RFFL_HUMAN
ID RFFL_HUMAN Reviewed; 363 AA.
AC Q8WZ73; E1P633; Q8NHW0; Q8TBY7; Q96BE6;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=E3 ubiquitin-protein ligase rififylin {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000269|PubMed:15069192};
DE AltName: Full=Caspase regulator CARP2;
DE AltName: Full=Caspases-8 and -10-associated RING finger protein 2;
DE Short=CARP-2;
DE AltName: Full=FYVE-RING finger protein Sakura;
DE Short=Fring;
DE AltName: Full=RING finger and FYVE-like domain-containing protein 1;
DE AltName: Full=RING finger protein 189;
DE AltName: Full=RING finger protein 34-like;
DE AltName: Full=RING-type E3 ubiquitin transferase rififylin {ECO:0000305};
GN Name=RFFL {ECO:0000312|HGNC:HGNC:24821}; Synonyms=RNF189, RNF34L;
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] (ISOFORM 1).
RA Hong W.;
RT "Fring, a protein with a modified FYVE domain and a ring domain.";
RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Kanbe D., Araki K., Nawa H.;
RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 MRNA] (ISOFORM 1).
RC TISSUE=Testis carcinoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
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 [7]
RP FUNCTION IN APOPTOSIS, INTERACTION WITH CASP8 AND CASP10, MUTAGENESIS OF
RP HIS-333, PROTEOLYTIC DEGRADATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP AND PATHWAY.
RX PubMed=15069192; DOI=10.1073/pnas.0307459101;
RA McDonald E.R. III, El-Deiry W.S.;
RT "Suppression of caspase-8- and -10-associated RING proteins results in
RT sensitization to death ligands and inhibition of tumor cell growth.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:6170-6175(2004).
RN [8]
RP FUNCTION IN P53/TP53 UBIQUITINATION, AND INTERACTION WITH P53/TP53.
RX PubMed=17121812; DOI=10.1074/jbc.m610793200;
RA Yang W., Rozan L.M., McDonald E.R. III, Navaraj A., Liu J.J., Matthew E.M.,
RA Wang W., Dicker D.T., El-Deiry W.S.;
RT "CARPs are ubiquitin ligases that promote MDM2-independent p53 and phospho-
RT p53ser20 degradation.";
RL J. Biol. Chem. 282:3273-3281(2007).
RN [9]
RP FUNCTION IN UBIQUITINATION OF SFN, INTERACTION WITH MDM2 AND P53/TP53, AND
RP INDUCTION.
RX PubMed=18382127; DOI=10.4161/cc.7.5.5701;
RA Yang W., Dicker D.T., Chen J., El-Deiry W.S.;
RT "CARPs enhance p53 turnover by degrading 14-3-3sigma and stabilizing
RT MDM2.";
RL Cell Cycle 7:670-682(2008).
RN [10]
RP FUNCTION IN TNF SIGNALING, INTERACTION WITH RIPK1, AND SUBCELLULAR
RP LOCATION.
RX PubMed=18450452; DOI=10.1016/j.cub.2008.04.017;
RA Liao W., Xiao Q., Tchikov V., Fujita K., Yang W., Wincovitch S.,
RA Garfield S., Conze D., El-Deiry W.S., Schuetze S., Srinivasula S.M.;
RT "CARP-2 is an endosome-associated ubiquitin ligase for RIP and regulates
RT TNF-induced NF-kappaB activation.";
RL Curr. Biol. 18:641-649(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226 AND SER-229, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [12]
RP FUNCTION IN UBIQUITINATION OF PRR5L, INTERACTION WITH PRR5L AND THE MTORC2
RP COMPLEX, AND DOMAIN.
RX PubMed=22609986; DOI=10.1038/ncb2507;
RA Gan X., Wang J., Wang C., Sommer E., Kozasa T., Srinivasula S., Alessi D.,
RA Offermanns S., Simon M.I., Wu D.;
RT "PRR5L degradation promotes mTORC2-mediated PKC-delta phosphorylation and
RT cell migration downstream of Galpha12.";
RL Nat. Cell Biol. 14:686-696(2012).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-229, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 26-145.
