Q8WZ73 (RFFL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
E3 ubiquitin-protein ligase rififylin
EC=6.3.2.-

Alternative name(s):
Caspase regulator CARP2
Caspases-8 and -10-associated RING finger protein 2
Short name=CARP-2
FYVE-RING finger protein Sakura
Short name=Fring
RING finger and FYVE-like domain-containing protein 1
RING finger protein 189
RING finger protein 34-like

Gene names

Name:	RFFL
Synonyms:	RNF189, RNF34L

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	363 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Has E3 ubiquitin protein ligase activity. Regulates the levels of CASP8 and CASP10 by targeting them for proteasomal degradation. Has anti-apoptotic activity. May bind phosphatidylinositol phosphates. Ref.7
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Binds CASP8 and CASP10.
Subcellular location	Cytoplasm. Membrane; Peripheral membrane protein Ref.7.
Tissue specificity	Ubiquitous. Detected in spleen, thymus, prostate, testis, ovary, small intestine, colon and peripheral blood leukocytes. Ref.7
Post-translational modification	Rapidly degraded after stimulation with TNFSF10, probably by caspases. Auto-ubiquitinated (in vitro) By similarity. Palmitoylated By similarity.
Sequence similarities	Contains 1 FYVE-type zinc finger. Contains 1 RING-type zinc finger. Contains 2 SAP domains.

Ontologies

Keywords
Biological process	Apoptosis Ubl conjugation pathway
Cellular component	Cytoplasm Membrane
Coding sequence diversity	Alternative splicing
Domain	Repeat Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
PTM	Lipoprotein Palmitate Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW protein ubiquitination Inferred from electronic annotation. Source: UniProtKB-UniPathway
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ligase activity Inferred from electronic annotation. Source: UniProtKB-KW zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8WZ73-1)

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.

Isoform 2 (identifier: Q8WZ73-2)

The sequence of this isoform differs from the canonical sequence as follows:
     296-303: Missing.

Isoform 3 (identifier: Q8WZ73-3)

The sequence of this isoform differs from the canonical sequence as follows:
     197-224: Missing.
     296-303: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 363

363

E3 ubiquitin-protein ligase rififylin

PRO_0000056025

Regions

Domain

101 – 120

20

SAP 1

Domain

250 – 264

15

SAP 2

Zinc finger

41 – 96

56

FYVE-type

Zinc finger

316 – 351

36

RING-type

Amino acid modifications

Modified residue

226

1

Phosphoserine Ref.8

Modified residue

229

1

Phosphoserine Ref.8

Modified residue

240

1

Phosphoserine By similarity

Natural variations

Alternative sequence

197 – 224

28

Missing in isoform 3.

VSP_015751

Alternative sequence

296 – 303

8

Missing in isoform 2 and isoform 3.

VSP_015752

Experimental info

Mutagenesis

333

1

H → A: Loss of E3 ubiquitin protein ligase activity. Ref.7

Sequence conflict

127

1

E → G in AAH28424. Ref.6

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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363

Helix Strand Turn

Details...

