HSPA9
entrez
3313
canonical
uniprot
P38646
canonical
ensembl
ENSG00000113013
resolver
ensp
ENSP00000297185
resolver
enst
ENST00000297185
resolver
genesymbol
HSPA9
resolver
genesymbol_syn
GRP75
resolver
genesymbol_syn
HSPA9B
resolver
genesymbol_syn
mt-HSP70
resolver
hgnc
HGNC:5244
resolver
uniprot
A0A384P5G6
resolver
uniprot
B2RCM1
resolver
uniprot
P30036
resolver
uniprot
P31932
resolver
uniprot
Q1HB43
resolver
uniprot
Q53H23
resolver
uniprot
Q6GU03
resolver
uniprot
Q9BWB7
resolver
uniprot
Q9UC56
resolver
uniprot_entry
A0A384P5G6_HUMAN
resolver
uniprot_entry
HSPA9_HUMAN
resolver
uniprot_sec
B2RCM1
resolver
uniprot_sec
P30036
resolver
uniprot_sec
P31932
resolver
uniprot_sec
Q1HB43
resolver
uniprot_sec
Q53H23
resolver
uniprot_sec
Q6GU03
resolver
uniprot_sec
Q9BWB7
resolver
uniprot_sec
Q9UC56
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 NBD 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 (PubMed:18632665). Regulated by nucleotide exchange factors (NEFs) including GRPEL1 and GRPEL2, which facilitate the release of bound ADP to allow ATP rebinding (PubMed:28848044). {ECO:0000250|UniProtKB:P11021, ECO:0000269|PubMed:18632665, ECO:0000269|PubMed:28848044}.
uniprot
proteins
amino_acid_sequence
MISASRAAAARLVGAAASRGPTAARHQDSWNGLSHEAFRLVSRRDYASEAIKGAVVGIDLGTTNSCVAVMEGKQAKVLENAEGARTTPSVVAFTADGERLVGMPAKRQAVTNPNNTFYATKRLIGRRYDDPEVQKDIKNVPFKIVRASNGDAWVEAHGKLYSPSQIGAFVLMKMKETAENYLGHTAKNAVITVPAYFNDSQRQATKDAGQISGLNVLRVINEPTAAALAYGLDKSEDKVIAVYDLGGGTFDISILEIQKGVFEVKSTNGDTFLGGEDFDQALLRHIVKEFKRETGVDLTKDNMALQRVREAAEKAKCELSSSVQTDINLPYLTMDSSGPKHLNMKLTRAQFEGIVTDLIRRTIAPCQKAMQDAEVSKSDIGEVILVGGMTRMPKVQQTVQDLFGRAPSKAVNPDEAVAIGAAIQGGVLAGDVTDVLLLDVTPLSLGIETLGGVFTKLINRNTTIPTKKSQVFSTAADGQTQVEIKVCQGEREMAGDNKLLGQFTLIGIPPAPRGVPQIEVTFDIDANGIVHVSAKDKGTGREQQIVIQSSGGLSKDDIENMVKNAEKYAEEDRRKKERVEAVNMAEGIIHDTETKMEEFKDQLPADECNKLKEEISKMRELLARKDSETGENIRQAASSLQQASLKLFEMAYKKMASEREGSGSSGTGEQKEDQKEEKQ
uniprot
proteins
disease_involvement
DISEASE: Anemia, sideroblastic, 4 (SIDBA4) [MIM:182170]: A form of sideroblastic anemia, a bone marrow disorder defined by the presence of pathologic iron deposits in erythroblast mitochondria. Sideroblastic anemia is characterized by anemia of varying severity, hypochromic peripheral erythrocytes, systemic iron overload secondary to chronic ineffective erythropoiesis, and the presence of bone marrow ringed sideroblasts. Sideroblasts are characterized by iron-loaded mitochondria clustered around the nucleus. SIDBA4 has been reported to be inherited as an autosomal recessive disease, with a pseudodominant pattern of inheritance in some families. {ECO:0000269|PubMed:26491070}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Even-plus syndrome (EVPLS) [MIM:616854]: An autosomal recessive syndrome characterized by epiphyseal and vertebral dysplasia, prenatal-onset short stature, a distinct craniofacial phenotype with microtia, a flat facial profile with flat nose and triangular nares, cardiac malformations, and additional findings such as anal atresia, hypodontia, aplasia cutis, and others. {ECO:0000269|PubMed:26598328, ECO:0000269|PubMed:30933555}. Note=The disease is caused by variants affecting the gene represented in this entry.
