HSPA1B

Summary

HSPA1B (heat shock protein family A (Hsp70) member 1B, HGNC:5233) is a protein-coding gene on chromosome 6p21.33, encoding Heat shock 70 kDa protein 1B (P0DMV9). 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 comple….

This intronless gene encodes a 70kDa heat shock protein which is a member of the heat shock protein 70 family. In conjuction with other heat shock proteins, this protein stabilizes existing proteins against aggregation and mediates the folding of newly translated proteins in the cytosol and in organelles. It is also involved in the ubiquitin-proteasome pathway through interaction with the AU-rich element RNA-binding protein 1. The gene is located in the major histocompatibility complex class III region, in a cluster with two closely related genes which encode similar proteins.

Source: NCBI Gene 3304 — RefSeq curated summary.

At a glance

• GWAS associations: 25
• Clinical variants (ClinVar): 28 total
• Druggable target: yes
• MANE Select transcript: NM_005346

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5233
Approved symbol	HSPA1B
Name	heat shock protein family A (Hsp70) member 1B
Location	6p21.33
Locus type	gene with protein product
Status	Approved
Aliases	HSP70-2
Ensembl gene	ENSG00000204388
Ensembl biotype	protein_coding
OMIM	603012
Entrez	3304

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000375650

RefSeq mRNA: 1 — MANE Select: NM_005346 NM_005346

CCDS: CCDS34415

Canonical transcript exons

ENST00000375650 — 1 exons

Exon	Start	End
ENSE00002287005	31827738	31830254

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 197.9684 / max 19443.1198, expressed in 1816 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67059	191.2891	1816
67063	2.1641	667
67061	1.7276	712
67064	1.0237	351
67060	0.5454	278
67066	0.4611	149
67062	0.3371	137
67065	0.3369	132
67058	0.0834	29

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.72	gold quality
ventricular zone	UBERON:0003053	99.68	gold quality
gall bladder	UBERON:0002110	99.33	gold quality
ganglionic eminence	UBERON:0004023	99.12	gold quality
mucosa of transverse colon	UBERON:0004991	98.92	gold quality
mucosa of stomach	UBERON:0001199	98.80	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.65	gold quality
hypothalamus	UBERON:0001898	98.45	gold quality
right uterine tube	UBERON:0001302	98.29	gold quality
pituitary gland	UBERON:0000007	98.25	gold quality
substantia nigra	UBERON:0002038	98.15	gold quality
omental fat pad	UBERON:0010414	98.11	gold quality
adult mammalian kidney	UBERON:0000082	97.95	gold quality
Ammon’s horn	UBERON:0001954	97.95	gold quality
caudate nucleus	UBERON:0001873	97.92	gold quality
nucleus accumbens	UBERON:0001882	97.89	gold quality
esophagus mucosa	UBERON:0002469	97.88	gold quality
right atrium auricular region	UBERON:0006631	97.85	gold quality
right lobe of liver	UBERON:0001114	97.70	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.66	gold quality
fallopian tube	UBERON:0003889	97.64	gold quality
skin of abdomen	UBERON:0001416	97.61	gold quality
temporal lobe	UBERON:0001871	97.58	gold quality
adenohypophysis	UBERON:0002196	97.58	gold quality
amygdala	UBERON:0001876	97.56	gold quality
putamen	UBERON:0001874	97.50	gold quality
anterior cingulate cortex	UBERON:0009835	97.50	gold quality
esophagus	UBERON:0001043	97.42	gold quality
heart left ventricle	UBERON:0002084	97.33	gold quality
vagina	UBERON:0000996	97.32	gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-MTAB-10137	yes	1933.73
E-CURD-46	yes	354.87
E-GEOD-81547	yes	353.87
E-HCAD-29	yes	340.47
E-CURD-95	yes	321.44
E-HCAD-4	yes	226.97
E-GEOD-149689	yes	158.19
E-MTAB-8207	yes	124.66
E-MTAB-10290	yes	104.71
E-HCAD-8	yes	66.30
E-HCAD-1	yes	56.31
E-CURD-120	yes	48.04
E-MTAB-10287	yes	47.64
E-GEOD-135922	yes	22.80
E-MTAB-9543	no	7125.64

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
KCNH2	Activation

Upstream regulators (CollecTRI, top): AR, CREB1, FOXA1, HIF1A, HSF1, HSF2, HSPH1, NFAT5, NFKB1, NFYA, NFYB, NFYC, PARP1, RELA, SP1, SP3, STAT3, TCF3

miRNA regulators (miRDB)

40 targeting HSPA1B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-548AU-3P	99.70	68.22	1373

Literature-anchored findings (GeneRIF, showing 40)

