RNF43_HUMAN
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 03-AUG-2022, entry version 160.
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. [Q68DV7-4]
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; 36.
DR CORUM; Q68DV7; -.
DR IntAct; Q68DV7; 15.
DR STRING; 9606.ENSP00000463069; -.
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; Q68DV7; -.
DR PeptideAtlas; Q68DV7; -.
DR PRIDE; Q68DV7; -.
DR ProteomicsDB; 66105; -. [Q68DV7-1]
DR ProteomicsDB; 66106; -. [Q68DV7-2]
DR ProteomicsDB; 66107; -. [Q68DV7-3]
DR ProteomicsDB; 66108; -. [Q68DV7-4]
DR ABCD; Q68DV7; 3 sequenced antibodies.
DR Antibodypedia; 1979; 205 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 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; 1487241at2759; -.
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 1058 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 142 other tissues.
DR ExpressionAtlas; Q68DV7; baseline and differential.
DR Genevisible; Q68DV7; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005635; C:nuclear envelope; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
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; 3.30.40.10; -; 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 Pfam; PF13639; zf-RING_2; 1.
DR Pfam; PF18212; ZNRF_3_ecto; 1.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
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
