P0DMV9 · HS71B_HUMAN
- ProteinHeat shock 70 kDa protein 1B
- GeneHSPA1B
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids641 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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).
(Microbial infection) In case of rotavirus A infection, serves as a post-attachment receptor for the virus to facilitate entry into the cell.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 12-15 | ATP (UniProtKB | ChEBI) | ||||
Sequence: GTTY | ||||||
Binding site | 71 | ATP (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 202-204 | ATP (UniProtKB | ChEBI) | ||||
Sequence: GGT | ||||||
Binding site | 268-275 | ATP (UniProtKB | ChEBI) | ||||
Sequence: ERAKRTLS | ||||||
Binding site | 339-342 | ATP (UniProtKB | ChEBI) | ||||
Sequence: GSTR |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameHeat shock 70 kDa protein 1B
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP0DMV9
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Localized in cytoplasmic mRNP granules containing untranslated mRNAs.
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 10 | Reduces affinity for ADP. | ||||
Sequence: D → A | ||||||
Mutagenesis | 77 | 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. | ||||
Sequence: K → Q | ||||||
Mutagenesis | 77 | 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. | ||||
Sequence: K → R | ||||||
Natural variant | VAR_032152 | 95 | ||||
Sequence: I → V | ||||||
Mutagenesis | 199 | Reduces affinity for ADP. | ||||
Sequence: D → A | ||||||
Natural variant | VAR_032153 | 467 | in dbSNP:rs538280104 | |||
Sequence: A → V | ||||||
Natural variant | VAR_029054 | 499 | in dbSNP:rs483638 | |||
Sequence: N → S | ||||||
Mutagenesis | 561 | Complete loss of in vitro methylation by METTL21A. | ||||
Sequence: K → R |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 668 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Modified residue | 2 | UniProt | N-acetylalanine | ||||
Sequence: A | |||||||
Chain | PRO_0000433115 | 2-641 | UniProt | Heat shock 70 kDa protein 1B | |||
Sequence: AKAAAIGIDLGTTYSCVGVFQHGKVEIIANDQGNRTTPSYVAFTDTERLIGDAAKNQVALNPQNTVFDAKRLIGRKFGDPVVQSDMKHWPFQVINDGDKPKVQVSYKGETKAFYPEEISSMVLTKMKEIAEAYLGYPVTNAVITVPAYFNDSQRQATKDAGVIAGLNVLRIINEPTAAAIAYGLDRTGKGERNVLIFDLGGGTFDVSILTIDDGIFEVKATAGDTHLGGEDFDNRLVNHFVEEFKRKHKKDISQNKRAVRRLRTACERAKRTLSSSTQASLEIDSLFEGIDFYTSITRARFEELCSDLFRSTLEPVEKALRDAKLDKAQIHDLVLVGGSTRIPKVQKLLQDFFNGRDLNKSINPDEAVAYGAAVQAAILMGDKSENVQDLLLLDVAPLSLGLETAGGVMTALIKRNSTIPTKQTQIFTTYSDNQPGVLIQVYEGERAMTKDNNLLGRFELSGIPPAPRGVPQIEVTFDIDANGILNVTATDKSTGKANKITITNDKGRLSKEEIERMVQEAEKYKAEDEVQRERVSAKNALESYAFNMKSAVEDEGLKGKISEADKKKVLDKCQEVISWLDANTLAEKDEFEHKRKELEQVCNPIISGLYQGAGGPGPGGFGAQGPKGGSGSGPTIEEVD | |||||||
Modified residue (large scale data) | 40 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 41 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 45 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 77 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 85 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 106 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 108 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 111 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 222 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 246 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 307 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 348 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 362 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 418 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 469 | UniProt | Omega-N-methylarginine | ||||
Sequence: R | |||||||
Modified residue (large scale data) | 502 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 537 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 544 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 561 | UniProt | N6,N6,N6-trimethyllysine; by METTL21A; alternate | ||||
Sequence: K | |||||||
Modified residue | 561 | UniProt | N6,N6-dimethyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 611 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 631 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 631 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 633 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 633 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 636 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 636 | PRIDE | Phosphothreonine | ||||
Sequence: T |
Post-translational modification
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.
Keywords
- PTM
Proteomic databases
2D gel databases
PTM databases
Expression
Tissue specificity
HSPA1B is testis-specific.
Induction
By heat shock.
Gene expression databases
Organism-specific databases
Interaction
Subunit
May be an auxiliary component of the CatSper complex. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (PubMed:17289661).
Interacts with CHCHD3, DNAJC7, IRAK1BP1, PPP5C and TSC2 (PubMed:12853476, PubMed:15383005, PubMed:15963462, PubMed:17233114, PubMed:18620420, PubMed:21081504).
Interacts with TERT; the interaction occurs in the absence of the RNA component, TERC, and dissociates once the TERT complex has formed (PubMed:11274138).
Interacts with TRIM5 (via B30.2/SPRY domain) (PubMed:20053985).
Interacts with METTL21A (PubMed:23921388).
Interacts with PRKN (PubMed:24270810).
Interacts with FOXP3 (PubMed:23973223).
Interacts with NOD2; the interaction enhances NOD2 stability (PubMed:24790089).
Interacts with DNAJC9 (via J domain) (PubMed:17182002, PubMed:33857403).