• Effect of hyaluronan oligosaccharides on the expression of heat shock protein 72. (PMID:11864979)
• These data strongly suggest that in TNF-induced apoptosis, Hsp72 specifically interferes with Bid-dependent apoptotic pathway via inhibition of JNK. (PMID:11971973)
• IL-6 activates HSP72 gene expression in human skeletal muscle. (PMID:12207910)
• These observations suggest that heat shock protein 72 functions as an endogenous inhibitor of ASK1. (PMID:12391142)
• Increase in arterial HSP72 was accounted for, at least in part, by release from the hepatosplanchnic viscera with values increasing (P < 0.05) from undetectable levels at rest to 5.2 +/- 0.2 pg min(-1) after 120 min. (PMID:12411538)
• HSP72 may protect intestinal epithelial cells from Clostridium difficile toxin A-mediated damage through actin stabilization, mitochondrial protection, and inhibition of apoptosis activation, but not by prevention of RhoA glucosylation. (PMID:12490434)
• Heat shock protein 70 genotypes HSPA1B and HSPA1L influence cytokine concentrations, clinical outcome after severe injury (PMID:12544996)
• HSP70-2 gene may have a role in susceptibility to nasopharyngeal carcinoma (PMID:12691826)
• Caucasian patients carrying the HSP70-2 PstI-polymorphism seem to have a more severe form of Crohn’s disease (perforations, abscesses, fistulas, conglomerate tumors). (PMID:12730033)
• HSP70-2 polymorphism has susceptibility implications in both obesity and diabetes. (PMID:15223990)
• High frequencies of the HSP70-2 G and the TNF-alpha -308 A alleles were associated with risk of severe acute pancreatitis. (PMID:15714129)
• There is a significantly increased association of HSP70-2 B/B genotype with the risk of acute mountain sickness. (PMID:15748471)
• HSP70-2 polymorphism may have a role in development of carotid plaque rupture and cerebral ischaemia in NIDDM patients (PMID:15992611)
• The genetic determination of the defense mechanisms in Crohn’s disease appears to be associated with the polymorphism of the Hsp70-2 gene. (PMID:16165702)
• HSP70-2 genetic polymorphisms and zinc deficiency are independently associated with susceptibility to coronary artery disease. (PMID:16953332)
• Upon heat shock, the Hsp70.1 promoter-bound PARP-1 is released to activate transcription through ADP-ribosylation of other Hsp70.1 promoter-bound proteins. (PMID:17158748)
• the absence of association between Crohn’s disease and HSP70-2 gene in the Tunisian population (PMID:17301649)
• A change in the pattern of GC-box-interacting factors corresponds to activation of the Hsp70.2/Hst70 gene, confirming the importance of this regulatory element. (PMID:17311111)
• relationship between the carrier status of HSPA1B (1267)G and TLR4 (896)G alleles and the development of recurrent UTI in childhood independently of other renal abnormalities (PMID:17314700)
• identification of the most common polymorphisms in HSPA1A & HSPA1B in asthmatics & controls from 3 ethnic groups; study indicates most of the HSPA1A and HSPA1B polymorphisms identified in dbSNP are rare or were derived during post transcriptional events (PMID:17364813)
• Crohn’s disease patients with BB genotype of HSP70-2 polymorphism tend to experience a more severe clinical course; allele A is associated with more severe ulcerative colitis (PMID:17532782)
• Data presented in this report provide further insight and direct evidence of the functions of hELP3 in HSP70-2 gene transcriptional elongation in human cells. (PMID:17558451)
• HSP70-2 polymorphism does not play a major role in the development of alcoholic chronic pancreatits in Koreans. (PMID:17940904)
• An association of inflammatory fDCM with the HSPA1B 1267 A–>G polymorphism was identified. The HSPA1B 1267 A–>G polymorphism has been associated with autoimmune disorders, this may point to a pathogenetic role of autoimmune phenomena in familial DCM. (PMID:18191480)
• The frequencies of the HSPA1B P2/P2 genotype and the HSPA1B P2 allele in HCC patients were higher than in unrelated controls (each p = 0.0001). (PMID:18344806)
• P2/P2 polymorphism of HSP70-2 at position 1267 was associated with a lower risk of gastric cancer in females. (PMID:18478330)
• clathrin-FKBP36-Hsp72 complexes resulting from both identified interactions are bound to the matrices of clathrin-coated vesicles in spermatocytes, which indicates a possible role of FKBP36 and Hsp72 in the disassembly of clathrin coats (PMID:18529014)
• HSPA1B polymorphisms studied seem not to play a role in determining the severity of alcoholic pancreatitis or the risk of developing alcoholic pancreatitis. (PMID:18580445)
• An association of HspA1B (also known as Hsp70-2) +1267 alleles with serum Hsp70 levels was found in congestive heart failure. (PMID:18759004)
• polymorphisms in HSP70-2 genes associated with noise-induced hearing loss (PMID:18813331)
• HSP70-2 down-regulation induces apoptosis of HCC cells through the mitochondrial apoptotic pathway. (PMID:18822209)
• HSP70-2 is transcriptionally upregulated by HIF-1 in cancer cells in response to hypoxia (PMID:18844219)
• These results suggest that the HSPA1B-179C>T:1267A>G haplotype is functional and may explain the association of the HSP70 gene with development of septic shock. (PMID:19046306)
• significant individual and interactive influences of five polymorphisms in three genes of Hsp70 family on essential hypertension. (PMID:19085089)
• HSP70-2 expression is up-regulated in response to hypoxia. (PMID:19335985)
• The aim of this paper is to investigate a set of mutations in three genes, HSPA1A, HSPA1B and HSPA1L, in schizophrenia; findings further support a role of heat shock proteins in the pathophysiology of schizophrenia (PMID:19439993)
• we did not find an association of HSP70-2 SNP at position +1267 with gastric cancer (PMID:19626584)
• The BB genotype of heat-shock protein 70-2 gene is associated with gastric pre-malignant condition in H. pylori-infected older patients. (PMID:19661373)
• HSPA1B genotyping showed that AG genotype was significantly associated with the severity of foot ulceration, need for amputation and median length of hospital stay but HSPA1L genotypes did not show any significant association with these parameters. (PMID:19731315)
• The data indicate that the minor allele at rs9281590 reduces HSPA1B mRNA stability and expression and that the same allele is associated with lower fasting glucose and triglyceride levels. (PMID:19754858)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
mus_musculus	Hspa1b	ENSMUSG00000090877
mus_musculus	Hspa1a	ENSMUSG00000091971
rattus_norvegicus	Hspa1b	ENSRNOG00000045654
drosophila_melanogaster	Hsp110	FBGN0026418
caenorhabditis_elegans	hsp-70	WBGENE00002026
caenorhabditis_elegans		WBGENE00009691
caenorhabditis_elegans		WBGENE00009692
caenorhabditis_elegans		WBGENE00016250

