HSPA8 heat shock protein family A (Hsp70) member 8 [Homo sapiens (human)] - Gene

Summary

Official Symbol: HSPA8provided by HGNC
Official Full Name: heat shock protein family A (Hsp70) member 8provided by HGNC
Primary source: HGNC:HGNC:5241
See related: Ensembl:ENSG00000109971 MIM:600816; AllianceGenome:HGNC:5241
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: LAP1; HSC54; HSC70; HSC71; HSP71; HSP73; LAP-1; NIP71; HEL-33; HSPA10; HEL-S-72p
Summary: This gene encodes a member of the heat shock protein 70 family, which contains both heat-inducible and constitutively expressed members. This protein belongs to the latter group, which are also referred to as heat-shock cognate proteins. It functions as a chaperone, and binds to nascent polypeptides to facilitate correct folding. It also functions as an ATPase in the disassembly of clathrin-coated vesicles during transport of membrane components through the cell. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]
Expression: Ubiquitous expression in brain (RPKM 443.0), kidney (RPKM 352.5) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11q24.1

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (123057489..123062462, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (123086071..123093285, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (122928197..122932844, complement)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

HSPA8 Chaperone Complex Drives Chaperone-Mediated Autophagy Regulation in Acute Promyelocytic Leukemia Cell Differentiation.
Title: HSPA8 Chaperone Complex Drives Chaperone-Mediated Autophagy Regulation in Acute Promyelocytic Leukemia Cell Differentiation.
Experimental and computational investigation of the effect of Hsc70 structural variants on inhibiting amylin aggregation.
Title: Experimental and computational investigation of the effect of Hsc70 structural variants on inhibiting amylin aggregation.
Heat shock protein family A member 8 is a prognostic marker for bladder cancer: Evidences based on experiments and machine learning.
Title: Heat shock protein family A member 8 is a prognostic marker for bladder cancer: Evidences based on experiments and machine learning.
Plasmodium falciparum J-dot localized J domain protein A8iJp modulates the chaperone activity of human HSPA8.
Title: Plasmodium falciparum J-dot localized J domain protein A8iJp modulates the chaperone activity of human HSPA8.
HSPA8-mediated stability of the CLPP protein regulates mitochondrial autophagy in cisplatin-resistant ovarian cancer cells.
Title: HSPA8-mediated stability of the CLPP protein regulates mitochondrial autophagy in cisplatin-resistant ovarian cancer cells.
RPL35A promotes the progression of cholangiocarcinoma by mediating HSPA8 ubiquitination.
Title: RPL35A promotes the progression of cholangiocarcinoma by mediating HSPA8 ubiquitination.
Hemin competitively inhibits HSPA8 ATPase activity mitigating its foldase function.
Title: Hemin competitively inhibits HSPA8 ATPase activity mitigating its foldase function.
Arginine methylation of HSPA8 by PRMT9 inhibits ferroptosis to accelerate hepatitis B virus-associated hepatocellular carcinoma progression.
Title: Arginine methylation of HSPA8 by PRMT9 inhibits ferroptosis to accelerate hepatitis B virus-associated hepatocellular carcinoma progression.
The self-association equilibrium of DNAJA2 regulates its interaction with unfolded substrate proteins and with Hsc70.
Title: The self-association equilibrium of DNAJA2 regulates its interaction with unfolded substrate proteins and with Hsc70.
Association between HSPA8 Gene Variants and Ischemic Stroke: A Pilot Study Providing Additional Evidence for the Role of Heat Shock Proteins in Disease Pathogenesis.
Title: Association between HSPA8 Gene Variants and Ischemic Stroke: A Pilot Study Providing Additional Evidence for the Role of Heat Shock Proteins in Disease Pathogenesis.

