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Protein

E3 ubiquitin-protein ligase RNF216

Gene

RNF216

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Isoform 1 acts as an E3 ubiquitin ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome. Promotes degradation of TRAF3, TLR4 and TLR9. Contributes to the regulation of antiviral responses. Down-regulates activation of NF-kappa-B, IRF3 activation and IFNB production. Isoform 3 inhibits TNF and IL-1 mediated activation of NF-kappa-B. Promotes TNF and RIP mediated apoptosis.2 Publications

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
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)DescriptionActionsGraphical viewLength
Zinc fingeri515 – 566RING-type 1Add BLAST52
Zinc fingeri583 – 648IBR-typeAdd BLAST66
Zinc fingeri675 – 714RING-type 2Add BLAST40

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processApoptosis, Host-virus interaction, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-936440 Negative regulators of DDX58/IFIH1 signaling
UniPathwayi
UPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase RNF216 (EC:2.3.2.27)
Alternative name(s):
RING finger protein 216
RING-type E3 ubiquitin transferase RNF216Curated
Triad domain-containing protein 3
Ubiquitin-conjugating enzyme 7-interacting protein 1
Zinc finger protein inhibiting NF-kappa-B
Gene namesi
Name:RNF216
Synonyms:TRIAD3, UBCE7IP1, ZIN
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000011275.18
HGNCiHGNC:21698 RNF216
MIMi609948 gene
neXtProtiNX_Q9NWF9

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Gordon Holmes syndrome (GDHS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by cerebellar symptoms and signs of sex steroid deficiency. Clinical features include cerebellar and brain stem atrophy, cerebellar ataxia, hypothalamic LHRH deficiency, hypogonadotrophic hypogonadism, lack of secondary sexual characteristics, and infertility.
See also OMIM:212840
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_070048660R → C in GDHS. 1 Publication1
Natural variantiVAR_070049694R → C in GDHS. 1 PublicationCorresponds to variant dbSNP:rs387907368Ensembl.1

Keywords - Diseasei

Disease mutation, Hypogonadotropic hypogonadism

Organism-specific databases

DisGeNETi54476
MalaCardsiRNF216
MIMi212840 phenotype
OpenTargetsiENSG00000011275
Orphaneti1173 Cerebellar ataxia - hypogonadism
PharmGKBiPA162401829

Polymorphism and mutation databases

BioMutaiRNF216
DMDMi57015417

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000562931 – 866E3 ubiquitin-protein ligase RNF216Add BLAST866

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki100Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki351Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki354Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei419PhosphoserineCombined sources1
Cross-linki425Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki430Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki448Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki459Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki485Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki619Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki658Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki666Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki765Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki773Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Isoform 2 (identifier: Q9NWF9-1)
Cross-linki80Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Cross-linki89Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)

Post-translational modificationi

Auto-ubiquitinated.

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9NWF9
PeptideAtlasiQ9NWF9
PRIDEiQ9NWF9
ProteomicsDBi82933
82934 [Q9NWF9-1]
82935 [Q9NWF9-3]

PTM databases

iPTMnetiQ9NWF9
PhosphoSitePlusiQ9NWF9

Expressioni

Tissue specificityi

Ubiquitous, with the highest levels of expression in testis and peripheral blood leukocytes.

Gene expression databases

BgeeiENSG00000011275 Expressed in 220 organ(s), highest expression level in testis
CleanExiHS_RNF216
ExpressionAtlasiQ9NWF9 baseline and differential
GenevisibleiQ9NWF9 HS

Organism-specific databases

HPAiHPA018955
HPA021123

Interactioni

Subunit structurei

Interacts with UBE2L3 and to some extent with UBE2L6. Interacts with TRAF3, TLR3, TLR4, TLR5 and TLR9. Isoform 3/ZIN binds RIPK1.3 Publications
(Microbial infection) Isoform 3/ZIN binds RIPK1 and HIV Vif.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
vifP125044EBI-723337,EBI-779991From Human immunodeficiency virus type 1 group M subtype B (isolate NY5).