Paralogs (13): HSPA5 (ENSG00000044574), HSPA8 (ENSG00000109971), HSPA9 (ENSG00000113013), HSPH1 (ENSG00000120694), HSPA2 (ENSG00000126803), HYOU1 (ENSG00000149428), HSPA13 (ENSG00000155304), HSPA4L (ENSG00000164070), HSPA4 (ENSG00000170606), HSPA6 (ENSG00000173110), HSPA14 (ENSG00000187522), HSPA1A (ENSG00000204389), HSPA1L (ENSG00000204390)

Protein

Protein identifiers

Heat shock 70 kDa protein 1B — P0DMV9 (reviewed: P0DMV9)

Alternative names: Heat shock 70 kDa protein 2, Heat shock protein family A member 1B

All UniProt accessions (2): P0DMV9, A8K5I0

UniProt curated annotations — full annotation on UniProt →

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 co-chaperones have been shown to not only regulate different steps of the ATPase cycle, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation. 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. The co-chaperones are of three types: J-domain co-chaperones such as HSP40s (stimulate ATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF) such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP-bound state thereby promoting substrate release), and the TPR domain chaperones such as HOPX and STUB1. Maintains protein homeostasis during cellular stress through two opposing mechanisms: protein refolding and degradation. Its acetylation/deacetylation state determines whether it functions in protein refolding or protein degradation by controlling the competitive binding of co-chaperones HOPX and STUB1. During the early stress response, the acetylated form binds to HOPX which assists in chaperone-mediated protein refolding, thereafter, it is deacetylated and binds to ubiquitin ligase STUB1 that promotes ubiquitin-mediated protein degradation. Regulates centrosome integrity during mitosis, and is required for the maintenance of a functional mitotic centrosome that supports the assembly of a bipolar mitotic spindle. Enhances STUB1-mediated SMAD3 ubiquitination and degradation and facilitates STUB1-mediated inhibition of TGF-beta signaling. Essential for STUB1-mediated ubiquitination and degradation of FOXP3 in regulatory T-cells (Treg) during inflammation. (Microbial infection) In case of rotavirus A infection, serves as a post-attachment receptor for the virus to facilitate entry into the cell.

Subunit / interactions. May be an auxiliary component of the CatSper complex. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with CHCHD3, DNAJC7, IRAK1BP1, PPP5C and TSC2. Interacts with TERT; the interaction occurs in the absence of the RNA component, TERC, and dissociates once the TERT complex has formed. Interacts with TRIM5 (via B30.2/SPRY domain). Interacts with METTL21A. Interacts with PRKN. Interacts with FOXP3. Interacts with NOD2; the interaction enhances NOD2 stability. Interacts with DNAJC9 (via J domain). Interacts with ATF5; the interaction protects ATF5 from degradation via proteasome-dependent and caspase-dependent processes. Interacts with NAA10, HSP40, HSP90 and HDAC4. The acetylated form and the non-acetylated form interact with HOPX and STUB1 respectively. Interacts with NEDD1. Interacts (via NBD) with BAG1, BAG2, BAG3 and HSPH1/HSP105. Interacts with SMAD3. Interacts with DNAJC8.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome.

Tissue specificity. HSPA1B is testis-specific.

Post-translational modifications. In response to cellular stress, acetylated at Lys-77 by NA110 and then gradually deacetylated by HDAC4 at later stages. Acetylation enhances its chaperone activity and also determines whether it will function as a chaperone for protein refolding or degradation by controlling its binding to co-chaperones HOPX and STUB1. The acetylated form and the non-acetylated form bind to HOPX and STUB1 respectively. Acetylation also protects cells against various types of cellular stress.

Domain organisation. The N-terminal nucleotide binding domain (NBD) (also known as the ATPase domain) is responsible for binding and hydrolyzing ATP. The C-terminal substrate-binding domain (SBD) (also known as peptide-binding domain) binds to the client/substrate proteins. The two domains are allosterically coupled so that, when ATP is bound to the NBD, the SBD binds relatively weakly to clients. When ADP is bound in the NBD, a conformational change enhances the affinity of the SBD for client proteins.

Induction. By heat shock.

Similarity. Belongs to the heat shock protein 70 family.

