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Q68DV7 (RNF43_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 102. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
E3 ubiquitin-protein ligase RNF43

EC=6.3.2.-
Alternative name(s):
RING finger protein 43
Gene names
Name:RNF43
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length783 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.6 Ref.8 Ref.9

Pathway

Protein modification; protein ubiquitination.

Subunit structure

Interacts with AKAP8L, NONO and SFPQ. Interacts with FZD5. Identified in a complex composed of RNF43, LGR5 and RSPO1. Ref.6 Ref.7 Ref.9 Ref.10

Subcellular location

Cell membrane; Single-pass type I membrane protein. Endoplasmic reticulum membrane; Single-pass type I membrane protein. Nucleus envelope. Note: According to a report, may be secreted (Ref.1). Ref.1 Ref.6 Ref.7 Ref.8 Ref.9

Tissue specificity

Expressed in fetal kidney, fetal lung, in colon cancer tissues, hepatocellular carcinomas and lung adenocarcinomas. Overexpressed in colorectal cancer cell lines. Ref.1 Ref.6

Post-translational modification

Autoubiquitinated.

Miscellaneous

Acts as a cytotoxic T-lymphocyte tumor antigen, suggesting that it may be used as a target for cancer immunotherapy (Ref.5).

Sequence similarities

Belongs to the ZNRF3 family.

Contains 1 RING-type zinc finger.

Sequence caution

The sequence BAH12871.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Biological processUbl conjugation pathway
Wnt signaling pathway
   Cellular componentCell membrane
Endoplasmic reticulum
Membrane
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSignal
Transmembrane
Transmembrane helix
Zinc-finger
   LigandMetal-binding
Zinc
   Molecular functionLigase
   PTMDisulfide bond
Glycoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processWnt receptor catabolic process

Inferred from direct assay Ref.9. Source: UniProtKB

Wnt signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of Wnt signaling pathway

Inferred from mutant phenotype Ref.8Ref.9. Source: UniProtKB

protein ubiquitination

Inferred from direct assay Ref.8. Source: UniProtKB

protein ubiquitination involved in ubiquitin-dependent protein catabolic process

Inferred from direct assay Ref.9. Source: UniProtKB

stem cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentendoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of plasma membrane

Inferred from direct assay Ref.8Ref.9. Source: UniProtKB

nuclear envelope

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionfrizzled binding

Inferred from physical interaction Ref.9. Source: UniProtKB

ubiquitin-protein ligase activity

Inferred from direct assay Ref.8Ref.9. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q68DV7-1)

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.
Isoform 2 (identifier: Q68DV7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     85-125: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q68DV7-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-127: Missing.
Note: No experimental confirmation available.
Isoform 4 (identifier: Q68DV7-4)

The sequence of this isoform differs from the canonical sequence as follows:
     771-783: SEEELEELCEQAV → EFSEGSGCGR...WKAGCDGSCL
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Potential
Chain24 – 783760E3 ubiquitin-protein ligase RNF43
PRO_0000278239

Regions

Topological domain24 – 197174Extracellular Potential
Transmembrane198 – 21821Helical; Potential
Topological domain219 – 783565Cytoplasmic Potential
Zinc finger272 – 31342RING-type; atypical
Compositional bias443 – 50361Ser-rich
Compositional bias547 – 55711His-rich
Compositional bias569 – 760192Pro-rich

Amino acid modifications

Glycosylation621N-linked (GlcNAc...) Potential
Glycosylation921N-linked (GlcNAc...) Potential
Disulfide bond91 ↔ 119

Natural variations

Alternative sequence1 – 127127Missing in isoform 3.
VSP_037338
Alternative sequence85 – 12541Missing in isoform 2.
VSP_037339
Alternative sequence771 – 78313SEEEL…CEQAV → EFSEGSGCGRERRLQLNISG QVKSANKGLMEAEKDTAEMT TKILNHRDSVSCWLECRNTP PLPGATPLVGRSQGGPREVL VWLRHQKGTWKAGCDGSCL in isoform 4.
VSP_037340
Natural variant471I → V. Ref.2
Corresponds to variant rs3744093 [ dbSNP | Ensembl ].
VAR_030713
Natural variant1171R → H.
Corresponds to variant rs2257205 [ dbSNP | Ensembl ].
VAR_030714
Natural variant2211R → Q.
Corresponds to variant rs2285990 [ dbSNP | Ensembl ].
VAR_030715
Natural variant2311P → L. Ref.2
Corresponds to variant rs2680701 [ dbSNP | Ensembl ].
VAR_030716
Natural variant3431R → H.
Corresponds to variant rs34523089 [ dbSNP | Ensembl ].
VAR_052103
Natural variant4181L → M. Ref.1 Ref.2
Corresponds to variant rs2526374 [ dbSNP | Ensembl ].
VAR_030717
Natural variant6861P → R. Ref.3
Corresponds to variant rs9652855 [ dbSNP | Ensembl ].
VAR_030718

