U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Links from GEO Profiles

    • Showing Current items.

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

    Gene ID: 3309, updated on 28-Oct-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
    NEW
    Try the new Gene table
    Try the new Transcript table

    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 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 protein folding chaperone IEA
    Inferred from Electronic Annotation
    more info
     
    enables cadherin binding HDA 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 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)