HSP7C_RAT - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: HSP7C_RAT
• UniProt AC: P63018
• Protein Name: Heat shock cognate 71 kDa protein
• Gene Name: Hspa8
• Organism: Rattus norvegicus (Rat).
• Sequence Length: 646
• Subcellular Localization: Cytoplasm. Melanosome. Nucleus, nucleolus. Cell membrane. Localized in cytoplasmic mRNP granules containing untranslated mRNAs. Translocates rapidly from the cytoplasm to the nuclei, and especially to the nucleoli, upon heat shock (By similarity)..
• 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 of HSP70, 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 of HSP70 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. HSP70 goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The HSP70-associated co-chaperones are of three types: J-domain co-chaperones 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. Acts as a repressor of transcriptional activation. Inhibits the transcriptional coactivator activity of CITED1 on Smad-mediated transcription. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex. Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion. Participates in the ER-associated degradation (ERAD) quality control pathway in conjunction with J domain-containing co-chaperones and the E3 ligase STUB1..
• Protein Sequence: MSKGPAVGIDLGTTYSCVGVFQHGKVEIIANDQGNRTTPSYVAFTDTERLIGDAAKNQVAMNPTNTVFDAKRLIGRRFDDAVVQSDMKHWPFMVVNDAGRPKVQVEYKGETKSFYPEEVSSMVLTKMKEIAEAYLGKTVTNAVVTVPAYFNDSQRQATKDAGTIAGLNVLRIINEPTAAAIAYGLDKKVGAERNVLIFDLGGGTFDVSILTIEDGIFEVKSTAGDTHLGGEDFDNRMVNHFIAEFKRKHKKDISENKRAVRRLRTACERAKRTLSSSTQASIEIDSLYEGIDFYTSITRARFEELNADLFRGTLDPVEKALRDAKLDKSQIHDIVLVGGSTRIPKIQKLLQDFFNGKELNKSINPDEAVAYGAAVQAAILSGDKSENVQDLLLLDVTPLSLGIETAGGVMTVLIKRNTTIPTKQTQTFTTYSDNQPGVLIQVYEGERAMTKDNNLLGKFELTGIPPAPRGVPQIEVTFDIDANGILNVSAVDKSTGKENKITITNDKGRLSKEDIERMVQEAEKYKAEDEKQRDKVSSKNSLESYAFNMKATVEDEKLQGKINDEDKQKILDKCNEIISWLDKNQTAEKEEFEHQQKELEKVCNPIITKLYQSAGGMPGGMPGGFPGGGAPPSGGASSGPTIEEVD

