UniProt Accession

 HSP71_HUMAN; P08107; B4E3B6; P19790; Q5JQI4; Q5SP17; Q9UQL9; Q9UQM0 

Genbank Protein ID

 M59828; M59830; M11717; AF134726; AF134726; BA000025; BA000025; AK304652; DQ388429; DQ451402; AL662834; AL662834; AL671762; AL671762; AL929592; AL929592; BC002453; BC009322; BC018740; BC057397; BC063507; M24743; M24744; X04676; X04677 

Genbank Nucleotide ID

 AAA63226.1; AAA63227.1; AAA52697.1; AAD21815.1; AAD21816.1; BAB63299.1; BAB63300.1; BAG65428.1; ABD48956.1; ABD96830.1; CAI17737.1; CAI17738.1; CAI18216.1; CAI18217.1; CAI18464.1; CAI18466.1; AAH02453.1; AAH09322.1; AAH18740.1; AAH57397.1; AAH63507.1; AAA59844.1; AAA59845.1; CAA28381.1; CAA28382.1 

Protein Name

 Heat shock 70 kDa protein 1A/1B 

Protein Synonyms/Alias

 Heat shock 70 kDa protein 1/2; HSP70-1/HSP70-2; HSP70.1/HSP70.2 

Gene Name

 HSPA1A; HSPA1B 

Gene Synonyms/Alias

 HSPA1 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
3	*****MAKAAAIGID	ubiquitination	[1]
56	RLIGDAAKNQVALNP	acetylation	[2]
56	RLIGDAAKNQVALNP	ubiquitination	[1, 3, 4, 5, 6, 7, 8]
71	QNTVFDAKRLIGRKF	ubiquitination	[1, 3, 4, 6, 7, 8, 9, 10, 11]
77	AKRLIGRKFGDPVVQ	ubiquitination	[1, 3, 4, 6, 7, 8]
88	PVVQSDMKHWPFQVI	acetylation	[2, 12]
88	PVVQSDMKHWPFQVI	ubiquitination	[1, 3, 4, 7, 8, 9]
100	QVINDGDKPKVQVSY	ubiquitination	[3]
102	INDGDKPKVQVSYKG	ubiquitination	[1]
108	PKVQVSYKGETKAFY	acetylation	[2, 13, 14]
108	PKVQVSYKGETKAFY	ubiquitination	[1, 3, 4, 6, 7, 8, 11]
112	VSYKGETKAFYPEEI	ubiquitination	[1, 3, 4, 8, 15]
126	ISSMVLTKMKEIAEA	ubiquitination	[1, 3, 4, 7, 8, 15]
128	SMVLTKMKEIAEAYL	ubiquitination	[3, 7, 15]
159	DSQRQATKDAGVIAG	ubiquitination	[1, 3, 5, 8, 10, 16]
190	YGLDRTGKGERNVLI	ubiquitination	[8]
246	NHFVEEFKRKHKKDI	acetylation	[13]
246	NHFVEEFKRKHKKDI	ubiquitination	[1, 3, 6, 8]
257	KKDISQNKRAVRRLR	ubiquitination	[1, 3, 10]
319	STLEPVEKALRDAKL	acetylation	[13]
319	STLEPVEKALRDAKL	ubiquitination	[1, 3, 6, 8]
325	EKALRDAKLDKAQIH	ubiquitination	[3]
328	LRDAKLDKAQIHDLV	ubiquitination	[1, 6, 7, 8]
348	TRIPKVQKLLQDFFN	acetylation	[13]
348	TRIPKVQKLLQDFFN	ubiquitination	[1, 3, 6, 7, 8, 16]
361	FNGRDLNKSINPDEA	ubiquitination	[1, 3]
415	GVMTALIKRNSTIPT	ubiquitination	[6]
423	RNSTIPTKQTQIFTT	ubiquitination	[1, 3, 8]
451	EGERAMTKDNNLLGR	ubiquitination	[1, 3, 5, 8, 10]
497	ATDKSTGKANKITIT	ubiquitination	[1]
500	KSTGKANKITITNDK	acetylation	[13]
500	KSTGKANKITITNDK	ubiquitination	[1, 3, 6, 8]
507	KITITNDKGRLSKEE	ubiquitination	[1, 3, 8]
512	NDKGRLSKEEIERMV	ubiquitination	[1, 3, 5, 8, 16]
524	RMVQEAEKYKAEDEV	acetylation	[13]
524	RMVQEAEKYKAEDEV	ubiquitination	[1, 3, 6, 7, 8, 10, 15, 16]
526	VQEAEKYKAEDEVQR	ubiquitination	[1, 3, 5, 6, 8, 15]
539	QRERVSAKNALESYA	ubiquitination	[1, 3, 5, 8]
550	ESYAFNMKSAVEDEG	ubiquitination	[1, 3, 6, 8, 15]
559	AVEDEGLKGKISEAD	ubiquitination	[1, 3, 6, 8]
561	EDEGLKGKISEADKK	ubiquitination	[1, 3]
573	DKKKVLDKCQEVISW	ubiquitination	[3, 6]
597	DEFEHKRKELEQVCN	ubiquitination	[1, 3, 5, 6, 8, 15]
628	GFGAQGPKGGSGSGP	ubiquitination	[1, 3, 5, 8, 10]

