ZNRF3_DANRE
ID ZNRF3_DANRE Reviewed; 868 AA.
AC A5WWA0;
DT 11-JUL-2012, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2012, sequence version 2.
DT 03-AUG-2022, entry version 87.
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; ORFNames=si:dkeyp-7c9.3;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP FUNCTION.
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).
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
CC (PubMed:22575959). Along with RSPO2 and RNF43, constitutes a master
CC switch that governs limb specification (By similarity).
CC {ECO:0000250|UniProtKB:Q08D68, ECO:0000269|PubMed:22575959}.
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 -!- SIMILARITY: Belongs to the ZNRF3 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAN88080.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; CT737139; CAN88080.1; ALT_SEQ; Genomic_DNA.
DR PDB; 4C84; X-ray; 1.60 A; A/B=30-181.
DR PDB; 4C85; X-ray; 2.50 A; A/B=30-181.
DR PDBsum; 4C84; -.
DR PDBsum; 4C85; -.
DR AlphaFoldDB; A5WWA0; -.
DR SMR; A5WWA0; -.
DR STRING; 7955.ENSDARP00000085090; -.
DR PaxDb; A5WWA0; -.
DR ZFIN; ZDB-GENE-070705-262; kremen1.
DR ZFIN; ZDB-GENE-070705-263; znrf3.
DR eggNOG; KOG0800; Eukaryota.
DR InParanoid; A5WWA0; -.
DR TreeFam; TF317074; -.
DR UniPathway; UPA00143; -.
DR ChiTaRS; znrf3; zebrafish.
DR PRO; PR:A5WWA0; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; IGI:ZFIN.
DR GO; GO:0048903; P:anterior lateral line neuromast hair cell differentiation; IMP:ZFIN.
DR GO; GO:0001889; P:liver development; IGI:ZFIN.
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:0048884; P:neuromast development; IMP:ZFIN.
DR GO; GO:0048916; P:posterior lateral line development; IMP:ZFIN.
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; Membrane; Metal-binding; Reference proteome;
KW Signal; Transferase; Transmembrane; Transmembrane helix;
KW Ubl conjugation pathway; Wnt signaling pathway; Zinc; Zinc-finger.
FT SIGNAL 1..29
FT /evidence="ECO:0000255"
FT CHAIN 30..868
FT /note="E3 ubiquitin-protein ligase znrf3"
FT /id="PRO_0000418383"
FT TOPO_DOM 30..193
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 194..214
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 215..868
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT ZN_FING 267..308
FT /note="RING-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 792..813
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT STRAND 32..42
FT /evidence="ECO:0007829|PDB:4C84"
FT STRAND 48..59
FT /evidence="ECO:0007829|PDB:4C84"
FT STRAND 68..74
FT /evidence="ECO:0007829|PDB:4C84"
FT HELIX 77..81
FT /evidence="ECO:0007829|PDB:4C84"
FT STRAND 95..99
FT /evidence="ECO:0007829|PDB:4C84"
FT HELIX 103..105
FT /evidence="ECO:0007829|PDB:4C84"
FT HELIX 112..121
FT /evidence="ECO:0007829|PDB:4C84"
FT STRAND 125..130
FT /evidence="ECO:0007829|PDB:4C84"
FT HELIX 136..141
FT /evidence="ECO:0007829|PDB:4C84"
FT STRAND 149..151
FT /evidence="ECO:0007829|PDB:4C85"
FT STRAND 153..156
FT /evidence="ECO:0007829|PDB:4C84"
FT HELIX 158..168
FT /evidence="ECO:0007829|PDB:4C84"
FT STRAND 172..179
FT /evidence="ECO:0007829|PDB:4C84"
SQ SEQUENCE 868 AA; 94667 MW; 67B10731DF3A87A1 CRC64;
MMILPRTGFG RGADSVVLVL LWVLGSVLAK DTAFVEVVLF ESSPNGDYTT YTTGLQGRFS
RAGATISAEG EIVQMHPLGL CNNNDEEDLY EYGWVGVVKL EQPELDPSCL TVLGKAKRAV
QRGATAVIFD VSENPDAIDQ LNQVSEDPLK RPVVYVKGAD AVKLMNIVNK QKVARARIQH
RPPRVRPTEY FDMGIFLAFF VVVSLVCLIL LIKIKLKQRR SQSSMNRMAI QALEKMETCK
FKAKFKGQRE ASCGASDSVS SSSTSDCAIC LEKYIDGEEL RVIPCAHRFH KKCVDPWLLQ
HHTCPHCRHN IIDQKKGNPG AVCLDPGNPV HGRQQRVVLP VHYPGRVHRA GQVTAYPTRT
SMDPHGNPIT VLTVDQHPEQ GLYPSQSSFI RGYPALHLDH TLNPHHCGLE HRGPAYPQTH
TFKRPKFHGR NFSRAACFSQ YETMYQHYYF QGLTFPQPEG QPSNGLHKGH NRPFQPGLLY
PTVVHMAPAS SSRLGDSGST SGLSCYHGHR SVCSGYLADC PGSDSSSSSG QCHCSSSDSM
LDCTEVSNQG VYGSCSTFRS SLSSDYDPYV YRSKSPCRGS AGEAGAVFSA APPADDTSAP
VSGMIDCLQP PGGACYSSGD QLSNCSLEPN CSNHSSVETR ELTSTTSAGP LEGNVAERSH
NSVKPCGEQG VACNCCFEVP KLNLERKGKE GEDRGHCRWA TEAQAVASSQ NFYSVSTEQL
PSPDHVSYDG LPCCFYTEMT VHRGGANHYA EDCSVNIQYA QTDSDGCMGQ GCCELAQRIP
IIPEDTDCEL GLGPEPQTSL LSSRLTTERE ERTSSEDTCD LFFTSGQCRG QVYQQPQDEE
ARALFSSKCN AVSETQGSST SSFDGSGL
