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Protein

E3 ubiquitin-protein ligase rififylin

Gene

Rffl

Organism
Mus musculus (Mouse)
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.2 Publications

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 fingeri55 – 10753FYVE-typeAdd
BLAST
Zinc fingeri330 – 36536RING-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

ReactomeiR-MMU-6804757. Regulation of TP53 Degradation.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase rififylinCurated (EC:6.3.2.-By similarity)
Alternative name(s):
RING finger and FYVE-like domain-containing protein 1
Short name:
FringImported
Gene namesi
Name:RfflImported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1914588. Rffl.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Endosome, Membrane

Pathology & Biotechi

Disruption phenotypei

No visible phenotype.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 377377E3 ubiquitin-protein ligase rififylinPRO_0000056026Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei240 – 2401PhosphoserineCombined sources
Modified residuei243 – 2431PhosphoserineCombined sources
Modified residuei246 – 2461PhosphoserineCombined sources
Modified residuei254 – 2541PhosphoserineCombined sources

Post-translational modificationi

Autoubiquitinated.By similarity
Palmitoylated.By similarity
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

EPDiQ6ZQM0.
MaxQBiQ6ZQM0.
PaxDbiQ6ZQM0.
PRIDEiQ6ZQM0.
TopDownProteomicsiQ6ZQM0-2. [Q6ZQM0-2]

PTM databases

iPTMnetiQ6ZQM0.
PhosphoSiteiQ6ZQM0.

Expressioni

Tissue specificityi

Ubiquitous. Detected in heart, brain, spleen, lung, liver, skeletal muscle, kidney, testis, thymus, whole embryo and embryonic stem cells.1 Publication

Inductioni

Up-regulation by LPA/lysophosphatidic acid is dependent on GNA12.1 Publication

Gene expression databases

BgeeiQ6ZQM0.
ExpressionAtlasiQ6ZQM0. baseline and differential.
GenevisibleiQ6ZQM0. MM.

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

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000071150.

Structurei

3D structure databases

ProteinModelPortaliQ6ZQM0.
SMRiQ6ZQM0. Positions 59-153, 289-375.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini115 – 13420SAP 1Add
BLAST
Domaini264 – 27815SAP 2Add
BLAST

Domaini

The FYVE-type zinc finger domain is required for localization to the recycling endosome membranes and the function in endocytic recycling.1 Publication
The RING-type zinc finger is required for the ubiquitination of target proteins.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 fingeri55 – 10753FYVE-typeAdd
BLAST
Zinc fingeri330 – 36536RING-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG4275. Eukaryota.
ENOG41101VR. LUCA.
GeneTreeiENSGT00390000012719.
HOGENOMiHOG000068080.
HOVERGENiHBG055079.
InParanoidiQ6ZQM0.
OrthoDBiEOG70GMFS.
TreeFamiTF325195.

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 (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q6ZQM0-1) [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
MSQPSLWKDS HYFIMWASCC NWFCLDGQPE EAPPPQGART QAYSNPGYSS
60 70 80 90 100
FPSPTGSEPS CKACGVHFAS TTRKQTCLDC KKNFCMTCSS QEGNGPRLCL
110 120 130 140 150
LCLRFRATAF QREELMKMKV KDLRDYLSLH DISTEMCREK EELVFLVLGQ
160 170 180 190 200
QPVISEADRT RVPHLPQAFP EQQAFLTQPQ TSTVPPTSPG LPSSPAQVTS
210 220 230 240 250
VPLAQDQETQ QAVGHVSQDH EEPIFPESTA RVPTEDETQS VDSEDSFVPG
260 270 280 290 300
RRASLSDLTH LEDIEGLTVR QLKEILARNF VNYKGCCEKW ELMERVTRLY
310 320 330 340 350
KDQKGLQHLV SGNEDQNGGA VPSGLEENLC KICMDSPIDC VLLECGHMVT
360 370
CTKCGKRMNE CPICRQYVIR AVHVFRS
Length:377
Mass (Da):42,249
Last modified:July 5, 2004 - v1
Checksum:iB0E9E87D446902D1
GO
Isoform 2 (identifier: Q6ZQM0-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-14: Missing.