RefSeq proteins (1): NP_005337* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013126	Hsp_70_fam	Family
IPR018181	Heat_shock_70_CS	Conserved_site
IPR029047	HSP70_peptide-bd_sf	Homologous_superfamily
IPR029048	HSP70_C_sf	Homologous_superfamily
IPR043129	ATPase_NBD	Homologous_superfamily

Pfam: PF00012

UniProt features (70 total): strand 18, helix 18, modified residue 11, binding site 5, mutagenesis site 5, turn 4, region of interest 3, sequence variant 3, initiator methionine 1, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
7F50	X-RAY DIFFRACTION	1.7
7F4Z	X-RAY DIFFRACTION	1.8
4J8F	X-RAY DIFFRACTION	2.7
6FDT	SOLUTION NMR
7F4X	X-RAY DIFFRACTION, NEUTRON DIFFRACTION	1.6,2.199

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DMV9-F1	89.33	0.70

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (5): 339–342; 12–15; 71; 202–204; 268–275

Post-translational modifications (11): 2, 77, 108, 246, 348, 469, 561, 561, 631, 633, 636

Mutagenesis-validated functional residues (5):

Position	Phenotype
10	reduces affinity for adp.
77	no loss of acetylation and atpase activity. exhibits normal protein refolding activity during the early phase but exhibi
77	significant loss of acetylation and atpase activity. decreased binding to hopx and hsp90 and increased binding to stub1
199	reduces affinity for adp.
561	complete loss of in vitro methylation by mettl21a.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-3371453	Regulation of HSF1-mediated heat shock response
R-HSA-3371497	HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand
R-HSA-3371568	Attenuation phase
R-HSA-3371571	HSF1-dependent transactivation
R-HSA-6798695	Neutrophil degranulation
R-HSA-9833482	PKR-mediated signaling
R-HSA-9841251	Mitochondrial unfolded protein response (UPRmt)
R-HSA-9918487	Dengue Virus Genome Translation and Replication
R-HSA-3371511	HSF1 activation

MSigDB gene sets: 539 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_CHROMOSOME_ORGANIZATION, LEE_NEURAL_CREST_STEM_CELL_DN, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, BENPORATH_ES_WITH_H3K27ME3, GOBP_POSITIVE_REGULATION_OF_ERYTHROCYTE_DIFFERENTIATION, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_8_PRODUCTION, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOCC_SECRETORY_GRANULE

GO Biological Process (25): mRNA catabolic process (GO:0006402), negative regulation of cell population proliferation (GO:0008285), positive regulation of gene expression (GO:0010628), negative regulation of cell growth (GO:0030308), regulation of protein ubiquitination (GO:0031396), negative regulation of protein ubiquitination (GO:0031397), positive regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032436), positive regulation of interleukin-8 production (GO:0032757), cellular response to oxidative stress (GO:0034599), cellular response to heat (GO:0034605), protein refolding (GO:0042026), negative regulation of apoptotic process (GO:0043066), positive regulation of erythrocyte differentiation (GO:0045648), ATP metabolic process (GO:0046034), protein stabilization (GO:0050821), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), cellular heat acclimation (GO:0070370), positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway (GO:0070434), cellular response to steroid hormone stimulus (GO:0071383), positive regulation of microtubule nucleation (GO:0090063), negative regulation of inclusion body assembly (GO:0090084), regulation of mitotic spindle assembly (GO:1901673), positive regulation of tumor necrosis factor-mediated signaling pathway (GO:1903265), negative regulation of extrinsic apoptotic signaling pathway in absence of ligand (GO:2001240), symbiont entry into host cell (GO:0046718)

GO Molecular Function (17): virus receptor activity (GO:0001618), G protein-coupled receptor binding (GO:0001664), RNA binding (GO:0003723), signaling receptor binding (GO:0005102), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), enzyme binding (GO:0019899), heat shock protein binding (GO:0031072), ubiquitin protein ligase binding (GO:0031625), histone deacetylase binding (GO:0042826), protein folding chaperone (GO:0044183), obsolete unfolded protein binding (GO:0051082), C3HC4-type RING finger domain binding (GO:0055131), ATP-dependent protein disaggregase activity (GO:0140545), ATP-dependent protein folding chaperone (GO:0140662), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (22): extracellular region (GO:0005576), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), endoplasmic reticulum (GO:0005783), centrosome (GO:0005813), centriole (GO:0005814), cytosol (GO:0005829), plasma membrane (GO:0005886), focal adhesion (GO:0005925), inclusion body (GO:0016234), aggresome (GO:0016235), nuclear speck (GO:0016607), vesicle (GO:0031982), protein-containing complex (GO:0032991), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), blood microparticle (GO:0072562), ficolin-1-rich granule lumen (GO:1904813), ribonucleoprotein complex (GO:1990904), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Cellular response to heat stress	3
Cellular responses to stress	2
HSF1-dependent transactivation	1
Innate Immune System	1
Antimicrobial mechanism of IFN-stimulated genes	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
protein binding	4
cytoplasm	4
ATP-dependent activity	3
intracellular membrane-bounded organelle	3
negative regulation of cellular process	2
protein ubiquitination	2
protein folding	2
intracellular anatomical structure	2
microtubule organizing center	2
RNA catabolic process	1
negative regulation of gene expression	1
mRNA metabolic process	1
cell population proliferation	1
regulation of cell population proliferation	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
regulation of protein modification by small protein conjugation or removal	1
regulation of protein ubiquitination	1
negative regulation of protein modification by small protein conjugation or removal	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
positive regulation of proteasomal protein catabolic process	1
positive regulation of ubiquitin-dependent protein catabolic process	1
positive regulation of cytokine production	1
interleukin-8 production	1
regulation of interleukin-8 production	1
response to oxidative stress	1
cellular response to chemical stress	1
response to heat	1
cellular response to stress	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
erythrocyte differentiation	1
positive regulation of myeloid cell differentiation	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

69 interactions, top by confidence:

