HSPA5 heat shock protein family A (Hsp70) member 5 [Homo sapiens (human)] - Gene

Summary

Official Symbol: HSPA5provided by HGNC
Official Full Name: heat shock protein family A (Hsp70) member 5provided by HGNC
Primary source: HGNC:HGNC:5238
See related: Ensembl:ENSG00000044574 MIM:138120; AllianceGenome:HGNC:5238
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: BIP; GRP78; HEL-S-89n
Summary: The protein encoded by this gene is a member of the heat shock protein 70 (HSP70) family. This protein localizes to the lumen of the endoplasmic reticulum (ER) where it operates as a typical HSP70 chaperone involved in the folding and assembly of proteins in the ER and is a master regulator of ER homeostasis. During cellular stress, as during viral infection or tumorogenesis, this protein interacts with the transmembrane stress sensor proteins PERK (protein kinase R-like endoplasmic reticulum kinase), IRE1 (inositol-requiring kinase 1), and ATF6 (activating transcription factor 6) where it acts as a repressor of the unfolded protein response (UPR) and also plays a role in cellular apoptosis and senescence. Elevated expression and atypical translocation of this protein to the cell surface has been reported in viral infections and some types of cancer cells. At the cell surface this protein may facilitate viral attachment and entry to host cells. This gene is a therapeutic target for the treatment of coronavirus diseases and chemoresistant cancers. [provided by RefSeq, Jul 2020]
Annotation information: Note: This gene has been reviewed for its involvement in coronavirus biology, and is relevant for COVID-19 treatment.
Expression: Broad expression in thyroid (RPKM 442.6), bone marrow (RPKM 284.6) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 9q33.3

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	9	NC_000009.12 (125234853..125241343, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	9	NC_060933.1 (137433170..137439661, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	9	NC_000009.11 (127997132..128003622, complement)

Chromosome 9 - NC_000009.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Prediction of the binding location between the nuclear inhibitor of DNA binding and differentiation 2 (ID2) and HSPA5.
Title: Prediction of the binding location between the nuclear inhibitor of DNA binding and differentiation 2 (ID2) and HSPA5.
Structural basis for the mechanism of interaction of SARS-CoV-2 B.1.640.2 variant RBD with the host receptors hACE2 and GRP78.
Title: Structural basis for the mechanism of interaction of SARS-CoV-2 B.1.640.2 variant RBD with the host receptors hACE2 and GRP78.
GRP78 promotes bone metastasis of prostate cancer by regulating bone microenvironment through Sonic hedgehog signaling.
Title: GRP78 promotes bone metastasis of prostate cancer by regulating bone microenvironment through Sonic hedgehog signaling.
lncRNA HOTAIRM1 Activated by HOXA4 Drives HUVEC Proliferation Through Direct Interaction with Protein Partner HSPA5.
Title: lncRNA HOTAIRM1 Activated by HOXA4 Drives HUVEC Proliferation Through Direct Interaction with Protein Partner HSPA5.
Nuclear GRP78 Promotes Metabolic Reprogramming and Therapeutic Resistance in Pancreatic Ductal Adenocarcinoma.
Title: Nuclear GRP78 Promotes Metabolic Reprogramming and Therapeutic Resistance in Pancreatic Ductal Adenocarcinoma.
Mechanistic characterization of disulfide bond reduction of an ERAD substrate mediated by cooperation between ERdj5 and BiP.
Title: Mechanistic characterization of disulfide bond reduction of an ERAD substrate mediated by cooperation between ERdj5 and BiP.
Valosin-containing protein (VCP/p97) is prognostically unfavorable in pediatric AML, and negatively correlates with unfolded protein response proteins IRE1 and GRP78: A report from the Children's Oncology Group.
Title: Valosin-containing protein (VCP/p97) is prognostically unfavorable in pediatric AML, and negatively correlates with unfolded protein response proteins IRE1 and GRP78: A report from the Children's Oncology Group.
NRF3 suppresses squamous carcinogenesis, involving the unfolded protein response regulator HSPA5.
Title: NRF3 suppresses squamous carcinogenesis, involving the unfolded protein response regulator HSPA5.
The chaperone protein GRP78 released from MPN cells increases the expression of lysyl oxidase in a human stromal cell line.
Title: The chaperone protein GRP78 released from MPN cells increases the expression of lysyl oxidase in a human stromal cell line.
Research progress on the GRP78 gene in the diagnosis, treatment and immunity of cervical cancer.
Title: Research progress on the GRP78 gene in the diagnosis, treatment and immunity of cervical cancer.

