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

Gene ID: 3309, updated on 27-Nov-2024

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
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Genomic context

See HSPA5 in Genome Data Viewer
Location:
9q33.3
Exon count:
8
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 9 NC_000009.12 (125234853..125241343, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 9 NC_060933.1 (137433170..137439661, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 9 NC_000009.11 (127997132..128003622, complement)

Chromosome 9 - NC_000009.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105376271 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20275 Neighboring gene Rab9 effector protein with kelch motifs Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29000 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancers GRCh37_chr9:128003252-128003756 and GRCh37_chr9:128003757-128004261 Neighboring gene Sharpr-MPRA regulatory region 12295 Neighboring gene HSPA5 divergent transcript Neighboring gene ReSE screen-validated silencer GRCh37_chr9:128020420-128020678 Neighboring gene ReSE screen-validated silencer GRCh37_chr9:128024002-128024183 Neighboring gene ribosomal protein S10 pseudogene 17 Neighboring gene GTPase activating protein and VPS9 domains 1

Genomic regions, transcripts, and products

Expression

  • 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

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

HIV-1 interactions

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

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Clone Names

  • FLJ26106

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 H2AZ histone chaperone activity IEA
Inferred from Electronic Annotation
more info
 
enables ATP-dependent H3-H4 histone complex chaperone activity IEA
Inferred from Electronic Annotation
more info
 
enables ATP-dependent protein folding chaperone IEA
Inferred from Electronic Annotation
more info
 
enables DNA clamp loader activity IEA
Inferred from Electronic Annotation
more info
 
enables cadherin binding HDA PubMed 
enables calcium ion binding TAS
Traceable Author Statement
more info
PubMed 
enables chromatin extrusion motor activity IEA
Inferred from Electronic Annotation
more info
 
enables cohesin loader activity IEA
Inferred from Electronic Annotation
more info
 
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 serine/threonine kinase inhibitor activity IDA
Inferred from Direct Assay
more info
PubMed 
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 chromatin looping IEA
Inferred from Electronic Annotation
more info
 
involved_in chromatin remodeling IEA
Inferred from Electronic Annotation
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 PERK-mediated unfolded protein response IDA
Inferred from Direct Assay
more info
PubMed 
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 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 PubMed 
located_in focal adhesion HDA 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 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 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

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

NCBI Reference Sequences (RefSeq)

NEW Try the new Transcript table

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.

Genomic

  1. NG_027761.1 RefSeqGene

    Range
    5045..11535
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_005347.5NP_005338.1  endoplasmic reticulum chaperone BiP precursor

    See identical proteins and their annotated locations for NP_005338.1

    Status: REVIEWED

    Source sequence(s)
    BC020235, DA549454, X87949
    Consensus CDS
    CCDS6863.1
    UniProtKB/Swiss-Prot
    B0QZ61, P11021, Q2EF78, Q9NPF1, Q9UK02
    UniProtKB/TrEMBL
    A0A7P0TB36, V9HWB4
    Related
    ENSP00000324173.6, ENST00000324460.7
    Conserved Domains (1) summary
    pfam00012
    Location:30635
    HSP70; Hsp70 protein

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000009.12 Reference GRCh38.p14 Primary Assembly

    Range
    125234853..125241343 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060933.1 Alternate T2T-CHM13v2.0

    Range
    137433170..137439661 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)