A	B	Type	Score
MAP3K14	CHUK	psi-mi:“MI:0914”(association)	0.950
PSMB2	PSMD11	psi-mi:“MI:0914”(association)	0.730
CRK	ARHGAP42	psi-mi:“MI:0914”(association)	0.530
GNB2	PFDN6	psi-mi:“MI:0914”(association)	0.530
HSPA1B	F2RL1	psi-mi:“MI:0915”(physical association)	0.510
	HSPA1B	psi-mi:“MI:0915”(physical association)	0.400
SULT1C4	HSPA1B	psi-mi:“MI:0915”(physical association)	0.400
HSPA1B	BAG2	psi-mi:“MI:0915”(physical association)	0.400
MAPKAPK2	HSPA1B	psi-mi:“MI:0915”(physical association)	0.400
HSPA1B	MTNAP1	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
CTU1	HSPA1B	psi-mi:“MI:0914”(association)	0.350
ANG	DDX39A	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
N	DHX15	psi-mi:“MI:0914”(association)	0.350
N	PHGDH	psi-mi:“MI:0914”(association)	0.350
	DDX3X	psi-mi:“MI:0914”(association)	0.350
USP29	HSPA1B	psi-mi:“MI:0914”(association)	0.350
ARHGAP18	CLTB	psi-mi:“MI:0914”(association)	0.350
CAPZB	ENAH	psi-mi:“MI:0914”(association)	0.350
CLTA	CLTB	psi-mi:“MI:0914”(association)	0.350
CSNK2A1	RPS3A	psi-mi:“MI:0914”(association)	0.350
DNAJA1	HSPA8	psi-mi:“MI:0914”(association)	0.350
DNAJB1	HSPA8	psi-mi:“MI:0914”(association)	0.350

ESM2 similar proteins: A2Q0Z1, O59855, O65719, O73885, P02827, P08106, P08108, P08418, P09446, P0DMV8, P0DMV9, P0DMW0, P0DMW1, P11142, P11147, P14659, P17156, P19120, P19378, P22953, P27541, P34930, P34933, P36415, P41753, P47773, P53421, P53623, P54652, P63017, P63018, Q01233, Q01877, Q05944, Q06248, Q10265, Q27965, Q27975, Q4U0F3, Q557E0

Diamond homologs: A0A0D1CD96, A0A509AJG0, A2Q0Z1, A5A8V7, F5HB71, G3I8R9, J9VZ70, O24581, O59855, O73885, O93866, P02827, P06761, P07823, P08108, P08418, P09189, P0CB32, P0DMV8, P0DMV9, P10591, P10592, P11021, P11142, P14659, P16474, P17156, P17879, P19120, P19208, P19378, P20029, P20163, P22010, P22202, P24067, P26413, P27420, P29844, P34933

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
HSPA1B	“up-regulates quantity”	ENPP1	“post transcriptional regulation”
HSPA1B	“up-regulates quantity by stabilization”	NOD2	binding
FOXA1	“up-regulates quantity by expression”	HSPA1B	“transcriptional regulation”
STAT3	“up-regulates quantity by expression”	HSPA1B	“transcriptional regulation”
HSPH1	“up-regulates quantity by expression”	HSPA1B	“transcriptional regulation”
BAG5	“down-regulates activity”	HSPA1B	binding
HSPA1B	“up-regulates activity”	GSTA4	relocalization
HSPA1B	“up-regulates quantity by stabilization”	PACRG	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 97 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
NIK–>noncanonical NF-kB signaling	5	16.3×	3e-03
Regulation of HSF1-mediated heat shock response	8	15.9×	2e-05
Dectin-1 mediated noncanonical NF-kB signaling	5	15.4×	3e-03
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	5	13.8×	4e-03
Regulation of PTEN stability and activity	5	13.2×	5e-03
CLEC7A (Dectin-1) signaling	5	10.2×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
response to unfolded protein	7	24.2×	5e-06
protein folding	12	14.3×	3e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

28 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1 predictions. Top by Δscore:

Variant	Effect	Δscore
6:31829907:G:GC	acceptor_gain	0.2600

AlphaMissense

4221 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:31827984:G:C	G12R	1.000
6:31827985:G:A	G12D	1.000
6:31827985:G:T	G12V	1.000
6:31827988:C:T	T13I	1.000
6:31828005:G:T	G19W	1.000
6:31828043:C:A	N31K	1.000
6:31828043:C:G	N31K	1.000
6:31828068:A:C	S40R	1.000
6:31828070:C:A	S40R	1.000
6:31828070:C:G	S40R	1.000
6:31828105:G:A	G52E	1.000
6:31828114:C:A	A55D	1.000
6:31828163:G:C	K71N	1.000
6:31828163:G:T	K71N	1.000
6:31828390:C:A	P147Q	1.000
6:31828390:C:G	P147R	1.000
6:31828393:C:A	A148D	1.000
6:31828398:T:C	F150L	1.000
6:31828400:C:A	F150L	1.000
6:31828400:C:G	F150L	1.000
6:31828412:G:C	Q154H	1.000
6:31828412:G:T	Q154H	1.000
6:31828413:C:A	R155S	1.000
6:31828414:G:C	R155P	1.000
6:31828435:G:A	G162D	1.000
6:31828474:A:C	E175A	1.000
6:31828474:A:T	E175V	1.000
6:31828483:C:A	A178D	1.000
6:31828486:C:A	A179D	1.000
6:31828546:A:C	D199A	1.000