Note: No experimental confirmation available.
Show »
Length:363
Mass (Da):40,528
Checksum:iFCC3F65559D77646
GO
Isoform 3 (identifier: Q6ZQM0-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-14: Missing.
     211-238: Missing.

Show »
Length:335
Mass (Da):37,440
Checksum:i42DE557838E3F5DB
GO
Isoform 4 (identifier: Q6ZQM0-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-14: Missing.
     211-238: Missing.
     318-335: GGAVPSGLEENLCKICMD → ASHLLWEVFFDLMFHSYV
     336-377: Missing.

Note: No experimental confirmation available.
Show »
Length:293
Mass (Da):33,065
Checksum:iE17BCE423F093754
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti52 – 521P → L in BAB29984 (PubMed:16141072).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 1414Missing in isoform 2, isoform 3 and isoform 4. 2 PublicationsVSP_015753Add
BLAST
Alternative sequencei211 – 23828Missing in isoform 3 and isoform 4. 2 PublicationsVSP_015754Add
BLAST
Alternative sequencei318 – 33518GGAVP…KICMD → ASHLLWEVFFDLMFHSYV in isoform 4. 1 PublicationVSP_015755Add
BLAST
Alternative sequencei336 – 37742Missing in isoform 4. 1 PublicationVSP_015756Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF434814 mRNA. Translation: AAL30769.1.
AK007189 mRNA. Translation: BAB24891.1.
AK015806 mRNA. Translation: BAB29984.1.
AK028095 mRNA. Translation: BAC25744.1.
AK128983 mRNA. Translation: BAC87665.1.
AL645594 Genomic DNA. Translation: CAI25096.1.
AL645594 Genomic DNA. Translation: CAI25097.1.
AL645594 Genomic DNA. Translation: CAI25098.1.
CCDSiCCDS25148.1. [Q6ZQM0-2]
CCDS25149.1. [Q6ZQM0-3]
CCDS48867.1. [Q6ZQM0-1]
RefSeqiNP_001158042.1. NM_001164570.1. [Q6ZQM0-1]
NP_080373.1. NM_026097.3. [Q6ZQM0-3]
XP_006534049.1. XM_006533986.2. [Q6ZQM0-1]
UniGeneiMm.341608.

Genome annotation databases

EnsembliENSMUST00000021036; ENSMUSP00000021036; ENSMUSG00000020696. [Q6ZQM0-3]
ENSMUST00000074515; ENSMUSP00000074108; ENSMUSG00000020696. [Q6ZQM0-2]
ENSMUST00000093975; ENSMUSP00000091510; ENSMUSG00000020696. [Q6ZQM0-1]
ENSMUST00000103218; ENSMUSP00000099507; ENSMUSG00000020696. [Q6ZQM0-4]
ENSMUST00000108173; ENSMUSP00000103808; ENSMUSG00000020696. [Q6ZQM0-2]
GeneIDi67338.
KEGGimmu:67338.
UCSCiuc007kni.2. mouse. [Q6ZQM0-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF434814 mRNA. Translation: AAL30769.1.
AK007189 mRNA. Translation: BAB24891.1.
AK015806 mRNA. Translation: BAB29984.1.
AK028095 mRNA. Translation: BAC25744.1.
AK128983 mRNA. Translation: BAC87665.1.
AL645594 Genomic DNA. Translation: CAI25096.1.
AL645594 Genomic DNA. Translation: CAI25097.1.
AL645594 Genomic DNA. Translation: CAI25098.1.
CCDSiCCDS25148.1. [Q6ZQM0-2]
CCDS25149.1. [Q6ZQM0-3]
CCDS48867.1. [Q6ZQM0-1]
RefSeqiNP_001158042.1. NM_001164570.1. [Q6ZQM0-1]
NP_080373.1. NM_026097.3. [Q6ZQM0-3]
XP_006534049.1. XM_006533986.2. [Q6ZQM0-1]
UniGeneiMm.341608.

