ZNRF3_XENTR
ID ZNRF3_XENTR Reviewed; 853 AA.
AC Q08D68;
DT 11-JUL-2012, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 93.
DE RecName: Full=E3 ubiquitin-protein ligase ZNRF3;
DE EC=2.3.2.27;
DE AltName: Full=RING-type E3 ubiquitin transferase ZNRF3;
DE AltName: Full=Zinc/RING finger protein 3;
DE Flags: Precursor;
GN Name=znrf3;
OS Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX NCBI_TaxID=8364;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=20431018; DOI=10.1126/science.1183670;
RA Hellsten U., Harland R.M., Gilchrist M.J., Hendrix D., Jurka J.,
RA Kapitonov V., Ovcharenko I., Putnam N.H., Shu S., Taher L., Blitz I.L.,
RA Blumberg B., Dichmann D.S., Dubchak I., Amaya E., Detter J.C., Fletcher R.,
RA Gerhard D.S., Goodstein D., Graves T., Grigoriev I.V., Grimwood J.,
RA Kawashima T., Lindquist E., Lucas S.M., Mead P.E., Mitros T., Ogino H.,
RA Ohta Y., Poliakov A.V., Pollet N., Robert J., Salamov A., Sater A.K.,
RA Schmutz J., Terry A., Vize P.D., Warren W.C., Wells D., Wills A.,
RA Wilson R.K., Zimmerman L.B., Zorn A.M., Grainger R., Grammer T.,
RA Khokha M.K., Richardson P.M., Rokhsar D.S.;
RT "The genome of the Western clawed frog Xenopus tropicalis.";
RL Science 328:633-636(2010).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
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).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
CC of the Wnt signaling pathway by mediating the ubiquitination and
CC subsequent degradation of Wnt receptor complex components (By
CC similarity). Along with RSPO2 and RNF43, constitutes a master switch
CC that governs limb specification (PubMed:29769720).
CC {ECO:0000250|UniProtKB:Q9ULT6, ECO:0000269|PubMed:29769720}.
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 -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9ULT6};
CC Single-pass type I membrane protein {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Simultaneous knockdown of RNF43 and ZNRF3 results
CC in ectopic limb development. {ECO:0000269|PubMed:29769720}.
CC -!- SIMILARITY: Belongs to the ZNRF3 family. {ECO:0000305}.
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DR EMBL; AAMC01003629; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01003630; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01003631; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01003632; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01003633; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01003634; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01003635; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC123917; AAI23918.1; -; mRNA.
DR RefSeq; NP_001072864.1; NM_001079396.1.
DR PDB; 4C8T; X-ray; 2.40 A; A/B=24-191.
DR PDB; 4C8U; X-ray; 3.01 A; A/B=24-191.
DR PDB; 4C9R; X-ray; 2.10 A; A/C=24-191.
DR PDB; 4C9U; X-ray; 3.00 A; A/C=24-191.
DR PDBsum; 4C8T; -.
DR PDBsum; 4C8U; -.
DR PDBsum; 4C9R; -.
DR PDBsum; 4C9U; -.
DR AlphaFoldDB; Q08D68; -.
DR SMR; Q08D68; -.
DR STRING; 8364.ENSXETP00000016703; -.
DR PaxDb; Q08D68; -.
DR PRIDE; Q08D68; -.
DR DNASU; 780325; -.
DR Ensembl; ENSXETT00000070371; ENSXETP00000090450; ENSXETG00000019942.
DR GeneID; 780325; -.
DR KEGG; xtr:780325; -.
DR CTD; 84133; -.
DR Xenbase; XB-GENE-5937936; znrf3.
DR eggNOG; KOG0800; Eukaryota.
DR HOGENOM; CLU_018099_1_0_1; -.
DR InParanoid; Q08D68; -.
DR OMA; CGPTGGE; -.
DR OrthoDB; 1487241at2759; -.
DR PhylomeDB; Q08D68; -.
DR TreeFam; TF317074; -.
DR Reactome; R-XTR-4641263; Regulation of FZD by ubiquitination.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000008143; Chromosome 1.
DR Proteomes; UP000790000; Unplaced.
DR Bgee; ENSXETG00000019942; Expressed in surface structure and 20 other tissues.
DR ExpressionAtlas; Q08D68; baseline.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005109; F:frizzled binding; IBA:GO_Central.
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:0060173; P:limb development; IMP:UniProtKB.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:2000051; P:negative regulation of non-canonical Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0072089; P:stem cell proliferation; ISS: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; cd16799; RING-H2_ZNRF3; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR040700; ZNRF-3_ecto.