RX PubMed=15576038; DOI=10.1016/j.str.2004.10.007;
RA Tibbetts M.D., Shiozaki E.N., Gu L., McDonald E.R. III, El-Deiry W.S.,
RA Shi Y.;
RT "Crystal structure of a FYVE-type zinc finger domain from the caspase
RT regulator CARP2.";
RL Structure 12:2257-2263(2004).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that regulates several biological
CC processes through the ubiquitin-mediated proteasomal degradation of
CC various target proteins. Mediates 'Lys-48'-linked polyubiquitination of
CC PRR5L and its subsequent proteasomal degradation thereby indirectly
CC regulating cell migration through the mTORC2 complex. Ubiquitinates the
CC caspases CASP8 and CASP10, promoting their proteasomal degradation, to
CC negatively regulate cell death downstream of death domain receptors in
CC the extrinsic pathway of apoptosis. Negatively regulates the tumor
CC necrosis factor-mediated signaling pathway through targeting of RIPK1
CC to ubiquitin-mediated proteasomal degradation. Negatively regulates
CC p53/TP53 through its direct ubiquitination and targeting to proteasomal
CC degradation. Indirectly, may also negatively regulate p53/TP53 through
CC ubiquitination and degradation of SFN. May also play a role in
CC endocytic recycling. {ECO:0000269|PubMed:15069192,
CC ECO:0000269|PubMed:17121812, ECO:0000269|PubMed:18382127,
CC ECO:0000269|PubMed:18450452, ECO:0000269|PubMed:22609986}.
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:15069192};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:15069192}.
CC -!- SUBUNIT: Interacts with CASP8 and CASP10. Interacts with RIPK1 (via
CC protein kinase domain); involved in RIPK1 ubiquitination. Interacts
CC with PRR5L. Interacts (via RING-type zinc finger) with p53/TP53;
CC involved in p53/TP53 ubiquitination. Interacts (via RING-type zinc
CC finger) with MDM2; the interaction stabilizes MDM2.
CC {ECO:0000269|PubMed:15069192, ECO:0000269|PubMed:17121812,
CC ECO:0000269|PubMed:18382127, ECO:0000269|PubMed:18450452,
CC ECO:0000269|PubMed:22609986}.
CC -!- INTERACTION:
CC Q8WZ73-3; Q9Y5Z0: BACE2; NbExp=3; IntAct=EBI-25839575, EBI-11282723;
CC Q8WZ73-3; P02489: CRYAA; NbExp=3; IntAct=EBI-25839575, EBI-6875961;
CC Q8WZ73-3; P00488: F13A1; NbExp=3; IntAct=EBI-25839575, EBI-2565863;
CC Q8WZ73-3; Q9UQC2: GAB2; NbExp=3; IntAct=EBI-25839575, EBI-975200;
CC Q8WZ73-3; O14908-2: GIPC1; NbExp=3; IntAct=EBI-25839575, EBI-25913156;
CC Q8WZ73-3; P31942-2: HNRNPH3; NbExp=3; IntAct=EBI-25839575, EBI-16399628;
CC Q8WZ73-3; Q9Y2W7: KCNIP3; NbExp=3; IntAct=EBI-25839575, EBI-751501;
CC Q8WZ73-3; Q13153: PAK1; NbExp=3; IntAct=EBI-25839575, EBI-1307;
CC Q8WZ73-3; P23219: PTGS1; NbExp=3; IntAct=EBI-25839575, EBI-6655935;
CC Q8WZ73-3; Q8IVP1: SH3GL3; NbExp=3; IntAct=EBI-25839575, EBI-6503765;
CC Q8WZ73-3; Q8IUH5: ZDHHC17; NbExp=3; IntAct=EBI-25839575, EBI-524753;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol. Cell membrane; Peripheral
CC membrane protein. Recycling endosome membrane {ECO:0000250}; Peripheral
CC membrane protein {ECO:0000250}. Note=The FYVE-type zinc finger may
CC mediate phosphatidylinositol phosphate-binding and control subcellular
CC localization.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8WZ73-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8WZ73-2; Sequence=VSP_015752;
CC Name=3;
CC IsoId=Q8WZ73-3; Sequence=VSP_015751, VSP_015752;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Detected in spleen, thymus, prostate,
CC testis, ovary, small intestine, colon and peripheral blood leukocytes.
CC {ECO:0000269|PubMed:15069192}.
CC -!- INDUCTION: Down-regulated upon DNA damage.
CC {ECO:0000269|PubMed:18382127}.
CC -!- DOMAIN: The RING-type zinc finger is required for the ubiquitination of
CC target proteins. {ECO:0000269|PubMed:22609986}.
CC -!- DOMAIN: The FYVE-type zinc finger domain is required for localization
CC to the recycling endosome membranes and the function in endocytic
CC recycling. {ECO:0000250|UniProtKB:Q6ZQM0}.
CC -!- PTM: Autoubiquitinated. {ECO:0000250}.
