Human Gene HSPA5 (uc004bpn.3)
  Description: Homo sapiens heat shock 70kDa protein 5 (glucose-regulated protein, 78kDa) (HSPA5), mRNA.
RefSeq Summary (NM_005347): 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].
Transcript (Including UTRs)
   Position: hg19 chr9:127,997,127-128,003,666 Size: 6,540 Total Exon Count: 8 Strand: -
Coding Region
   Position: hg19 chr9:127,998,871-128,003,405 Size: 4,535 Coding Exon Count: 8 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesModel Information
Methods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr9:127,997,127-128,003,666)mRNA (may differ from genome)Protein (654 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
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MGIneXtProtOMIMPubMedReactomeTreefam
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: GRP78_HUMAN
DESCRIPTION: RecName: Full=78 kDa glucose-regulated protein; Short=GRP-78; AltName: Full=Endoplasmic reticulum lumenal Ca(2+)-binding protein grp78; AltName: Full=Heat shock 70 kDa protein 5; AltName: Full=Immunoglobulin heavy chain-binding protein; Short=BiP; Flags: Precursor;
FUNCTION: Probably plays a role in facilitating the assembly of multimeric protein complexes inside the ER.
SUBUNIT: Interacts with DNAJC1 (via J domain) (By similarity). Component of an EIF2 complex at least composed of CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5. Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGT1A1 and very small amounts of ERP29, but not, or at very low levels, CALR nor CANX. Interacts with TMEM132A and TRIM21. May form a complex with ERLEC1, OS9, SEL1L and SYVN1.
INTERACTION: Q96IZ0:PAWR; NbExp=8; IntAct=EBI-354921, EBI-595869; Q62627:Pawr (xeno); NbExp=4; IntAct=EBI-354921, EBI-1187240; P04049:RAF1; NbExp=4; IntAct=EBI-354921, EBI-365996;
SUBCELLULAR LOCATION: Endoplasmic reticulum lumen. Melanosome. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV.
DISEASE: Note=Autoantigen in rheumatoid arthritis.
SIMILARITY: Belongs to the heat shock protein 70 family.
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/hspa5/";

-  Primer design for this transcript
 

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Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): HSPA5
CDC HuGE Published Literature: HSPA5

-  MalaCards Disease Associations
  MalaCards Gene Search: HSPA5
Diseases sorted by gene-association score: borna disease (21), wolfram syndrome (13), short-rib thoracic dysplasia 2 with or without polydactyly (9), hepatitis a (6), transient cerebral ischemia (5), spinocerebellar ataxia 14 (4), rheumatoid arthritis (3), colorectal cancer (2), hepatocellular carcinoma (2), amyotrophic lateral sclerosis 1 (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 228.40 RPKM in Thyroid
Total median expression: 4481.98 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -102.90261-0.394 Picture PostScript Text
3' UTR -552.461744-0.317 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR018181 - Heat_shock_70_CS
IPR013126 - Hsp_70_fam

Pfam Domains:
PF00012 - Hsp70 protein
PF06723 - MreB/Mbl protein

SCOP Domains:
100934 - Heat shock protein 70kD (HSP70), C-terminal subdomain
100920 - Heat shock protein 70kD (HSP70), peptide-binding domain
53067 - Actin-like ATPase domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
3IUC - X-ray MuPIT 3LDL - X-ray MuPIT 3LDN - X-ray MuPIT 3LDO - X-ray MuPIT 3LDP - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P11021
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserGenome BrowserGenome BrowserGenome BrowserGenome Browser
Gene DetailsGene Details Gene DetailsGene DetailsGene Details
Gene SorterGene Sorter Gene SorterGene SorterGene Sorter
 RGDEnsemblFlyBaseWormBaseSGD
 Protein SequenceProtein SequenceProtein SequenceProtein SequenceProtein Sequence
 AlignmentAlignmentAlignmentAlignmentAlignment

