O88907 (PIAS1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
E3 SUMO-protein ligase PIAS1
EC=6.3.2.-

Alternative name(s):
DEAD/H box-binding protein 1
Protein inhibitor of activated STAT protein 1

Gene names

Name:	Pias1
Synonyms:	Ddxbp1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	651 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 and the steroid hormone signaling pathway. In vitro, binds A/T-rich DNA By similarity. The effects of this transcriptional coregulation, transactivation or silencing, may vary depending upon the biological context. Together with PRMT1, may repress STAT1 transcriptional activity, in the late phase of interferon gamma (IFN-gamma) signaling. Sumoylates PML (at'Lys-65' and 'Lys-160') and PML-RAR and promotes their ubiquitin-mediated degradation. PIAS1-mediated sumoylation of PML promotes its interaction with CSNK2A1/CK2 which in turn promotes PML phosphorylation and degradation. Ref.11
Pathway	Protein modification; protein sumoylation.
Subunit structure	Interacts with STAT1 By similarity. Interacts with NR2C1; the interaction promotes its sumoylation. Interacts with DDX21, CSRP2, AXIN1, JUN, SATB2, PLAG1, TP53 and STAT1 (dimer), following IFNA1-stimulation. Interacts with SP3 (preferentially when SUMO-modified). Interacts with KLF8; the interaction results in SUMO ligation and repression of KLF8 transcriptional activity and of its cell cycle progression into G1 phase By similarity. Interacts with CHUK/IKKA; this interaction induces PIAS1 phosphorylation. Interacts with PTK2/FAK1; the interaction promotes its sumoylation By similarity. Interacts with SUMO1, UBE2I, NCOA2 and AR. Interacts with NR2C1; the interaction promotes its sumoylation. Interacts with DDX5 By similarity. Interacts with PML (isoform PML-12). Ref.5 Ref.6 Ref.9 Ref.11
Subcellular location	Nucleus speckle By similarity. Nucleus › PML body. Note: Interaction with CSRP2 may induce a partial redistribution along the cytoskeleton By similarity. Ref.6 Ref.11
Tissue specificity	Expressed in kidney, heart, spleen, brain and cerebellum; weak expression, if any, in liver and lung. Ref.4
Developmental stage	Expressed as early as 7.6 dpc. Expression remains high through 15.5 dpc. Ref.4
Domain	The LXXLL motif is a transcriptional coregulator signature. The SP-RING-type domain is required for promoting EKLF sumoylation.
Post-translational modification	Sumoylated By similarity. Ref.6 Ref.7 Ref.8 Dimethylated by PRMT1 at Arg-303 in the late phase of interferon gamma (IFN-gamma) signaling, leading to preferential interaction with STAT1 and thus resulting in release of STAT1 from its target gene By similarity.
Sequence similarities	Belongs to the PIAS family. Contains 1 PINIT domain. Contains 1 SAP domain. Contains 1 SP-RING-type zinc finger.

Ontologies

Keywords
Biological process	Transcription Transcription regulation Ubl conjugation pathway
Cellular component	Nucleus
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Ligase
PTM	Acetylation Methylation Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	JAK-STAT cascade Inferred from sequence alignment Ref.1. Source: MGI negative regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype PubMed 16127449. Source: BHF-UCL positive regulation of proteasomal ubiquitin-dependent protein catabolic process Inferred from mutant phenotype Ref.11. Source: UniProtKB positive regulation of protein sumoylation Inferred from sequence or structural similarity. Source: UniProtKB protein sumoylation Inferred from direct assay Ref.11. Source: UniProtKB regulation of cell proliferation Inferred from mutant phenotype Ref.11. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	PML body Inferred from electronic annotation. Source: UniProtKB-SubCell nuclear speck Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from direct assay PubMed 16522640. Source: MGI
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW SUMO ligase activity Inferred from electronic annotation. Source: Ensembl transcription corepressor activity Inferred from sequence alignment Ref.1. Source: MGI zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Sufu	Q9Z0P7	3	EBI-3508327,EBI-3508336