Experimental info

Mutagenesis2901C → S: Dominant-negative mutant, loss of E3 ligase activity and activation of the Wnt signaling pathway; when associated with S-292. Ref.6 Ref.9
Mutagenesis2921H → S: Dominant-negative mutant, loss of E3 ligase activity and activation of the Wnt signaling pathway; when associated with S-290. Ref.6 Ref.9
Mutagenesis2951H → S: Dominant-negative mutant, loss of E3 ligase activity and activation of the Wnt signaling pathway; when associated with S-298. Ref.9
Mutagenesis2981C → S: Dominant-negative mutant, loss of E3 ligase activity and activation of the Wnt signaling pathway; when associated with S-295. Ref.9
Sequence conflict2251R → H in BAH12429. Ref.2
Sequence conflict3131M → V in BAD51435. Ref.1
Sequence conflict3131M → V in BAA91085. Ref.2
Sequence conflict4011E → K in BAH12429. Ref.2
Sequence conflict6001R → G in BAD51435. Ref.1
Sequence conflict6001R → G in BAA91085. Ref.2

Secondary structure

................................. 783
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 11, 2004. Version 1.
Checksum: 4E87EA0CC359C858

FASTA78385,722
        10         20         30         40         50         60 
MSGGHQLQLA ALWPWLLMAT LQAGFGRTGL VLAAAVESER SAEQKAIIRV IPLKMDPTGK 

        70         80         90        100        110        120 
LNLTLEGVFA GVAEITPAEG KLMQSHPLYL CNASDDDNLE PGFISIVKLE SPRRAPRPCL 

       130        140        150        160        170        180 
SLASKARMAG ERGASAVLFD ITEDRAAAEQ LQQPLGLTWP VVLIWGNDAE KLMEFVYKNQ 

       190        200        210        220        230        240 
KAHVRIELKE PPAWPDYDVW ILMTVVGTIF VIILASVLRI RCRPRHSRPD PLQQRTAWAI 

       250        260        270        280        290        300 
SQLATRRYQA SCRQARGEWP DSGSSCSSAP VCAICLEEFS EGQELRVISC LHEFHRNCVD 

       310        320        330        340        350        360 
PWLHQHRTCP LCMFNITEGD SFSQSLGPSR SYQEPGRRLH LIRQHPGHAH YHLPAAYLLG 

       370        380        390        400        410        420 
PSRSAVARPP RPGPFLPSQE PGMGPRHHRF PRAAHPRAPG EQQRLAGAQH PYAQGWGLSH 

       430        440        450        460        470        480 
LQSTSQHPAA CPVPLRRARP PDSSGSGESY CTERSGYLAD GPASDSSSGP CHGSSSDSVV 

       490        500        510        520        530        540 
NCTDISLQGV HGSSSTFCSS LSSDFDPLVY CSPKGDPQRV DMQPSVTSRP RSLDSVVPTG 

       550        560        570        580        590        600 
ETQVSSHVHY HRHRHHHYKK RFQWHGRKPG PETGVPQSRP PIPRTQPQPE PPSPDQQVTR 

       610        620        630        640        650        660 
SNSAAPSGRL SNPQCPRALP EPAPGPVDAS SICPSTSSLF NLQKSSLSAR HPQRKRRGGP 

       670        680        690        700        710        720 
SEPTPGSRPQ DATVHPACQI FPHYTPSVAY PWSPEAHPLI CGPPGLDKRL LPETPGPCYS 

       730        740        750        760        770        780 
NSQPVWLCLT PRQPLEPHPP GEGPSEWSSD TAEGRPCPYP HCQVLSAQPG SEEELEELCE 


QAV 

« Hide

Isoform 2 [UniParc].

Checksum: 7A177F5F2AC13F1B
Show »

FASTA74281,229
Isoform 3 [UniParc].

Checksum: 6278F14330DC2A94
Show »

FASTA65672,106
Isoform 4 [UniParc].

