Details of Protein

General Information of Protein (ID: PRT01144)
Name Lipopolysaccharide-associated 1 (HSPA8)
Synonyms   Click to Show/Hide Synonyms of This Protein
Heat shock 70 kDa protein 8; Lipopolysaccharide-associated protein 1; LAP-1; LPS-associated protein 1; HSPA8; HSC70; HSP73; HSPA10
Gene Name HSPA8 Gene ID
3312
UniProt ID
P11142
Family Hydrolases (EC 3)
EC Number   EC: 3.6.4.10  (Click to Show/Hide the Complete EC Tree)
Hydrolases
Acid anhydride hydrolase
Cellular and subcellular movement acid anhydride hydrolase
EC: 3.6.4.10
  Click to Show/Hide the Molecular/Functional Data (Sequence/Structure/Function) of This Protein
Sequence
MSKGPAVGIDLGTTYSCVGVFQHGKVEIIANDQGNRTTPSYVAFTDTERLIGDAAKNQVA
MNPTNTVFDAKRLIGRRFDDAVVQSDMKHWPFMVVNDAGRPKVQVEYKGETKSFYPEEVS
SMVLTKMKEIAEAYLGKTVTNAVVTVPAYFNDSQRQATKDAGTIAGLNVLRIINEPTAAA
IAYGLDKKVGAERNVLIFDLGGGTFDVSILTIEDGIFEVKSTAGDTHLGGEDFDNRMVNH
FIAEFKRKHKKDISENKRAVRRLRTACERAKRTLSSSTQASIEIDSLYEGIDFYTSITRA
RFEELNADLFRGTLDPVEKALRDAKLDKSQIHDIVLVGGSTRIPKIQKLLQDFFNGKELN
KSINPDEAVAYGAAVQAAILSGDKSENVQDLLLLDVTPLSLGIETAGGVMTVLIKRNTTI
PTKQTQTFTTYSDNQPGVLIQVYEGERAMTKDNNLLGKFELTGIPPAPRGVPQIEVTFDI
DANGILNVSAVDKSTGKENKITITNDKGRLSKEDIERMVQEAEKYKAEDEKQRDKVSSKN
SLESYAFNMKATVEDEKLQGKINDEDKQKILDKCNEIINWLDKNQTAEKEEFEHQQKELE
KVCNPIITKLYQSAGGMPGGMPGGFPGGGAPPSGGASSGPTIEEVD
Structure
3AGY ; 3AGZ ; 3ESK ; 3FZF ; 3FZH ; 3FZK ; 3FZL ; 3FZM ; 3LDQ ; 3M3Z ; 4H5N ; 4H5R ; 4H5T ; 4H5V ; 4H5W ; 4HWI ; 4KBQ ; 5AQF ; 5AQG ; 5AQH ; 5AQI ; 5AQJ ; 5AQK ; 5AQL ; 5AQM ; 5AQN ; 5AQO ; 5AQP ; 5AQQ ; 5AQR ; 5AQS ; 5AQT ; 5AQU ; 5AQV ; 6B1I ; 6B1M ; 6B1N ; 6ZYJ
Function Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The co-chaperones have been shown to not only regulate different steps of the ATPase cycle of HSP70, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation. The affinity of HSP70 for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. HSP70 goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The HSP70-associated co-chaperones are of three types: J-domain co-chaperones HSP40s (stimulate ATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF) such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP-bound state thereby promoting substrate release), and the TPR domain chaperones such as HOPX and STUB1. Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70. Acts as a repressor of transcriptional activation. Inhibits the transcriptional coactivator activity of CITED1 on Smad-mediated transcription. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex. Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes. Participates in the ER-associated degradation (ERAD) quality control pathway in conjunction with J domain-containing co-chaperones and the E3 ligase STUB1. Interacts with VGF-derived peptide TLQP-21.
Regulatory Network
Full List of Metabolite(s) Regulating This Protein
      Organic acids and derivatives
            Arginine Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Arginine decrease (48 hours)
                      Induced Change HSPA8 protein abundance levels: decrease (FC = 2.2)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Colon cancer [ICD-11: 2B90]
                      Details It is reported that arginine decrease causes the decrease of HSPA8 protein abundance compared with control group.
      Organic oxygen compounds
            Glucose Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Glucose addition (16 hours)
                      Induced Change HSPA8 protein expression levels: decrease (FC = 4)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Hyperglycemic hyperosmolar syndrome [ICD-11: 5A20]
                      Details It is reported that glucose addition causes the decrease of HSPA8 protein expression compared with control group.
References
1 Arginine deficiency in preconfluent intestinal Caco-2 cells modulates expression of proteins involved in proliferation, apoptosis, and heat shock response. Proteomics. 2007 Feb;7(4):565-577.
2 High-glucose-induced changes in macrophage secretome: regulation of immune response. Mol Cell Biochem. 2019 Feb;452(1-2):51-62.

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