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    HSPA4 heat shock protein family A (Hsp70) member 4 [ Homo sapiens (human) ]

    Gene ID: 3308, updated on 27-Nov-2024

    Summary

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    Official Symbol
    HSPA4provided by HGNC
    Official Full Name
    heat shock protein family A (Hsp70) member 4provided by HGNC
    Primary source
    HGNC:HGNC:5237
    See related
    Ensembl:ENSG00000170606 MIM:601113; AllianceGenome:HGNC:5237
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    RY; APG-2; HSPH2; hsp70; hsp70RY; HEL-S-5a; HS24/P52
    Summary
    Predicted to enable adenyl-nucleotide exchange factor activity. Involved in chaperone-mediated protein complex assembly and protein insertion into mitochondrial outer membrane. Located in cytosol and extracellular exosome. Implicated in Chagas disease. Biomarker of chronic obstructive pulmonary disease; rheumatoid arthritis; type 2 diabetes mellitus; and ulcerative colitis. [provided by Alliance of Genome Resources, Nov 2024]
    Expression
    Ubiquitous expression in testis (RPKM 45.7), esophagus (RPKM 33.4) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See HSPA4 in Genome Data Viewer
    Location:
    5q31.1
    Exon count:
    19
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (133052013..133106449)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (133562175..133626191)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (132387705..132442141)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene small nuclear ribonucleoprotein U4/U6.U5 subunit 27 pseudogene Neighboring gene cytochrome c oxidase subunit NDUFA4-like Neighboring gene zinc finger CCHC-type containing 10 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23097 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16345 Neighboring gene Sharpr-MPRA regulatory region 5371 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:132386992-132387954 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:132388919-132389881 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:132393803-132394303 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23101 Neighboring gene uncharacterized LOC105379178 Neighboring gene ribosomal protein L6 pseudogene 15

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: 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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    Related articles in PubMed

    1. Unique peptide substrate binding properties of 110-kDa heat-shock protein (Hsp110) determine its distinct chaperone activity. Xu X, et al. J Biol Chem, 2012 Feb 17. PMID 22157767, Free PMC Article
    2. ERK-dependent phosphorylation of the linker and substrate-binding domain of HSP70 increases folding activity and cell proliferation. Lim S, et al. Exp Mol Med, 2019 Sep 26. PMID 31558706, Free PMC Article
    3. Human keratinocytes release high levels of inducible heat shock protein 70 that enhances peptide uptake. Wang D, et al. Exp Dermatol, 2011 Aug. PMID 21539621
    4. Heat shock proteins and myocardial protection during cardiopulmonary bypass. Yavuz S, et al. J Int Med Res, 2011. PMID 21672353
    5. Cytosolic Hsp70 as a biomarker to predict clinical outcome in patients with glioblastoma. Lämmer F, et al. PLoS One, 2019. PMID 31430337, Free PMC Article

    See all (918) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Dynamically changed HSP70 after reperfusion following cerebral infarction in human and rats: correlation with p38 MAPK.
      Title: Dynamically changed HSP70 after reperfusion following cerebral infarction in human and rats: correlation with p38 MAPK.
    2. HSPA4 regulated glioma progression via activation of AKT signaling pathway.
      Title: HSPA4 regulated glioma progression via activation of AKT signaling pathway.
    3. HSP70 binds to specific non-coding RNA and regulates human RNA polymerase III.
      Title: HSP70 binds to specific non-coding RNA and regulates human RNA polymerase III.
    4. Effects of resistance training on heat shock response (HSR), HSP70 expression, oxidative stress, inflammation, and metabolism in middle-aged people.
      Title: Effects of resistance training on heat shock response (HSR), HSP70 expression, oxidative stress, inflammation, and metabolism in middle-aged people.
    5. [The Protective Action of Hsp70 and Hydrogen Sulfide Donors in THP-1 Macrophages in the Lipopolysaccharide-Induced Inflammatory Response by Modulating Endocytosis].
      Title: [The Protective Action of Hsp70 and Hydrogen Sulfide Donors in THP-1 Macrophages in the Lipopolysaccharide-Induced Inflammatory Response by Modulating Endocytosis].
    6. HSP-27 and HSP-70 negatively regulate protective defence responses from macrophages during mycobacterial infection.
      Title: HSP-27 and HSP-70 negatively regulate protective defence responses from macrophages during mycobacterial infection.
    7. A new look at Hsp70 activity in phosphatidylserine-enriched membranes: chaperone-induced quasi-interdigitated lipid phase.
      Title: A new look at Hsp70 activity in phosphatidylserine-enriched membranes: chaperone-induced quasi-interdigitated lipid phase.
    8. HSP70 attenuates neuronal necroptosis through the HSP90alpha-RIPK3 pathway following neuronal trauma.
      Title: HSP70 attenuates neuronal necroptosis through the HSP90α-RIPK3 pathway following neuronal trauma.
    9. The multifunction of HSP70 in cancer: Guardian or traitor to the survival of tumor cells and the next potential therapeutic target.
      Title: The multifunction of HSP70 in cancer: Guardian or traitor to the survival of tumor cells and the next potential therapeutic target.
    10. SATB1 Chromatin Loops Regulate Megakaryocyte/Erythroid Progenitor Expansion by Facilitating HSP70 and GATA1 Induction.
      Title: SATB1 Chromatin Loops Regulate Megakaryocyte/Erythroid Progenitor Expansion by Facilitating HSP70 and GATA1 Induction.
    Submit: New GeneRIF Correction See all GeneRIFs (337)

