UniProt Accession

 HSP74_HUMAN; P34932; O95756; Q2TAL4 

Genbank Protein ID

 AB023420; AC113410; BC110861; BC126122; BC126124; L12723 

Genbank Nucleotide ID

 BAA75062.1; AAI10862.1; AAI26123.1; AAI26125.1; AAA02807.1 

Protein Name

 Heat shock 70 kDa protein 4 

Protein Synonyms/Alias

 HSP70RY; Heat shock 70-related protein APG-2 

Gene Name

 HSPA4 

Gene Synonyms/Alias

 APG2 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
44	ACISFGPKNRSIGAA	ubiquitination	[1, 2]
53	RSIGAAAKSQVISNA	ubiquitination	[1, 2, 3]
61	SQVISNAKNTVQGFK	ubiquitination	[1, 2]
84	DPFVEAEKSNLAYDI	ubiquitination	[1]
124	VTAMLLSKLKETAES	ubiquitination	[1, 3, 4, 5, 6]
126	AMLLSKLKETAESVL	ubiquitination	[1, 2, 3]
135	TAESVLKKPVVDCVV	ubiquitination	[1, 2]
194	DLPALEEKPRNVVFV	acetylation	[2, 7]
194	DLPALEEKPRNVVFV	ubiquitination	[1, 2, 3, 5, 8]
221	AFNRGKLKVLATAFD	ubiquitination	[1, 2, 4]
235	DTTLGGRKFDEVLVN	ubiquitination	[1, 2]
272	RLSQECEKLKKLMSA	acetylation	[2, 7, 9, 10]
305	SGTMNRGKFLEMCND	ubiquitination	[1, 2, 6, 8, 11]
329	RSVLEQTKLKKEDIY	acetylation	[2]
329	RSVLEQTKLKKEDIY	ubiquitination	[1]
331	VLEQTKLKKEDIYAV	ubiquitination	[1]
332	LEQTKLKKEDIYAVE	ubiquitination	[1]
351	ATRIPAVKEKISKFF	ubiquitination	[2]
353	RIPAVKEKISKFFGK	ubiquitination	[1]
356	AVKEKISKFFGKELS	acetylation	[2]
356	AVKEKISKFFGKELS	ubiquitination	[1]
360	KISKFFGKELSTTLN	ubiquitination	[1, 3, 6]
388	AILSPAFKVREFSIT	ubiquitination	[1, 3, 4, 12]
422	SDCEVFSKNHAAPFS	acetylation	[2]
422	SDCEVFSKNHAAPFS	ubiquitination	[1, 2, 5, 11]
430	NHAAPFSKVLTFYRK	acetylation	[2, 9, 10]
430	NHAAPFSKVLTFYRK	ubiquitination	[1, 4]
437	KVLTFYRKEPFTLEA	ubiquitination	[3]
477	QSDGSSSKVKVKVRV	ubiquitination	[1, 2]
479	DGSSSKVKVKVRVNV	ubiquitination	[1]
517	METDQNAKEEEKMQV	ubiquitination	[3]
543	QQTPAENKAESEEME	ubiquitination	[3, 5, 6]
557	ETSQAGSKDKKMDQP	acetylation	[7]
557	ETSQAGSKDKKMDQP	methylation	[13]
557	ETSQAGSKDKKMDQP	ubiquitination	[3, 6]
559	SQAGSKDKKMDQPPQ	methylation	[13]
568	MDQPPQAKKAKVKTS	ubiquitination	[3]
573	QAKKAKVKTSTVDLP	ubiquitination	[3, 6]
609	GKMIMQDKLEKERND	ubiquitination	[1, 3]
618	EKERNDAKNAVEEYV	ubiquitination	[1, 2]
631	YVYEMRDKLSGEYEK	acetylation	[2]
631	YVYEMRDKLSGEYEK	ubiquitination	[2]
638	KLSGEYEKFVSEDDR	ubiquitination	[3, 4, 6, 8]
668	EDGEDQPKQVYVDKL	ubiquitination	[3, 6]
674	PKQVYVDKLAELKNL	acetylation	[2, 7, 10]
674	PKQVYVDKLAELKNL	ubiquitination	[1, 2, 4]
679	VDKLAELKNLGQPIK	acetylation	[9, 10]
679	VDKLAELKNLGQPIK	ubiquitination	[1, 4]
686	KNLGQPIKIRFQESE	ubiquitination	[1, 2, 3, 4]
697	QESEERPKLFEELGK	ubiquitination	[4]
704	KLFEELGKQIQQYMK	ubiquitination	[1, 4]
711	KQIQQYMKIISSFKN	ubiquitination	[1, 2, 4]
719	IISSFKNKEDQYDHL	ubiquitination	[4]
733	LDAADMTKVEKSTNE	acetylation	[7]
736	ADMTKVEKSTNEAME	ubiquitination	[1, 4]
748	AMEWMNNKLNLQNKQ	ubiquitination	[1, 4]
754	NKLNLQNKQSLTMDP	ubiquitination	[2, 3, 4, 6]
773	KEIEAKIKELTSTCS	ubiquitination	[4]
785	TCSPIISKPKPKVEP	ubiquitination	[4]
794	KPKVEPPKEEQKNAE	ubiquitination	[3, 5]
798	EPPKEEQKNAEQNGP	ubiquitination	[3]
833	VPSDSDKKLPEMDID	ubiquitination	[3]

Reference

 [1] 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]
 [2] 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]
 [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] 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]
 [5] 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]
 [6] 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]
 [7] 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]
 [8] 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]
 [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] 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]
 [11] 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]
 [12] 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]
 [13] Large-scale global identification of protein lysine methylation in vivo.
 Cao XJ, Arnaudo AM, Garcia BA.
 Epigenetics. 2013 May 1;8(5):477-85. [PMID: 23644510] 

Functional Description

  

Sequence Annotation

 MOD_RES 76 76 Phosphoserine.
 MOD_RES 89 89 Phosphotyrosine.
 MOD_RES 336 336 Phosphotyrosine.
 MOD_RES 430 430 N6-acetyllysine.
 MOD_RES 538 538 Phosphothreonine.
 MOD_RES 546 546 Phosphoserine.
 MOD_RES 660 660 Phosphotyrosine (By similarity).
 MOD_RES 679 679 N6-acetyllysine.  

Keyword

 Acetylation; ATP-binding; Complete proteome; Cytoplasm; Direct protein sequencing; Nucleotide-binding; Phosphoprotein; Reference proteome; Stress response. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 840 AA 

Protein Sequence

Gene Ontology

 GO:0005737; C:cytoplasm; NAS:UniProtKB.
 GO:0005634; C:nucleus; IDA:HPA.
 GO:0005524; F:ATP binding; NAS:UniProtKB.
 GO:0051131; P:chaperone-mediated protein complex assembly; IDA:BHF-UCL.
 GO:0045040; P:protein import into mitochondrial outer membrane; IDA:BHF-UCL.
 GO:0006986; P:response to unfolded protein; NAS: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.