Full text data of RFFL
RFFL
(RNF189, RNF34L)
[Confidence: low (only semi-automatic identification from reviews)]
E3 ubiquitin-protein ligase rififylin; 6.3.2.- (Caspase regulator CARP2; Caspases-8 and -10-associated RING finger protein 2; CARP-2; FYVE-RING finger protein Sakura; Fring; RING finger and FYVE-like domain-containing protein 1; RING finger protein 189; RING finger protein 34-like)
E3 ubiquitin-protein ligase rififylin; 6.3.2.- (Caspase regulator CARP2; Caspases-8 and -10-associated RING finger protein 2; CARP-2; FYVE-RING finger protein Sakura; Fring; RING finger and FYVE-like domain-containing protein 1; RING finger protein 189; RING finger protein 34-like)
UniProt
Q8WZ73
ID RFFL_HUMAN Reviewed; 363 AA.
AC Q8WZ73; E1P633; Q8NHW0; Q8TBY7; Q96BE6;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAR-2002, sequence version 1.
DT 22-JAN-2014, entry version 110.
DE RecName: Full=E3 ubiquitin-protein ligase rififylin;
DE EC=6.3.2.-;
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;
GN Name=RFFL; Synonyms=RNF189, RNF34L;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION, INTERACTION WITH CASP8 AND CASP10, MUTAGENESIS OF HIS-333,
RP PROTEOLYTIC DEGRADATION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226 AND SER-229, AND
RP MASS SPECTROMETRY.
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 [9]
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: Has E3 ubiquitin protein ligase activity. Regulates the
CC levels of CASP8 and CASP10 by targeting them for proteasomal
CC degradation. Has anti-apoptotic activity. May bind
CC phosphatidylinositol phosphates.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Binds CASP8 and CASP10.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Membrane; Peripheral membrane
CC protein.
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,
CC prostate, testis, ovary, small intestine, colon and peripheral
CC blood leukocytes.
CC -!- PTM: Rapidly degraded after stimulation with TNFSF10, probably by
CC caspases.
CC -!- PTM: Auto-ubiquitinated (in vitro) (By similarity).
CC -!- PTM: Palmitoylated (By similarity).
CC -!- SIMILARITY: Contains 1 FYVE-type zinc finger.
CC -!- SIMILARITY: Contains 1 RING-type zinc finger.
CC -!- SIMILARITY: Contains 2 SAP domains.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
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 RefSeq; NP_001017368.1; NM_001017368.1.
DR UniGene; Hs.13680; -.
DR PDB; 1Y02; X-ray; 1.80 A; A=26-145.
DR PDBsum; 1Y02; -.
DR ProteinModelPortal; Q8WZ73; -.
DR SMR; Q8WZ73; 45-139, 275-361.
DR IntAct; Q8WZ73; 1.
DR STRING; 9606.ENSP00000326170; -.
DR PhosphoSite; Q8WZ73; -.
DR DMDM; 74760639; -.
DR PaxDb; Q8WZ73; -.
DR PRIDE; Q8WZ73; -.
DR DNASU; 117584; -.
DR Ensembl; ENST00000268850; ENSP00000268850; ENSG00000092871.
DR Ensembl; ENST00000315249; ENSP00000326170; ENSG00000092871.
DR Ensembl; ENST00000378516; ENSP00000367777; ENSG00000092871.
DR Ensembl; ENST00000394597; ENSP00000378096; ENSG00000092871.
DR Ensembl; ENST00000413582; ENSP00000408513; ENSG00000092871.
DR Ensembl; ENST00000415395; ENSP00000412322; ENSG00000092871.
DR Ensembl; ENST00000447669; ENSP00000389832; ENSG00000092871.
DR Ensembl; ENST00000584655; ENSP00000463035; ENSG00000092871.
DR GeneID; 117584; -.
DR KEGG; hsa:117584; -.
DR UCSC; uc002hin.1; human.
DR CTD; 117584; -.
DR GeneCards; GC17M033333; -.
DR HGNC; HGNC:24821; RFFL.
DR HPA; CAB008096; -.
DR HPA; HPA017910; -.
DR HPA; HPA019492; -.
DR MIM; 609735; gene.
DR neXtProt; NX_Q8WZ73; -.
DR PharmGKB; PA142671086; -.
DR eggNOG; NOG121302; -.
DR HOGENOM; HOG000068080; -.
DR HOVERGEN; HBG055079; -.
DR InParanoid; Q8WZ73; -.
DR OMA; QAQESQQ; -.
DR OrthoDB; EOG70GMFS; -.
DR PhylomeDB; Q8WZ73; -.
DR UniPathway; UPA00143; -.