CC -!- PTM: Palmitoylated. {ECO:0000250}.
CC -!- PTM: Undergoes caspase-mediated cleavage upon death-receptor
CC activation, by TNFSF10 for instance. May be mediated by the caspases
CC CASP8 and CASP10 in a negative feedback loop.
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DR EMBL; AF434816; AAL30771.1; -; mRNA.
DR EMBL; AY098935; AAM29181.1; -; mRNA.
DR EMBL; AK093112; BAC04059.1; -; mRNA.
DR EMBL; CR933651; CAI45952.1; -; mRNA.
DR EMBL; CH471147; EAW80172.1; -; Genomic_DNA.
DR EMBL; CH471147; EAW80173.1; -; Genomic_DNA.
DR EMBL; CH471147; EAW80176.1; -; Genomic_DNA.
DR EMBL; CH471147; EAW80177.1; -; Genomic_DNA.
DR EMBL; CH471147; EAW80178.1; -; Genomic_DNA.
DR EMBL; BC015681; AAH15681.2; -; mRNA.
DR EMBL; BC028424; AAH28424.1; -; mRNA.
DR CCDS; CCDS11286.1; -. [Q8WZ73-1]
DR RefSeq; NP_001017368.1; NM_001017368.1. [Q8WZ73-1]
DR PDB; 1Y02; X-ray; 1.80 A; A=26-145.
DR PDBsum; 1Y02; -.
DR AlphaFoldDB; Q8WZ73; -.
DR SMR; Q8WZ73; -.
DR BioGRID; 125593; 78.
DR IntAct; Q8WZ73; 19.
DR STRING; 9606.ENSP00000326170; -.
DR iPTMnet; Q8WZ73; -.
DR PhosphoSitePlus; Q8WZ73; -.
DR SwissPalm; Q8WZ73; -.
DR BioMuta; RFFL; -.
DR DMDM; 74760639; -.
DR EPD; Q8WZ73; -.
DR jPOST; Q8WZ73; -.
DR MassIVE; Q8WZ73; -.
DR MaxQB; Q8WZ73; -.
DR PaxDb; Q8WZ73; -.
DR PeptideAtlas; Q8WZ73; -.
DR PRIDE; Q8WZ73; -.
DR ProteomicsDB; 75228; -. [Q8WZ73-1]
DR ProteomicsDB; 75229; -. [Q8WZ73-2]
DR ProteomicsDB; 75230; -. [Q8WZ73-3]
DR Antibodypedia; 3764; 263 antibodies from 29 providers.
DR DNASU; 117584; -.
DR Ensembl; ENST00000315249.11; ENSP00000326170.7; ENSG00000092871.17. [Q8WZ73-1]
DR Ensembl; ENST00000394597.7; ENSP00000378096.3; ENSG00000092871.17. [Q8WZ73-1]
DR Ensembl; ENST00000413582.6; ENSP00000408513.2; ENSG00000092871.17. [Q8WZ73-2]
DR Ensembl; ENST00000415395.6; ENSP00000412322.2; ENSG00000092871.17. [Q8WZ73-1]
DR Ensembl; ENST00000447669.6; ENSP00000389832.2; ENSG00000092871.17. [Q8WZ73-1]
DR Ensembl; ENST00000584655.5; ENSP00000463035.1; ENSG00000092871.17. [Q8WZ73-3]
DR GeneID; 117584; -.
DR KEGG; hsa:117584; -.
DR MANE-Select; ENST00000394597.7; ENSP00000378096.3; NM_001017368.2; NP_001017368.1.
DR UCSC; uc002hin.2; human. [Q8WZ73-1]
DR CTD; 117584; -.
DR DisGeNET; 117584; -.
DR GeneCards; RFFL; -.
DR HGNC; HGNC:24821; RFFL.
DR HPA; ENSG00000092871; Tissue enhanced (brain).
DR MIM; 609735; gene.
DR neXtProt; NX_Q8WZ73; -.
DR OpenTargets; ENSG00000092871; -.
DR PharmGKB; PA142671086; -.
DR VEuPathDB; HostDB:ENSG00000092871; -.
DR eggNOG; KOG4275; Eukaryota.
DR GeneTree; ENSGT00390000012719; -.
DR HOGENOM; CLU_041431_1_0_1; -.
DR InParanoid; Q8WZ73; -.
DR OMA; EMCREKD; -.
DR OrthoDB; 1361306at2759; -.
DR PhylomeDB; Q8WZ73; -.
DR TreeFam; TF325195; -.
