Details of the Target

General Information of Target

Target ID LDTP03617
Target Name 14-3-3 protein beta/alpha (YWHAB)
Gene Name YWHAB
Gene ID 7529
Synonyms
14-3-3 protein beta/alpha; Protein 1054; Protein kinase C inhibitor protein 1; KCIP-1) [Cleaved into: 14-3-3 protein beta/alpha, N-terminally processed]
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Sequence
MTMDKSELVQKAKLAEQAERYDDMAAAMKAVTEQGHELSNEERNLLSVAYKNVVGARRSS
WRVISSIEQKTERNEKKQQMGKEYREKIEAELQDICNDVLELLDKYLIPNATQPESKVFY
LKMKGDYFRYLSEVASGDNKQTTVSNSQQAYQEAFEISKKEMQPTHPIRLGLALNFSVFY
YEILNSPEKACSLAKTAFDEAIAELDTLNEESYKDSTLIMQLLRDNLTLWTSENQGDEGD
AGEGEN
Target Bioclass
Other
Family
14-3-3 family
Subcellular location
Cytoplasm; Vacuole membrane
Function
Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negative regulator of osteogenesis. Blocks the nuclear translocation of the phosphorylated form (by AKT1) of SRPK2 and antagonizes its stimulatory effect on cyclin D1 expression resulting in blockage of neuronal apoptosis elicited by SRPK2. Negative regulator of signaling cascades that mediate activation of MAP kinases via AKAP13.
Uniprot ID
P31946
Ensemble ID
ENST00000353703.9
HGNC ID
HGNC:12849
ChEMBL ID
CHEMBL3710403

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
JURKAT Deletion: p.G125del .
KARPAS422 SNV: p.K122Q .
MDAMB453 SNV: p.E72Q .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 39 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
m-APA
 Probe Info  		12.96  LDD0402  [1]
P1
 Probe Info  		1.82  LDD0448  [2]
P2
 Probe Info  		3.30  LDD0449  [2]
P3
 Probe Info  		3.13  LDD0450  [2]
P8
 Probe Info  		4.77  LDD0451  [2]
CY-1
 Probe Info  		6.05  LDD0243  [3]
N1
 Probe Info  		100.00  LDD0242  [3]
C-Sul
 Probe Info  		2.18  LDD0066  [4]
TH211
 Probe Info  		Y213(10.74)  LDD0257  [5]
TH214
 Probe Info  		Y120(20.00); Y50(13.97)  LDD0258  [5]
TH216
 Probe Info  		Y50(17.86); Y130(8.58); Y213(6.51)  LDD0259  [5]
AZ-9
 Probe Info  		E156(0.99); E16(1.06); E115(1.33); E161(1.32)  LDD2208  [6]
ONAyne
 Probe Info  		K77(0.00); K70(0.00); K11(0.00)  LDD0273  [7]
OPA-S-S-alkyne
 Probe Info  		K70(3.41); K51(6.52)  LDD3494  [8]
Probe 1
 Probe Info  		Y21(40.72); Y130(398.86); Y151(40.40); Y213(16.73)  LDD3495  [9]
DBIA
 Probe Info  		C96(3.06)  LDD3323  [10]
SAHA-CA-4PAP
 Probe Info  		5.30  LDD0269  [11]
HHS-482
 Probe Info  		Y130(1.10); Y21(1.10)  LDD0285  [12]
HHS-475
 Probe Info  		Y151(0.65); Y50(1.01); Y213(1.35); Y130(1.65)  LDD0264  [13]
HHS-465
 Probe Info  		Y130(7.92); Y50(10.00)  LDD2237  [14]
W1
 Probe Info  		K11(1.33); Q10(1.33)  LDD0237  [15]
5E-2FA
 Probe Info  		N.A.  LDD2235  [16]
AMP probe
 Probe Info  		K51(0.00); K70(0.00)  LDD0200  [17]
