ID RN111_PONAB Reviewed; 986 AA.
AC Q5R476;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 27-MAR-2024, entry version 105.
DE RecName: Full=E3 ubiquitin-protein ligase Arkadia;
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q6ZNA4};
DE AltName: Full=RING finger protein 111;
DE AltName: Full=RING-type E3 ubiquitin transferase Arkadia {ECO:0000305};
GN Name=RNF111;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: E3 ubiquitin-protein ligase (By similarity). Required for
CC mesoderm patterning during embryonic development (By similarity). Acts
CC as an enhancer of the transcriptional responses of the SMAD2/SMAD3
CC effectors, which are activated downstream of BMP. Acts by mediating
CC ubiquitination and degradation of SMAD inhibitors such as SMAD7,
CC inducing their proteasomal degradation and thereby enhancing the
CC transcriptional activity of TGF-beta and BMP (By similarity). In
CC addition to enhance transcription of SMAD2/SMAD3 effectors, also
CC regulates their turnover by mediating their ubiquitination and
CC subsequent degradation, coupling their activation with degradation,
CC thereby ensuring that only effectors 'in use' are degraded (By
CC similarity). Activates SMAD3/SMAD4-dependent transcription by
CC triggering signal-induced degradation of SNON isoform of SKIL.
CC Associates with UBE2D2 as an E2 enzyme. Specifically binds
CC polysumoylated chains via SUMO interaction motifs (SIMs) and mediates
CC ubiquitination of sumoylated substrates. Catalyzes 'Lys-63'-linked
CC ubiquitination of sumoylated XPC in response to UV irradiation,
CC promoting nucleotide excision repair (By similarity). Mediates
CC ubiquitination and degradation of sumoylated PML (By similarity). The
CC regulation of the BMP-SMAD signaling is however independent of
CC sumoylation and is not dependent of SUMO interaction motifs (SIMs) (By
CC similarity). {ECO:0000250|UniProtKB:Q6ZNA4,
CC ECO:0000250|UniProtKB:Q99ML9}.
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:Q6ZNA4};
CC -!- ACTIVITY REGULATION: Binds free ubiquitin non-covalently via its RING-
CC type zinc finger. Ubiquitin-binding leads to enhance the E3 ubiquitin-
CC protein ligase activity by stabilizing the ubiquitin-conjugating enzyme
CC E2 (donor ubiquitin) in the 'closed' conformation and activating
CC ubiquitin transfer. {ECO:0000250|UniProtKB:Q6ZSG1}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q6ZNA4}.
CC -!- SUBUNIT: Monomer. Interacts with SMAD6, SMAD7, AXIN1, AXIN2 and SKIL
CC isoform SNON (By similarity). Interacts with (phosphorylated) SMAD2 and
CC SMAD3 (By similarity). Part of a complex containing RNF111, AXIN1 and
CC SMAD7. Interacts (via SIM domains) with SUMO1 and SUMO2 (By
CC similarity). {ECO:0000250|UniProtKB:Q6ZNA4,
CC ECO:0000250|UniProtKB:Q99ML9}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q6ZNA4}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q6ZNA4}. Nucleus, PML body
CC {ECO:0000250|UniProtKB:Q99ML9}. Note=Upon TGF-beta treatment,
CC translocates from nucleus to cytosol. {ECO:0000250|UniProtKB:Q6ZNA4}.
CC -!- DOMAIN: The SUMO interaction motifs (SIMs) mediates the binding to
CC polysumoylated substrate. {ECO:0000250|UniProtKB:Q6ZNA4}.
CC -!- DOMAIN: The RING-type zinc finger mediates the E3 ubiquitin-protein
CC ligase activity and binds directly to free ubiquitin (By similarity).
CC Non-covalent ubiquitin-binding stabilizes the ubiquitin-conjugating
CC enzyme E2 (donor ubiquitin) in the 'closed' conformation and stimulates
CC ubiquitin transfer (By similarity). {ECO:0000250|UniProtKB:Q6ZNA4,
CC ECO:0000250|UniProtKB:Q6ZSG1}.
CC -!- SIMILARITY: Belongs to the Arkadia family. {ECO:0000305}.
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DR EMBL; CR861381; CAH93440.1; -; mRNA.
DR RefSeq; NP_001124565.1; NM_001131093.1.
DR AlphaFoldDB; Q5R476; -.
DR BMRB; Q5R476; -.
DR SMR; Q5R476; -.
DR STRING; 9601.ENSPPYP00000007390; -.
DR GeneID; 100169738; -.
DR KEGG; pon:100169738; -.
DR eggNOG; KOG0800; Eukaryota.
DR InParanoid; Q5R476; -.
DR OrthoDB; 5474929at2759; -.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0032184; F:SUMO polymer binding; ISS:UniProtKB.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR CDD; cd16681; RING-H2_RNF111; 1.
DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1.
DR InterPro; IPR029306; RNF111_N.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR16200:SF1; E3 UBIQUITIN-PROTEIN LIGASE PLR-1-RELATED; 1.
DR PANTHER; PTHR16200; RING ZINC FINGER; 1.
DR Pfam; PF15303; RNF111_N; 1.
DR Pfam; PF13639; zf-RING_2; 1.
