ID   RNF43_HUMAN             Reviewed;         783 AA.
AC   Q68DV7; A8K4R2; B7Z443; B7Z5D5; B7Z5J5; Q65ZA4; Q6AI04; Q9NXD0;
DT   20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT   11-OCT-2004, sequence version 1.
DT   24-JAN-2024, entry version 167.
DE   RecName: Full=E3 ubiquitin-protein ligase RNF43;
DE            EC=2.3.2.27;
DE   AltName: Full=RING finger protein 43;
DE   AltName: Full=RING-type E3 ubiquitin transferase RNF43 {ECO:0000305};
DE   Flags: Precursor;
GN   Name=RNF43;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE
RP   SPECIFICITY, AND VARIANT MET-418.
RC   TISSUE=Colon carcinoma;
RX   PubMed=15492824;
RA   Yagyu R., Furukawa Y., Lin Y.-M., Shimokawa T., Yamamura T., Nakamura Y.;
RT   "A novel oncoprotein RNF43 functions in an autocrine manner in colorectal
RT   cancer.";
RL   Int. J. Oncol. 25:1343-1348(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), NUCLEOTIDE
RP   SEQUENCE [LARGE SCALE MRNA] OF 214-783 (ISOFORM 4), AND VARIANTS VAL-47;
RP   LEU-231 AND MET-418.
RC   TISSUE=Hepatoma, Teratocarcinoma, and Tongue;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ARG-686.
RC   TISSUE=Colon carcinoma;
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   IDENTIFICATION AS A CYTOTOXIC T LYMPHOCYTE TUMOR ANTIGEN.
RX   PubMed=15623641; DOI=10.1158/1078-0432.ccr-04-0104;
RA   Uchida N., Tsunoda T., Wada S., Furukawa Y., Nakamura Y., Tahara H.;
RT   "Ring finger protein 43 as a new target for cancer immunotherapy.";
RL   Clin. Cancer Res. 10:8577-8586(2004).
RN   [6]
RP   FUNCTION, INTERACTION WITH AKAP8L, AUTOUBIQUITINATION, TISSUE SPECIFICITY,
RP   SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-290 AND HIS-292.
RX   PubMed=18313049; DOI=10.1016/j.yexcr.2008.01.013;
RA   Sugiura T., Yamaguchi A., Miyamoto K.;
RT   "A cancer-associated RING finger protein, RNF43, is a ubiquitin ligase that
RT   interacts with a nuclear protein, HAP95.";
RL   Exp. Cell Res. 314:1519-1528(2008).
RN   [7]
RP   INTERACTION WITH NONO AND SFPQ, AND SUBCELLULAR LOCATION.
RX   PubMed=18655028; DOI=10.1002/pmic.200800083;
RA   Miyamoto K., Sakurai H., Sugiura T.;
RT   "Proteomic identification of a PSF/p54nrb heterodimer as RNF43 oncoprotein-
RT   interacting proteins.";
RL   Proteomics 8:2907-2910(2008).
RN   [8]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=22575959; DOI=10.1038/nature11019;
RA   Hao H.X., Xie Y., Zhang Y., Charlat O., Oster E., Avello M., Lei H.,
RA   Mickanin C., Liu D., Ruffner H., Mao X., Ma Q., Zamponi R., Bouwmeester T.,
RA   Finan P.M., Kirschner M.W., Porter J.A., Serluca F.C., Cong F.;
RT   "ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner.";
RL   Nature 485:195-200(2012).
RN   [9]
RP   FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH FZD5, AND MUTAGENESIS OF
RP   CYS-290; HIS-292; HIS-295 AND CYS-298.
RX   PubMed=22895187; DOI=10.1038/nature11308;
RA   Koo B.K., Spit M., Jordens I., Low T.Y., Stange D.E., van de Wetering M.,
RA   van Es J.H., Mohammed S., Heck A.J., Maurice M.M., Clevers H.;
RT   "Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis
RT   of Wnt receptors.";
RL   Nature 488:665-669(2012).
RN   [10]
RP   INVOLVEMENT IN SSPCS.
RX   PubMed=24512911; DOI=10.1053/j.gastro.2013.10.045;
RA   Gala M.K., Mizukami Y., Le L.P., Moriichi K., Austin T., Yamamoto M.,
RA   Lauwers G.Y., Bardeesy N., Chung D.C.;
RT   "Germline mutations in oncogene-induced senescence pathways are associated
RT   with multiple sessile serrated adenomas.";
RL   Gastroenterology 146:520-529(2014).