ATP probe
 Probe Info  		K51(0.00); K70(0.00); K13(0.00); K117(0.00)  LDD0199  [17]
4-Iodoacetamidophenylacetylene
 Probe Info  		N.A.  LDD0038  [18]
IA-alkyne
 Probe Info  		N.A.  LDD0036  [18]
Lodoacetamide azide
 Probe Info  		N.A.  LDD0037  [18]
ATP probe
 Probe Info  		K13(0.00); K51(0.00); K124(0.00); K29(0.00)  LDD0035  [19]
NHS
 Probe Info  		K160(0.00); K70(0.00); K51(0.00); K117(0.00)  LDD0010  [20]
SF
 Probe Info  		Y50(0.00); K51(0.00); K13(0.00); Y130(0.00)  LDD0028  [21]
STPyne
 Probe Info  		K70(0.00); K13(0.00); K51(0.00)  LDD0009  [20]
Ox-W18
 Probe Info  		N.A.  LDD2175  [22]
1c-yne
 Probe Info  		K140(0.00); K29(0.00); K195(0.00)  LDD0228  [23]
1d-yne
 Probe Info  		N.A.  LDD0357  [23]
Acrolein
 Probe Info  		N.A.  LDD0217  [24]
Crotonaldehyde
 Probe Info  		N.A.  LDD0219  [24]
Methacrolein
 Probe Info  		N.A.  LDD0218  [24]
AOyne
 Probe Info  		8.40  LDD0443  [25]
NAIA_5
 Probe Info  		C96(0.00); C191(0.00)  LDD2223  [26]
PAL-AfBPP Probe
Click To Hide/Show 8 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
C278
 Probe Info  		65.34  LDD1948  [27]
FFF probe12
 Probe Info  		5.13  LDD0473  [28]
FFF probe13
 Probe Info  		7.29  LDD0475  [28]
STS-2
 Probe Info  		N.A.  LDD0139  [29]
VE-P
 Probe Info  		N.A.  LDD0396  [30]
Diazir
 Probe Info  		N.A.  LDD0011  [20]
DA-2
 Probe Info  		N.A.  LDD0071  [31]
STS-1
 Probe Info  		N.A.  LDD0068  [32]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0214  AC1 HEK-293T C96(1.10)  LDD1507  [33]
 LDCM0259  AC14 HEK-293T C96(0.93)  LDD1512  [33]
 LDCM0276  AC17 HEK-293T C96(0.84)  LDD1515  [33]
 LDCM0282  AC22 HEK-293T C96(1.09)  LDD1521  [33]
 LDCM0285  AC25 HEK-293T C96(0.87)  LDD1524  [33]
 LDCM0291  AC30 HEK-293T C96(0.98)  LDD1530  [33]
 LDCM0294  AC33 HEK-293T C96(0.97)  LDD1533  [33]
 LDCM0299  AC38 HEK-293T C96(0.96)  LDD1538  [33]
 LDCM0303  AC41 HEK-293T C96(0.98)  LDD1542  [33]
 LDCM0308  AC46 HEK-293T C96(1.11)  LDD1547  [33]
 LDCM0311  AC49 HEK-293T C96(0.83)  LDD1550  [33]
 LDCM0317  AC54 HEK-293T C96(0.95)  LDD1556  [33]
 LDCM0320  AC57 HEK-293T C96(0.93)  LDD1559  [33]
 LDCM0323  AC6 HEK-293T C96(1.09)  LDD1562  [33]
 LDCM0326  AC62 HEK-293T C96(0.98)  LDD1565  [33]
 LDCM0356  AKOS034007680 HEK-293T C96(1.01)  LDD1570  [33]
 LDCM0156  Aniline NCI-H1299 11.98  LDD0403  [1]
 LDCM0630  CCW28-3 231MFP C96(0.95); C96(0.54)  LDD2214  [34]
 LDCM0108  Chloroacetamide HeLa N.A.  LDD0222  [24]
 LDCM0368  CL10 HEK-293T C96(1.02)  LDD1572  [33]
 LDCM0404  CL17 HEK-293T C96(1.10)  LDD1608  [33]
 LDCM0410  CL22 HEK-293T C96(1.48)  LDD1614  [33]
 LDCM0417  CL29 HEK-293T C96(0.96)  LDD1621  [33]
 LDCM0423  CL34 HEK-293T C96(1.15)  LDD1627  [33]