Submit: New GeneRIF Correction See all GeneRIFs (537)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 Env gp120 upregulates HSPA5 (GRP78/BiP) in SVGA cells and human fetal astrocytes	PubMed
	env	Tandem affinity purification and mass spectrometry analysis identify heat shock 70kDa protein 5 (HSPA5; 78kDa glucose-regulated protein), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
	env	Over expression of hsp70 with a herpes viral amplicon vector protects cultured hippocampal rat neurons from gp120 neurotoxicity	PubMed
	env	The exposure of permissive CD4+ cells to HIV-1 gp120 increases the synthesis and nuclear translocation of 70kDa heat shock protein	PubMed
Envelope surface glycoprotein gp160, precursor	env	HIV-1 gp160 interacts with HSPA5; predicted interaction to be within the endoplasmic reticulum and function as chaperone for endoplasmic reticulum-associated degradation	PubMed
	env	Newly synthesized HIV-1 gp160 interacts with GRP78-BiP in pulse-chase experiments; the interaction sites of gp160 with BiP include residues 115-132, 484-490, 602-616, 676-690, and 776-807	PubMed
Gag-Pol	gag-pol	Tandem affinity purification and mass spectrometry analysis identify heat shock 70kDa protein 5 (HSPA5; 78kDa glucose-regulated protein), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
Nef	nef	Tandem affinity purification and mass spectrometry analysis identify heat shock 70kDa protein 5 (HSPA5; 78kDa glucose-regulated protein), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
	nef	Heat shock proteins Hsp40 and Hsp70 interact with HIV-1 Nef and form a complex in cells	PubMed
Pr55(Gag)	gag	Tandem affinity purification and mass spectrometry analysis identify heat shock 70kDa protein 5 (HSPA5; 78kDa glucose-regulated protein), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
	gag	Hsp70 is incorporated into HIV-1 virions through an interaction with HIV-1 Gag	PubMed
	gag	Hsp70 co-sediments with HIV-1 capsid protein in sucrose density gradients, providing evidence that it is specifically incorporated into HIV-1 virions through an interaction with HIV-1 Gag proteins	PubMed
Tat	tat	Exposure of human umbilical vein endothelial cells to HIV-1 Tat causes broad activation of the unfolded-protein response in ER with phosphorylation of PERK, eIF2alpha, and JNK and induction of Grp78/BiP	PubMed
	tat	Hsp70 and Hsp90 and Cdc37 regulate the stabilization and folding of CDK9 as well as the assembly of an active CDK9/cyclin T1 complex responsible for P-TEFb-mediated HIV-1 Tat transactivation	PubMed
Vpr	vpr	A stable-isotope labeling by amino acids in cell culture coupled with mass spectrometry-based proteomics identifies upregulation of heat shock 70kDa protein 5 (HSPA5, GRP78) expression by HIV-1 Vpr in Vpr transduced macrophages	PubMed
	vpr	HIV-1 Vpr is required for the inhibitory effect of Hsp70 on viral gene expression and replication	PubMed
	vpr	HIV-1 Vpr significantly increases expression level of GRP78 in the endoplasmic reticulum	PubMed
	vpr	HIV-1 Vpr competes with Hsp70 for binding to karyopherin alpha	PubMed
matrix	gag	Hsp70 facilitates nuclear import of HIV-1 preintegration complexes by stimulating the binding of HIV-1 Matrix to karyopherin alpha	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D9S1138 (e-PCR)
- UniSTS:48897