Interacts with ATF5; the interaction protects ATF5 from degradation via proteasome-dependent and caspase-dependent processes (PubMed:22528486).
Interacts with NAA10, HSP40, HSP90 and HDAC4. The acetylated form and the non-acetylated form interact with HOPX and STUB1 respectively (PubMed:27708256).
Interacts with NEDD1 (PubMed:27137183).
Interacts (via NBD) with BAG1, BAG2, BAG3 and HSPH1/HSP105 (PubMed:24318877).
Interacts with SMAD3 (PubMed:24613385).
Interacts with DNAJC8 (PubMed:27133716).
Interacts with CHCHD3, DNAJC7, IRAK1BP1, PPP5C and TSC2 (PubMed:12853476, PubMed:15383005, PubMed:15963462, PubMed:17233114, PubMed:18620420, PubMed:21081504).
Interacts with TERT; the interaction occurs in the absence of the RNA component, TERC, and dissociates once the TERT complex has formed (PubMed:11274138).
Interacts with TRIM5 (via B30.2/SPRY domain) (PubMed:20053985).
Interacts with METTL21A (PubMed:23921388).
Interacts with PRKN (PubMed:24270810).
Interacts with FOXP3 (PubMed:23973223).
Interacts with NOD2; the interaction enhances NOD2 stability (PubMed:24790089).
Interacts with DNAJC9 (via J domain) (PubMed:17182002, PubMed:33857403).
Interacts with ATF5; the interaction protects ATF5 from degradation via proteasome-dependent and caspase-dependent processes (PubMed:22528486).
Interacts with NAA10, HSP40, HSP90 and HDAC4. The acetylated form and the non-acetylated form interact with HOPX and STUB1 respectively (PubMed:27708256).
Interacts with NEDD1 (PubMed:27137183).
Interacts (via NBD) with BAG1, BAG2, BAG3 and HSPH1/HSP105 (PubMed:24318877).
Interacts with SMAD3 (PubMed:24613385).
Interacts with DNAJC8 (PubMed:27133716).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P0DMV9 | F2RL1 P55085 | 2 | EBI-14100688, EBI-4303189 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 2-386 | Nucleotide-binding domain (NBD) | ||||
Sequence: AKAAAIGIDLGTTYSCVGVFQHGKVEIIANDQGNRTTPSYVAFTDTERLIGDAAKNQVALNPQNTVFDAKRLIGRKFGDPVVQSDMKHWPFQVINDGDKPKVQVSYKGETKAFYPEEISSMVLTKMKEIAEAYLGYPVTNAVITVPAYFNDSQRQATKDAGVIAGLNVLRIINEPTAAAIAYGLDRTGKGERNVLIFDLGGGTFDVSILTIDDGIFEVKATAGDTHLGGEDFDNRLVNHFVEEFKRKHKKDISQNKRAVRRLRTACERAKRTLSSSTQASLEIDSLFEGIDFYTSITRARFEELCSDLFRSTLEPVEKALRDAKLDKAQIHDLVLVGGSTRIPKVQKLLQDFFNGRDLNKSINPDEAVAYGAAVQAAILMGDKSE | ||||||
Region | 394-509 | Substrate-binding domain (SBD) | ||||
Sequence: LDVAPLSLGLETAGGVMTALIKRNSTIPTKQTQIFTTYSDNQPGVLIQVYEGERAMTKDNNLLGRFELSGIPPAPRGVPQIEVTFDIDANGILNVTATDKSTGKANKITITNDKGR | ||||||
Region | 614-641 | Disordered | ||||
Sequence: AGGPGPGGFGAQGPKGGSGSGPTIEEVD |
Domain
The N-terminal nucleotide binding domain (NBD) (also known as the ATPase domain) is responsible for binding and hydrolyzing ATP. The C-terminal substrate-binding domain (SBD) (also known as peptide-binding domain) binds to the client/substrate proteins. The two domains are allosterically coupled so that, when ATP is bound to the NBD, the SBD binds relatively weakly to clients. When ADP is bound in the NBD, a conformational change enhances the affinity of the SBD for client proteins.
Sequence similarities
Belongs to the heat shock protein 70 family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length641
- Mass (Da)70,052
- Last updated2015-05-27 v1
- Checksum78F513118C96DE66
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A0G2JIW1 | A0A0G2JIW1_HUMAN | HSPA1B | 642 |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M59830 EMBL· GenBank· DDBJ | AAA63227.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BA000025 EMBL· GenBank· DDBJ | BAB63299.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF134726 EMBL· GenBank· DDBJ | AAD21815.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ388429 EMBL· GenBank· DDBJ | ABD48956.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AL671762 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC009322 EMBL· GenBank· DDBJ | AAH09322.1 EMBL· GenBank· DDBJ | mRNA | ||
BC018740 EMBL· GenBank· DDBJ | AAH18740.1 EMBL· GenBank· DDBJ | mRNA | ||
BC057397 EMBL· GenBank· DDBJ | AAH57397.1 EMBL· GenBank· DDBJ | mRNA | ||
BC063507 EMBL· GenBank· DDBJ | AAH63507.1 EMBL· GenBank· DDBJ | mRNA | ||
M24744 EMBL· GenBank· DDBJ | AAA59845.1 EMBL· GenBank· DDBJ | Genomic DNA |