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Protein

E3 ubiquitin-protein ligase RNF43

Gene

RNF43

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

Functioni

E3 ubiquitin-protein ligase that acts as a negative regulator of the Wnt signaling pathway by mediating the ubiquitination, endocytosis and subsequent degradation of Wnt receptor complex components Frizzled. Acts on both canonical and non-canonical Wnt signaling pathway (PubMed:18313049, PubMed:22575959, PubMed:22895187). Along with RSPO2 and ZNRF3, constitutes a master switch that governs limb specification (By similarity).By similarity3 Publications

Miscellaneous

Acts as a cytotoxic T-lymphocyte tumor antigen, suggesting that it may be used as a target for cancer immunotherapy.1 Publication

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 fingeri272 – 313RING-type; atypicalPROSITE-ProRule annotationAdd BLAST42

GO - Molecular functioni

  • frizzled binding Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • ubiquitin protein ligase activity Source: GO_Central
  • ubiquitin-protein transferase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, Transferase
Biological processUbl conjugation pathway, Wnt signaling pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

BRENDAi2.3.2.B10 2681
6.3.2.19 2681
ReactomeiR-HSA-4641263 Regulation of FZD by ubiquitination
R-HSA-5340588 RNF mutants show enhanced WNT signaling and proliferation
SIGNORiQ68DV7
UniPathwayi
UPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase RNF43 (EC:2.3.2.27)
Alternative name(s):
RING finger protein 43
RING-type E3 ubiquitin transferase RNF43Curated
Gene namesi
Name:RNF43
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000108375.12
HGNCiHGNC:18505 RNF43
MIMi612482 gene
neXtProtiNX_Q68DV7

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

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini24 – 197ExtracellularSequence analysisAdd BLAST174
Transmembranei198 – 218HelicalSequence analysisAdd BLAST21
Topological domaini219 – 783CytoplasmicSequence analysisAdd BLAST565

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

Sessile serrated polyposis cancer syndrome (SSPCS)2 Publications
Disease susceptibility may be associated with variations affecting the gene represented in this entry.
Disease descriptionA rare disease characterized by multiple and/or large serrated polyps developing in the colon, and an increased personal and familial risk of colorectal cancer. A patient is diagnosed with SSPCS if at least one of the following criteria is met: the presence of at least five sessile serrated polyps proximal to the sigmoid colon, two of which are greater than 10 mm in diameter; the presence of any number of serrated polyps occurring proximal to the sigmoid colon in an individual who has a first-degree relative with serrated polyposis; the presence of more than 20 serrated polyps of any size distributed throughout the colon. Sessile serrated polyps are also known as sessile serrated adenomas (SSA) and are estimated to be responsible for 20 to 35% of all colon cancers. Individuals with SSPCS may have a strong personal or family history of extracolonic cancers.
See also OMIM:617108

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi290C → S: Dominant-negative mutant, loss of E3 ligase activity and activation of the Wnt signaling pathway; when associated with S-292. 2 Publications1
Mutagenesisi292H → S: Dominant-negative mutant, loss of E3 ligase activity and activation of the Wnt signaling pathway; when associated with S-290. 2 Publications1
Mutagenesisi295H → S: Dominant-negative mutant, loss of E3 ligase activity and activation of the Wnt signaling pathway; when associated with S-298. 1 Publication1
Mutagenesisi298C → S: Dominant-negative mutant, loss of E3 ligase activity and activation of the Wnt signaling pathway; when associated with S-295. 1 Publication1

Organism-specific databases

DisGeNETi54894
MalaCardsiRNF43
MIMi617108 phenotype
OpenTargetsiENSG00000108375
Orphaneti157798 Hyperplastic polyposis syndrome
PharmGKBiPA34441

Polymorphism and mutation databases

BioMutaiRNF43
DMDMi74757361

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Sequence analysisAdd BLAST23
ChainiPRO_000027823924 – 783E3 ubiquitin-protein ligase RNF43Add BLAST760

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi62N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi91 ↔ 119Combined sources1 Publication
Glycosylationi92N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

Autoubiquitinated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ68DV7
PeptideAtlasiQ68DV7
PRIDEiQ68DV7
ProteomicsDBi66105
66106 [Q68DV7-2]
66107 [Q68DV7-3]
66108 [Q68DV7-4]