RN   [11]
RP   INVOLVEMENT IN SSPCS, AND VARIANT LEU-231.
RX   PubMed=27081527; DOI=10.1038/hgv.2015.13;
RA   Taupin D., Lam W., Rangiah D., McCallum L., Whittle B., Zhang Y.,
RA   Andrews D., Field M., Goodnow C.C., Cook M.C.;
RT   "A deleterious RNF43 germline mutation in a severely affected serrated
RT   polyposis kindred.";
RL   Hum. Genome Var. 2:15013-15013(2015).
RN   [12]
RP   INTERACTION WITH RSPO2.
RX   PubMed=29769720; DOI=10.1038/s41586-018-0118-y;
RA   Szenker-Ravi E., Altunoglu U., Leushacke M., Bosso-Lefevre C., Khatoo M.,
RA   Thi Tran H., Naert T., Noelanders R., Hajamohideen A., Beneteau C.,
RA   de Sousa S.B., Karaman B., Latypova X., Basaran S., Yuecel E.B., Tan T.T.,
RA   Vlaminck L., Nayak S.S., Shukla A., Girisha K.M., Le Caignec C.,
RA   Soshnikova N., Uyguner Z.O., Vleminckx K., Barker N., Kayserili H.,
RA   Reversade B.;
RT   "RSPO2 inhibition of RNF43 and ZNRF3 governs limb development independently
RT   of LGR4/5/6.";
RL   Nature 557:564-569(2018).
RN   [13]
RP   X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 44-198 IN COMPLEX WITH RSPO1 AND
RP   LGR5, SUBUNIT, AND DISULFIDE BONDS.
RX   PubMed=23756651; DOI=10.1101/gad.219915.113;
RA   Chen P.H., Chen X., Lin Z., Fang D., He X.;
RT   "The structural basis of R-spondin recognition by LGR5 and RNF43.";
RL   Genes Dev. 27:1345-1350(2013).
CC   -!- FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
CC       of the Wnt signaling pathway by mediating the ubiquitination,
CC       endocytosis and subsequent degradation of Wnt receptor complex
CC       components Frizzled. Acts on both canonical and non-canonical Wnt
CC       signaling pathway (PubMed:18313049, PubMed:22575959, PubMed:22895187).
CC       Along with RSPO2 and ZNRF3, constitutes a master switch that governs
CC       limb specification (By similarity). {ECO:0000250|UniProtKB:P0DPR2,
CC       ECO:0000269|PubMed:18313049, ECO:0000269|PubMed:22575959,
CC       ECO:0000269|PubMed:22895187}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC         [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC         cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC         EC=2.3.2.27;
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC   -!- SUBUNIT: Interacts with AKAP8L, NONO and SFPQ (PubMed:18313049,
CC       PubMed:18655028). Interacts with FZD5 (PubMed:22895187). Identified in
CC       a complex composed of RNF43, LGR5 and RSPO1 (PubMed:23756651).
CC       Interacts with RSPO2 (PubMed:29769720). Interacts with LMBR1L (By
CC       similarity). {ECO:0000250|UniProtKB:Q5NCP0,
CC       ECO:0000269|PubMed:18313049, ECO:0000269|PubMed:18655028,
CC       ECO:0000269|PubMed:22895187, ECO:0000269|PubMed:23756651,
CC       ECO:0000269|PubMed:29769720}.
CC   -!- INTERACTION:
CC       Q68DV7; Q9ULX6: AKAP8L; NbExp=2; IntAct=EBI-1647060, EBI-357530;
CC       Q68DV7; P0CG47: UBB; NbExp=2; IntAct=EBI-1647060, EBI-413034;
CC       Q68DV7; P62837: UBE2D2; NbExp=2; IntAct=EBI-1647060, EBI-347677;
CC       Q68DV7; P61077: UBE2D3; NbExp=2; IntAct=EBI-1647060, EBI-348268;
CC   -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC       protein. Endoplasmic reticulum membrane; Single-pass type I membrane
CC       protein. Nucleus envelope. Note=According to a report, may be secreted.