DR InterPro; IPR045903; ZNRF3_Znf_RING.
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; Cell membrane; Developmental protein; Membrane;
KW Metal-binding; Reference proteome; Signal; Transferase; Transmembrane;
KW Transmembrane helix; Ubl conjugation pathway; Wnt signaling pathway; Zinc;
KW Zinc-finger.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT CHAIN 29..853
FT /note="E3 ubiquitin-protein ligase ZNRF3"
FT /id="PRO_0000418385"
FT TOPO_DOM 29..192
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 193..213
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 214..853
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT ZN_FING 266..307
FT /note="RING-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 583..629
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 650..673
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 685..713
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 834..853
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 614..629
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT STRAND 31..41
FT /evidence="ECO:0007829|PDB:4C9R"
FT STRAND 43..45
FT /evidence="ECO:0007829|PDB:4C9U"
FT STRAND 47..58
FT /evidence="ECO:0007829|PDB:4C9R"
FT STRAND 60..62
FT /evidence="ECO:0007829|PDB:4C8U"
FT STRAND 67..73
FT /evidence="ECO:0007829|PDB:4C9R"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:4C9R"
FT STRAND 81..83
FT /evidence="ECO:0007829|PDB:4C9R"
FT STRAND 91..98
FT /evidence="ECO:0007829|PDB:4C9R"
FT HELIX 102..104
FT /evidence="ECO:0007829|PDB:4C9R"
FT STRAND 105..107
FT /evidence="ECO:0007829|PDB:4C9R"
FT HELIX 112..121
FT /evidence="ECO:0007829|PDB:4C9R"
FT STRAND 124..130
FT /evidence="ECO:0007829|PDB:4C9R"
FT HELIX 136..142
FT /evidence="ECO:0007829|PDB:4C9R"
FT STRAND 149..151
FT /evidence="ECO:0007829|PDB:4C8T"
FT STRAND 153..156
FT /evidence="ECO:0007829|PDB:4C9R"
FT HELIX 158..170
FT /evidence="ECO:0007829|PDB:4C9R"
FT STRAND 175..179
FT /evidence="ECO:0007829|PDB:4C9R"
SQ SEQUENCE 853 AA; 92605 MW; 33A70DAAC3E6453F CRC64;
MKEPRIRGGL PLVWLWVLLA VAPGESLAKE TAFVEVVLFE SSPNGDYKTH TTELQGRFSR
AGATISAEGE IVQMHPLGLC NNNDEEDLYE YGWVGVVKLE QPEMDPKPCL TVLGKAKRAV
QRGATAVIFD VSDNPDAVEQ LNQGLEDPLK RPVVYMKGMD AIKLMNIVNK QKGARARIQH
RPPRQPTEYF DMGIFLAFFV VVSLVCLILL IKIKLKQRRS QNSMNRMAVQ ALEKMETRKF
KAKGKVPREG SCGGLDTLSS SSTSDCAICL EKYIDGEELR VIPCTHRFHK RCVDPWLLQN
HTCPHCRHNI IEQKKGGHGP VCVENSSNRG RQQQQQRVIL PVHYPGRVQR TGPIAAYPTR
TSMGPHGNPI TVLTVERPLE PDLYPARTPT FLAGYRPVSL DHASSGHHCD LEHPPYPAPP
AGHGFRRAKY SGRGFNNGTC YSQYETMYQH YYFQGLSYPH QQEVGGSQAP RVVENGHNHS
FHSGNNMLYQ PAPTLMHMAP PSSVGSCYLH SQHQHRSVCS GYLADVPCSD SSSSSSASSA
QGHASSSDSM LDCTEASNQG VYGSCSTFRS SLSSDFDPYV YRSRSPARTG GGDAPGCGGE
GGTGSGRGRV ECRSHQTFPN SPSRDRLSSC SMEMNYSSNS SLERRGAVIS SGTVPDASVS
ISQGGGKDRR GPEKGCTCCF QRQAGDPSSD CTNLYLGPDP HQTSGPSSSG GLYSVTSSIL
HRTDPGTVLG HPSRPCCLYE ENHGSCYNED YAVSIQYALA EAAAAAAAAA VAGCEAGQPI
PIIPEDPGYD GGLECVGHVS WEMEGEEEEE EVLYCQEGPC CALAEETRAL CRSTGKEGAG
STTGQDCHPT DRD