PTM databases

iPTMnetiQ68DV7
PhosphoSitePlusiQ68DV7

Expressioni

Tissue specificityi

Expressed in fetal kidney, fetal lung, in colon cancer tissues, hepatocellular carcinomas and lung adenocarcinomas. Overexpressed in colorectal cancer cell lines.2 Publications

Gene expression databases

BgeeiENSG00000108375 Expressed in 143 organ(s), highest expression level in colonic mucosa
CleanExiHS_RNF43
ExpressionAtlasiQ68DV7 baseline and differential
GenevisibleiQ68DV7 HS

Organism-specific databases

HPAiHPA008079

Interactioni

Subunit structurei

Interacts with AKAP8L, NONO and SFPQ (PubMed:18313049, PubMed:18655028). Interacts with FZD5 (PubMed:22895187). Identified in a complex composed of RNF43, LGR5 and RSPO1 (PubMed:23756651). Interacts with RSPO2 (PubMed:29769720).5 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi120241, 23 interactors
IntActiQ68DV7, 12 interactors
STRINGi9606.ENSP00000385328

Structurei

Secondary structure

1783
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ68DV7
SMRiQ68DV7
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi443 – 503Ser-richAdd BLAST61
Compositional biasi547 – 557His-richAdd BLAST11
Compositional biasi569 – 760Pro-richAdd BLAST192

Sequence similaritiesi

Belongs to the ZNRF3 family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri272 – 313RING-type; atypicalPROSITE-ProRule annotationAdd BLAST42

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix, Zinc-finger

Phylogenomic databases

eggNOGiKOG0800 Eukaryota
ENOG41121N2 LUCA
GeneTreeiENSGT00760000119057
HOVERGENiHBG093916
InParanoidiQ68DV7
KOiK15694
OrthoDBiEOG091G01HM
PhylomeDBiQ68DV7
TreeFamiTF317074

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
PfamiView protein in Pfam
PF13639 zf-RING_2, 1 hit
SMARTiView protein in SMART
SM00184 RING, 1 hit
PROSITEiView protein in PROSITE
PS50089 ZF_RING_2, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: Q68DV7-1) [UniParc]FASTAAdd to basket

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
MSGGHQLQLA ALWPWLLMAT LQAGFGRTGL VLAAAVESER SAEQKAIIRV
60 70 80 90 100
IPLKMDPTGK LNLTLEGVFA GVAEITPAEG KLMQSHPLYL CNASDDDNLE
110 120 130 140 150
PGFISIVKLE SPRRAPRPCL SLASKARMAG ERGASAVLFD ITEDRAAAEQ
160 170 180 190 200
LQQPLGLTWP VVLIWGNDAE KLMEFVYKNQ KAHVRIELKE PPAWPDYDVW
210 220 230 240 250
ILMTVVGTIF VIILASVLRI RCRPRHSRPD PLQQRTAWAI SQLATRRYQA
260 270 280 290 300
SCRQARGEWP DSGSSCSSAP VCAICLEEFS EGQELRVISC LHEFHRNCVD
310 320 330 340 350
PWLHQHRTCP LCMFNITEGD SFSQSLGPSR SYQEPGRRLH LIRQHPGHAH
360 370 380 390 400
YHLPAAYLLG PSRSAVARPP RPGPFLPSQE PGMGPRHHRF PRAAHPRAPG
410 420 430 440 450
EQQRLAGAQH PYAQGWGLSH LQSTSQHPAA CPVPLRRARP PDSSGSGESY
460 470 480 490 500
CTERSGYLAD GPASDSSSGP CHGSSSDSVV NCTDISLQGV HGSSSTFCSS
510 520 530 540 550
LSSDFDPLVY CSPKGDPQRV DMQPSVTSRP RSLDSVVPTG ETQVSSHVHY
560 570 580 590 600
HRHRHHHYKK RFQWHGRKPG PETGVPQSRP PIPRTQPQPE PPSPDQQVTR
610 620 630 640 650
SNSAAPSGRL SNPQCPRALP EPAPGPVDAS SICPSTSSLF NLQKSSLSAR
660 670 680 690 700
HPQRKRRGGP SEPTPGSRPQ DATVHPACQI FPHYTPSVAY PWSPEAHPLI
710 720 730 740 750
CGPPGLDKRL LPETPGPCYS NSQPVWLCLT PRQPLEPHPP GEGPSEWSSD
760 770 780
TAEGRPCPYP HCQVLSAQPG SEEELEELCE QAV
Length:783
Mass (Da):85,722
Last modified:October 11, 2004 - v1
Checksum:i4E87EA0CC359C858
GO
Isoform 2 (identifier: Q68DV7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     85-125: Missing.

