Nomenclature
Short Name:
MARK1
Full Name:
Serine-threonine-protein kinase MARK1
Alias:
- EC 2.7.11.1
- KIAA1477
- MAP/microtubule affinity-regulating kinase 1
- MARK
Classification
Type:
Protein-serine/threonine kinase
Group:
CAMK
Family:
CAMKL
SubFamily:
MARK
Specific Links
Structure
Mol. Mass (Da):
89003
# Amino Acids:
795
# mRNA Isoforms:
3
mRNA Isoforms:
89,003 Da (795 AA; Q9P0L2); 84,911 Da (758 AA; Q9P0L2-3); 72,073 Da (645 AA; Q9P0L2-2)
4D Structure:
NA
1D Structure:
3D Image (rendered using PV Viewer):
PDB ID
Subfamily Alignment
Domain Distribution:
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:
S36, S46, S219-, S382, S393, S399, S403, S423, S444, S463, S468, S470, S475, S498, S556, S573, S588, S590, S593, S595, S612, S624, S633, S649, S679, S681, S699, S710, S711, S766, S787.
Threonine phosphorylated:
T5, T65, T208+, T215+, T465, T504, T580, T581, T596, T598, T613-, T708, T709.
Tyrosine phosphorylated:
Y494, Y505+.
Ubiquitinated:
K783.
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:
100
1169
37
958
2
18
11
13
6
68
1
0
19
224
115
333
46
533
41
401
4
46
64
47
0.9
10
45
9
37
437
22
612
23
274
10
263
4
42
85
31
4
45
16
41
60
705
85
489
3
38
12
22
2
28
6
16
5
54
13
46
2
20
22
26
6
66
106
37
4
47
6
47
5
55
73
31
43
506
135
401
8
96
12
77
4
47
14
41
4
51
2
7
9
103
6
69
4
52
12
51
47
548
74
476
4
42
15
21
5
53
6
49
5
54
6
51
11
132
42
85
27
315
18
218
24
277
36
418
24
279
88
1035
51
596
104
519
17
197
61
191
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
99.3
99.4
99
68.9
80.3
99.5
-
-
97
-
-
-
96
96.9
98
-
-
-
95
97.4
94
94.3
97
95
-
-
-
92.8
96
-
30.4
51.4
92
88.7
94.2
89
27.9
44.1
84
-
-
-
-
-
-
-
-
-
40.8
51.1
39
-
-
-
-
-
-
-
-
-
-
-
-
27.9
44.4
-
28.1
46.7
-
-
-
-
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 | STK11 - Q15831 |
| 2 | TAOK1 - Q7L7X3 |
| 3 | NUAK1 - O60285 |
| 4 | YWHAZ - P63104 |
| 5 | YWHAE - P62258 |
Regulation
Activation:
Activated by phosphorylation on Thr-215 by STK11 in complex with STE20-related adapter-alpha (STRAD alpha) pseudo kinase and CAB39.
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 |
|---|
Protein Kinase Specificity
Matrix of observed frequency (%) of amino acids in aligned protein substrate phosphosites
Matrix Type:
Experimentally derived from alignment of 10 known protein substrate phosphosites and 33 peptides phosphorylated by recombinant MARK1 in vitro tested in-house by Kinexus.
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:
Several SNPs in the MARK1 gene have been identified from genotyping of 276 families with autism. Overexpression of MARK1 in mouse cortical neurons resulted in shorter dendrite length and decreased transport speed. It has been proposed that MARK1 overexpression in autistic individuals may underlie subtle changes in synaptic plasticity linked to dendritic trafficking. MARK1 is over-expressed in the prefrontal cortex of autism patients and affects the function of cortical dendrites.
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= -51, p<0.01); Bladder carcinomas (%CFC= +126, p<0.014); Breast epithelial carcinomas (%CFC= +137, p<0.063); Oral squamous cell carcinomas (OSCC) (%CFC= +50, p<0.068); and Skin squamous cell carcinomas (%CFC= +91, p<0.046). The COSMIC website notes an up-regulated expression score for MARK1 in diverse human cancers of 590, which is 1.3-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 12 for this protein kinase in human cancers was 0.2-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: 0.12 % in 24766 diverse cancer specimens. This rate is a modest 1.57-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: 0.6 % in 1270 large intestine cancers tested; 0.41 % in 864 skin cancers tested; 0.4 % in 603 endometrium cancers tested; 0.28 % in 1634 lung cancers tested; 0.26 % in 629 stomach cancers tested; 0.21 % in 238 bone cancers tested; 0.18 % in 548 urinary tract cancers tested; 0.18 % in 273 cervix cancers tested; 0.11 % in 1459 pancreas cancers tested; 0.08 % in 1512 liver cancers tested; 0.08 % in 1316 breast cancers tested; 0.08 % in 1276 kidney cancers tested; 0.06 % in 833 ovary cancers tested; 0.05 % in 710 oesophagus cancers tested; 0.04 % in 942 upper aerodigestive tract cancers tested; 0.04 % in 2082 central nervous system cancers tested.
Frequency of Mutated Sites:
Most frequent mutations with the number of reports indicated in brackets: N355S (2); N355D (2); N355T (1).
Comments:
Only 1 deletion, 2 insertions and 1 complex mutations are noted on the COSMIC website.