 LDCM0431  CL41 HEK-293T C96(0.94)  LDD1635  [33]
 LDCM0436  CL46 HEK-293T C96(1.20)  LDD1640  [33]
 LDCM0440  CL5 HEK-293T C96(0.82)  LDD1644  [33]
 LDCM0444  CL53 HEK-293T C96(0.86)  LDD1647  [33]
 LDCM0449  CL58 HEK-293T C96(1.19)  LDD1652  [33]
 LDCM0457  CL65 HEK-293T C96(0.98)  LDD1660  [33]
 LDCM0463  CL70 HEK-293T C96(1.18)  LDD1666  [33]
 LDCM0470  CL77 HEK-293T C96(0.94)  LDD1673  [33]
 LDCM0476  CL82 HEK-293T C96(1.15)  LDD1679  [33]
 LDCM0483  CL89 HEK-293T C96(0.95)  LDD1686  [33]
 LDCM0489  CL94 HEK-293T C96(1.22)  LDD1692  [33]
 LDCM0116  HHS-0101 DM93 Y151(0.65); Y50(1.01); Y213(1.35); Y130(1.65)  LDD0264  [13]
 LDCM0117  HHS-0201 DM93 Y151(0.44); Y50(0.88); Y130(1.82); Y213(3.64)  LDD0265  [13]
 LDCM0118  HHS-0301 DM93 Y151(0.42); Y130(0.79); Y50(0.82); Y213(1.15)  LDD0266  [13]
 LDCM0119  HHS-0401 DM93 Y151(0.82); Y50(0.89); Y213(1.26); Y130(2.53)  LDD0267  [13]
 LDCM0120  HHS-0701 DM93 Y50(0.75); Y151(0.85); Y213(1.32); Y130(2.33)  LDD0268  [13]
 LDCM0107  IAA HeLa N.A.  LDD0221  [24]
 LDCM0123  JWB131 DM93 Y130(1.10); Y21(1.10)  LDD0285  [12]
 LDCM0124  JWB142 DM93 Y130(0.42); Y21(0.35)  LDD0286  [12]
 LDCM0125  JWB146 DM93 Y130(0.96); Y21(0.88)  LDD0287  [12]
 LDCM0126  JWB150 DM93 Y130(3.31); Y21(3.50)  LDD0288  [12]
 LDCM0127  JWB152 DM93 Y130(2.18); Y21(3.04)  LDD0289  [12]
 LDCM0128  JWB198 DM93 Y130(0.96); Y21(1.30)  LDD0290  [12]
 LDCM0129  JWB202 DM93 Y130(0.37); Y21(0.36)  LDD0291  [12]
 LDCM0130  JWB211 DM93 Y130(0.88); Y21(0.69)  LDD0292  [12]
 LDCM0022  KB02 CC-LP-1 C96(1.13)  LDD2298  [10]
 LDCM0023  KB03 CC-LP-1 C96(1.53)  LDD2715  [10]
 LDCM0024  KB05 SKMEL24 C96(3.06)  LDD3323  [10]
 LDCM0109  NEM HeLa N.A.  LDD0223  [24]
 LDCM0096  SAHA K562 5.30  LDD0269  [11]
 LDCM0110  W12 Hep-G2 K11(1.33); Q10(1.33)  LDD0237  [15]
 LDCM0111  W14 Hep-G2 K11(0.69)  LDD0238  [15]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 19 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Histone deacetylase 4 (HDAC4) Histone deacetylase family P56524
M-phase inducer phosphatase 1 (CDC25A) MPI phosphatase family P30304
M-phase inducer phosphatase 2 (CDC25B) MPI phosphatase family P30305
M-phase inducer phosphatase 3 (CDC25C) MPI phosphatase family P30307
MAP/microtubule affinity-regulating kinase 3 (MARK3) CAMK Ser/Thr protein kinase family P27448
Serine/threonine-protein kinase MARK2 (MARK2) CAMK Ser/Thr protein kinase family Q7KZI7
SRSF protein kinase 2 (SRPK2) CMGC Ser/Thr protein kinase family P78362
Cyclin-dependent kinase 14 (CDK14) CMGC Ser/Thr protein kinase family O94921
Mitogen-activated protein kinase kinase kinase 3 (MAP3K3) STE Ser/Thr protein kinase family Q99759