Note: No experimental confirmation available.
Show »
Length:742
Mass (Da):81,229
Checksum:i7A177F5F2AC13F1B
GO
Isoform 3 (identifier: Q68DV7-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-127: Missing.

Note: No experimental confirmation available.
Show »
Length:656
Mass (Da):72,106
Checksum:i6278F14330DC2A94
GO
Isoform 4 (identifier: Q68DV7-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     771-783: SEEELEELCEQAV → EFSEGSGCGR...WKAGCDGSCL

Note: No experimental confirmation available.
Show »
Length:869
Mass (Da):95,038
Checksum:iAFB4B8ECFA217C83
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
J3KSE3J3KSE3_HUMAN
E3 ubiquitin-protein ligase RNF43
RNF43
742Annotation score:

Sequence cautioni

The sequence BAH12871 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti225R → H in BAH12429 (PubMed:14702039).Curated1
Sequence conflicti313M → V in BAD51435 (PubMed:15492824).Curated1
Sequence conflicti313M → V in BAA91085 (PubMed:14702039).Curated1
Sequence conflicti401E → K in BAH12429 (PubMed:14702039).Curated1
Sequence conflicti600R → G in BAD51435 (PubMed:15492824).Curated1
Sequence conflicti600R → G in BAA91085 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03071347I → V1 PublicationCorresponds to variant dbSNP:rs3744093EnsemblClinVar.1
Natural variantiVAR_030714117R → H. Corresponds to variant dbSNP:rs2257205Ensembl.1
Natural variantiVAR_030715221R → Q. Corresponds to variant dbSNP:rs2285990Ensembl.1
Natural variantiVAR_030716231P → L2 PublicationsCorresponds to variant dbSNP:rs2680701Ensembl.1
Natural variantiVAR_052103343R → H. Corresponds to variant dbSNP:rs34523089Ensembl.1
Natural variantiVAR_030717418L → M2 PublicationsCorresponds to variant dbSNP:rs2526374EnsemblClinVar.1
Natural variantiVAR_030718686P → R1 PublicationCorresponds to variant dbSNP:rs9652855Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0373381 – 127Missing in isoform 3. 1 PublicationAdd BLAST127
Alternative sequenceiVSP_03733985 – 125Missing in isoform 2. 1 PublicationAdd BLAST41
Alternative sequenceiVSP_037340771 – 783SEEEL…CEQAV → EFSEGSGCGRERRLQLNISG QVKSANKGLMEAEKDTAEMT TKILNHRDSVSCWLECRNTP PLPGATPLVGRSQGGPREVL VWLRHQKGTWKAGCDGSCL in isoform 4. 1 PublicationAdd BLAST13

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB081837 mRNA Translation: BAD51435.1
AK000322 mRNA Translation: BAA91085.1
AK291027 mRNA Translation: BAF83716.1
AK296769 mRNA Translation: BAH12429.1
AK298789 mRNA Translation: BAH12871.1 Different initiation.
AK299024 mRNA Translation: BAH12931.1
CR627423 mRNA Translation: CAH10510.1
CR749257 mRNA Translation: CAH18113.1
BC109028 mRNA Translation: AAI09029.1
CCDSiCCDS11607.1 [Q68DV7-1]
CCDS82172.1 [Q68DV7-3]
RefSeqiNP_001292473.1, NM_001305544.1 [Q68DV7-1]
NP_001292474.1, NM_001305545.1 [Q68DV7-3]
NP_060233.3, NM_017763.5 [Q68DV7-1]
XP_011523257.1, XM_011524955.2 [Q68DV7-4]
XP_016880289.1, XM_017024800.1 [Q68DV7-4]
UniGeneiHs.584916

