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Symbol HSPA4 contributors: mct/npt/shn - updated : 15-05-2016
HGNC name heat shock 70kDa protein 4
HGNC id 5237
Location 5q31.1      Physical location : 132.387.661 - 132.440.708
Synonym name
  • heat shock 70 kDa protein 4
  • heat shock 70-related protein APG-2
  • heat shock 70kD protein 4
  • heat shock protein, 110 kDa
  • Synonym symbol(s) RY, APG2, HSP70, hsp70RY, HS24/P52, HSPG1R2, MGC131852, APG-2
    TYPE functioning gene
    STRUCTURE 53.05 kb     19 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map cen - D5S1984 - D5S2002 - HSPA4 - D5S2117 - D5S2053 - qter
    Physical map
    FACL6 5q31 fatty-acid-Coenzyme A ligase, long-chain 6 IL3 5q31.1 interleukin 3 (colony-stimulating factor, multiple) CSF2 5q31.1 colony stimulating factor 2 (granulocyte-macrophage) LOC389325 5 LOC389325 P4HA2 5q31.1 procollagen-proline, 2-oxoglutarate 4-dioxygenase (proline 4-hydroxylase), alpha polypeptide II RIL 5q31.1 procollagen-proline, 2-oxoglutarate 4-dioxygenase (proline 4-hydroxylase), alpha polypeptide II SLC22A4 5q31.2 solute carrier family 22 (organic cation transporter), member 4 SLC22A5 5q31.1-q32 solute carrier family 22 (organic cation transporter), member 5 LOC389326 5 hypothetical gene supported by AK096941; AK128882 IRF1 5q31.1 interferon regulatory factor 1 IL5 5q31.1 interleukin 5 (colony-stimulating factor, eosinophil) RAD50 5q31 RAD50 homolog (S. cerevisiae) IL13 5q31.1 interleukin 13 IL4 5q31.1 interleukin 4 KIF3A 5q31 kinesin family member 3A SEPT8 5q31 kinesin family member 3A LOC134548 5q31.1 hypothetical protein LOC134548 APXL2 5q31.1 hypothetical protein LOC134548 GDF9 5q31.1 growth differentiation factor 9 QP-C 5q31.1 low molecular mass ubiquinone-binding protein (9.5kD) LEAP-2 5q31.1 liver-expressed antimicrobial peptide 2 AF5Q31 5q31 liver-expressed antimicrobial peptide 2 LOC389327 5 hypothetical gene supported by AK129671 LOC391832 5 similar to putative nucleic acid binding protein RY-1 FLJ20094 5q31.1 hypothetical protein FLJ20094 HSPA4 5q31.1-q32 heat shock 70kDa protein 4 KIAA1061 5q31.1 KIAA1061 protein HTGN29 5q31.1 HTGN29 protein VDAC1 5q31 voltage-dependent anion channel 1
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    19 splicing 3385 94 840 - Lee (2008)
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
     mouth   highly
     stomach   predominantly
    Reproductivemale systemprostate   
    Skin/Tegumentskin   highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    SystemCellPubmedSpeciesStageRna symbol
    cell lineage
    cell lines
    at STAGE
  • an N-terminal ATP-binding domain
  • a C-terminal peptide-binding domain characteristic of HSP proteins
    interspecies ortholog to Hspa4, Rattus norvegicus
    ortholog to Hspa4, Mus musculus
    ortholog to HSPA4, Pan troglodytes
    ortholog to hspa4b, Danio rerio
    intraspecies homolog to aconitase,structurally
  • heat shock protein 70 family
  • CATEGORY chaperone/stress
    SUBCELLULAR LOCALIZATION     intracellular
    basic FUNCTION
  • may be acting in protein folding, translocation, and assembly into complexes
  • involved in the targeting of a subset of mitochondrial preproteins to the TOM70 receptor
  • inhibiting alpha-Synuclein (AS) fibril formation via preventing the formation of prefibrillar AS (PreAS), binding with PreAS to impede nuclei formation, and binding with nuclei to retard fibril elongation
  • plays an important role in the pathogenesis of tauopathies
  • in erythroid precursors undergoing terminal differentiation, Hsp70 prevents active caspase-3 from cleaving GATA-1 and inducing apoptosis
