Nomenclature
Short Name:
p38b
Full Name:
Mitogen-activated protein kinase 11
Alias:
- EC 2.7.1.37
- EC 2.7.11.24
- p38b
- PRKM11
- SAPK2
- Stress-activated protein kinase-2; p28b MARPK
- MAPK11
- MK11
- p38 MAPK-beta
- p38-2
Classification
Type:
Protein-serine/threonine kinase
Group:
CMGC
Family:
MAPK
SubFamily:
p38
Structure
Mol. Mass (Da):
41357
# Amino Acids:
364
# mRNA Isoforms:
2
mRNA Isoforms:
41,357 Da (364 AA; Q15759); 23,603 Da (213 AA; Q15759-3)
4D Structure:
NA
1D Structure:
3D Image (rendered using PV Viewer):
PDB ID
Subfamily Alignment
Domain Distribution:
| Start | End | Domain |
|---|---|---|
| 24 | 308 | 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
Serine phosphorylated:
S243.
Threonine phosphorylated:
T180+.
Tyrosine phosphorylated:
Y182+.
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:
72
670
42
1100
5
49
22
76
4
39
14
40
35
323
129
529
40
370
33
310
6
51
117
172
29
267
47
577
51
476
53
593
27
249
24
180
14
127
123
260
6
53
41
63
63
581
243
588
3
25
47
32
4
34
15
30
7
62
34
104
2
21
22
36
6
54
213
57
6
60
25
70
4
33
128
40
31
285
162
325
9
84
28
98
5
48
35
65
4
34
25
34
4
41
25
49
6
56
29
71
56
518
77
571
3
28
50
31
6
51
25
59
5
43
25
37
18
164
42
163
44
410
30
506
100
927
57
1127
20
189
80
464
74
685
83
671
6
54
48
47
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
71.4
86
100
99.7
99.7
-
-
-
96
-
-
92
71.6
74
95
-
-
-
96.7
98.1
97
74.2
86.8
97
-
-
-
-
-
-
84.1
92
84
74.5
86.5
82
71.2
86.3
83
-
-
-
65.8
79.2
67
67.3
81
-
59.1
73.5
45
-
-
-
-
-
-
-
-
-
-
-
-
-
-
47
-
-
-
47.5
67.9
-
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 | ATF2 - P15336 |
| 2 | TAB1 - Q15750 |
| 3 | HDAC3 - O15379 |
| 4 | PML - P29590 |
| 5 | RPS6KA5 - O75582 |
| 6 | SKIV2L2 - P42285 |
| 7 | KRT1 - P04264 |
| 8 | ZNHIT1 - O43257 |
| 9 | TP53 - P04637 |
| 10 | MAPKAPK5 - Q8IW41 |
| 11 | DUSP16 - Q9BY84 |
| 12 | EEF2K - O00418 |
| 13 | MAP2K1 - Q02750 |
| 14 | MAP2K2 - P36507 |
Regulation
Activation:
Phosphorylation at Tyr-182 and probably Thr-180 by MKK6 increases phosphotransferase activity.
Inhibition:
Inhibited by pyridinyl-imidazole related compounds.
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 |
|---|
| Cdc25B | P30305 | S249 | KMEVEELSPLALGRF | |
| Cyclin D3 (CCND3) | P30281 | T283 | QGPSQTSTPTDVTAI | |
| E2F1 | Q01094 | S403 | PEEFISLSPPHEALD | |
| E2F1 | Q01094 | T433 | DCDFGDLTPLDF___ | |
| eEF2K | O00418 | S396 | TFDSLPSSPSSATPH | |
| EWS | Q01844 | T79 | QPPTGYTTPTAPQAY | |
| GYS1 | P13807 | S645 | RPASVPPSPSLSRHS | - |
| GYS1 | P13807 | S653 | PSLSRHSSPHQSEDE | |
| GYS1 | P13807 | S727 | STPSEPLSPTSSLGE | |
| GYS1 | P13807 | T721 | ATSSSLSTPSEPLSP | |
| GYS2 | P54840 | S645 | RPSSVPPSPSGSQAS | - |
| HNF4A | P41235 | S167 | VLSRQITSPVSGING | |
| MAPKAPK5 | Q8IW41 | T182 | IDQGDLMTPQFTPYY | + |
| PIAS2 | O75928 | S113 | STSVTPHSPSSPVGS | |
| PIAS2 | O75928 | S116 | VTPHSPSSPVGSVLL | |
| PKCe (PRKCE) | Q02156 | S350 | RSKSAPTSPCDQEIK |
Protein Kinase Specificity
Matrix of observed frequency (%) of amino acids in aligned protein substrate phosphosites
Matrix Type:
Experimentally derived from alignment of 19 known protein substrate phosphosites. Note that additional binding sites on p38 substrates with D motifs (consensus= K/R-k-x-s-l/p-l-l-l-p-p or p-x-L/v/i-x-p-p-x-x-x-x-l-l-x-r/k-k/r-R/k-K/r) facilitate higher selectivity for phosphorylation by this protein kinase.
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
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 human Prostate cancer (%CFC= -64, p<0.008). The COSMIC website notes an up-regulated expression score for p38b in diverse human cancers of 347, which is 0.8-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 5 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: 0.04 % in 25371 diverse cancer specimens. This rate is -42 % lower than the average rate of 0.075 % calculated for human protein kinases in general.
Frequency of Mutated Sites:
None > 2 in 20,654 cancer specimens
Comments:
Only 2 deletions, 2 insertions, and no complex mutations are noted on the COSMIC website.