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Protein

E3 ubiquitin-protein ligase RNF43

Gene

RNF43

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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. Acts as a tumor suppressor in the intestinal stem cell zone by inhibiting the Wnt signaling pathway, thereby resticting the size of the intestinal stem cell zone.3 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: ParkinsonsUK-UCL
  • ubiquitin-protein transferase activity Source: UniProtKB

GO - Biological processi

  • negative regulation of Wnt signaling pathway Source: UniProtKB
  • protein ubiquitination Source: UniProtKB
  • protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: UniProtKB
  • stem cell proliferation Source: UniProtKB
  • Wnt receptor catabolic process Source: UniProtKB
  • Wnt signaling pathway Source: UniProtKB-KW

Keywordsi

Molecular functionTransferase
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.
UniPathwayiUPA00143.

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.

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.
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 ↔ 119
Glycosylationi92N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

Autoubiquitinated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ68DV7.
PeptideAtlasiQ68DV7.
PRIDEiQ68DV7.

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.
CleanExiHS_RNF43.
ExpressionAtlasiQ68DV7. baseline and differential.
GenevisibleiQ68DV7. HS.

Organism-specific databases

HPAiHPA008079.

Interactioni

Subunit structurei

Interacts with AKAP8L, NONO and SFPQ. Interacts with FZD5. Identified in a complex composed of RNF43, LGR5 and RSPO1.4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • frizzled binding Source: UniProtKB

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
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi45 – 54Combined sources10
Beta strandi57 – 59Combined sources3
Beta strandi63 – 69Combined sources7
Beta strandi71 – 73Combined sources3
Beta strandi78 – 84Combined sources7
Turni87 – 89Combined sources3
Beta strandi104 – 108Combined sources5
Turni112 – 114Combined sources3
Helixi122 – 131Combined sources10
Beta strandi135 – 140Combined sources6
Helixi142 – 146Combined sources5
Helixi147 – 150Combined sources4
Beta strandi157 – 159Combined sources3
Beta strandi161 – 164Combined sources4
Helixi166 – 176Combined sources11
Beta strandi177 – 179Combined sources3
Beta strandi184 – 189Combined sources6

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...

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

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

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:rs3744093Ensembl.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:rs2526374Ensembl.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

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: September 27, 2017
This is version 134 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. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families