Mitogen-activated protein kinase kinase kinase 5 (MAP3K5) STE Ser/Thr protein kinase family Q99683
Leucine-rich repeat serine/threonine-protein kinase 2 (LRRK2) TKL Ser/Thr protein kinase family Q5S007
RAF proto-oncogene serine/threonine-protein kinase (RAF1) TKL Ser/Thr protein kinase family P04049
Serine/threonine-protein kinase B-raf (BRAF) TKL Ser/Thr protein kinase family P15056
Protein phosphatase Slingshot homolog 1 (SSH1) Protein-tyrosine phosphatase family Q8WYL5
Tyrosine-protein phosphatase non-receptor type 3 (PTPN3) Protein-tyrosine phosphatase family P26045
GTP-binding protein GEM (GEM) RGK family P55040
Rho-related GTP-binding protein RhoE (RND3) Rho family P61587
E3 SUMO-protein ligase CBX4 (CBX4) . O00257
E3 ubiquitin-protein ligase CBL (CBL) . P22681
Transporter and channel
Click To Hide/Show 5 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
14-3-3 protein epsilon (YWHAE) 14-3-3 family P62258
14-3-3 protein gamma (YWHAG) 14-3-3 family P61981
14-3-3 protein theta (YWHAQ) 14-3-3 family P27348
Amyloid-beta precursor protein (APP) APP family P05067
Huntingtin (HTT) Huntingtin family P42858
Other
Click To Hide/Show 8 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
14-3-3 protein beta/alpha (YWHAB) 14-3-3 family P31946
Ataxin-1 (ATXN1) ATXN1 family P54253
Bcl2-associated agonist of cell death (BAD) Bcl-2 family Q92934
Dapper homolog 1 (DACT1) Dapper family Q9NYF0
GRB2-associated-binding protein 2 (GAB2) GAB family Q9UQC2
Regulator of microtubule dynamics protein 3 (RMDN3) RMDN family Q96TC7
Transcriptional coactivator YAP1 (YAP1) YAP1 family P46937
Tuberin (TSC2) . P49815

The Drug(s) Related To This Target

Approved
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Copper . DB09130
Investigative
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Phenethyl Isothiocyanate Small molecular drug DB12695

References

1 Quantitative and Site-Specific Chemoproteomic Profiling of Targets of Acrolein. Chem Res Toxicol. 2019 Mar 18;32(3):467-473. doi: 10.1021/acs.chemrestox.8b00343. Epub 2019 Jan 15.
2 Comparison of Different Competitive Proteome Profiling Approaches in Target Identification of Covalent Inhibitors. Chembiochem. 2022 Dec 16;23(24):e202200389. doi: 10.1002/cbic.202200389. Epub 2022 Nov 22.
3 Cyclopropenone, Cyclopropeniminium Ion, and Cyclopropenethione as Novel Electrophilic Warheads for Potential Target Discovery of Triple-Negative Breast Cancer. J Med Chem. 2023 Feb 23;66(4):2851-2864. doi: 10.1021/acs.jmedchem.2c01889. Epub 2023 Feb 10.
4 Low-Toxicity Sulfonium-Based Probes for Cysteine-Specific Profiling in Live Cells. Anal Chem. 2022 Mar 15;94(10):4366-4372. doi: 10.1021/acs.analchem.1c05129. Epub 2022 Mar 4.