Submit: New GeneRIF Correction See all GeneRIFs (179)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Tandem affinity purification and mass spectrometry analysis identify heat shock 70kDa protein 8 (HSPA8, HSC70), 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
Gag-Pol	gag-pol	Tandem affinity purification and mass spectrometry analysis identify heat shock 70kDa protein 8 (HSPA8, HSC70), 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 8 (HSPA8, HSC70), 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
	nef	HIV-1 Nef increases the production of exosomes and co-localizes with exosomal proteins CD63, AIP/Alix, AChE, Hsc70, LAMP2, and annexin A2 in HeLa cells	PubMed
Pr55(Gag)	gag	Tandem affinity purification and mass spectrometry analysis identify heat shock 70kDa protein 8 (HSPA8, HSC70), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
	gag	Hsc70 is specifically incorporated into HIV-1 virions, similar to Hsp70 which is incorporated into virions through an interaction with HIV-1 Gag	PubMed
Tat	tat	Heat shock 70kDa protein 8 (HSPA8) is identified to interact with HIV-1 Tat mutant Nullbasic in HeLa cells by LC MS/MS	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
Vif	vif	HIV-1 Vif interacts with HSPA8; predicted interaction to be relevant to gene regulation	PubMed
Vpr	vpr	HIV-1 Vpr is required for the inhibitory effect of Hsp70 on viral gene expression and replication	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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-8020 (e-PCR)
- UniSTS:90642

