RFFL
E3 ubiquitin-protein ligase rififylin
Also known as: CARP-2, CARP2, fring, RFFL_HUMAN, rififylin, RNF189, RNF34L
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q8WZ73
- Gene
- RFFL
- Ensembl
- ENSG00000092871
- Chromosome
- 17
- Canonical length
- 363 aa
- Protein class
- Enzymes, Predicted intracellular proteins
- Subcellular location
- Vesicles
OverviewNCBI Gene
Enables enzyme binding activity; p53 binding activity; and ubiquitin protein ligase activity. Involved in negative regulation of signal transduction; proteasome-mediated ubiquitin-dependent protein catabolic process; and protein K48-linked ubiquitination. Located in endosome membrane and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]
Canonical amino-acid sequenceUniProt
363 residues, UniProt reviewed canonical sequence.
>Q8WZ73|RFFL
1 MWATCCNWFC LDGQPEEVPP PQGARMQAYS NPGYSSFPSP TGLEPSCKSC GAHFANTARK
61 QTCLDCKKNF CMTCSSQVGN GPRLCLLCQR FRATAFQREE LMKMKVKDLR DYLSLHDIST
121 EMCREKEELV LLVLGQQPVI SQEDRTRAST LSPDFPEQQA FLTQPHSSMV PPTSPNLPSS
181 SAQATSVPPA QVQENQQANG HVSQDQEEPV YLESVARVPA EDETQSIDSE DSFVPGRRAS
241 LSDLTDLEDI EGLTVRQLKE ILARNFVNYK GCCEKWELME RVTRLYKDQK GLQHLVSGAE
301 DQNGGAVPSG LEENLCKICM DSPIDCVLLE CGHMVTCTKC GKRMNECPIC RQYVIRAVHV
361 FRSLocalizationUniProt · AlphaFold · HPA
Whether an antibody against RFFL can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.49
- Highest tissue expression
- 55 nTPM
Expression across tissuesHPA
Tissue
- spinal cord: 55 nTPM
- liver: 45 nTPM
- bone marrow: 39 nTPM
- thyroid gland: 37 nTPM
- esophagus: 34 nTPM
- midbrain: 28 nTPM
Single-cell type
- late spermatids: 152 nCPM
- oligodendrocytes: 106 nCPM
- esophageal apical cells: 85 nCPM
- neutrophils: 75 nCPM
- early spermatids: 46 nCPM
- hepatocytes: 42 nCPM
Immune cell
- neutrophil: 56 nTPM
- eosinophil: 34 nTPM
- T-reg: 30 nTPM
- basophil: 29 nTPM
- MAIT T-cell: 21 nTPM
- memory CD4 T-cell: 19 nTPM
Brain region
- white matter: 203 nTPM
- medulla oblongata: 172 nTPM
- basal ganglia: 137 nTPM
- pons: 129 nTPM
- midbrain: 126 nTPM
- thalamus: 124 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.5
- gnomAD pLI
- 0.41
- gnomAD missense Z
- 1.4
- DepMap mean gene effect
- -0.1
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- apoptotic process
- intracellular protein transport
- negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
- negative regulation of signal transduction by p53 class mediator
- negative regulation of tumor necrosis factor-mediated signaling pathway
- proteasome-mediated ubiquitin-dependent protein catabolic process
- protein K48-linked ubiquitination
- regulation of fibroblast migration
- regulation of signal transduction by p53 class mediator
- regulation of TOR signaling
- ubiquitin-dependent protein catabolic process
Molecular functions
- p53 binding
- protease binding
- protein kinase binding
- ubiquitin protein ligase activity
- ubiquitin protein ligase binding
- zinc ion binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Zinc finger, RING-type
- Zinc finger, FYVE/PHD-type
- Zinc finger, RING/FYVE/PHD-type
- SAP domain superfamily
- E3 ubiquitin-protein ligase CARP1/2, FYVE/PHD zinc finger
- RING-FYVE domain-containing E3 ubiquitin-protein ligase
- RNF34/RFFL, HeH domain
- RNF34/RFFL, SAP domain
- Zinc finger, C3HC4 type (RING finger)
- E3 ubiquitin-protein ligase CARP1/2, FYVE/PHD zinc finger
- E3 ubiquitin-protein ligase rififylin-like domain
- RNF34/RFFL SAP domain
- E3 ubiquitin-protein ligase CARP2, FYVE/PHD zinc finger
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of RFFL in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads RFFL as an antibody target. Whether an autoantibody or antibody against RFFL could matter depends on whether native RFFL is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
RFFL is annotated at the cell surface, where native RFFL is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label RFFL as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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