RN115_HUMAN
ID RN115_HUMAN Reviewed; 304 AA.
AC Q9Y4L5; A8K3Y4; Q5T2V9; Q7Z2J2;
DT 12-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 07-DEC-2004, sequence version 2.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=E3 ubiquitin-protein ligase RNF115 {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000269|PubMed:18819927};
DE AltName: Full=RING finger protein 115 {ECO:0000312|HGNC:HGNC:18154};
DE AltName: Full=RING-type E3 ubiquitin transferase RNF115 {ECO:0000305};
DE AltName: Full=Rab7-interacting RING finger protein {ECO:0000250|UniProtKB:Q9D0C1};
DE Short=Rabring 7 {ECO:0000250|UniProtKB:Q9D0C1};
DE AltName: Full=Zinc finger protein 364 {ECO:0000303|Ref.1};
GN Name=RNF115 {ECO:0000312|HGNC:HGNC:18154};
GN Synonyms=ZNF364 {ECO:0000303|Ref.1};
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 [MRNA].
RA Zhang D.L., Cai J.J., Ma D.L.;
RT "Cloning and characterization of zinc finger protein 364, C3HC4 type
RT (ZNF364), a novel human member of zinc finger protein family.";
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Guo J.H., She X.Y., Yu L.;
RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas, and Skin;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 73-304.
RC TISSUE=Uterus;
RG The European IMAGE consortium;
RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP FUNCTION, AUTOUBIQUITINATION, AND TISSUE SPECIFICITY.
RX PubMed=16288031; DOI=10.1158/0008-5472.can-05-2103;
RA Burger A.M., Gao Y., Amemiya Y., Kahn H.J., Kitching R., Yang Y., Sun P.,
RA Narod S.A., Hanna W.M., Seth A.K.;
RT "A novel RING-type ubiquitin ligase breast cancer-associated gene 2
RT correlates with outcome in invasive breast cancer.";
RL Cancer Res. 65:10401-10412(2005).
RN [9]
RP INTERACTION WITH RAB7A.
RX PubMed=16925951; DOI=10.1593/neo.06469;
RA Burger A., Amemiya Y., Kitching R., Seth A.K.;
RT "Novel RING E3 ubiquitin ligases in breast cancer.";
RL Neoplasia 8:689-695(2006).
RN [10]
RP FUNCTION, PATHWAY, CATALYTIC ACTIVITY, AUTOUBIQUITINATION, AND MUTAGENESIS
RP OF LYS-26; LYS-32; CYS-228 AND CYS-231.
RX PubMed=18819927; DOI=10.1158/1541-7786.mcr-08-0094;
RA Amemiya Y., Azmi P., Seth A.;
RT "Autoubiquitination of BCA2 RING E3 ligase regulates its own stability and
RT affects cell migration.";
RL Mol. Cancer Res. 6:1385-1396(2008).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [12]
RP FUNCTION, AND INTERACTION WITH EGFR AND FLT3.
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).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that mediates E2-dependent, 'Lys-
CC 48'- and/or 'Lys-63'-linked polyubiquitination of substrates and may
CC play a role in diverse biological processes. Through their
CC polyubiquitination, may play a role in the endosomal trafficking and
CC degradation of membrane receptors including EGFR, FLT3, MET and CXCR4.
CC {ECO:0000269|PubMed:16288031, ECO:0000269|PubMed:18819927,
CC ECO:0000303|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:18819927};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:18819927}.
CC -!- SUBUNIT: Interacts with RAB7A. Interacts with EGFR and FLT3.
CC {ECO:0000269|PubMed:16925951, ECO:0000269|PubMed:23418353}.
CC -!- INTERACTION:
CC Q9Y4L5; Q15038: DAZAP2; NbExp=5; IntAct=EBI-2129242, EBI-724310;
CC Q9Y4L5; Q00987: MDM2; NbExp=3; IntAct=EBI-2129242, EBI-389668;
CC Q9Y4L5; O15151: MDM4; NbExp=3; IntAct=EBI-2129242, EBI-398437;
CC Q9Y4L5; P51668: UBE2D1; NbExp=12; IntAct=EBI-2129242, EBI-743540;
CC Q9Y4L5; P62837: UBE2D2; NbExp=6; IntAct=EBI-2129242, EBI-347677;
CC Q9Y4L5; P61077: UBE2D3; NbExp=11; IntAct=EBI-2129242, EBI-348268;
CC Q9Y4L5; Q9Y2X8: UBE2D4; NbExp=12; IntAct=EBI-2129242, EBI-745527;
CC Q9Y4L5; Q96LR5: UBE2E2; NbExp=6; IntAct=EBI-2129242, EBI-2129763;
CC Q9Y4L5; Q969T4: UBE2E3; NbExp=4; IntAct=EBI-2129242, EBI-348496;
CC Q9Y4L5; P55072: VCP; NbExp=3; IntAct=EBI-2129242, EBI-355164;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q9D0C1}. Note=The GTP-bound form of RAB7A
CC recruits RNF115 from the cytosol onto late endosomes/lysosomes.
CC {ECO:0000250|UniProtKB:Q9D0C1}.
CC -!- TISSUE SPECIFICITY: Expressed at extremely low levels in normal breast,
CC prostate, lung, colon. Higher levels of expression are detected in
CC heart, skeletal muscle, testis as well as in breast and prostate cancer
CC cells. {ECO:0000269|PubMed:16288031}.
CC -!- PTM: RING-type zinc finger-dependent and E2-dependent
CC autoubiquitination. {ECO:0000269|PubMed:16288031,
CC ECO:0000269|PubMed:18819927}.
