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
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/";
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.
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.
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
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