General Information of Target

Target ID LDTP02884
Target Name Heat shock 70 kDa protein 6 (HSPA6)
Gene Name HSPA6
Gene ID 3310
Synonyms
HSP70B'; Heat shock 70 kDa protein 6; Heat shock 70 kDa protein B'
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MQAPRELAVGIDLGTTYSCVGVFQQGRVEILANDQGNRTTPSYVAFTDTERLVGDAAKSQ
AALNPHNTVFDAKRLIGRKFADTTVQSDMKHWPFRVVSEGGKPKVRVCYRGEDKTFYPEE
ISSMVLSKMKETAEAYLGQPVKHAVITVPAYFNDSQRQATKDAGAIAGLNVLRIINEPTA
AAIAYGLDRRGAGERNVLIFDLGGGTFDVSVLSIDAGVFEVKATAGDTHLGGEDFDNRLV
NHFMEEFRRKHGKDLSGNKRALRRLRTACERAKRTLSSSTQATLEIDSLFEGVDFYTSIT
RARFEELCSDLFRSTLEPVEKALRDAKLDKAQIHDVVLVGGSTRIPKVQKLLQDFFNGKE
LNKSINPDEAVAYGAAVQAAVLMGDKCEKVQDLLLLDVAPLSLGLETAGGVMTTLIQRNA
TIPTKQTQTFTTYSDNQPGVFIQVYEGERAMTKDNNLLGRFELSGIPPAPRGVPQIEVTF
DIDANGILSVTATDRSTGKANKITITNDKGRLSKEEVERMVHEAEQYKAEDEAQRDRVAA
KNSLEAHVFHVKGSLQEESLRDKIPEEDRRKMQDKCREVLAWLEHNQLAEKEEYEHQKRE
LEQICRPIFSRLYGGPGVPGGSSCGTQARQGDPSTGPIIEEVD
Target Bioclass
Other
Family
Heat shock protein 70 family
Function
Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The affinity for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release.
Uniprot ID
P17066
Ensemble ID
ENST00000309758.6
HGNC ID
HGNC:5239
ChEMBL ID
CHEMBL3232688

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 13 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
P2
 Probe Info 
1.88  LDD0449  [1]
P3
 Probe Info 
1.71  LDD0450  [1]
P8
 Probe Info 
2.27  LDD0451  [1]
YN-1
 Probe Info 
100.00  LDD0444  [2]
YN-4
 Probe Info 
100.00  LDD0445  [2]
AZ-9
 Probe Info 
E317(1.00); D354(0.89); D48(10.00); Y185(0.78)  LDD2208  [3]
ONAyne
 Probe Info 
K514(0.00); K330(0.00)  LDD0273  [4]
HHS-475
 Probe Info 
Y43(0.96); Y373(1.91)  LDD0264  [5]
HHS-465
 Probe Info 
Y185(5.12); Y43(10.00); Y433(4.63)  LDD2237  [6]
DBIA
 Probe Info 
C308(1.13)  LDD2171  [7]
5E-2FA
 Probe Info 
N.A.  LDD2235  [8]
IA-alkyne
 Probe Info 
C308(0.00); C269(0.00)  LDD0166  [9]
HHS-482
 Probe Info 
Y373(2.39)  LDD2239  [6]
PAL-AfBPP Probe
Click To Hide/Show 5 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
FFF probe13
 Probe Info 
6.13  LDD0475  [10]
FFF probe14
 Probe Info 
5.47  LDD0477  [10]
FFF probe3
 Probe Info 
5.61  LDD0465  [10]
OEA-DA
 Probe Info 
3.43  LDD0046  [11]
STS-1
 Probe Info 
N.A.  LDD0069  [12]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0020  ARS-1620 HCC44 C308(1.13)  LDD2171  [7]
 LDCM0116  HHS-0101 DM93 Y43(0.96); Y373(1.91)  LDD0264  [5]
 LDCM0117  HHS-0201 DM93 Y43(0.84); Y373(1.06)  LDD0265  [5]
 LDCM0118  HHS-0301 DM93 Y43(0.85); Y373(6.31)  LDD0266  [5]
 LDCM0119  HHS-0401 DM93 Y43(0.75); Y373(1.95)  LDD0267  [5]
 LDCM0120  HHS-0701 DM93 Y43(0.48); Y373(1.18)  LDD0268  [5]
 LDCM0021  THZ1 HCT 116 C308(1.13)  LDD2173  [7]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1) Adenosylhomocysteinase family O43865
Peptidyl-prolyl cis-trans isomerase B (PPIB) Cyclophilin-type PPIase family P23284
Other
Click To Hide/Show 7 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Keratin-like protein KRT222 (KRT222) Intermediate filament family Q8N1A0
Replication protein A 70 kDa DNA-binding subunit (RPA1) Replication factor A protein 1 family P27694
BAG family molecular chaperone regulator 4 (BAG4) . O95429
COMM domain-containing protein 6 (COMMD6) . Q7Z4G1
Galectin-7 (LGALS7; LGALS7B) . P47929
Proline-rich acidic protein 1 (PRAP1) . Q96NZ9
Telomeric repeat-binding factor 1 (TERF1) . P54274

References

1 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.
2 Ynamide Electrophile for the Profiling of Ligandable Carboxyl Residues in Live Cells and the Development of New Covalent Inhibitors. J Med Chem. 2022 Aug 11;65(15):10408-10418. doi: 10.1021/acs.jmedchem.2c00272. Epub 2022 Jul 26.
3 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.
4 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
5 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.
6 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.
7 Reimagining high-throughput profiling of reactive cysteines for cell-based screening of large electrophile libraries. Nat Biotechnol. 2021 May;39(5):630-641. doi: 10.1038/s41587-020-00778-3. Epub 2021 Jan 4.
8 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
9 SP3-FAIMS Chemoproteomics for High-Coverage Profiling of the Human Cysteinome*. Chembiochem. 2021 May 14;22(10):1841-1851. doi: 10.1002/cbic.202000870. Epub 2021 Feb 18.
Mass spectrometry data entry: PXD023056 , PXD023059 , PXD023058 , PXD023057 , PXD023060
10 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.
11 Mapping Protein Targets of Bioactive Small Molecules Using Lipid-Based Chemical Proteomics. ACS Chem Biol. 2017 Oct 20;12(10):2671-2681. doi: 10.1021/acschembio.7b00581. Epub 2017 Sep 20.
Mass spectrometry data entry: PXD007570
12 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.