DR EvolutionaryTrace; Q8WZ73; -.
DR GeneWiki; RFFL; -.
DR GenomeRNAi; 117584; -.
DR NextBio; 80230; -.
DR PRO; PR:Q8WZ73; -.
DR ArrayExpress; Q8WZ73; -.
DR Bgee; Q8WZ73; -.
DR CleanEx; HS_RFFL; -.
DR Genevestigator; Q8WZ73; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0016023; C:cytoplasmic membrane-bounded vesicle; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006886; P:intracellular protein transport; IEA:Ensembl.
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: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:0032006; P:regulation of TOR signaling cascade; IC:UniProtKB.
DR Gene3D; 3.30.40.10; -; 2.
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 PROSITE; PS50800; SAP; FALSE_NEG.
DR PROSITE; PS50178; ZF_FYVE; FALSE_NEG.
DR PROSITE; PS00518; ZF_RING_1; FALSE_NEG.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; Complete proteome;
KW Cytoplasm; Ligase; Lipoprotein; Membrane; Metal-binding; Palmitate;
KW Phosphoprotein; Reference proteome; Repeat; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1 363 E3 ubiquitin-protein ligase rififylin.
FT /FTId=PRO_0000056025.
FT DOMAIN 101 120 SAP 1.
FT DOMAIN 250 264 SAP 2.
FT ZN_FING 41 96 FYVE-type.
FT ZN_FING 316 351 RING-type.
FT MOD_RES 226 226 Phosphoserine.
FT MOD_RES 229 229 Phosphoserine.
FT VAR_SEQ 197 224 Missing (in isoform 3).
FT /FTId=VSP_015751.
FT VAR_SEQ 296 303 Missing (in isoform 2 and isoform 3).
FT /FTId=VSP_015752.
FT MUTAGEN 333 333 H->A: Loss of E3 ubiquitin protein ligase
FT activity.
FT CONFLICT 127 127 E -> G (in Ref. 6; AAH28424).
FT TURN 48 50
FT HELIX 57 59
FT TURN 64 66
FT HELIX 72 74
FT HELIX 86 93
FT TURN 94 96
FT HELIX 98 102
FT HELIX 106 115
FT HELIX 126 135
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
//
ID RFFL_HUMAN Reviewed; 363 AA.
AC Q8WZ73; E1P633; Q8NHW0; Q8TBY7; Q96BE6;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAR-2002, sequence version 1.
DT 22-JAN-2014, entry version 110.
DE RecName: Full=E3 ubiquitin-protein ligase rififylin;
DE EC=6.3.2.-;
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;
GN Name=RFFL; Synonyms=RNF189, RNF34L;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION, INTERACTION WITH CASP8 AND CASP10, MUTAGENESIS OF HIS-333,
RP PROTEOLYTIC DEGRADATION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226 AND SER-229, AND
RP MASS SPECTROMETRY.
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 [9]
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: Has E3 ubiquitin protein ligase activity. Regulates the
CC levels of CASP8 and CASP10 by targeting them for proteasomal
CC degradation. Has anti-apoptotic activity. May bind
CC phosphatidylinositol phosphates.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Binds CASP8 and CASP10.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Membrane; Peripheral membrane
CC protein.
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,
CC prostate, testis, ovary, small intestine, colon and peripheral
CC blood leukocytes.
CC -!- PTM: Rapidly degraded after stimulation with TNFSF10, probably by
CC caspases.
CC -!- PTM: Auto-ubiquitinated (in vitro) (By similarity).
CC -!- PTM: Palmitoylated (By similarity).
CC -!- SIMILARITY: Contains 1 FYVE-type zinc finger.
CC -!- SIMILARITY: Contains 1 RING-type zinc finger.
CC -!- SIMILARITY: Contains 2 SAP domains.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
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 RefSeq; NP_001017368.1; NM_001017368.1.
DR UniGene; Hs.13680; -.
DR PDB; 1Y02; X-ray; 1.80 A; A=26-145.
DR PDBsum; 1Y02; -.
DR ProteinModelPortal; Q8WZ73; -.
DR SMR; Q8WZ73; 45-139, 275-361.
DR IntAct; Q8WZ73; 1.
DR STRING; 9606.ENSP00000326170; -.
DR PhosphoSite; Q8WZ73; -.
DR DMDM; 74760639; -.
DR PaxDb; Q8WZ73; -.
DR PRIDE; Q8WZ73; -.
DR DNASU; 117584; -.
DR Ensembl; ENST00000268850; ENSP00000268850; ENSG00000092871.
DR Ensembl; ENST00000315249; ENSP00000326170; ENSG00000092871.
DR Ensembl; ENST00000378516; ENSP00000367777; ENSG00000092871.