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	------MSKGPAVGI ------CCCCCEEEE	46.44	-
41	Phosphorylation	GNRTTPSYVAFTDTE CCCCCCCEEEEECHH	9.30	-
56	Ubiquitination	RLIGDAAKNQVAMNP HHHHHHHHCCCCCCC	50.02	-
56	Acetylation	RLIGDAAKNQVAMNP HHHHHHHHCCCCCCC	50.02	51082509
71	Ubiquitination	TNTVFDAKRLIGRRF CCCHHHHHHHHCCCC	49.97	-
71	Acetylation	TNTVFDAKRLIGRRF CCCHHHHHHHHCCCC	49.97	174289
85	Phosphorylation	FDDAVVQSDMKHWPF CCCHHHCCCCCCCCE	28.23	30181290
88	Acetylation	AVVQSDMKHWPFMVV HHHCCCCCCCCEEEE	47.73	22902405
107	Phosphorylation	RPKVQVEYKGETKSF CCEEEEEECCCEECC	25.99	22609512
108	Ubiquitination	PKVQVEYKGETKSFY CEEEEEECCCEECCC	36.44	-
108	Acetylation	PKVQVEYKGETKSFY CEEEEEECCCEECCC	36.44	174303
112	Acetylation	VEYKGETKSFYPEEV EEECCCEECCCHHHH	33.98	22902405
128	Acetylation	SMVLTKMKEIAEAYL HHHHHHHHHHHHHHC	47.74	72627927
134	Phosphorylation	MKEIAEAYLGKTVTN HHHHHHHHCCCCCCC	13.90	30181290
137	Acetylation	IAEAYLGKTVTNAVV HHHHHCCCCCCCEEE	36.91	22902405
138	Phosphorylation	AEAYLGKTVTNAVVT HHHHCCCCCCCEEEE	30.66	22673903
140	Phosphorylation	AYLGKTVTNAVVTVP HHCCCCCCCEEEEEE	23.77	22673903
145	Phosphorylation	TVTNAVVTVPAYFND CCCCEEEEEECCCCH	17.74	23984901
153	Phosphorylation	VPAYFNDSQRQATKD EECCCCHHHCCHHCC	28.50	23984901
159	Ubiquitination	DSQRQATKDAGTIAG HHHCCHHCCCCCCCC	48.90	-
159	Acetylation	DSQRQATKDAGTIAG HHHCCHHCCCCCCCC	48.90	22902405
187	Ubiquitination	AIAYGLDKKVGAERN HHHHCCCCCCCCCCC	55.17	-
226	Phosphorylation	VKSTAGDTHLGGEDF EEECCCCCCCCCCCC	20.34	22673903
246	Ubiquitination	NHFIAEFKRKHKKDI HHHHHHHHHHHHCCC	52.63	-
246	Acetylation	NHFIAEFKRKHKKDI HHHHHHHHHHHHCCC	52.63	25786129
254	Phosphorylation	RKHKKDISENKRAVR HHHHCCCHHHHHHHH	45.29	26437020
257	Acetylation	KKDISENKRAVRRLR HCCCHHHHHHHHHHH	37.37	2401839
319	Ubiquitination	GTLDPVEKALRDAKL CCCCHHHHHHHHCCC	53.61	-
319	Succinylation	GTLDPVEKALRDAKL CCCCHHHHHHHHCCC	53.61	-
319	Succinylation	GTLDPVEKALRDAKL CCCCHHHHHHHHCCC	53.61	-
319	Acetylation	GTLDPVEKALRDAKL CCCCHHHHHHHHCCC	53.61	22902405
325	Ubiquitination	EKALRDAKLDKSQIH HHHHHHCCCCHHHCC	62.60	-
325	Acetylation	EKALRDAKLDKSQIH HHHHHHCCCCHHHCC	62.60	22902405
328	Acetylation	LRDAKLDKSQIHDIV HHHCCCCHHHCCEEE	55.48	22902405
328	Ubiquitination	LRDAKLDKSQIHDIV HHHCCCCHHHCCEEE	55.48	-
329	Phosphorylation	RDAKLDKSQIHDIVL HHCCCCHHHCCEEEE	33.75	28432305
345	Ubiquitination	GGSTRIPKIQKLLQD CCCCCCHHHHHHHHH	56.23	-
348	Ubiquitination	TRIPKIQKLLQDFFN CCCHHHHHHHHHHHC	55.42	-
348	Acetylation	TRIPKIQKLLQDFFN CCCHHHHHHHHHHHC	55.42	22640793
357	Acetylation	LQDFFNGKELNKSIN HHHHHCCCCCCCCCC	61.20	72584815
361	Acetylation	FNGKELNKSINPDEA HCCCCCCCCCCHHHH	66.39	66710025
362	Phosphorylation	NGKELNKSINPDEAV CCCCCCCCCCHHHHH	26.90	27097102
371	Phosphorylation	NPDEAVAYGAAVQAA CHHHHHHHHHHHHHH	10.74	-
400	Phosphorylation	LLDVTPLSLGIETAG EEECCCCCCCCEECC	26.25	16641100
405	Phosphorylation	PLSLGIETAGGVMTV CCCCCCEECCCEEEE	28.78	16641100
411	Phosphorylation	ETAGGVMTVLIKRNT EECCCEEEEEEECCC	15.11	16641100
451	Ubiquitination	EGERAMTKDNNLLGK ECCCCCCCCCCCCCE	45.43	-
451	Acetylation	EGERAMTKDNNLLGK ECCCCCCCCCCCCCE	45.43	66734677
458	Acetylation	KDNNLLGKFELTGIP CCCCCCCEEEEECCC	35.32	22902405
469	Methylation	TGIPPAPRGVPQIEV ECCCCCCCCCCEEEE	61.93	18600831
500	Ubiquitination	KSTGKENKITITNDK CCCCCCCCEEEECCC	42.17	-