dbSNP variants (sampled 300 via entrez): RS1000261968 (6:31830136 G>T), RS1000695337 (6:31827760 C>G,T), RS1000762955 (6:31830235 A>T), RS1001260474 (6:31829224 C>T), RS1002874434 (6:31827603 TG>T,TGG), RS1003259906 (6:31826065 T>C,G), RS1004209616 (6:31830615 C>G,T), RS1004544458 (6:31827860 G>C), RS1005137496 (6:31827169 T>C), RS1005438599 (6:31826763 A>G), RS1006217811 (6:31827232 G>C,T), RS1006499535 (6:31827454 C>A,T), RS1007339512 (6:31827084 A>G), RS1010302802 (6:31827621 G>A), RS1012607512 (6:31826032 C>G)

Disease associations

OMIM: gene MIM:603012 | disease phenotypes: MIM:606963

GenCC curated gene-disease

Mondo (1): chronic obstructive pulmonary disease (MONDO:0005002)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST004131_25	Inflammatory bowel disease	2.000000e-31
GCST004133_79	Ulcerative colitis	5.000000e-65
GCST004521_114	Autism spectrum disorder or schizophrenia	3.000000e-17
GCST004521_117	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_118	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_126	Autism spectrum disorder or schizophrenia	2.000000e-10
GCST004521_154	Autism spectrum disorder or schizophrenia	3.000000e-08
GCST004521_17	Autism spectrum disorder or schizophrenia	2.000000e-12
GCST004521_173	Autism spectrum disorder or schizophrenia	4.000000e-14
GCST004521_209	Autism spectrum disorder or schizophrenia	5.000000e-16
GCST004521_211	Autism spectrum disorder or schizophrenia	5.000000e-15
GCST004521_213	Autism spectrum disorder or schizophrenia	5.000000e-13
GCST004521_224	Autism spectrum disorder or schizophrenia	5.000000e-10
GCST004521_227	Autism spectrum disorder or schizophrenia	4.000000e-12
GCST004521_265	Autism spectrum disorder or schizophrenia	7.000000e-14
GCST004521_281	Autism spectrum disorder or schizophrenia	5.000000e-09
GCST004521_296	Autism spectrum disorder or schizophrenia	6.000000e-18
GCST004521_45	Autism spectrum disorder or schizophrenia	2.000000e-16
GCST004521_70	Autism spectrum disorder or schizophrenia	8.000000e-20
GCST004521_81	Autism spectrum disorder or schizophrenia	1.000000e-14
GCST008916_30	Asthma	1.000000e-09
GCST008917_2	Asthma (childhood onset)	4.000000e-07
GCST008921_1	Asthma and major depressive disorder	2.000000e-16
GCST009070_2	Eosinophilic esophagitis	3.000000e-09
GCST011426_16	Systemic lupus erythematosus	6.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D029424	Pulmonary Disease, Chronic Obstructive	C08.381.495.389; C23.550.291.500.875

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3885585 (PROTEIN FAMILY)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Heat shock proteins

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.79	Kd	162.6	nM	CHEMBL3752910
6.74	ED50	181.1	nM	CHEMBL3752910
5.84	Kd	1449	nM	CHEMBL5653589
5.79	ED50	1614	nM	CHEMBL5653589

