ID RN138_RAT Reviewed; 209 AA. AC Q99PD2; DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2001, sequence version 1. DT 24-JAN-2024, entry version 128. DE RecName: Full=E3 ubiquitin-protein ligase RNF138 {ECO:0000305}; DE EC=2.3.2.27 {ECO:0000305}; DE AltName: Full=RING finger protein 138 {ECO:0000305}; DE AltName: Full=RING-type E3 ubiquitin transferase RNF138 {ECO:0000305}; GN Name=Rnf138 {ECO:0000312|RGD:621485}; GN ORFNames=RSD-4 {ECO:0000303|Ref.1}; 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=Testis; RA Wang L., Gou D., Zhang X.; RT "A rat testis-specific gene including a RING finger domain homolog to HSD- RT 4."; RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Prostate; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). CC -!- FUNCTION: E3 ubiquitin-protein ligase involved in DNA damage response CC by promoting DNA resection and homologous recombination. Recruited to CC sites of double-strand breaks following DNA damage and specifically CC promotes double-strand break repair via homologous recombination. Two CC different, non-exclusive, mechanisms have been proposed. According to a CC report, regulates the choice of double-strand break repair by favoring CC homologous recombination over non-homologous end joining (NHEJ): acts CC by mediating ubiquitination of XRCC5/Ku80, leading to remove the Ku CC complex from DNA breaks, thereby promoting homologous recombination. CC According to another report, cooperates with UBE2Ds E2 ubiquitin CC ligases (UBE2D1, UBE2D2, UBE2D3 or UBE2D4) to promote homologous CC recombination by mediating ubiquitination of RBBP8/CtIP. Together with CC NLK, involved in the ubiquitination and degradation of TCF/LEF. Also CC exhibits auto-ubiquitination activity in combination with UBE2K. May CC act as a negative regulator in the Wnt/beta-catenin-mediated signaling CC pathway. {ECO:0000250|UniProtKB:Q8WVD3}. 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:0000305}; CC -!- PATHWAY: Protein modification; protein ubiquitination. CC {ECO:0000250|UniProtKB:Q8WVD3}. CC -!- SUBUNIT: Interacts with NLK. Interacts with XRCC5/Ku80. Interacts with CC RBBP8/CtIP. {ECO:0000250|UniProtKB:Q8WVD3}. CC -!- SUBCELLULAR LOCATION: Chromosome {ECO:0000250|UniProtKB:Q8WVD3}. CC Note=Recruited at DNA damage sites. Localizes to sites of double-strand CC break: localization to double-strand break sites is mediated by the CC zinc fingers. {ECO:0000250|UniProtKB:Q8WVD3}. CC -!- DOMAIN: The zinc finger domains (C2H2-type and C2HC-type zinc fingers) CC bind DNA and mediate recruitment to double-strand break sites. They CC show strong preference for DNA with 5'- or 3'-single-stranded CC overhangs, while they do not bind blunt-ended double-stranded DNA or CC poly(ADP-ribose) (PAR) polymers. {ECO:0000250|UniProtKB:Q8WVD3}. CC -!- PTM: Auto-ubiquitinated. {ECO:0000250|UniProtKB:Q8WVD3}. 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; AF315468; AAK11282.1; -; mRNA. DR EMBL; BC061821; AAH61821.1; -; mRNA. DR RefSeq; NP_446040.1; NM_053588.2. DR AlphaFoldDB; Q99PD2; -. DR SMR; Q99PD2; -. DR BioGRID; 250176; 2. DR STRING; 10116.ENSRNOP00000021061; -. DR PhosphoSitePlus; Q99PD2; -. DR Ensembl; ENSRNOT00000102423.1; ENSRNOP00000084639.1; ENSRNOG00000015645.7. DR Ensembl; ENSRNOT00055031274; ENSRNOP00055025233; ENSRNOG00055018403. DR Ensembl; ENSRNOT00060020850; ENSRNOP00060016436; ENSRNOG00060012283. DR Ensembl; ENSRNOT00065025598; ENSRNOP00065020107; ENSRNOG00065015419. DR GeneID; 94196; -. DR KEGG; rno:94196; -. DR AGR; RGD:621485; -. DR CTD; 51444; -. DR RGD; 621485; Rnf138. DR GeneTree; ENSGT00950000182909; -. DR InParanoid; Q99PD2; -. DR OrthoDB; 26661at2759; -. DR Reactome; R-RNO-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR UniPathway; UPA00143; -. DR PRO; PR:Q99PD2; -. DR Proteomes; UP000002494; Chromosome 18. DR GO; GO:0035861; C:site of double-strand break; ISS:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0019901; F:protein kinase binding; ISO:RGD. DR GO; GO:0003697; F:single-stranded DNA binding; ISS:UniProtKB. DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISS:UniProtKB. DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; ISO:RGD. DR GO; GO:0010792; P:DNA double-strand break processing involved in repair via single-strand annealing; ISS:UniProtKB. DR GO; GO:0000724; P:double-strand break repair via homologous recombination; ISS:UniProtKB. DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB. DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW. DR CDD; cd16544; RING-HC_RNF138; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR034734; ZF_C2HC_RNF. DR InterPro; IPR001841; Znf_RING. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR PANTHER; PTHR46968; E3 UBIQUITIN-PROTEIN LIGASE RNF138; 1. DR PANTHER; PTHR46968:SF2; E3 UBIQUITIN-PROTEIN LIGASE RNF138; 1. DR Pfam; PF13923; zf-C3HC4_2; 1. DR Pfam; PF18574; zf_C2HC_14; 1. DR SMART; SM00184; RING; 1. DR SUPFAM; SSF57850; RING/U-box; 1. DR PROSITE; PS51803; ZF_C2HC_RNF; 1. DR PROSITE; PS50089; ZF_RING_2; 1. PE 2: Evidence at transcript level; KW Chromosome; DNA damage; DNA repair; DNA-binding; Metal-binding; KW Phosphoprotein; Reference proteome; Transferase; Ubl conjugation; KW Ubl conjugation pathway; Wnt signaling pathway; Zinc; Zinc-finger. FT CHAIN 1..209 FT /note="E3 ubiquitin-protein ligase RNF138" FT /id="PRO_0000261609" FT DOMAIN 189..207 FT /note="UIM" FT /evidence="ECO:0000250|UniProtKB:Q8WVD3" FT ZN_FING 18..58 FT /note="RING-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175" FT ZN_FING 86..105 FT /note="C2HC RNF-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01144" FT ZN_FING 157..180 FT /note="C2H2-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT REGION 125..154 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 86 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01144" FT BINDING 89 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01144" FT BINDING 101 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01144" FT BINDING 105 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01144" FT MOD_RES 142 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q8WVD3" SQ SEQUENCE 209 AA; 24072 MW; 8C3A06E4EB24CFDB CRC64; MSEELSADTS YTEDDFYCPV CQEVLKTPVR TAACQHVFCR KCFLTAMRES GIHCPLCRGS VTRRERACPE RAIDLENIMR RVSGSCRCCS KKIKFYRMRH HYKSCKKYQD EYGVSSVIPN VKISQDSVRS SNRSETSASD NTETYQEDTS SSGHPTFKCP LCQESNFTRQ RLLDHCNSNH LFQIVPVNLQ LDEETQYQTA VEESFQVNM //