RN126_MOUSE
ID RN126_MOUSE Reviewed; 313 AA.
AC Q91YL2;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=E3 ubiquitin-protein ligase RNF126 {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000269|PubMed:23418353};
DE AltName: Full=RING finger protein 126 {ECO:0000312|MGI:MGI:1917544};
GN Name=Rnf126 {ECO:0000312|MGI:MGI:1917544};
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 [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen, 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 [3]
RP FUNCTION, PATHWAY, CATALYTIC ACTIVITY, MUTAGENESIS OF CYS-13; CYS-16 AND
RP CYS-231, AND INTERACTION WITH CCDC50; EGFR; FLT3 AND SCAMP3.
RX PubMed=23418353; DOI=10.1242/jcs.116129;
RA Smith C.J., Berry D.M., McGlade C.J.;
RT "The E3 ubiquitin ligases RNF126 and Rabring7 regulate endosomal sorting of
RT the epidermal growth factor receptor.";
RL J. Cell Sci. 126:1366-1380(2013).
RN [4]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=23277564; DOI=10.1073/pnas.1214538110;
RA Delker R.K., Zhou Y., Strikoudis A., Stebbins C.E., Papavasiliou F.N.;
RT "Solubility-based genetic screen identifies RING finger protein 126 as an
RT E3 ligase for activation-induced cytidine deaminase.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:1029-1034(2013).
RN [5]
RP STRUCTURE BY NMR OF 221-291.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the zinc finger, C3HC4 type (RING finger) domain of
RT RING finger protein 126.";
RL Submitted (FEB-2008) to the PDB data bank.
CC -!- FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination oF
CC target proteins (By similarity). Depending on the associated E2 ligase,
CC mediates 'Lys-48'- and 'Lys-63'-linked polyubiquitination of substrates
CC (PubMed:23418353). Part of a BAG6-dependent quality control process
CC ensuring that proteins of the secretory pathway that are mislocalized
CC to the cytosol are degraded by the proteasome (By similarity). Probably
CC acts by providing the ubiquitin ligase activity associated with the
CC BAG6 complex and be responsible for ubiquitination of the hydrophobic
CC mislocalized proteins and their targeting to the proteasome (By
CC similarity). May also play a role in the endosomal recycling of IGF2R,
CC the cation-independent mannose-6-phosphate receptor (By similarity).
CC May play a role in the endosomal sorting and degradation of several
CC membrane receptors including EGFR, FLT3, MET and CXCR4, by mediating
CC their ubiquitination (PubMed:23418353). By ubiquitinating CDKN1A/p21
CC and targeting it for degradation, may also promote cell proliferation
CC (By similarity). May monoubiquitinate AICDA (By similarity).
CC {ECO:0000250|UniProtKB:Q9BV68, ECO:0000269|PubMed:23418353}.
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:23418353};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:23418353}.
CC -!- SUBUNIT: Interacts with CCDC50, EGFR, FLT3 and SCAMP3
CC (PubMed:23418353). Interacts with BAG6 (via ubiquitin-like domain);
CC required for BAG6-dependent ubiquitination of proteins mislocalized to
CC the cytosol (By similarity). Interacts with CDKN1A (By similarity).
CC Interacts with AICDA (By similarity). {ECO:0000250|UniProtKB:Q9BV68,
CC ECO:0000269|PubMed:23418353}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9BV68}. Nucleus
CC {ECO:0000250|UniProtKB:Q9BV68}.
CC -!- TISSUE SPECIFICITY: Detected in B-cells (at protein level).
CC {ECO:0000269|PubMed:23277564}.
CC -!- INDUCTION: Up-regulated in B-cells that undergo class-switch
CC recombination (at protein level). {ECO:0000269|PubMed:23277564}.
CC -!- DOMAIN: The C4-type zinc finger is required for interaction with BAG6.
CC {ECO:0000250|UniProtKB:Q9BV68}.
CC -!- PTM: Ubiquitinated. May undergo autoubiquitination.
CC {ECO:0000250|UniProtKB:Q9BV68, ECO:0000303|PubMed:23418353}.
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DR EMBL; BC016543; AAH16543.1; -; mRNA.
DR CCDS; CCDS23989.1; -.
DR RefSeq; NP_653111.1; NM_144528.3.
DR PDB; 2ECT; NMR; -; A=221-291.
DR PDBsum; 2ECT; -.
DR AlphaFoldDB; Q91YL2; -.
DR BMRB; Q91YL2; -.
DR SMR; Q91YL2; -.
DR BioGRID; 213968; 5.
DR IntAct; Q91YL2; 1.
DR MINT; Q91YL2; -.
DR STRING; 10090.ENSMUSP00000039486; -.
DR iPTMnet; Q91YL2; -.
DR PhosphoSitePlus; Q91YL2; -.
DR EPD; Q91YL2; -.
DR MaxQB; Q91YL2; -.
DR PaxDb; Q91YL2; -.
DR PRIDE; Q91YL2; -.
DR ProteomicsDB; 301610; -.
DR Antibodypedia; 22343; 162 antibodies from 23 providers.
DR DNASU; 70294; -.