DR Ensembl; ENST00000394597; ENSP00000378096; ENSG00000092871.
DR Ensembl; ENST00000413582; ENSP00000408513; ENSG00000092871.
DR Ensembl; ENST00000415395; ENSP00000412322; ENSG00000092871.
DR Ensembl; ENST00000447669; ENSP00000389832; ENSG00000092871.
DR Ensembl; ENST00000584655; ENSP00000463035; ENSG00000092871.
DR GeneID; 117584; -.
DR KEGG; hsa:117584; -.
DR UCSC; uc002hin.1; human.
DR CTD; 117584; -.
DR GeneCards; GC17M033333; -.
DR HGNC; HGNC:24821; RFFL.
DR HPA; CAB008096; -.
DR HPA; HPA017910; -.
DR HPA; HPA019492; -.
DR MIM; 609735; gene.
DR neXtProt; NX_Q8WZ73; -.
DR PharmGKB; PA142671086; -.
DR eggNOG; NOG121302; -.
DR HOGENOM; HOG000068080; -.
DR HOVERGEN; HBG055079; -.
DR InParanoid; Q8WZ73; -.
DR OMA; QAQESQQ; -.
DR OrthoDB; EOG70GMFS; -.
DR PhylomeDB; Q8WZ73; -.
DR UniPathway; UPA00143; -.
DR EvolutionaryTrace; Q8WZ73; -.
DR GeneWiki; RFFL; -.
DR GenomeRNAi; 117584; -.
DR NextBio; 80230; -.
DR PRO; PR:Q8WZ73; -.
DR ArrayExpress; Q8WZ73; -.
DR Bgee; Q8WZ73; -.
DR CleanEx; HS_RFFL; -.
DR Genevestigator; Q8WZ73; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0016023; C:cytoplasmic membrane-bounded vesicle; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006886; P:intracellular protein transport; IEA:Ensembl.
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: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:0032006; P:regulation of TOR signaling cascade; IC:UniProtKB.
DR Gene3D; 3.30.40.10; -; 2.
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 PROSITE; PS50800; SAP; FALSE_NEG.
DR PROSITE; PS50178; ZF_FYVE; FALSE_NEG.
DR PROSITE; PS00518; ZF_RING_1; FALSE_NEG.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; Complete proteome;
KW Cytoplasm; Ligase; Lipoprotein; Membrane; Metal-binding; Palmitate;
KW Phosphoprotein; Reference proteome; Repeat; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1 363 E3 ubiquitin-protein ligase rififylin.
FT /FTId=PRO_0000056025.
FT DOMAIN 101 120 SAP 1.
FT DOMAIN 250 264 SAP 2.
FT ZN_FING 41 96 FYVE-type.
FT ZN_FING 316 351 RING-type.
FT MOD_RES 226 226 Phosphoserine.
FT MOD_RES 229 229 Phosphoserine.
FT VAR_SEQ 197 224 Missing (in isoform 3).
FT /FTId=VSP_015751.
FT VAR_SEQ 296 303 Missing (in isoform 2 and isoform 3).
FT /FTId=VSP_015752.
FT MUTAGEN 333 333 H->A: Loss of E3 ubiquitin protein ligase
FT activity.
FT CONFLICT 127 127 E -> G (in Ref. 6; AAH28424).
FT TURN 48 50
FT HELIX 57 59
FT TURN 64 66
FT HELIX 72 74
FT HELIX 86 93
FT TURN 94 96
FT HELIX 98 102
FT HELIX 106 115
FT HELIX 126 135
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
//
MIM
609735
*RECORD*
*FIELD* NO
609735
*FIELD* TI
*609735 RING FINGER AND FYVE-LIKE DOMAIN CONTAINING 1; RFFL
;;RIFIFYLIN
*FIELD* TX
read more
CLONING
By EST database searching, Coumailleau et al. (2004) identified and
subsequently cloned rififylin (RING finger and FYVE-like
domain-containing) from mouse testis cDNA. The mouse Rffl cDNA encodes 2
proteins of 336 and 364 amino acids, generated by alternative splicing.
The N-terminal region contains a domain related to the FYVE double zinc
finger domain that mediates binding to phosphatidylinositol 3-phosphate
(PIK3; see 171834), and the C-terminal region contains a consensus
sequence for a C3HC4 RING finger domain. Northern blot analysis revealed
a ubiquitously expressed transcript of approximately 4 kb and a smaller
transcript of about 2 kb at a very high level in testis and at a
moderate level in liver. RT-PCR indicated that both proteins are
ubiquitously expressed, with the larger isoform almost exclusively
expressed in adult mouse liver and kidney cells and in HeLa cells.
