• Gene id: 3309

Gene Summary

• Gene Symbol: HSPA5   Gene   UCSC   Ensembl
• Aliases: BIP, GRP78, HEL-S-89n, MIF2
• Gene name: heat shock protein family A (Hsp70) member 5
• Alternate names: endoplasmic reticulum chaperone BiP, 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,
• Gene location: 9q33.3 (125241386: 125234847)     Exons: 8     NC_000009.12
• Gene summary(Entrez): 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 man
• OMIM: 138120

SNPs

rs17840762

Strand:    Allele origin:   Allele change:   Mutation type: snv

NC_000009.12   g.125241708G>A
NC_000009.11   g.128003987G>A
NG_027761.1   g.4680C>T
NG_063123.1   g.439G>A
XR_001746927.1   n.46G>A|SEQ=[G/A]|GENE=HSPA5
LOC107987127   107987127

rs17840761

Strand:    Allele origin:   Allele change:   Mutation type: snv

NC_000009.12   g.125241700G>A
NC_000009.11   g.128003979G>A
NG_027761.1   g.4688C>T
NG_063123.1   g.431G>A
XR_001746927.1   n.38G>A|SEQ=[G/A]|GENE=HSPA5
LOC107987127   107987127

rs16927997

Strand:    Allele origin:   Allele change:   Mutation type: snv

NC_000009.12   g.125236118A>G
NC_000009.11   g.127998397A>G
NG_027761.1   g.10270T>C
NM_005347.5   c.*474T>C
NM_005347.4   c.*474T>C|SEQ=[A/G]|GENE=HSPA5

rs3216733

Strand:    Allele origin:   Allele change:   Mutation type: delins

NC_000009.12   g.125241516_125241517del
NC_000009.12   g.125241517del
NC_000009.12   g.125241517dup
NC_000009.12   g.125241516_125241517dup
NC_000009.11   g.128003795_128003796del
NC_000009.11   g.128003796del
NC_000009.11   g.128003796dup
NC_000009.11   g.128003795

Protein Summary

• Protein general information: P11021  
  • Name: Endoplasmic reticulum chaperone BiP (EC 3.6.4.10) (78 kDa glucose regulated protein) (GRP 78) (Binding immunoglobulin protein) (BiP) (Heat shock protein 70 family protein 5) (HSP70 family protein 5) (Heat shock protein family A member 5) (Immunoglobulin h
  • Length: 654  
  • Mass: 72,333
• Sequence:

  MKLSLVAAMLLLLSAARAEEEDKKEDVGTVVGIDLGTTYSCVGVFKNGRVEIIANDQGNRITPSYVAFTPEGERL
  IGDAAKNQLTSNPENTVFDAKRLIGRTWNDPSVQQDIKFLPFKVVEKKTKPYIQVDIGGGQTKTFAPEEISAMVL
  TKMKETAEAYLGKKVTHAVVTVPAYFNDAQRQATKDAGTIAGLNVMRIINEPTAAAIAYGLDKREGEKNILVFDL
  GGGTFDVSLLTIDNGVFEVVATNGDTHLGGEDFDQRVMEHFIKLYKKKTGKDVRKDNRAVQKLRREVEKAKRALS
  SQHQARIEIESFYEGEDFSETLTRAKFEELNMDLFRSTMKPVQKVLEDSDLKKSDIDEIVLVGGSTRIPKIQQLV
  KEFFNGKEPSRGINPDEAVAYGAAVQAGVLSGDQDTGDLVLLDVCPLTLGIETVGGVMTKLIPRNTVVPTKKSQI
  FSTASDNQPTVTIKVYEGERPLTKDNHLLGTFDLTGIPPAPRGVPQIEVTFEIDVNGILRVTAEDKGTGNKNKIT
  ITNDQNRLTPEEIERMVNDAEKFAEEDKKLKERIDTRNELESYAYSLKNQIGDKEKLGGKLSSEDKETMEKAVEE
  KIEWLESHQDADIEDFKAKKKELEEIVQPIISKLYGSAGPPPTGEEDTAEKDEL