CC       {ECO:0000269|PubMed:15492824}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=4;
CC       Name=1;
CC         IsoId=Q68DV7-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q68DV7-2; Sequence=VSP_037339;
CC       Name=3;
CC         IsoId=Q68DV7-3; Sequence=VSP_037338;
CC       Name=4;
CC         IsoId=Q68DV7-4; Sequence=VSP_037340;
CC   -!- TISSUE SPECIFICITY: Expressed in fetal kidney, fetal lung, in colon
CC       cancer tissues, hepatocellular carcinomas and lung adenocarcinomas.
CC       Overexpressed in colorectal cancer cell lines.
CC       {ECO:0000269|PubMed:15492824, ECO:0000269|PubMed:18313049}.
CC   -!- PTM: Autoubiquitinated. {ECO:0000269|PubMed:18313049}.
CC   -!- DISEASE: Sessile serrated polyposis cancer syndrome (SSPCS)
CC       [MIM:617108]: A rare disease characterized by multiple and/or large
CC       serrated polyps developing in the colon, and an increased personal and
CC       familial risk of colorectal cancer. A patient is diagnosed with SSPCS
CC       if at least one of the following criteria is met: the presence of at
CC       least five sessile serrated polyps proximal to the sigmoid colon, two
CC       of which are greater than 10 mm in diameter; the presence of any number
CC       of serrated polyps occurring proximal to the sigmoid colon in an
CC       individual who has a first-degree relative with serrated polyposis; the
CC       presence of more than 20 serrated polyps of any size distributed
CC       throughout the colon. Sessile serrated polyps are also known as sessile
CC       serrated adenomas (SSA) and are estimated to be responsible for 20 to
CC       35% of all colon cancers. Individuals with SSPCS may have a strong
CC       personal or family history of extracolonic cancers.
CC       {ECO:0000269|PubMed:24512911, ECO:0000269|PubMed:27081527}.
CC       Note=Disease susceptibility may be associated with variants affecting
CC       the gene represented in this entry.
CC   -!- MISCELLANEOUS: Acts as a cytotoxic T-lymphocyte tumor antigen,
CC       suggesting that it may be used as a target for cancer immunotherapy.
CC       {ECO:0000305|PubMed:15623641}.
CC   -!- SIMILARITY: Belongs to the ZNRF3 family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAH12871.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AB081837; BAD51435.1; -; mRNA.
DR   EMBL; AK000322; BAA91085.1; -; mRNA.
DR   EMBL; AK291027; BAF83716.1; -; mRNA.
DR   EMBL; AK296769; BAH12429.1; -; mRNA.
DR   EMBL; AK298789; BAH12871.1; ALT_INIT; mRNA.
DR   EMBL; AK299024; BAH12931.1; -; mRNA.
DR   EMBL; CR627423; CAH10510.1; -; mRNA.
DR   EMBL; CR749257; CAH18113.1; -; mRNA.
DR   EMBL; BC109028; AAI09029.1; -; mRNA.
DR   CCDS; CCDS11607.1; -. [Q68DV7-1]
DR   CCDS; CCDS82172.1; -. [Q68DV7-3]
DR   RefSeq; NP_001292473.1; NM_001305544.1. [Q68DV7-1]
DR   RefSeq; NP_001292474.1; NM_001305545.1. [Q68DV7-3]
DR   RefSeq; NP_060233.3; NM_017763.5. [Q68DV7-1]
DR   RefSeq; XP_011523257.1; XM_011524955.2.
DR   RefSeq; XP_016880289.1; XM_017024800.1. [Q68DV7-4]
DR   PDB; 4KNG; X-ray; 2.50 A; E/F=44-198.
DR   PDBsum; 4KNG; -.
DR   AlphaFoldDB; Q68DV7; -.
DR   SMR; Q68DV7; -.
DR   BioGRID; 120241; 426.
DR   CORUM; Q68DV7; -.
DR   IntAct; Q68DV7; 15.
DR   STRING; 9606.ENSP00000463069; -.
DR   GlyCosmos; Q68DV7; 2 sites, No reported glycans.
DR   GlyGen; Q68DV7; 2 sites.
DR   iPTMnet; Q68DV7; -.
DR   PhosphoSitePlus; Q68DV7; -.
DR   BioMuta; RNF43; -.
DR   DMDM; 74757361; -.