5 Chemoproteomic profiling of kinases in live cells using electrophilic sulfonyl triazole probes. Chem Sci. 2021 Jan 21;12(9):3295-3307. doi: 10.1039/d0sc06623k.
6 2H-Azirine-Based Reagents for Chemoselective Bioconjugation at Carboxyl Residues Inside Live Cells. J Am Chem Soc. 2020 Apr 1;142(13):6051-6059. doi: 10.1021/jacs.9b12116. Epub 2020 Mar 23.
7 A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells. Chem Sci. 2021 Oct 15;12(43):14557-14563. doi: 10.1039/d1sc02230j. eCollection 2021 Nov 10.
Mass spectrometry data entry: PXD028270
8 A chemical proteomics approach for global mapping of functional lysines on cell surface of living cell. Nat Commun. 2024 Apr 8;15(1):2997. doi: 10.1038/s41467-024-47033-w.
Mass spectrometry data entry: PXD042888
9 An Azo Coupling-Based Chemoproteomic Approach to Systematically Profile the Tyrosine Reactivity in the Human Proteome. Anal Chem. 2021 Jul 27;93(29):10334-10342. doi: 10.1021/acs.analchem.1c01935. Epub 2021 Jul 12.
10 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
11 Streamlined Target Deconvolution Approach Utilizing a Single Photoreactive Chloroalkane Capture Tag. ACS Chem Biol. 2021 Feb 19;16(2):404-413. doi: 10.1021/acschembio.0c00987. Epub 2021 Feb 5.
12 Chemoproteomic profiling of kinases in live cells using electrophilic sulfonyl triazole probes. Chem Sci. 2021 Jan 21;12(9):3295-3307. doi: 10.1039/d0sc06623k.
13 Discovery of a Cell-Active SuTEx Ligand of Prostaglandin Reductase 2. Chembiochem. 2021 Jun 15;22(12):2134-2139. doi: 10.1002/cbic.202000879. Epub 2021 Apr 29.
14 Global targeting of functional tyrosines using sulfur-triazole exchange chemistry. Nat Chem Biol. 2020 Feb;16(2):150-159. doi: 10.1038/s41589-019-0404-5. Epub 2019 Nov 25.
15 Oxidant-Induced Bioconjugation for Protein Labeling in Live Cells. ACS Chem Biol. 2023 Jan 20;18(1):112-122. doi: 10.1021/acschembio.2c00740. Epub 2022 Dec 21.
16 Global profiling of functional histidines in live cells using small-molecule photosensitizer and chemical probe relay labelling. Nat Chem. 2024 Jun 4. doi: 10.1038/s41557-024-01545-6. Online ahead of print.
Mass spectrometry data entry: PXD042377
17 Targeted Proteomic Approaches for Proteome-Wide Characterizations of the AMP-Binding Capacities of Kinases. J Proteome Res. 2022 Aug 5;21(8):2063-2070. doi: 10.1021/acs.jproteome.2c00225. Epub 2022 Jul 12.
18 Enhancing Cysteine Chemoproteomic Coverage through Systematic Assessment of Click Chemistry Product Fragmentation. Anal Chem. 2022 Mar 8;94(9):3800-3810. doi: 10.1021/acs.analchem.1c04402. Epub 2022 Feb 23.
Mass spectrometry data entry: PXD028853
19 Comparison of Quantitative Mass Spectrometry Platforms for Monitoring Kinase ATP Probe Uptake in Lung Cancer. J Proteome Res. 2018 Jan 5;17(1):63-75. doi: 10.1021/acs.jproteome.7b00329. Epub 2017 Nov 22.
Mass spectrometry data entry: PXD006095 , PXD006096
20 A modification-centric assessment tool for the performance of chemoproteomic probes. Nat Chem Biol. 2022 Aug;18(8):904-912. doi: 10.1038/s41589-022-01074-8. Epub 2022 Jul 21.
