RNF43_MOUSE
ID RNF43_MOUSE Reviewed; 784 AA.
AC Q5NCP0; B2KGH3; Q6DI76; Q8BME0; Q8C191; Q8K0X4;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 132.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC STRAIN=C57BL/6J; TISSUE=Skin, and Wolffian duct;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 84-784 (ISOFORM 1).
RC STRAIN=Czech II, and FVB/N; TISSUE=Mammary tumor;
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 [4]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
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 [5]
RP DEVELOPMENTAL STAGE.
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 [6]
RP INTERACTION WITH LMBR1L.
RX PubMed=31073040; DOI=10.1126/science.aau0812;
RA Choi J.H., Zhong X., McAlpine W., Liao T.C., Zhang D., Fang B., Russell J.,
RA Ludwig S., Nair-Gill E., Zhang Z., Wang K.W., Misawa T., Zhan X., Choi M.,
RA Wang T., Li X., Tang M., Sun Q., Yu L., Murray A.R., Moresco E.M.Y.,
RA Beutler B.;
RT "LMBR1L regulates lymphopoiesis through Wnt/beta-catenin signaling.";
RL Science 364:0-0(2019).
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:22895187). Along with RSPO2 and ZNRF3,
CC constitutes a master switch that governs limb specification (By
CC similarity). {ECO:0000250|UniProtKB:P0DPR2,
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. Interacts with FZD5 (By
CC similarity). Identified in a complex composed of RNF43, LGR5 and RSPO1
CC (By similarity). Interacts with RSPO2 (By similarity). Interacts with
CC LMBR1L (PubMed:31073040). {ECO:0000250|UniProtKB:Q68DV7,
CC ECO:0000269|PubMed:31073040}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}. Endoplasmic reticulum membrane
CC {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}.
CC Nucleus envelope {ECO:0000250}. Note=May be secreted. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q5NCP0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5NCP0-2; Sequence=VSP_023203;
CC Name=3;
CC IsoId=Q5NCP0-3; Sequence=VSP_023204, VSP_023205;
CC -!- TISSUE SPECIFICITY: Expressed in crypt base columnar cells of small
CC intestinal epithelium. Crypt base columnar cells are small cycling
CC cells residing between the terminally differentiated Paneth cells at
CC crypt bottoms. Colocalizes with Lgr5-positive stem cells.
CC {ECO:0000269|PubMed:22895187}.
CC -!- DEVELOPMENTAL STAGE: At 14.5 dpc, in the developing limb, expressed
CC only in the ectoderm and, in developing lungs, detected in the
CC epithelium. {ECO:0000269|PubMed:29769720}.
CC -!- PTM: Autoubiquitinated. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Conditional knockout mice lacking both Rnf43 and
CC Znrf3 in intestine show a marked expansion of the proliferative
CC compartment, resembling the effects of acute deletion of Apc.
CC {ECO:0000269|PubMed:22895187}.
CC -!- SIMILARITY: Belongs to the ZNRF3 family. {ECO:0000305}.
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DR EMBL; AK028750; BAC26097.1; -; mRNA.
DR EMBL; AK032782; BAC28018.1; -; mRNA.
DR EMBL; AL596086; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL604022; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CU393486; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC029717; AAH29717.1; -; mRNA.
DR EMBL; BC075707; AAH75707.1; -; mRNA.
DR CCDS; CCDS25215.2; -. [Q5NCP0-1]
DR CCDS; CCDS88216.1; -. [Q5NCP0-2]
DR RefSeq; NP_766036.2; NM_172448.3. [Q5NCP0-1]
DR RefSeq; XP_006532764.1; XM_006532701.3.
DR RefSeq; XP_011247146.1; XM_011248844.2.
DR AlphaFoldDB; Q5NCP0; -.
DR SMR; Q5NCP0; -.
DR DIP; DIP-59915N; -.
DR IntAct; Q5NCP0; 1.
DR STRING; 10090.ENSMUSP00000130685; -.
DR GlyGen; Q5NCP0; 2 sites.
DR PhosphoSitePlus; Q5NCP0; -.
DR PaxDb; Q5NCP0; -.
DR PRIDE; Q5NCP0; -.
DR DNASU; 207742; -.
DR Ensembl; ENSMUST00000040089; ENSMUSP00000044241; ENSMUSG00000034177. [Q5NCP0-2]
DR Ensembl; ENSMUST00000092800; ENSMUSP00000090476; ENSMUSG00000034177. [Q5NCP0-1]
DR Ensembl; ENSMUST00000165679; ENSMUSP00000130685; ENSMUSG00000034177. [Q5NCP0-1]
DR GeneID; 207742; -.
