Nomenclature
Short Name:
CaMK1a
Full Name:
Calcium-calmodulin-dependent protein kinase type 1
Alias:
- Calcium/calmodulin-dependent protein kinase I
- Calcium/calmodulin-dependent protein kinase type I
- EC 2.7.11.17
- KCC1
- KCC1A
- Kinase CaMK1-alpha
- CAM kinase I
- CAMK1
- CaMK1-alpha
- CaMKI
Classification
Type:
Protein-serine/threonine kinase
Group:
CAMK
Family:
CAMK1
SubFamily:
NA
Specific Links
Structure
Mol. Mass (Da):
41,337
# Amino Acids:
370
# mRNA Isoforms:
1
mRNA Isoforms:
41,337 Da (370 AA; Q14012)
4D Structure:
Monomer. Interacts with XPO1
1D Structure:
3D Image (rendered using PV Viewer):
PDB ID
Subfamily Alignment
Domain Distribution:
| Start | End | Domain |
|---|---|---|
| 20 | 276 | Pkinase |
| 276 | 316 | Autoinhibitory |
| 296 | 317 | CaM_binding |
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
Serine phosphorylated:
S176, S324, S363, .
Threonine phosphorylated:
T177+, T181-, T323.
Tyrosine phosphorylated:
Y20, Y131+, Y184-, Y235.
Ubiquitinated:
K59.
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:
95
1168
22
990
16
198
11
71
9
105
11
43
21
261
85
383
49
609
21
439
21
254
58
547
16
191
29
437
34
416
37
801
19
234
10
207
7
83
45
52
8
97
24
70
43
525
110
541
7
86
22
37
5
63
8
64
5
63
21
45
21
254
12
300
14
168
177
577
4
45
16
30
5
60
53
29
37
458
79
412
8
93
20
62
6
78
22
53
5
67
20
52
8
101
18
79
5
67
20
59
100
1231
56
1981
6
72
25
35
7
90
16
54
10
124
18
63
20
252
14
69
46
572
18
408
57
703
26
1394
43
534
67
925
56
692
57
646
8
97
35
70
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
99.5
99.7
99.5
98.9
99.2
99
-
-
96
-
-
99
96.5
97.3
96.5
-
-
-
96
96.8
98
96.3
97.1
98
-
-
-
86.9
89.9
-
54.5
65.5
87
42.2
62.3
84
39.2
58
85
38.5
57.5
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
29
44
-
-
-
42
31.8
46.5
-
32.7
49.8
42
-
-
43
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
Binding Proteins
Examples of known interacting proteins
hiddentext
| No. | Name – UniProt ID |
|---|---|
| 1 | CAMKK2 - Q96RR4 |
| 2 | HDAC5 - Q9UQL6 |
| 3 | CALM1 - P62158 |
| 4 | CAMKK1 - Q8N5S9 |
| 5 | ATF1 - P18846 |
| 6 | EIF4G3 - O43432 |
| 7 | SYN1 - P17600 |
| 8 | NOS1 - P29475 |
| 9 | GAPDH - P04406 |
Regulation
Activation:
Phosphorylation at Thr-177 increases phosphotransferase activity by approximately 25-fold in a Ca(2+)-CaM dependent manner. Thr-177 is phosphorylated by CAMKK1 or CAMKK2.
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 |
|---|
| ARHGEF7 (BETAPIX) | Q14155 | S694 | RKPERKPSDEEFASR | + |
| CaMKK1 | Q8N5S9 | T108 | PRAWRRPTIESHHVA | + |
| CREB1 | P16220 | S133 | EILSRRPSYRKILND | + |
| DRP1 | O00429 | S637 | VPVARKLSAREQRDC | |
| eIF4G3 | O43432 | S1156 | NTFMRGGSSKDLLDN | |
| HDAC4 | P56524 | S246 | FPLRKTASEPNLKLR | |
| HDAC5 | Q9UQL6 | S259 | FPLRKTASEPNLKVR | - |
| HDAC5 | Q9UQL6 | S498 | RPLSRTQSSPLPQSP | - |
| HDAC7 | Q8WUI4 | S358 | WPLSRTRSEPLPPSA | |
| HDAC7 | Q8WUI4 | S486 | RPLSRAQSSPAAPAS | |
| HMGCR | P04035 | S872 | SHMIHNRSKINLQDL | |
| KRT18 | P05783 | S53 | ISVSRSTSFRGGMGS | |
| LIPE (HSL) | Q05469 | S855 | EPMRRSVSEAALAQP | |
| MARK2 | Q7KZI7 | S91 | IDKTQLNSSSLQKLF | + |
| MARK2 | Q7KZI7 | S92 | DKTQLNSSSLQKLFR | + |
| MARK2 | Q7KZI7 | S93 | KTQLNSSSLQKLFR | + |
| MARK2 | Q7KZI7 | T294 | LNPSKRGTLEQIMKD | + |
| MRLC1 (MYL9) | P24844 | S20 | KRPQRATSNVFAMFD | |
| nNOS | P29475 | S746 | LAEAVKFSAKLMGQA | |
| NUMB | P49757 | S276 | EQLARQGSFRGFPAL | |
| NUMB | P49757 | S295 | SPFKRQLSLRINELP | |
| NUMBL | Q9Y6R0 | S305 | EQLVRQGSFRGFPAL | |
| PKLR | P30613 | T48 | RASVAQLTQELGTAF | |
| PKLR | P30613 | T53 | QLTQELGTAFFQQQQ | |
| RPS19 | P39019 | S59 | WFYTRAASTARHLYL | |
| RyR1 | P21817 | S2843 | KKKTRKISQSAQTYD | |
| SYN1 | P17600 | S9 | NYLRRRLSDSNFMAN | |
| TH | P07101 | S19 | KGFRRAVSEQDAKQA | + |
| TH | P07101 | S71 | RFIGRRQSLIEDARK | + |
Protein Kinase Specificity
Matrix of observed frequency (%) of amino acids in aligned protein substrate phosphosites
Matrix Type:
Experimentally derived from alignment of 45 known protein substrate phosphosites.
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
Comments:
CaMK1a inhibition with either KN-93 or a specific interfering RNA caused cell cycle arrest in the MCF-7 human breast tumour cell line.
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 cell carcinomas (%CFC= +47, p<0.01); Prostate cancer - primary (%CFC= -49, p<0.0001); and Uterine fibroids (%CFC= +66, p<0.0008). The COSMIC website notes an up-regulated expression score for CaMK1a in diverse human cancers of 384, which is 0.8-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 8 for this protein kinase in human cancers was 0.1-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: 0.08 % in 24726 diverse cancer specimens. This rate is very similar (+ 6% 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: 0.47 % in 1270 large intestine cancers tested; 0.31 % in 864 skin cancers tested; 0.31 % in 603 endometrium cancers tested; 0.28 % in 589 stomach cancers tested.
Frequency of Mutated Sites:
None > 5 in 20,009 cancer specimens
Comments:
Only 1 insertion, and no deletions or complex mutations are noted in COSMIC website