
-
-
-
30.1
46.6
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
Binding Proteins
Examples of known interacting proteins
hiddentext
| No. | Name – UniProt ID |
|---|---|
| 1 | HSPB1 - P04792 |
| 2 | HSPB2 - Q16082 |
| 3 | HSPB7 - Q9UBY9 |
| 4 | BAG3 - O95817 |
| 5 | PRKCA - P17252 |
| 6 | MAPK3 - P27361 |
| 7 | CSNK2A1 - P68400 |
| 8 | HSPB6 - O14558 |
| 9 | HSPB3 - Q12988 |
| 10 | CRYAB - P02511 |
Regulation
Activation:
NA
Inhibition:
NA
Synthesis:
By 17-beta-estradiol.
Degradation:
NA
Known Upstream Kinases
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
| Kinase Short Name | UniProt ID (Human) | Phosphosite Location | Phosphosite Sequence | Effect of Phosphorylation |
|---|
Disease Linkage
General Disease Association:
Cancer, neurological disorders
Specific Diseases (Non-cancerous):
Charcot-Marie-Tooth disease; Tooth disease; Charcot-Marie-Tooth Neuropathy Type 2; Charcot-Marie-Tooth disease, axonal, Type 2l (CMT2L); Neuropathy, distal hereditary motor, Type 1IA (HMN2A); Distal hereditary motor neuropathy; Charcot-Marie-Tooth disease Type 2; Hereditary cerebral hemorrhage with amyloidosis; Distal hereditary motor neuropathy, Type 1i; autosomal dominant Charcot-Marie-Tooth disease Type 2; Neuronopathy, distal hereditary motor, Type 1id; Charcot-Marie-Tooth neuropathy Type 2l; distal hereditary motor neuronopathy, Type 1ia
Comments:
K141E or K141N is associated with neuronopathy, distal hereditary motor, 2A, which is a neuromuscular disorder caused by selective degeneration of motor neurons in the anterior horn of the spinal cord. K141N is also associated with Charcot-Marie-Tooth disease 2L, which characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms.
Specific Cancer Types:
Breast cancer
Comments:
The expression of H11 is induced by estrogen in estrogen receptor-positive breast cancer cells.
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: Barrett's esophagus epithelial metaplasia (%CFC= -70, p<0.004); Bladder carcinomas (%CFC= -63, p<0.062); Cervical epithelial cancer (%CFC= +182, p<0.002); Clear cell renal cell carcinomas (cRCC) (%CFC= +125, p<0.008); Clear cell renal cell carcinomas (cRCC) stage I (%CFC= -64, p<0.001); Colorectal adenocarcinomas (early onset) (%CFC= +862, p<0.046); Malignant pleural mesotheliomas (MPM) tumours (%CFC= +100, p<0.0001); Oral squamous cell carcinomas (OSCC) (%CFC= -62, p<0.014); Pituitary adenomas (ACTH-secreting) (%CFC= -58); Pituitary adenomas (aldosterone-secreting) (%CFC= +137, p<0.049); Prostate cancer - metastatic (%CFC= -88, p<0.0001); Prostate cancer - primary (%CFC= -50, p<0.0001); Skin fibrosarcomas (%CFC= -80); Skin melanomas - malignant (%CFC= -73, p<0.0002); and Uterine leiomyomas from fibroids (%CFC= +84, p<0.051).
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: 0.11 % in 24433 diverse cancer specimens. This rate is a modest 1.53-fold 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: 0.41 % in 864 skin cancers tested; 0.33 % in 1229 large intestine cancers tested; 0.28 % in 555 stomach cancers tested; 0.16 % in 1608 lung cancers tested; 0.08 % in 603 endometrium cancers tested.
Frequency of Mutated Sites:
Most frequent mutations with the number of reports indicated in brackets: E84K (3).
Comments:
Only 1 deletion and 1 insertion, and no complex mutations are noted on the COSMIC website.