Tchem HSPA5 Endoplasmic reticulum chaperone BiP

Protein Summary

Description

Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen (PubMed:2294010, PubMed:23769672, PubMed:23990668, PubMed:28332555). Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10/ERdj5, probably to facilitate the release of DNAJC10/ERdj5 from its substrate (By similarity). Acts as a key repressor of the ERN1/IRE1-mediated unfolded protein response (UPR) (PubMed:1550958, PubMed:19538957). In the unstressed endoplasmic reticulum, recruited by DNAJB9/ERdj4 to the luminal region of ERN1/IRE1, leading to disrupt the dimerization of ERN1/IRE1, thereby inactivating ERN1/IRE1 (By similarity). Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP from ERN1/IRE1, allowing homodimerization and subsequent activation of ERN1/IRE1 (By similarity). Plays an auxiliary role in post-translational transport of small presecretory proteins across endoplasmic reticulum (ER). May function as an allosteric modulator for SEC61 channel-forming translocon complex, likely cooperating with SEC62 to enable the productive insertion of these precursors into SEC61 channel. Appears to specifically regulate translocation of precursors having inhibitory residues in their mature region that weaken channel gating. The protein encoded by this gene is a member of the heat shock protein 70 (HSP70) family. It is localized in the lumen of the endoplasmic reticulum (ER), and is involved in the folding and assembly of proteins in the ER. As this protein interacts with many ER proteins, it may play a key role in monitoring protein transport through the cell.[provided by RefSeq, Sep 2010]

Uniprot Accession IDs

• P11021
• B0QZ61
• Q2EF78
• Q9NPF1
• Q9UK02

Gene Name

• HSPA5

Ensembl ID

• ENST00000324460
• ENSP00000324173
• ENSG00000044574

Symbol

• GRP78
• BIP
• MIF2
• GRP78
• HEL-S-89n

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
chemical	1
disease perturbation	1
hub protein	1
interacting protein	1
molecular function	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: 2634.13   (req: < 5)

Gene RIFs: 403   (req: <= 3)

Antibodies: 1556   (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: 2634.13   (req: >= 5)

Gene RIFs: 403   (req: > 3)

Antibodies: 1556   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 58

Tchem

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

Active Ligands: 8

Tclin

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

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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GlyGen

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ARCHS4

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

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Approved Drugs (0)

No approved drugs found

Active Ligands (8)

Explore Active Ligands

1 – 8 of 8

CHEMBL515570

HSPA5Tchem

pKd : 6.14

CHEMBL462871

HSPA5Tchem

pKd : 7

CHEMBL470334

HSPA5Tchem

pKd : 6.7

CHEMBL473972

HSPA5Tchem

pKd : 6.6

versipelostatin F

HSPA5Tchem

pIC50 : 6.52

CHEMBL538168

HSPA5Tchem

pKd : 6.11

CHEMBL516357

HSPA5Tchem

pKd : 6

CHEMBL1784882

HSPA5Tchem

pKd : 6

Protein-Protein Interactions (734)

Explore Interacting Targets

1 – 10 of 734

• See Interactions on String-DB

FUT7

Tchem

Family:  Enzyme

Novelty:  0.01257357

p_int:  0.98907021

p_ni:  0.01092979

Data Source:  BioPlex

OLFML2B

Tbio

Novelty:  0.19222155

p_int:  0.988169196

p_ni:  0.011830804

Data Source:  BioPlex

PATE1

Tbio

Novelty:  0.0705075

p_int:  0.983280882

p_ni:  0.016719118

Data Source:  BioPlex

VIT

Tbio

Novelty:  0.13376369

p_int:  0.982697951

p_ni:  0.017302049

Score:  0.194

Data Source:  BioPlex,STRINGDB

GAL

Tbio

Novelty:  0.0005132

p_int:  0.982334773

p_ni:  0.017665227

Data Source:  BioPlex

SPAG11B

Tbio

Novelty:  0.07935181

p_int:  0.981672421

p_ni:  0.018327579

Data Source:  BioPlex

ANGPTL2

Tbio

Novelty:  0.01134724

p_int:  0.980932022

p_ni:  0.019067978

Score:  0.177

Data Source:  BioPlex,STRINGDB

PODN

Tbio

Novelty:  0.01466791

p_int:  0.978805073

p_ni:  0.021194927

Data Source:  BioPlex

PRSS1

Tclin

Family:  Enzyme

Novelty:  0.00157396

p_int:  0.974112244

p_ni:  0.025887756

Score:  0.166

Data Source:  BioPlex,STRINGDB

NTF3

Tbio

Novelty:  0.00089023

p_int:  0.973868514

p_ni:  0.026131486

Data Source:  BioPlex

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (34)