    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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    Replication interactions

    Interaction Pubs
    HIV-1 infection (VSV-G pseudotyped) of CEMT4 T cells downregulates plasma membrane expression of HSPA4 PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env The exposure of permissive CD4+ cells to HIV-1 gp120 increases the synthesis and nuclear translocation of 70kDa heat shock protein PubMed
    env Over expression of hsp70 with a herpes viral amplicon vector protects cultured hippocampal rat neurons from gp120 neurotoxicity PubMed
    Nef nef Heat shock proteins Hsp40 and Hsp70 interact with HIV-1 Nef and form a complex in cells PubMed
    Pr55(Gag) 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
    gag Hsp70 is incorporated into HIV-1 virions through an interaction with HIV-1 Gag PubMed
    Tat 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 HSP70 interacts with both APOBEC3G and HIV-1 Vif, which stabilizes APOBEC3G and blocks Vif-mediated degradation of APOBEC3G. The N-terminal region of Vif involves the interaction with HSP70 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

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC131852

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables ATP-dependent protein folding chaperone IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables adenyl-nucleotide exchange factor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in chaperone-mediated protein complex assembly IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein folding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein insertion into mitochondrial outer membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in response to unfolded protein NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    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 extracellular exosome HDA PubMed 
    located_in extracellular exosome IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrion IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    heat shock 70 kDa protein 4
    Names
    epididymis secretory sperm binding protein Li 5a
    heat shock 70-related protein APG-2
    heat shock 70kD protein 4
    heat shock protein family H member 2
    heat shock protein, 110 kDa
    hsp70 RY

    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.

    mRNA and Protein(s)

    1. NM_002154.4 → NP_002145.3  heat shock 70 kDa protein 4

      See identical proteins and their annotated locations for NP_002145.3

      Status: VALIDATED

      Source sequence(s)
      AB023420, AC113410, BG723797, BQ431980, BU171424, BU686725, CF145856
      Consensus CDS
      CCDS4166.1
      UniProtKB/Swiss-Prot
      O95756, P34932, Q2TAL4, Q9BUK9
      UniProtKB/TrEMBL
      B4DH02
      Related
      ENSP00000302961.2, ENST00000304858.7
      Conserved Domains (2) summary
      cd11737
      Location:2 → 384
      HSPA4_NBD; Nucleotide-binding domain of HSPA4
      pfam00012
      Location:3 → 607
      HSP70; Hsp70 protein

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

      Range
      133052013..133106449
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060929.1 Alternate T2T-CHM13v2.0

      Range
      133562175..133626191
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054352493.1 → XP_054208468.1  heat shock 70 kDa protein 4 isoform X1

      UniProtKB/Swiss-Prot
      O95756, P34932, Q2TAL4, Q9BUK9

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_198431.1: Suppressed sequence

      Description
      NM_198431.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P34932.4 GenPept UniProtKB/Swiss-Prot:P34932

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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