Search results for HSPA8

Showing 16 results out of 59

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Types

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Protein (3 results from a total of 10)

Identifier: R-HSA-264476
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: HSPA8: P11142
Identifier: R-HSA-888599
Species: Homo sapiens
Compartment: clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane
Primary external reference: UniProt: HSPA8: P11142
Identifier: R-HSA-6801530
Species: Homo sapiens
Compartment: secretory granule lumen
Primary external reference: UniProt: HSPA8: P11142

DNA Sequence (1 results from a total of 1)

Identifier: R-HSA-6789521
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: ENSEMBL: ENSG00000109971

Reaction (3 results from a total of 31)

Identifier: R-HSA-9626253
Species: Homo sapiens
Compartment: cytosol, lysosomal membrane
Intracellular proteins are targeted for proteolytic degradation in lysosome with the aid of chaperones. Heat shock cognate 71 kDa protein (HSPA8) transports substrates from the cytosol to the lysosomal membrane where it binds to Lysosome-associated membrane glycoprotein 2 (LAMP2a). Subsequently, LAMP2a forms a multimeric complex and transfers the substrate into the lumen. The stability of this complex is regulated by the dynamics of HSPA8. Cytosolic HSPA8 binds with LAMP2a multimers in the lysosomal membrane and triggers their disassembly. Interestingly, substrate bound HSPA8 do not have this effect on LAMP2a (Bandyopadhyay U et al. 2008). Experiments confirming this event were performed in rats.
Identifier: R-HSA-9626235
Species: Homo sapiens
Compartment: cytosol, lysosomal membrane
Intracellular proteins are targeted for proteolytic degradation in lysosome with the aid of chaperones. Heat shock cognate 71 kDa protein (HSPA8) transports substrates from the cytosol to the lysosomal membrane where it binds to Lysosome-associated membrane glycoprotein 2 (LAMP2a). Subsequently, LAMP2a forms a multimeric complex and transfers the substrate into the lumen. The stability of this complex is regulated by the dynamics of HSPA8. Cytosolic HSPA8 binds with LAMP2a multimers in the lysosomal membrane and triggers their disassembly into monomeric units (Bandyopadhyay U et al. 2008). HSPA8 dissociates from LAMP2a to make it available for further substrate autophagy. Experiments related to this event were performed in rats.
Identifier: R-HSA-9615721
Species: Homo sapiens
Compartment: cytosol
Intracellular proteins are targeted for proteolytic degradation in the lysosome with the aid of chaperones. Heat shock cognate 71 kDa protein (HSPA8) acts as the constitutive chaperone that binds substrate proteins in the cytosol. HSPA8 recognizes a motif based on the charge of the amino acids (Chiang H et al. 1989, Dice JF et al. 1990). This allows the motif to have multiple sequence possibilities and also create a motif through post-translational modifications such as phosphorylation and acetylation. Once bound with HSPA8, the substrates are targeted to the lysosome or endosome.

Complex (3 results from a total of 11)

Identifier: R-HSA-9615717
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-9631103
Species: Homo sapiens
Compartment: late endosome lumen
Identifier: R-HSA-9620204
Species: Homo sapiens
Compartment: lysosomal membrane

Set (2 results from a total of 2)

Identifier: R-HSA-6797266
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-6797275
Species: Homo sapiens
Compartment: cytosol

Polymer (1 results from a total of 1)

Identifier: R-HSA-9626247
Species: Homo sapiens
Compartment: cytosol, lysosomal membrane

Pathway (2 results from a total of 2)

Identifier: R-HSA-9615710
Species: Homo sapiens
Compartment: cytosol, phagocytic vesicle
Microautophagy (MI) is a non-selective autophagic pathway that involves internalisation of cytosolic cargo through invaginations of the lysosomal membrane. MI can be induced by nitrogen starvation and complements other related self-eating processes such as Macroautophagy (MA) and Chaperone Mediated Autophagy (CMA). MI can degrade cell organelles and bulk cytosolic proteins directly via the lysosome and late endosome. MI can also target substrates with KFERQ motifs with the help of HSPA8 (Li W W et al. 2012).
Identifier: R-HSA-8856828
Species: Homo sapiens
Clathrin-mediated endocytosis (CME) is one of a number of process that control the uptake of material from the plasma membrane, and leads to the formation of clathrin-coated vesicles (Pearse et al, 1975; reviewed in Robinson, 2015; McMahon and Boucrot, 2011; Kirchhausen et al, 2014). CME contributes to signal transduction by regulating the cell surface expression and signaling of receptor tyrosine kinases (RTKs) and G-protein coupled receptors (GPCRs). Most RTKs exhibit a robust increase in internalization rate after binding specific ligands; however, some RTKs may also exhibit significant ligand-independent internalization (reviewed in Goh and Sorkin, 2013). CME controls RTK and GPCR signaling by organizing signaling both within the plasma membrane and on endosomes (reviewed in Eichel et al, 2016; Garay et al, 2015; Vieira et al, 1996; Sorkin and von Zastrow, 2014; Di Fiori and von Zastrow, 2014; Barbieri et al, 2016). CME also contributes to the uptake of material such as metabolites, hormones and other proteins from the extracellular space, and regulates membrane composition by recycling membrane components and/or targeting them for degradation.