Checksum: AFB4B8ECFA217C83
Show »

FASTA86995,038

References

« Hide 'large scale' references
[1]"A novel oncoprotein RNF43 functions in an autocrine manner in colorectal cancer."
Yagyu R., Furukawa Y., Lin Y.-M., Shimokawa T., Yamamura T., Nakamura Y.
Int. J. Oncol. 25:1343-1348(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANT MET-418.
Tissue: Colon carcinoma.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 214-783 (ISOFORM 4), VARIANTS VAL-47; LEU-231 AND MET-418.
Tissue: Hepatoma, Teratocarcinoma and Tongue.
[3]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ARG-686.
Tissue: Colon carcinoma.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]"Ring finger protein 43 as a new target for cancer immunotherapy."
Uchida N., Tsunoda T., Wada S., Furukawa Y., Nakamura Y., Tahara H.
Clin. Cancer Res. 10:8577-8586(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION AS A CYTOTOXIC T LYMPHOCYTE TUMOR ANTIGEN.
[6]"A cancer-associated RING finger protein, RNF43, is a ubiquitin ligase that interacts with a nuclear protein, HAP95."
Sugiura T., Yamaguchi A., Miyamoto K.
Exp. Cell Res. 314:1519-1528(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH AKAP8L, AUTOUBIQUITINATION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-290 AND HIS-292.
[7]"Proteomic identification of a PSF/p54nrb heterodimer as RNF43 oncoprotein-interacting proteins."
Miyamoto K., Sakurai H., Sugiura T.
Proteomics 8:2907-2910(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NONO AND SFPQ, SUBCELLULAR LOCATION.
[8]"ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner."
Hao H.X., Xie Y., Zhang Y., Charlat O., Oster E., Avello M., Lei H., Mickanin C., Liu D., Ruffner H., Mao X., Ma Q., Zamponi R., Bouwmeester T., Finan P.M., Kirschner M.W., Porter J.A., Serluca F.C., Cong F.
Nature 485:195-200(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[9]"Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors."
Koo B.K., Spit M., Jordens I., Low T.Y., Stange D.E., van de Wetering M., van Es J.H., Mohammed S., Heck A.J., Maurice M.M., Clevers H.
Nature 488:665-669(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH FZD5, MUTAGENESIS OF CYS-290; HIS-292; HIS-295 AND CYS-298.
[10]"The structural basis of R-spondin recognition by LGR5 and RNF43."
Chen P.H., Chen X., Lin Z., Fang D., He X.
Genes Dev. 27:1345-1350(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 44-198 IN COMPLEX WITH RSPO1 AND LGR5, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_060233.3. NM_017763.4.
UniGeneHs.584916.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4KNGX-ray2.50E/F44-198[»]
ProteinModelPortalQ68DV7.
SMRQ68DV7. Positions 44-191, 237-317.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120241. 15 interactions.
IntActQ68DV7. 12 interactions.
STRING9606.ENSP00000385328.

Polymorphism databases

DMDM74757361.

Proteomic databases

PaxDbQ68DV7.
PRIDEQ68DV7.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000407977; ENSP00000385328; ENSG00000108375. [Q68DV7-1]
ENST00000500597; ENSP00000441969; ENSG00000108375. [Q68DV7-2]
ENST00000577625; ENSP00000463716; ENSG00000108375. [Q68DV7-3]
ENST00000577716; ENSP00000462764; ENSG00000108375. [Q68DV7-1]
ENST00000583753; ENSP00000462502; ENSG00000108375. [Q68DV7-2]
ENST00000584437; ENSP00000463069; ENSG00000108375. [Q68DV7-1]
GeneID54894.
KEGGhsa:54894.
UCSCuc002iwf.3. human. [Q68DV7-1]
uc010wnv.2. human. [Q68DV7-2]

Organism-specific databases

CTD54894.
GeneCardsGC17M056429.
HGNCHGNC:18505. RNF43.
HPAHPA008079.
MIM612482. gene.
neXtProtNX_Q68DV7.
PharmGKBPA34441.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG329235.
HOVERGENHBG093916.
InParanoidQ68DV7.
KOK15694.
OMAHPLIFGP.
OrthoDBEOG7P5T06.
PhylomeDBQ68DV7.
TreeFamTF317074.

Enzyme and pathway databases

UniPathwayUPA00143.

Gene expression databases

ArrayExpressQ68DV7.
BgeeQ68DV7.
CleanExHS_RNF43.
GenevestigatorQ68DV7.

Family and domain databases

Gene3D3.30.40.10. 1 hit.
InterProIPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamPF13639. zf-RING_2. 1 hit.
[Graphical view]
SMARTSM00184. RING. 1 hit.
[Graphical view]
PROSITEPS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSRNF43. human.
GenomeRNAi54894.
NextBio57898.
PROQ68DV7.
SOURCESearch...

Entry information

Entry nameRNF43_HUMAN
AccessionPrimary (citable) accession number: Q68DV7
Secondary accession number(s): A8K4R2 expand/collapse secondary AC list , B7Z443, B7Z5D5, B7Z5J5, Q65ZA4, Q6AI04, Q9NXD0
Entry history
Integrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: October 11, 2004
Last modified: April 16, 2014
This is version 102 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM