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

Gene ID: 3309, updated on 8-May-2016
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 HPRD:00682; MIM:138120; Vega:OTTHUMG00000020672
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; MIF2; GRP78; HEL-S-89n
Summary
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]
Orthologs
Location:
9q33.3
Exon count:
8
Annotation release Status Assembly Chr Location
107 current GRCh38.p2 (GCF_000001405.28) 9 NC_000009.12 (125234848..125241387, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 9 NC_000009.11 (127997127..128003666, complement)

Chromosome 9 - NC_000009.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105376271 Neighboring gene Rab9 effector protein with kelch motifs Neighboring gene GTPase activating protein and VPS9 domains 1 Neighboring gene ribosomal protein S10 pseudogene 17 Neighboring gene uncharacterized LOC101929014

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 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 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

  • ATF6-alpha activates chaperone genes, organism-specific biosystem (from REACTOME)
    ATF6-alpha activates chaperone genes, organism-specific biosystemThe N-terminal fragment of ATF6-alpha contains a bZIP domain and binds the sequence CCACG in ER Stress Response Elements (ERSEs). ATF6-alpha binds ERSEs together with the heterotrimeric transcription...
  • ATF6-alpha activates chaperones, organism-specific biosystem (from REACTOME)
    ATF6-alpha activates chaperones, organism-specific biosystemATF6-alpha is a transmembrane protein that normally resides in the Endoplasmic Reticulum (ER) membrane. Here its luminal C-terminal domain is associated with BiP, shielding 2 Golgi-targeting regions ...
  • Adaptive Immune System, organism-specific biosystem (from REACTOME)
    Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
  • Antigen Presentation: Folding, assembly and peptide loading of class I MHC, organism-specific biosystem (from REACTOME)
    Antigen Presentation: Folding, assembly and peptide loading of class I MHC, organism-specific biosystemUnlike other glycoproteins, correct folding of MHC class I molecules is not sufficient to trigger their exit from the ER, they exit only after peptide loading. Described here is the process of antige...
  • Antigen processing and presentation, organism-specific biosystem (from KEGG)
    Antigen processing and presentation, organism-specific biosystem
    Antigen processing and presentation
  • Antigen processing and presentation, conserved biosystem (from KEGG)
    Antigen processing and presentation, conserved biosystem
    Antigen processing and presentation
  • Cellular response to heat stress, organism-specific biosystem (from REACTOME)
    Cellular response to heat stress, organism-specific biosystemIn response to exposure to elevated temperature and certain other proteotoxic stimuli (e.g., hypoxia, free radicals) cells activate a number of cytoprotective mechanisms known collectively as "heat s...
  • Cellular responses to stress, organism-specific biosystem (from REACTOME)
    Cellular responses to stress, organism-specific biosystemCells are subject to external molecular and physical stresses such as foreign molecules that perturb metabolic or signaling processes, and changes in temperature or pH. The ability of cells and tissu...
  • Class I MHC mediated antigen processing & presentation, organism-specific biosystem (from REACTOME)
    Class I MHC mediated antigen processing & presentation, organism-specific biosystemMajor histocompatibility complex (MHC) class I molecules play an important role in cell mediated immunity by reporting on intracellular events such as viral infection, the presence of intracellular b...
  • Hemostasis, organism-specific biosystem (from REACTOME)
    Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...
  • IRE1alpha activates chaperones, organism-specific biosystem (from REACTOME)
    IRE1alpha activates chaperones, organism-specific biosystemIRE1-alpha is a single-pass transmembrane protein that resides in the endoplasmic reticulum (ER) membrane. The C-terminus of IRE1-alpha is located in the cytosol; the N-terminus is located in the ER ...
  • Immune System, organism-specific biosystem (from REACTOME)
    Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
  • MAPK signaling pathway, organism-specific biosystem (from WikiPathways)
    MAPK signaling pathway, organism-specific biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
  • Metabolism of proteins, organism-specific biosystem (from REACTOME)
    Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
  • PERK regulates gene expression, organism-specific biosystem (from REACTOME)
    PERK regulates gene expression, organism-specific biosystemPERK (EIF2AK3) is a single-pass transmembrane protein located in the endoplasmic reticulum (ER) membrane such that the N-terminus of PERK is luminal and the C-terminus is cytosolic. PERK is maintaine...
  • Parkin-Ubiquitin Proteasomal System pathway, organism-specific biosystem (from WikiPathways)
    Parkin-Ubiquitin Proteasomal System pathway, organism-specific biosystemThis pathway describes the Parkin-Ubiquitin proteasome degradation system.
  • Platelet activation, signaling and aggregation, organism-specific biosystem (from REACTOME)
    Platelet activation, signaling and aggregation, organism-specific biosystemPlatelet activation begins with the initial binding of adhesive ligands and of the excitatory platelet agonists (released or generated at the sites of vascular trauma) to cognate receptors on the pla...
  • Platelet degranulation, organism-specific biosystem (from REACTOME)
    Platelet degranulation, organism-specific biosystemPlatelets function as exocytotic cells, secreting a plethora of effector molecules at sites of vascular injury. Platelets contain a number of distinguishable storage granules including alpha granules...
  • Prion diseases, organism-specific biosystem (from KEGG)
    Prion diseases, organism-specific biosystemPrion diseases, also termed transmissible spongiform encephalopathies (TSEs), are a group of fatal neurodegenerative diseases that affect humans and a number of other animal species. The etiology of ...
  • Prion diseases, conserved biosystem (from KEGG)
    Prion diseases, conserved biosystemPrion diseases, also termed transmissible spongiform encephalopathies (TSEs), are a group of fatal neurodegenerative diseases that affect humans and a number of other animal species. The etiology of ...
  • Protein export, organism-specific biosystem (from KEGG)
    Protein export, organism-specific biosystemThe protein export is the active transport of proteins from the cytoplasm to the exterior of the cell, or to the periplasmic compartment in Gram-negative bacteria. The sec dependent pathway is the ge...
  • Protein export, conserved biosystem (from KEGG)
    Protein export, conserved biosystemThe protein export is the active transport of proteins from the cytoplasm to the exterior of the cell, or to the periplasmic compartment in Gram-negative bacteria. The sec dependent pathway is the ge...
  • Protein processing in endoplasmic reticulum, organism-specific biosystem (from KEGG)
    Protein processing in endoplasmic reticulum, organism-specific biosystemThe endoplasmic reticulum (ER) is a subcellular organelle where proteins are folded with the help of lumenal chaperones. Newly synthesized peptides enter the ER via the sec61 pore and are glycosylate...
  • Protein processing in endoplasmic reticulum, conserved biosystem (from KEGG)
    Protein processing in endoplasmic reticulum, conserved biosystemThe endoplasmic reticulum (ER) is a subcellular organelle where proteins are folded with the help of lumenal chaperones. Newly synthesized peptides enter the ER via the sec61 pore and are glycosylate...
  • Regulation of HSF1-mediated heat shock response, organism-specific biosystem (from REACTOME)
    Regulation of HSF1-mediated heat shock response, organism-specific biosystemThe ability of HSF1 to respond to cellular stresses is under negative regulation by chaperones, modulation of nucleocytoplasmic shuttling, post-translational modifications and transition from monomer...
  • Response to elevated platelet cytosolic Ca2+, organism-specific biosystem (from REACTOME)
    Response to elevated platelet cytosolic Ca2+, organism-specific biosystemActivation of phospholipase C enzymes results in the generation of second messengers of the phosphatidylinositol pathway. The events resulting from this pathway are a rise in intracellular calcium an...
  • Thyroid hormone synthesis, organism-specific biosystem (from KEGG)
    Thyroid hormone synthesis, organism-specific biosystemThyroid hormones triiodothyronine (T3) and thyroxine (T4) are essential for normal development, growth and metabolic homeostasis in all vertebrates, and synthesized in the thyroid gland. The function...
  • Thyroid hormone synthesis, conserved biosystem (from KEGG)
    Thyroid hormone synthesis, conserved biosystemThyroid hormones triiodothyronine (T3) and thyroxine (T4) are essential for normal development, growth and metabolic homeostasis in all vertebrates, and synthesized in the thyroid gland. The function...
  • Unfolded Protein Response (UPR), organism-specific biosystem (from REACTOME)
    Unfolded Protein Response (UPR), organism-specific biosystemThe Unfolded Protein Response (UPR) is a regulatory system that protects the Endoplasmic Reticulum (ER) from overload. The UPR is provoked by the accumulation of improperly folded protein in the ER d...
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Clone Names

