RFFL_RAT
ID RFFL_RAT Reviewed; 362 AA.
AC Q8CIN9; Q6AY29;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=E3 ubiquitin-protein ligase rififylin;
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q8WZ73};
DE AltName: Full=FYVE-RING finger protein Sakura {ECO:0000303|PubMed:12859687};
DE AltName: Full=RING finger and FYVE-like domain-containing protein 1;
DE AltName: Full=RING-type E3 ubiquitin transferase rififylin {ECO:0000305};
GN Name=Rffl {ECO:0000312|RGD:727916};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, UBIQUITINATION,
RP SUBCELLULAR LOCATION, PALMITOYLATION, AND TISSUE SPECIFICITY.
RC TISSUE=Hippocampus;
RX PubMed=12859687; DOI=10.1046/j.1471-4159.2003.01875.x;
RA Araki K., Kawamura M., Suzuki T., Matsuda N., Kanbe D., Ishii K.,
RA Ichikawa T., Kumanishi T., Chiba T., Tanaka K., Nawa H.;
RT "A palmitoylated RING finger ubiquitin ligase and its homologue in the
RT brain membranes.";
RL J. Neurochem. 86:749-762(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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-225; SER-228 AND SER-239, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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. Also
CC ubiquitinates the caspases CASP8 and CASP10, promoting their
CC proteasomal degradation, to negatively regulate apoptosis downstream of
CC death domain receptors. Also negatively regulates the tumor necrosis
CC factor-mediated signaling pathway through targeting of RIPK1 to
CC 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:12859687}.
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:0000250|UniProtKB:Q8WZ73};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q8WZ73}.
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:0000250|UniProtKB:Q8WZ73}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:12859687}.
CC Cell membrane {ECO:0000269|PubMed:12859687}; Peripheral membrane
CC protein {ECO:0000269|PubMed:12859687}. Recycling endosome membrane
CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Note=The
CC FYVE-type zinc finger may mediate phosphatidylinositol phosphate-
CC binding and control subcellular localization.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8CIN9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8CIN9-2; Sequence=VSP_015757;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Detected in cerebrum, cerebellum,
CC midbrain, brain stem, hippocampus, striatum, liver, heart, lung,
CC kidney, muscle, spleen and testis. {ECO:0000269|PubMed:12859687}.
CC -!- DOMAIN: The RING-type zinc finger is required for the ubiquitination of
CC target proteins. {ECO:0000250|UniProtKB:Q8WZ73}.
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:0000305|PubMed:12859687}.
CC -!- PTM: Palmitoylated. {ECO:0000269|PubMed:12859687}.
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 (By similarity).
CC {ECO:0000250}.
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DR EMBL; AY157969; AAN60074.1; -; mRNA.
DR EMBL; BC079216; AAH79216.1; -; mRNA.
DR RefSeq; NP_001004068.1; NM_001004068.1. [Q8CIN9-2]
DR RefSeq; XP_006247040.1; XM_006246978.3. [Q8CIN9-1]
DR RefSeq; XP_006247041.1; XM_006246979.3. [Q8CIN9-1]
DR AlphaFoldDB; Q8CIN9; -.
DR SMR; Q8CIN9; -.
DR STRING; 10116.ENSRNOP00000045245; -.
DR iPTMnet; Q8CIN9; -.
DR PhosphoSitePlus; Q8CIN9; -.
DR PaxDb; Q8CIN9; -.
DR Ensembl; ENSRNOT00000076598; ENSRNOP00000067950; ENSRNOG00000007596. [Q8CIN9-2]
DR GeneID; 282844; -.
DR KEGG; rno:282844; -.
DR CTD; 117584; -.
DR RGD; 727916; Rffl.
DR VEuPathDB; HostDB:ENSRNOG00000007596; -.
DR eggNOG; KOG4275; Eukaryota.
DR GeneTree; ENSGT00390000012719; -.
DR InParanoid; Q8CIN9; -.
DR OMA; EMCREKD; -.
DR OrthoDB; 1361306at2759; -.
DR PhylomeDB; Q8CIN9; -.
DR Reactome; R-RNO-6804757; Regulation of TP53 Degradation.
DR UniPathway; UPA00143; -.
DR PRO; PR:Q8CIN9; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000007596; Expressed in testis and 19 other tissues.
DR ExpressionAtlas; Q8CIN9; baseline and differential.
DR Genevisible; Q8CIN9; RN.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:RGD.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0010008; C:endosome membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS: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; ISO:RGD.
DR GO; GO:0002020; F:protease binding; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISS:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0006886; P:intracellular protein transport; ISO:RGD.
DR GO; GO:2001271; P:negative regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis; ISS:UniProtKB.
DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; ISS:UniProtKB.
DR GO; GO:1901797; P:negative regulation of signal transduction by p53 class mediator; ISS:UniProtKB.
DR GO; GO:0010804; P:negative regulation of tumor necrosis factor-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0010762; P:regulation of fibroblast migration; ISS:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS: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 Alternative splicing; Apoptosis; Cell membrane; Cytoplasm; Endosome;
KW Lipoprotein; Membrane; Metal-binding; Palmitate; Phosphoprotein;
KW Reference proteome; Repeat; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..362
FT /note="E3 ubiquitin-protein ligase rififylin"
FT /id="PRO_0000056027"
FT DOMAIN 101..120
FT /note="SAP 1"
FT DOMAIN 249..263
FT /note="SAP 2"
FT ZN_FING 41..93
FT /note="FYVE-type"
FT ZN_FING 315..350
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 17..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 162..183
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 20..37
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 225
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 228
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 231
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6ZQM0"
FT MOD_RES 239
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT VAR_SEQ 196..223
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015757"
SQ SEQUENCE 362 AA; 40409 MW; A410851306F48AD9 CRC64;
MWASCCNWFC LDGQPEETPP PQGARTQAYS NPGYSSFPSP TGSEPSCKAC GVHFASTTRK
QTCLDCKKNF CMTCSSQEGN GPRLCLLCLR FRATAFQREE LMKMKVKDLR DYLSLHDIST
EMCREKEELV FLVLGQQPVI SEADRTRAPT LPQAFPEQQA FLTQPQSSTV PPTSPGLPSS
PAQVTSVLAQ DQETQQAIGH VSQDHEEPIF LESTARVPPE DETQSVDSED SFVPGRRASL
SDLTHLEDIE GLTVRQLKEI LARNFVNYKG CCEKWELMER VTRLYKDQKG LQHLVSGNED
QNGGAVPSGL EENLCKICMD SPIDCVLLEC GHMVTCTKCG KRMNECPICR QYVIRAVHVF
RS