DR Ensembl; ENSMUST00000047203; ENSMUSP00000039486; ENSMUSG00000035890.
DR GeneID; 70294; -.
DR KEGG; mmu:70294; -.
DR UCSC; uc007fzr.3; mouse.
DR CTD; 55658; -.
DR MGI; MGI:1917544; Rnf126.
DR VEuPathDB; HostDB:ENSMUSG00000035890; -.
DR eggNOG; KOG0800; Eukaryota.
DR GeneTree; ENSGT00940000157113; -.
DR HOGENOM; CLU_034892_0_0_1; -.
DR InParanoid; Q91YL2; -.
DR OMA; GVRYWCH; -.
DR OrthoDB; 1249953at2759; -.
DR PhylomeDB; Q91YL2; -.
DR TreeFam; TF317985; -.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 70294; 10 hits in 74 CRISPR screens.
DR ChiTaRS; Rnf126; mouse.
DR EvolutionaryTrace; Q91YL2; -.
DR PRO; PR:Q91YL2; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q91YL2; protein.
DR Bgee; ENSMUSG00000035890; Expressed in dorsal pancreas and 244 other tissues.
DR ExpressionAtlas; Q91YL2; baseline and differential.
DR Genevisible; Q91YL2; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005154; F:epidermal growth factor receptor binding; IPI:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:0071629; P:cytoplasm protein quality control by the ubiquitin-proteasome system; ISS:UniProtKB.
DR GO; GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0006513; P:protein monoubiquitination; ISS:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; ISS:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0043162; P:ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway; ISS:UniProtKB.
DR CDD; cd16801; RING-H2_RNF126; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR039572; RNF126.
DR InterPro; IPR039525; RNF126-like_zinc-ribbon.
DR InterPro; IPR039571; RNF126_RING-H2.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR15710:SF21; PTHR15710:SF21; 1.
DR Pfam; PF13639; zf-RING_2; 1.
DR Pfam; PF14369; zinc_ribbon_9; 1.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Metal-binding; Nucleus;
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:Q9BV68"
FT CHAIN 2..313
FT /note="E3 ubiquitin-protein ligase RNF126"
FT /id="PRO_0000056094"
FT ZN_FING 13..32
FT /note="C4-type"
FT /evidence="ECO:0000250|UniProtKB:Q9BV68"
FT ZN_FING 231..272
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 5..100
FT /note="Required for interaction with BAG6"
FT /evidence="ECO:0000250|UniProtKB:Q9BV68"
FT REGION 42..63
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 95..128
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 202..306
FT /note="Sufficient for interaction with AICDA"
FT /evidence="ECO:0000250|UniProtKB:Q9BV68"
FT REGION 279..313
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 46..63
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 104..122
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 13
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9BV68"
FT BINDING 16
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9BV68"
FT BINDING 29
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9BV68"
FT BINDING 32
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9BV68"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q9BV68"
FT MOD_RES 5
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BV68"
FT MUTAGEN 13
FT /note="C->A: Loss of interaction with EGFR and FLT3. No
FT effect on E3 ubiquitin protein ligase activity but alters
FT specificity for 'Lys-48'-linked chains; when associated
FT with A-16."
FT /evidence="ECO:0000269|PubMed:23418353"
FT MUTAGEN 16
FT /note="C->A: Loss of interaction with EGFR and FLT3. No
FT effect on E3 ubiquitin protein ligase activity but alters
FT specificity for 'Lys-48'-linked chains; when associated
FT with A-13."
FT /evidence="ECO:0000269|PubMed:23418353"
FT MUTAGEN 231
FT /note="C->A: Loss of E3 ubiquitin protein ligase activity."
FT /evidence="ECO:0000269|PubMed:23418353"
FT STRAND 225..228
FT /evidence="ECO:0007829|PDB:2ECT"
FT TURN 232..235
FT /evidence="ECO:0007829|PDB:2ECT"
FT STRAND 244..246
FT /evidence="ECO:0007829|PDB:2ECT"
FT STRAND 252..254
FT /evidence="ECO:0007829|PDB:2ECT"
FT TURN 255..257
FT /evidence="ECO:0007829|PDB:2ECT"
FT HELIX 259..262
FT /evidence="ECO:0007829|PDB:2ECT"
FT TURN 269..271
FT /evidence="ECO:0007829|PDB:2ECT"
SQ SEQUENCE 313 AA; 34081 MW; A1BA6A8C2711D0C7 CRC64;
MAEASPQPGR YFCHCCSVEI VPRLPDYICP RCESGFIEEL PEETRNTENG SAPSTAPTDQ
NRQPFENVDQ HLFTLPQGYS QFAFGIFDDS FEIPTFPPGA QADDGRDPES RREREHQSRH
RYGARQPRAR LTARRATGRH EGVPTLEGII QQLVNGIISP AAVPSLGLGP WGVLHSNPMD
YAWGANGLDT IITQLLNQFE NTGPPPADKE KIQALPTVPV TEEHVGSGLE CPVCKEDYAL
GESVRQLPCN HLFHDSCIVP WLEQHDSCPV CRKSLTGQNT ATNPPGLTGV GFSSSSSSSS
SSSPSNENAT SNS
