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Protein

E3 ubiquitin-protein ligase rififylin

Gene

Rffl

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

E3 ubiquitin-protein ligase that regulates several biological processes through the ubiquitin-mediated proteasomal degradation of various target proteins. Mediates 'Lys-48'-linked polyubiquitination of PRR5L and its subsequent proteasomal degradation thereby indirectly regulating cell migration through the mTORC2 complex. Also ubiquitinates the caspases CASP8 and CASP10, promoting their proteasomal degradation, to negatively regulate apoptosis downstream of death domain receptors. Also negatively regulates the tumor necrosis factor-mediated signaling pathway through targeting of RIPK1 to ubiquitin-mediated proteasomal degradation. Negatively regulates p53/TP53 through its direct ubiquitination and targeting to proteasomal degradation. Indirectly, may also negatively regulate p53/TP53 through ubiquitination and degradation of SFN. May also play a role in endocytic recycling.1 Publication

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.By similarity
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri41 – 9353FYVE-typeAdd
BLAST
Zinc fingeri315 – 35036RING-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Apoptosis, Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase rififylin (EC:6.3.2.-By similarity)
Alternative name(s):
FYVE-RING finger protein Sakura1 Publication
RING finger and FYVE-like domain-containing protein 1
Gene namesi
Name:RfflImported
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 10

Organism-specific databases

RGDi727916. Rffl.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Endosome, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 362362E3 ubiquitin-protein ligase rififylinPRO_0000056027Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei225 – 2251PhosphoserineCombined sources
Modified residuei228 – 2281PhosphoserineCombined sources
Modified residuei231 – 2311PhosphoserineBy similarity
Modified residuei239 – 2391PhosphoserineCombined sources

Post-translational modificationi

Autoubiquitinated.1 Publication
Palmitoylated.1 Publication
Undergoes caspase-mediated cleavage upon death-receptor activation, by TNFSF10 for instance. May be mediated by the caspases CASP8 and CASP10 in a negative feedback loop (By similarity).By similarity

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ8CIN9.

Expressioni

Tissue specificityi

Ubiquitous. Detected in cerebrum, cerebellum, midbrain, brain stem, hippocampus, striatum, liver, heart, lung, kidney, muscle, spleen and testis.1 Publication

Gene expression databases

ExpressionAtlasiQ8CIN9. baseline and differential.
GenevisibleiQ8CIN9. RN.

Interactioni

Subunit structurei

Interacts with CASP8 and CASP10. Interacts with RIPK1 (via protein kinase domain); involved in RIPK1 ubiquitination. Interacts with PRR5L. Interacts (via RING-type zinc finger) with p53/TP53; involved in p53/TP53 ubiquitination. Interacts (via RING-type zinc finger) with MDM2; the interaction stabilizes MDM2.By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000045245.

Structurei

3D structure databases

ProteinModelPortaliQ8CIN9.
SMRiQ8CIN9. Positions 45-139.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini101 – 12020SAP 1Add
BLAST
Domaini249 – 26315SAP 2Add
BLAST

Domaini

The RING-type zinc finger is required for the ubiquitination of target proteins.By similarity
The FYVE-type zinc finger domain is required for localization to the recycling endosome membranes and the function in endocytic recycling.By similarity

Sequence similaritiesi

Contains 1 FYVE-type zinc finger.Curated
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation
Contains 2 SAP domains.Curated

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri41 – 9353FYVE-typeAdd
BLAST
Zinc fingeri315 – 35036RING-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG4275. Eukaryota.
ENOG41101VR. LUCA.
GeneTreeiENSGT00390000012719.
HOGENOMiHOG000068080.
HOVERGENiHBG055079.
InParanoidiQ8CIN9.
OMAiHLHEVST.
OrthoDBiEOG70GMFS.
PhylomeDBiQ8CIN9.

Family and domain databases

Gene3Di3.30.40.10. 2 hits.
InterProiIPR011011. Znf_FYVE_PHD.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
[Graphical view]
SUPFAMiSSF57903. SSF57903. 1 hit.
PROSITEiPS50089. ZF_RING_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8CIN9-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MWASCCNWFC LDGQPEETPP PQGARTQAYS NPGYSSFPSP TGSEPSCKAC
60 70 80 90 100
GVHFASTTRK QTCLDCKKNF CMTCSSQEGN GPRLCLLCLR FRATAFQREE
110 120 130 140 150
LMKMKVKDLR DYLSLHDIST EMCREKEELV FLVLGQQPVI SEADRTRAPT
160 170 180 190 200
LPQAFPEQQA FLTQPQSSTV PPTSPGLPSS PAQVTSVLAQ DQETQQAIGH
210 220 230 240 250
VSQDHEEPIF LESTARVPPE DETQSVDSED SFVPGRRASL SDLTHLEDIE
260 270 280 290 300
GLTVRQLKEI LARNFVNYKG CCEKWELMER VTRLYKDQKG LQHLVSGNED
310 320 330 340 350
QNGGAVPSGL EENLCKICMD SPIDCVLLEC GHMVTCTKCG KRMNECPICR
360
QYVIRAVHVF RS
Length:362
Mass (Da):40,409
Last modified:March 1, 2003 - v1
Checksum:iA410851306F48AD9
GO
Isoform 2 (identifier: Q8CIN9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     196-223: Missing.

