ID RN123_MOUSE Reviewed; 1314 AA.
AC Q5XPI3; Q6PGE0;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 27-MAR-2024, entry version 147.
DE RecName: Full=E3 ubiquitin-protein ligase RNF123 {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q5XPI4};
DE AltName: Full=Kip1 ubiquitination-promoting complex protein 1 {ECO:0000303|PubMed:15531880};
DE AltName: Full=RING finger protein 123;
GN Name=Rnf123; Synonyms=Kpc1 {ECO:0000303|PubMed:15531880};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J;
RX PubMed=15531880; DOI=10.1038/ncb1194;
RA Kamura T., Hara T., Matsumoto M., Ishida N., Okumura F., Hatakeyama S.,
RA Yoshida M., Nakayama K., Nakayama K.;
RT "Cytoplasmic ubiquitin ligase KPC regulates proteolysis of p27(Kip1) at G1
RT phase.";
RL Nat. Cell Biol. 6:1229-1235(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Brain;
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).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Liver, Lung, Pancreas, Spleen,
RC and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-683, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryo;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
CC -!- FUNCTION: Catalytic subunit of the KPC complex that acts as E3
CC ubiquitin-protein ligase. Promotes the ubiquitination and proteasome-
CC mediated degradation of CDKN1B which is the cyclin-dependent kinase
CC inhibitor at the G0-G1 transition of the cell cycle. Also acts as a key
CC regulator of the NF-kappa-B signaling by promoting maturation of the
CC NFKB1 component of NF-kappa-B: acts by catalyzing ubiquitination of the
CC NFKB1 p105 precursor, leading to limited proteasomal degradation of
CC NFKB1 p105 and generation of the active NFKB1 p50 subunit. Functions
CC also as an inhibitor of innate antiviral signaling mediated by RIGI and
CC IFIH1 independently of its E3 ligase activity. Interacts with the N-
CC terminal CARD domains of RIGI and IFIH1 and competes with the
CC downstream adapter MAVS. {ECO:0000250|UniProtKB:Q5XPI4}.
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:Q5XPI4};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q5XPI4}.
CC -!- SUBUNIT: Component of the KPC complex composed of RNF123/KPC1 and
CC UBAC1/KPC2. Interacts with UBAC1 and CDKN1B via its N-terminal domain.
CC Interacts with RIGI (via N-terminus) and IFIH1 (via N-terminus).
CC {ECO:0000250|UniProtKB:Q5XPI4}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q5XPI4}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q5XPI3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5XPI3-2; Sequence=VSP_020651;
CC -!- PTM: Ubiquitinated, leading to its degradation. Deubiquitinated by
CC USP19, thereby stimulating CDKN1B ubiquitin-dependent degradation.
CC {ECO:0000250|UniProtKB:D3ZXK7}.
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DR EMBL; AY744153; AAU93471.1; -; mRNA.
DR EMBL; BC057082; AAH57082.1; -; mRNA.
DR CCDS; CCDS52922.1; -. [Q5XPI3-1]
DR CCDS; CCDS81072.1; -. [Q5XPI3-2]
DR RefSeq; NP_001298081.1; NM_001311152.1. [Q5XPI3-2]
DR RefSeq; NP_115932.1; NM_032543.2. [Q5XPI3-1]
DR RefSeq; XP_006511940.1; XM_006511877.3.
DR RefSeq; XP_006511941.1; XM_006511878.2. [Q5XPI3-2]
DR RefSeq; XP_006511942.1; XM_006511879.3. [Q5XPI3-2]
DR RefSeq; XP_017169196.1; XM_017313707.1.
DR AlphaFoldDB; Q5XPI3; -.
DR SMR; Q5XPI3; -.
DR BioGRID; 220011; 17.
DR STRING; 10090.ENSMUSP00000125745; -.
DR GlyGen; Q5XPI3; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q5XPI3; -.
DR PhosphoSitePlus; Q5XPI3; -.
DR SwissPalm; Q5XPI3; -.
DR EPD; Q5XPI3; -.
