TRI48_HUMAN
ID TRI48_HUMAN Reviewed; 224 AA.
AC Q8IWZ4; Q9BUW4;
DT 23-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 3.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=E3 ubiquitin-protein ligase TRIM48 {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000269|PubMed:29186683};
DE AltName: Full=RING finger protein 101 {ECO:0000312|HGNC:HGNC:19021};
DE AltName: Full=Tripartite motif-containing protein 48 {ECO:0000312|HGNC:HGNC:19021};
GN Name=TRIM48 {ECO:0000312|HGNC:HGNC:19021};
GN Synonyms=RNF101 {ECO:0000312|HGNC:HGNC:19021};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Meroni G.;
RT "Novel tripartite motif family members.";
RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
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 FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH PRMT1; MAP3K5 AND STRAP,
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-46.
RX PubMed=29186683; DOI=10.1016/j.celrep.2017.11.007;
RA Hirata Y., Katagiri K., Nagaoka K., Morishita T., Kudoh Y., Hatta T.,
RA Naguro I., Kano K., Udagawa T., Natsume T., Aoki J., Inada T., Noguchi T.,
RA Ichijo H., Matsuzawa A.;
RT "TRIM48 Promotes ASK1 Activation and Cell Death through Ubiquitination-
RT Dependent Degradation of the ASK1-Negative Regulator PRMT1.";
RL Cell Rep. 21:2447-2457(2017).
CC -!- FUNCTION: E3 ubiquitin-protein ligase which promotes K48-linked
CC polyubiquitination of protein methyltransferase PRMT1, leading to PRMT1
CC degradation (PubMed:29186683). This suppresses methylation of the PRMT1
CC substrate MAP3K5/ASK1, promoting its activation and increasing MAP3K5-
CC dependent cell death induced by oxidative stress (PubMed:29186683).
CC TRIM48-mediated ubiquitination of PRMT1 also suppresses methylation of
CC FOXO1 by PRMT1, leading to inhibition of FOXO1 transcriptional activity
CC (PubMed:29186683). {ECO:0000269|PubMed:29186683}.
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:0000269|PubMed:29186683};
CC -!- SUBUNIT: Interacts with PRMT1; the interaction leads to ubiquitination
CC of PRMT1 by TRIM48 (PubMed:29186683). Interacts with MAP3K5
CC (PubMed:29186683). Interacts with STRAP (PubMed:29186683).
CC {ECO:0000269|PubMed:29186683}.
CC -!- INTERACTION:
CC Q8IWZ4; Q9Y5B8: NME7; NbExp=3; IntAct=EBI-17555779, EBI-744782;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:29186683}.
CC -!- SIMILARITY: Belongs to the TRIM/RBCC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH01862.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAO14946.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAO14946.1; Type=Erroneous termination; Note=Extended C-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF521869; AAO14946.1; ALT_SEQ; mRNA.
DR EMBL; BC001862; AAH01862.1; ALT_INIT; mRNA.
DR CCDS; CCDS7947.2; -.
DR RefSeq; NP_077019.2; NM_024114.3.
DR AlphaFoldDB; Q8IWZ4; -.
DR BioGRID; 122544; 2.
DR IntAct; Q8IWZ4; 1.
DR STRING; 9606.ENSP00000402414; -.
DR iPTMnet; Q8IWZ4; -.
DR PhosphoSitePlus; Q8IWZ4; -.
DR BioMuta; TRIM48; -.
DR DMDM; 251757349; -.
DR MassIVE; Q8IWZ4; -.
DR PaxDb; Q8IWZ4; -.
DR PeptideAtlas; Q8IWZ4; -.
DR PRIDE; Q8IWZ4; -.
DR Antibodypedia; 27102; 110 antibodies from 16 providers.
DR DNASU; 79097; -.
DR Ensembl; ENST00000417545.5; ENSP00000402414.2; ENSG00000150244.12.
DR GeneID; 79097; -.
DR KEGG; hsa:79097; -.
DR MANE-Select; ENST00000417545.5; ENSP00000402414.2; NM_024114.5; NP_077019.2.
DR UCSC; uc010rid.2; human.
DR CTD; 79097; -.
DR DisGeNET; 79097; -.
DR GeneCards; TRIM48; -.
DR HGNC; HGNC:19021; TRIM48.
DR HPA; ENSG00000150244; Not detected.
DR neXtProt; NX_Q8IWZ4; -.
DR OpenTargets; ENSG00000150244; -.
DR PharmGKB; PA134981425; -.
DR VEuPathDB; HostDB:ENSG00000150244; -.
DR eggNOG; KOG2177; Eukaryota.
DR GeneTree; ENSGT00940000163213; -.
DR HOGENOM; CLU_013137_6_4_1; -.
DR InParanoid; Q8IWZ4; -.
DR OrthoDB; 83515at2759; -.
DR PhylomeDB; Q8IWZ4; -.
DR TreeFam; TF338674; -.
DR PathwayCommons; Q8IWZ4; -.
DR Reactome; R-HSA-877300; Interferon gamma signaling.
DR SignaLink; Q8IWZ4; -.
DR BioGRID-ORCS; 79097; 59 hits in 1022 CRISPR screens.
DR ChiTaRS; TRIM48; human.
DR GenomeRNAi; 79097; -.
DR Pharos; Q8IWZ4; Tdark.
DR PRO; PR:Q8IWZ4; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q8IWZ4; protein.
DR Bgee; ENSG00000150244; Expressed in skin of leg.
DR Genevisible; Q8IWZ4; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR000315; Znf_B-box.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF00643; zf-B_box; 1.
DR SMART; SM00336; BBOX; 1.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS50119; ZF_BBOX; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Metal-binding; Reference proteome; Transferase;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..224
FT /note="E3 ubiquitin-protein ligase TRIM48"
FT /id="PRO_0000056272"
FT ZN_FING 31..72
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 104..145
FT /note="B box-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 109
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 112
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 131
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 137
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT MUTAGEN 46
FT /note="C->S: Abolishes PRMT1 ubiquitination and MAP3K5
FT activation."
FT /evidence="ECO:0000269|PubMed:29186683"
SQ SEQUENCE 224 AA; 26409 MW; 1FA5F0B008C16322 CRC64;
MSRRIIVGTL QRTQRNMNSG ISQVFQRELT CPICMNYFID PVTIDCGHSF CRPCFYLNWQ
DIPILTQCFE CIKTIQQRNL KTNIRLKKMA SLARKASLWL FLSSEEQMCG IHRETKKMFC
EVDRSLLCLL CSSSQEHRYH RHCPAEWAAE EHWEKLLKKM QSLWEKACEN QRNLNVETTR
ISHWKAFGDI LYRSESVLLH MPQPLNLALR AGPITGLRDR LNQF