• Structural information:
  • Interpro: IPR018181  IPR029048  IPR029047  IPR013126  
  • Prosite: PS00014 PS00297 PS00329 PS01036
  • PDB: 3IUC 3LDL 3LDN 3LDO 3LDP 5E84 5E85 5E86 5EVZ 5EX5 5EXW 5EY4 5F0X 5F1X 5F2R 6ASY
  • PDBsum: 3IUC 3LDL 3LDN 3LDO 3LDP 5E84 5E85 5E86 5EVZ 5EX5 5EXW 5EY4 5F0X 5F1X 5F2R 6ASY
  • DIP: 33189
  • STRING: ENSP00000324173
• Other Databases: GeneCards:  HSPA5  Malacards:  HSPA5

Gene ontology

GO accession	Term name	Evidence code	Go category
GO:0001948	glycoprotein binding	IPI	molecular function
GO:0005509	calcium ion binding	TAS	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005524	ATP binding	IEA	molecular function
GO:0005634	nucleus	IMP	cellular component
GO:0005634	nucleus	IDA	cellular component
GO:0005739	mitochondrion	IEA	cellular component
GO:0005783	endoplasmic reticulum	IMP	cellular component
GO:0005783	endoplasmic reticulum	TAS	cellular component
GO:0005783	endoplasmic reticulum	IDA	cellular component
GO:0005788	endoplasmic reticulum lumen	TAS	cellular component
GO:0005788	endoplasmic reticulum lumen	TAS	cellular component
GO:0005788	endoplasmic reticulum lumen	TAS	cellular component
GO:0005789	endoplasmic reticulum membrane	TAS	cellular component
GO:0005789	endoplasmic reticulum membrane	TAS	cellular component
GO:0005789	endoplasmic reticulum membrane	TAS	cellular component
GO:0005789	endoplasmic reticulum membrane	TAS	cellular component
GO:0005790	smooth endoplasmic reticulum	IEA	cellular component
GO:0005793	endoplasmic reticulum-Golgi intermediate compartment	IDA	cellular component
GO:0005886	plasma membrane	IEA	cellular component
GO:0005925	focal adhesion	IDA	cellular component
GO:0006983	ER overload response	IEA	biological process
GO:0006987	activation of signaling protein activity involved in unfolded protein response	IEA	biological process
GO:0009986	cell surface	IEA	cellular component
GO:0016020	membrane	IDA	cellular component
GO:0016887	ATPase activity	ISS	molecular function
GO:0016887	ATPase activity	IDA	molecular function
GO:0016887	ATPase activity	IDA	molecular function
GO:0019899	enzyme binding	IPI	molecular function
GO:0019904	protein domain specific binding	IPI	molecular function
GO:0021589	cerebellum structural organization	IEA	biological process
GO:0021680	cerebellar Purkinje cell layer development	IEA	biological process
GO:0021762	substantia nigra development	IEP	biological process
GO:0030176	integral component of endoplasmic reticulum membrane	IDA	cellular component
GO:0030335	positive regulation of cell migration	IMP	biological process
GO:0030433	ER-associated ubiquitin-dependent protein catabolic process	TAS	biological process
GO:0030496	midbody	IDA	cellular component
GO:0030512	negative regulation of transforming growth factor beta receptor signaling pathway	IEA	biological process
GO:0030968	endoplasmic reticulum unfolded protein response	TAS	biological process
GO:0031398	positive regulation of protein ubiquitination	IEA	biological process
GO:0031625	ubiquitin protein ligase binding	IPI	molecular function
GO:0034663	endoplasmic reticulum chaperone complex	IDA	cellular component
GO:0034975	protein folding in endoplasmic reticulum	TAS	biological process
GO:0035437	maintenance of protein localization in endoplasmic reticulum	IMP	biological process
GO:0036498	IRE1-mediated unfolded protein response	TAS	biological process
GO:0036499	PERK-mediated unfolded protein response	TAS	biological process
GO:0036500	ATF6-mediated unfolded protein response	TAS	biological process
GO:0042149	cellular response to glucose starvation	IDA	biological process
GO:0042470	melanosome	IEA	cellular component
GO:0043022	ribosome binding	IEA	molecular function
GO:0043066	negative regulation of apoptotic process	IMP	biological process
GO:0043066	negative regulation of apoptotic process	IMP	biological process
GO:0043066	negative regulation of apoptotic process	TAS	biological process
GO:0043209	myelin sheath	IEA	cellular component
GO:0051082	unfolded protein binding	TAS	molecular function
GO:0051082	unfolded protein binding	TAS	molecular function
GO:0051082	unfolded protein binding	TAS	molecular function
GO:0051087	chaperone binding	TAS	molecular function
GO:0051787	misfolded protein binding	IDA	molecular function
GO:0060904	regulation of protein folding in endoplasmic reticulum	TAS	biological process
GO:0070062	extracellular exosome	IDA	cellular component
GO:0070062	extracellular exosome	IDA	cellular component
GO:0070062	extracellular exosome	IDA	cellular component
GO:0070062	extracellular exosome	IDA	cellular component
GO:0071236	cellular response to antibiotic	IEA	biological process
GO:0071287	cellular response to manganese ion	IEA	biological process
GO:0071353	cellular response to interleukin-4	IEA	biological process
GO:0090074	negative regulation of protein homodimerization activity	TAS	biological process
GO:1901998	toxin transport	IEA	biological process
