ID   RWDD3_RAT               Reviewed;         267 AA.
AC   P0C7N0;
DT   10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT   10-JUN-2008, sequence version 1.
DT   03-AUG-2022, entry version 69.
DE   RecName: Full=RWD domain-containing protein 3;
DE   AltName: Full=RWD domain-containing sumoylation enhancer;
DE            Short=RSUME {ECO:0000303|PubMed:17956732};
GN   Name=Rwdd3; Synonyms=Rsume;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Pituitary tumor;
RX   PubMed=17956732; DOI=10.1016/j.cell.2007.07.044;
RA   Carbia-Nagashima A., Gerez J., Perez-Castro C., Paez-Pereda M.,
RA   Silberstein S., Stalla G.K., Holsboer F., Arzt E.;
RT   "RSUME, a small RWD-containing protein, enhances SUMO conjugation and
RT   stabilizes HIF-1alpha during hypoxia.";
RL   Cell 131:309-323(2007).
CC   -!- FUNCTION: Enhancer of SUMO conjugation. Via its interaction with
CC       UBE2I/UBC9, increases SUMO conjugation to proteins by promoting the
CC       binding of E1 and E2 enzymes, thioester linkage between SUMO and
CC       UBE2I/UBC9 and transfer of SUMO to specific target proteins which
CC       include HIF1A, PIAS, NFKBIA, NR3C1 and TOP1. Positively regulates the
CC       NF-kappa-B signaling pathway by enhancing the sumoylation of NF-kappa-B
CC       inhibitor alpha (NFKBIA), promoting its stabilization which
CC       consequently leads to an increased inhibition of NF-kappa-B
CC       transcriptional activity. Negatively regulates the hypoxia-inducible
CC       factor-1 alpha (HIF1A) signaling pathway by increasing the sumoylation
CC       of HIF1A, promoting its stabilization, transcriptional activity and the
CC       expression of its target gene VEGFA during hypoxia. Has no effect on
CC       ubiquitination. {ECO:0000250|UniProtKB:Q9Y3V2}.
CC   -!- SUBUNIT: Interacts with UBE2I/UBC9, NFKBIA, HIF1A and NCOA2.
CC       {ECO:0000250|UniProtKB:Q9Y3V2}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9Y3V2}. Cytoplasm
CC       {ECO:0000250|UniProtKB:Q9Y3V2}. Note=Colocalizes with UBC9/UBE2I in
CC       nuclear spots. {ECO:0000250|UniProtKB:Q9Y3V2}.
CC   -!- DOMAIN: The RWD domain is required for the sumoylation enhancement
CC       activity. {ECO:0000250}.
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   RefSeq; NP_001121624.1; NM_001128152.1.
DR   AlphaFoldDB; P0C7N0; -.
DR   SMR; P0C7N0; -.
DR   STRING; 10116.ENSRNOP00000039966; -.
DR   PaxDb; P0C7N0; -.
DR   GeneID; 65026; -.
DR   KEGG; rno:65026; -.
DR   UCSC; RGD:620472; rat.
DR   CTD; 25950; -.
DR   RGD; 620472; Rwdd3.
DR   VEuPathDB; HostDB:ENSRNOG00000029893; -.
DR   eggNOG; ENOG502S87K; Eukaryota.
DR   HOGENOM; CLU_087636_0_0_1; -.
DR   InParanoid; P0C7N0; -.
DR   OMA; PMVHQLV; -.
DR   OrthoDB; 1437243at2759; -.
DR   PhylomeDB; P0C7N0; -.
DR   TreeFam; TF324344; -.
DR   Reactome; R-RNO-3065678; SUMO is transferred from E1 to E2 (UBE2I, UBC9).
DR   PRO; PR:P0C7N0; -.
DR   Proteomes; UP000002494; Chromosome 2.
DR   Bgee; ENSRNOG00000029893; Expressed in testis and 20 other tissues.
DR   Genevisible; P0C7N0; RN.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR   GO; GO:1902073; P:positive regulation of hypoxia-inducible factor-1alpha signaling pathway; ISS:UniProtKB.
DR   GO; GO:0033235; P:positive regulation of protein sumoylation; ISS:UniProtKB.
DR   Gene3D; 3.10.110.10; -; 1.
DR   InterPro; IPR006575; RWD-domain.
DR   InterPro; IPR038840; RWDD3.
DR   InterPro; IPR016135; UBQ-conjugating_enzyme/RWD.
DR   PANTHER; PTHR15628; PTHR15628; 1.
DR   Pfam; PF05773; RWD; 1.
DR   SMART; SM00591; RWD; 1.
DR   SUPFAM; SSF54495; SSF54495; 1.
DR   PROSITE; PS50908; RWD; 1.
PE   2: Evidence at transcript level;
KW   Cytoplasm; Nucleus; Reference proteome.
FT   CHAIN           1..267
FT                   /note="RWD domain-containing protein 3"
FT                   /id="PRO_0000340085"
FT   DOMAIN          7..114
FT                   /note="RWD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00179"
FT   REGION          13..15
FT                   /note="Interaction with UBE2I/UBC9"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y3V2"
FT   REGION          100..102
FT                   /note="Interaction with UBE2I/UBC9"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y3V2"
SQ   SEQUENCE   267 AA;  30138 MW;  764BFB3384E6407A CRC64;
     MAEEMRQELS ALAAIFCGPH EWEMLSCSET DGAVFRIHTT AEGLAGEDVP LELAFHLPAG
     YPSCLPGISV NSERLTRAQC VTVKEKLLGE ARRLLSEPMV HELVLWTQQN LRHILSQTET
     ESSNGTCTLP ESSTVDGGLW MTLLRLDHMR ARTKYVKVVE KWASELRLTG RLMFMGKMIL
     ILLQGDRSNI KEYLILQKTS KVDVDSSGKK CKEKMISVLS ETKVQTEHKR FLAFEVKEYS
     TLEELQKEFE TAGLQELFSE CVLGLVK