HS71A_BOVIN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: HS71A_BOVIN
• UniProt AC: Q27975
• Protein Name: Heat shock 70 kDa protein 1A
• Gene Name: HSPA1A
• Organism: Bos taurus (Bovine).
• Sequence Length: 641
• Subcellular Localization: Cytoplasm . Nucleus . Cytoplasm, cytoskeleton, microtubule organizing center, centrosome . Localized in cytoplasmic mRNP granules containing untranslated mRNAs.
• Protein Description: 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. 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. 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. Enhances STUB1-mediated SMAD3 ubiquitination and degradation and facilitates STUB1-mediated inhibition of TGF-beta signaling. Essential for STUB1-mediated ubiquitination and degradation of FOXP3 in regulatory T-cells (Treg) during inflammation. Negatively regulates heat shock-induced HSF1 transcriptional activity during the attenuation and recovery phase period of the heat shock response..
• Protein Sequence: MAKNMAIGIDLGTTYSCVGVFQHGKVEIIANDQGNRTTPSYVAFTDTERLIGDAAKNQVALNPQNTVFDAKRLIGRKFGDPVVQSDMKHWPFRVINDGDKPKVQVSYKGETKAFYPEEISSMVLTKMKEIAEAYLGHPVTNAVITVPAYFNDSQRQATKDAGVIAGLNVLRIINEPTAAAIAYGLDRTGKGERNVLIFDLGGGTFDVSILTIDDGIFEVKATAGDTHLGGEDFDNRLVNHFVEEFKRKHKKDISQNKRAVRRLRTACERAKRTLSSSTQASLEIDSLFEGIDFYTSITRARFEELCSDLFRSTLEPVEKALRDAKLDKAQIHDLVLVGGSTRIPKVQKLLQDFFNGRDLNKSINPDEAVAYGAAVQAAILMGDKSENVQDLLLLDVAPLSLGLETAGGVMTALIKRNSTIPTKQTQIFTTYSDNQPGVLIQVYEGERAMTRDNNLLGRFELSGIPPAPRGVPQIEVTFDIDANGILNVTATDKSTGKANKITITNDKGRLSKEEIERMVQEAEKYKAEDEVQRERVSAKNALESYAFNMKSAVEDEGLKGKISEADKKKVLDKCQEVISWLDANTLAEKDEFEHKRKELEQVCNPIISRLYQGAGGPGAGGFGAQGPKGGSGSGPTIEEVD

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Acetylation	------MAKNMAIGI ------CCCCCEEEE	16.36	-
77	Acetylation	AKRLIGRKFGDPVVQ HHHHHCHHHCCCCCC	48.78	-
106	Phosphorylation	DKPKVQVSYKGETKA CCCEEEEEECCCCEE	12.20	29541418
108	Acetylation	PKVQVSYKGETKAFY CEEEEEECCCCEEEC	42.64	-
246	Acetylation	NHFVEEFKRKHKKDI HHHHHHHHHHHHHCH	64.91	-
348	Acetylation	TRIPKVQKLLQDFFN CCCHHHHHHHHHHHC	54.90	-
469	Methylation	SGIPPAPRGVPQIEV CCCCCCCCCCCEEEE	61.93	-
561	"N6,N6,N6-trimethyllysine"	EDEGLKGKISEADKK HCCCCCCCCCHHHHH	41.28	-
561	Methylation	EDEGLKGKISEADKK HCCCCCCCCCHHHHH	41.28	-
631	Phosphorylation	AQGPKGGSGSGPTIE CCCCCCCCCCCCCCC	38.15	-
633	Phosphorylation	GPKGGSGSGPTIEEV CCCCCCCCCCCCCCC	43.21	-
636	Phosphorylation	GGSGSGPTIEEVD-- CCCCCCCCCCCCC--	44.54	-

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Oops, there are no upstream regulatory protein records of HS71A_BOVIN !!

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of HS71A_BOVIN !!

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of HS71A_BOVIN !!

Protein-Protein Interaction

Oops, there are no PPI records of HS71A_BOVIN !!

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.