DR MaxQB; Q5XPI3; -.
DR PaxDb; 10090-ENSMUSP00000125745; -.
DR ProteomicsDB; 300531; -. [Q5XPI3-1]
DR ProteomicsDB; 300532; -. [Q5XPI3-2]
DR Pumba; Q5XPI3; -.
DR Antibodypedia; 30603; 125 antibodies from 19 providers.
DR DNASU; 84585; -.
DR Ensembl; ENSMUST00000047746.13; ENSMUSP00000040803.7; ENSMUSG00000041528.16. [Q5XPI3-2]
DR Ensembl; ENSMUST00000160249.8; ENSMUSP00000124548.2; ENSMUSG00000041528.16. [Q5XPI3-1]
DR Ensembl; ENSMUST00000162355.8; ENSMUSP00000125745.2; ENSMUSG00000041528.16. [Q5XPI3-2]
DR Ensembl; ENSMUST00000178267.8; ENSMUSP00000136953.2; ENSMUSG00000041528.16. [Q5XPI3-1]
DR GeneID; 84585; -.
DR KEGG; mmu:84585; -.
DR UCSC; uc009roi.3; mouse. [Q5XPI3-2]
DR UCSC; uc033jmw.1; mouse. [Q5XPI3-1]
DR AGR; MGI:2148796; -.
DR CTD; 63891; -.
DR MGI; MGI:2148796; Rnf123.
DR VEuPathDB; HostDB:ENSMUSG00000041528; -.
DR eggNOG; KOG2242; Eukaryota.
DR eggNOG; KOG4692; Eukaryota.
DR GeneTree; ENSGT00940000155781; -.
DR HOGENOM; CLU_006687_2_0_1; -.
DR InParanoid; Q5XPI3; -.
DR OMA; ICATCFD; -.
DR OrthoDB; 3145419at2759; -.
DR PhylomeDB; Q5XPI3; -.
DR TreeFam; TF313546; -.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 84585; 1 hit in 78 CRISPR screens.
DR ChiTaRS; Rnf123; mouse.
DR PRO; PR:Q5XPI3; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q5XPI3; Protein.
DR Bgee; ENSMUSG00000041528; Expressed in retinal neural layer and 250 other cell types or tissues.
DR ExpressionAtlas; Q5XPI3; baseline and differential.
DR Genevisible; Q5XPI3; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0031965; C:nuclear membrane; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISS:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IBA:GO_Central.
DR GO; GO:0051604; P:protein maturation; ISS:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; ISO:MGI.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IBA:GO_Central.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR CDD; cd16541; RING-HC_RNF123; 1.
DR CDD; cd12882; SPRY_RNF123; 1.
DR Gene3D; 2.60.120.920; -; 1.
DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1.
DR InterPro; IPR001870; B30.2/SPRY.
DR InterPro; IPR043136; B30.2/SPRY_sf.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR InterPro; IPR045129; RNF123/RSPRY1-like.
DR InterPro; IPR003877; SPRY_dom.
DR InterPro; IPR035773; SPRY_RNF123.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR13363:SF5; E3 UBIQUITIN-PROTEIN LIGASE RNF123; 1.
DR PANTHER; PTHR13363; RING FINGER AND SRY DOMAIN-CONTAINING; 1.
DR Pfam; PF00622; SPRY; 1.
DR Pfam; PF13920; zf-C3HC4_3; 1.
DR SMART; SM00184; RING; 1.
DR SMART; SM00449; SPRY; 1.
DR SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 1.
DR SUPFAM; SSF57850; RING/U-box; 1.