Turn

48 – 50

3

Helix

57 – 59

3

Turn

64 – 66

3

Helix

72 – 74

3

Helix

86 – 93

8

Turn

94 – 96

3

Helix

98 – 102

5

Helix

106 – 115

10

Helix

126 – 135

10

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2002. Version 1. Checksum: 9456ED5A0503AFFB	FASTA	363	40,514
	10 20 30 40 50 60 MWATCCNWFC LDGQPEEVPP PQGARMQAYS NPGYSSFPSP TGLEPSCKSC GAHFANTARK 70 80 90 100 110 120 QTCLDCKKNF CMTCSSQVGN GPRLCLLCQR FRATAFQREE LMKMKVKDLR DYLSLHDIST 130 140 150 160 170 180 EMCREKEELV LLVLGQQPVI SQEDRTRAST LSPDFPEQQA FLTQPHSSMV PPTSPNLPSS 190 200 210 220 230 240 SAQATSVPPA QVQENQQANG HVSQDQEEPV YLESVARVPA EDETQSIDSE DSFVPGRRAS 250 260 270 280 290 300 LSDLTDLEDI EGLTVRQLKE ILARNFVNYK GCCEKWELME RVTRLYKDQK GLQHLVSGAE 310 320 330 340 350 360 DQNGGAVPSG LEENLCKICM DSPIDCVLLE CGHMVTCTKC GKRMNECPIC RQYVIRAVHV FRS
	Isoform 2 [UniParc]. Checksum: 0F22B82AD059DE03	FASTA	355	39,713
	10 20 30 40 50 60 MWATCCNWFC LDGQPEEVPP PQGARMQAYS NPGYSSFPSP TGLEPSCKSC GAHFANTARK 70 80 90 100 110 120 QTCLDCKKNF CMTCSSQVGN GPRLCLLCQR FRATAFQREE LMKMKVKDLR DYLSLHDIST 130 140 150 160 170 180 EMCREKEELV LLVLGQQPVI SQEDRTRAST LSPDFPEQQA FLTQPHSSMV PPTSPNLPSS 190 200 210 220 230 240 SAQATSVPPA QVQENQQANG HVSQDQEEPV YLESVARVPA EDETQSIDSE DSFVPGRRAS 250 260 270 280 290 300 LSDLTDLEDI EGLTVRQLKE ILARNFVNYK GCCEKWELME RVTRLYKDQK GLQHLGGAVP 310 320 330 340 350 SGLEENLCKI CMDSPIDCVL LECGHMVTCT KCGKRMNECP ICRQYVIRAV HVFRS
	Isoform 3 [UniParc]. Checksum: 34CE0CD40417BE8E	FASTA	327	36,633
	10 20 30 40 50 60 MWATCCNWFC LDGQPEEVPP PQGARMQAYS NPGYSSFPSP TGLEPSCKSC GAHFANTARK 70 80 90 100 110 120 QTCLDCKKNF CMTCSSQVGN GPRLCLLCQR FRATAFQREE LMKMKVKDLR DYLSLHDIST 130 140 150 160 170 180 EMCREKEELV LLVLGQQPVI SQEDRTRAST LSPDFPEQQA FLTQPHSSMV PPTSPNLPSS 190 200 210 220 230 240 SAQATSVPPA QVQENQQSID SEDSFVPGRR ASLSDLTDLE DIEGLTVRQL KEILARNFVN 250 260 270 280 290 300 YKGCCEKWEL MERVTRLYKD QKGLQHLGGA VPSGLEENLC KICMDSPIDC VLLECGHMVT 310 320 CTKCGKRMNE CPICRQYVIR AVHVFRS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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 1).
[2]	Kanbe D., Araki K., Nawa H. Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Testis.
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Testis carcinoma.
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] (ISOFORMS 1 AND 3). Tissue: Testis.
[7]	"Suppression of caspase-8- and -10-associated RING proteins results in sensitization to death ligands and inhibition of tumor cell growth." McDonald E.R. III, El-Deiry W.S. Proc. Natl. Acad. Sci. U.S.A. 101:6170-6175(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CASP8 AND CASP10, MUTAGENESIS OF HIS-333, PROTEOLYTIC DEGRADATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[8]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226 AND SER-229, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[9]	"Crystal structure of a FYVE-type zinc finger domain from the caspase regulator CARP2." Tibbetts M.D., Shiozaki E.N., Gu L., McDonald E.R. III, El-Deiry W.S., Shi Y. Structure 12:2257-2263(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 26-145.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF434816 mRNA. Translation: AAL30771.1.
AY098935 mRNA. Translation: AAM29181.1.
AK093112 mRNA. Translation: BAC04059.1.
CR933651 mRNA. Translation: CAI45952.1.
CH471147 Genomic DNA. Translation: EAW80172.1.
CH471147 Genomic DNA. Translation: EAW80173.1.
CH471147 Genomic DNA. Translation: EAW80176.1.
CH471147 Genomic DNA. Translation: EAW80177.1.
CH471147 Genomic DNA. Translation: EAW80178.1.
BC015681 mRNA. Translation: AAH15681.2.
BC028424 mRNA. Translation: AAH28424.1.

IPI

IPI00103867.
IPI00290939.
IPI00651650.

RefSeq

NP_001017368.1. NM_001017368.1.

UniGene

Hs.13680.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1Y02	X-ray	1.80	A	26-145	[»]

ProteinModelPortal

Q8WZ73.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q8WZ73. 1 interaction.

STRING

9606.ENSP00000326170.

PTM databases

PhosphoSite

Q8WZ73.

Polymorphism databases

DMDM

74760639.

Proteomic databases

PaxDb

Q8WZ73.

PRIDE

Q8WZ73.

Protocols and materials databases

DNASU

117584.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000268850; ENSP00000268850; ENSG00000092871.
ENST00000315249; ENSP00000326170; ENSG00000092871.
ENST00000378516; ENSP00000367777; ENSG00000092871.
ENST00000394597; ENSP00000378096; ENSG00000092871.
ENST00000413582; ENSP00000408513; ENSG00000092871.
ENST00000415395; ENSP00000412322; ENSG00000092871.
ENST00000447669; ENSP00000389832; ENSG00000092871.
ENST00000584655; ENSP00000463035; ENSG00000092871.

GeneID

117584.

KEGG

hsa:117584.

UCSC

uc002him.1. human.
uc002hin.1. human.
uc002hip.2. human.

Organism-specific databases

CTD

117584.

GeneCards

GC17M033333.

HGNC

HGNC:24821. RFFL.

HPA

CAB008096.
HPA017910.
HPA019492.

MIM

609735. gene.

neXtProt

NX_Q8WZ73.

PharmGKB

PA142671086.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG121302.

HOGENOM

HOG000068080.

HOVERGEN

HBG055079.

InParanoid

Q8WZ73.

OMA

IMWATCC.

OrthoDB

EOG4DJJWK.

PhylomeDB

Q8WZ73.

Enzyme and pathway databases

Pathway_Interaction_DB

tnfpathway. TNF receptor signaling pathway.

UniPathway

UPA00143.

Gene expression databases

ArrayExpress

Q8WZ73.

Bgee

Q8WZ73.

CleanEx

HS_RFFL.

Genevestigator

Q8WZ73.

GermOnline

ENSG00000092871. Homo sapiens.

Family and domain databases

Gene3D

3.30.40.10. 2 hits.

InterPro

IPR011011. Znf_FYVE_PHD.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]

SMART

SM00184. RING. 1 hit.
[Graphical view]

SUPFAM

SSF57903. FYVE_PHD_ZnF. 1 hit.

PROSITE

PS50800. SAP. False negative.
PS50178. ZF_FYVE. False negative.
PS00518. ZF_RING_1. False negative.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q8WZ73.

GenomeRNAi

117584.

NextBio

80230.

SOURCE

Search...

Entry information

Entry name

RFFL_HUMAN

Accession

Primary (citable) accession number: Q8WZ73
Secondary accession number(s): E1P633 , Q8NHW0, Q8TBY7, Q96BE6

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 27, 2005
Last sequence update:	March 1, 2002
Last modified:	May 1, 2013
This is version 103 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.