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0005509 calcium ion binding
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016787 hydrolase activity
GO:0016887 ATPase activity
GO:0019899 enzyme binding
GO:0019904 protein domain specific binding
GO:0031625 ubiquitin protein ligase binding
GO:0043022 ribosome binding
GO:0045296 cadherin binding
GO:0051082 unfolded protein binding
GO:0051087 chaperone binding
GO:0051787 misfolded protein binding

Biological Process:
GO:0006983 ER overload response
GO:0006987 activation of signaling protein activity involved in unfolded protein response
GO:0009314 response to radiation
GO:0010976 positive regulation of neuron projection development
GO:0021589 cerebellum structural organization
GO:0021680 cerebellar Purkinje cell layer development
GO:0021762 substantia nigra development
GO:0030182 neuron differentiation
GO:0030335 positive regulation of cell migration
GO:0030433 ER-associated ubiquitin-dependent protein catabolic process
GO:0030512 negative regulation of transforming growth factor beta receptor signaling pathway
GO:0030968 endoplasmic reticulum unfolded protein response
GO:0031398 positive regulation of protein ubiquitination
GO:0034975 protein folding in endoplasmic reticulum
GO:0034976 response to endoplasmic reticulum stress
GO:0035437 maintenance of protein localization in endoplasmic reticulum
GO:0035690 cellular response to drug
GO:0036498 IRE1-mediated unfolded protein response
GO:0036499 PERK-mediated unfolded protein response
GO:0036500 ATF6-mediated unfolded protein response
GO:0042149 cellular response to glucose starvation
GO:0042220 response to cocaine
GO:0043066 negative regulation of apoptotic process
GO:0051402 neuron apoptotic process
GO:0051603 proteolysis involved in cellular protein catabolic process
GO:0060904 regulation of protein folding in endoplasmic reticulum
GO:0071236 cellular response to antibiotic
GO:0071277 cellular response to calcium ion
GO:0071287 cellular response to manganese ion
GO:0071320 cellular response to cAMP
GO:0071353 cellular response to interleukin-4
GO:0071480 cellular response to gamma radiation
GO:0090074 negative regulation of protein homodimerization activity
GO:0097501 stress response to metal ion
GO:1901998 toxin transport
GO:1903891 regulation of ATF6-mediated unfolded protein response
GO:1903894 regulation of IRE1-mediated unfolded protein response
GO:1903895 negative regulation of IRE1-mediated unfolded protein response
GO:1903897 regulation of PERK-mediated unfolded protein response
GO:1904313 response to methamphetamine hydrochloride
GO:1990090 cellular response to nerve growth factor stimulus
GO:1990440 positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress

Cellular Component:
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005783 endoplasmic reticulum
GO:0005788 endoplasmic reticulum lumen
GO:0005789 endoplasmic reticulum membrane
GO:0005790 smooth endoplasmic reticulum
GO:0005793 endoplasmic reticulum-Golgi intermediate compartment
GO:0005886 plasma membrane
GO:0005925 focal adhesion
GO:0009986 cell surface
GO:0016020 membrane
GO:0030176 integral component of endoplasmic reticulum membrane
GO:0030496 midbody
GO:0032991 macromolecular complex
GO:0034663 endoplasmic reticulum chaperone complex
GO:0042470 melanosome
GO:0043209 myelin sheath
GO:0070062 extracellular exosome
GO:0008180 COP9 signalosome