DR   jPOST; Q68DV7; -.
DR   MassIVE; Q68DV7; -.
DR   PaxDb; 9606-ENSP00000463069; -.
DR   PeptideAtlas; Q68DV7; -.
DR   ProteomicsDB; 66108; -. [Q68DV7-4]
DR   ABCD; Q68DV7; 3 sequenced antibodies.
DR   Antibodypedia; 1979; 226 antibodies from 26 providers.
DR   DNASU; 54894; -.
DR   Ensembl; ENST00000407977.7; ENSP00000385328.2; ENSG00000108375.13. [Q68DV7-1]
DR   Ensembl; ENST00000577625.5; ENSP00000463716.1; ENSG00000108375.13. [Q68DV7-3]
DR   Ensembl; ENST00000577716.5; ENSP00000462764.1; ENSG00000108375.13. [Q68DV7-1]
DR   Ensembl; ENST00000583753.5; ENSP00000462502.1; ENSG00000108375.13. [Q68DV7-2]
DR   Ensembl; ENST00000584437.5; ENSP00000463069.1; ENSG00000108375.13. [Q68DV7-1]
DR   GeneID; 54894; -.
DR   KEGG; hsa:54894; -.
DR   MANE-Select; ENST00000407977.7; ENSP00000385328.2; NM_017763.6; NP_060233.3.
DR   UCSC; uc002iwf.4; human. [Q68DV7-1]
DR   AGR; HGNC:18505; -.
DR   CTD; 54894; -.
DR   DisGeNET; 54894; -.
DR   GeneCards; RNF43; -.
DR   HGNC; HGNC:18505; RNF43.
DR   HPA; ENSG00000108375; Tissue enhanced (intestine).
DR   MalaCards; RNF43; -.
DR   MIM; 612482; gene.
DR   MIM; 617108; phenotype.
DR   neXtProt; NX_Q68DV7; -.
DR   OpenTargets; ENSG00000108375; -.
DR   Orphanet; 157798; Serrated polyposis syndrome.
DR   PharmGKB; PA34441; -.
DR   VEuPathDB; HostDB:ENSG00000108375; -.
DR   eggNOG; KOG0800; Eukaryota.
DR   GeneTree; ENSGT00940000154006; -.
DR   HOGENOM; CLU_401501_0_0_1; -.
DR   InParanoid; Q68DV7; -.
DR   OrthoDB; 5474929at2759; -.
DR   PhylomeDB; Q68DV7; -.
DR   TreeFam; TF317074; -.
DR   BRENDA; 2.3.2.27; 2681.
DR   PathwayCommons; Q68DV7; -.
DR   Reactome; R-HSA-4641263; Regulation of FZD by ubiquitination.
DR   Reactome; R-HSA-5340588; Signaling by RNF43 mutants.
DR   SignaLink; Q68DV7; -.
DR   SIGNOR; Q68DV7; -.
DR   UniPathway; UPA00143; -.
DR   BioGRID-ORCS; 54894; 10 hits in 1114 CRISPR screens.
DR   ChiTaRS; RNF43; human.
DR   GenomeRNAi; 54894; -.
DR   Pharos; Q68DV7; Tbio.
DR   PRO; PR:Q68DV7; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   RNAct; Q68DV7; Protein.
DR   Bgee; ENSG00000108375; Expressed in cervix squamous epithelium and 144 other cell types or tissues.
DR   ExpressionAtlas; Q68DV7; baseline and differential.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005635; C:nuclear envelope; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0005109; F:frizzled binding; IPI:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR   GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR   GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IMP:UniProtKB.
DR   GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR   GO; GO:0072089; P:stem cell proliferation; ISS:UniProtKB.
DR   GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR   GO; GO:0038018; P:Wnt receptor catabolic process; IDA:UniProtKB.
DR   GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR   CDD; cd16798; RING-H2_RNF43; 1.
DR   Gene3D; 3.50.30.30; -; 1.
DR   Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1.
DR   InterPro; IPR045907; RNF43_Znf_RING.
DR   InterPro; IPR001841; Znf_RING.
DR   InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR   InterPro; IPR040700; ZNRF-3_ecto.
DR   PANTHER; PTHR16200:SF2; E3 UBIQUITIN-PROTEIN LIGASE RNF43; 1.
