RN217_MOUSE
ID RN217_MOUSE Reviewed; 515 AA.
AC D3YYI7;
DT 22-FEB-2012, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 2.
DT 03-AUG-2022, entry version 76.
DE RecName: Full=E3 ubiquitin-protein ligase RNF217 {ECO:0000303|PubMed:33895792};
DE EC=2.3.2.31 {ECO:0000269|PubMed:33895792};
DE AltName: Full=IBR domain-containing protein 1;
DE AltName: Full=RING finger protein 217;
GN Name=Rnf217; Synonyms=Ibrdc1;
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 GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP CYS-236; CYS-239 AND CYS-409.
RX PubMed=33895792; DOI=10.1182/blood.2020008986;
RA Jiang L., Wang J., Wang K., Wang H., Wu Q., Yang C., Yu Y., Ni P.,
RA Zhong Y., Song Z., Xie E., Hu R., Min J., Wang F.;
RT "RNF217 regulates iron homeostasis through its E3 ubiquitin ligase activity
RT by modulating ferroportin degradation.";
RL Blood 138:689-705(2021).
CC -!- FUNCTION: E3 ubiquitin-protein ligase which accepts ubiquitin from E2
CC ubiquitin-conjugating enzymes in the form of a thioester and then
CC directly transfers the ubiquitin to targeted substrates. Mediates the
CC degradation of the iron exporter ferroportin/SLC40A1 and thus regulates
CC iron homeostasis. {ECO:0000269|PubMed:33895792}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + [acceptor protein]-N(6)-ubiquitinyl-L-lysine.;
CC EC=2.3.2.31; Evidence={ECO:0000269|PubMed:33895792};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with HAX1. {ECO:0000250|UniProtKB:Q8TC41}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass membrane
CC protein {ECO:0000305}. Cytoplasm {ECO:0000250|UniProtKB:Q8TC41}.
CC -!- DOMAIN: Members of the RBR family are atypical E3 ligases. They
CC interact with the E2 conjugating enzyme UBE2L3 and function like HECT-
CC type E3 enzymes: they bind E2s via the first RING domain, but require
CC an obligate trans-thiolation step during the ubiquitin transfer,
CC requiring a conserved cysteine residue in the second RING domain.
CC {ECO:0000250|UniProtKB:O60260}.
CC -!- DISRUPTION PHENOTYPE: Macrophage-specific knockout mice have increased
CC iron export and altered ferroportin/SLC40A1 degradation.
CC {ECO:0000269|PubMed:33895792}.
CC -!- SIMILARITY: Belongs to the RBR family. RNF217 subfamily. {ECO:0000305}.
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DR EMBL; AC116557; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS48531.1; -.
DR RefSeq; NP_001139821.1; NM_001146349.1.
DR AlphaFoldDB; D3YYI7; -.
DR STRING; 10090.ENSMUSP00000080650; -.
DR iPTMnet; D3YYI7; -.
DR PhosphoSitePlus; D3YYI7; -.
DR PaxDb; D3YYI7; -.
DR PRIDE; D3YYI7; -.
DR ProteomicsDB; 300494; -.
DR Antibodypedia; 32675; 125 antibodies from 18 providers.
DR Ensembl; ENSMUST00000081989; ENSMUSP00000080650; ENSMUSG00000063760.
DR GeneID; 268291; -.
DR KEGG; mmu:268291; -.
DR UCSC; uc007etu.2; mouse.
DR CTD; 154214; -.
DR MGI; MGI:3610311; Rnf217.
DR VEuPathDB; HostDB:ENSMUSG00000063760; -.
DR eggNOG; KOG1815; Eukaryota.
DR GeneTree; ENSGT00730000111285; -.
DR HOGENOM; CLU_035717_1_0_1; -.
DR InParanoid; D3YYI7; -.
DR OMA; VTECFEF; -.
DR OrthoDB; 1140368at2759; -.
DR PhylomeDB; D3YYI7; -.
DR TreeFam; TF330860; -.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 268291; 0 hits in 72 CRISPR screens.
DR ChiTaRS; Rnf217; mouse.
DR PRO; PR:D3YYI7; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; D3YYI7; protein.
DR Bgee; ENSMUSG00000063760; Expressed in endothelial cell of lymphatic vessel and 214 other tissues.
DR Genevisible; D3YYI7; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0000151; C:ubiquitin ligase complex; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0031624; F:ubiquitin conjugating enzyme binding; IBA:GO_Central.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR031127; E3_UB_ligase_RBR.
DR InterPro; IPR002867; IBR_dom.
DR InterPro; IPR044066; TRIAD_supradom.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR11685; PTHR11685; 1.
DR Pfam; PF01485; IBR; 2.
DR SMART; SM00647; IBR; 2.
DR PROSITE; PS51873; TRIAD; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Membrane; Metal-binding; Reference proteome; Repeat;
KW Transferase; Transmembrane; Transmembrane helix; Ubl conjugation pathway;
KW Zinc; Zinc-finger.
FT CHAIN 1..515
FT /note="E3 ubiquitin-protein ligase RNF217"
FT /id="PRO_0000415821"
FT TRANSMEM 476..496
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ZN_FING 236..282
FT /note="RING-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT ZN_FING 301..369
FT /note="IBR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT ZN_FING 396..425
FT /note="RING-type 2; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT REGION 1..125
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 147..189
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 232..451
FT /note="TRIAD supradomain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT COMPBIAS 154..185
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 409
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 236
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 239
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 256
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 259
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 356
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 359
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 364
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 369
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 396
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 399
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 414
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 417
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 422
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 425
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 438
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 447
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT MUTAGEN 236
FT /note="C->A: Loss of SLC40A1 degradation; when associated
FT with A-239."
FT /evidence="ECO:0000269|PubMed:33895792"
FT MUTAGEN 239
FT /note="C->A: Loss of SLC40A1 degradation; when associated
FT with A-236."
FT /evidence="ECO:0000269|PubMed:33895792"
FT MUTAGEN 409
FT /note="C->A: Loss of SLC40A1 degradation."
FT /evidence="ECO:0000269|PubMed:33895792"
SQ SEQUENCE 515 AA; 56036 MW; 718AF99658F9F55D CRC64;
MGEEQSTVSG SGGARASGGG SAGQPESPRP RGDRVRTAGP RAAASSSRPN GGGGGRDPGC
VDASVQEPAS NRAPAGQPAR LPLSGPLDPQ SLELQLEREA EGAGPREAPP GQQPPDGLLL
DVLAQRHPPP AKPQVLCSVY CVESDLPEAP SAESPSPSES PPQAPLGPIP ASPPPSFPSS
PLSLPADPLS PDGGSIELEF YLAPEPFSVP GLLGAPPYSG LGGVGDPYAP LMVLMCRVCL
EDKPIKPLPC CKKAVCEECL KIYLSSQVQL GQVEIKCPVT ECFEFLEETT VVYNLTHEDS
IKYKYFLELG RIDSSTKPCP QCKHFTTFKK KGHIPTPSRS ESRYKIQCPT CQLIWCFKCH
SPWHEGVNCK EYKKGDKLLR HWASEIEHGQ RNAQKCPKCK IHIQRTEGCD HMTCSQCNTN
FCYRCGERYR QLRFFGDHTS NLSIFGCKYR YLPERPHLRR LVRGSVCAGK LFIAPLILVL
GLALGAIAVV IGLFVFPIYC LCKKQRKRSR TGMHW