500	Acetylation	KSTGKENKITITNDK CCCCCCCCEEEECCC	42.17	24739131
507	Ubiquitination	KITITNDKGRLSKED CEEEECCCCCCCHHH	48.26	-
507	Acetylation	KITITNDKGRLSKED CEEEECCCCCCCHHH	48.26	22902405
512	Succinylation	NDKGRLSKEDIERMV CCCCCCCHHHHHHHH	65.09	-
512	Ubiquitination	NDKGRLSKEDIERMV CCCCCCCHHHHHHHH	65.09	-
512	Acetylation	NDKGRLSKEDIERMV CCCCCCCHHHHHHHH	65.09	22902405
512	Succinylation	NDKGRLSKEDIERMV CCCCCCCHHHHHHHH	65.09	-
524	Acetylation	RMVQEAEKYKAEDEK HHHHHHHHHCHHCHH	60.13	22902405
524	Ubiquitination	RMVQEAEKYKAEDEK HHHHHHHHHCHHCHH	60.13	-
525	Phosphorylation	MVQEAEKYKAEDEKQ HHHHHHHHCHHCHHH	13.61	-
526	Ubiquitination	VQEAEKYKAEDEKQR HHHHHHHCHHCHHHH	57.26	-
526	Acetylation	VQEAEKYKAEDEKQR HHHHHHHCHHCHHHH	57.26	22902405
531	Acetylation	KYKAEDEKQRDKVSS HHCHHCHHHHHHCCC	64.06	22902405
531	Ubiquitination	KYKAEDEKQRDKVSS HHCHHCHHHHHHCCC	64.06	-
537	Phosphorylation	EKQRDKVSSKNSLES HHHHHHCCCCHHHHH	41.14	28689409
538	Phosphorylation	KQRDKVSSKNSLESY HHHHHCCCCHHHHHH	38.55	25575281
539	Ubiquitination	QRDKVSSKNSLESYA HHHHCCCCHHHHHHH	42.95	-
541	Phosphorylation	DKVSSKNSLESYAFN HHCCCCHHHHHHHHE	36.93	27097102
544	Phosphorylation	SSKNSLESYAFNMKA CCCHHHHHHHHEEEC	27.36	22673903
545	Phosphorylation	SKNSLESYAFNMKAT CCHHHHHHHHEEECE	13.06	25575281
561	Methylation	EDEKLQGKINDEDKQ CCHHHCCCCCHHHHH	25.94	-
561	"N6,N6,N6-trimethyllysine"	EDEKLQGKINDEDKQ CCHHHCCCCCHHHHH	25.94	-
574	S-nitrosocysteine	KQKILDKCNEIISWL HHHHHHHHHHHHHHH	5.73	-
574	S-nitrosylation	KQKILDKCNEIISWL HHHHHHHHHHHHHHH	5.73	17629318
579	Phosphorylation	DKCNEIISWLDKNQT HHHHHHHHHHHHCCC	27.52	25575281
586	Phosphorylation	SWLDKNQTAEKEEFE HHHHHCCCHHHHHHH	46.29	25575281
589	Succinylation	DKNQTAEKEEFEHQQ HHCCCHHHHHHHHHH	61.14	26843850
589	Ubiquitination	DKNQTAEKEEFEHQQ HHCCCHHHHHHHHHH	61.14	-
589	Acetylation	DKNQTAEKEEFEHQQ HHCCCHHHHHHHHHH	61.14	22902405
597	Ubiquitination	EEFEHQQKELEKVCN HHHHHHHHHHHHHHH	58.66	-
597	Acetylation	EEFEHQQKELEKVCN HHHHHHHHHHHHHHH	58.66	22902405
601	Acetylation	HQQKELEKVCNPIIT HHHHHHHHHHHHHHH	65.79	22640833
603	S-nitrosocysteine	QKELEKVCNPIITKL HHHHHHHHHHHHHHH	8.10	-
603	S-nitrosylation	QKELEKVCNPIITKL HHHHHHHHHHHHHHH	8.10	17629318
611	Phosphorylation	NPIITKLYQSAGGMP HHHHHHHHHHCCCCC	11.28	25403869
613	Phosphorylation	IITKLYQSAGGMPGG HHHHHHHHCCCCCCC	18.48	25403869
633	Phosphorylation	PGGGAPPSGGASSGP CCCCCCCCCCCCCCC	49.12	27097102
637	Phosphorylation	APPSGGASSGPTIEE CCCCCCCCCCCCCCC	38.82	27097102
638	Phosphorylation	PPSGGASSGPTIEEV CCCCCCCCCCCCCCC	48.54	27097102
641	Phosphorylation	GGASSGPTIEEVD-- CCCCCCCCCCCCC--	44.54	27097102

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

Oops, there are no upstream regulatory protein records of HSP7C_RAT !!

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
561	K	Methylation	Trimethylation at Lys-561 reduces fibrillar SNCA binding.	-

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of HSP7C_RAT !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
DNJB1_HUMAN	DNAJB1	physical	9920933
DNJC3_BOVIN	DNAJC3	physical	9920933
DNJC7_HUMAN	DNAJC7	physical	10567422
TTC1_HUMAN	TTC1	physical	10567422
SGTA_HUMAN	SGTA	physical	10567422
STIP1_HUMAN	STIP1	physical	10567422

Drug and Disease Associations

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