Show »
Length:334
Mass (Da):37,295
Checksum:i5B459843CA5A36BA
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei196 – 22328Missing in isoform 2. 1 PublicationVSP_015757Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY157969 mRNA. Translation: AAN60074.1.
BC079216 mRNA. Translation: AAH79216.1.
RefSeqiNP_001004068.1. NM_001004068.1. [Q8CIN9-2]
XP_006247040.1. XM_006246978.2. [Q8CIN9-1]
XP_006247041.1. XM_006246979.2. [Q8CIN9-1]
UniGeneiRn.159718.

Genome annotation databases

EnsembliENSRNOT00000010015; ENSRNOP00000010015; ENSRNOG00000007596. [Q8CIN9-1]
ENSRNOT00000041389; ENSRNOP00000045245; ENSRNOG00000007596. [Q8CIN9-1]
ENSRNOT00000076089; ENSRNOP00000068502; ENSRNOG00000007596. [Q8CIN9-1]
ENSRNOT00000076596; ENSRNOP00000068131; ENSRNOG00000007596. [Q8CIN9-1]
ENSRNOT00000076598; ENSRNOP00000067950; ENSRNOG00000007596. [Q8CIN9-2]
GeneIDi282844.
KEGGirno:282844.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY157969 mRNA. Translation: AAN60074.1.
BC079216 mRNA. Translation: AAH79216.1.
RefSeqiNP_001004068.1. NM_001004068.1. [Q8CIN9-2]
XP_006247040.1. XM_006246978.2. [Q8CIN9-1]
XP_006247041.1. XM_006246979.2. [Q8CIN9-1]
UniGeneiRn.159718.

3D structure databases

ProteinModelPortaliQ8CIN9.
SMRiQ8CIN9. Positions 45-139.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000045245.

Proteomic databases

PaxDbiQ8CIN9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000010015; ENSRNOP00000010015; ENSRNOG00000007596. [Q8CIN9-1]
ENSRNOT00000041389; ENSRNOP00000045245; ENSRNOG00000007596. [Q8CIN9-1]
ENSRNOT00000076089; ENSRNOP00000068502; ENSRNOG00000007596. [Q8CIN9-1]
ENSRNOT00000076596; ENSRNOP00000068131; ENSRNOG00000007596. [Q8CIN9-1]
ENSRNOT00000076598; ENSRNOP00000067950; ENSRNOG00000007596. [Q8CIN9-2]
GeneIDi282844.
KEGGirno:282844.

Organism-specific databases

CTDi117584.
RGDi727916. Rffl.

Phylogenomic databases

eggNOGiKOG4275. Eukaryota.
ENOG41101VR. LUCA.
GeneTreeiENSGT00390000012719.
HOGENOMiHOG000068080.
HOVERGENiHBG055079.
InParanoidiQ8CIN9.
OMAiHLHEVST.
OrthoDBiEOG70GMFS.
PhylomeDBiQ8CIN9.

Enzyme and pathway databases

UniPathwayiUPA00143.

Miscellaneous databases

NextBioi624931.
PROiQ8CIN9.

Gene expression databases

ExpressionAtlasiQ8CIN9. baseline and differential.
GenevisibleiQ8CIN9. RN.

Family and domain databases

Gene3Di3.30.40.10. 2 hits.
InterProiIPR011011. Znf_FYVE_PHD.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
[Graphical view]
SUPFAMiSSF57903. SSF57903. 1 hit.
PROSITEiPS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "A palmitoylated RING finger ubiquitin ligase and its homologue in the brain membranes."
    Araki K., Kawamura M., Suzuki T., Matsuda N., Kanbe D., Ishii K., Ichikawa T., Kumanishi T., Chiba T., Tanaka K., Nawa H.
    J. Neurochem. 86:749-762(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, UBIQUITINATION, SUBCELLULAR LOCATION, PALMITOYLATION, TISSUE SPECIFICITY.
    Tissue: Hippocampus.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Testis.
  3. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-225; SER-228 AND SER-239, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiRFFL_RAT
AccessioniPrimary (citable) accession number: Q8CIN9
Secondary accession number(s): Q6AY29
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 27, 2005
Last sequence update: March 1, 2003
Last modified: May 11, 2016
This is version 98 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.