Protein-protein interaction databases

BioGridi119981, 24 interactors
IntActiQ9NWF9, 17 interactors
MINTiQ9NWF9

Structurei

3D structure databases

ProteinModelPortaliQ9NWF9
SMRiQ9NWF9
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili475 – 491Sequence analysisAdd BLAST17
Coiled coili737 – 763Sequence analysisAdd BLAST27

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi769 – 862Pro-richAdd BLAST94

Domaini

The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme.By similarity

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri515 – 566RING-type 1Add BLAST52
Zinc fingeri583 – 648IBR-typeAdd BLAST66
Zinc fingeri675 – 714RING-type 2Add BLAST40

Keywords - Domaini

Coiled coil, Repeat, Zinc-finger

Phylogenomic databases

GeneTreeiENSGT00510000048032
HOGENOMiHOG000154166
HOVERGENiHBG102854
InParanoidiQ9NWF9
KOiK11976
OMAiPAPQQHD
OrthoDBiEOG091G0IHF
PhylomeDBiQ9NWF9
TreeFamiTF330852

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR002867 IBR_dom
IPR013083 Znf_RING/FYVE/PHD
SMARTiView protein in SMART
SM00647 IBR, 2 hits

Sequences (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 3 potential isoforms that are computationally mapped.iShow all

Isoform 1 (identifier: Q9NWF9-2) [UniParc]FASTAAdd to basket
Also known as: TRIAD3A

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
MEEGNNNEEV IHLNNFHCHR GQEWINLRDG PITISDSSDE ERIPMLVTPA
60 70 80 90 100
PQQHEEEDLD DDVILTEDDS EDDYGEFLDL GPPGISEFTK PSGQTEREPK
110 120 130 140 150
PGPSHNQAAN DIVNPRSEQK VIILEEGSLL YTESDPLETQ NQSSEDSETE
160 170 180 190 200
LLSNLGESAA LADDQAIEED CWLDHPYFQS LNQQPREITN QVVPQERQPE
210 220 230 240 250
AELGRLLFQH EFPGPAFPRP EPQQGGISGP SSPQPAHPLG EFEDQQLASD
260 270 280 290 300
DEEPGPAFPM QESQEPNLEN IWGQEAAEVD QELVELLVKE TEARFPDVAN
310 320 330 340 350
GFIEEIIHFK NYYDLNVLCN FLLENPDYPK REDRIIINPS SSLLASQDET
360 370 380 390 400
KLPKIDFFDY SKLTPLDQRC FIQAADLLMA DFKVLSSQDI KWALHELKGH
410 420 430 440 450
YAITRKALSD AIKKWQELSP ETSGKRKKRK QMNQYSYIDF KFEQGDIKIE
460 470 480 490 500
KRMFFLENKR RHCRSYDRRA LLPAVQQEQE FYEQKIKEMA EHEDFLLALQ
510 520 530 540 550
MNEEQYQKDG QLIECRCCYG EFPFEELTQC ADAHLFCKEC LIRYAQEAVF
560 570 580 590 600
GSGKLELSCM EGSCTCSFPT SELEKVLPQT ILYKYYERKA EEEVAAAYAD
610 620 630 640 650
ELVRCPSCSF PALLDSDVKR FSCPNPHCRK ETCRKCQGLW KEHNGLTCEE
660 670 680 690 700
LAEKDDIKYR TSIEEKMTAA RIRKCHKCGT GLIKSEGCNR MSCRCGAQMC
710 720 730 740 750
YLCRVSINGY DHFCQHPRSP GAPCQECSRC SLWTDPTEDD EKLIEEIQKE
760 770 780 790 800
AEEEQKRKNG ENTFKRIGPP LEKPVEKVQR VEALPRPVPQ NLPQPQMPPY
810 820 830 840 850
AFAHPPFPLP PVRPVFNNFP LNMGPIPAPY VPPLPNVRVN YDFGPIHMPL
860
EHNLPMHFGP QPRHRF
Length:866
Mass (Da):99,406
Last modified:January 4, 2005 - v3
Checksum:i6A46B66A6569DE74
GO
Isoform 2 (identifier: Q9NWF9-1) [UniParc]FASTAAdd to basket
Also known as: TRIAD3B