-  Descriptions from all associated GenBank mRNAs
  BC020235 - Homo sapiens heat shock 70kDa protein 5 (glucose-regulated protein, 78kDa), mRNA (cDNA clone MGC:31939 IMAGE:5020098), complete cds.
LP895631 - Sequence 495 from Patent EP3253886.
JD130916 - Sequence 111940 from Patent EP1572962.
JD119936 - Sequence 100960 from Patent EP1572962.
JD104246 - Sequence 85270 from Patent EP1572962.
JD515106 - Sequence 496130 from Patent EP1572962.
JD313547 - Sequence 294571 from Patent EP1572962.
JD392500 - Sequence 373524 from Patent EP1572962.
JD565700 - Sequence 546724 from Patent EP1572962.
JD329437 - Sequence 310461 from Patent EP1572962.
JD523961 - Sequence 504985 from Patent EP1572962.
JD366270 - Sequence 347294 from Patent EP1572962.
JD474096 - Sequence 455120 from Patent EP1572962.
JD141992 - Sequence 123016 from Patent EP1572962.
JD105764 - Sequence 86788 from Patent EP1572962.
JD517377 - Sequence 498401 from Patent EP1572962.
JD149287 - Sequence 130311 from Patent EP1572962.
JD383566 - Sequence 364590 from Patent EP1572962.
JD185291 - Sequence 166315 from Patent EP1572962.
JD517139 - Sequence 498163 from Patent EP1572962.
JD149207 - Sequence 130231 from Patent EP1572962.
JD240803 - Sequence 221827 from Patent EP1572962.
JD224671 - Sequence 205695 from Patent EP1572962.
JD280432 - Sequence 261456 from Patent EP1572962.
JD097465 - Sequence 78489 from Patent EP1572962.
JD512538 - Sequence 493562 from Patent EP1572962.
JD350994 - Sequence 332018 from Patent EP1572962.
JD182516 - Sequence 163540 from Patent EP1572962.
JD331780 - Sequence 312804 from Patent EP1572962.
JD199007 - Sequence 180031 from Patent EP1572962.
JD083238 - Sequence 64262 from Patent EP1572962.
JD292921 - Sequence 273945 from Patent EP1572962.
JD565002 - Sequence 546026 from Patent EP1572962.
JD377216 - Sequence 358240 from Patent EP1572962.
JD507312 - Sequence 488336 from Patent EP1572962.
JD348910 - Sequence 329934 from Patent EP1572962.
JD320328 - Sequence 301352 from Patent EP1572962.
JD274017 - Sequence 255041 from Patent EP1572962.
JD141838 - Sequence 122862 from Patent EP1572962.
JD195991 - Sequence 177015 from Patent EP1572962.
JD047386 - Sequence 28410 from Patent EP1572962.
JD530971 - Sequence 511995 from Patent EP1572962.
JD102919 - Sequence 83943 from Patent EP1572962.
JD552666 - Sequence 533690 from Patent EP1572962.
JD498970 - Sequence 479994 from Patent EP1572962.
JD318321 - Sequence 299345 from Patent EP1572962.
JD438990 - Sequence 420014 from Patent EP1572962.
JD318320 - Sequence 299344 from Patent EP1572962.
JD425659 - Sequence 406683 from Patent EP1572962.
JD402064 - Sequence 383088 from Patent EP1572962.
JD255702 - Sequence 236726 from Patent EP1572962.
JD209816 - Sequence 190840 from Patent EP1572962.
X87949 - H.sapiens mRNA for BiP protein.
AK129617 - Homo sapiens cDNA FLJ26106 fis, clone SPL04458, highly similar to 78 kDa glucose-regulated protein precursor (GRP 78).
JD297307 - Sequence 278331 from Patent EP1572962.
JD316227 - Sequence 297251 from Patent EP1572962.
JD490801 - Sequence 471825 from Patent EP1572962.
AJ271729 - Homo sapiens mRNA for glucose-regulated protein (HSPA5 gene).
EU794617 - Homo sapiens epididymis secretory sperm binding protein Li 89n (HEL-S-89n) mRNA, complete cds.
JD102214 - Sequence 83238 from Patent EP1572962.
AF216292 - Homo sapiens endoplasmic reticulum lumenal Ca2+ binding protein grp78 mRNA, complete cds.
DQ892173 - Synthetic construct clone IMAGE:100004803; FLH183683.01X; RZPDo839F05142D heat shock 70kDa protein 5 (glucose-regulated protein, 78kDa) (HSPA5) gene, encodes complete protein.
DQ895368 - Synthetic construct Homo sapiens clone IMAGE:100009828; FLH183679.01L; RZPDo839F05141D heat shock 70kDa protein 5 (glucose-regulated protein, 78kDa) (HSPA5) gene, encodes complete protein.
AB527282 - Synthetic construct DNA, clone: pF1KB5550, Homo sapiens HSPA5 gene for heat shock 70kDa protein 5, without stop codon, in Flexi system.
AF188611 - Homo sapiens BiP protein (HSPA5) mRNA, partial cds.
AK293604 - Homo sapiens cDNA FLJ60062 complete cds, highly similar to 78 kDa glucose-regulated protein precursor.
DQ592419 - Homo sapiens piRNA piR-59531, complete sequence.
DQ588178 - Homo sapiens piRNA piR-55290, complete sequence.
JD057721 - Sequence 38745 from Patent EP1572962.
JD406542 - Sequence 387566 from Patent EP1572962.
JD181241 - Sequence 162265 from Patent EP1572962.
JD289175 - Sequence 270199 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa03060 - Protein export
hsa04612 - Antigen processing and presentation
hsa05020 - Prion diseases

