Q9Y6X2 (PIAS3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
E3 SUMO-protein ligase PIAS3
EC=6.3.2.-

Alternative name(s):
Protein inhibitor of activated STAT protein 3

Gene names

Name:

PIAS3

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	628 AA.
Sequence status	Complete.
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 and the steroid hormone signaling pathway. Involved in regulating STAT3 signaling via inhibiting STAT3 DNA-binding and suppressing cell growth. Ref.4
Pathway	Protein modification; protein sumoylation.
Subunit structure	Monomer By similarity. Binds SUMO1 and UBE2I. Interacts with BCL11A, HMGA2, IRF1, MITF and NCOA2. Interacts with STAT5; the interaction occurs on stimulation by PRL. Interacts with GFI1; the interaction relieves the inhibitory effect of PIAS3 on STAT3-mediated transcriptional activity By similarity. Interacts with AR, PLAG1 and ZFHX3. Interacts with STAT3; the interaction occurs on stimulation by IL6, CNTF or OSM and inhibits the DNA binding activity of STAT3. Ref.4 Ref.5 Ref.6 Ref.7 Ref.8
Subcellular location	Cytoplasm. Nucleus. Note: Mainly cytoplasmic but shuttles between the nucleus and cytoplasm. Transported to the nucleus on interaction with phosphorylated STAT3. Colocalizes with GFI1 in nuclear dots By similarity.
Tissue specificity	Isoform 1 is expressed in most tissues except thymus and small intestine. Isoform 3 is expressed only in brain, heart, thymus, muscle, lung, testis, lactating breast and embryonic stem cells. Ref.4
Induction	By dihydrotestosterone (DHT) in prostate cancer cells. Ref.5
Domain	The PINIT domain of PIAS3 is required for STAT3-PIAS3 interaction and for transloaction to the nucleus. The LXXLL motif is a transcriptional coregulator signature.
Post-translational modification	Sumoylated By similarity.
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 BAA78533.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Transcription Transcription regulation Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Domain	Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
PTM	Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	positive regulation of protein sumoylation Inferred from direct assay. Source: UniProtKB protein sumoylation Inferred from sequence or structural similarity. Source: UniProtKB regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nuclear speck Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	enzyme binding Inferred from physical interaction. Source: UniProtKB nucleic acid binding Inferred from electronic annotation. Source: InterPro protein C-terminus binding Inferred from physical interaction Ref.7. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 628	628	E3 SUMO-protein ligase PIAS3		PRO_0000218979
Regions
	Domain	11 – 45	35	SAP
	Domain	115 – 280	166	PINIT
	Zinc finger	303 – 380	78	SP-RING-type
	Region	450 – 460	11	SUMO1-binding By similarity
	Motif	19 – 23	5	LXXLL motif
	Compositional bias	81 – 133	53	Pro-rich
Natural variations
	Natural variant	390	1	S → C. Corresponds to variant rs17354559 [ dbSNP | Ensembl ].		VAR_050535