DR PROSITE; PS50188; B302_SPRY; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cytoplasm; Metal-binding; Methylation;
KW Phosphoprotein; Reference proteome; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q5XPI4"
FT CHAIN 2..1314
FT /note="E3 ubiquitin-protein ligase RNF123"
FT /id="PRO_0000250448"
FT DOMAIN 74..254
FT /note="B30.2/SPRY"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT ZN_FING 1254..1292
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 460..483
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 968..974
FT /note="Interaction with NFKB1"
FT /evidence="ECO:0000250|UniProtKB:Q5XPI4"
FT COMPBIAS 461..483
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 1254
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q5XPI4"
FT BINDING 1257
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q5XPI4"
FT BINDING 1269
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q5XPI4"
FT BINDING 1271
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q5XPI4"
FT BINDING 1274
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q5XPI4"
FT BINDING 1277
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q5XPI4"
FT BINDING 1288
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q5XPI4"
FT BINDING 1291
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q5XPI4"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q5XPI4"
FT MOD_RES 675
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:D3ZXK7"
FT MOD_RES 683
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT VAR_SEQ 653
FT /note="Q -> QVWQEGQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_020651"
SQ SEQUENCE 1314 AA; 148652 MW; 6DB1F01109FFFD28 CRC64;
MASKGTGMSF SRKSYRLTSD AEKSRVTGIV QEKLLSDYLY RIFSPPDRGP AAATSRKPLN
FHNLPEHVDQ LLQVDSEDNE SQGQVEGRLG PSTVVLDHTG GFEGLLLVDD DLLGVIGHSN
FGTIRSTTCV YKGKWVYEVL ISSQGLMQIG WCTINCRFNQ EEGVGDTHNS YAYDGNRVRK
WNVTTTNYGK AWAAGDIVSC LIDLDDGTLS FCLNGVSLGT AFENLSRGLG MAYFPAISLS
FKESVAFNFG SRPLRYPVAG FRPLQDPPFA DLVRAQRLLG CFQAVLSVEL DPVEGRLVET
ESSEWQLQGQ PTVLLTLAHI FHHFAPLLRK VYLVEAVLMS FLLGVVEKGT PEQAQSVVHQ
ILDLLWLFME DYEVQDCLKQ LMMSLLRLYR FSPIVPDLGL QIHYLRLTMS ILRHEKSRKF
LLSNVLFDML RSVVFFYIKS PLRVEEAGLK ELIPTTWWPH RSSRESRDGK EAREETTEER
QRRRAYERGC QRLKKRIEVV EELQVQILKL LLDNKDDNGG EASRYIFLTK FRKFLQENAS
GRGNTPVLCP PEYMVCFLHR LVSALRFYWD EYKASNPRAS FSEEAYIPPQ IFYNGKVDYF
DLQRLGGLLS HLRKTLKDDL ASKANIVIDP LELQAATMDD LDEDEEPAPS AAQRPMQALA
IGGALPLPRP GWLSSPTLGR ANRFLSTAAV SLMTPRRLLS TMEKVKVRSL NVEQRTREDI
EGSHWNEGLL LGRPPEEPEQ PLTENSLLEV LDGTVMMYNL SVHQQLGKMV GVSDDVNEYA
MALRDTEDKL RRCPKRRKDI LAELTKSQKV FSEKLDHLSR RLAWVHATVY SQEKMLDIYW
LLRVCLRTIE HGDRTGSLFA FMPEFYLSVA INSYSALKNY FGPVHSMEEL PGYEETLTRL
AAILAKHFAD PRIVGTDIRD SLMQALASYV CYPHSLRAVE RIPEEQRIAM VRNLLAPYEQ
RPWAQTNWIL VRLWRGCGFG YRYTRLPHLL KTKPEDANLP SLQKPCPSTL LQQHMADLLR
QGSDVAPSFL NSVLNQLNWA FSEFIGMIQE IQQAAERLER NFVDSRQLKV CATCFDLSVS
LLRVLEMTIT LVPEIFLDWS RPTSEMLLRR LAQLLNQVLN RVTAERNLFD RVVTLRLPGL
ESVDHYPILV AVTGILVRLL VHGPTSETEQ ATSVLLADPC FQLRSICYLL GQPEPLAPGT
TLPAPDRKRF SLQSYTDYIS AEELAQVEQM LAHLTAASAQ AAAASLPTNE EDLCPICYAH
PISAVFQPCG HKSCKACINQ HLMNNKDCFF CKATIVSVED WDKAANTSAM SSAA
//