SHGC-8077 (e-PCR)
- UniSTS:90678

MARC_24282-24283:1030043504:1 (e-PCR)
- UniSTS:268871

HSPA8 (e-PCR)
- UniSTS:78683

WI-12733 (e-PCR)
- UniSTS:24923

RH104170 (e-PCR)
- UniSTS:98495

RH27394 (e-PCR)
- UniSTS:88818

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables A1 adenosine receptor binding	IEA Inferred from Electronic Annotation more info
enables ADP binding	IEA Inferred from Electronic Annotation more info
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	NAS Non-traceable Author Statement more info	PubMed
enables ATP hydrolysis activity	TAS Traceable Author Statement more info
enables ATP-dependent protein disaggregase activity	IDA Inferred from Direct Assay more info	PubMed
enables ATP-dependent protein folding chaperone	IEA Inferred from Electronic Annotation more info
enables C3HC4-type RING finger domain binding	IPI Inferred from Physical Interaction more info	PubMed
enables G protein-coupled receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables MHC class II protein complex binding	HDA more info	PubMed
enables RNA binding	HDA more info	PubMed
enables cadherin binding	HDA more info	PubMed
enables clathrin-uncoating ATPase activity	IEA Inferred from Electronic Annotation more info
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 heat shock protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables peptide binding	IEA Inferred from Electronic Annotation more info
enables phosphatidylserine binding	IEA Inferred from Electronic Annotation more info
enables prostaglandin binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein carrier chaperone	TAS Traceable Author Statement more info	PubMed
enables protein folding chaperone	IBA Inferred from Biological aspect of Ancestor more info
enables protein-folding chaperone binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-macromolecule adaptor activity	IDA Inferred from Direct Assay more info	PubMed
enables protein-macromolecule adaptor activity	IPI Inferred from Physical Interaction more info	PubMed
enables receptor ligand activity	IDA Inferred from Direct Assay more info	PubMed
enables ubiquitin protein ligase binding	IPI Inferred from Physical Interaction more info	PubMed
enables unfolded protein binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in ATP metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in G1/S transition of mitotic cell cycle	IEA Inferred from Electronic Annotation more info
involved_in cellular response to cadmium ion	IEA Inferred from Electronic Annotation more info
involved_in cellular response to heat	IEA Inferred from Electronic Annotation more info
involved_in cellular response to hydrogen peroxide	IEA Inferred from Electronic Annotation more info
involved_in cellular response to starvation	TAS Traceable Author Statement more info	PubMed
involved_in cellular response to steroid hormone stimulus	TAS Traceable Author Statement more info
involved_in cerebellum development	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 chaperone-mediated autophagy	ISS Inferred from Sequence or Structural Similarity more info
involved_in chaperone-mediated autophagy	TAS Traceable Author Statement more info	PubMed
involved_in chaperone-mediated autophagy translocation complex disassembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in clathrin coat disassembly	IBA Inferred from Biological aspect of Ancestor more info
involved_in clathrin coat disassembly	IDA Inferred from Direct Assay more info	PubMed
involved_in estrous cycle	IEA Inferred from Electronic Annotation more info
involved_in forebrain development	IEA Inferred from Electronic Annotation more info
involved_in kidney development	IEA Inferred from Electronic Annotation more info
involved_in late endosomal microautophagy	IEA Inferred from Electronic Annotation more info
involved_in mRNA splicing, via spliceosome	NAS Non-traceable Author Statement more info	PubMed
involved_in maintenance of postsynaptic specialization structure	IEA Inferred from Electronic Annotation more info
involved_in membrane organization	TAS Traceable Author Statement more info
involved_in negative regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of NLRP3 inflammasome complex assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cardiac muscle cell apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of supramolecular fiber organization	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation by host of viral genome replication	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of T cell mediated cytotoxicity	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cell migration	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of lysosomal membrane permeability	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of mRNA splicing, via spliceosome	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of phagocytosis	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of protein refolding	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of proteolysis	IEA Inferred from Electronic Annotation more info
involved_in protein folding	NAS Non-traceable Author Statement more info	PubMed
involved_in protein import into nucleus	IEA Inferred from Electronic Annotation more info
involved_in protein refolding	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein refolding	IDA Inferred from Direct Assay more info	PubMed
involved_in protein targeting to lysosome involved in chaperone-mediated autophagy	IDA Inferred from Direct Assay more info	PubMed
involved_in protein targeting to lysosome involved in chaperone-mediated autophagy	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein targeting to lysosome involved in chaperone-mediated autophagy	TAS Traceable Author Statement more info	PubMed
involved_in protein transmembrane import into intracellular organelle	IEA Inferred from Electronic Annotation more info
involved_in regulation of cell cycle	IEA Inferred from Electronic Annotation more info
involved_in regulation of postsynapse organization	IEA Inferred from Electronic Annotation more info
involved_in regulation of protein complex stability	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of protein import	TAS Traceable Author Statement more info	PubMed
involved_in regulation of protein stability	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of protein-containing complex assembly	TAS Traceable Author Statement more info	PubMed
involved_in response to activity	IEA Inferred from Electronic Annotation more info
involved_in response to estradiol	IEA Inferred from Electronic Annotation more info
involved_in response to ethanol	IEA Inferred from Electronic Annotation more info
involved_in response to nickel cation	IEA Inferred from Electronic Annotation more info
involved_in response to odorant	IEA Inferred from Electronic Annotation more info
involved_in response to progesterone	IEA Inferred from Electronic Annotation more info
involved_in response to unfolded protein	NAS Non-traceable Author Statement more info	PubMed
involved_in response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	IEA Inferred from Electronic Annotation more info
involved_in skeletal muscle tissue development	IEA Inferred from Electronic Annotation more info
involved_in slow axonal transport	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of Prp19 complex	IDA Inferred from Direct Assay more info	PubMed
part_of Prp19 complex	IPI Inferred from Physical Interaction more info	PubMed
located_in autophagosome	IEA Inferred from Electronic Annotation more info
located_in blood microparticle	HDA more info	PubMed
located_in cell surface	IEA Inferred from Electronic Annotation more info
located_in clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane	TAS Traceable Author Statement more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in dendritic shaft	IEA Inferred from Electronic Annotation more info
located_in dendritic spine	IEA Inferred from Electronic Annotation more info
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular exosome	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in extracellular space	HDA more info	PubMed
is_active_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in ficolin-1-rich granule lumen	TAS Traceable Author Statement more info
located_in focal adhesion	HDA more info	PubMed
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
located_in glycinergic synapse	IEA Inferred from Electronic Annotation more info
located_in intermediate filament	IEA Inferred from Electronic Annotation more info
located_in late endosome	IEA Inferred from Electronic Annotation more info
located_in lumenal side of lysosomal membrane	TAS Traceable Author Statement more info	PubMed
located_in lysosomal lumen	TAS Traceable Author Statement more info	PubMed
located_in lysosomal matrix	IEA Inferred from Electronic Annotation more info
is_active_in lysosomal membrane	IDA Inferred from Direct Assay more info	PubMed
located_in lysosomal membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in melanosome	IEA Inferred from Electronic Annotation more info
located_in membrane	HDA more info	PubMed
located_in microtubule	IEA Inferred from Electronic Annotation more info
located_in nucleolus	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in perikaryon	IEA Inferred from Electronic Annotation more info
located_in perinuclear region of cytoplasm	IEA Inferred from Electronic Annotation more info
located_in photoreceptor inner segment	IEA Inferred from Electronic Annotation more info
located_in photoreceptor ribbon synapse	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	TAS Traceable Author Statement more info
located_in postsynaptic density	IEA Inferred from Electronic Annotation more info
located_in postsynaptic specialization membrane	IEA Inferred from Electronic Annotation more info
part_of protein folding chaperone complex	IPI Inferred from Physical Interaction more info	PubMed
part_of ribonucleoprotein complex	IDA Inferred from Direct Assay more info	PubMed
located_in secretory granule lumen	TAS Traceable Author Statement more info
part_of spliceosomal complex	IPI Inferred from Physical Interaction more info	PubMed
located_in synaptic vesicle	IEA Inferred from Electronic Annotation more info
located_in terminal bouton	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: heat shock cognate 71 kDa protein