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 651	650	E3 SUMO-protein ligase PIAS1		PRO_0000218975
Regions
	Domain	11 – 45	35	SAP
	Domain	124 – 288	165	PINIT
	Repeat	520 – 523	4	1
	Repeat	557 – 560	4	2
	Repeat	598 – 601	4	3; approximate
	Repeat	612 – 615	4	4; approximate
	Zinc finger	320 – 397	78	SP-RING-type
	Region	462 – 473	12	SUMO1-binding By similarity
	Region	520 – 615	96	4 X 4 AA repeats of N-T-S-L
	Motif	19 – 23	5	LXXLL motif
	Motif	56 – 64	9	Nuclear localization signal Potential
	Motif	368 – 380	13	Nuclear localization signal Potential
	Compositional bias	577 – 634	58	Ser-rich
Amino acid modifications
	Modified residue	2	1	N-acetylalanine By similarity
	Modified residue	303	1	Asymmetric dimethylarginine; by PRMT1 By similarity
	Modified residue	485	1	Phosphoserine Ref.10
	Modified residue	487	1	Phosphothreonine Ref.10
	Modified residue	503	1	Phosphoserine By similarity
	Modified residue	510	1	Phosphoserine By similarity
	Modified residue	522	1	Phosphoserine By similarity
Experimental info
	Mutagenesis	346	1	C → G: Loss of promotion of EKLF sumoylation; when associated with G-351 and A-356. Ref.8
	Mutagenesis	351	1	C → G: Loss of promotion of EKLF sumoylation; when associated with G-346 and A-356. Ref.8
	Mutagenesis	356	1	C → A: Loss of promotion of EKLF sumoylation; when associated with G-346 and G-351. Ref.8
	Mutagenesis	363	1	I → S: Loss of promotion of EKLF sumoylation. Ref.8
	Mutagenesis	372	1	W → A: Loss of promotion of NCOA2 sumoylation. Ref.6
	Mutagenesis	375 – 376	2	PV → AA: Loss of promotion of EKLF sumoylation.
	Sequence conflict	320	1	P → S in AAC36701. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O88907 [UniParc]. Last modified December 7, 2004. Version 2. Checksum: 8844364E8FEE4F7F	FASTA	651	71,618
	10 20 30 40 50 60 MADSAELKQM VMSLRVSELQ VLLGYAGRNK HGRKHELLTK ALHLLKAGCS PAVQMKIKEL 70 80 90 100 110 120 YRRRFPQKIM TPADLSIPNV HSSPMPPTLS PSTIPQLTYD GHPASSPLLP VSLLGPKHEL 130 140 150 160 170 180 ELPHLTSALH PVHPDIKLQK LPFYDLLDEL IKPTSLASDN SQRFRETCFA FALTPQQVQQ 190 200 210 220 230 240 ISSSMDISGT KCDFTVQVQL RFCLSETSCP QEDHFPPNLC VKVNTKPCSL PGYLPPTKNG 250 260 270 280 290 300 VEPKRPSRPI NITSLVRLST TVPNTIVVSW TAEIGRTYSM AVYLVKQLSS TVLLQRLRAK 310 320 330 340 350 360 GIRNPDHSRA LIKEKLTADP DSEIATTSLR VSLLCPLGKM RLTIPCRALT CSHLQCFDAT 370 380 390 400 410 420 LYIQMNEKKP TWVCPVCDKK APYEHLIIDG LFMEILKYCT DCDEIQFKED GSWAPMRSKK 430 440 450 460 470 480 EVQEVTASYN GVDGCLSSTL EHQVASHNQS SNKNKKVEVI DLTIDSSSDE EEEEPPAKRT 490 500 510 520 530 540 CPSLSPTSPL SNKGILSLPH QASPVSRTPS LPAVDTSYIN TSLIQDYRHP FHMTPMPYDL 550 560 570 580 590 600 QGLDFFPFLS GDNQHYNTSL LAAAAAAVSD DQDLLHSSRF FPYTSSQMFL DQLSAGGSTS 610 620 630 640 650 LPATNGSSSG SNSSLVSSNS LRESHGHGVA SRSSADTASI FGIIPDIISL D