DR   PANTHER; PTHR16200; RING ZINC FINGER; 1.
DR   Pfam; PF13639; zf-RING_2; 1.
DR   Pfam; PF18212; ZNRF_3_ecto; 1.
DR   SMART; SM00184; RING; 1.
DR   SUPFAM; SSF57850; RING/U-box; 1.
DR   PROSITE; PS50089; ZF_RING_2; 1.
DR   Genevisible; Q68DV7; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cell membrane; Developmental protein;
KW   Disulfide bond; Endoplasmic reticulum; Glycoprotein; Membrane;
KW   Metal-binding; Nucleus; Reference proteome; Signal; Transferase;
KW   Transmembrane; Transmembrane helix; Ubl conjugation;
KW   Ubl conjugation pathway; Wnt signaling pathway; Zinc; Zinc-finger.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000255"
FT   CHAIN           24..783
FT                   /note="E3 ubiquitin-protein ligase RNF43"
FT                   /id="PRO_0000278239"
FT   TOPO_DOM        24..197
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        198..218
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        219..783
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   ZN_FING         272..313
FT                   /note="RING-type; atypical"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT   REGION          363..406
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          421..477
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          514..673
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          731..760
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        521..545
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        548..564
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        574..594
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        595..610
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        630..648
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        62
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        92
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        91..119
FT                   /evidence="ECO:0000269|PubMed:23756651,
FT                   ECO:0007744|PDB:4KNG"
FT   VAR_SEQ         1..127
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_037338"
FT   VAR_SEQ         85..125
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_037339"
FT   VAR_SEQ         771..783
FT                   /note="SEEELEELCEQAV -> EFSEGSGCGRERRLQLNISGQVKSANKGLMEAEKD
FT                   TAEMTTKILNHRDSVSCWLECRNTPPLPGATPLVGRSQGGPREVLVWLRHQKGTWKAGC
FT                   DGSCL (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_037340"
FT   VARIANT         47
FT                   /note="I -> V (in dbSNP:rs3744093)"
FT                   /evidence="ECO:0000269|PubMed:14702039"
FT                   /id="VAR_030713"
FT   VARIANT         117
FT                   /note="R -> H (in dbSNP:rs2257205)"
FT                   /id="VAR_030714"
FT   VARIANT         221
FT                   /note="R -> Q (in dbSNP:rs2285990)"
FT                   /id="VAR_030715"
FT   VARIANT         231
FT                   /note="P -> L (in dbSNP:rs2680701)"
FT                   /evidence="ECO:0000269|PubMed:14702039,
FT                   ECO:0000269|PubMed:27081527"
FT                   /id="VAR_030716"
FT   VARIANT         343
FT                   /note="R -> H (in dbSNP:rs34523089)"
FT                   /id="VAR_052103"
FT   VARIANT         418
FT                   /note="L -> M (in dbSNP:rs2526374)"
FT                   /evidence="ECO:0000269|PubMed:14702039,
FT                   ECO:0000269|PubMed:15492824"
FT                   /id="VAR_030717"
FT   VARIANT         686
FT                   /note="P -> R (in dbSNP:rs9652855)"
FT                   /evidence="ECO:0000269|PubMed:17974005"
FT                   /id="VAR_030718"
FT   MUTAGEN         290
FT                   /note="C->S: Dominant-negative mutant, loss of E3 ligase
FT                   activity and activation of the Wnt signaling pathway; when
FT                   associated with S-292."
FT                   /evidence="ECO:0000269|PubMed:18313049,
FT                   ECO:0000269|PubMed:22895187"
FT   MUTAGEN         292
FT                   /note="H->S: Dominant-negative mutant, loss of E3 ligase
FT                   activity and activation of the Wnt signaling pathway; when
FT                   associated with S-290."
FT                   /evidence="ECO:0000269|PubMed:18313049,
FT                   ECO:0000269|PubMed:22895187"
FT   MUTAGEN         295
FT                   /note="H->S: Dominant-negative mutant, loss of E3 ligase
FT                   activity and activation of the Wnt signaling pathway; when
FT                   associated with S-298."
FT                   /evidence="ECO:0000269|PubMed:22895187"
FT   MUTAGEN         298
FT                   /note="C->S: Dominant-negative mutant, loss of E3 ligase
FT                   activity and activation of the Wnt signaling pathway; when
FT                   associated with S-295."
