UniProt Accession

 HSP7C_HUMAN; P11142; Q9H3R6 

Genbank Protein ID

 Y00371; AB034951; AF352832; BC016179; BC016660; BC019816 

Genbank Nucleotide ID

 CAA68445.1; BAB18615.1; AAK17898.1; AAH16179.1; AAH16660.1; AAH19816.1 

Protein Name

 Heat shock cognate 71 kDa protein 

Protein Synonyms/Alias

 Heat shock 70 kDa protein 8 

Gene Name

 HSPA8 

Gene Synonyms/Alias

 HSC70; HSP73; HSPA10 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
3	*****MSKGPAVGID	ubiquitination	[1, 2, 3]
56	RLIGDAAKNQVAMNP	ubiquitination	[1, 2, 3, 4, 5, 6, 7]
71	TNTVFDAKRLIGRRF	ubiquitination	[1, 2, 3, 4, 6, 7, 8]
88	AVVQSDMKHWPFMVV	acetylation	[9]
88	AVVQSDMKHWPFMVV	ubiquitination	[1, 2, 3, 4, 7]
108	PKVQVEYKGETKSFY	acetylation	[9]
108	PKVQVEYKGETKSFY	ubiquitination	[2, 3, 4, 6, 7, 8]
112	VEYKGETKSFYPEEV	ubiquitination	[1, 3, 4, 7]
126	VSSMVLTKMKEIAEA	ubiquitination	[1, 2, 3, 4, 6, 7, 10]
128	SMVLTKMKEIAEAYL	ubiquitination	[2, 3, 4, 7]
137	IAEAYLGKTVTNAVV	ubiquitination	[1, 3, 4, 5, 7]
159	DSQRQATKDAGTIAG	ubiquitination	[1, 2, 3, 4, 5, 6, 7]
187	AIAYGLDKKVGAERN	ubiquitination	[1, 2, 3, 4, 5, 7]
188	IAYGLDKKVGAERNV	ubiquitination	[2, 3, 4, 5, 7]
246	NHFIAEFKRKHKKDI	acetylation	[9]
246	NHFIAEFKRKHKKDI	ubiquitination	[1, 2, 3, 4, 5, 6, 7]
248	FIAEFKRKHKKDISE	ubiquitination	[3]
251	EFKRKHKKDISENKR	ubiquitination	[4]
257	KKDISENKRAVRRLR	ubiquitination	[1, 2, 4]
319	GTLDPVEKALRDAKL	acetylation	[9]
319	GTLDPVEKALRDAKL	ubiquitination	[1, 2, 3, 4, 5, 6, 7]
325	EKALRDAKLDKSQIH	ubiquitination	[2, 3, 4, 7, 11]
328	LRDAKLDKSQIHDIV	ubiquitination	[1, 2, 3, 4, 6, 7]
345	GGSTRIPKIQKLLQD	ubiquitination	[3, 7]
348	TRIPKIQKLLQDFFN	acetylation	[9, 12]
348	TRIPKIQKLLQDFFN	ubiquitination	[1, 2, 3, 4, 6, 7, 8]
357	LQDFFNGKELNKSIN	ubiquitination	[1, 2, 3, 4, 7]
361	FNGKELNKSINPDEA	ubiquitination	[1, 3, 4, 5, 7]
423	RNTTIPTKQTQTFTT	ubiquitination	[1, 3, 4, 5, 6, 7]
451	EGERAMTKDNNLLGK	ubiquitination	[1, 3, 4, 5, 6, 7]
458	KDNNLLGKFELTGIP	ubiquitination	[1, 4, 6, 7]
497	AVDKSTGKENKITIT	ubiquitination	[3, 6, 7]
500	KSTGKENKITITNDK	ubiquitination	[3, 4, 6, 7]
507	KITITNDKGRLSKED	ubiquitination	[2, 3, 4, 5, 6, 7, 8, 11]
512	NDKGRLSKEDIERMV	acetylation	[9]
512	NDKGRLSKEDIERMV	ubiquitination	[1, 2, 3, 4, 5, 6, 7, 11]
524	RMVQEAEKYKAEDEK	acetylation	[9]
524	RMVQEAEKYKAEDEK	ubiquitination	[1, 2, 3, 4, 5, 6, 7, 11]
526	VQEAEKYKAEDEKQR	ubiquitination	[3, 4, 7]
531	KYKAEDEKQRDKVSS	ubiquitination	[2, 4, 6, 7]
535	EDEKQRDKVSSKNSL	ubiquitination	[2]
539	QRDKVSSKNSLESYA	ubiquitination	[1, 2, 3, 4, 6, 7]
550	ESYAFNMKATVEDEK	ubiquitination	[4, 5, 7]
557	KATVEDEKLQGKIND	ubiquitination	[3, 4, 7]
561	EDEKLQGKINDEDKQ	ubiquitination	[4]
573	DKQKILDKCNEIINW	ubiquitination	[3, 4]
583	EIINWLDKNQTAEKE	ubiquitination	[1, 2, 3, 4, 6, 7]
589	DKNQTAEKEEFEHQQ	acetylation	[9]
589	DKNQTAEKEEFEHQQ	ubiquitination	[3, 4, 7]
597	EEFEHQQKELEKVCN	acetylation	[9]
597	EEFEHQQKELEKVCN	ubiquitination	[1, 3, 4, 5, 7]
601	HQQKELEKVCNPIIT	acetylation	[9]
601	HQQKELEKVCNPIIT	ubiquitination	[1, 3, 4, 5, 6, 7, 8]
609	VCNPIITKLYQSAGG	ubiquitination	[7]

