PIS4A_DANRE
ID PIS4A_DANRE Reviewed; 505 AA.
AC F1R4C4; H8YLC1; Q6IS20; Q6PFJ4;
DT 16-JAN-2019, integrated into UniProtKB/Swiss-Prot.
DT 16-JAN-2019, sequence version 2.
DT 03-AUG-2022, entry version 71.
DE RecName: Full=E3 SUMO-protein ligase PIAS4-A {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q8N2W9};
DE AltName: Full=Protein inhibitor of activated STAT protein 4 {ECO:0000303|PubMed:22345667};
GN Name=pias4a {ECO:0000303|PubMed:22345667,
GN ECO:0000312|ZFIN:ZDB-GENE-040426-2734};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955 {ECO:0000312|Proteomes:UP000000437};
RN [1] {ECO:0000312|EMBL:AEF32112.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, AND INDUCTION.
RX PubMed=22345667; DOI=10.4049/jimmunol.1100959;
RA Xiong R., Nie L., Xiang L.X., Shao J.Z.;
RT "Characterization of a PIAS4 Homologue from Zebrafish: Insights into Its
RT Conserved Negative Regulatory Mechanism in the TRIF, MAVS, and IFN
RT Signaling Pathways during Vertebrate Evolution.";
RL J. Immunol. 188:2653-2668(2012).
RN [2] {ECO:0000312|Proteomes:UP000000437}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen {ECO:0000312|Proteomes:UP000000437};
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [3] {ECO:0000312|EMBL:AAH70017.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo {ECO:0000312|EMBL:AAH70017.1};
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000312|EMBL:CBX19728.1}
RP IDENTIFICATION.
RX PubMed=22412924; DOI=10.1371/journal.pone.0032777;
RA Liongue C., O'Sullivan L.A., Ward A.C.;
RT "Evolution of JAK-STAT pathway components: mechanisms and role in immune
RT system development.";
RL PLoS ONE 7:E32777-E32777(2012).
CC -!- FUNCTION: Functions as an E3-type small ubiquitin-like modifier (SUMO)
CC ligase (By similarity). May play a role as a transcriptional
CC coregulator in various cellular pathways (By similarity). Negatively
CC regulates induction of interferon phi 1 (ifnphi1) mediated by mavs and
CC ticam1/trif. Also inhibits ifnphi1-mediated activation of the
CC interferon-stimulated genes (ISGs) pkz and cd40, and to a lesser extent
CC rsad2 and isg15 (PubMed:22345667). May inhibit ticam1/trif-mediated
CC activation of NF-kappa-B (PubMed:22345667).
CC {ECO:0000250|UniProtKB:Q8N2W9, ECO:0000269|PubMed:22345667}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000250|UniProtKB:Q8N2W9};
CC -!- PATHWAY: Protein modification; protein sumoylation.
CC {ECO:0000250|UniProtKB:Q8N2W9}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22345667}.
CC -!- TISSUE SPECIFICITY: Highly expressed in spleen, liver, and brain.
CC Expressed at lower levels in heart, intestine, kidney, gill, skin, and
CC muscle. {ECO:0000269|PubMed:22345667}.
CC -!- DEVELOPMENTAL STAGE: Highly expressed in early development (6 hours to
CC 24 hours post fertilization), with lower expression thereafter.
CC {ECO:0000269|PubMed:22345667}.
CC -!- INDUCTION: Up-regulated in response to polyinosinic-polycytidylic acid
CC (poly(I:C)), and interferon phi 1 (ifnphi1).
CC {ECO:0000269|PubMed:22345667}.
CC -!- DOMAIN: The LXXLL motif is a coregulator signature that is essential
CC for transcriptional corepression. {ECO:0000250|UniProtKB:Q8N2W9}.
CC -!- PTM: Sumoylated. Lys-35 is the main site of sumoylation.
CC {ECO:0000250|UniProtKB:Q8N2W9}.
CC -!- SIMILARITY: Belongs to the PIAS family. {ECO:0000305}.
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DR EMBL; JF759916; AEF32112.1; -; mRNA.
DR EMBL; BX088720; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC057528; AAH57528.1; -; mRNA.
DR EMBL; BC070017; AAH70017.1; -; mRNA.
DR EMBL; BN001519; CBX19728.1; -; mRNA.
DR RefSeq; NP_998568.2; NM_213403.2.
DR AlphaFoldDB; F1R4C4; -.
DR SMR; F1R4C4; -.
DR STRING; 7955.ENSDARP00000096293; -.
DR PaxDb; F1R4C4; -.
DR GeneID; 406712; -.
DR KEGG; dre:406712; -.
DR CTD; 406712; -.
DR ZFIN; ZDB-GENE-040426-2734; pias4a.
DR eggNOG; KOG2169; Eukaryota.
DR HOGENOM; CLU_020768_1_1_1; -.
DR InParanoid; F1R4C4; -.
DR OrthoDB; 1205949at2759; -.
DR PhylomeDB; F1R4C4; -.
DR TreeFam; TF323787; -.
DR Reactome; R-DRE-196791; Vitamin D (calciferol) metabolism.
DR Reactome; R-DRE-3108214; SUMOylation of DNA damage response and repair proteins.
