RN165_HUMAN
ID RN165_HUMAN Reviewed; 346 AA.
AC Q6ZSG1; B3KVD1;
DT 11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=E3 ubiquitin-protein ligase RNF165 {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000269|PubMed:26656854};
DE AltName: Full=RING finger protein 165 {ECO:0000312|HGNC:HGNC:31696};
GN Name=RNF165 {ECO:0000312|HGNC:HGNC:31696};
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 MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Cerebellum, and Thalamus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [3] {ECO:0007744|PDB:5D0I, ECO:0007744|PDB:5D0K, ECO:0007744|PDB:5D0M}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 255-346 IN COMPLEX WITH ZINC;
RP UBIQUITIN AND UBE2D2, CATALYTIC ACTIVITY, SUBUNIT, ACTIVITY REGULATION,
RP DOMAIN, AND MUTAGENESIS OF ARG-309; MET-313 AND ARG-335.
RX PubMed=26656854; DOI=10.1038/nsmb.3142;
RA Wright J.D., Mace P.D., Day C.L.;
RT "Secondary ubiquitin-RING docking enhances Arkadia and Ark2C E3 ligase
RT activity.";
RL Nat. Struct. Mol. Biol. 23:45-52(2016).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that acts as a regulator of motor
CC axon elongation. Required for efficient motor axon extension in the
CC dorsal forelimb by enhancing the transcriptional responses of the
CC SMAD1/SMAD5/SMAD8 effectors, which are activated downstream of BMP.
CC Acts by mediating ubiquitination and degradation of SMAD inhibitors
CC such as SMAD6, SMAD7, SKI and SNON isoform of SKIL.
CC {ECO:0000250|UniProtKB:E9QAU8}.
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:26656854};
CC -!- ACTIVITY REGULATION: Binds free ubiquitin non-covalently via its RING-
CC type zinc finger. Ubiquitin-binding leads to enhance the E3 ubiquitin-
CC protein ligase activity by stabilizing the ubiquitin-conjugating enzyme
CC E2 (donor ubiquitin) in the 'closed' conformation and activating
CC ubiquitin transfer (PubMed:26656854).
CC -!- SUBUNIT: Monomer; binding to the ubiquitin-conjugating enzyme E2 does
CC not trigger homodimerization (PubMed:26656854).
CC {ECO:0000269|PubMed:26656854}.
CC -!- INTERACTION:
CC Q6ZSG1; P12755: SKI; NbExp=2; IntAct=EBI-2129206, EBI-347281;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:E9QAU8}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6ZSG1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6ZSG1-2; Sequence=VSP_045128;
CC -!- DOMAIN: The RING-type zinc finger mediates the E3 ubiquitin-protein
CC ligase activity and binds directly to free ubiquitin (PubMed:26656854).
CC Non-covalent ubiquitin-binding stabilizes the ubiquitin-conjugating
CC enzyme E2 (donor ubiquitin) in the 'closed' conformation and stimulates
CC ubiquitin transfer (PubMed:26656854). {ECO:0000269|PubMed:26656854}.
CC -!- SIMILARITY: Belongs to the Arkadia family. {ECO:0000305}.
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DR EMBL; AK127467; BAC86992.1; -; mRNA.
DR EMBL; AK122819; BAG53743.1; -; mRNA.
DR EMBL; AC015959; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC018931; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC021763; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS32823.1; -. [Q6ZSG1-1]
DR CCDS; CCDS58621.1; -. [Q6ZSG1-2]
DR RefSeq; NP_001243687.1; NM_001256758.1. [Q6ZSG1-2]
DR RefSeq; NP_689683.2; NM_152470.2. [Q6ZSG1-1]
DR PDB; 5D0I; X-ray; 1.90 A; A/B=255-346.
DR PDB; 5D0K; X-ray; 2.65 A; C/F/I/L=255-346.
DR PDB; 5D0M; X-ray; 1.91 A; C=255-346.
DR PDB; 5ULH; X-ray; 1.95 A; C=255-346.
DR PDB; 5ULK; X-ray; 2.38 A; C=255-346.
DR PDB; 7R70; X-ray; 2.50 A; A/B=255-346.
DR PDB; 7R71; X-ray; 2.80 A; A=255-346.
DR PDBsum; 5D0I; -.
DR PDBsum; 5D0K; -.
DR PDBsum; 5D0M; -.
DR PDBsum; 5ULH; -.
DR PDBsum; 5ULK; -.
DR PDBsum; 7R70; -.
DR PDBsum; 7R71; -.
DR AlphaFoldDB; Q6ZSG1; -.
DR SMR; Q6ZSG1; -.
DR BioGRID; 138966; 11.
DR DIP; DIP-52693N; -.
DR IntAct; Q6ZSG1; 13.
DR STRING; 9606.ENSP00000269439; -.
DR BioMuta; RNF165; -.
DR DMDM; 74762404; -.
DR PaxDb; Q6ZSG1; -.
DR PeptideAtlas; Q6ZSG1; -.
DR PRIDE; Q6ZSG1; -.
DR Antibodypedia; 9062; 134 antibodies from 17 providers.
DR DNASU; 494470; -.
DR Ensembl; ENST00000269439.12; ENSP00000269439.6; ENSG00000141622.14. [Q6ZSG1-1]
DR Ensembl; ENST00000543885.2; ENSP00000444285.1; ENSG00000141622.14. [Q6ZSG1-2]
DR GeneID; 494470; -.
DR KEGG; hsa:494470; -.
DR MANE-Select; ENST00000269439.12; ENSP00000269439.6; NM_152470.3; NP_689683.2.
DR UCSC; uc002lcb.2; human. [Q6ZSG1-1]
DR CTD; 494470; -.
DR DisGeNET; 494470; -.