Reference

 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [2] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [3] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [4] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [5] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
 [6] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [7] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [8] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [9] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [10] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
 Xu G, Paige JS, Jaffrey SR.
 Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865]
 [11] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
 Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
 Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
 [12] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786] 

Functional Description

 Acts as a repressor of transcriptional activation. Inhibits the transcriptional coactivator activity of CITED1 on Smad-mediated transcription. Chaperone. 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. 

Sequence Annotation

 REGION 186 377 Interaction with BAG1.
 MOD_RES 2 2 N-acetylserine.
 MOD_RES 15 15 Phosphotyrosine (By similarity).
 MOD_RES 41 41 Phosphotyrosine (By similarity).
 MOD_RES 153 153 Phosphoserine.
 MOD_RES 246 246 N6-acetyllysine.
 MOD_RES 319 319 N6-acetyllysine.
 MOD_RES 362 362 Phosphoserine.
 MOD_RES 561 561 N6,N6,N6-trimethyllysine; by METTL21A; in
 MOD_RES 589 589 N6-acetyllysine.
 MOD_RES 597 597 N6-acetyllysine.
 MOD_RES 601 601 N6-acetyllysine.  

Keyword

 3D-structure; Acetylation; Alternative splicing; ATP-binding; Chaperone; Complete proteome; Cytoplasm; Direct protein sequencing; Host-virus interaction; Methylation; mRNA processing; mRNA splicing; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repressor; Spliceosome; Stress response; Transcription; Transcription regulation; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 646 AA 

Protein Sequence

Gene Ontology

 GO:0009986; C:cell surface; IDA:UniProtKB.
 GO:0061202; C:clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane; TAS:Reactome.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
 GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
 GO:0005730; C:nucleolus; IDA:UniProtKB.
 GO:0005886; C:plasma membrane; TAS:Reactome.
 GO:0000974; C:Prp19 complex; IDA:UniProtKB.
 GO:0030529; C:ribonucleoprotein complex; IDA:UniProtKB.
 GO:0005681; C:spliceosomal complex; IEA:UniProtKB-KW.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0042623; F:ATPase activity, coupled; NAS:UniProtKB.
 GO:0016044; P:cellular membrane organization; TAS:Reactome.
 GO:0051085; P:chaperone mediated protein folding requiring cofactor; IEA:Compara.
 GO:0010467; P:gene expression; TAS:Reactome.
 GO:0016071; P:mRNA metabolic process; TAS:Reactome.
 GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
 GO:0045892; P:negative regulation of transcription, DNA-dependent; IDA:UniProtKB.
 GO:0007269; P:neurotransmitter secretion; TAS:Reactome.
 GO:0006892; P:post-Golgi vesicle-mediated transport; TAS:Reactome.
 GO:0006457; P:protein folding; NAS:UniProtKB.
 GO:0051726; P:regulation of cell cycle; IEA:Compara.
 GO:0006986; P:response to unfolded protein; NAS:UniProtKB.
 GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 

Interpro

 IPR018181; Heat_shock_70_CS.
 IPR013126; Hsp_70_fam. 

Pfam

 PF00012; HSP70 

SMART

  

PROSITE

 PS00297; HSP70_1
 PS00329; HSP70_2
 PS01036; HSP70_3 

PRINTS

 PR00301; HEATSHOCK70.