Nomenclature
Short Name:
CRK7
Full Name:
Cell division cycle 2-related protein kinase 7
Alias:
- CD2L7
- CDC2 related protein kinase 7
- CRKR
- CRKRS
- CrkRS
- KIAA0904
- CDC2- related protein kinase 7
- Cdc2-related kinase, arginine/serine-rich
- CDC2-related protein kinase 7
- CDK12
Classification
Type:
Protein-serine/threonine kinase
Group:
CMGC
Family:
CDK
SubFamily:
CRK7
Structure
Mol. Mass (Da):
164,155
# Amino Acids:
1490
# mRNA Isoforms:
3
mRNA Isoforms:
164,155 Da (1490 AA; Q9NYV4); 163,228 Da (1481 AA; Q9NYV4-2); 141,449 Da (1273 AA; Q9NYV4-3)
4D Structure:
Interacts with CCNL1 and CCNL2
1D Structure:
3D Image (rendered using PV Viewer):
PDB ID
Subfamily Alignment
Domain Distribution:
| Start | End | Domain |
|---|---|---|
| 727 | 1020 | Pkinase |
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:
K203, K211, K504 (N6), K509, K796, K973, K1470.
Methylated:
R329 (M2), R330 (M2), R331 (M2), R449, R1404 (M1), R1473 (M1).
O-GlcNAcylated:
T592, S597.
Serine phosphorylated:
S14, S18, S24, S25, S29, S30, S32, S62, S77, S78, S80, S84, S148, S176, S177, S215, S222, S228, S230, S231, S236, S238, S249, S251, S256, S257, S261, S265, S274, S276, S283, S287, S288, S291, S293, S296, S301, S303, S306, S310, S311, S312, S318, S320, S323, S325, S332, S333, S334, S338, S341, S343, S345, S349, S355, S357, S359, S363, S379, S382, S383, S385, S393, S394, S400, S420, S423, .
Threonine phosphorylated:
T57, T65, T158, T206, T255, T514, T520, T592, T692, T770, T893+, T1002, T1070, T1071, T1076, T1244, T1246, T1375.
Tyrosine phosphorylated:
Y73+, Y161, Y246, Y279, Y285, Y305, Y313, Y319, Y327, Y362, Y892+.
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:
48
1435
53
1034
2
60
17
50
2
65
2
40
17
511
192
1199
27
797
65
548
1.5
44
110
23
3
98
71
187
100
2991
48
4584
14
418
17
334
3
93
176
66
2
65
28
40
26
764
184
639
2
67
24
32
0.9
26
11
19
2
74
23
61
2
50
35
35
9
256
313
2177
2
48
11
55
2
67
149
53
26
775
221
594
3
80
20
67
3
97
23
77
3
82
4
36
2
68
11
57
4
119
19
110
38
1136
122
1574
2
60
27
31
2
54
10
56
1.3
38
10
33
5
150
84
106
26
787
24
693
58
1744
56
4442
2
50
118
125
34
1002
156
801
9
261
87
297
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
42.3
54.2
98
98.4
99.1
99
-
-
93.5
-
-
95
95.1
96.9
95
-
-
-
91.1
94.7
91
91.7
95
91
-
-
-
-
-
-
-
-
77
-
-
70
39.1
50.4
-
-
-
-
-
-
-
36
51.7
-
27.6
36
-
35.7
49.5
-
-
-
-
-
-
-
-
-
-
-
-
47
-
-
45
-
-
25
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
Binding Proteins
Examples of known interacting proteins
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| No. | Name – UniProt ID |
|---|---|
| 1 | MBP - P02686 |
| 2 | POLR2A - P24928 |
| 3 | KRT32 - Q14532 |
| 4 | KRTAP9-3 - Q9BYQ3 |
| 5 | PRPF40A - O75400 |
| 6 | KRT31 - Q15323 |
| 7 | KRT85 - P78386 |
Regulation
Activation:
NA
Inhibition:
NA
Synthesis:
NA
Degradation:
NA
Protein Kinase Specificity
Matrix of observed frequency (%) of amino acids in aligned protein substrate phosphosites
Matrix Type:
Predicted from the application of the Kinexus Kinase Substrate Predictor Version 2.0 algorithm, which was trained with over 10,000 kinase-protein substrate pairs and 8,000 kinase-peptide substrate pairs.
Domain #:
1
Disease Linkage
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: Breast epithelial hyperplastic enlarged lobular units (HELU) (%CFC= +53, p<0.002); and Clear cell renal cell carcinomas (cRCC) stage I (%CFC= +110, p<0.0002). The COSMIC website notes an up-regulated expression score for CRK7 in diverse human cancers of 682, which is 1.5-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 123 for this protein kinase in human cancers was 2.1-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.
Mutation Rate in All Cancers:
Percent mutation rates per 100 amino acids length in human cancers: 0.08 % in 25495 diverse cancer specimens. This rate is very similar (+ 5% 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: 0.3 % in 1631 large intestine cancers tested; 0.27 % in 569 stomach cancers tested; 0.23 % in 895 skin cancers tested; 0.19 % in 603 endometrium cancers tested; 0.16 % in 891 ovary cancers tested; 0.13 % in 548 urinary tract cancers tested; 0.12 % in 273 cervix cancers tested; 0.1 % in 710 oesophagus cancers tested; 0.08 % in 939 prostate cancers tested; 0.07 % in 1491 breast cancers tested; 0.05 % in 1957 lung cancers tested; 0.05 % in 1512 liver cancers tested.
Frequency of Mutated Sites:
Most frequent mutations with the number of reports indicated in brackets: R890H (6); Y901C (3). These are located in the kinase catalytic domain.
Comments:
Eighteen deletions, 8 insertions and 1 complex mutation are noted on the COSMIC website.