  • FLJ26106

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IEA
Inferred from Electronic Annotation
more info
 
ATPase activity IDA
Inferred from Direct Assay
more info
PubMed 
ATPase activity ISS
Inferred from Sequence or Structural Similarity
more info
 
calcium ion binding TAS
Traceable Author Statement
more info
PubMed 
chaperone binding TAS
Traceable Author Statement
more info
PubMed 
enzyme binding IPI
Inferred from Physical Interaction
more info
PubMed 
glycoprotein binding IPI
Inferred from Physical Interaction
more info
PubMed 
misfolded protein binding IDA
Inferred from Direct Assay
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein domain specific binding IPI
Inferred from Physical Interaction
more info
PubMed 
ribosome binding IEA
Inferred from Electronic Annotation
more info
 
ubiquitin protein ligase binding IPI
Inferred from Physical Interaction
more info
PubMed 
unfolded protein binding TAS
Traceable Author Statement
more info
PubMed 
Process Evidence Code Pubs
ATF6-mediated unfolded protein response TAS
Traceable Author Statement
more info
 
ER overload response IEA
Inferred from Electronic Annotation
more info
 
ER-associated ubiquitin-dependent protein catabolic process TAS
Traceable Author Statement
more info
PubMed 
IRE1-mediated unfolded protein response TAS
Traceable Author Statement
more info
 