  • plays a role in the regulation of mTORC2/Akt signaling in response to heat shock
  • a role in misfolding of the islet betta-cell peptide human amylin
  • CELLULAR PROCESS protein, post translation, folding
    pathway (NBN-HSF4-HSPA4/HSPA14 axis) to induce migration, invasion, and transformation, suggesting the activation of multiple signaling events induced by NBN overexpression
    a component
  • component of mTORC2 that is required for proper assembly and activity of the kinase both constitutively and following heat shock
  • PGLYRP1 forms with HSPA4 a stable complex with cytotoxic and antitumor activity
    small molecule nucleotide,
  • ATP
  • protein
  • Keratin polypeptides 8 and 18, K8/18
  • heat shock transcription factor 1, HSF1
  • heat shock factor binding protein 1, HSBP1
  • Fanconi anemia (FA) complementation group C gene product, FANCC
  • apobec-1-binding protein-2, ABBP-2
  • NAD(P)H:quinone oxidoreductase 1, NQO1
  • CHIP, Parkin, and Pael-R
  • CD40
  • docking protein CAIR-1
  • SMAD family member 3, SMAD3
  • Hsp40 and TPR1
  • Hypoxia inducible factor 1 alpha, HIF-1alpha
  • superoxide dismutase 1, SOD1
  • the mutants of multiple endocrine neoplasia type 1, MEN1
  • interferon gamma receptor accessory factor-1, AF-1
  • bcl-2-associated athanogene 5, BAG5
  • antigen presenting cells, APC and lectin-type oxidized LDL receptor 1, LOX-1
  • associate to RICTOR, as components of mTORC2, in intact mammalian cells
  • Endonuclease G, EndoG
  • bcl-2-associated athanogene 2, BAG2
  • specific interaction between HSPA4 and MBP suggestive of a possible role for HSPA4 in the immunopathology associated with multiple sclerosis (Lund 2006)
  • umor necrosis factor receptor-associated factor 6, TRAF6
  • protein kinase C, PKC
  • heat shock protein 110 kDa, Hsp110
  • LIM Kinase 1, LIMK1
  • substrate for parkin
  • TTC4 is a nucleoplasmic protein which interacts with HSP90AA1 and HSPA4, and also with the replication protein CDC6
  • TPR repeat protein 2, TRP2
  • corepressor REST, CoREST
  • interacting with ENPP1 (by affecting ENPP1 expression, may be a novel mediator of altered insulin signaling) (Marucci 2009)
  • HSPA4 binds MGP and enhances BMP activity, thereby functioning as a potential link between cellular stress, inflammation, and BMP signaling
  • HSPH1 suppressed the expanded polyQ tract-induced protein aggregation and apoptosis through the induction of HSPA4
  • misfolded human amylin oligomers
  • interaction between HSBP1 and the ATPase domain of the major heat shock protein HSPA4 up-regulates nucleotide exchange and reduces the affinity between HSPA4 and the peptide in its peptide-binding site
  • cytoplasmic HSPA4 plays a critical role in selecting immature forms of SLC12A3 for ERAD
  • HSPBP1 incapacitates the HSPA4-PGLYRP1 complex
  • functional interaction between TCL1A and HSPA4 and TCL1A is a novel HSPA4 client protein
  • HIF1A positively regulates the induction of NFAT5 and HSPA4 by placental hypoxia
  • ubiquitin-proteasomal regulation of DNAJC7 and HSPA4 are important contributors to the regulation of cytoplasmic NR1I3 levels
  • DNAJB6 and HSPA4 cooperate to suppress SNCA aggregation
  • STIP1 is a co-chaperone of HSPA4 and HSP90AA1 that regulates a number of cell biology processes via interactions with cellular proteins
  • DNAJA2 and DNAJA1 were both important for CFTR folding, however overexpressing DNAJA2 but not DNAJA1 enhanced CFTR degradation at the endoplasmic reticulum by HSPA4/HSPA8 and the E3 ubiquitin ligase STUB1
  • cell & other
    Other modulated by bcl-2-associated athanogene 1, BAG1 (