The sequence of this isoform differs from the canonical sequence as follows:
     67-67: E → ETNKPQRSRPNLIKPAAQWQDLKRLGEERPKKSRAAFESDKSSYFSVCNNPLFDSGAQ

Show »
Length:923
Mass (Da):105,882
Checksum:iFFAA15927AE14608
GO
Isoform 3 (identifier: Q9NWF9-3) [UniParc]FASTAAdd to basket
Also known as: ZIN, TRIAD3

The sequence of this isoform differs from the canonical sequence as follows:
     1-378: Missing.

Note: 4 different alternatively spliced mRNAs code for this protein isoform.
Show »
Length:488
Mass (Da):56,697
Checksum:i6EB1D218DE2E4E6A
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F8W6D1F8W6D1_HUMAN
E3 ubiquitin-protein ligase RNF216
RNF216
326Annotation score:
C9JIV3C9JIV3_HUMAN
E3 ubiquitin-protein ligase RNF216
RNF216
19Annotation score:
F8WDI8F8WDI8_HUMAN
E3 ubiquitin-protein ligase RNF216
RNF216
49Annotation score:

Sequence cautioni

The sequence BAA91422 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti408L → F in AAL38043 (PubMed:11854271).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_070048660R → C in GDHS. 1 Publication1
Natural variantiVAR_070049694R → C in GDHS. 1 PublicationCorresponds to variant dbSNP:rs387907368Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0124431 – 378Missing in isoform 3. 2 PublicationsAdd BLAST378
Alternative sequenceiVSP_01244467E → ETNKPQRSRPNLIKPAAQWQ DLKRLGEERPKKSRAAFESD KSSYFSVCNNPLFDSGAQ in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY062174 mRNA Translation: AAL38043.1
AF513717 mRNA Translation: AAP47174.1
AF513718 mRNA Translation: AAP47175.1
AY177396 mRNA Translation: AAO60361.1
AY177397 mRNA Translation: AAO60362.1
AY177398 mRNA Translation: AAO60363.1
BX537406 mRNA Translation: CAD97648.1
AC008167 Genomic DNA Translation: AAS07532.1
BC000787 mRNA Translation: AAH00787.2
BC063825 mRNA Translation: AAH63825.1
AK000916 mRNA Translation: BAA91422.1 Different initiation.
AF228527 mRNA Translation: AAF36723.1
CCDSiCCDS34594.1 [Q9NWF9-1]
CCDS34595.1 [Q9NWF9-2]
RefSeqiNP_996994.1, NM_207111.3 [Q9NWF9-1]
NP_996999.1, NM_207116.2 [Q9NWF9-2]
XP_005249842.1, XM_005249785.2 [Q9NWF9-1]
XP_011513738.1, XM_011515436.1 [Q9NWF9-3]
XP_016867852.1, XM_017012363.1 [Q9NWF9-2]
XP_016867854.1, XM_017012365.1 [Q9NWF9-3]
UniGeneiHs.487458
Hs.733601

