Nomenclature
Short Name:
FGR
Full Name:
Proto-oncogene tyrosine-protein kinase FGR
Alias:
- C-FGR
- P55-FGR
- Proto-oncogene tyrosine-protein kinase FGR
- SRC2
- EC 2.7.10.2
- FGR protein
- Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene
- Kinase Fgr
- P55c-fgr
Classification
Type:
Protein-tyrosine kinase
Group:
TK
Family:
Src
SubFamily:
NA
Specific Links
Structure
Mol. Mass (Da):
59,479
# Amino Acids:
529
# mRNA Isoforms:
1
mRNA Isoforms:
59,479 Da (529 AA; P09769)
4D Structure:
Binds PTPNS1
1D Structure:
Subfamily Alignment
Domain Distribution:
Kinexus Products
Click on entries below for direct links to relevant products from Kinexus for this protein kinase.
hiddentext
Post-translation Modifications
For detailed information on phosphorylation of this kinase go to PhosphoNET
Myristoylated:
G2 (predicted).
Palmitoylated:
C3 (predicted), C6 (predicted).
Serine phosphorylated:
S173, S181, S183, S341.
Threonine phosphorylated:
T176, T211, T212, T292, T453.
Tyrosine phosphorylated:
Y28, Y34, Y86, Y180, Y208, Y209, Y412+, Y523-.
Ubiquitinated:
K16, K177, K301.
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:
62
1037
16
1581
3
48
10
55
3
57
11
46
12
207
56
389
33
549
14
548
7
111
44
195
21
345
19
645
54
898
30
2150
10
173
10
173
9
142
45
214
5
82
24
78
46
770
104
650
10
163
22
126
3
55
9
55
3
55
20
79
3
47
8
36
6
100
112
64
3
46
18
60
3
50
53
36
27
452
56
475
5
88
20
72
25
411
22
334
10
168
20
187
2
39
18
40
6
96
20
86
52
868
37
1734
5
83
25
51
4
63
18
65
4
68
18
52
4
61
14
53
51
853
18
498
43
724
21
673
28
466
57
752
100
1666
31
535
9
157
22
146
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
69
78.9
100
97.5
98.5
97.5
-
-
90
-
-
98
89
93.2
89
-
-
-
84.5
89.8
86
69.5
79.1
87
-
-
-
76.2
85
-
71.8
82.1
74
69.3
78.4
74
70.9
82.6
72
-
-
-
54.3
67.7
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
Binding Proteins
Examples of known interacting proteins
hiddentext
| No. | Name – UniProt ID |
|---|---|
| 1 | CBL - P22681 |
| 2 | HCLS1 - P14317 |
| 3 | VDR - P11473 |
| 4 | CSK - P41240 |
| 5 | SLAMF1 - Q13291 |
| 6 | DAB2 - P98082 |
| 7 | DOK1 - Q99704 |
| 8 | ERBB2 - P04626 |
Regulation
Activation:
NA
Inhibition:
NA
Synthesis:
NA
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 |
|---|
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 |
|---|
| CK2a1 (CSNK2A1) | P68400 | S194 | EYNVRVASRYFKGPE | + |
| CK2a1 (CSNK2A1) | P68400 | S2 | ______MSGPVPSRA | |
| CK2a1 (CSNK2A1) | P68400 | Y255 | VLGTEDLYDYIDKYN | |
| FAK (PTK2) | Q05397 | Y397 | SVSETDDYAEIIDEE | + |
| FAK (PTK2) | Q05397 | Y576 | RYMEDSTYYKASKGK | + |
| FAK (PTK2) | Q05397 | Y925 | DRSNDKVYENVTGLV | + |
| Fgr | P09769 | Y412 | RLIKDDEYNPCQGSK | + |
| Fgr | P09769 | Y523 | FTSAEPQYQPGDQT_ | - |
| HS1 (HCLS1) | P14317 | Y222 | MEAPTTAYKKTTPIE | ? |
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
Inhibitors
For further details on these inhibitors click on the Compound Name and enter it into DrugKiNET or click on the ID's
Based on in vitro and/or in vivo phosphorylation data
| Compound Name | KD, Ki or IC50 (nM) | PubChem ID | ChEMBL ID | PubMed ID |
|---|
Disease Linkage
General Disease Association:
Cancer, cardiovascular disorders
Specific Diseases (Non-cancerous):
Pre-eclampsia
Specific Cancer Types:
Sarcomas
Comments:
FGR appears to be an oncoprotein (OP). A Y523F mutation in Fgr is associated with strongly increased catalytic activity, which can be oncogenic and promote abnormal cell proliferation. Fgr oncogene mRNA was found to be induced in B lymphocytes by Epstein-Barr virus infection.
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: Bladder carcinomas (%CFC= -49, p<0.009); Cervical cancer (%CFC= -56, p<0.002); Clear cell renal cell carcinomas (cRCC) (%CFC= +82, p<0.033); Colorectal adenocarcinomas (early onset) (%CFC= +117, p<0.005); and Lung adenocarcinomas (%CFC= -47, p<0.0001). The COSMIC website notes an up-regulated expression score for FGR in diverse human cancers of 284, which is 0.6-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 25 for this protein kinase in human cancers was 0.4-fold of 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: 0.07 % in 25231 diverse cancer specimens. This rate is only -1 % lower and is very similar 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: 0.52 % in 805 skin cancers tested; 0.24 % in 1093 large intestine cancers tested.
Frequency of Mutated Sites:
None > 4 in 20,497 cancer specimens
Comments:
No deletions, insertions or complex mutations are noted on the COSMIC website.