PERK-mediated unfolded protein response TAS
Traceable Author Statement
more info
 
activation of signaling protein activity involved in unfolded protein response IEA
Inferred from Electronic Annotation
more info
 
cellular response to antibiotic IEA
Inferred from Electronic Annotation
more info
 
cellular response to glucose starvation IDA
Inferred from Direct Assay
more info
PubMed 
cellular response to interleukin-4 IEA
Inferred from Electronic Annotation
more info
 
cellular response to manganese ion IEA
Inferred from Electronic Annotation
more info
 
cerebellar Purkinje cell layer development IEA
Inferred from Electronic Annotation
more info
 
cerebellum structural organization IEA
Inferred from Electronic Annotation
more info
 
endoplasmic reticulum unfolded protein response TAS
Traceable Author Statement
more info
PubMed 
maintenance of protein localization in endoplasmic reticulum IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of apoptotic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of apoptotic process TAS
Traceable Author Statement
more info
PubMed 
negative regulation of protein homodimerization activity TAS
Traceable Author Statement
more info
PubMed 
negative regulation of transforming growth factor beta receptor signaling pathway IEA
Inferred from Electronic Annotation
more info
 
positive regulation of cell migration IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of protein ubiquitination IEA
Inferred from Electronic Annotation
more info
 
positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress TAS
Traceable Author Statement
more info
PubMed 
protein folding in endoplasmic reticulum TAS
Traceable Author Statement
more info
PubMed 
regulation of ATF6-mediated unfolded protein response TAS
Traceable Author Statement
more info
PubMed 
regulation of IRE1-mediated unfolded protein response TAS
Traceable Author Statement
more info
PubMed 
regulation of PERK-mediated unfolded protein response TAS
Traceable Author Statement
more info
PubMed 
regulation of protein folding in endoplasmic reticulum TAS
Traceable Author Statement
more info
PubMed 
substantia nigra development IEP
Inferred from Expression Pattern
more info
PubMed 
toxin transport IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
colocalizes_with COP9 signalosome IDA
Inferred from Direct Assay
more info
PubMed 
cell surface IEA
Inferred from Electronic Annotation
more info
 
endoplasmic reticulum IDA
Inferred from Direct Assay
more info
PubMed 
endoplasmic reticulum IMP
Inferred from Mutant Phenotype
more info
PubMed 
endoplasmic reticulum TAS
Traceable Author Statement
more info
PubMed 
endoplasmic reticulum chaperone complex IDA
Inferred from Direct Assay
more info
PubMed 
endoplasmic reticulum lumen TAS
Traceable Author Statement
more info
 
endoplasmic reticulum membrane TAS
Traceable Author Statement
more info
 
endoplasmic reticulum-Golgi intermediate compartment IDA
Inferred from Direct Assay
more info
PubMed 
extracellular exosome IDA
Inferred from Direct Assay
more info
PubMed 
focal adhesion IDA
Inferred from Direct Assay
more info
PubMed 
integral component of endoplasmic reticulum membrane IDA
Inferred from Direct Assay
more info
PubMed 
melanosome IEA
Inferred from Electronic Annotation
more info
 
membrane IDA
Inferred from Direct Assay
more info
PubMed 
midbody IDA
Inferred from Direct Assay
more info
PubMed 
mitochondrion IEA
Inferred from Electronic Annotation
more info
 
myelin sheath IEA
Inferred from Electronic Annotation
more info
 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 
nucleus IMP
Inferred from Mutant Phenotype
more info
PubMed 
plasma membrane IEA
Inferred from Electronic Annotation
more info
 
smooth endoplasmic reticulum IEA
Inferred from Electronic Annotation
more info
 
Preferred Names
78 kDa glucose-regulated protein
Names
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)
immunoglobulin heavy chain-binding protein

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
    5001..11540
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_005347.4NP_005338.1  78 kDa glucose-regulated protein precursor

    See identical proteins and their annotated locations for NP_005338.1

    Status: REVIEWED

    Source sequence(s)
    AA433933, BC020235, DA549454, X87949
    Consensus CDS
    CCDS6863.1
    UniProtKB/Swiss-Prot
    P11021
    UniProtKB/TrEMBL
    V9HWB4
    Related
    ENSP00000324173, OTTHUMP00000022124, ENST00000324460, OTTHUMT00000054062
    Conserved Domains (2) summary
    cd10241
    Location:28403
    HSPA5-like_NBD; Nucleotide-binding domain of human HSPA5 and similar proteins
    pfam00012
    Location:30635
    HSP70; Hsp70 protein

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 107 details...

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

Reference GRCh38.p2 Primary Assembly

Genomic

  1. NC_000009.12 Reference GRCh38.p2 Primary Assembly

    Range
    125234848..125241387 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018920.2 Alternate CHM1_1.1

    Range
    128146874..128153413 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)