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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: B-cell.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Lung.
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: FVB/N-3. Tissue: Mammary tumor.
[4]	"Cloning and analysis of a murine Pias family member, Pias-gamma, in developing skin and neurons." Sturm S., Koch M., White F.A. J. Mol. Neurosci. 14:107-121(2000) [PubMed] [Europe PMC] [Abstract] Cited for: DEVELOPMENTAL STAGE, TISSUE SPECIFICITY. Tissue: Brain.
[5]	"ARIP3 (androgen receptor-interacting protein 3) and other PIAS (protein inhibitor of activated STAT) proteins differ in their ability to modulate steroid receptor-dependent transcriptional activation." Kotaja N., Aittomaeki S., Silvennoinen O., Palvimo J.J., Jaenne O.A. Mol. Endocrinol. 14:1986-2000(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH AR.
[6]	"PIAS proteins modulate transcription factors by functioning as SUMO-1 ligases." Kotaja N., Karvonen U., Jaenne O.A., Palvimo J.J. Mol. Cell. Biol. 22:5222-5234(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SUMO1; UBE2I AND NCOA2, SUBCELLULAR LOCATION, SUMOYLATION OF AR AND NCOA2, MUTAGENESIS OF TRP-372.
[7]	"PIAS proteins promote SUMO-1 conjugation to STAT1." Ungureanu D., Vanhatupa S., Kotaja N., Yang J., Aittomaeki S., Jaenne O.A., Palvimo J.J., Silvennoinen O. Blood 102:3311-3313(2003) [PubMed] [Europe PMC] [Abstract] Cited for: STAT1 SUMOYLATION.
[8]	"Sumoylation of EKLF promotes transcriptional repression and is involved in inhibition of megakaryopoiesis." Siatecka M., Xue L., Bieker J.J. Mol. Cell. Biol. 27:8547-8560(2007) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION OF KLF1, MUTAGENESIS OF CYS-346; CYS-351; CYS-356; ILE-363 AND 375-PRO-VAL-376.
[9]	"SUMOylation of Tr2 orphan receptor involves Pml and fine-tunes Oct4 expression in stem cells." Park S.W., Hu X., Gupta P., Lin Y.P., Ha S.G., Wei L.N. Nat. Struct. Mol. Biol. 14:68-75(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NR2C1.
[10]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-485 AND THR-487, MASS SPECTROMETRY. Tissue: Liver.
[11]	"The SUMO E3-ligase PIAS1 regulates the tumor suppressor PML and its oncogenic counterpart PML-RARA." Rabellino A., Carter B., Konstantinidou G., Wu S.Y., Rimessi A., Byers L.A., Heymach J.V., Girard L., Chiang C.M., Teruya-Feldstein J., Scaglioni P.P. Cancer Res. 72:2275-2284(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PML.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF077950 mRNA. Translation: AAC36701.1. AK075708 mRNA. Translation: BAC35902.1. BC051417 mRNA. Translation: AAH51417.1.
IPI	IPI00268676.
RefSeq	NP_062637.2. NM_019663.3.
UniGene	Mm.431253. Mm.491651.
3D structure databases
ProteinModelPortal	O88907.
SMR	O88907. Positions 1-65, 137-415.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-29277N.
IntAct	O88907. 16 interactions.
MINT	MINT-4107556.
PTM databases
PhosphoSite	O88907.
Proteomic databases
PaxDb	O88907.
PRIDE	O88907.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000098651; ENSMUSP00000096248; ENSMUSG00000032405.
GeneID	56469.
KEGG	mmu:56469.
UCSC	uc009qas.1. mouse.
Organism-specific databases
CTD	8554.
MGI	MGI:1913125. Pias1.
Phylogenomic databases
eggNOG	NOG125513.
HOGENOM	HOG000230594.
HOVERGEN	HBG053598.
InParanoid	O88907.
KO	K04706.
OMA	LRENHGH.
OrthoDB	EOG7HF1JB.
Enzyme and pathway databases
UniPathway	UPA00886.
Gene expression databases
ArrayExpress	O88907.
Bgee	O88907.
CleanEx	MM_PIAS1.
Genevestigator	O88907.
Family and domain databases
Gene3D	1.10.720.30. 1 hit.
InterPro	IPR027227. PIAS1. IPR023321. PINIT. IPR003034. SAP_dom. IPR004181. Znf_MIZ. [Graphical view]
PANTHER	PTHR10782:SF11. PTHR10782:SF11. 1 hit.
Pfam	PF14324. PINIT. 1 hit. 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
ChiTaRS	PIAS1. mouse.
NextBio	312730.
PRO	O88907.
SOURCE	Search...

Entry information

Entry name

PIAS1_MOUSE

Accession

Primary (citable) accession number: O88907
Secondary accession number(s): Q8C6H5

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 5, 2002
Last sequence update:	December 7, 2004
Last modified:	November 13, 2013
This is version 120 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program