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] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [3] 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]
 [4] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [5] 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]
 [6] 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]
 [7] 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]
 [8] 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]
 [9] A data set of human endogenous protein ubiquitination sites.
 Shi Y, Chan DW, Jung SY, Malovannaya A, Wang Y, Qin J.
 Mol Cell Proteomics. 2011 May;10(5):M110.002089. [PMID: 20972266]
 [10] 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]
 [11] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [12] Monoclonal antibody cocktail as an enrichment tool for acetylome analysis.
 Shaw PG, Chaerkady R, Zhang Z, Davidson NE, Pandey A.
 Anal Chem. 2011 May 15;83(10):3623-6. [PMID: 21466224]
 [13] 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]
 [14] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
 [15] 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]
 [16] 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] 

Functional Description

 In cooperation with other chaperones, Hsp70s stabilize preexistent proteins against aggregation and mediate the folding of newly translated polypeptides in the cytosol as well as within organelles. These chaperones participate in all these processes through their ability to recognize nonnative conformations of other proteins. They bind extended peptide segments with a net hydrophobic character exposed by polypeptides during translation and membrane translocation, or following stress-induced damage. In case of rotavirus A infection, serves as a post-attachment receptor for the virus to facilitate entry into the cell. 

Sequence Annotation

 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 108 108 N6-acetyllysine.
 MOD_RES 246 246 N6-acetyllysine.
 MOD_RES 348 348 N6-acetyllysine.
 MOD_RES 561 561 N6,N6,N6-trimethyllysine; by METTL21A; in
 MOD_RES 631 631 Phosphoserine.
 MOD_RES 633 633 Phosphoserine.
 MOD_RES 636 636 Phosphothreonine.  

Keyword

 3D-structure; Acetylation; Alternative splicing; ATP-binding; Chaperone; Complete proteome; Cytoplasm; Direct protein sequencing; Host cell receptor for virus entry; Methylation; Nucleotide-binding; Phosphoprotein; Polymorphism; Receptor; Reference proteome; Stress response. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 641 AA 

Protein Sequence

Gene Ontology

 GO:0016235; C:aggresome; IDA:UniProtKB.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005783; C:endoplasmic reticulum; TAS:UniProtKB.
 GO:0005739; C:mitochondrion; TAS:UniProtKB.
 GO:0016607; C:nuclear speck; IDA:UniProtKB.
 GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
 GO:0030529; C:ribonucleoprotein complex; IDA:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0044183; F:protein binding involved in protein folding; IDA:BHF-UCL.
 GO:0051082; F:unfolded protein binding; TAS:UniProtKB.
 GO:0010467; P:gene expression; TAS:Reactome.
 GO:0006402; P:mRNA catabolic process; IDA:UniProtKB.
 GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
 GO:0030308; P:negative regulation of cell growth; IMP:UniProtKB.
 GO:0008285; P:negative regulation of cell proliferation; IMP:UniProtKB.
 GO:0090084; P:negative regulation of inclusion body assembly; IDA:BHF-UCL.
 GO:0045648; P:positive regulation of erythrocyte differentiation; IMP:UniProtKB.
 GO:0042026; P:protein refolding; IDA:BHF-UCL.
 GO:0006986; P:response to unfolded protein; IDA:UniProtKB. 

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.