DR SMART; SM00184; RING; 1.
DR SUPFAM; SSF57850; RING/U-box; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 2: Evidence at transcript level;
KW Cytoplasm; Developmental protein; DNA damage; DNA repair; Isopeptide bond;
KW Metal-binding; Nucleus; Reference proteome; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..986
FT /note="E3 ubiquitin-protein ligase Arkadia"
FT /id="PRO_0000280692"
FT ZN_FING 934..975
FT /note="RING-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 66..106
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 120..191
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 241..404
FT /note="Interaction with AXIN1"
FT /evidence="ECO:0000250|UniProtKB:Q6ZSG1"
FT REGION 248..277
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 337..373
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 389..471
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 506..561
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 609..646
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 659..684
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 696..719
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 907..909
FT /note="Ubiquitin binding"
FT /evidence="ECO:0000250|UniProtKB:Q6ZSG1"
FT REGION 949..953
FT /note="Ubiquitin binding"
FT /evidence="ECO:0000250|UniProtKB:Q6ZSG1"
FT MOTIF 300..304
FT /note="SUMO interaction motif 1 (SIM)"
FT /evidence="ECO:0000250|UniProtKB:Q6ZNA4"
FT MOTIF 325..331
FT /note="SUMO interaction motif 2 (SIM)"
FT /evidence="ECO:0000250|UniProtKB:Q6ZNA4"
FT MOTIF 382..386
FT /note="SUMO interaction motif 3 (SIM)"
FT /evidence="ECO:0000250|UniProtKB:Q6ZNA4"
FT COMPBIAS 66..93
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 127..150
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 249..277
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 397..468
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 508..523
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 547..561
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 610..627
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 670..684
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 934
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q6ZSG1"
FT BINDING 937
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q6ZSG1"
FT BINDING 957
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q6ZSG1"
FT BINDING 960
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q6ZSG1"
FT CROSSLNK 19
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q6ZNA4"
FT CROSSLNK 28
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q6ZNA4"
FT CROSSLNK 34
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q6ZNA4"
FT CROSSLNK 47
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q6ZNA4"
FT CROSSLNK 59
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q6ZNA4"
FT CROSSLNK 73
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q6ZNA4"
FT CROSSLNK 87
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q6ZNA4"
FT CROSSLNK 96
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q6ZNA4"
FT CROSSLNK 110
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q6ZNA4"
FT CROSSLNK 173
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q6ZNA4"
FT CROSSLNK 198
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q6ZNA4"
FT CROSSLNK 218
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q6ZNA4"
FT CROSSLNK 915
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q6ZNA4"
FT CROSSLNK 919
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q6ZNA4"
SQ SEQUENCE 986 AA; 107942 MW; 2455AF15218850C7 CRC64;
MSQWTPEYNE LYTLKVDMKS EIPSDAPKTQ ESLKGILLHP EPIGAAKSFP AGVEMINSKV
GNEFSHLCDD SQKQEKDMNG NQQEQEKSLV VRKKRKSQQA GPSYVQNCVK ENQGILGLRQ
HLGTPSDEDN DSSFSDCLSS PSSSLHFGDS DTVTSDEDKE VSVRHSQTIL NAKSRSHSAR
SHKWPRTETE SVSGLLMKRP CLHGSSLRRL PCRKRFVKNN SSQRTQKQKE RILMQRKKRE
VLARRKYALL PSSSSSSEND LSSESSSSSS TEGEEDLFVS ASENHQNNPA VPSGSIDEDV
VVIEASSTPQ VTANEEINVT STDSEVEIVT VGESYRSRST LGHSRSHWSQ GSSSHASRPQ
EPRNRSRIST VIQPLRQNAA EVVDLTVDED EPTVVPTTSA RMESQATSAS INNSNPSTSE
QASDTASAVT GSQPSTVSET SATLTSNSTT GTSIGDDSRR TTSSAVMETG PPAMPRLPSC
CPQHSPCGGS SQNHHALGHP HTSCFQQHGH HFQHHHHHHH TPHPAVPVSP SFSDPACPVE
RPPQVQAPCG ANSSSGTSYH EQQALPVDLS NNGIRSHGSG SFHGASAFDP CCPVSSSRAA
IFGHQAAAAA PSQPLSSIDG YGSSMVAQPQ PQPPPQPSLS SCRHYMPPTY ASLTRPLHHQ
ASACPHSHGN PPPQTQPPPQ VDYVIPHPVH AFHSQISSHA TSHPVAPPPP THLASTAAPI
PQHLPPTHQP ISHHIPATAP PAQRLHPHEV MQRMEVRRRR MMQHPTRAHE RPPPHPHRMH
PNYGHGHHIH VPQTMSSHPR QAPERSAWEL GIEAGVTAAT YTPGALHPHL AHYHAPPRLH
HLQLGALPLM VPDMAGYPHI RYISSGLDGT SFRGPFRGNF EELIHLEERL GNVNRGASQG
TIERCTYPHK YKKRKLHCKQ DGEEGTEEDT EEKCTICLSI LEEGEDVRRL PCMHLFHQVC
VDQWLITNKK CPICRVDIEA QLPSES
//
