RN217_HUMAN
ID RN217_HUMAN Reviewed; 542 AA.
AC Q8TC41; H7C5V4; Q5TCA4; Q9BX48;
DT 04-JAN-2005, integrated into UniProtKB/Swiss-Prot.
DT 14-MAY-2014, sequence version 4.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=E3 ubiquitin-protein ligase RNF217;
DE EC=2.3.2.31 {ECO:0000250|UniProtKB:D3YYI7};
DE AltName: Full=IBR domain-containing protein 1;
DE AltName: Full=Opposite STL {ECO:0000303|PubMed:25298122};
DE AltName: Full=RING finger protein 217;
GN Name=RNF217; Synonyms=C6orf172, IBRDC1, OSTL {ECO:0000303|PubMed:25298122};
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
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 SUBCELLULAR LOCATION, INTERACTION WITH HAX1, AND TISSUE SPECIFICITY.
RX PubMed=25298122; DOI=10.1038/srep06565;
RA Fontanari Krause L.M., Japp A.S., Krause A., Mooster J., Chopra M.,
RA Mueschen M., Bohlander S.K.;
RT "Identification and characterization of OSTL (RNF217) encoding a RING-IBR-
RT RING protein adjacent to a translocation breakpoint involving ETV6 in
RT childhood ALL.";
RL Sci. Rep. 4:6565-6565(2014).
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:0000250|UniProtKB:D3YYI7}.
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:0000250|UniProtKB:D3YYI7};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with HAX1. {ECO:0000269|PubMed:25298122}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass membrane
CC protein {ECO:0000305}. Cytoplasm {ECO:0000269|PubMed:25298122}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8TC41-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8TC41-2; Sequence=VSP_054705, VSP_054706;
CC -!- TISSUE SPECIFICITY: Mainly expressed in testis and skeletal muscle.
CC {ECO:0000269|PubMed:25298122}.
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 -!- SIMILARITY: Belongs to the RBR family. RNF217 subfamily. {ECO:0000305}.
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DR EMBL; AL136128; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL355296; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC026087; AAH26087.1; -; mRNA.
DR CCDS; CCDS5129.1; -. [Q8TC41-2]
DR CCDS; CCDS69191.1; -. [Q8TC41-1]
DR RefSeq; NP_001273327.1; NM_001286398.2. [Q8TC41-1]
DR RefSeq; NP_689766.1; NM_152553.4. [Q8TC41-2]
DR AlphaFoldDB; Q8TC41; -.
DR BioGRID; 127540; 9.
DR IntAct; Q8TC41; 4.
DR STRING; 9606.ENSP00000428698; -.
DR iPTMnet; Q8TC41; -.
DR PhosphoSitePlus; Q8TC41; -.
DR BioMuta; RNF217; -.
DR DMDM; 313104196; -.
DR EPD; Q8TC41; -.
DR MassIVE; Q8TC41; -.
DR MaxQB; Q8TC41; -.
DR PaxDb; Q8TC41; -.
DR PeptideAtlas; Q8TC41; -.
DR PRIDE; Q8TC41; -.
DR Antibodypedia; 32675; 125 antibodies from 18 providers.
DR DNASU; 154214; -.
DR Ensembl; ENST00000359704.2; ENSP00000352734.2; ENSG00000146373.17. [Q8TC41-2]
DR Ensembl; ENST00000521654.7; ENSP00000428698.2; ENSG00000146373.17. [Q8TC41-1]
DR GeneID; 154214; -.
DR KEGG; hsa:154214; -.
DR MANE-Select; ENST00000521654.7; ENSP00000428698.2; NM_001286398.3; NP_001273327.1.
DR UCSC; uc003pzr.5; human. [Q8TC41-1]
DR CTD; 154214; -.
DR DisGeNET; 154214; -.
DR GeneCards; RNF217; -.
DR HGNC; HGNC:21487; RNF217.
DR HPA; ENSG00000146373; Tissue enhanced (parathyroid).
DR MIM; 618592; gene.
DR neXtProt; NX_Q8TC41; -.
DR OpenTargets; ENSG00000146373; -.
DR PharmGKB; PA162401868; -.
DR VEuPathDB; HostDB:ENSG00000146373; -.
DR eggNOG; KOG1815; Eukaryota.
DR GeneTree; ENSGT00730000111285; -.
