Tchem HSPA8 Heat shock cognate 71 kDa protein

Protein Summary

Description

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 (PubMed:21150129, PubMed:21148293, PubMed:24732912, PubMed:27916661, PubMed:23018488). This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones (PubMed:21150129, PubMed:21148293, PubMed:24732912, PubMed:27916661, PubMed:23018488). The co-chaperones have been shown to not only regulate different steps of the ATPase cycle of HSP70, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation (PubMed:21150129, PubMed:21148293, PubMed:24732912, PubMed:27916661, PubMed:23018488). The affinity of HSP70 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. HSP70 goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The HSP70-associated co-chaperones are of three types: J-domain co-chaperones 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 (PubMed:24318877, PubMed:27474739, PubMed:24121476, PubMed:26865365). Acts as a repressor of transcriptional activation. Inhibits the transcriptional coactivator activity of CITED1 on Smad-mediated transcription. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex. Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:10722728, PubMed:11276205). Participates in the ER-associated degradation (ERAD) quality control pathway in conjunction with J domain-containing co-chaperones and the E3 ligase STUB1 (PubMed:23990462). This gene encodes a member of the heat shock protein 70 family, which contains both heat-inducible and constitutively expressed members. This protein belongs to the latter group, which are also referred to as heat-shock cognate proteins. It functions as a chaperone, and binds to nascent polypeptides to facilitate correct folding. It also functions as an ATPase in the disassembly of clathrin-coated vesicles during transport of membrane components through the cell. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

Uniprot Accession IDs

• P11142
• Q9H3R6

Gene Name

• HSPA8

Ensembl ID

• ENST00000227378
• ENSP00000227378
• ENSG00000109971
• ENST00000453788
• ENSP00000404372
• ENST00000532636
• ENSP00000437125
• ENST00000534624
• ENSP00000432083

Symbol

• HSC70
• HSP73
• HSPA10
• LAP1
• HSC54
• HSC70
• HSC71
• HSP71
• HSP73
• LAP-1
• NIP71
• HEL-33
• HSPA10
• HEL-S-72p

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
hub protein	1
interacting protein	1
kinase perturbation	1
molecular function	1
virus perturbation	1

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1184.53   (req: < 5)

Gene RIFs: 132   (req: <= 3)

Antibodies: 1027   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1184.53   (req: >= 5)

Gene RIFs: 132   (req: > 3)

Antibodies: 1027   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 51

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 9

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

Find Targets by Sequence

Show Full Sequence

ProtVista Viewer

Expression Data (0 Tissues)

tutorial

No expression data found

Related Tools

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

Go To Tool

GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

Go To Tool

GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

Go To Tool

ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

Go To Tool

Approved Drugs (0)

No approved drugs found

Active Ligands (9)

Explore Active Ligands

1 – 9 of 9

ADP

HSPA8Tchem

pKd : 6.49

CHEMBL515570

HSPA8Tchem

pKd : 6.14

CHEMBL3427682

HSPA8Tchem

pKd : 6.55

CHEMBL3427679

HSPA8Tchem

pKd : 6.52

CHEMBL3091929

HSPA8Tchem

pKd : 6.4

CHEMBL3822603

HSPA8Tchem

pKd : 6.34

CHEMBL4168736

HSPA8Tchem

pKd : 6.18

CHEMBL3091928

HSPA8Tchem

pKd : 6.05

CHEMBL3091931

HSPA8Tchem

pKd : 6

Protein-Protein Interactions (1068)

Explore Interacting Targets

1 – 10 of 1068

• See Interactions on String-DB

HSF2

Tbio

Family:  TF

Novelty:  0.06458223

p_int:  0.999997478

p_ni:  0.000002522

Score:  0.524

Data Source:  BioPlex,STRINGDB

CD207

Tbio

Novelty:  0.00313729

p_int:  0.999997434

p_ni:  0.000002554

p_wrong:  1.2e-8

Score:  0.151

Data Source:  BioPlex,STRINGDB

ARMC1

Tbio

Novelty:  0.02018109

p_int:  0.999989234

p_ni:  0.000010766

Data Source:  BioPlex

HSF1

Tchem

Family:  TF

Novelty:  0.00450276

p_int:  0.99998756

p_ni:  0.000012437

p_wrong:  3e-9

Score:  0.983

Data Source:  BioPlex,Reactome,STRINGDB

METTL21A

Tbio

Family:  Enzyme

Novelty:  0.31897774

p_int:  0.999980016

p_ni:  0.000019984

Score:  0.956

Data Source:  BioPlex,Reactome,STRINGDB

ABL2

Tchem

Family:  Kinase

Novelty:  0.00952983

p_int:  0.999954485

p_ni:  0.000045368

p_wrong:  1.46e-7

Score:  0.294

Data Source:  BioPlex,STRINGDB

EDRF1

Tbio

Novelty:  0.24333657

p_int:  0.999947181

p_ni:  0.000052819

Data Source:  BioPlex

CCDC117

Tdark

Novelty:  1.11966553

p_int:  0.999934759

p_ni:  0.000065241

Score:  0.154

Data Source:  BioPlex,STRINGDB

PDPK1

Tchem

Family:  Kinase

Novelty:  0.00430458

p_int:  0.99987861

p_ni:  0.00012139

Score:  0.183

Data Source:  BioPlex,STRINGDB

DNAJC13

Tbio

Novelty:  0.03251995

p_int:  0.999854637

p_ni:  0.000145363

Score:  0.745

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets (2)

