Hspa9
entrez
291671
canonical
uniprot
P48721
canonical
ensembl
ENSRNOG00000019525
resolver
ensp
ENSRNOP00000026696
resolver
enst
ENSRNOT00000026696
resolver
genesymbol
Hspa9
resolver
genesymbol_syn
Grp75
resolver
genesymbol_syn
Hspa9a
resolver
uniprot
F1M953
resolver
uniprot_entry
HSPA9_RAT
resolver
uniprot_sec
F1M953
resolver
activity_regulation
ACTIVITY REGULATION: The chaperone activity is regulated by ATP-induced allosteric coupling of the nucleotide-binding (NBD) and substrate-binding (SBD) domains. ATP binding in the nucleotide-binding pocket (NBP) leads to a conformational change in the NBD, which is transferred through the interdomain linker (IDL) to the substrate-binding domain (SBD). This elicits a reduced substrate affinity and a faster substrate exchange rate. Upon hydrolysis of ATP to ADP, the protein undergoes a conformational change that increases its affinity for substrate proteins. It cycles through repeated phases of ATP hydrolysis and nucleotide exchange, facilitating repeated cycles of substrate binding and release (By similarity). Functions in collaboration with co-chaperones. Functions with the co-chaperone, DNLZ, to maintain solubility and regulate ATP hydrolysis. Regulated by nucleotide exchange factors (NEFs) including GRPEL1 and GRPEL2, which facilitate the release of bound ADP to allow ATP rebinding (By similarity). {ECO:0000250|UniProtKB:P11021, ECO:0000250|UniProtKB:P38646}.
uniprot
proteins
amino_acid_sequence
MISASRAAAARLVGTTASRSPAAARHQDGWNGLSHEAFRFVSRRDYASEAIKGAVVGIDLGTTNSCVAVMEGKQAKVLENAEGARTTPSVVAFTPDGERLVGMPAKRQAVTNPNNTFYATKRLIGRRYDDPEVQKDTKNVPFKIVRASNGDAWVEAHGKLYSPSQIGAFVLMKMKETAENYLGHTAKNAVITVPAYFNDSQRQATKDAGQISGLNVLRVINEPTAAALAYGLDKSEDKVIAVYDLGGGTFDISILEIQKGVFEVKSTNGDTFLGGEDFDQALLRHIVKEFKRETGVDLTKDNMALQRVREAAEKAKCELSSSVQTDINLPYLTMDASGPKHLNMKLTRAQFEGIVTDLIKRTIAPCQKAMQDAEVSKSDIGEVILVGGMTRMPKVQQTVQDLFGRAPSKAVNPDEAVAIGAAIQGGVLAGDVTDVLLLDVTPLSLGIETLGGVFTKLINRNTTIPTKKSQVFSTAADGQTQVEIKVCQGEREMAGDNKLLGQFTLIGIPPAPRGVPQIEVTFDIDANGIVHVSAKDKGTGREQQIVIQSSGGLSKDDIENMVKNAEKYAEEDRRKKERVEAVNMAEGIIHDTETKMEEFKDQLPADECNKLKEEISKMRELLARKDSETGENIRQAASSLQQASLKLFEMAYKKMASEREGSGSSSTGEQKEDQKEEKQ
uniprot
proteins
ec_number
3.6.4.10
uniprot
proteins
function
FUNCTION: Mitochondrial chaperone that plays a key role in mitochondrial protein import, folding, and assembly. Plays an essential role in the protein quality control system, the correct folding of proteins, the re-folding of misfolded proteins, and the targeting of proteins for subsequent degradation. These processes are achieved through cycles of ATP binding, ATP hydrolysis, and ADP release, mediated by co-chaperones. In mitochondria, it associates with the TIM (translocase of the inner membrane) protein complex to assist in the import and folding of mitochondrial proteins (By similarity). Plays an important role in mitochondrial iron-sulfur cluster (ISC) biogenesis, interacts with and stabilizes ISC cluster assembly proteins FXN, NFU1, NFS1 and ISCU. Regulates erythropoiesis via stabilization of ISC assembly. Regulates mitochondrial calcium-dependent apoptosis by coupling two calcium channels, ITPR1 and VDAC1, at the mitochondria-associated endoplasmic reticulum (ER) membrane to facilitate calcium transport from the ER lumen to the mitochondria intermembrane space, providing calcium for the downstream calcium channel MCU, which releases it into the mitochondrial matrix (By similarity). Although primarily located in the mitochondria, it is also found in other cellular compartments. In the cytosol, it associates with proteins involved in signaling, apoptosis, or senescence. It may play a role in cell cycle regulation via its interaction with and promotion of degradation of TP53 (By similarity). May play a role in the control of cell proliferation and cellular aging (By similarity). Protects against reactive oxygen species (ROS) (By similarity). Extracellular HSPA9 plays a cytoprotective role by preventing cell lysis following immune attack by the membrane attack complex by disrupting formation of the complex (By similarity). {ECO:0000250|UniProtKB:P0CS90, ECO:0000250|UniProtKB:P38646, ECO:0000250|UniProtKB:P38647}.
uniprot
proteins
mass_dalton
73745
uniprot
proteins
protein_family
Heat shock protein 70 family
uniprot
proteins
pubmed
15057822
uniprot
proteins
pubmed
17178908
uniprot
proteins
pubmed
2372296
uniprot
proteins
pubmed
7629893
uniprot
proteins
pubmed
7811387
uniprot
proteins
sequence_length
679
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:7811387}. Nucleus, nucleolus {ECO:0000250|UniProtKB:P38646}. Cytoplasm {ECO:0000269|PubMed:17178908}. Mitochondrion matrix {ECO:0000269|PubMed:17178908}. Note=Found in a complex with HSPA9 and VDAC1 at the endoplasmic reticulum-mitochondria contact sites. {ECO:0000269|PubMed:17178908}.
uniprot
proteins