3D structure databases

ProteinModelPortaliQ6ZQM0.
SMRiQ6ZQM0. Positions 59-153, 289-375.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000071150.

PTM databases

iPTMnetiQ6ZQM0.
PhosphoSiteiQ6ZQM0.

Proteomic databases

EPDiQ6ZQM0.
MaxQBiQ6ZQM0.
PaxDbiQ6ZQM0.
PRIDEiQ6ZQM0.
TopDownProteomicsiQ6ZQM0-2. [Q6ZQM0-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000021036; ENSMUSP00000021036; ENSMUSG00000020696. [Q6ZQM0-3]
ENSMUST00000074515; ENSMUSP00000074108; ENSMUSG00000020696. [Q6ZQM0-2]
ENSMUST00000093975; ENSMUSP00000091510; ENSMUSG00000020696. [Q6ZQM0-1]
ENSMUST00000103218; ENSMUSP00000099507; ENSMUSG00000020696. [Q6ZQM0-4]
ENSMUST00000108173; ENSMUSP00000103808; ENSMUSG00000020696. [Q6ZQM0-2]
GeneIDi67338.
KEGGimmu:67338.
UCSCiuc007kni.2. mouse. [Q6ZQM0-1]

Organism-specific databases

CTDi117584.
MGIiMGI:1914588. Rffl.

Phylogenomic databases

eggNOGiKOG4275. Eukaryota.
ENOG41101VR. LUCA.
GeneTreeiENSGT00390000012719.
HOGENOMiHOG000068080.
HOVERGENiHBG055079.
InParanoidiQ6ZQM0.
OrthoDBiEOG70GMFS.
TreeFamiTF325195.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-MMU-6804757. Regulation of TP53 Degradation.

Miscellaneous databases

ChiTaRSiRffl. mouse.
PROiQ6ZQM0.
SOURCEiSearch...

Gene expression databases

BgeeiQ6ZQM0.
ExpressionAtlasiQ6ZQM0. baseline and differential.
GenevisibleiQ6ZQM0. MM.

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. "Fring, a protein with a modified FYVE domain and a RING domain."
    Hong W.
    Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
    Strain: C57BL/6J.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2; 3 AND 4).
    Strain: C57BL/6J.
    Tissue: Testis.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORMS 2 AND 3).
    Strain: C57BL/6J.
  4. "Over-expression of Rififylin, a new RING finger and FYVE-like domain-containing protein, inhibits recycling from the endocytic recycling compartment."
    Coumailleau F., Das V., Alcover A., Raposo G., Vandormael-Pournin S., Le Bras S., Baldacci P., Dautry-Varsat A., Babinet C., Cohen-Tannoudji M.
    Mol. Biol. Cell 15:4444-4456(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN ENDOCYTIC RECYCLING, SUBCELLULAR LOCATION, DOMAIN, TISSUE SPECIFICITY.
  5. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  6. Cited for: DISRUPTION PHENOTYPE.
  7. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-240; SER-243; SER-246 AND SER-254, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, Spleen and Testis.
  8. "PRR5L degradation promotes mTORC2-mediated PKC-delta phosphorylation and cell migration downstream of Galpha12."
    Gan X., Wang J., Wang C., Sommer E., Kozasa T., Srinivasula S., Alessi D., Offermanns S., Simon M.I., Wu D.
    Nat. Cell Biol. 14:686-696(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN CELL MIGRATION, INDUCTION BY LPA.

Entry informationi

Entry nameiRFFL_MOUSE
AccessioniPrimary (citable) accession number: Q6ZQM0
Secondary accession number(s): Q5SVC2
, Q5SVC4, Q9D543, Q9D9B1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 27, 2005
Last sequence update: July 5, 2004
Last modified: June 8, 2016
This is version 110 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. 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.