Search results for HSPA5

Showing 17 results out of 18

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Protein (5 results from a total of 6)

Identifier: R-HSA-351322
Species: Homo sapiens
Compartment: extracellular region
Primary external reference: UniProt: HSPA5: P11021
Identifier: R-HSA-985498
Species: Homo sapiens
Compartment: integral component of lumenal side of endoplasmic reticulum membrane
Primary external reference: UniProt: HSPA5: P11021
Identifier: R-HSA-5252042
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: HSPA5: P11021
Identifier: R-HSA-5252115
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: P11021
Identifier: R-HSA-351315
Species: Homo sapiens
Compartment: endoplasmic reticulum membrane
Primary external reference: UniProt: P11021

DNA Sequence (1 results from a total of 1)

Identifier: R-HSA-5642261
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: ENSEMBL: ENSG00000044574

Reaction (5 results from a total of 5)

Identifier: R-HSA-381158
Species: Homo sapiens
Compartment: endoplasmic reticulum membrane, endoplasmic reticulum lumen
ATF6-alpha is a transmembrane protein located in the endoplasmic reticulum (ER) membrane with N-terminal cytoplasmic and C-terminal luminal domains. BiP binds the luminal domain of ATF6-alpha via the substrate binding domain of BiP. Binding of BiP blocks 2 Golgi localization sequences on ATF6-alpha, maintaining ATF6-alpha in the ER.
BiP is also a general chaperone capable of binding unfolded proteins in the ER lumen. When chaperone activity in the ER is overwhelmed, BiP dissociates from ATF6-alpha and binds the excess unfolded proteins. It is unclear whether the dissociation is due to competition of unfolded proteins for BiP or to a more specific interaction between BiP and ATF6-alpha. The dissociation exposes the Golgi localization sequences of ATF6-alpha and allows ATF6-alpha to transit to the Golgi.
Identifier: R-HSA-1791150
Species: Homo sapiens
Compartment: nucleoplasm, endoplasmic reticulum membrane
The BIP (HSPA5) gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
Identifier: R-HSA-3371422
Species: Homo sapiens
Compartment: cytosol
Heat shock protein 70 (HSP70) proteins bind and release client polypeptides in a cycle of cochaperone-mediated conformational changes that is coupled to ATP binding and hydrolysis (Mayer MP 2013). The overall domain structure of all HSP70 chaperone proteins is evolutionary conserved: the N-terminal nucleotide-binding domain (NBD) with ATPase activity is joined by a flexible linker to the C-terminal polypeptide substrate-binding domain (SBD). Most of our mechanistic understanding of HSP70 structure and function has come from analyses of Escherichia coli HSP70 family member, DnaK (Pellecchia M et al. 2000; Schuermann, JP et al. 2008; Bertelsen EB et al. 2009; Kityk R et al. 2012; Qi R et al. 2013). Chaperone function of bacterial DnaK involves an allosteric control mechanism between its two functional domains NBD and SBD. ATP binding and hydrolysis modulates the affinity of bacterial HSP70 protein for polypeptides, and polypeptide binding stimulates ATP hydrolysis (Mayer MP et al. 2000; Kityk R et al. 2012; Qi R et al. 2013). Also in the ATP-bound form, the lid domain remains open, which facilitates transient interactions with substrates. Following ATP hydrolysis, a conformational change releases the SBD, resulting in closure of the lid and a ~10-fold increase in the affinity for substrate (Wittung-Stafshede P et al. 2003; Slepenkov SV & Witt SN 2002). The conformation change associated with ATP hydrolysis is communicated through a key proline switch and involves the conserved, hydrophobic linker that connects the NBD to the SBD (Vogel M et al. 2006; Swain JF et al. 2007). ATP hydrolysis is essential for HSP70 chaperones, but the intrinsic ATPase rate is very low (Chang L et al. 2008). This ATPase activity of HSP70 is stimulated by protein substrates in synergism with J domain cochaperones (HSP40s) (Karzai AW & McMacken R 1996; Russell R et al. 1999; Laufen T et al. 1999; Landry SJ 2003; Wittung-Stafshede P et al. 2003).

