P0DMV9
uniprot
P0DMV9
canonical
amino_acid_sequence
MAKAAAIGIDLGTTYSCVGVFQHGKVEIIANDQGNRTTPSYVAFTDTERLIGDAAKNQVALNPQNTVFDAKRLIGRKFGDPVVQSDMKHWPFQVINDGDKPKVQVSYKGETKAFYPEEISSMVLTKMKEIAEAYLGYPVTNAVITVPAYFNDSQRQATKDAGVIAGLNVLRIINEPTAAAIAYGLDRTGKGERNVLIFDLGGGTFDVSILTIDDGIFEVKATAGDTHLGGEDFDNRLVNHFVEEFKRKHKKDISQNKRAVRRLRTACERAKRTLSSSTQASLEIDSLFEGIDFYTSITRARFEELCSDLFRSTLEPVEKALRDAKLDKAQIHDLVLVGGSTRIPKVQKLLQDFFNGRDLNKSINPDEAVAYGAAVQAAILMGDKSENVQDLLLLDVAPLSLGLETAGGVMTALIKRNSTIPTKQTQIFTTYSDNQPGVLIQVYEGERAMTKDNNLLGRFELSGIPPAPRGVPQIEVTFDIDANGILNVTATDKSTGKANKITITNDKGRLSKEEIERMVQEAEKYKAEDEVQRERVSAKNALESYAFNMKSAVEDEGLKGKISEADKKKVLDKCQEVISWLDANTLAEKDEFEHKRKELEQVCNPIISGLYQGAGGPGPGGFGAQGPKGGSGSGPTIEEVD
uniprot
proteins
function
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). {ECO:0000269|PubMed:22528486, ECO:0000269|PubMed:23973223, ECO:0000269|PubMed:24318877, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:27137183, ECO:0000269|PubMed:27708256, ECO:0000303|PubMed:24012426, ECO:0000303|PubMed:26865365}.; FUNCTION: (Microbial infection) In case of rotavirus A infection, serves as a post-attachment receptor for the virus to facilitate entry into the cell. {ECO:0000269|PubMed:16537599}.
uniprot
proteins
mass_dalton
70052
uniprot
proteins
mutagenesis
MUTAGEN 10; /note="D->A: Reduces affinity for ADP."; /evidence="ECO:0000269|PubMed:21608060"; MUTAGEN 77; /note="K->Q: No loss of acetylation and ATPase activity. Exhibits normal protein refolding activity during the early phase but exhibits defects in ubiquitin-mediated protein degradation during the later phase."; /evidence="ECO:0000269|PubMed:27708256"; MUTAGEN 77; /note="K->R: Significant loss of acetylation and ATPase activity. Decreased binding to HOPX and HSP90 and increased binding to STUB1 and NAA10. Impaired capacity for protein refolding during the early phase after stress but shows normal protein degradation activity in the late phase."; /evidence="ECO:0000269|PubMed:27708256"; MUTAGEN 199; /note="D->A: Reduces affinity for ADP."; /evidence="ECO:0000269|PubMed:21608060"; MUTAGEN 561; /note="K->R: Complete loss of in vitro methylation by METTL21A."; /evidence="ECO:0000269|PubMed:23349634, ECO:0000269|PubMed:23921388
uniprot
proteins
post_translational_modification
PTM: In response to cellular stress, acetylated at Lys-77 by NA110 and then gradually deacetylated by HDAC4 at later stages. Acetylation enhances its chaperone activity and also determines whether it will function as a chaperone for protein refolding or degradation by controlling its binding to co-chaperones HOPX and STUB1. The acetylated form and the non-acetylated form bind to HOPX and STUB1 respectively. Acetylation also protects cells against various types of cellular stress. {ECO:0000269|PubMed:27708256}.
uniprot
proteins
protein_family
Heat shock protein 70 family
uniprot
proteins
pubmed
10216320
uniprot
proteins
pubmed
11274138
uniprot
proteins
pubmed
12853476
uniprot
proteins
pubmed
14574404
uniprot
proteins
pubmed
14656967
uniprot
proteins
pubmed
15383005
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15963462
uniprot
proteins
pubmed
16537599
uniprot
proteins
pubmed
1700760
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17182002
uniprot
proteins
pubmed
17233114
uniprot
proteins
pubmed
17289661
uniprot
proteins
pubmed
18620420
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
20053985
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20072699
uniprot
proteins
pubmed
20179333
uniprot
proteins
pubmed
20223214
uniprot
proteins
pubmed
21081504
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21608060
uniprot
proteins
pubmed
22528486
uniprot
proteins
pubmed
22905912
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23349634
uniprot
proteins
pubmed
23921388
uniprot
proteins
pubmed
23973223
uniprot
proteins
pubmed
24012426
uniprot
proteins
pubmed
24129315
uniprot
proteins
pubmed
24270810
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24318877
uniprot
proteins
pubmed
24613385
uniprot
proteins
pubmed
24790089
uniprot
proteins
pubmed
2538825
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26865365
uniprot
proteins
pubmed
27133716
uniprot
proteins
pubmed
27137183
uniprot
proteins
pubmed
27708256
uniprot
proteins
pubmed
33857403
uniprot
proteins
sequence_length
641
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17289661}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:27137183}. Note=Localized in cytoplasmic mRNP granules containing untranslated mRNAs.
uniprot
proteins