Heat shock 70 kDa protein 1A
Details
- Name
- Heat shock 70 kDa protein 1A
- Kind
- protein
- Synonyms
- Heat shock 70 kDa protein 1
- Heat shock protein family A member 1A
- HSP70-1
- HSP70.1
- HSP72
- HSPA1
- HSX70
- Gene Name
- HSPA1A
- UniProtKB Entry
- P0DMV8Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- Amino acid sequence
>lcl|BSEQ0053155|Heat shock 70 kDa protein 1A MAKAAAIGIDLGTTYSCVGVFQHGKVEIIANDQGNRTTPSYVAFTDTERLIGDAAKNQVA LNPQNTVFDAKRLIGRKFGDPVVQSDMKHWPFQVINDGDKPKVQVSYKGETKAFYPEEIS SMVLTKMKEIAEAYLGYPVTNAVITVPAYFNDSQRQATKDAGVIAGLNVLRIINEPTAAA IAYGLDRTGKGERNVLIFDLGGGTFDVSILTIDDGIFEVKATAGDTHLGGEDFDNRLVNH FVEEFKRKHKKDISQNKRAVRRLRTACERAKRTLSSSTQASLEIDSLFEGIDFYTSITRA RFEELCSDLFRSTLEPVEKALRDAKLDKAQIHDLVLVGGSTRIPKVQKLLQDFFNGRDLN KSINPDEAVAYGAAVQAAILMGDKSENVQDLLLLDVAPLSLGLETAGGVMTALIKRNSTI PTKQTQIFTTYSDNQPGVLIQVYEGERAMTKDNNLLGRFELSGIPPAPRGVPQIEVTFDI DANGILNVTATDKSTGKANKITITNDKGRLSKEEIERMVQEAEKYKAEDEVQRERVSAKN ALESYAFNMKSAVEDEGLKGKISEADKKKVLDKCQEVISWLDANTLAEKDEFEHKRKELE QVCNPIISGLYQGAGGPGPGGFGAQGPKGGSGSGPTIEEVD
- Number of residues
- 641
- Molecular Weight
- 70051.65
- Theoretical pI
- Not Available
- GO Classification
- Not Available
- General 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). Required as a co-chaperone for optimal STUB1/CHIP ubiquitination of NFATC3 (By similarity). Negatively regulates heat shock-induced HSF1 transcriptional activity during the attenuation and recovery phase period of the heat shock response (PubMed:9499401). Involved in the clearance of misfolded PRDM1/Blimp-1 proteins. Sequesters them in the cytoplasm and promotes their association with SYNV1/HRD1, leading to proteasomal degradation (PubMed:28842558)
- Specific Function
- Atp binding
- Pfam Domain Function
- HSP70 (PF00012)
- Signal Regions
- Not Available
- Transmembrane Regions
- Not Available
- Cellular Location
- Cytoplasm
- Gene sequence
>lcl|BSEQ0053156|Heat shock 70 kDa protein 1A (HSPA1A) ATGGCCAAAGCCGCGGCGATCGGCATCGACCTGGGCACCACCTACTCCTGCGTGGGGGTG TTCCAACACGGCAAGGTGGAGATCATCGCCAACGACCAGGGCAACCGCACCACCCCCAGC TACGTGGCCTTCACGGACACCGAGCGGCTCATCGGGGATGCGGCCAAGAACCAGGTGGCG CTGAACCCGCAGAACACCGTGTTTGACGCGAAGCGGCTGATTGGCCGCAAGTTCGGCGAC CCGGTGGTGCAGTCGGACATGAAGCACTGGCCTTTCCAGGTGATCAACGACGGAGACAAG CCCAAGGTGCAGGTGAGCTACAAGGGGGAGACCAAGGCATTCTACCCCGAGGAGATCTCG TCCATGGTGCTGACCAAGATGAAGGAGATCGCCGAGGCGTACCTGGGCTACCCGGTGACC