Mass spectrometry data entry: PXD027758 , PXD027755 , PXD027760 , PXD027762 , PXD027756 , PXD027591 , PXD007149 , PXD030064 , PXD032392 , PXD027789 , PXD027767 , PXD027764
21 Solid Phase Synthesis of Fluorosulfate Containing Macrocycles for Chemoproteomic Workflows. bioRxiv [Preprint]. 2023 Feb 18:2023.02.17.529022. doi: 10.1101/2023.02.17.529022.
Mass spectrometry data entry: PXD039931
22 Oxidative cyclization reagents reveal tryptophan cation- interactions. Nature. 2024 Mar;627(8004):680-687. doi: 10.1038/s41586-024-07140-6. Epub 2024 Mar 6.
Mass spectrometry data entry: PXD001377 , PXD005252
23 Tunable Amine-Reactive Electrophiles for Selective Profiling of Lysine. Angew Chem Int Ed Engl. 2022 Jan 26;61(5):e202112107. doi: 10.1002/anie.202112107. Epub 2021 Dec 16.
24 ACR-Based Probe for the Quantitative Profiling of Histidine Reactivity in the Human Proteome. J Am Chem Soc. 2023 Mar 8;145(9):5252-5260. doi: 10.1021/jacs.2c12653. Epub 2023 Feb 27.
25 Chemoproteomic profiling of targets of lipid-derived electrophiles by bioorthogonal aminooxy probe. Redox Biol. 2017 Aug;12:712-718. doi: 10.1016/j.redox.2017.04.001. Epub 2017 Apr 5.
26 N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics. Nat Commun. 2023 Jun 15;14(1):3564. doi: 10.1038/s41467-023-39268-w.
Mass spectrometry data entry: PXD041264
27 Large-scale chemoproteomics expedites ligand discovery and predicts ligand behavior in cells. Science. 2024 Apr 26;384(6694):eadk5864. doi: 10.1126/science.adk5864. Epub 2024 Apr 26.
Mass spectrometry data entry: PXD041587
28 Ligand and Target Discovery by Fragment-Based Screening in Human Cells. Cell. 2017 Jan 26;168(3):527-541.e29. doi: 10.1016/j.cell.2016.12.029. Epub 2017 Jan 19.
29 Design and synthesis of minimalist terminal alkyne-containing diazirine photo-crosslinkers and their incorporation into kinase inhibitors for cell- and tissue-based proteome profiling. Angew Chem Int Ed Engl. 2013 Aug 12;52(33):8551-6. doi: 10.1002/anie.201300683. Epub 2013 Jun 10.
30 Pharmacological Targeting of Vacuolar H(+)-ATPase via Subunit V1G Combats Multidrug-Resistant Cancer. Cell Chem Biol. 2020 Nov 19;27(11):1359-1370.e8. doi: 10.1016/j.chembiol.2020.06.011. Epub 2020 Jul 9.
31 Cell-based proteome profiling of potential dasatinib targets by use of affinity-based probes. J Am Chem Soc. 2012 Feb 15;134(6):3001-14. doi: 10.1021/ja208518u. Epub 2012 Feb 1.
32 Proteome profiling reveals potential cellular targets of staurosporine using a clickable cell-permeable probe. Chem Commun (Camb). 2011 Oct 28;47(40):11306-8. doi: 10.1039/c1cc14824a. Epub 2011 Sep 16.
33 Accelerating multiplexed profiling of protein-ligand interactions: High-throughput plate-based reactive cysteine profiling with minimal input. Cell Chem Biol. 2024 Mar 21;31(3):565-576.e4. doi: 10.1016/j.chembiol.2023.11.015. Epub 2023 Dec 19.
Mass spectrometry data entry: PXD044402
34 Covalent Ligand Screening Uncovers a RNF4 E3 Ligase Recruiter for Targeted Protein Degradation Applications. ACS Chem Biol. 2019 Nov 15;14(11):2430-2440. doi: 10.1021/acschembio.8b01083. Epub 2019 May 13.