Search Results
Overview
| Uniprot ID | P0DMV8 |
|---|---|
| Protein Name | Heat shock 70 kDa protein 1A |
| Gene Name | HSPA1A |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position | Flanking peptide |
|---|---|
| 108 | PKVQVSYKGETKAFY |
| 246 | NHFVEEFKRKHKKDI |
| 319 | STLEPVEKALRDAKL |
| 328 | LRDAKLDKAQIHDLV |
| 451 | EGERAMTKDNNLLGR |
| 500 | KSTGKANKITITNDK |
| 507 | KITITNDKGRLSKEE |
| 512 | NDKGRLSKEEIERMV |
| 524 | RMVQEAEKYKAEDEV |
| 526 | VQEAEKYKAEDEVQR |
| 71 | QNTVFDAKRLIGRKF |
| 77 | AKRLIGRKFGDPVVQ |
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 (PubMed:24012426, PubMed:24318877, PubMed:26865365). 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 (PubMed:27708256). 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 (PubMed:27137183). Enhances STUB1-mediated SMAD3 ubiquitination and degradation and facilitates STUB1-mediated inhibition of TGF-beta signaling (PubMed:24613385). Essential for STUB1-mediated ubiquitination and degradation of FOXP3 in regulatory T-cells (Treg) during inflammation (PubMed:23973223). Required as a co-chaperone for optimal STUB1/CHIP ubiquitination of NFATC3 (By similarity). Negatively regulates heat shock-induced HSF1 transcriptional activity during the attenuation and recovery phase period of the heat shock response (PubMed:9499401). 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 (PubMed:28842558)
Protein Sequence
Gene Ontology
| Classification | GO ID | Description |
|---|---|---|
| Cellular Component | GO:0016235 | aggresome |
| Biological Process | GO:0033120 | positive regulation of RNA splicing |
| Biological Process | GO:1903265 | positive regulation of tumor necrosis factor-mediated signaling pathway |
| Biological Process | GO:0042026 | protein refolding |
| Biological Process | GO:0050821 | protein stabilization |
| Biological Process | GO:1901673 | regulation of mitotic spindle assembly |
| Biological Process | GO:0031396 | regulation of protein ubiquitination |
| Biological Process | GO:0006986 | response to unfolded protein |
| Cellular Component | GO:0072562 | blood microparticle |
| Cellular Component | GO:0005814 | centriole |
| Cellular Component | GO:0005813 | centrosome |
| Cellular Component | GO:0005737 | cytoplasm |
| Cellular Component | GO:0005829 | cytosol |
| Cellular Component | GO:0005783 | endoplasmic reticulum |
| Cellular Component | GO:0070062 | extracellular exosome |
| Cellular Component | GO:0005576 | extracellular region |
| Cellular Component | GO:0005615 | extracellular space |
| Cellular Component | GO:1904813 | ficolin-1-rich granule lumen |
| Cellular Component | GO:0005925 | focal adhesion |
| Cellular Component | GO:0016234 | inclusion body |
| Cellular Component | GO:0005739 | mitochondrion |
| Cellular Component | GO:0016607 | nuclear speck |
| Cellular Component | GO:0005654 | nucleoplasm |
| Cellular Component | GO:0005634 | nucleus |
| Cellular Component | GO:0048471 | perinuclear region of cytoplasm |
| Cellular Component | GO:0005886 | plasma membrane |
| Cellular Component | GO:0032991 | protein-containing complex |
| Cellular Component | GO:1990904 | ribonucleoprotein complex |
| Cellular Component | GO:0031982 | vesicle |
| Molecular Function | GO:0005524 | ATP binding |
| Molecular Function | GO:0016887 | ATP hydrolysis activity |
| Molecular Function | GO:0140545 | ATP-dependent protein disaggregase activity |
| Molecular Function | GO:0055131 | C3HC4-type RING finger domain binding |
| Molecular Function | GO:0045296 | cadherin binding |
| Molecular Function | GO:0031249 | denatured protein binding |
| Molecular Function | GO:0097718 | disordered domain specific binding |
| Molecular Function | GO:0019899 | enzyme binding |
| Molecular Function | GO:0001664 | G protein-coupled receptor binding |
| Molecular Function | GO:0031072 | heat shock protein binding |
| Molecular Function | GO:0042826 | histone deacetylase binding |
| Molecular Function | GO:0051787 | misfolded protein binding |
| Molecular Function | GO:0044183 | protein folding chaperone |
| Molecular Function | GO:0048018 | receptor ligand activity |
| Molecular Function | GO:0003723 | RNA binding |
| Molecular Function | GO:0005102 | signaling receptor binding |
| Molecular Function | GO:0003714 | transcription corepressor activity |
| Molecular Function | GO:0140416 | transcription regulator inhibitor activity |
| Molecular Function | GO:0031625 | ubiquitin protein ligase binding |
| Molecular Function | GO:0051082 | unfolded protein binding |
| Molecular Function | GO:0001618 | virus receptor activity |
| Biological Process | GO:0046034 | ATP metabolic process |
| Biological Process | GO:0070370 | cellular heat acclimation |
| Biological Process | GO:0034605 | cellular response to heat |
| Biological Process | GO:0034599 | cellular response to oxidative stress |
| Biological Process | GO:0071383 | cellular response to steroid hormone stimulus |
| Biological Process | GO:0034620 | cellular response to unfolded protein |
| Biological Process | GO:0051131 | chaperone-mediated protein complex assembly |
| Biological Process | GO:0030968 | endoplasmic reticulum unfolded protein response |
| Biological Process | GO:0007041 | lysosomal transport |
| Biological Process | GO:0006402 | mRNA catabolic process |
| Biological Process | GO:0043066 | negative regulation of apoptotic process |
| Biological Process | GO:0030308 | negative regulation of cell growth |
| Biological Process | GO:0008285 | negative regulation of cell population proliferation |
| Biological Process | GO:1902236 | negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway |
| Biological Process | GO:2001240 | negative regulation of extrinsic apoptotic signaling pathway in absence of ligand |
| Biological Process | GO:0090084 | negative regulation of inclusion body assembly |
| Biological Process | GO:1901029 | negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway |
| Biological Process | GO:0031397 | negative regulation of protein ubiquitination |
| Biological Process | GO:0000122 | negative regulation of transcription by RNA polymerase II |
| Biological Process | GO:0030512 | negative regulation of transforming growth factor beta receptor signaling pathway |
| Biological Process | GO:0043123 | positive regulation of canonical NF-kappaB signal transduction |
| Biological Process | GO:0045648 | positive regulation of erythrocyte differentiation |
| Biological Process | GO:0010628 | positive regulation of gene expression |
| Biological Process | GO:0032757 | positive regulation of interleukin-8 production |
| Biological Process | GO:0090063 | positive regulation of microtubule nucleation |
| Biological Process | GO:0070434 | positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway |
| Biological Process | GO:0032436 | positive regulation of proteasomal ubiquitin-dependent protein catabolic process |
Reference
[1] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.
[2] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.