DR PathwayCommons; Q8WZ73; -.
DR Reactome; R-HSA-6804757; Regulation of TP53 Degradation.
DR SignaLink; Q8WZ73; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 117584; 140 hits in 1115 CRISPR screens.
DR ChiTaRS; RFFL; human.
DR EvolutionaryTrace; Q8WZ73; -.
DR GeneWiki; RFFL; -.
DR GenomeRNAi; 117584; -.
DR Pharos; Q8WZ73; Tbio.
DR PRO; PR:Q8WZ73; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q8WZ73; protein.
DR Bgee; ENSG00000092871; Expressed in oviduct epithelium and 196 other tissues.
DR ExpressionAtlas; Q8WZ73; baseline and differential.
DR Genevisible; Q8WZ73; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0055038; C:recycling endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0002039; F:p53 binding; IPI:UniProtKB.
DR GO; GO:0002020; F:protease binding; IPI:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:2001271; P:negative regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis; IMP:UniProtKB.
DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; IMP:UniProtKB.
DR GO; GO:1901797; P:negative regulation of signal transduction by p53 class mediator; IMP:UniProtKB.
DR GO; GO:0010804; P:negative regulation of tumor necrosis factor-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0010762; P:regulation of fibroblast migration; ISS:UniProtKB.
DR GO; GO:1901796; P:regulation of signal transduction by p53 class mediator; TAS:Reactome.
DR GO; GO:0032006; P:regulation of TOR signaling; IC:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR036361; SAP_dom_sf.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR SMART; SM00184; RING; 1.
DR SUPFAM; SSF57903; SSF57903; 1.
DR SUPFAM; SSF68906; SSF68906; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; Cell membrane; Cytoplasm;
KW Endosome; Lipoprotein; Membrane; Metal-binding; Palmitate; Phosphoprotein;
KW Reference proteome; Repeat; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..363
FT /note="E3 ubiquitin-protein ligase rififylin"
FT /id="PRO_0000056025"
FT DOMAIN 101..120
FT /note="SAP 1"
FT DOMAIN 250..264
FT /note="SAP 2"
FT ZN_FING 41..96
FT /note="FYVE-type"
FT ZN_FING 316..351
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 165..209
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 165..204
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 226
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 229
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 232
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6ZQM0"
FT MOD_RES 240
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6ZQM0"
FT VAR_SEQ 197..224
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015751"
FT VAR_SEQ 296..303
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.2"
FT /id="VSP_015752"
FT MUTAGEN 333
FT /note="H->A: Loss of E3 ubiquitin protein ligase activity."
FT /evidence="ECO:0000269|PubMed:15069192"
FT CONFLICT 127
FT /note="E -> G (in Ref. 6; AAH28424)"
FT /evidence="ECO:0000305"
FT TURN 48..50
FT /evidence="ECO:0007829|PDB:1Y02"
FT HELIX 57..59
FT /evidence="ECO:0007829|PDB:1Y02"
FT TURN 64..66
FT /evidence="ECO:0007829|PDB:1Y02"
FT HELIX 72..74
FT /evidence="ECO:0007829|PDB:1Y02"
FT HELIX 86..93
FT /evidence="ECO:0007829|PDB:1Y02"
FT TURN 94..96
FT /evidence="ECO:0007829|PDB:1Y02"
FT HELIX 98..102
FT /evidence="ECO:0007829|PDB:1Y02"
FT HELIX 106..115
FT /evidence="ECO:0007829|PDB:1Y02"
FT HELIX 126..135
FT /evidence="ECO:0007829|PDB:1Y02"
SQ SEQUENCE 363 AA; 40514 MW; 9456ED5A0503AFFB CRC64;
MWATCCNWFC LDGQPEEVPP PQGARMQAYS NPGYSSFPSP TGLEPSCKSC GAHFANTARK
QTCLDCKKNF CMTCSSQVGN GPRLCLLCQR FRATAFQREE LMKMKVKDLR DYLSLHDIST
EMCREKEELV LLVLGQQPVI SQEDRTRAST LSPDFPEQQA FLTQPHSSMV PPTSPNLPSS
SAQATSVPPA QVQENQQANG HVSQDQEEPV YLESVARVPA EDETQSIDSE DSFVPGRRAS
LSDLTDLEDI EGLTVRQLKE ILARNFVNYK GCCEKWELME RVTRLYKDQK GLQHLVSGAE
DQNGGAVPSG LEENLCKICM DSPIDCVLLE CGHMVTCTKC GKRMNECPIC RQYVIRAVHV
FRS