GENE FUNCTION
Coumailleau et al. (2004) found that Rffl-GFP localized to globular
structures at the perinuclear region. Coexpression of Rffl-GFP with
various endosomal markers demonstrated that the Rffl-positive structures
belonged to the endocytic recycling compartment (ERC). Morphologic
analysis of HeLa cells overexpressing Rffl revealed an aggregation of
perinuclear transferrin receptor-positive tubules. Pulse-chase
experiments showed that overexpression of Rffl significantly slowed
recycling from the ERC to the plasma membrane. Deletion mutant
experiments demonstrated that the Rffl N-terminal FYVE domain is
necessary and sufficient for targeting Rffl to the ERC and for
inhibiting transferrin recycling. In contrast, the C-terminal zinc
finger domain is dispensable for the effect mediated by Rffl
overexpression on recycling endosomes. Using inhibitors of
phosphatidylinositol 3-kinases, Coumailleau et al. (2004) found that
Rffl acts mainly on a PIK3-independent pathway.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the RFFL
gene to chromosome 17 (TMAP WI-15077). Coumailleau et al. (2004)
identified the mouse Rffl gene on chromosome 11.
*FIELD* RF
1. Coumailleau, F.; Das, V.; Alcover, A.; Raposo, G.; Vandormael-Pournin,
S.; Le Bras, S.; Baldacci, P.; Dautry-Varsat, A.; Babinet, C.; Cohen-Tannoudji,
M.: Over-expression of rififylin, a new RING finger and FYVE-like
domain-containing protein, inhibits recycling from the endocytic recycling
compartment. Molec. Biol. Cell 15: 4444-4456, 2004.
*FIELD* CD
Jennifer L. Goldstein: 11/23/2005
*FIELD* ED
carol: 11/23/2005
*RECORD*
*FIELD* NO
609735
*FIELD* TI
*609735 RING FINGER AND FYVE-LIKE DOMAIN CONTAINING 1; RFFL
;;RIFIFYLIN
*FIELD* TX
read more
CLONING
By EST database searching, Coumailleau et al. (2004) identified and
subsequently cloned rififylin (RING finger and FYVE-like
domain-containing) from mouse testis cDNA. The mouse Rffl cDNA encodes 2
proteins of 336 and 364 amino acids, generated by alternative splicing.
The N-terminal region contains a domain related to the FYVE double zinc
finger domain that mediates binding to phosphatidylinositol 3-phosphate
(PIK3; see 171834), and the C-terminal region contains a consensus
sequence for a C3HC4 RING finger domain. Northern blot analysis revealed
a ubiquitously expressed transcript of approximately 4 kb and a smaller
transcript of about 2 kb at a very high level in testis and at a
moderate level in liver. RT-PCR indicated that both proteins are
ubiquitously expressed, with the larger isoform almost exclusively
expressed in adult mouse liver and kidney cells and in HeLa cells.
GENE FUNCTION
Coumailleau et al. (2004) found that Rffl-GFP localized to globular
structures at the perinuclear region. Coexpression of Rffl-GFP with
various endosomal markers demonstrated that the Rffl-positive structures
belonged to the endocytic recycling compartment (ERC). Morphologic
analysis of HeLa cells overexpressing Rffl revealed an aggregation of
perinuclear transferrin receptor-positive tubules. Pulse-chase
experiments showed that overexpression of Rffl significantly slowed
recycling from the ERC to the plasma membrane. Deletion mutant
experiments demonstrated that the Rffl N-terminal FYVE domain is
necessary and sufficient for targeting Rffl to the ERC and for
inhibiting transferrin recycling. In contrast, the C-terminal zinc
finger domain is dispensable for the effect mediated by Rffl
overexpression on recycling endosomes. Using inhibitors of
phosphatidylinositol 3-kinases, Coumailleau et al. (2004) found that
Rffl acts mainly on a PIK3-independent pathway.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the RFFL
gene to chromosome 17 (TMAP WI-15077). Coumailleau et al. (2004)
identified the mouse Rffl gene on chromosome 11.
*FIELD* RF
1. Coumailleau, F.; Das, V.; Alcover, A.; Raposo, G.; Vandormael-Pournin,
S.; Le Bras, S.; Baldacci, P.; Dautry-Varsat, A.; Babinet, C.; Cohen-Tannoudji,
M.: Over-expression of rififylin, a new RING finger and FYVE-like
domain-containing protein, inhibits recycling from the endocytic recycling
compartment. Molec. Biol. Cell 15: 4444-4456, 2004.
*FIELD* CD
Jennifer L. Goldstein: 11/23/2005
*FIELD* ED
carol: 11/23/2005