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DR EMBL; AF542552; AAQ09535.1; -; mRNA.
DR EMBL; AF419857; AAP97292.1; -; mRNA.
DR EMBL; AK290749; BAF83438.1; -; mRNA.
DR EMBL; AL390725; CAI13717.1; -; Genomic_DNA.
DR EMBL; AL160282; CAI13717.1; JOINED; Genomic_DNA.
DR EMBL; CH471244; EAW71437.1; -; Genomic_DNA.
DR EMBL; BC054049; AAH54049.1; -; mRNA.
DR EMBL; BC064903; AAH64903.1; -; mRNA.
DR EMBL; AL079314; CAB45280.1; -; mRNA.
DR CCDS; CCDS72863.1; -.
DR RefSeq; NP_055270.1; NM_014455.3.
DR AlphaFoldDB; Q9Y4L5; -.
DR SMR; Q9Y4L5; -.
DR BioGRID; 118094; 122.
DR IntAct; Q9Y4L5; 28.
DR MINT; Q9Y4L5; -.
DR STRING; 9606.ENSP00000463650; -.
DR MoonDB; Q9Y4L5; Predicted.
DR iPTMnet; Q9Y4L5; -.
DR PhosphoSitePlus; Q9Y4L5; -.
DR BioMuta; RNF115; -.
DR DMDM; 56405389; -.
DR EPD; Q9Y4L5; -.
DR jPOST; Q9Y4L5; -.
DR MassIVE; Q9Y4L5; -.
DR MaxQB; Q9Y4L5; -.
DR PaxDb; Q9Y4L5; -.
DR PeptideAtlas; Q9Y4L5; -.
DR PRIDE; Q9Y4L5; -.
DR ProteomicsDB; 86228; -.
DR Antibodypedia; 74554; 103 antibodies from 24 providers.
DR DNASU; 27246; -.
DR Ensembl; ENST00000582693.5; ENSP00000463650.1; ENSG00000265491.5.
DR GeneID; 27246; -.
DR KEGG; hsa:27246; -.
DR MANE-Select; ENST00000582693.5; ENSP00000463650.1; NM_014455.4; NP_055270.1.
DR UCSC; uc031utf.2; human.
DR CTD; 27246; -.
DR DisGeNET; 27246; -.
DR GeneCards; RNF115; -.
DR HGNC; HGNC:18154; RNF115.
DR HPA; ENSG00000265491; Low tissue specificity.
DR MIM; 619535; gene.
DR neXtProt; NX_Q9Y4L5; -.
DR OpenTargets; ENSG00000265491; -.
DR PharmGKB; PA162401519; -.
DR VEuPathDB; HostDB:ENSG00000265491; -.
DR eggNOG; KOG0800; Eukaryota.
DR GeneTree; ENSGT00940000157203; -.
DR HOGENOM; CLU_034892_0_2_1; -.
DR InParanoid; Q9Y4L5; -.
DR OMA; RMDNSTS; -.
DR OrthoDB; 1249953at2759; -.
DR PhylomeDB; Q9Y4L5; -.
DR TreeFam; TF317985; -.
DR PathwayCommons; Q9Y4L5; -.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q9Y4L5; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 27246; 20 hits in 1111 CRISPR screens.
DR ChiTaRS; RNF115; human.
DR GeneWiki; ZNF364; -.
DR GenomeRNAi; 27246; -.
DR Pharos; Q9Y4L5; Tbio.
DR PRO; PR:Q9Y4L5; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9Y4L5; protein.
DR Bgee; ENSG00000265491; Expressed in gluteal muscle and 205 other tissues.
DR Genevisible; Q9Y4L5; HS.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISS:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; IDA:UniProtKB.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0043162; P:ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway; IMP:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF13639; zf-RING_2; 1.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Metal-binding; Reference proteome; Transferase;
KW Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..304
FT /note="E3 ubiquitin-protein ligase RNF115"
FT /id="PRO_0000056314"
FT ZN_FING 228..269
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 95..138
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 272..304
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT VARIANT 194
FT /note="G -> R (in dbSNP:rs11577731)"
FT /id="VAR_052105"
FT MUTAGEN 26
FT /note="K->R: Loss of autoubiquitination; when associated
FT with R-32."
FT /evidence="ECO:0000269|PubMed:18819927"
FT MUTAGEN 32
FT /note="K->R: Loss of autoubiquitination; when associated
FT with R-26."
FT /evidence="ECO:0000269|PubMed:18819927"
FT MUTAGEN 228
FT /note="C->A: Loss of autoubiquitination."
FT /evidence="ECO:0000269|PubMed:18819927"
FT MUTAGEN 231
FT /note="C->A: Loss of autoubiquitination."
FT /evidence="ECO:0000269|PubMed:18819927"
FT CONFLICT 299
FT /note="H -> N (in Ref. 7; CAB45280)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 304 AA; 33703 MW; 22F0C8FCC0F55045 CRC64;
MAEASAAGAD SGAAVAAHRF FCHFCKGEVS PKLPEYICPR CESGFIEEVT DDSSFLGGGG
SRIDNTTTTH FAELWGHLDH TMFFQDFRPF LSSSPLDQDN RANERGHQTH TDFWGARPPR
LPLGRRYRSR GSSRPDRSPA IEGILQHIFA GFFANSAIPG SPHPFSWSGM LHSNPGDYAW
GQTGLDAIVT QLLGQLENTG PPPADKEKIT SLPTVTVTQE QVDMGLECPV CKEDYTVEEE
VRQLPCNHFF HSSCIVPWLE LHDTCPVCRK SLNGEDSTRQ SQSTEASASN RFSNDSQLHD
RWTF