DR KEGG; mmu:207742; -.
DR UCSC; uc007kue.2; mouse. [Q5NCP0-1]
DR CTD; 54894; -.
DR MGI; MGI:2442609; Rnf43.
DR VEuPathDB; HostDB:ENSMUSG00000034177; -.
DR eggNOG; KOG0800; Eukaryota.
DR GeneTree; ENSGT00940000154006; -.
DR HOGENOM; CLU_401501_0_0_1; -.
DR InParanoid; Q5NCP0; -.
DR OMA; GCGYHLP; -.
DR PhylomeDB; Q5NCP0; -.
DR TreeFam; TF317074; -.
DR Reactome; R-MMU-4641263; Regulation of FZD by ubiquitination.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 207742; 2 hits in 59 CRISPR screens.
DR ChiTaRS; Rnf43; mouse.
DR PRO; PR:Q5NCP0; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q5NCP0; protein.
DR Bgee; ENSMUSG00000034177; Expressed in saccule of membranous labyrinth and 114 other tissues.
DR ExpressionAtlas; Q5NCP0; baseline and differential.
DR Genevisible; Q5NCP0; MM.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005635; C:nuclear envelope; IEA:UniProtKB-SubCell.
DR GO; GO:0005109; F:frizzled binding; ISO:MGI.
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; ISS:UniProtKB.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0072089; P:stem cell proliferation; IMP:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0038018; P:Wnt receptor catabolic process; ISS: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 Alternative splicing; Cell membrane; Developmental protein; Disulfide bond;
KW Endoplasmic reticulum; Glycoprotein; Membrane; Metal-binding; Nucleus;
KW Reference proteome; Signal; Transferase; Transmembrane;
KW Transmembrane helix; Ubl conjugation; Ubl conjugation pathway;
KW Wnt signaling pathway; Zinc; Zinc-finger.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..784
FT /note="E3 ubiquitin-protein ligase RNF43"
FT /id="PRO_0000278240"
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..784
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 364..407
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 459..478
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 516..671
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 521..542
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 578..611
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:0000250|UniProtKB:Q68DV7"
FT VAR_SEQ 1..127
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_023203"
FT VAR_SEQ 112..116
FT /note="PRRAP -> QRSTL (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_023204"
FT VAR_SEQ 117..784
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_023205"
FT CONFLICT 367
FT /note="A -> S (in Ref. 3; AAH75707)"
FT /evidence="ECO:0000305"
FT CONFLICT 631
FT /note="P -> PSP (in Ref. 3; AAH75707)"
FT /evidence="ECO:0000305"
FT CONFLICT 755
FT /note="G -> D (in Ref. 3; AAH75707)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 784 AA; 86304 MW; 53D4DBE8EE43C755 CRC64;
MSGGHQLQLA VLWPWLLMAT LHAGFGHTGR VLAAAVESER SAEQKAVIRV IPLKMDPTGK
LNLTLEGVFA GVAEVTPAEG KLMQSHPLYL CNASDDDNLE PGFISIVKLE SPRRAPRPCL
SLASKARMAG ERGANAVLFD ITEDRSAAEQ LQQPLGLTKP VVLIWGSDAA KLMEFVYKNR
KAYVWIELKE PPAGANYDVW ILLTVVGTVF VIILASVLRI RCRPHHSRPD PLQQRTARAI
SQLATRRYQA GCRRARAEWP DSGSSCSSTP VCAICLEEFS EGQELRVISC LHEFHRTCVD
PWLYQHRTCP LCMFNIVEGD SFSQAPAASP SYQEPGRRLH LIRQHPGHAH YHLPSAYLLG
PSRTSVARTP RPRPFLPSQE PSMGSRHQRL PRTSHLRAPE EQQHLAVSPH PYAQGWGLNR
LRCTSQHPAA CPVALRRARP HESSGSGESY CTERSGYLAD GPASDSSSGP CHGSSSDSVV
NCTDVSLQGI HGSSSTFRSS LSSDFDPLVY CSPEGDLQGK GIQPSVTSRP RSLDSVVPRG
ETQVSSHIHY HRHRHHHYKR QFQWHGRKPG PETGIPQSMP AASHTQLEPS LPDQQLITPN
PTASSMLPNP QRPRALTEPA PGLAEASSPS PSPKPNPSGL LNLQKSSLTV RHPHRKRRGG
PSEPLPTSLP PDLTVHTACP VFPHYSPRLA YPWPPEVHPL MFRPPGPDRR LLHEVPGPCY
SSSQPVWLYL NPCQPLGPCL PGEGHSKWTF DSPEGRRCPY SHCQVLPAQP GSEEELEELC
EQAV