DR GeneCards; RNF165; -.
DR HGNC; HGNC:31696; RNF165.
DR HPA; ENSG00000141622; Tissue enhanced (retina).
DR neXtProt; NX_Q6ZSG1; -.
DR OpenTargets; ENSG00000141622; -.
DR PharmGKB; PA134972127; -.
DR VEuPathDB; HostDB:ENSG00000141622; -.
DR eggNOG; KOG0800; Eukaryota.
DR GeneTree; ENSGT00940000156997; -.
DR HOGENOM; CLU_056012_0_0_1; -.
DR InParanoid; Q6ZSG1; -.
DR OMA; NPHMATA; -.
DR PhylomeDB; Q6ZSG1; -.
DR TreeFam; TF317681; -.
DR PathwayCommons; Q6ZSG1; -.
DR SignaLink; Q6ZSG1; -.
DR BioGRID-ORCS; 494470; 9 hits in 1106 CRISPR screens.
DR ChiTaRS; RNF165; human.
DR GenomeRNAi; 494470; -.
DR Pharos; Q6ZSG1; Tdark.
DR PRO; PR:Q6ZSG1; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q6ZSG1; protein.
DR Bgee; ENSG00000141622; Expressed in cortical plate and 133 other tissues.
DR ExpressionAtlas; Q6ZSG1; baseline and differential.
DR Genevisible; Q6ZSG1; HS.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
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:0035136; P:forelimb morphogenesis; IEA:Ensembl.
DR GO; GO:0060384; P:innervation; IEA:Ensembl.
DR GO; GO:0008045; P:motor neuron axon guidance; IBA:GO_Central.
DR GO; GO:0010259; P:multicellular organism aging; IEA:Ensembl.
DR GO; GO:0061061; P:muscle structure development; IEA:Ensembl.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; IBA:GO_Central.
DR GO; GO:0030163; P:protein catabolic process; IEA:Ensembl.
DR GO; GO:0000209; P:protein polyubiquitination; IEA:Ensembl.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR011016; Znf_RING-CH.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF13639; zf-RING_2; 1.
DR SMART; SM00184; RING; 1.
DR SMART; SM00744; RINGv; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Metal-binding; Nucleus;
KW Reference proteome; Transferase; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT CHAIN 1..346
FT /note="E3 ubiquitin-protein ligase RNF165"
FT /id="PRO_0000245587"
FT ZN_FING 294..335
FT /note="RING-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 23..76
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 266..268
FT /note="Ubiquitin binding"
FT /evidence="ECO:0000269|PubMed:26656854,
FT ECO:0007744|PDB:5D0K"
FT REGION 267..288
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 309..313
FT /note="Ubiquitin binding"
FT /evidence="ECO:0000269|PubMed:26656854,
FT ECO:0007744|PDB:5D0K"
FT BINDING 294
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:26656854,
FT ECO:0007744|PDB:5D0I, ECO:0007744|PDB:5D0K,
FT ECO:0007744|PDB:5D0M"
FT BINDING 297
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:26656854,
FT ECO:0007744|PDB:5D0I, ECO:0007744|PDB:5D0K,
FT ECO:0007744|PDB:5D0M"
FT BINDING 317
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:26656854,
FT ECO:0007744|PDB:5D0I, ECO:0007744|PDB:5D0K,
FT ECO:0007744|PDB:5D0M"
FT BINDING 320
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:26656854,
FT ECO:0007744|PDB:5D0I, ECO:0007744|PDB:5D0K,
FT ECO:0007744|PDB:5D0M"
FT VAR_SEQ 1..192
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045128"
FT MUTAGEN 309
FT /note="R->A: Reduced binding to free ubiquitin."
FT /evidence="ECO:0000269|PubMed:26656854"
FT MUTAGEN 313
FT /note="M->A: Reduced binding to free ubiquitin and reduced
FT E3 ubiquitin-protein ligase activity."
FT /evidence="ECO:0000269|PubMed:26656854"
FT MUTAGEN 335
FT /note="R->A: Reduced ubiquitin discharge."
FT /evidence="ECO:0000269|PubMed:26656854"
FT HELIX 261..264
FT /evidence="ECO:0007829|PDB:5D0I"
FT STRAND 265..269
FT /evidence="ECO:0007829|PDB:5D0I"
FT TURN 295..297
FT /evidence="ECO:0007829|PDB:5D0I"
FT STRAND 299..305
FT /evidence="ECO:0007829|PDB:5ULH"
FT STRAND 306..309
FT /evidence="ECO:0007829|PDB:5D0I"
FT STRAND 315..317
FT /evidence="ECO:0007829|PDB:5D0I"
FT HELIX 318..328
FT /evidence="ECO:0007829|PDB:5D0I"
FT TURN 332..334
FT /evidence="ECO:0007829|PDB:5D0I"
SQ SEQUENCE 346 AA; 39526 MW; 93A5B777988C339C CRC64;
MVLVHVGYLV LPVFGSVRNR GAPFQRSQHP HATSCRHFHL GPPQPQQLAP DFPLAHPVQS
QPGLSAHMAP AHQHSGALHQ SLTPLPTLQF QDVTGPSFLP QALHQQYLLQ QQLLEAQHRR
LVSHPRRSQE RVSVHPHRLH PSFDFGQLQT PQPRYLAEGT DWDLSVDAGL SPAQFQVRPI
PQHYQHYLAT PRMHHFPRNS SSTQMVVHEI RNYPYPQLHF LALQGLNPSR HTSAVRESYE
ELLQLEDRLG NVTRGAVQNT IERFTFPHKY KKRRPQDGKG KKDEGEESDT DEKCTICLSM
LEDGEDVRRL PCMHLFHQLC VDQWLAMSKK CPICRVDIET QLGADS