Sequences

	Sequence		Length	Mass (Da)
	Q9Y6X2 [UniParc]. Last modified December 7, 2004. Version 2. Checksum: 7C06EF599D48F87D	FASTA	628	68,017
	10 20 30 40 50 60 MAELGELKHM VMSFRVSELQ VLLGFAGRNK SGRKHELLAK ALHLLKSSCA PSVQMKIKEL 70 80 90 100 110 120 YRRRFPRKTL GPSDLSLLSL PPGTSPVGSP GPLAPIPPTL LAPGTLLGPK REVDMHPPLP 130 140 150 160 170 180 QPVHPDVTMK PLPFYEVYGE LIRPTTLAST SSQRFEEAHF TFALTPQQVQ QILTSREVLP 190 200 210 220 230 240 GAKCDYTIQV QLRFCLCETS CPQEDYFPPN LFVKVNGKLC PLPGYLPPTK NGAEPKRPSR 250 260 270 280 290 300 PINITPLARL SATVPNTIVV NWSSEFGRNY SLSVYLVRQL TAGTLLQKLR AKGIRNPDHS 310 320 330 340 350 360 RALIKEKLTA DPDSEVATTS LRVSLMCPLG KMRLTVPCRA LTCAHLQSFD AALYLQMNEK 370 380 390 400 410 420 KPTWTCPVCD KKAPYESLII DGLFMEILSS CSDCDEIQFM EDGSWCPMKP KKEASEVCPP 430 440 450 460 470 480 PGYGLDGLQY SPVQGGDPSE NKKKVEVIDL TIESSSDEED LPPTKKHCSV TSAAIPALPG 490 500 510 520 530 540 SKGVLTSGHQ PSSVLRSPAM GTLGGDFLSS LPLHEYPPAF PLGADIQGLD LFSFLQTESQ 550 560 570 580 590 600 HYGPSVITSL DEQDALGHFF QYRGTPSHFL GPLAPTLGSS HCSATPAPPP GRVSSIVAPG 610 620 GALREGHGGP LPSGPSLTGC RSDIISLD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and chromosomal assignment of a human gene encoding protein inhibitor of activated STAT3 (PIAS3)." Ueki N., Seki N., Yano K., Saito T., Masuho Y., Muramatsu M.-A. J. Hum. Genet. 44:193-196(1999) [PubMed: 10319586] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 2-628.
[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: Blood and Muscle.
[3]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 310-628. Tissue: Mammary cancer.
[4]	"Specific inhibition of Stat3 signal transduction by PIAS3." Chung C.D., Liao J., Liu B., Rao X., Jay P., Berta P., Shuai K. Science 278:1803-1805(1997) [PubMed: 9388184] [Abstract] Cited for: FUNCTION, INTERACTION WITH STAT3, TISSUE SPECIFICITY.
[5]	"Protein inhibitor of activated STAT3 regulates androgen receptor signaling in prostate carcinoma cells." Junicho A., Matsuda T., Yamamoto T., Kishi H., Korkmaz K., Saatcioglu F., Fuse H., Muraguchi A. Biochem. Biophys. Res. Commun. 278:9-13(2000) [PubMed: 11071847] [Abstract] Cited for: INTERACTION WITH AR, INDUCTION.
[6]	"The zinc finger protein Gfi-1 can enhance STAT3 signaling by interacting with the STAT3 inhibitor PIAS3." Roedel B., Tavassoli K., Karsunky H., Schmidt T., Bachmann M., Schaper F., Heinrich P., Shuai K., Elsaesser H.-P., Moeroey T. EMBO J. 19:5845-5855(2000) [PubMed: 11060035] [Abstract] Cited for: INTERACTION WITH GFI1.
[7]	"ATBF1 enhances the suppression of STAT3 signaling by interaction with PIAS3." Nojiri S., Joh T., Miura Y., Sakata N., Nomura T., Nakao H., Sobue S., Ohara H., Asai K., Ito M. Biochem. Biophys. Res. Commun. 314:97-103(2004) [PubMed: 14715251] [Abstract] Cited for: INTERACTION WITH ZFHX3.
[8]	"Repression of the transactivating capacity of the oncoprotein PLAG1 by SUMOylation." Van Dyck F., Delvaux E.L.D., Van de Ven W.J.M., Chavez M.V. J. Biol. Chem. 279:36121-36131(2004) [PubMed: 15208321] [Abstract] Cited for: INTERACTION WITH PLAG1.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB021868 mRNA. Translation: BAA78533.1. Different initiation. BC001154 mRNA. Translation: AAH01154.2. BC030556 mRNA. Translation: AAH30556.2.
IPI	IPI00005789.
PIR	T34525.
RefSeq	NP_006090.2. NM_006099.3.
UniGene	Hs.435761.
3D structure databases
ProteinModelPortal	Q9Y6X2.
SMR	Q9Y6X2. Positions 1-65, 124-408.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-5969N.
IntAct	Q9Y6X2. 15 interactions.
MINT	MINT-149343.
STRING	Q9Y6X2.
PTM databases
PhosphoSite	Q9Y6X2.
Polymorphism databases
DMDM	56405390.
Proteomic databases
PRIDE	Q9Y6X2.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000393045; ENSP00000376765; ENSG00000131788.
GeneID	10401.
KEGG	hsa:10401.
UCSC	uc001eoc.1. human.
Organism-specific databases
CTD	10401.
GeneCards	GC01P145575.
H-InvDB	HIX0199813.
HGNC	HGNC:16861. PIAS3.
MIM	605987. gene.
neXtProt	NX_Q9Y6X2.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00550000074410.
HOGENOM	HBG315609.
HOVERGEN	HBG053598.
InParanoid	Q9Y6X2.
OMA	HCSVTSA.
OrthoDB	EOG4KSPJF.
PhylomeDB	Q9Y6X2.
Enzyme and pathway databases
Pathway_Interaction_DB	ar_pathway. Coregulation of Androgen receptor activity. il6_7pathway. IL6-mediated signaling events. smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling.
Gene expression databases
ArrayExpress	Q9Y6X2.
Bgee	Q9Y6X2.
CleanEx	HS_PIAS3.
Genevestigator	Q9Y6X2.
GermOnline	ENSG00000131788. 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	39416.
SOURCE	Search...

Entry information

Entry name

PIAS3_HUMAN

Accession

Primary (citable) accession number: Q9Y6X2
Secondary accession number(s): Q9UFI3

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 5, 2002
Last sequence update:	December 7, 2004
Last modified:	January 25, 2012
This is version 102 of the entry and version 2 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.