PubChem BioAssay actives

40 with measured affinity, of 132 total; 23 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-[[(2R,3S,4R,5R)-5-[6-amino-8-(quinolin-6-ylmethylamino)purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxymethyl]benzonitrile	1799196: HSP70 Biacore Direct Binding Assay from Article 10.1021/jm801627a: “Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design.”	kd	0.0500	uM
(2R,3R,4S,5R)-2-[6-amino-8-(quinolin-6-ylmethylamino)purin-9-yl]-5-[[4-(trifluoromethyl)phenyl]methoxymethyl]oxolane-3,4-diol	1799196: HSP70 Biacore Direct Binding Assay from Article 10.1021/jm801627a: “Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design.”	kd	0.0600	uM
[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] hydrogen phosphate	1799593: Fluorescence-Polarization (FP) Binding Assay from Article 10.1021/jm101625x: “Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity.”	ki	0.1100	uM
4-[[(2R,3S,4R,5R)-5-[6-amino-8-[(3,4-dichlorophenyl)methylamino]purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxymethyl]benzonitrile	1799593: Fluorescence-Polarization (FP) Binding Assay from Article 10.1021/jm101625x: “Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity.”	ki	0.1200	uM
(2R,3R,4S,5R)-2-[6-amino-8-(quinolin-6-ylmethylamino)purin-9-yl]-5-[(3,4,5-trifluorophenyl)methoxymethyl]oxolane-3,4-diol	1799196: HSP70 Biacore Direct Binding Assay from Article 10.1021/jm801627a: “Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design.”	kd	0.1200	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148550: Binding affinity to human HSPA1B/HSPA1A incubated for 45 mins by Kinobead based pull down assay	kd	0.1626	uM
4-[[(2R,3S,4R,5R)-5-[6-amino-8-(benzylamino)purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxymethyl]benzonitrile	1799196: HSP70 Biacore Direct Binding Assay from Article 10.1021/jm801627a: “Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design.”	kd	0.2000	uM
(2R,3R,4S,5R)-2-[6-amino-8-(methylamino)purin-9-yl]-5-(pyridin-3-ylmethoxymethyl)oxolane-3,4-diol	1799593: Fluorescence-Polarization (FP) Binding Assay from Article 10.1021/jm101625x: “Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity.”	ki	0.4500	uM
[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate	1799195: HSP70 Fluorescence Polarization Assay from Article 10.1021/jm801627a: “Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design.”	ic50	0.5000	uM
[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphono hydrogen phosphate	1799195: HSP70 Fluorescence Polarization Assay from Article 10.1021/jm801627a: “Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design.”	ic50	0.5000	uM
(2R,3R,4S,5R)-2-[6-amino-8-[(3,4-dichlorophenyl)methylamino]purin-9-yl]-5-(phenylmethoxymethyl)oxolane-3,4-diol	1799593: Fluorescence-Polarization (FP) Binding Assay from Article 10.1021/jm101625x: “Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity.”	ki	1.0500	uM
(2R,3R,4S,5R)-2-[6-amino-8-(methylamino)purin-9-yl]-5-(phenylmethoxymethyl)oxolane-3,4-diol	1799593: Fluorescence-Polarization (FP) Binding Assay from Article 10.1021/jm101625x: “Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity.”	ki	1.1000	uM
(2R,3R,4S,5R)-2-[6-amino-8-(quinolin-6-ylmethylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1799593: Fluorescence-Polarization (FP) Binding Assay from Article 10.1021/jm101625x: “Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity.”	ki	1.2900	uM
(2R,3R,4S,5R)-2-[6-amino-8-[(3,4-dichlorophenyl)methylamino]purin-9-yl]-5-(methoxymethyl)oxolane-3,4-diol	1799593: Fluorescence-Polarization (FP) Binding Assay from Article 10.1021/jm101625x: “Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity.”	ki	1.4400	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148550: Binding affinity to human HSPA1B/HSPA1A incubated for 45 mins by Kinobead based pull down assay	kd	1.4489	uM
(2R,3R,4S,5R)-2-[6-amino-8-[(3,4-dichlorophenyl)methylamino]purin-9-yl]-5-[(3,4,5-trifluorophenyl)methoxymethyl]oxolane-3,4-diol	1799195: HSP70 Fluorescence Polarization Assay from Article 10.1021/jm801627a: “Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design.”	ic50	1.7000	uM
2-[[(2R,3S,4R,5R)-5-[6-amino-8-(methylamino)purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxy]acetamide	1799593: Fluorescence-Polarization (FP) Binding Assay from Article 10.1021/jm101625x: “Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity.”	ki	1.8500	uM
(2R,3R,4S,5R)-2-[6-amino-8-(methylamino)purin-9-yl]-5-(cyclohexylmethoxymethyl)oxolane-3,4-diol	1799593: Fluorescence-Polarization (FP) Binding Assay from Article 10.1021/jm101625x: “Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity.”	ki	4.0700	uM
(2R,3R,4S,5R)-2-[6-amino-8-[(3,4-dichlorophenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1799593: Fluorescence-Polarization (FP) Binding Assay from Article 10.1021/jm101625x: “Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity.”	ki	4.3100	uM
(2R,3R,4S,5R)-2-[6-amino-8-(quinolin-2-ylmethylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1799593: Fluorescence-Polarization (FP) Binding Assay from Article 10.1021/jm101625x: “Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity.”	ki	4.3200	uM
(2R,3R,4S,5R)-2-(6,8-diaminopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol	1799593: Fluorescence-Polarization (FP) Binding Assay from Article 10.1021/jm101625x: “Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity.”	ki	4.4600	uM
(2R,3R,4S,5R)-2-[6-amino-8-(1,3-benzodioxol-5-ylmethylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1799195: HSP70 Fluorescence Polarization Assay from Article 10.1021/jm801627a: “Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design.”	ic50	4.9000	uM
(2R,3R,4S,5R)-2-[6-amino-8-(methylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1799593: Fluorescence-Polarization (FP) Binding Assay from Article 10.1021/jm101625x: “Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity.”	ki	8.3000	uM

CTD chemical–gene interactions

172 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, affects cotreatment, increases expression	7
Arsenic Trioxide	affects expression, increases expression, affects response to substance	7
Cadmium Chloride	decreases expression, increases abundance, increases expression, increases methylation	7
Cadmium	increases abundance, increases expression	5
Tobacco Smoke Pollution	increases methylation, affects expression, increases expression	5
bisphenol A	affects expression, affects cotreatment, decreases methylation, decreases expression	4
Arsenic	increases reaction, increases expression, affects methylation, decreases expression, affects binding (+1 more)	4
Benzo(a)pyrene	affects methylation, increases expression	4
Cisplatin	affects cotreatment, increases expression, decreases expression, increases reaction	4
Quercetin	decreases expression, decreases phosphorylation	4
cobaltous chloride	increases expression	3
Bortezomib	increases expression, affects response to substance, decreases response to substance	3
Copper	affects binding, increases expression, decreases expression	3
Cyclosporine	increases expression	3
Particulate Matter	affects expression, increases reaction, decreases expression, increases abundance, affects cotreatment	3
methylmercuric chloride	increases expression	2
arsenite	affects binding, increases reaction, increases expression	2
chloropicrin	increases expression	2
Acetylcysteine	decreases reaction, increases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases expression, decreases expression	2
Disulfiram	affects binding, decreases expression, increases expression	2
Hydrogen Peroxide	increases expression	2
Oxygen	decreases expression	2
Rotenone	decreases expression	2
Silver	increases expression	2
Dronabinol	affects cotreatment, increases expression, decreases expression	2
Tunicamycin	decreases expression	2
Zinc	affects abundance, affects cotreatment, increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3803750	Binding	Binding affinity to HSPA1A/HSPA1B in HEK293 proteomes assessed as spectral count ratio at 20 uM incubated for 16 hrs by TAMRA biotin-azide dye based LC-MS/MS analysis relative to control	Characterizing the Covalent Targets of a Small Molecule Inhibitor of the Lysine Acetyltransferase P300. — ACS Med Chem Lett

