E3 SUMO-protein ligase PIAS4 - Homo sapiens (Human)

Contribute

Send feedback

Read comments (?) or add your own

Q8N2W9 (PIAS4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 98. History...

Clusters with 100%, 90%, 50% identity |

Documents (4) |

Third-party data

text xml rdf/xml gff fasta

Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
E3 SUMO-protein ligase PIAS4
EC=6.3.2.-

Alternative name(s):
PIASy
Protein inhibitor of activated STAT protein 4
Protein inhibitor of activated STAT protein gamma
Short name=PIAS-gamma

Gene names

Name:	PIAS4
Synonyms:	PIASG

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	510 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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 pathway, the Wnt pathway and the steroid hormone signaling pathway. Involved in gene silencing. Promotes PARK7 sumoylation. In Wnt signaling, represses LEF1 and enhances TCF4 transcriptional activities through promoting their sumoylations. Ref.8 Ref.9 Ref.10 Ref.12 Ref.13
Pathway	Protein modification; protein sumoylation.
Subunit structure	Interacts with AR, AXIN1, GATA2, LEF1, TP53 and STAT1 (IFNG-induced). Binds to AT-rich DNA sequences, known as matrix or scaffold attachment regions (MARs/SARs) By similarity. Interacts with TICAM1. Interacts with KLF8; the interaction results in SUMO ligation and repression of KLF8 transcriptional activity and of its cell cycle progression into G₁ phase. Ref.3 Ref.4 Ref.5 Ref.6 Ref.7 Ref.11 Ref.14
Subcellular location	Nucleus › PML body. Note: Colocalizes with SUMO1 and TCF7L2/TCF4 and LEF1 in a subset of PML (promyelocytic leukemia) nuclear bodies. Ref.4 Ref.8 Ref.12
Tissue specificity	Highly expressed in testis and, at lower levels, in spleen, prostate, ovary, colon and peripheral blood leukocytes. Ref.5
Domain	The LXXLL motif is a coregulator signature that is essential for transcriptional corepression.
Post-translational modification	Sumoylated. Lys-35 is the main site of sumoylation. Sumoylation is required for TCF4 sumoylation and transcriptional activitation. Represses LEF1 transcriptional activity. SUMO1 is the preferred conjugate. Ref.8 Ref.9 Ref.10 Ref.12 Ref.13
Sequence similarities	Belongs to the PIAS family. Contains 1 PINIT domain. Contains 1 SAP domain. Contains 1 SP-RING-type zinc finger.
Sequence caution	The sequence AAD45155.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Transcription Transcription regulation Ubl conjugation pathway Wnt signaling pathway
Cellular component	Nucleus
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Ligase Repressor
PTM	Acetylation Isopeptide bond Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of protein sumoylation Inferred from direct assay. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	PML body Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasm Inferred from direct assay. Source: BHF-UCL
Molecular function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW SUMO ligase activity Inferred from direct assay. Source: BHF-UCL ubiquitin protein ligase binding Inferred from physical interaction. Source: BHF-UCL zinc ion binding Non-traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct
HIF1A	Q16665	3	EBI-473160,EBI-447269
HTT	P42858	3	EBI-473160,EBI-466029
SUMO2	P61956	3	EBI-473160,EBI-473220
TADA3	O75528	2	EBI-473160,EBI-473249
TP53	P04637	2	EBI-473160,EBI-366083

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

Removed

Chain

2 – 510

509

E3 SUMO-protein ligase PIAS4

PRO_0000218982

Regions

Domain

12 – 46

SAP

Domain

119 – 279

161

PINIT

Zinc finger

311 – 388

SP-RING-type

Motif

20 – 24

LXXLL motif

Compositional bias

464 – 492

Asp/Glu-rich (acidic)

Amino acid modifications

Modified residue

N-acetylalanine Ref.15

Modified residue

114

N6-acetyllysine Ref.16

Modified residue

125

N6-acetyllysine Ref.16

Cross-link

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.12

Cross-link

128

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.12

Experimental info

Mutagenesis

23 – 24

LL → AA: Loss of repression of AR- and STAT1-induced transcription; no effect on AR- and STAT1-binding. Ref.4 Ref.5

Mutagenesis

K → R: Complete loss of sumoylation. No enhancement of TCF4 sumoylation. No effect on interaction with TCF4. Colocalizes with SUMO1 in nucleus but concentrated into nuclear granules. Ref.4 Ref.5 Ref.8 Ref.12

Mutagenesis

128

K → R: Some loss of sumoylation. Ref.4 Ref.5 Ref.8 Ref.12

Mutagenesis

342

C → A: Inhibits TCF4 sumoylation. Inhibits beta-catenin-mediated TCF7L2/TCF4 activity. No colocalization with TCF7L2/TCF4 in nuclear punctate structures; when associated with A-347. Ref.4 Ref.5

Mutagenesis

347

C → A: Inhibits TCF4 sumoylation. Inhibits beta-catenin-mediated TCF7L2/TCF4 activity. No colocalization with TCF7L2/TCF4 in nuclear punctate structures; when associated with A-342. AR- and STAT1-binding. Ref.4 Ref.5

Sequence conflict

178

N → K Ref.1

Sequence conflict

179 – 182

SREL → FQGM Ref.1

Sequence conflict

179 – 182

SREL → FQGM Ref.3

Sequence conflict

482

E → G in AAH66895. Ref.2

Sequences

Sequence

Length

Mass (Da)

Tools

Q8N2W9 [UniParc].