GO:1903891	regulation of ATF6-mediated unfolded protein response	TAS	biological process
GO:1903894	regulation of IRE1-mediated unfolded protein response	TAS	biological process
GO:1903897	regulation of PERK-mediated unfolded protein response	TAS	biological process
GO:1990440	positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress	TAS	biological process
GO:0008180	COP9 signalosome	IDA	cellular component
GO:0000166	nucleotide binding	IEA	molecular function
GO:0001948	glycoprotein binding	IPI	molecular function
GO:0005509	calcium ion binding	TAS	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005524	ATP binding	IEA	molecular function
GO:0005634	nucleus	IMP	cellular component
GO:0005634	nucleus	IDA	cellular component
GO:0005737	cytoplasm	IEA	cellular component
GO:0005737	cytoplasm	IEA	cellular component
GO:0005739	mitochondrion	IEA	cellular component
GO:0005783	endoplasmic reticulum	IEA	cellular component
GO:0005783	endoplasmic reticulum	IEA	cellular component
GO:0005783	endoplasmic reticulum	IMP	cellular component
GO:0005783	endoplasmic reticulum	TAS	cellular component
GO:0005783	endoplasmic reticulum	IDA	cellular component
GO:0005788	endoplasmic reticulum lumen	IEA	cellular component
GO:0005788	endoplasmic reticulum lumen	IEA	cellular component
GO:0005788	endoplasmic reticulum lumen	TAS	cellular component
GO:0005788	endoplasmic reticulum lumen	TAS	cellular component
GO:0005788	endoplasmic reticulum lumen	TAS	cellular component
GO:0005789	endoplasmic reticulum membrane	IEA	cellular component
GO:0005789	endoplasmic reticulum membrane	TAS	cellular component
GO:0005789	endoplasmic reticulum membrane	TAS	cellular component
GO:0005789	endoplasmic reticulum membrane	TAS	cellular component
GO:0005789	endoplasmic reticulum membrane	TAS	cellular component
GO:0005790	smooth endoplasmic reticulum	IEA	cellular component
GO:0005793	endoplasmic reticulum-Golgi intermediate compartment	IEA	cellular component
GO:0005793	endoplasmic reticulum-Golgi intermediate compartment	IDA	cellular component
GO:0005886	plasma membrane	IEA	cellular component
GO:0005925	focal adhesion	IDA	cellular component
GO:0006983	ER overload response	IEA	biological process
GO:0006987	activation of signaling protein activity involved in unfolded protein response	IEA	biological process
GO:0009986	cell surface	IEA	cellular component
GO:0016020	membrane	IEA	cellular component
GO:0016020	membrane	IDA	cellular component
GO:0016887	ATPase activity	ISS	molecular function
GO:0016887	ATPase activity	IDA	molecular function
GO:0016887	ATPase activity	IDA	molecular function
GO:0019899	enzyme binding	IPI	molecular function
GO:0019904	protein domain specific binding	IPI	molecular function
GO:0021589	cerebellum structural organization	IEA	biological process
GO:0021680	cerebellar Purkinje cell layer development	IEA	biological process
GO:0021762	substantia nigra development	IEP	biological process
GO:0030176	integral component of endoplasmic reticulum membrane	IDA	cellular component
GO:0030335	positive regulation of cell migration	IMP	biological process
GO:0030433	ER-associated ubiquitin-dependent protein catabolic process	TAS	biological process
GO:0030496	midbody	IDA	cellular component
GO:0030512	negative regulation of transforming growth factor beta receptor signaling pathway	IEA	biological process
GO:0030968	endoplasmic reticulum unfolded protein response	TAS	biological process
GO:0031398	positive regulation of protein ubiquitination	IEA	biological process
GO:0031625	ubiquitin protein ligase binding	IPI	molecular function
GO:0034663	endoplasmic reticulum chaperone complex	IEA	cellular component
GO:0034663	endoplasmic reticulum chaperone complex	IDA	cellular component
GO:0034975	protein folding in endoplasmic reticulum	TAS	biological process
GO:0034976	response to endoplasmic reticulum stress	IEA	biological process
GO:0035437	maintenance of protein localization in endoplasmic reticulum	IMP	biological process
GO:0036498	IRE1-mediated unfolded protein response	TAS	biological process
GO:0036499	PERK-mediated unfolded protein response	TAS	biological process
GO:0036500	ATF6-mediated unfolded protein response	TAS	biological process
GO:0042149	cellular response to glucose starvation	IDA	biological process
GO:0042470	melanosome	IEA	cellular component
GO:0043022	ribosome binding	IEA	molecular function
GO:0043066	negative regulation of apoptotic process	IMP	biological process
GO:0043066	negative regulation of apoptotic process	IMP	biological process
GO:0043066	negative regulation of apoptotic process	TAS	biological process
GO:0043209	myelin sheath	IEA	cellular component
GO:0051082	unfolded protein binding	IEA	molecular function
GO:0051082	unfolded protein binding	TAS	molecular function
GO:0051082	unfolded protein binding	TAS	molecular function
GO:0051082	unfolded protein binding	TAS	molecular function
GO:0051087	chaperone binding	TAS	molecular function