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 (PubMed:18632665, PubMed:25615450, PubMed:28848044, PubMed:30933555, PubMed:31177526). 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 (PubMed:26702583). Regulates erythropoiesis via stabilization of ISC assembly (PubMed:21123823, PubMed:26702583). 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 (PubMed:24625977, PubMed:26634371). 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 (PubMed:16091382). {ECO:0000250|UniProtKB:P0CS90, ECO:0000250|UniProtKB:P38647, ECO:0000269|PubMed:16091382, ECO:0000269|PubMed:18632665, ECO:0000269|PubMed:21123823, ECO:0000269|PubMed:24625977, ECO:0000269|PubMed:25615450, ECO:0000269|PubMed:26634371, ECO:0000269|PubMed:26702583, ECO:0000269|PubMed:28848044, ECO:0000269|PubMed:30933555, ECO:0000269|PubMed:31177526}.
uniprot
proteins
mass_dalton
73680
uniprot
proteins
mutagenesis
MUTAGEN 441; /note="T->A: No effect on interaction with UBXN2A."; /evidence="ECO:0000269|PubMed:26634371"; MUTAGEN 442; /note="P->A: Abolishes interaction with UBXN2A."; /evidence="ECO:0000269|PubMed:26634371"; MUTAGEN 489; /note="G->E: Significant loss of interaction with FXN and ISCU. Significant increase in interaction with NFS1."; /evidence="ECO:0000269|PubMed:26702583"; MUTAGEN 555; /note="K->A: Reduces interaction with UBXN2A."; /evidence="ECO:0000269|PubMed:26634371"; MUTAGEN 558; /note="I->A: Abolishes interaction with UBXN2A."; /evidence="ECO:0000269|PubMed:26634371
uniprot
proteins
protein_family
Heat shock protein 70 family
uniprot
proteins
pubmed
10339406
uniprot
proteins
pubmed
1286669
uniprot
proteins
pubmed
14654843
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16091382
uniprot
proteins
pubmed
17331979
uniprot
proteins
pubmed
18632665
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
20668094
uniprot
proteins
pubmed
21123823
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21908771
uniprot
proteins
pubmed
22002106
uniprot
proteins
pubmed
22114354
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23462535
uniprot
proteins
pubmed
23501103
uniprot
proteins
pubmed
23541579
uniprot
proteins
pubmed
23940031
uniprot
proteins
pubmed
24129315
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24625977
uniprot
proteins
pubmed
24687350
uniprot
proteins
pubmed
25615450
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26491070
uniprot
proteins
pubmed
26598328
uniprot
proteins
pubmed
26634371
uniprot
proteins
pubmed
26702583
uniprot
proteins
pubmed
28848044
uniprot
proteins
pubmed
30933555
uniprot
proteins
pubmed
31177526
uniprot
proteins
pubmed
39737924
uniprot
proteins
pubmed
7498169
uniprot
proteins
pubmed
7684501
uniprot
proteins
pubmed
7829505
uniprot
proteins
pubmed
8313870
uniprot
proteins
pubmed
9150948
uniprot
proteins
sequence_length
679
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:22002106, ECO:0000269|PubMed:26702583}. Nucleus, nucleolus {ECO:0000269|PubMed:22002106, ECO:0000269|PubMed:24625977}. Cytoplasm {ECO:0000269|PubMed:24625977}. Mitochondrion matrix {ECO:0000250|UniProtKB:P48721}. Note=Found in a complex with HSPA9 and VDAC1 at the endoplasmic reticulum-mitochondria contact sites. {ECO:0000250|UniProtKB:P48721}.
uniprot
proteins