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00120978	PHASE4	UNKNOWN	Can Advair and Flovent Reduce Systemic Inflammation Related to Chronic Obstructive Pulmonary Disease (COPD)? A Multi-Center Randomized Controlled Trial
NCT00134979	PHASE4	COMPLETED	Formoterol Certihaler, Tiotropium HandiHaler and Tiotropium HandiHaler in Combination With Formoterol Certihaler in Patients With Stable Chronic Obstructive Pulmonary Disease
NCT00158847	PHASE4	TERMINATED	Modification Of Disease Outcome In COPD
NCT00170222	PHASE4	COMPLETED	Placebo Versus Antibiotics in Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD)
NCT00175565	PHASE4	COMPLETED	Inhaled Steroid Reduces Systemic Inflammation in COPD
NCT00181207	PHASE4	COMPLETED	Airway Clearance for Prevention of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
NCT00186706	PHASE4	COMPLETED	Selenium Supplementation in Chronic Obstructive Pulmonary Disease (COPD) Patients
NCT00190437	PHASE4	COMPLETED	ANTEAB: a Study of Early Antibiotherapy in the ICU Management of Acute Exacerbations of COPD
NCT00202176	PHASE4	COMPLETED	Effects of Bronchodilators in Mild Chronic Obstructive Pulmonary Disease (COPD)
NCT00202189	PHASE4	COMPLETED	Effects of Inhaled Corticosteroids in Chronic Obstructive Pulmonary Disease (COPD)
NCT00232674	PHASE4	COMPLETED	Efficacy Study of the Effect of Budesonide on Emphysema
NCT00288548	PHASE4	UNKNOWN	Metoprolol and Formoterol in Chronic Obstructive Pulmonary Disease (COPD)
NCT00291408	PHASE4	WITHDRAWN	Effect of Symbicort on HAT and HDAC in Sputum Macrophages of COPD
NCT00291460	PHASE4	UNKNOWN	Inspiratory Muscle Training in Hypercapnic COPD
NCT00292838	PHASE4	COMPLETED	Relative Potency of Inhaled Corticosteroids
NCT00311961	PHASE4	COMPLETED	Intravenous Versus Oral Administration of Prednisolone in Exacerbations of Chronic Obstructive Pulmonary Disease (COPD)
NCT00316992	PHASE4	COMPLETED	Safety of Ramelteon in Subjects With Chronic Obstructive Pulmonary Disease
NCT00331656	PHASE4	UNKNOWN	Comparative Study of Non-Invasive Mask Ventilation vs Cuirass Ventilation in Patients With Acute Respiratory Failure.
NCT00335621	PHASE4	WITHDRAWN	Replacement of Nebulised Ipratropium With Inhaled Tiotropium in Stable Chronic Obstructive Pulmonary Disease (COPD)
NCT00354354	PHASE4	COMPLETED	Bronchodilators and Oxygen Kinetics With Exercise in Chronic Obstructive Pulmonary Disease (COPD) Patients
NCT00379028	PHASE4	COMPLETED	Airway Clearance Study
NCT00405236	PHASE4	COMPLETED	Effect of Tiotropium on Inflammation and Exacerbations in COPD
NCT00412204	PHASE4	COMPLETED	Study to Evaluate the Effects of Tiotropium Bromide on Chronic Obstructive Pulmonary Disease (COPD) During Exercise
NCT00424528	PHASE4	COMPLETED	Efficacy Safety Study of Arformoterol/Tiotropium Combination Versus Either Therapy Alone in Chronic Obstructive Pulmonary Disease (COPD)
NCT00440245	PHASE4	COMPLETED	Bronchoprotection of Salbutamol in Asthma and Chronic Obstructive Pulmonary Disease
NCT00440687	PHASE4	COMPLETED	Withdrawal of Inhaled Corticosteroids in Patients With COPD in Primary Care
NCT00489853	PHASE4	COMPLETED	Evaluation of Efficacy on Exercise Tolerance of Symbicort (Budesonide/Formoterol) Compared to Placebo and Oxis in Patients With Severe COPD
NCT00491803	PHASE4	COMPLETED	Sildenafil Effects on Pulmonary Haemodynamics and Gas Exchange in Chronic Obstructive Pulmonary Disease (COPD)
NCT00495586	PHASE4	COMPLETED	Effectiveness of Antibiotic Therapy for Exacerbations of Chronic Obstructive Pulmonary Disease
NCT00525564	PHASE4	COMPLETED	Effects of Salmeterol on Walking Capacity in Patients With COPD
NCT00532584	PHASE4	WITHDRAWN	Effect of Steroids on Gene Expression in the Healthy Smokers Lungs
NCT00542880	PHASE4	COMPLETED	Evaluation of Onset of Effect in Patients With Severe Chronic Obstructive Pulmonary Disease (COPD) Treated With Symbicort® Compared to Seretide®
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