GO:0051603	proteolysis involved in cellular protein catabolic process	IEA	biological process
GO:0051787	misfolded protein binding	IEA	molecular function
GO:0051787	misfolded protein binding	IDA	molecular function
GO:0060904	regulation of protein folding in endoplasmic reticulum	TAS	biological process
GO:0070062	extracellular exosome	IDA	cellular component
GO:0070062	extracellular exosome	IDA	cellular component
GO:0070062	extracellular exosome	IDA	cellular component
GO:0070062	extracellular exosome	IDA	cellular component
GO:0071236	cellular response to antibiotic	IEA	biological process
GO:0071287	cellular response to manganese ion	IEA	biological process
GO:0071353	cellular response to interleukin-4	IEA	biological process
GO:0090074	negative regulation of protein homodimerization activity	TAS	biological process
GO:1901998	toxin transport	IEA	biological process
GO:1903891	regulation of ATF6-mediated unfolded protein response	TAS	biological process
GO:1903894	regulation of IRE1-mediated unfolded protein response	TAS	biological process
GO:1903897	regulation of PERK-mediated unfolded protein response	TAS	biological process
GO:1990440	positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress	TAS	biological process
GO:0008180	COP9 signalosome	IDA	cellular component
GO:0001948	glycoprotein binding	IPI	molecular function
GO:0005509	calcium ion binding	TAS	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005634	nucleus	IMP	cellular component
GO:0005634	nucleus	IDA	cellular component
GO:0005783	endoplasmic reticulum	IMP	cellular component
GO:0005783	endoplasmic reticulum	TAS	cellular component
GO:0005783	endoplasmic reticulum	IDA	cellular component
GO:0005788	endoplasmic reticulum lumen	TAS	cellular component
GO:0005788	endoplasmic reticulum lumen	TAS	cellular component
GO:0005788	endoplasmic reticulum lumen	TAS	cellular component
GO:0005789	endoplasmic reticulum membrane	TAS	cellular component
GO:0005789	endoplasmic reticulum membrane	TAS	cellular component
GO:0005789	endoplasmic reticulum membrane	TAS	cellular component
GO:0005789	endoplasmic reticulum membrane	TAS	cellular component
GO:0005793	endoplasmic reticulum-Golgi intermediate compartment	IDA	cellular component
GO:0005925	focal adhesion	IDA	cellular component
GO:0016020	membrane	IDA	cellular component
GO:0016887	ATPase activity	ISS	molecular function
GO:0016887	ATPase activity	IDA	molecular function
GO:0016887	ATPase activity	IDA	molecular function
GO:0019899	enzyme binding	IPI	molecular function
GO:0019904	protein domain specific binding	IPI	molecular function
GO:0021762	substantia nigra development	IEP	biological process
GO:0030176	integral component of endoplasmic reticulum membrane	IDA	cellular component
GO:0030335	positive regulation of cell migration	IMP	biological process
GO:0030433	ER-associated ubiquitin-dependent protein catabolic process	TAS	biological process
GO:0030496	midbody	IDA	cellular component
GO:0030968	endoplasmic reticulum unfolded protein response	TAS	biological process
GO:0031625	ubiquitin protein ligase binding	IPI	molecular function
GO:0034663	endoplasmic reticulum chaperone complex	IDA	cellular component
GO:0034975	protein folding in endoplasmic reticulum	TAS	biological process
GO:0035437	maintenance of protein localization in endoplasmic reticulum	IMP	biological process
GO:0036498	IRE1-mediated unfolded protein response	TAS	biological process
GO:0036499	PERK-mediated unfolded protein response	TAS	biological process
GO:0036500	ATF6-mediated unfolded protein response	TAS	biological process
GO:0042149	cellular response to glucose starvation	IDA	biological process
GO:0043066	negative regulation of apoptotic process	IMP	biological process
GO:0043066	negative regulation of apoptotic process	IMP	biological process
GO:0043066	negative regulation of apoptotic process	TAS	biological process
GO:0051082	unfolded protein binding	TAS	molecular function
GO:0051082	unfolded protein binding	TAS	molecular function
GO:0051082	unfolded protein binding	TAS	molecular function
GO:0051087	chaperone binding	TAS	molecular function
GO:0051787	misfolded protein binding	IDA	molecular function
GO:0060904	regulation of protein folding in endoplasmic reticulum	TAS	biological process
GO:0070062	extracellular exosome	IDA	cellular component
GO:0070062	extracellular exosome	IDA	cellular component
GO:0070062	extracellular exosome	IDA	cellular component
GO:0070062	extracellular exosome	IDA	cellular component
GO:0090074	negative regulation of protein homodimerization activity	TAS	biological process
GO:1903891	regulation of ATF6-mediated unfolded protein response	TAS	biological process
GO:1903894	regulation of IRE1-mediated unfolded protein response	TAS	biological process
GO:1903897	regulation of PERK-mediated unfolded protein response	TAS	biological process
GO:1990440	positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress	TAS	biological process
GO:0008180	COP9 signalosome	IDA	cellular component