Last modified October 1, 2002. Version 1.
Checksum: 26AAA18246E1ACE3
Show »

FASTA

510

56,504

        10         20         30         40         50         60 
MAAELVEAKN MVMSFRVSDL QMLLGFVGRS KSGLKHELVT RALQLVQFDC SPELFKKIKE 

        70         80         90        100        110        120 
LYETRYAKKN SEPAPQPHRP LDPLTMHSTY DRAGAVPRTP LAGPNIDYPV LYGKYLNGLG 

       130        140        150        160        170        180 
RLPAKTLKPE VRLVKLPFFN MLDELLKPTE LVPQNNEKLQ ESPCIFALTP RQVELIRNSR 

       190        200        210        220        230        240 
ELQPGVKAVQ VVLRICYSDT SCPQEDQYPP NIAVKVNHSY CSVPGYYPSN KPGVEPKRPC 

       250        260        270        280        290        300 
RPINLTHLMY LSSATNRITV TWGNYGKSYS VALYLVRQLT SSELLQRLKT IGVKHPELCK 

       310        320        330        340        350        360 
ALVKEKLRLD PDSEIATTGV RVSLICPLVK MRLSVPCRAE TCAHLQCFDA VFYLQMNEKK 

       370        380        390        400        410        420 
PTWMCPVCDK PAPYDQLIID GLLSKILSEC EDADEIEYLV DGSWCPIRAE KERSCSPQGA 

       430        440        450        460        470        480 
ILVLGPSDAN GLLPAPSVNG SGALGSTGGG GPVGSMENGK PGADVVDLTL DSSSSSEDEE 

