P54652 · HSP72_HUMAN
- ProteinHeat shock-related 70 kDa protein 2
- GeneHSPA2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids639 (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 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 (PubMed:26865365).
Plays a role in spermatogenesis. In association with SHCBP1L may participate in the maintenance of spindle integrity during meiosis in male germ cells (By similarity).
Plays a role in spermatogenesis. In association with SHCBP1L may participate in the maintenance of spindle integrity during meiosis in male germ cells (By similarity).
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 13-16 | ATP (UniProtKB | ChEBI) | ||||
Sequence: GTTY | ||||||
Binding site | 72 | ATP (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 205-207 | ATP (UniProtKB | ChEBI) | ||||
Sequence: GGT | ||||||
Binding site | 271-278 | ATP (UniProtKB | ChEBI) | ||||
Sequence: ERAKRTLS | ||||||
Binding site | 342-345 | ATP (UniProtKB | ChEBI) | ||||
Sequence: GSTR |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameHeat shock-related 70 kDa protein 2
- Short namesHeat shock 70 kDa protein 2
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP54652
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Colocalizes with SHCBP1L at spindle during the meiosis process.
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_032706 | 191 | in dbSNP:rs45456191 | |||
Sequence: C → S | ||||||
Natural variant | VAR_032707 | 496 | in dbSNP:rs45447398 | |||
Sequence: K → E | ||||||
Mutagenesis | 564 | Abolishes methylation by METTL21A. | ||||
Sequence: K → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 699 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 chain, modified residue (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000078258 | 1-639 | UniProt | Heat shock-related 70 kDa protein 2 | |||
Sequence: MSARGPAIGIDLGTTYSCVGVFQHGKVEIIANDQGNRTTPSYVAFTDTERLIGDAAKNQVAMNPTNTIFDAKRLIGRKFEDATVQSDMKHWPFRVVSEGGKPKVQVEYKGETKTFFPEEISSMVLTKMKEIAEAYLGGKVHSAVITVPAYFNDSQRQATKDAGTITGLNVLRIINEPTAAAIAYGLDKKGCAGGEKNVLIFDLGGGTFDVSILTIEDGIFEVKSTAGDTHLGGEDFDNRMVSHLAEEFKRKHKKDIGPNKRAVRRLRTACERAKRTLSSSTQASIEIDSLYEGVDFYTSITRARFEELNADLFRGTLEPVEKALRDAKLDKGQIQEIVLVGGSTRIPKIQKLLQDFFNGKELNKSINPDEAVAYGAAVQAAILIGDKSENVQDLLLLDVTPLSLGIETAGGVMTPLIKRNTTIPTKQTQTFTTYSDNQSSVLVQVYEGERAMTKDNNLLGKFDLTGIPPAPRGVPQIEVTFDIDANGILNVTAADKSTGKENKITITNDKGRLSKDDIDRMVQEAERYKSEDEANRDRVAAKNALESYTYNIKQTVEDEKLRGKISEQDKNKILDKCQEVINWLDRNQMAEKDEYEHKQKELERVCNPIISKLYQGGPGGGSGGGGSGASGGPTIEEVD | |||||||
Modified residue (large scale data) | 41 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 42 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 46 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 108 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 112 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 178 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 224 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 225 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 229 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 403 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 408 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 414 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 421 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 564 | UniProt | N6,N6,N6-trimethyllysine; by METTL21A; in vitro | ||||
Sequence: K |
Keywords
- PTM
Proteomic databases
2D gel databases
PTM databases
Expression
Interaction
Subunit
Interacts with FKBP6 (PubMed:18529014).
Interacts with ZNF541. Component of the CatSper complex. Interacts with RABL2/RABL2A; binds preferentially to GTP-bound RABL2. Interacts with SHCBP1L; this interaction may promote the recruitment of HSPA2 to the spindle (By similarity).
Interacts with ZNF541. Component of the CatSper complex. Interacts with RABL2/RABL2A; binds preferentially to GTP-bound RABL2. Interacts with SHCBP1L; this interaction may promote the recruitment of HSPA2 to the spindle (By similarity).
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 2-389 | Nucleotide-binding domain (NBD) | ||||
Sequence: SARGPAIGIDLGTTYSCVGVFQHGKVEIIANDQGNRTTPSYVAFTDTERLIGDAAKNQVAMNPTNTIFDAKRLIGRKFEDATVQSDMKHWPFRVVSEGGKPKVQVEYKGETKTFFPEEISSMVLTKMKEIAEAYLGGKVHSAVITVPAYFNDSQRQATKDAGTITGLNVLRIINEPTAAAIAYGLDKKGCAGGEKNVLIFDLGGGTFDVSILTIEDGIFEVKSTAGDTHLGGEDFDNRMVSHLAEEFKRKHKKDIGPNKRAVRRLRTACERAKRTLSSSTQASIEIDSLYEGVDFYTSITRARFEELNADLFRGTLEPVEKALRDAKLDKGQIQEIVLVGGSTRIPKIQKLLQDFFNGKELNKSINPDEAVAYGAAVQAAILIGDKSE | ||||||
Region | 397-512 | Substrate-binding domain (SBD) | ||||
Sequence: LDVTPLSLGIETAGGVMTPLIKRNTTIPTKQTQTFTTYSDNQSSVLVQVYEGERAMTKDNNLLGKFDLTGIPPAPRGVPQIEVTFDIDANGILNVTAADKSTGKENKITITNDKGR | ||||||
Region | 613-639 | Disordered | ||||
Sequence: LYQGGPGGGSGGGGSGASGGPTIEEVD |
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
- Length639
- Mass (Da)70,021
- Last updated1996-10-01 v1
- Checksum3851755494E7B729
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 14 | in Ref. 5; AAH36107 | ||||
Sequence: T → P | ||||||
Sequence conflict | 54 | in Ref. 6; AAC50076 | ||||
Sequence: Missing | ||||||
Sequence conflict | 80 | in Ref. 5; AAH36107 | ||||
Sequence: E → G | ||||||
Sequence conflict | 266 | in Ref. 2; AAD11466 | ||||
Sequence: L → S |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
L26336 EMBL· GenBank· DDBJ | AAA52698.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U56725 EMBL· GenBank· DDBJ | AAD11466.1 EMBL· GenBank· DDBJ | mRNA | ||
BT009815 EMBL· GenBank· DDBJ | AAP88817.1 EMBL· GenBank· DDBJ | mRNA | ||
DQ489378 EMBL· GenBank· DDBJ | ABE96830.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC001752 EMBL· GenBank· DDBJ | AAH01752.1 EMBL· GenBank· DDBJ | mRNA | ||
BC036107 EMBL· GenBank· DDBJ | AAH36107.1 EMBL· GenBank· DDBJ | mRNA | ||
AH006615 EMBL· GenBank· DDBJ | AAC50076.1 EMBL· GenBank· DDBJ | Genomic DNA |