Genome annotation databases

EnsembliENST00000407977; ENSP00000385328; ENSG00000108375 [Q68DV7-1]
ENST00000577625; ENSP00000463716; ENSG00000108375 [Q68DV7-3]
ENST00000577716; ENSP00000462764; ENSG00000108375 [Q68DV7-1]
ENST00000583753; ENSP00000462502; ENSG00000108375 [Q68DV7-2]
ENST00000584437; ENSP00000463069; ENSG00000108375 [Q68DV7-1]
GeneIDi54894
KEGGihsa:54894
UCSCiuc002iwf.4 human [Q68DV7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB081837 mRNA Translation: BAD51435.1
AK000322 mRNA Translation: BAA91085.1
AK291027 mRNA Translation: BAF83716.1
AK296769 mRNA Translation: BAH12429.1
AK298789 mRNA Translation: BAH12871.1 Different initiation.
AK299024 mRNA Translation: BAH12931.1
CR627423 mRNA Translation: CAH10510.1
CR749257 mRNA Translation: CAH18113.1
BC109028 mRNA Translation: AAI09029.1
CCDSiCCDS11607.1 [Q68DV7-1]
CCDS82172.1 [Q68DV7-3]
RefSeqiNP_001292473.1, NM_001305544.1 [Q68DV7-1]
NP_001292474.1, NM_001305545.1 [Q68DV7-3]
NP_060233.3, NM_017763.5 [Q68DV7-1]
XP_011523257.1, XM_011524955.2 [Q68DV7-4]
XP_016880289.1, XM_017024800.1 [Q68DV7-4]
UniGeneiHs.584916

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4KNGX-ray2.50E/F44-198[»]
ProteinModelPortaliQ68DV7
SMRiQ68DV7
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120241, 23 interactors
IntActiQ68DV7, 12 interactors
STRINGi9606.ENSP00000385328

PTM databases

iPTMnetiQ68DV7
PhosphoSitePlusiQ68DV7

Polymorphism and mutation databases

BioMutaiRNF43
DMDMi74757361

Proteomic databases

PaxDbiQ68DV7
PeptideAtlasiQ68DV7
PRIDEiQ68DV7
ProteomicsDBi66105
66106 [Q68DV7-2]
66107 [Q68DV7-3]
66108 [Q68DV7-4]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000407977; ENSP00000385328; ENSG00000108375 [Q68DV7-1]
ENST00000577625; ENSP00000463716; ENSG00000108375 [Q68DV7-3]
ENST00000577716; ENSP00000462764; ENSG00000108375 [Q68DV7-1]
ENST00000583753; ENSP00000462502; ENSG00000108375 [Q68DV7-2]
ENST00000584437; ENSP00000463069; ENSG00000108375 [Q68DV7-1]
GeneIDi54894
KEGGihsa:54894
UCSCiuc002iwf.4 human [Q68DV7-1]

Organism-specific databases

CTDi54894
DisGeNETi54894
EuPathDBiHostDB:ENSG00000108375.12
GeneCardsiRNF43
HGNCiHGNC:18505 RNF43
HPAiHPA008079
MalaCardsiRNF43
MIMi612482 gene
617108 phenotype
neXtProtiNX_Q68DV7
OpenTargetsiENSG00000108375
Orphaneti157798 Hyperplastic polyposis syndrome
PharmGKBiPA34441
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0800 Eukaryota
ENOG41121N2 LUCA
GeneTreeiENSGT00760000119057
HOVERGENiHBG093916
InParanoidiQ68DV7
KOiK15694
OrthoDBiEOG091G01HM
PhylomeDBiQ68DV7
TreeFamiTF317074

Enzyme and pathway databases

UniPathwayi
UPA00143

BRENDAi2.3.2.B10 2681
6.3.2.19 2681
ReactomeiR-HSA-4641263 Regulation of FZD by ubiquitination
R-HSA-5340588 RNF mutants show enhanced WNT signaling and proliferation
SIGNORiQ68DV7

Miscellaneous databases

ChiTaRSiRNF43 human
GenomeRNAii54894
PROiPR:Q68DV7
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000108375 Expressed in 143 organ(s), highest expression level in colonic mucosa
CleanExiHS_RNF43
ExpressionAtlasiQ68DV7 baseline and differential
GenevisibleiQ68DV7 HS

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
PfamiView protein in Pfam
PF13639 zf-RING_2, 1 hit
SMARTiView protein in SMART
SM00184 RING, 1 hit
PROSITEiView protein in PROSITE
PS50089 ZF_RING_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiRNF43_HUMAN
AccessioniPrimary (citable) accession number: Q68DV7
Secondary accession number(s): A8K4R2
, B7Z443, B7Z5D5, B7Z5J5, Q65ZA4, Q6AI04, Q9NXD0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: October 11, 2004
Last modified: November 7, 2018
This is version 138 of the entry and version 1 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  7. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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