DR Reactome; R-DRE-3232118; SUMOylation of transcription factors.
DR Reactome; R-DRE-3232142; SUMOylation of ubiquitinylation proteins.
DR Reactome; R-DRE-3899300; SUMOylation of transcription cofactors.
DR Reactome; R-DRE-4085377; SUMOylation of SUMOylation proteins.
DR Reactome; R-DRE-4090294; SUMOylation of intracellular receptors.
DR Reactome; R-DRE-4615885; SUMOylation of DNA replication proteins.
DR Reactome; R-DRE-4755510; SUMOylation of immune response proteins.
DR Reactome; R-DRE-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR Reactome; R-DRE-5693571; Nonhomologous End-Joining (NHEJ).
DR Reactome; R-DRE-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-DRE-69473; G2/M DNA damage checkpoint.
DR UniPathway; UPA00886; -.
DR PRO; PR:F1R4C4; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005634; C:nucleus; IDA:ZFIN.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0061665; F:SUMO ligase activity; ISS:UniProtKB.
DR GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0032480; P:negative regulation of type I interferon production; IMP:ZFIN.
DR GO; GO:0060339; P:negative regulation of type I interferon-mediated signaling pathway; IMP:ZFIN.
DR GO; GO:1905168; P:positive regulation of double-strand break repair via homologous recombination; ISS:UniProtKB.
DR GO; GO:0016925; P:protein sumoylation; IBA:GO_Central.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR Gene3D; 1.10.720.30; -; 1.
DR Gene3D; 2.60.120.780; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR027224; PIAS4.
DR InterPro; IPR023321; PINIT.
DR InterPro; IPR038654; PINIT_sf.
DR InterPro; IPR003034; SAP_dom.
DR InterPro; IPR036361; SAP_dom_sf.
DR InterPro; IPR004181; Znf_MIZ.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR10782:SF9; PTHR10782:SF9; 1.
DR Pfam; PF14324; PINIT; 1.
DR Pfam; PF02891; zf-MIZ; 1.
DR SMART; SM00513; SAP; 1.
DR SUPFAM; SSF68906; SSF68906; 1.
DR PROSITE; PS51466; PINIT; 1.
DR PROSITE; PS50800; SAP; 1.
DR PROSITE; PS51044; ZF_SP_RING; 1.
PE 2: Evidence at transcript level;
KW DNA-binding; Isopeptide bond; Metal-binding; Nucleus; Reference proteome;
KW Transcription; Transcription regulation; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..505
FT /note="E3 SUMO-protein ligase PIAS4-A"
FT /id="PRO_0000446085"
FT DOMAIN 12..46
FT /note="SAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00186"
FT DOMAIN 104..264
FT /note="PINIT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00799"
FT ZN_FING 296..381
FT /note="SP-RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00452"
FT REGION 374..505
FT /note="Required for nuclear localization"
FT /evidence="ECO:0000269|PubMed:22345667"
FT REGION 395..505
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 20..24
FT /note="LXXLL motif"
FT /evidence="ECO:0000250|UniProtKB:Q8N2W9"
FT COMPBIAS 395..409
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 425..456
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 463..483
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 484..505
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 327
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00452"
FT BINDING 329
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00452"
FT BINDING 350
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00452"
FT BINDING 353
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00452"
FT CROSSLNK 35
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8N2W9"
FT CROSSLNK 35
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8N2W9"
FT CROSSLNK 56
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q8N2W9"
FT CROSSLNK 68
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q8N2W9"
FT CONFLICT 126
FT /note="N -> S (in Ref. 3; AAH57528)"
FT /evidence="ECO:0000305"
FT CONFLICT 137
FT /note="V -> I (in Ref. 1; AEF32112)"
FT /evidence="ECO:0000305"
FT CONFLICT 152
FT /note="D -> E (in Ref. 3; AAH57528)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 505 AA; 55810 MW; 91947E15A006079C CRC64;
MAAELVEAMN MVKSFRVSDL QTLLASMGRS KSGLKQDLVG RALRLVQTEY SPELLKNVRQ
LYETRFPKAS AWLAARRPET VAVNYPALNS SPRGTGQGTD YLNGIPKPAP PPAAEVKLVP
LPFYHNLETL LPPTELVAQN SEKLQESQCV FDLTPNQVDQ IRNSSELRPG MKSVQVVLRI
CYTDSIGVQE DQYPPNIAVK VNQSYCHVPG YYPSNKPGVE PRRPCRPVNI TPWLHLSTVT
NRVTITWGNF GKRYSVAVYL VRVFTSGELF NQLKHCSVEN PDRCRERIQD KLRFDPESEI
ATTGLRVSLI CPLVKMRLGV PCRVLTCAHL QCFDAVFFLQ MNEKKPTWTC PVCDKPAPFE
LLTIDGLLSE ILKETPEDVE EIEYLTDGSW RPIRDDKEKE RERENSRTPD YPVVDICVPE
ANGHSPAHSG TNQTGKSGSG GASAGTGSTS GGSGGGTVVD LTLDDSSEEE GGGGAEDSEE
TDDSQDSPAP KRGRYDYDKD LVTAY