       490        500        510 
EEEEEEEDED EEGPRPKRRC PFQKGLVPAC

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Inhibition of Stat1-mediated gene activation by PIAS1." Liu B., Liao J., Rao X., Kushner S.A., Chung C.D., Chang D.D., Shuai K. Proc. Natl. Acad. Sci. U.S.A. 95:10626-10631(1998) [PubMed: 9724754] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: B-cell.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain, Lung and Skin.
[3]	"A putative protein inhibitor of activated STAT (PIASy) interacts with p53 and inhibits p53-mediated transactivation but not apoptosis." Nelson V., Davis G.E., Maxwell S.A. Apoptosis 6:221-234(2001) [PubMed: 11388671] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 10-510, INTERACTION WITH TP53.
[4]	"A transcriptional corepressor of Stat1 with an essential LXXLL signature motif." Liu B., Gross M., ten Hoeve J., Shuai K. Proc. Natl. Acad. Sci. U.S.A. 98:3203-3207(2001) [PubMed: 11248056] [Abstract] Cited for: INTERACTION WITH STAT1, SUBCELLULAR LOCATION, MUTAGENESIS OF 23-LEU-LEU-24.
[5]	"Distinct effects of PIAS proteins on androgen-mediated gene activation in prostate cancer cells." Gross M., Liu B., Tan J.-A., French F.S., Carey M., Shuai K. Oncogene 20:3880-3887(2001) [PubMed: 11439351] [Abstract] Cited for: INTERACTION WITH AR, TISSUE SPECIFICITY, MUTAGENESIS OF 23-LEU-LEU-24.
[6]	"SUMO-1 modification of the C-terminal KVEKVD of Axin is required for JNK activation but has no effect on Wnt signaling." Rui H.L., Fan E., Zhou H.M., Xu Z., Zhang Y., Lin S.C. J. Biol. Chem. 277:42981-42986(2002) [PubMed: 12223491] [Abstract] Cited for: INTERACTION WITH AXIN1.
[7]	"Modification of GATA-2 transcriptional activity in endothelial cells by the SUMO E3 ligase PIASy." Chun T.-H., Itoh H., Subramanian L., Iniguez-Lluhi J.A., Nakao K. Circ. Res. 92:1201-1208(2003) [PubMed: 12750312] [Abstract] Cited for: INTERACTION WITH GATA2.
[8]	"Sumoylation is involved in beta-catenin-dependent activation of Tcf-4." Yamamoto H., Ihara M., Matsuura Y., Kikuchi A. EMBO J. 22:2047-2059(2003) [PubMed: 12727872] [Abstract] Cited for: FUNCTION IN TCF4 SUMOYLATION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-35 AND LYS-128.
[9]	"Transactivation properties of c-Myb are critically dependent on two SUMO-1 acceptor sites that are conjugated in a PIASy enhanced manner." Dahle O., Andersen T.O., Nordgaard O., Matre V., Del Sal G., Gabrielsen O.S. Eur. J. Biochem. 270:1338-1348(2003) [PubMed: 12631292] [Abstract] Cited for: FUNCTION IN MYB SUMOYLATION.
[10]	"A synergy control motif within the attenuator domain of CCAAT/enhancer-binding protein alpha inhibits transcriptional synergy through its PIASy-enhanced modification by SUMO-1 or SUMO-3." Subramanian L., Benson M.D., Iniguez-Lluhi J.A. J. Biol. Chem. 278:9134-9141(2003) [PubMed: 12511558] [Abstract] Cited for: FUNCTION IN CEBPA SUMOYLATION.
[11]	"PIASy represses TRIF-induced ISRE and NF-kappaB activation but not apoptosis." Zhang J., Xu L.G., Han K.J., Wei X., Shu H.B. FEBS Lett. 570:97-101(2004) [PubMed: 15251447] [Abstract] Cited for: INTERACTION WITH TICAM1.
[12]	"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. 25:3506-3518(2005) [PubMed: 15831457] [Abstract] Cited for: SUMOYLATION AT LYS-35 AND LYS-128, FUNCTION IN TCF4 SUMOYLATION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-35 AND LYS-128.
[13]	"Proper SUMO-1 conjugation is essential to DJ-1 to exert its full activities." Shinbo Y., Niki T., Taira T., Ooe H., Takahashi-Niki K., Maita C., Seino C., Iguchi-Ariga S.M.M., Ariga H. Cell Death Differ. 13:96-108(2006) [PubMed: 15976810] [Abstract] Cited for: FUNCTION IN PARK7 SUMOYLATION.
[14]	"Sumoylation delimits KLF8 transcriptional activity associated with the cell cycle regulation." Wei H., Wang X., Gan B., Urvalek A.M., Melkoumian Z.K., Guan J.-L., Zhao J. J. Biol. Chem. 281:16664-16671(2006) [PubMed: 16617055] [Abstract] Cited for: INTERACTION WITH KLF8.
[15]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[16]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-114 AND LYS-125, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF077952 mRNA. Translation: AAC36703.1. BC010047 mRNA. Translation: AAH10047.2. BC029874 mRNA. Translation: AAH29874.1. BC066895 mRNA. Translation: AAH66895.1. AF164437 mRNA. Translation: AAD45155.1. Different initiation.
IPI	IPI00166500.
RefSeq	NP_056981.2. NM_015897.2.
UniGene	Hs.105779.
3D structure databases
ProteinModelPortal	Q8N2W9.
SMR	Q8N2W9. Positions 3-66, 122-407.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8N2W9. 45 interactions.
MINT	MINT-1181821.
STRING	Q8N2W9.
PTM databases
PhosphoSite	Q8N2W9.
Polymorphism databases
DMDM	34922831.
Proteomic databases
PRIDE	Q8N2W9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000262971; ENSP00000262971; ENSG00000105229.
GeneID	51588.
KEGG	hsa:51588.
UCSC	uc002lzg.1. human.
Organism-specific databases
CTD	51588.
GeneCards	GC19P004007.
H-InvDB	HIX0014651.
HGNC	HGNC:17002. PIAS4.
HPA	HPA010598.
MIM	605989. gene.
neXtProt	NX_Q8N2W9.
PharmGKB	PA134945903.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG17380.
GeneTree	ENSGT00550000074410.
HOGENOM	HBG315609.
HOVERGEN	HBG053598.
InParanoid	Q8N2W9.
OMA	LVPQNNE.
OrthoDB	EOG4THVT3.
PhylomeDB	Q8N2W9.
Enzyme and pathway databases
Pathway_Interaction_DB	ar_pathway. Coregulation of Androgen receptor activity. ifngpathway. IFN-gamma pathway. smad2_3pathway. Regulation of cytoplasmic and nuclear SMAD2/3 signaling. smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling.
Gene expression databases
ArrayExpress	Q8N2W9.
Bgee	Q8N2W9.
CleanEx	HS_PIAS4.
Genevestigator	Q8N2W9.
GermOnline	ENSG00000105229. Homo sapiens.
Family and domain databases
InterPro	IPR023321. PINIT. IPR003034. SAP_DNA-bd. IPR004181. Znf_MIZ. IPR013083. Znf_RING/FYVE/PHD. [Graphical view]
Gene3D	G3DSA:1.10.720.30. G3DSA:1.10.720.30. 1 hit. G3DSA:3.30.40.10. Znf_RING/FYVE/PHD. 1 hit.
KO	K04706.
Pfam	PF02891. zf-MIZ. 1 hit. [Graphical view]
SMART	SM00513. SAP. 1 hit. [Graphical view]
PROSITE	PS51466. PINIT. 1 hit. PS50800. SAP. 1 hit. PS51044. ZF_SP_RING. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	55429.
SOURCE	Search...

Entry information

Entry name

PIAS4_HUMAN

Accession

Primary (citable) accession number: Q8N2W9
Secondary accession number(s): O75926, Q96G19, Q9UN16

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 19, 2003
Last sequence update:	October 1, 2002
Last modified:	January 25, 2012
This is version 98 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Polymorphism databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents