R111A_XENLA
ID R111A_XENLA Reviewed; 923 AA.
AC Q90ZT7;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 81.
DE RecName: Full=E3 ubiquitin-protein ligase arkadia-A;
DE EC=2.3.2.27;
DE AltName: Full=RING finger protein 111-A;
DE AltName: Full=RING-type E3 ubiquitin transferase arkadia-A {ECO:0000305};
DE Flags: Fragment;
GN Name=rnf111-a; Synonyms=arkadia;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION, AND
RP FUNCTION.
RX PubMed=11298453; DOI=10.1038/35071103;
RA Niederlaender C., Walsh J.J., Episkopou V., Jones C.M.;
RT "Arkadia enhances nodal-related signalling to induce mesendoderm.";
RL Nature 410:830-834(2001).
CC -!- FUNCTION: E3 ubiquitin-protein ligase required for mesoderm patterning
CC during embryonic development by enhancing signaling of the subset of
CC TGF-beta factors responsible for the formation of dorso-anterior
CC tissues of Spemann's organizer (PubMed:11298453). Acts as an enhancer
CC of the transcriptional responses of the smad2/smad3 effectors, which
CC are activated downstream of BMP (By similarity). 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).
CC Specifically binds polysumoylated chains via SUMO interaction motifs
CC (SIMs) and mediates ubiquitination of sumoylated substrates (By
CC similarity). The regulation of the BMP-SMAD signaling is however
CC independent of sumoylation and is not dependent of SUMO interaction
CC motifs (SIMs) (By similarity). {ECO:0000250|UniProtKB:Q6ZNA4,
CC ECO:0000250|UniProtKB:Q99ML9, ECO:0000269|PubMed:11298453}.
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. {ECO:0000250|UniProtKB:Q6ZNA4,
CC ECO:0000250|UniProtKB:Q99ML9}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11298453}. 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 -!- DEVELOPMENTAL STAGE: Maternally and ubiquitously expressed in
CC fertilized eggs, with highest levels on the presumptive dorsal side of
CC blastula. At gastrula stages, expressed throughout the marginal zone
CC and endoderm. {ECO:0000269|PubMed:11298453}.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF329847; AAK38637.1; -; mRNA.
DR AlphaFoldDB; Q90ZT7; -.
DR SMR; Q90ZT7; -.
DR PRIDE; Q90ZT7; -.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000186698; Genome assembly.
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: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 Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR029306; RNF111_N.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF15303; RNF111_N; 1.
DR Pfam; PF13639; zf-RING_2; 1.
DR SMART; SM00184; RING; 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;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN <1..923
FT /note="E3 ubiquitin-protein ligase arkadia-A"
FT /id="PRO_0000280693"
FT ZN_FING 871..912
FT /note="RING-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 15..136
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 154..174
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 190..237
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 282..305
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 329..365
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 441..465
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 579..613
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 625..645
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 836..838
FT /note="Ubiquitin binding"
FT /evidence="ECO:0000250|UniProtKB:Q6ZSG1"
FT REGION 886..890
FT /note="Ubiquitin binding"
FT /evidence="ECO:0000250|UniProtKB:Q6ZSG1"
FT MOTIF 241..245
FT /note="SUMO interaction motif 1 (SIM)"
FT /evidence="ECO:0000250|UniProtKB:Q6ZNA4"
FT MOTIF 266..272
FT /note="SUMO interaction motif 2 (SIM)"
FT /evidence="ECO:0000250|UniProtKB:Q6ZNA4"
FT MOTIF 321..325
FT /note="SUMO interaction motif 3 (SIM)"
FT /evidence="ECO:0000250|UniProtKB:Q6ZNA4"
FT COMPBIAS 15..34
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 43..57
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 63..77
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 78..95
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 104..130
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 190..216
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 285..305
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 336..363
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 579..593
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 594..613
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 629..643
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 871
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q6ZSG1"
FT BINDING 874
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q6ZSG1"
FT BINDING 894
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q6ZSG1"
FT BINDING 897
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q6ZSG1"
FT NON_TER 1
SQ SEQUENCE 923 AA; 101298 MW; A93CBDA3E05787C8 CRC64;
VEMIASKVSN EFNHLCSDTN KQQSDLNSNG TEQDKSLVVH KKRKSQQAGT SYAQSCEVKE
YQRLLRLQPK SDEDNDSSFS DCISSPSSSS HFGDSDTMTS DEDKDNPLSS VNSTPRTQSA
RAQKWPRPHT DSVSSLLMKR PCYQVSSLRR PLHRKRFVKN VSSQRTQKQK ERIMLQRKKR
EVLARQKYAL LPSSSSSSEN DLSSESSSSS STEGEEDLFV SPGENHQDGT TLPSGGMDED
VVVIEASSTP QVTANEEINV TSTDSEVEIV TVGETYRSRA TLGHPRSHWG QNSQSGRTQE
QRTRNRVSTI IQPLRQNTTE VVDLTVDEDD PTVVPTTSGR VESQPVSIVS SLTSTSEPAS
DSMSGLMGSA VPEIPAIPPN TVGTIADDSR TCTSGANADG GPPAMPRLPS CCPQHSPCGG
SSQNHVLGHP HSSCFPPHSH HFPHHHHHHH HSSHPGVPLS PSFRDSHCTV ERNAAVPPPC
GVSSSSGSTY HDPQALPVDL SNNGIRSHGS VGFHSTSAFD PCCPGSSSRS TVYGHQATTS
TAQTMAIDGY GSSMVAQAQP PPPLSSCRHY MHASYTSLPR PLHHQTSSCP HSNSASQPPP
PPPPPPPPPM DYVIAHQVPF ISPLPSLTST HAVPPPPPSH HLSAAAAPLP QHLSTSHQSM
SHHISATAPA TQRLHAHEVI QRMEVQRRRM MQHPTRAHER PPPHPHRMHP NYGHGHHIHV
PQTMSSHPRQ GPERSAWEIA IETGVTAAPY QTGPLHTHLA PYHPPPRLHH LQIGALPLMV
PDMAGYPHIR YISSGLDGRS FRVPFRGNFE ELIHLEERLG NVNRGASQGT IERCTYPHKY
KKVSTDWFSQ RKLHSKQDGE EAPEEDTEEK CTICLSILEE GEDVRRLPCM HLFHQVCVDQ
WLITNKKCPI CRVDIDTQLP TES