AACGCGGTGATCACCGTGCCGGCCTACTTCAACGACTCGCAGCGCCAGGCCACCAAGGAT GCGGGTGTGATCGCGGGGCTCAACGTGCTGCGGATCATCAACGAGCCCACGGCCGCCGCC ATCGCCTACGGCCTGGACAGAACGGGCAAGGGGGAGCGCAACGTGCTCATCTTTGACCTG GGCGGGGGCACCTTCGACGTGTCCATCCTGACGATCGACGACGGCATCTTCGAGGTGAAG GCCACGGCCGGGGACACCCACCTGGGTGGGGAGGACTTTGACAACAGGCTGGTGAACCAC TTCGTGGAGGAGTTCAAGAGAAAACACAAGAAGGACATCAGCCAGAACAAGCGAGCCGTG AGGCGGCTGCGCACCGCCTGCGAGAGGGCCAAGAGGACCCTGTCGTCCAGCACCCAGGCC AGCCTGGAGATCGACTCCCTGTTTGAGGGCATCGACTTCTACACGTCCATCACCAGGGCG AGGTTCGAGGAGCTGTGCTCCGACCTGTTCCGAAGCACCCTGGAGCCCGTGGAGAAGGCT CTGCGCGACGCCAAGCTGGACAAGGCCCAGATTCACGACCTGGTCCTGGTCGGGGGCTCC ACCCGCATCCCCAAGGTGCAGAAGCTGCTGCAGGACTTCTTCAACGGGCGCGACCTGAAC AAGAGCATCAACCCCGACGAGGCTGTGGCCTACGGGGCGGCGGTGCAGGCGGCCATCCTG ATGGGGGACAAGTCCGAGAACGTGCAGGACCTGCTGCTGCTGGACGTGGCTCCCCTGTCG CTGGGGCTGGAGACGGCCGGAGGCGTGATGACTGCCCTGATCAAGCGCAACTCCACCATC CCCACCAAGCAGACGCAGATCTTCACCACCTACTCCGACAACCAACCCGGGGTGCTGATC CAGGTGTACGAGGGCGAGAGGGCCATGACGAAAGACAACAATCTGTTGGGGCGCTTCGAG CTGAGCGGCATCCCTCCGGCCCCCAGGGGCGTGCCCCAGATCGAGGTGACCTTCGACATC GATGCCAACGGCATCCTGAACGTCACGGCCACGGACAAGAGCACCGGCAAGGCCAACAAG ATCACCATCACCAACGACAAGGGCCGCCTGAGCAAGGAGGAGATCGAGCGCATGGTGCAG GAGGCGGAGAAGTACAAAGCGGAGGACGAGGTGCAGCGCGAGAGGGTGTCAGCCAAGAAC GCCCTGGAGTCCTACGCCTTCAACATGAAGAGCGCCGTGGAGGATGAGGGGCTCAAGGGC AAGATCAGCGAGGCGGACAAGAAGAAGGTGCTGGACAAGTGTCAAGAGGTCATCTCGTGG CTGGACGCCAACACCTTGGCCGAGAAGGACGAGTTTGAGCACAAGAGGAAGGAGCTGGAG CAGGTGTGTAACCCCATCATCAGCGGACTGTACCAGGGTGCCGGTGGTCCCGGGCCTGGG GGCTTCGGGGCTCAGGGTCCCAAGGGAGGGTCTGGGTCAGGCCCCACCATTGAGGAGGTA GATTAG
- Chromosome Location
- 6
- Locus
- 6p21.33
- External Identifiers
Resource Link UniProtKB ID P0DMV8 UniProtKB Entry Name HS71A_HUMAN GeneCard ID HSPA1A HGNC ID HGNC:5232 PDB ID(s) 1HJO, 1S3X, 1XQS, 2E88, 2E8A, 2LMG, 3A8Y, 3ATU, 3ATV, 3AY9, 3D2E, 3D2F, 3JXU, 3LOF, 3Q49, 4IO8, 4J8F, 4PO2, 4WV5, 4WV7, 5AQW, 5AQX, 5AQY, 5AQZ, 5AR0, 5BN8, 5BN9, 5BPL, 5BPM, 5BPN, 5GJJ, 5MKR, 5MKS, 5XI9, 5XIR, 6FHK, 6G3R, 6G3S, 6JPV, 6K39, 6ZYI, 7FGM, 7KW7, 7Q4R KEGG ID hsa:3304 NCBI Gene ID 3304 - General References
- Not Available
Associated Data
- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details Iroxanadine investigational yes target modulator Details Ellagic acid investigational yes target inhibitor Details Bimoclomol investigational yes target modulator Details Minnelide investigational yes target inhibitor Details