Clathrin-mediated endocytosis involves initiation of clathrin-coated pit (CCP) formation, cargo selection, coat assembly and stabilization, membrane scission and vesicle uncoating. Although for simplicity in this pathway, the steps leading to a mature CCP are represented in a linear and temporally distinct fashion, the formation of a clathrin-coated vesicle is a highly heterogeneous process and clear temporal boundaries between these processes may not exist (see for instance Taylor et al, 2011; Antonescu et al, 2011; reviewed in Kirchhausen et al, 2014). Cargo selection in particular is a critical aspect of the formation of a mature and stable CCP, and many of the proteins involved in the initiation and maturation of a CCP contribute to cargo selection and are themselves stabilized upon incorporation of cargo into the nascent vesicle (reviewed in Kirchhausen et al, 2014; McMahon and Boucrot, 2011).



Although the clathrin triskelion was identified early as a major component of the coated vesicles, clathrin does not bind directly to membranes or to the endocytosed cargo. Vesicle formation instead relies on many proteins and adaptors that can bind the plasma membrane and interact with cargo molecules. Cargo selection depends on the recognition of endocytic signals in cytoplasmic tails of the cargo proteins by adaptors that interact with components of the vesicle's inner coat. The classic adaptor for clathrin-coated vesicles is the tetrameric AP-2 complex, which along with clathrin was identified early as a major component of the coat. Some cargo indeed bind directly to AP-2, but subsequent work has revealed a large family of proteins collectively known as CLASPs (clathrin- associated sorting proteins) that mediate the recruitment of diverse cargo into the emerging clathrin-coated vesicles (reviewed in Traub and Bonifacino, 2013). Many of these CLASP proteins themselves interact with AP-2 and clathrin, coordinating cargo recruitment with coat formation (Schmid et al, 2006; Edeling et al, 2006; reviewed in Traub and Bonifacino, 2013; Kirchhausen et al, 2014).


Initiation of CCP formation is also influenced by lipid composition, regulated by clathrin-associated phosphatases and kinases (reviewed in Picas et al, 2016). The plasma membrane is enriched in PI(4,5)P2. Many of the proteins involved in initiating clathrin-coated pit formation bind to PI(4,5)P2 and induce membrane curvature through their BAR domains (reviewed in McMahon and Boucrot, 2011; Daumke et al, 2014). Epsin also contributes to early membrane curvature through its Epsin N-terminal homology (ENTH) domain, which promotes membrane curvature by inserting into the lipid bilayer (Ford et al, 2002).

Following initiation, some CCPs progress to formation of vesicles, while others undergo disassembly at the cell surface without producing vesicles (Ehrlich et al, 2004; Loerke et al, 2009; Loerke et al, 2011; Aguet et al, 2013; Taylor et al, 2011). The assembly and stabilization of nascent CCPs is regulated by several proteins and lipids (Mettlen et al, 2009; Antonescu et al, 2011).


Maturation of the emerging clathrin-coated vesicle is accompanied by further changes in the lipid composition of the membrane and increased membrane curvature, promoted by the recruitment of N-BAR domain containing proteins (reviewed in Daumke et al, 2014; Ferguson and De Camilli, 2012; Picas et al, 2016). Some N-BAR domain containing proteins also contribute to the recruitment of the large GTPase dynamin, which is responsible for scission of the mature vesicle from the plasma membrane (Koh et al, 2007; Lundmark and Carlsson, 2003; Soulet et al, 2005; David et al, 1996; Owen et al, 1998; Shupliakov et al, 1997; Taylor et al, 2011; Ferguson et al, 2009; Aguet et al, 2013; Posor et al, 2013; Chappie et al, 2010; Shnyrova et al, 2013; reviewed in Mettlen et al, 2009; Daumke et al, 2014). After vesicle scission, the clathrin coat is dissociated from the new vesicle by the ATPase HSPA8 (also known as HSC70) and its DNAJ cofactor auxilin, priming the vesicle for fusion with a subsequent endocytic compartment and releasing clathrin for reuse (reviewed in McMahon and Boucrot, 2011; Sousa and Laufer, 2015).

Icon (1 results from a total of 1)

Species: Homo sapiens
Heat shock cognate 71 kDa protein
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