Explore Nearest Tclin Targets

Downstream (2)

1 – 2 of 2

MAP2K1

Tclin

Family:  Kinase

KEGG Distance:  4

Common Pathways:  2

1: Estrogen signaling pathway

2: MAPK signaling pathway

MAP2K2

Tclin

Family:  Kinase

KEGG Distance:  4

Common Pathways:  2

1: Estrogen signaling pathway

2: MAPK signaling pathway

Pathways (62)

Reactome (40)

KEGG (10)

PathwayCommons (9)

WikiPathways (3)

AUF1 (hnRNP D0) binds and destabilizes mRNA (R-HSA-450408)

Click on a row in the table to change the structure displayed.

Find Similar Targets

Items per page:

5

1 – 5 of 40

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	AUF1 (hnRNP D0) binds and destabilizes mRNA	56 targets	R-HSA-450408
Reactome	Attenuation phase	26 targets	R-HSA-3371568
Reactome	Autophagy	109 targets	R-HSA-9612973
Reactome	Axon guidance	533 targets	R-HSA-422475
Reactome	CHL1 interactions	9 targets	R-HSA-447041

Name	Explore in Pharos	Explore in Source
AUF1 (hnRNP D0) binds and destabilizes mRNA	56 targets	R-HSA-450408
Attenuation phase	26 targets	R-HSA-3371568
Autophagy	109 targets	R-HSA-9612973
Axon guidance	533 targets	R-HSA-422475
CHL1 interactions	9 targets	R-HSA-447041

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (89)

Functions (18)

Components (38)

Processes (33)

Find Similar Targets

Items per page:

10

1 – 10 of 18

GO Term	Evidence	Assigned by
ATP binding	Inferred from Direct Assay (IDA)	BHF-UCL
ATPase activity	Inferred from Direct Assay (IDA)	BHF-UCL
unfolded protein binding	Inferred from Direct Assay (IDA)	UniProtKB
C3HC4-type RING finger domain binding	Inferred from Physical Interaction (IPI)	BHF-UCL
chaperone binding	Inferred from Physical Interaction (IPI)	ARUK-UCL
enzyme binding	Inferred from Physical Interaction (IPI)	BHF-UCL
G protein-coupled receptor binding	Inferred from Physical Interaction (IPI)	ParkinsonsUK-UCL
heat shock protein binding	Inferred from Physical Interaction (IPI)	UniProtKB
protein binding, bridging	Inferred from Physical Interaction (IPI)	ARUK-UCL
ubiquitin protein ligase binding	Inferred from Physical Interaction (IPI)	ParkinsonsUK-UCL

Disease Associations ()

No disease associations found

GWAS Traits (6)

• Explore on Target Illumination GWAS Analytics (TIGA)

Items per page:

5

1 – 5 of 6

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
red blood cell distribution width	EFO_0005192	4	3	4		92.2
mean corpuscular hemoglobin concentration	EFO_0004528	4	3	4		90
age at menarche	EFO_0004703	2	2	1	2.7	78.4
myeloid white cell count	EFO_0007988	1	1	1		39.6
BMI-adjusted hip circumference	EFO_0008039	1	2	2		39.5

• Explore on Target Illumination GWAS Analytics (TIGA)

Items per page:

5

1 – 5 of 6

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
red blood cell distribution width	EFO_0005192	4		92.2
mean corpuscular hemoglobin concentration	EFO_0004528	4		90
age at menarche	EFO_0004703	1	2.7	78.4
myeloid white cell count	EFO_0007988	1		39.6
BMI-adjusted hip circumference	EFO_0008039	2		39.5

Reset Zoom  Beta Count   Odds Ratio

Find similar targets by:

UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
Alternative splicing
ATP-binding
Cell membrane
Chaperone
Complete proteome
Cytoplasm
Direct protein sequencing
Host-virus interaction

GWAS Trait Find Similar Targets

No Header	No Header
age at menarche
BMI-adjusted hip circumference
mean corpuscular hemoglobin concentration
myeloid white cell count
red blood cell distribution width
sleep duration

IDG Resources

No IDG generated resources found

Orthologs (10)

1 – 5 of 10

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	heat shock protein family A (Hsp70) member 8	VGNC:11823	451629
Macaque	heat shock protein family A (Hsp70) member 8		707989
Mouse	heat shock protein 8	MGI:105384	15481
Rat	heat shock protein family A (Hsp70) member 8	RGD:621725	24468
Dog	heat shock protein family A (Hsp70) member 8		479406

Species	Name	OMA	EggNOG	Inparanoid
Chimp	heat shock protein family A (Hsp70) member 8
Macaque	heat shock protein family A (Hsp70) member 8
Mouse	heat shock protein 8
Rat	heat shock protein family A (Hsp70) member 8
Dog	heat shock protein family A (Hsp70) member 8

Publication Statistics

PubMed Score 1184.53

PubMed score by year

Reset Zoom

PubTator Score 652.13

PubTator score by year

Reset Zoom

Related Publications

Text Mined References (285)

GeneRif Annotations (132)

Items per page:

10

0 of 0

PMID	Year	Title