Reactome (by CSHL, EBI, and GO)

Protein P11021 (Reactome details) participates in the following event(s):

R-HSA-351323 Release of 78 kDa glucose-regulated protein
R-HSA-381158 ATF6:HSPA5 (ATF6-alpha:BiP) dissociates and HSPA5 binds unfolded protein
R-HSA-381217 IRE1:BiP dissociates in response to unfolded protein
R-HSA-381086 Dissociation of PERK:BiP Heterodimer
R-HSA-983145 Binding of newly synthesized MHC class I heavy chain (HC) with calnexin
R-HSA-983146 Interaction of beta-2-microglobulin (B2M) chain with class I HC
R-HSA-983148 Interaction of Erp57 with MHC class I HC
R-HSA-5251955 HSP40s activate intrinsic ATPase activity of HSP70s in the nucleoplasm
R-HSA-5252079 HSP110s exchange ATP for ADP on HSP70s:ADP
R-HSA-5251959 HSP40s activate intrinsic ATPase activity of HSP70s in the cytosol
R-HSA-5251942 Hikeshi binds HSP70s:ATP
R-HSA-5252041 NPC transports Hikeshi:HSP70s:ATP from cytosol to nucleoplasm
R-HSA-114608 Platelet degranulation
R-HSA-381183 ATF6 (ATF6-alpha) activates chaperone genes
R-HSA-381033 ATF6 (ATF6-alpha) activates chaperones
R-HSA-381070 IRE1alpha activates chaperones
R-HSA-381042 PERK regulates gene expression
R-HSA-76005 Response to elevated platelet cytosolic Ca2+
R-HSA-983170 Antigen Presentation: Folding, assembly and peptide loading of class I MHC
R-HSA-381119 Unfolded Protein Response (UPR)
R-HSA-76002 Platelet activation, signaling and aggregation
R-HSA-983169 Class I MHC mediated antigen processing & presentation
R-HSA-3371453 Regulation of HSF1-mediated heat shock response
R-HSA-392499 Metabolism of proteins
R-HSA-109582 Hemostasis
R-HSA-1280218 Adaptive Immune System
R-HSA-3371556 Cellular response to heat stress
R-HSA-168256 Immune System
R-HSA-2262752 Cellular responses to stress
R-HSA-8953897 Cellular responses to external stimuli

-  Other Names for This Gene
  Alternate Gene Symbols: B0QZ61, GRP78, GRP78_HUMAN, NM_005347, NP_005338, P11021, Q2EF78, Q9NPF1, Q9UK02
UCSC ID: uc004bpn.3
RefSeq Accession: NM_005347
Protein: P11021 (aka GRP78_HUMAN)
CCDS: CCDS6863.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_005347.4
exon count: 8CDS single in 3' UTR: no RNA size: 3973
ORF size: 1965CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 4130.00frame shift in genome: no % Coverage: 99.92
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.