RN165_MOUSE
ID RN165_MOUSE Reviewed; 347 AA.
AC E9QAU8; Q3UZA7;
DT 22-FEB-2012, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 1.
DT 03-AUG-2022, entry version 75.
DE RecName: Full=E3 ubiquitin-protein ligase RNF165 {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000269|PubMed:23610558};
DE AltName: Full=Arkadia-like protein 2C {ECO:0000303|PubMed:23610558};
DE Short=Ark2C {ECO:0000303|PubMed:23610558};
DE AltName: Full=RING finger protein 165 {ECO:0000312|MGI:MGI:2444521};
GN Name=Rnf165 {ECO:0000312|MGI:MGI:2444521};
GN Synonyms=Ark2c {ECO:0000303|PubMed:23610558},
GN Gm96 {ECO:0000312|MGI:MGI:2444521};
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 194-347.
RC STRAIN=C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE,
RP AND TISSUE SPECIFICITY.
RX PubMed=23610558; DOI=10.1371/journal.pbio.1001538;
RA Kelly C.E., Thymiakou E., Dixon J.E., Tanaka S., Godwin J., Episkopou V.;
RT "Rnf165/Ark2C enhances BMP-Smad signaling to mediate motor axon
RT extension.";
RL PLoS Biol. 11:E1001538-E1001538(2013).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that acts as a regulator of motor
CC axon elongation (PubMed:23610558). Required for efficient motor axon
CC extension in the dorsal forelimb by enhancing the transcriptional
CC responses of the SMAD1/SMAD5/SMAD8 effectors, which are activated
CC downstream of BMP (PubMed:23610558). Acts by mediating ubiquitination
CC and degradation of SMAD inhibitors such as SMAD6, SMAD7, SKI and SNON
CC isoform of SKIL (PubMed:23610558). {ECO:0000269|PubMed:23610558}.
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:23610558};
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. {ECO:0000250|UniProtKB:Q6ZSG1}.
CC -!- SUBUNIT: Monomer; binding to the ubiquitin-conjugating enzyme E2 does
CC not trigger homodimerization. {ECO:0000250|UniProtKB:Q6ZSG1}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23610558}.
CC -!- TISSUE SPECIFICITY: Expressed in neurons of the nervous system.
CC {ECO:0000269|PubMed:23610558}.
CC -!- DOMAIN: The RING-type zinc finger mediates the E3 ubiquitin-protein
CC ligase activity and binds directly to free ubiquitin. Non-covalent
CC ubiquitin-binding stabilizes the ubiquitin-conjugating enzyme E2 (donor
CC ubiquitin) in the 'closed' conformation and stimulates ubiquitin
CC transfer. {ECO:0000250|UniProtKB:Q6ZSG1}.
CC -!- DISRUPTION PHENOTYPE: Around 10% of mice die at birth. While surviving
CC pups are the same size as their littermates at birth, they fail to
CC thrive and grow, reaching only 50% of the size of their siblings at
CC postnatal day 15. They die before weaning during the first 3 postnatal
CC weeks. Null pups display relaxed forepaws and reduced dorsiflexion.
CC Hind limb defects are also observed. Defects are caused by inefficient
CC growth of motor axons to distant muscles.
CC {ECO:0000269|PubMed:23610558}.
CC -!- SIMILARITY: Belongs to the Arkadia family. {ECO:0000305}.
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DR EMBL; AC102135; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK133955; BAE21950.1; -; mRNA.
DR CCDS; CCDS50327.1; -.
DR RefSeq; NP_001157976.1; NM_001164504.1.
DR AlphaFoldDB; E9QAU8; -.
DR SMR; E9QAU8; -.
DR STRING; 10090.ENSMUSP00000026494; -.
DR PaxDb; E9QAU8; -.
DR PRIDE; E9QAU8; -.
DR Antibodypedia; 9062; 134 antibodies from 17 providers.
DR Ensembl; ENSMUST00000026494; ENSMUSP00000026494; ENSMUSG00000025427.
DR GeneID; 225743; -.
DR KEGG; mmu:225743; -.
DR UCSC; uc008frj.2; mouse.
DR CTD; 494470; -.
DR MGI; MGI:2444521; Rnf165.
DR VEuPathDB; HostDB:ENSMUSG00000025427; -.
DR eggNOG; KOG0800; Eukaryota.
DR GeneTree; ENSGT00940000156997; -.
DR HOGENOM; CLU_056012_0_0_1; -.
DR InParanoid; E9QAU8; -.
DR OMA; NPHMATA; -.
DR OrthoDB; 1098052at2759; -.
DR PhylomeDB; E9QAU8; -.
DR TreeFam; TF317681; -.
DR BioGRID-ORCS; 225743; 0 hits in 72 CRISPR screens.
DR ChiTaRS; Rnf165; mouse.
DR PRO; PR:E9QAU8; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; E9QAU8; protein.
DR Bgee; ENSMUSG00000025427; Expressed in rostral migratory stream and 191 other tissues.
DR ExpressionAtlas; E9QAU8; baseline and differential.
DR Genevisible; E9QAU8; MM.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0007409; P:axonogenesis; IMP:MGI.
DR GO; GO:0035136; P:forelimb morphogenesis; IMP:MGI.
DR GO; GO:0060384; P:innervation; IMP:MGI.
DR GO; GO:0060173; P:limb development; IGI:MGI.
DR GO; GO:0008045; P:motor neuron axon guidance; IMP:MGI.
DR GO; GO:0010259; P:multicellular organism aging; IMP:MGI.
DR GO; GO:0061061; P:muscle structure development; IMP:MGI.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; IMP:MGI.
DR GO; GO:0030163; P:protein catabolic process; IDA:MGI.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:MGI.
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 Metal-binding; Nucleus; Reference proteome; Transferase;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..347
FT /note="E3 ubiquitin-protein ligase RNF165"
FT /id="PRO_0000415819"
FT ZN_FING 295..336
FT /note="RING-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 23..79
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 267..269
FT /note="Ubiquitin binding"
FT /evidence="ECO:0000250|UniProtKB:Q6ZSG1"
FT REGION 268..289
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 310..314
FT /note="Ubiquitin binding"
FT /evidence="ECO:0000250|UniProtKB:Q6ZSG1"
FT BINDING 295
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q6ZSG1"
FT BINDING 298
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q6ZSG1"
FT BINDING 318
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q6ZSG1"
FT BINDING 321
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q6ZSG1"
SQ SEQUENCE 347 AA; 39736 MW; A1BAA91E1E649820 CRC64;
MVLVHVGYLV LPVFGSVRNR GAPFQRSQHP HATSCRHFHL GPPQPQQLAP DFPLAHPVQS
QPGLSAHMAP AHQHSGTLHQ SLTPLPTLQF QDVTGPSFLP QALHQQYLLQ QQLLEAQHRR
LVSHPRRNQD RVSVHPHRLH PSFDFGHQLQ TPQPRYLAEG TDWDLSVDAG LSPAQFQVRP
IPQHYQHYLA TPRMHHFPRN SSSTQMVVHE IRNYPYPQLH FLALQGLNPS RHTSAVRESY
EELLQLEDRL GNVTRGAVQN TIERFTFPHK YKKRRPQDSK GKKDEGEESD TDEKCTICLS
MLEDGEDVRR LPCMHLFHQL CVDQWLAMSK KCPICRVDIE TQLGADS