KEGG pathways

Pathway id	Pathway name
hsa04612	Antigen processing and presentation
hsa04918	Thyroid hormone synthesis
hsa05020	Prion diseases

Diseases

Associated diseases	References
Cancer	GAD: 19533686
Cancer (Hepatocellular)	GAD: 19533686
Parkinson disease	GAD: 18343577
Schizophrenia	GAD: 16168956
Chronic renal failure	GAD: 21085059
Premature ovarian failure (POF)	INFBASE: 21890413
Male factor infertility	MIK: 23455884
Defective endometrial receptivity	INFBASE: 25935494
Asthenozoospermia	MIK: 23455884
Asthenozoospermia	MIK: 26618558
Spermatogenic defects	MIK: 19207617
May affect human sperm intracellular signalling pathways and capacitation	MIK: 17670764
Teratozoospermia	MIK: 17327269

PubMed references

PMID	Condition	Mutation	Ethnicity	Population details	Infertility_type	Associated_genes
23455884	Idiopathic asthenozoospermia				Male infertility	GRP78 lactoferrin SPANXB PGK2 flagellin DJ-1 XPA binding protein 2 CAB2 GPX4 and GAPDH
19207617	Involved in spermatogenesis				Male infertility
17670764	May affect human sperm intracellular signalling pathways and capacitation				Male infertility
15064947	May be important for spermatogenesis				Male infertility
30229503	Asthenozoospermia	rs3216733, rs17840761, and rs17840762		800 (400 subjects with AZS patients, 400 healthy controls)	Male infertility
26618558	Asthenozoospermia				Male infertility
17327269	Teratozoospermia			19 (6 controls, 13 cases)	Male infertility	GSE6872 analyzed by GEO2R (cutoff 1.5 fold)
31037746	Spermatogenic defects			16 (1 control, 15 cases)	Male infertility	GSE6023 analyzed using GEO2R