The HSP70 family of chaperone proteins is one of the most conserved protein families in evolution (Takayama S et al. 1999; Boorstein WR et al. 1994; Brocchieri L et al. 2008). The sequence alignment of eukaryotic and bacterial HSP70 proteins revealed that the human HSP70 SBD is highly homologous to the DnaK SBD (51% sequence identity in the full-length protein and 47% identity in the SBD) (Zhang P et al. 2014). Moreover, the crystal structure of the substrate-bound human HSP70-SBD resembled the overall fold of the corresponding domain in the substrate-bound DnaK structures, confirming a similar overall architecture of the orthologous bacterial and human HSP70 proteins (Zhang P et al. 2014). Structures of nucleotide-binding domains of four human HSP70 isoforms: HSPA1L, HSPA2, HSPA6 and HSPA5 also support the view that the NBDs of human HSP70 function by conserved mechanisms (Wisniewska M et al. 2014). Structural analysis of a functionally intact bovine Hsp70 family member Hsc70 together with analysis of mutants in the interdomain linker and interface support the allosteric mechanism of the mammalian HSP70 chaperones (Wilbanks SM & McKay DB 1998; Jiang J et al. 2005).

Identifier: R-HSA-8874218
Species: Homo sapiens
Compartment: nucleoplasm, cytosol
The N-terminal domain of CREB3L4 (CREB4, AIbZIP) containing the bZIP and transcription activation domains trafficks from the cytosol to the nucleus (Stirling and O'Hare 2006, inferred from mouse Creb3l4 (Tisp40)) where it activates transcription of target genes such as HSPA5 (BiP), BAG3, DNAJC12, and KDELR3 (Qi et al. 2002, Ben Aicha et al. 2007). Expression of CREB3L4 is itself induced by androgens in prostate tissue (Qi et al. 2002).
Identifier: R-HSA-8874208
Species: Homo sapiens
Compartment: Golgi membrane, endoplasmic reticulum membrane
Unlike ATF6, CREB3L3 (and probably other CREB3 family members) does not interact with HSPA5 (BiP) (Llarena 2010). Instead, retention in the endoplasmic reticulum (ER) is mediated by a membrane-proximal cytoplasmic motif (Bailey et al. 2007). When the motif is deleted CREB3L3 is constitutively trafficked to the Golgi where it is cleaved (Bailey et al. 2007). In cells not experiencing ER stress, CREB3L3 is located in the ER membrane (Stirling and O'Hare 2006, Bailey et al. 2007, Llarena et al. 2010) and is rapidly turned over by the endoplasmic reticulum associated degradation (ERAD) pathway (Bailey et al. 2007). During ER stress CREB3L3 is translocated by an uncharacterized mechanism to the Golgi (Bailey et al. 2007, Llarena et al. 2010, also inferred from the mouse homolog in Zhang et al. 2006). CREB3L3 is expressed strongly in the liver and more weakly in the stomach and small intestine.

Complex (4 results from a total of 4)

Identifier: R-HSA-5252117
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-5252008
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-5252063
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-5252012
Species: Homo sapiens
Compartment: cytosol

Pathway (1 results from a total of 1)

Identifier: R-HSA-8874211
Species: Homo sapiens
Members of the CREB3 family (also known as the OASIS family) are tissue-specific proteins that each contain a transcription activation domain, a basic leucine zipper (bZIP) domain that promotes dimerization and DNA binding, and a transmembrane domain that anchors the protein to the membrane of the endoplasmic reticulum (ER) (reviewed in Asada et al. 2011, Chan et al. 2011, Kondo et al. 2011, Fox and Andrew 2015). The family includes CREB3 (LUMAN), CREB3L1 (OASIS), CREB3L2 (BBF2H7, Tisp40), CREB3L3 (CREB-H), and CREB3L4 (CREB4). Activation of the proteins occurs when they transit from the ER to the Golgi and are cleaved sequentially by the Golgi resident proteases MBTPS1 (S1P) and MBTPS2 (S2P), a process known as regulated intramembrane proteolysis that releases the cytoplasmic region of the protein containing the transcription activation domain and the bZIP domain. This protein fragment then transits from the cytosol to the nucleus where it activates transcription of target genes. CREB3L1, CREB3L2, and CREB3L3 are activated by ER stress, although the mechanisms that cause the transit of the CREB3 proteins are not fully characterized. Unlike the ATF6 factors, CREB3 proteins do not appear to interact with HSPA5 (BiP) and therefore do not appear to sense unfolded proteins by dissociation of HSPA5 when HSPA5 binds the unfolded proteins.

Icon (1 results from a total of 1)

Species: Homo sapiens
Curator: Bruce May
Designer: Cristoffer Sevilla
HSPA5 icon
Endoplasmic reticulum chaperone BiP
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