D10S275 (e-PCR)
- UniSTS:147992

D2Wsu17e (e-PCR), detects polymorphism
- UniSTS:142375

PMC108893P1 (e-PCR)
- UniSTS:270143

RH102504 (e-PCR)
- UniSTS:96838

HSPA5_988 (e-PCR)
- UniSTS:277334

RH94472 (e-PCR)
- UniSTS:119720

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IDA Inferred from Direct Assay more info	PubMed
enables ATP hydrolysis activity	IBA Inferred from Biological aspect of Ancestor more info
enables ATP hydrolysis activity	IDA Inferred from Direct Assay more info	PubMed
enables ATP hydrolysis activity	ISS Inferred from Sequence or Structural Similarity more info
enables ATP-dependent protein folding chaperone	IEA Inferred from Electronic Annotation more info
enables cadherin binding	HDA more info	PubMed
enables calcium ion binding	TAS Traceable Author Statement more info	PubMed
enables enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
enables heat shock protein binding	IBA Inferred from Biological aspect of Ancestor more info
enables misfolded protein binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein domain specific binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein folding chaperone	IBA Inferred from Biological aspect of Ancestor more info
enables protein-folding chaperone binding	TAS Traceable Author Statement more info	PubMed
enables ribosome binding	IEA Inferred from Electronic Annotation more info
enables ubiquitin protein ligase binding	IPI Inferred from Physical Interaction more info	PubMed
enables unfolded protein binding	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in ER overload response	IEA Inferred from Electronic Annotation more info
involved_in ERAD pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in ERAD pathway	TAS Traceable Author Statement more info	PubMed
involved_in cellular response to glucose starvation	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to interleukin-4	IEA Inferred from Electronic Annotation more info
involved_in cerebellar Purkinje cell layer development	IEA Inferred from Electronic Annotation more info
involved_in cerebellum structural organization	IEA Inferred from Electronic Annotation more info
involved_in chaperone cofactor-dependent protein refolding	IBA Inferred from Biological aspect of Ancestor more info
involved_in endoplasmic reticulum unfolded protein response	IBA Inferred from Biological aspect of Ancestor more info
involved_in endoplasmic reticulum unfolded protein response	TAS Traceable Author Statement more info	PubMed
involved_in maintenance of protein localization in endoplasmic reticulum	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of IRE1-mediated unfolded protein response	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of apoptotic process	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of protein-containing complex assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of transforming growth factor beta receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein ubiquitination	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of transcription by RNA polymerase II	TAS Traceable Author Statement more info	PubMed
involved_in post-translational protein targeting to membrane, translocation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein folding in endoplasmic reticulum	TAS Traceable Author Statement more info	PubMed
involved_in protein refolding	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of ATF6-mediated unfolded protein response	TAS Traceable Author Statement more info	PubMed
involved_in regulation of IRE1-mediated unfolded protein response	TAS Traceable Author Statement more info	PubMed
involved_in regulation of PERK-mediated unfolded protein response	TAS Traceable Author Statement more info	PubMed
involved_in regulation of protein folding in endoplasmic reticulum	TAS Traceable Author Statement more info	PubMed
involved_in response to endoplasmic reticulum stress	TAS Traceable Author Statement more info	PubMed
involved_in substantia nigra development	HEP more info	PubMed

Component	Evidence Code	Pubs
part_of COP9 signalosome	IDA Inferred from Direct Assay more info	PubMed
located_in cell surface	IEA Inferred from Electronic Annotation more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum	IMP Inferred from Mutant Phenotype more info	PubMed
located_in endoplasmic reticulum	TAS Traceable Author Statement more info	PubMed
part_of endoplasmic reticulum chaperone complex	IBA Inferred from Biological aspect of Ancestor more info
part_of endoplasmic reticulum chaperone complex	IDA Inferred from Direct Assay more info	PubMed
is_active_in endoplasmic reticulum lumen	IBA Inferred from Biological aspect of Ancestor more info
located_in endoplasmic reticulum lumen	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum lumen	TAS Traceable Author Statement more info
located_in endoplasmic reticulum membrane	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	TAS Traceable Author Statement more info
located_in endoplasmic reticulum-Golgi intermediate compartment	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
located_in focal adhesion	HDA more info	PubMed
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info	PubMed
located_in melanosome	IEA Inferred from Electronic Annotation more info
located_in membrane	HDA more info	PubMed
is_active_in membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in midbody	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	HDA more info	PubMed
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IMP Inferred from Mutant Phenotype more info	PubMed
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: endoplasmic reticulum chaperone BiP

Names: 78 kDa glucose-regulated protein; HSP70 family protein 5; binding-immunoglobulin protein; endoplasmic reticulum lumenal Ca(2+)-binding protein grp78; epididymis secretory sperm binding protein Li 89n; glucose-regulated protein, 78kDa; heat shock 70kDa protein 5 (glucose-regulated protein, 78kDa); heat shock protein 70 family protein 5; heat shock protein family A member 5; immunoglobulin heavy chain-binding protein

NP_005338.1

EC 3.6.4.10

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.