Seroatlas · Human Serome Atlas

RNF216

E3 ubiquitin-protein ligase RNF216

Also known as: RN216_HUMAN, TRIAD3, UBCE7IP1, ZIN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q9NWF9
Gene: RNF216
Ensembl: ENSG00000011275
Chromosome: 7
Canonical length: 866 aa
Protein class: Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins
Subcellular location: Nucleoplasm,Cytosol

OverviewNCBI Gene

This gene encodes a cytoplasmic protein which specifically colocalizes and interacts with the serine/threonine protein kinase, receptor-interacting protein (RIP). Zinc finger domains of the encoded protein are required for its interaction with RIP and for inhibition of TNF- and IL1-induced NF-kappa B activation pathways. The encoded protein may also function as an E3 ubiquitin-protein ligase which accepts ubiquitin from E2 ubiquitin-conjugating enzymes and transfers it to substrates. Several alternatively spliced transcript variants have been described for this locus but the full-length natures of only some are known. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

866 residues, UniProt reviewed canonical sequence.

>Q9NWF9|RNF216
     1  MEEGNNNEEV IHLNNFHCHR GQEWINLRDG PITISDSSDE ERIPMLVTPA PQQHEEEDLD
    61  DDVILTEDDS EDDYGEFLDL GPPGISEFTK PSGQTEREPK PGPSHNQAAN DIVNPRSEQK
   121  VIILEEGSLL YTESDPLETQ NQSSEDSETE LLSNLGESAA LADDQAIEED CWLDHPYFQS
   181  LNQQPREITN QVVPQERQPE AELGRLLFQH EFPGPAFPRP EPQQGGISGP SSPQPAHPLG
   241  EFEDQQLASD DEEPGPAFPM QESQEPNLEN IWGQEAAEVD QELVELLVKE TEARFPDVAN
   301  GFIEEIIHFK NYYDLNVLCN FLLENPDYPK REDRIIINPS SSLLASQDET KLPKIDFFDY
   361  SKLTPLDQRC FIQAADLLMA DFKVLSSQDI KWALHELKGH YAITRKALSD AIKKWQELSP
   421  ETSGKRKKRK QMNQYSYIDF KFEQGDIKIE KRMFFLENKR RHCRSYDRRA LLPAVQQEQE
   481  FYEQKIKEMA EHEDFLLALQ MNEEQYQKDG QLIECRCCYG EFPFEELTQC ADAHLFCKEC
   541  LIRYAQEAVF GSGKLELSCM EGSCTCSFPT SELEKVLPQT ILYKYYERKA EEEVAAAYAD
   601  ELVRCPSCSF PALLDSDVKR FSCPNPHCRK ETCRKCQGLW KEHNGLTCEE LAEKDDIKYR
   661  TSIEEKMTAA RIRKCHKCGT GLIKSEGCNR MSCRCGAQMC YLCRVSINGY DHFCQHPRSP
   721  GAPCQECSRC SLWTDPTEDD EKLIEEIQKE AEEEQKRKNG ENTFKRIGPP LEKPVEKVQR
   781  VEALPRPVPQ NLPQPQMPPY AFAHPPFPLP PVRPVFNNFP LNMGPIPAPY VPPLPNVRVN
   841  YDFGPIHMPL EHNLPMHFGP QPRHRF

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against RNF216 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: Intracellular
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.52
Highest tissue expression: 24 nTPM

Expression across tissuesHPA

Tissue

colon: 24 nTPM
testis: 22 nTPM
blood vessel: 21 nTPM
heart muscle: 20 nTPM
endometrium: 19 nTPM
spleen: 18 nTPM

Single-cell type

late spermatids: 422 nCPM
early primary spermatocytes: 304 nCPM
microglia: 185 nCPM
early spermatids: 183 nCPM
neutrophils: 176 nCPM
neutrophil progenitors: 172 nCPM

Immune cell

eosinophil: 24 nTPM
neutrophil: 13 nTPM
NK-cell: 13 nTPM
naive CD8 T-cell: 11 nTPM
naive CD4 T-cell: 11 nTPM
gdT-cell: 10 nTPM

Brain region

hypothalamus: 36 nTPM
basal ganglia: 32 nTPM
midbrain: 32 nTPM
medulla oblongata: 31 nTPM
pons: 31 nTPM
cerebral cortex: 31 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about RNF216.

Disease | AllUniProt

Conditions RNF216 is implicated in, by any mechanism.

Gordon Holmes syndrome (GDHS) MIM:212840

Disease | GeneticClinVar

23 pathogenic / likely-pathogenic of 404 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Cerebellar ataxia-hypogonadism syndrome
Leukodystrophy
Hypogonadotropic hypogonadism 7 with or without anosmia

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): 0.55
gnomAD pLI: 0
gnomAD missense Z: -1.23
DepMap mean gene effect: -0.1
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 13% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

IBR domain
Zinc finger, RING/FYVE/PHD-type
TRIAD supradomain
Linear Ubiquitination-Associated E3 Ligases
E3 ubiquitin-protein ligase RNF216, RING finger, HC subclass
E3 ubiquitin-protein ligase RNF216, BRcat domain
E3 ubiquitin-protein ligase RNF216, Rcat domain
E3 ubiquitin-protein ligase RNF216, UBA domain
RNF216-like, UBA domain
RNF216 RING finger HC subclass domain
RNF216 Rcat domain

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of RNF216 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 RNF216 as an antibody target. Whether an autoantibody or antibody against RNF216 could matter depends on whether native RNF216 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

RNF216 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label RNF216 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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