DR HOGENOM; CLU_035717_1_0_1; -.
DR InParanoid; Q8TC41; -.
DR OrthoDB; 1140368at2759; -.
DR PhylomeDB; Q8TC41; -.
DR TreeFam; TF330860; -.
DR PathwayCommons; Q8TC41; -.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q8TC41; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 154214; 9 hits in 1113 CRISPR screens.
DR ChiTaRS; RNF217; human.
DR GenomeRNAi; 154214; -.
DR Pharos; Q8TC41; Tdark.
DR PRO; PR:Q8TC41; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q8TC41; protein.
DR Bgee; ENSG00000146373; Expressed in oviduct epithelium and 162 other tissues.
DR ExpressionAtlas; Q8TC41; baseline and differential.
DR Genevisible; Q8TC41; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
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:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
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; ISS:UniProtKB.
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 Alternative splicing; Cytoplasm; Membrane; Metal-binding;
KW Reference proteome; Repeat; Transferase; Transmembrane;
KW Transmembrane helix; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..542
FT /note="E3 ubiquitin-protein ligase RNF217"
FT /id="PRO_0000084128"
FT TRANSMEM 503..523
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ZN_FING 263..309
FT /note="RING-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT ZN_FING 328..396
FT /note="IBR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT ZN_FING 423..452
FT /note="RING-type 2; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT REGION 1..140
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 176..216
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 259..478
FT /note="TRIAD supradomain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT COMPBIAS 1..24
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 118..138
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 181..200
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 201..216
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 436
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 263
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 266
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 283
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 286
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 383
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 386
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 391
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="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 423
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 426
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 441
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 444
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 449
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 452
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 465
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 474
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT VAR_SEQ 1..294
FT /note="MGEEQSTVSGGGGPQESQTLASGTAGHPEPPRPQGDSARAPPLRAASAEPSG
FT GGCGSDWGCADTSAPEPARSLGPPGWSKSRAPAQPAGLALTGPLNPQTLPLQLELEEEE
FT EEAGDRKEGGDEQQEAPPGEELEPRTRVGAADGLVLDVLGQRRPSLAKRQVFCSVYCVE
FT SDLPEAPASEQLSPPASPPGAPPVLNPPSTRSSFPSPRLSLPTDSLSPDGGSIELEFYL
FT APEPFSMPSLLGAPPYSGLGGVGDPYVPLMVLMCRVCLEDKPIKPLPCCKKAVCEECLK
FT VYLSAQ -> MK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_054705"
FT VAR_SEQ 519..542
FT /note="GLFVFPIYCLCKKQRKRSRTGMHW -> VEEIKTYWNLISGRTRNQTQHLAP
FT QPVLLSDMLYCLKQVFICISYLLPL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_054706"
FT VARIANT 381
FT /note="V -> I (in dbSNP:rs475076)"
FT /id="VAR_024160"
SQ SEQUENCE 542 AA; 59372 MW; 99A463D91873CC6E CRC64;
MGEEQSTVSG GGGPQESQTL ASGTAGHPEP PRPQGDSARA PPLRAASAEP SGGGCGSDWG
CADTSAPEPA RSLGPPGWSK SRAPAQPAGL ALTGPLNPQT LPLQLELEEE EEEAGDRKEG
GDEQQEAPPG EELEPRTRVG AADGLVLDVL GQRRPSLAKR QVFCSVYCVE SDLPEAPASE
QLSPPASPPG APPVLNPPST RSSFPSPRLS LPTDSLSPDG GSIELEFYLA PEPFSMPSLL
GAPPYSGLGG VGDPYVPLMV LMCRVCLEDK PIKPLPCCKK AVCEECLKVY LSAQVQLGQV
EIKCPITECF EFLEETTVVY NLTHEDSIKY KYFLELGRID SSTKPCPQCK HFTTFKKKGH
IPTPSRSESK YKIQCPTCQF VWCFKCHSPW HEGVNCKEYK KGDKLLRHWA SEIEHGQRNA
QKCPKCKIHI QRTEGCDHMT CSQCNTNFCY RCGERYRQLR FFGDHTSNLS IFGCKYRYLP
ERPHLRRLVR GSVCAGKLFI APLIMVLGLA LGAIAVVIGL FVFPIYCLCK KQRKRSRTGM
HW
