HS71A_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: HS71A_MOUSE
• UniProt AC: Q61696
• Protein Name: Heat shock 70 kDa protein 1A
• Gene Name: Hspa1a
• Organism: Mus musculus (Mouse).
• 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: MAKNTAIGIDLGTTYSCVGVFQHGKVEIIANDQGNRTTPSYVAFTDTERLIGDAAKNQVALNPQNTVFDAKRLIGRKFGDAVVQSDMKHWPFQVVNDGDKPKVQVNYKGESRSFFPEEISSMVLTKMKEIAEAYLGHPVTNAVITVPAYFNDSQRQATKDAGVIAGLNVLRIINEPTAAAIAYGLDRTGKGERNVLIFDLGGGTFDVSILTIDDGIFEVKATAGDTHLGGEDFDNRLVSHFVEEFKRKHKKDISQNKRAVRRLRTACERAKRTLSSSTQASLEIDSLFEGIDFYTSITRARFEELCSDLFRGTLEPVEKALRDAKMDKAQIHDLVLVGGSTRIPKVQKLLQDFFNGRDLNKSINPDEAVAYGAAVQAAILMGDKSENVQDLLLLDVAPLSLGLETAGGVMTALIKRNSTIPTKQTQTFTTYSDNQPGVLIQVYEGERAMTRDNNLLGRFELSGIPPAPRGVPQIEVTFDIDANGILNVTATDKSTGKANKITITNDKGRLSKEEIERMVQEAERYKAEDEVQRDRVAAKNALESYAFNMKSAVEDEGLKGKLSEADKKKVLDKCQEVISWLDSNTLADKEEFVHKREELERVCSPIISGLYQGAGAPGAGGFGAQAPKGASGSGPTIEEVD

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	------MAKNTAIGI ------CCCCEEEEE	17.51	-
3	Ubiquitination	-----MAKNTAIGID -----CCCCEEEEEE	54.24	-
15	Phosphorylation	GIDLGTTYSCVGVFQ EEECCCCEEEEEEEE	10.42	15592455
37	Phosphorylation	ANDQGNRTTPSYVAF ECCCCCCCCCCEEEE	47.24	20415495
38	Phosphorylation	NDQGNRTTPSYVAFT CCCCCCCCCCEEEEE	13.65	25367039
40	Phosphorylation	QGNRTTPSYVAFTDT CCCCCCCCEEEEECH	30.10	24899341
41	Phosphorylation	GNRTTPSYVAFTDTE CCCCCCCEEEEECHH	9.30	22817900
45	Phosphorylation	TPSYVAFTDTERLIG CCCEEEEECHHHHHC	32.07	28066266
47	Phosphorylation	SYVAFTDTERLIGDA CEEEEECHHHHHCHH	21.68	25367039
56	Ubiquitination	RLIGDAAKNQVALNP HHHCHHHHCCEEECC	50.02	-
71	Ubiquitination	QNTVFDAKRLIGRKF CCCCHHHHHHHCHHH	49.97	-
71	Acetylation	QNTVFDAKRLIGRKF CCCCHHHHHHHCHHH	49.97	70225
77	Acetylation	AKRLIGRKFGDAVVQ HHHHHCHHHCCEEEC	48.78	-
108	Ubiquitination	PKVQVNYKGESRSFF CCEEEEECCCCCCCC	51.50	-
108	Acetylation	PKVQVNYKGESRSFF CCEEEEECCCCCCCC	51.50	-
126	Ubiquitination	ISSMVLTKMKEIAEA HHHHHHHHHHHHHHH	43.76	-
145	Phosphorylation	PVTNAVITVPAYFND CCCCEEEEEECCCCH	17.53	-
153	Phosphorylation	VPAYFNDSQRQATKD EECCCCHHHCCHHHC	28.50	26370283
159	Ubiquitination	DSQRQATKDAGVIAG HHHCCHHHCCCCCCC	48.90	-
177	Phosphorylation	LRIINEPTAAAIAYG HHHCCCHHHHHHHHC	23.81	-
190	Ubiquitination	YGLDRTGKGERNVLI HCCCCCCCCCCEEEE	57.92	-
222	Phosphorylation	GIFEVKATAGDTHLG CEEEEEEEECCCCCC	26.00	22817900
226	Phosphorylation	VKATAGDTHLGGEDF EEEEECCCCCCCCCC	20.34	22817900
246	Acetylation	SHFVEEFKRKHKKDI HHHHHHHHHHHHHCH	64.91	70221
254	Phosphorylation	RKHKKDISQNKRAVR HHHHHCHHHHHHHHH	37.52	22802335
257	Ubiquitination	KKDISQNKRAVRRLR HHCHHHHHHHHHHHH	33.81	-
265	Phosphorylation	RAVRRLRTACERAKR HHHHHHHHHHHHHHH	40.01	22817900
348	Acetylation	TRIPKVQKLLQDFFN CCCHHHHHHHHHHHC	54.90	-
348	Ubiquitination	TRIPKVQKLLQDFFN CCCHHHHHHHHHHHC	54.90	-
362	Phosphorylation	NGRDLNKSINPDEAV CCCCCCCCCCHHHHH	26.90	26643407
418	Phosphorylation	TALIKRNSTIPTKQT HHHHHCCCCCCCCCE	31.57	28507225
469	Methylation	SGIPPAPRGVPQIEV CCCCCCCCCCCEEEE	61.93	5169937
500	Ubiquitination	KSTGKANKITITNDK CCCCCCCEEEEECCC	46.19	-
507	Ubiquitination	KITITNDKGRLSKEE EEEEECCCCCCCHHH	48.26	-
512	Ubiquitination	NDKGRLSKEEIERMV CCCCCCCHHHHHHHH	65.05	-
539	Ubiquitination	QRDRVAAKNALESYA HHHHHHHHHHHHHHC	32.77	-
561	Methylation	EDEGLKGKLSEADKK CCCCCCCCCCHHHHH	47.45	-
561	"N6,N6,N6-trimethyllysine"	EDEGLKGKLSEADKK CCCCCCCCCCHHHHH	47.45	-
567	Acetylation	GKLSEADKKKVLDKC CCCCHHHHHHHHHHH	62.63	19861539
604	Phosphorylation	EELERVCSPIISGLY HHHHHHHHHHHHHHH	19.10	26643407
608	Phosphorylation	RVCSPIISGLYQGAG HHHHHHHHHHHCCCC	24.38	26643407
611	Phosphorylation	SPIISGLYQGAGAPG HHHHHHHHCCCCCCC	14.39	20415495
628	Ubiquitination	GFGAQAPKGASGSGP CCCCCCCCCCCCCCC	70.85	-
631	Phosphorylation	AQAPKGASGSGPTIE CCCCCCCCCCCCCCC	42.00	23375375
633	Phosphorylation	APKGASGSGPTIEEV CCCCCCCCCCCCCCC	38.82	26643407
636	Phosphorylation	GASGSGPTIEEVD-- CCCCCCCCCCCCC--	44.54	29899451

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

Oops, there are no upstream regulatory protein records of HS71A_MOUSE !!

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
77	K	Acetylation	In response to cellular stress, acetylated at Lys-77 by NA110 and then gradually deacetylated by HDAC4 at later stages.	-

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_MOUSE !!

Protein-Protein Interaction

Oops, there are no PPI records of HS71A_MOUSE !!

Drug and Disease Associations

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