Names: LPS-associated protein 1; N-myristoyltransferase inhibitor protein 71; constitutive heat shock protein 70; epididymis luminal protein 33; epididymis secretory sperm binding protein Li 72p; heat shock 70kDa protein 8; heat shock 70kd protein 10; heat shock cognate protein 54; heat shock protein family A member 8; lipopolysaccharide-associated protein 1

NP_006588.1

EC 3.6.4.10

NP_694881.1

EC 3.6.4.10

XP_011541100.1

EC 3.6.4.10

XP_054224589.1

EC 3.6.4.10

NCBI Reference Sequences (RefSeq)

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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

NG_029473.1 RefSeqGene

Range

5001..9648

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_006597.6 → NP_006588.1 heat shock cognate 71 kDa protein isoform 1

See identical proteins and their annotated locations for NP_006588.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the predominant transcript, and encodes the longer isoform (1).

Source sequence(s)

AK222628, AP000926, BC019816, DC395565

Consensus CDS

CCDS8440.1

UniProtKB/Swiss-Prot

P11142, Q9H3R6

UniProtKB/TrEMBL

Q53GZ6, V9HW22

Related

ENSP00000432083.1, ENST00000534624.6

Conserved Domains (1) summary

PTZ00009
Location:1 → 613

PTZ00009; heat shock 70 kDa protein; Provisional
NM_153201.4 → NP_694881.1 heat shock cognate 71 kDa protein isoform 2

See identical proteins and their annotated locations for NP_694881.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses alternate splice sites, and is missing an exon in the 3' coding region compared to variant 1. However, it maintains the reading frame, and encodes a shorter isoform (2) missing an internal protein segment compared to isoform 1.

Source sequence(s)

AB034951, AK222628, AP000926, DC395565

Consensus CDS

CCDS44754.1

UniProtKB/TrEMBL

Q53HF2

Related

ENSP00000404372.2, ENST00000453788.6

Conserved Domains (1) summary

PTZ00009
Location:1 → 462

PTZ00009; heat shock 70 kDa protein; Provisional