UniProt Accession

 PIAS4_HUMAN; Q8N2W9; O75926; Q96G19; Q9UN16 

Genbank Protein ID

 AF077952; BC010047; BC029874; BC066895; AF164437 

Genbank Nucleotide ID

 AAC36703.1; AAH10047.2; AAH29874.1; AAH66895.1; AAD45155.1 

Protein Name

 E3 SUMO-protein ligase PIAS4 

Protein Synonyms/Alias

 PIASy; Protein inhibitor of activated STAT protein 4; Protein inhibitor of activated STAT protein gamma; PIAS-gamma 

Gene Name

 PIAS4 

Gene Synonyms/Alias

 PIASG 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
9	AAELVEAKNMVMSFR	ubiquitination	[1]
31	LGFVGRSKSGLKHEL	ubiquitination	[1]
35	GRSKSGLKHELVTRA	sumoylation	[2]
35	GRSKSGLKHELVTRA	ubiquitination	[1]
56	DCSPELFKKIKELYE	ubiquitination	[3]
57	CSPELFKKIKELYET	ubiquitination	[1]
59	PELFKKIKELYETRY	ubiquitination	[1]
69	YETRYAKKNSEPAPQ	ubiquitination	[1]
114	DYPVLYGKYLNGLGR	acetylation	[4]
114	DYPVLYGKYLNGLGR	ubiquitination	[1, 3, 5, 6, 7]
125	GLGRLPAKTLKPEVR	acetylation	[4, 8]
125	GLGRLPAKTLKPEVR	ubiquitination	[1]
128	RLPAKTLKPEVRLVK	ubiquitination	[1, 8]
187	RELQPGVKAVQVVLR	ubiquitination	[1]
231	PGYYPSNKPGVEPKR	ubiquitination	[1, 6, 8]
294	RLKTIGVKHPELCKA	ubiquitination	[1]
300	VKHPELCKALVKEKL	ubiquitination	[1, 6]
306	CKALVKEKLRLDPDS	ubiquitination	[1]
330	SLICPLVKMRLSVPC	ubiquitination	[1, 6]
411	WCPIRAEKERSCSPQ	ubiquitination	[1]
504	KRRCPFQKGLVPAC*	ubiquitination	[1]

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] SUMO-1 modification of PIASy, an E3 ligase, is necessary for PIASy-dependent activation of Tcf-4.
 Ihara M, Yamamoto H, Kikuchi A.
 Mol Cell Biol. 2005 May;25(9):3506-18. [PMID: 15831457]
 [3] 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]
 [4] 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]
 [5] 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]
 [6] 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]
 [7] 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]
 [8] 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] 

Functional Description

 Functions as an E3-type small ubiquitin-like modifier (SUMO) ligase, stabilizing the interaction between UBE2I and the substrate, and as a SUMO-tethering factor. Plays a crucial role as a transcriptional coregulation in various cellular pathways, including the STAT pathway, the p53/TP53 pathway, the Wnt pathway and the steroid hormone signaling pathway. Involved in gene silencing. Mediates sumoylation of CEBPA, PARK7, HERC2, MYB, TCF4 and RNF168. In Wnt signaling, represses LEF1 and enhances TCF4 transcriptional activities through promoting their sumoylations. 

Sequence Annotation

 DOMAIN 12 46 SAP.
 DOMAIN 119 279 PINIT.
 ZN_FING 311 388 SP-RING-type.
 MOTIF 20 24 LXXLL motif.
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 114 114 N6-acetyllysine.
 CROSSLNK 35 35 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 128 128 Glycyl lysine isopeptide (Lys-Gly)  

Keyword

 Acetylation; Complete proteome; DNA-binding; Isopeptide bond; Ligase; Metal-binding; Nucleus; Reference proteome; Repressor; Transcription; Transcription regulation; Ubl conjugation; Ubl conjugation pathway; Wnt signaling pathway; Zinc; Zinc-finger. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 510 AA 

Protein Sequence

Gene Ontology

 GO:0005737; C:cytoplasm; IDA:BHF-UCL.
 GO:0016363; C:nuclear matrix; IEA:Compara.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
 GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
 GO:0019789; F:SUMO ligase activity; IMP:UniProtKB.
 GO:0008270; F:zinc ion binding; NAS:UniProtKB.
 GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IEA:Compara.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Compara.
 GO:0045892; P:negative regulation of transcription, DNA-dependent; IDA:UniProtKB.
 GO:1902174; P:positive regulation of keratinocyte apoptotic process; ISS:BHF-UCL.
 GO:0033235; P:positive regulation of protein sumoylation; IDA:UniProtKB.
 GO:0016925; P:protein sumoylation; IMP:UniProtKB.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
 GO:0016055; P:Wnt receptor signaling pathway; IEA:UniProtKB-KW. 

Interpro

 IPR027224; PIAS4.
 IPR023321; PINIT.
 IPR003034; SAP_dom.
 IPR004181; Znf_MIZ. 

Pfam

 PF14324; PINIT
 PF02891; zf-MIZ 

SMART

 SM00513; SAP 

PROSITE

 PS51466; PINIT
 PS50800; SAP
 PS51044; ZF_SP_RING 

PRINTS