Reactome (18)

KEGG (5)

PathwayCommons (7)

WikiPathways (4)

ATF6 (ATF6-alpha) activates chaperone genes (R-HSA-381183)

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1 – 5 of 18

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	ATF6 (ATF6-alpha) activates chaperone genes	11 targets	R-HSA-381183
Reactome	ATF6 (ATF6-alpha) activates chaperones	13 targets	R-HSA-381033
Reactome	Adaptive Immune System	894 targets	R-HSA-1280218
Reactome	Antigen Presentation: Folding, assembly and peptide loading of class I MHC	92 targets	R-HSA-983170
Reactome	Cellular response to heat stress	100 targets	R-HSA-3371556

Name	Explore in Pharos	Explore in Source
ATF6 (ATF6-alpha) activates chaperone genes	11 targets	R-HSA-381183
ATF6 (ATF6-alpha) activates chaperones	13 targets	R-HSA-381033
Adaptive Immune System	894 targets	R-HSA-1280218
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	92 targets	R-HSA-983170
Cellular response to heat stress	100 targets	R-HSA-3371556

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (77)

Functions (14)

Components (19)

Processes (44)

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1 – 10 of 14

GO Term	Evidence	Assigned by
ATPase activity	Inferred from Direct Assay (IDA)	AgBase
misfolded protein binding	Inferred from Direct Assay (IDA)	UniProtKB
enzyme binding	Inferred from Physical Interaction (IPI)	BHF-UCL
protein domain specific binding	Inferred from Physical Interaction (IPI)	UniProtKB
ubiquitin protein ligase binding	Inferred from Physical Interaction (IPI)	UniProtKB
cadherin binding	Inferred from High Throughput Direct Assay (HDA)	BHF-UCL
ATP binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
ATPase activity, coupled	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
heat shock protein binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
protein binding involved in protein folding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central

Disease Associations ()

No disease associations found

GWAS Traits (8)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
smoking status measurement	EFO_0006527	2	2	2		67.8
smoking cessation	EFO_0004319	2	1	2		65.9
worry measurement	EFO_0009589	1	1	0	6.1	35
cigarettes per day measurement	EFO_0006525	1	1	1		24.5
neuroticism measurement	EFO_0007660	1	1	1		11.1

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
smoking status measurement	EFO_0006527	2		67.8
smoking cessation	EFO_0004319	2		65.9
worry measurement	EFO_0009589	0	6.1	35
cigarettes per day measurement	EFO_0006525	1		24.5
neuroticism measurement	EFO_0007660	1		11.1

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
ATP-binding
Chaperone
Complete proteome
Cytoplasm
Direct protein sequencing
Endoplasmic reticulum
Hydrolase
Isopeptide bond

GWAS Trait Find Similar Targets

No Header	No Header
anxiety measurement
appendicular lean mass
cigarettes per day measurement
neuroticism measurement
smoking cessation
smoking initiation
smoking status measurement
worry measurement

MGI Phenotype Find Similar Targets

No Header	No Header
adipose tissue phenotype
cardiovascular system phenotype
cellular phenotype
craniofacial phenotype
digestive/alimentary phenotype
embryo phenotype
growth/size/body region phenotype
homeostasis/metabolism phenotype
integument phenotype
mortality/aging

IDG Resources

No IDG generated resources found

Orthologs (17)

1 – 5 of 17

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	heat shock protein family A (Hsp70) member 5	VGNC:4760	464733
Macaque	heat shock protein family A (Hsp70) member 5		703193
Mouse	heat shock protein 5	MGI:95835	14828
Rat	heat shock protein family A member 5	RGD:2843	25617
Dog	heat shock protein family A (Hsp70) member 5		480726

Species	Name	OMA	EggNOG	Inparanoid
Chimp	heat shock protein family A (Hsp70) member 5
Macaque	heat shock protein family A (Hsp70) member 5
Mouse	heat shock protein 5
Rat	heat shock protein family A member 5
Dog	heat shock protein family A (Hsp70) member 5

Publication Statistics

PubMed Score 2634.13

PubMed score by year

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PubTator Score 1622.86

PubTator score by year

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Related Publications

Text Mined References (511)

GeneRif Annotations (403)

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PMID	Year	Title