FT                   /evidence="ECO:0000269|PubMed:22895187"
FT   CONFLICT        225
FT                   /note="R -> H (in Ref. 2; BAH12429)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        313
FT                   /note="M -> V (in Ref. 1; BAD51435 and 2; BAA91085)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        401
FT                   /note="E -> K (in Ref. 2; BAH12429)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        600
FT                   /note="R -> G (in Ref. 1; BAD51435 and 2; BAA91085)"
FT                   /evidence="ECO:0000305"
FT   STRAND          45..54
FT                   /evidence="ECO:0007829|PDB:4KNG"
FT   STRAND          57..59
FT                   /evidence="ECO:0007829|PDB:4KNG"
FT   STRAND          63..69
FT                   /evidence="ECO:0007829|PDB:4KNG"
FT   STRAND          71..73
FT                   /evidence="ECO:0007829|PDB:4KNG"
FT   STRAND          78..84
FT                   /evidence="ECO:0007829|PDB:4KNG"
FT   TURN            87..89
FT                   /evidence="ECO:0007829|PDB:4KNG"
FT   STRAND          104..108
FT                   /evidence="ECO:0007829|PDB:4KNG"
FT   TURN            112..114
FT                   /evidence="ECO:0007829|PDB:4KNG"
FT   HELIX           122..131
FT                   /evidence="ECO:0007829|PDB:4KNG"
FT   STRAND          135..140
FT                   /evidence="ECO:0007829|PDB:4KNG"
FT   HELIX           142..146
FT                   /evidence="ECO:0007829|PDB:4KNG"
FT   HELIX           147..150
FT                   /evidence="ECO:0007829|PDB:4KNG"
FT   STRAND          157..159
FT                   /evidence="ECO:0007829|PDB:4KNG"
FT   STRAND          161..164
FT                   /evidence="ECO:0007829|PDB:4KNG"
FT   HELIX           166..176
FT                   /evidence="ECO:0007829|PDB:4KNG"
FT   STRAND          177..179
FT                   /evidence="ECO:0007829|PDB:4KNG"
FT   STRAND          184..189
FT                   /evidence="ECO:0007829|PDB:4KNG"
SQ   SEQUENCE   783 AA;  85722 MW;  4E87EA0CC359C858 CRC64;
     MSGGHQLQLA ALWPWLLMAT LQAGFGRTGL VLAAAVESER SAEQKAIIRV IPLKMDPTGK
     LNLTLEGVFA GVAEITPAEG KLMQSHPLYL CNASDDDNLE PGFISIVKLE SPRRAPRPCL
     SLASKARMAG ERGASAVLFD ITEDRAAAEQ LQQPLGLTWP VVLIWGNDAE KLMEFVYKNQ
     KAHVRIELKE PPAWPDYDVW ILMTVVGTIF VIILASVLRI RCRPRHSRPD PLQQRTAWAI
     SQLATRRYQA SCRQARGEWP DSGSSCSSAP VCAICLEEFS EGQELRVISC LHEFHRNCVD
     PWLHQHRTCP LCMFNITEGD SFSQSLGPSR SYQEPGRRLH LIRQHPGHAH YHLPAAYLLG
     PSRSAVARPP RPGPFLPSQE PGMGPRHHRF PRAAHPRAPG EQQRLAGAQH PYAQGWGLSH
     LQSTSQHPAA CPVPLRRARP PDSSGSGESY CTERSGYLAD GPASDSSSGP CHGSSSDSVV
     NCTDISLQGV HGSSSTFCSS LSSDFDPLVY CSPKGDPQRV DMQPSVTSRP RSLDSVVPTG
     ETQVSSHVHY HRHRHHHYKK RFQWHGRKPG PETGVPQSRP PIPRTQPQPE PPSPDQQVTR
     SNSAAPSGRL SNPQCPRALP EPAPGPVDAS SICPSTSSLF NLQKSSLSAR HPQRKRRGGP
     SEPTPGSRPQ DATVHPACQI FPHYTPSVAY PWSPEAHPLI CGPPGLDKRL LPETPGPCYS
     NSQPVWLCLT PRQPLEPHPP GEGPSEWSSD TAEGRPCPYP HCQVLSAQPG SEEELEELCE
     QAV
//