Genome annotation databases

EnsembliENST00000389902; ENSP00000374552; ENSG00000011275 [Q9NWF9-1]
ENST00000425013; ENSP00000404602; ENSG00000011275 [Q9NWF9-2]
GeneIDi54476
KEGGihsa:54476
UCSCiuc003sox.3 human [Q9NWF9-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY062174 mRNA Translation: AAL38043.1
AF513717 mRNA Translation: AAP47174.1
AF513718 mRNA Translation: AAP47175.1
AY177396 mRNA Translation: AAO60361.1
AY177397 mRNA Translation: AAO60362.1
AY177398 mRNA Translation: AAO60363.1
BX537406 mRNA Translation: CAD97648.1
AC008167 Genomic DNA Translation: AAS07532.1
BC000787 mRNA Translation: AAH00787.2
BC063825 mRNA Translation: AAH63825.1
AK000916 mRNA Translation: BAA91422.1 Different initiation.
AF228527 mRNA Translation: AAF36723.1
CCDSiCCDS34594.1 [Q9NWF9-1]
CCDS34595.1 [Q9NWF9-2]
RefSeqiNP_996994.1, NM_207111.3 [Q9NWF9-1]
NP_996999.1, NM_207116.2 [Q9NWF9-2]
XP_005249842.1, XM_005249785.2 [Q9NWF9-1]
XP_011513738.1, XM_011515436.1 [Q9NWF9-3]
XP_016867852.1, XM_017012363.1 [Q9NWF9-2]
XP_016867854.1, XM_017012365.1 [Q9NWF9-3]
UniGeneiHs.487458
Hs.733601

3D structure databases

ProteinModelPortaliQ9NWF9
SMRiQ9NWF9
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119981, 24 interactors
IntActiQ9NWF9, 17 interactors
MINTiQ9NWF9

PTM databases

iPTMnetiQ9NWF9
PhosphoSitePlusiQ9NWF9

Polymorphism and mutation databases

BioMutaiRNF216
DMDMi57015417

Proteomic databases

EPDiQ9NWF9
PeptideAtlasiQ9NWF9
PRIDEiQ9NWF9
ProteomicsDBi82933
82934 [Q9NWF9-1]
82935 [Q9NWF9-3]

Protocols and materials databases

DNASUi54476
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000389902; ENSP00000374552; ENSG00000011275 [Q9NWF9-1]
ENST00000425013; ENSP00000404602; ENSG00000011275 [Q9NWF9-2]
GeneIDi54476
KEGGihsa:54476
UCSCiuc003sox.3 human [Q9NWF9-2]

Organism-specific databases

CTDi54476
DisGeNETi54476
EuPathDBiHostDB:ENSG00000011275.18
GeneCardsiRNF216
HGNCiHGNC:21698 RNF216
HPAiHPA018955
HPA021123
MalaCardsiRNF216
MIMi212840 phenotype
609948 gene
neXtProtiNX_Q9NWF9
OpenTargetsiENSG00000011275
Orphaneti1173 Cerebellar ataxia - hypogonadism
PharmGKBiPA162401829
GenAtlasiSearch...

Phylogenomic databases

GeneTreeiENSGT00510000048032
HOGENOMiHOG000154166
HOVERGENiHBG102854
InParanoidiQ9NWF9
KOiK11976
OMAiPAPQQHD
OrthoDBiEOG091G0IHF
PhylomeDBiQ9NWF9
TreeFamiTF330852

Enzyme and pathway databases

UniPathwayi
UPA00143

ReactomeiR-HSA-936440 Negative regulators of DDX58/IFIH1 signaling

Miscellaneous databases

ChiTaRSiRNF216 human
GeneWikiiRNF216
GenomeRNAii54476
PROiPR:Q9NWF9
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000011275 Expressed in 220 organ(s), highest expression level in testis
CleanExiHS_RNF216
ExpressionAtlasiQ9NWF9 baseline and differential
GenevisibleiQ9NWF9 HS

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR002867 IBR_dom
IPR013083 Znf_RING/FYVE/PHD
SMARTiView protein in SMART
SM00647 IBR, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiRN216_HUMAN
AccessioniPrimary (citable) accession number: Q9NWF9
Secondary accession number(s): Q6Y691
, Q75ML7, Q7Z2H7, Q7Z7C1, Q8NHW7, Q9NYT1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: January 4, 2005
Last modified: September 12, 2018
This is version 166 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health

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