General Information of Binding Target of SBP (BTS) (ID: ST00060)
BTS Name
Heat shock 70 kDa protein 1A
Synonyms
Heat shock 70 kDa protein 1; HSP70-1; HSP70.1
BTS Type
Protein
Family
Heat shock protein 70 family
Gene Name
HSPA1A
Organism
Homo sapiens (Human)
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, 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 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. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The co-chaperones are of three types: J-domain co-chaperones such as 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 Maintains protein homeostasis during cellular stress through two opposing mechanisms: protein refolding and degradation. Its acetylation/deacetylation state determines whether it functions in protein refolding or protein degradation by controlling the competitive binding of co-chaperones HOPX and STUB1. During the early stress response, the acetylated form binds to HOPX which assists in chaperone-mediated protein refolding, thereafter, it is deacetylated and binds to ubiquitin ligase STUB1 that promotes ubiquitin-mediated protein degradation Regulates centrosome integrity during mitosis, and is required for the maintenance of a functional mitotic centrosome that supports the assembly of a bipolar mitotic spindle Enhances STUB1-mediated SMAD3 ubiquitination and degradation and facilitates STUB1-mediated inhibition of TGF-beta signaling Essential for STUB1-mediated ubiquitination and degradation of FOXP3 in regulatory T-cells (Treg) during inflammation Negatively regulates heat shock-induced HSF1 transcriptional activity during the attenuation and recovery phase period of the heat shock response Involved in the clearance of misfolded PRDM1/Blimp-1 proteins. Sequesters them in the cytoplasm and promotes their association with SYNV1/HRD1, leading to proteasomal degradation ; (Microbial infection) In case of rotavirus A infection, serves as a post-attachment receptor for the virus to facilitate entry into the cell.
UniProt ID
P0DMV8
UniProt Entry
HS71A_HUMAN
PFam
PF00012
Gene ID
3303;3304
Sequence
MAKAAAIGIDLGTTYSCVGVFQHGKVEIIANDQGNRTTPSYVAFTDTERLIGDAAKNQVA
LNPQNTVFDAKRLIGRKFGDPVVQSDMKHWPFQVINDGDKPKVQVSYKGETKAFYPEEIS
SMVLTKMKEIAEAYLGYPVTNAVITVPAYFNDSQRQATKDAGVIAGLNVLRIINEPTAAA
IAYGLDRTGKGERNVLIFDLGGGTFDVSILTIDDGIFEVKATAGDTHLGGEDFDNRLVNH
FVEEFKRKHKKDISQNKRAVRRLRTACERAKRTLSSSTQASLEIDSLFEGIDFYTSITRA
RFEELCSDLFRSTLEPVEKALRDAKLDKAQIHDLVLVGGSTRIPKVQKLLQDFFNGRDLN
KSINPDEAVAYGAAVQAAILMGDKSENVQDLLLLDVAPLSLGLETAGGVMTALIKRNSTI
PTKQTQIFTTYSDNQPGVLIQVYEGERAMTKDNNLLGRFELSGIPPAPRGVPQIEVTFDI
DANGILNVTATDKSTGKANKITITNDKGRLSKEEIERMVQEAEKYKAEDEVQRERVSAKN
ALESYAFNMKSAVEDEGLKGKISEADKKKVLDKCQEVISWLDANTLAEKDEFEHKRKELE
QVCNPIISGLYQGAGGPGPGGFGAQGPKGGSGSGPTIEEVD
Sequence Length
641
Synthetic Binding Protein (SBP) Targeting This BTS
SBP Name Highest Status Mechanism Affinity Application Details Ref
Anticalin anti-Hsp70 BBG10 Research Binder Kd: 12.5 nM Tumors [ICD-11: XH1N44]
SBP Info
[1]
Anticalin anti-Hsp70 BBG10C/I Research Binder Kd: 0.51 nM Tumors [ICD-11: XH1N44]
SBP Info
[1]
Anticalin anti-Hsp70 BBG10I Research Binder Kd: 2.2 nM Tumors [ICD-11: XH1N44]
SBP Info
[1]
Anticalin anti-Hsp70 BBG10I-1 Research Binder Kd: 0.39 nM Tumors [ICD-11: XH1N44]
SBP Info
[1]
Designed TPR protein anti-HSP90/Hsp70 D334K/T332R double mutant Research Binder Kd: 3200 nM Cancers [ICD-11: 2D4Z]
SBP Info
[2]
Peptide aptamer anti-Hsp70 A8/17 Research Binder N.A. Cancers [ICD-11: 2D4Z]
SBP Info
[3], [4]
References
1 Selection of an Anticalin? against the membrane form of Hsp70 via bacterial surface display and its theranostic application in tumour models. Biol Chem. 2018 Feb 23;399(3):235-252.
2 Electrostatic interactions of Hsp-organizing protein tetratricopeptide domains with Hsp70 and Hsp90: computational analysis and protein engineering. J Biol Chem. 2009 Sep 11;284(37):25364-74.
3 Peptides and aptamers targeting HSP70: a novel approach for anticancer chemotherapy. Cancer Res. 2011 Jan 15;71(2):484-95.
4 Peptide aptamers with biological and therapeutic applications. Curr Med Chem. 2011;18(27):4215-22.