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Protein

E3 ubiquitin-protein ligase ZNRF3

Gene

Znrf3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

E3 ubiquitin-protein ligase that acts as a negative regulator of the Wnt signaling pathway by mediating the ubiquitination and subsequent degradation of Wnt receptor complex components Frizzled and LRP6. Acts on both canonical and non-canonical Wnt signaling pathway. Acts as a tumor suppressor in the intestinal stem cell zone by inhibiting the Wnt signaling pathway, thereby resticting the size of the intestinal stem cell zone.2 Publications

Enzyme regulationi

Negatively regulated by R-spondin proteins such as RSPO1: interaction with RSPO1 induces the indirect association between ZNRF3 and LGR4, promoting membrane clearance of ZNRF3.By similarity

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri290 – 33142RING-type; atypicalPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

  • canonical Wnt signaling pathway Source: UniProtKB
  • negative regulation of canonical Wnt signaling pathway Source: UniProtKB
  • negative regulation of non-canonical Wnt signaling pathway Source: UniProtKB
  • negative regulation of Wnt signaling pathway Source: UniProtKB
  • protein ubiquitination Source: UniProtKB
  • stem cell proliferation Source: UniProtKB
  • ubiquitin-dependent protein catabolic process Source: UniProtKB
  • Wnt receptor catabolic process Source: UniProtKB
  • Wnt signaling pathway, planar cell polarity pathway Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Ubl conjugation pathway, Wnt signaling pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-4641263. Regulation of FZD by ubiquitination.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase ZNRF3 (EC:6.3.2.-)
Alternative name(s):
Zinc/RING finger protein 3
Gene namesi
Name:Znrf3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:3039616. Znrf3.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini53 – 216164ExtracellularSequence analysisAdd
BLAST
Transmembranei217 – 23721HelicalSequence analysisAdd
BLAST
Topological domaini238 – 913676CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Embryos die around birth due to activation of Wnt signaling pathway. Embryos display a lack of lens formation due to Wnt activation. Conditional knockout mice lacking both Rnf43 and Znrf3 in intestine show a marked expansion of the proliferative compartment, resembling the effects of acute deletion of Apc.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 5252Sequence analysisAdd
BLAST
Chaini53 – 913861E3 ubiquitin-protein ligase ZNRF3PRO_0000277807Add
BLAST

Proteomic databases

PaxDbiQ5SSZ7.
PRIDEiQ5SSZ7.

PTM databases

iPTMnetiQ5SSZ7.
PhosphoSiteiQ5SSZ7.

Expressioni

Gene expression databases

BgeeiQ5SSZ7.
CleanExiMM_ZNRF3.
ExpressionAtlasiQ5SSZ7. baseline and differential.
GenevisibleiQ5SSZ7. MM.

Interactioni

Subunit structurei

Interacts with LRP6, FZD4, FZD5, FZD6 and FZD8. Interacts with RSPO1; interaction promotes indirect interaction with LGR4 and membrane clearance of ZNRF3 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi240468. 5 interactions.
STRINGi10090.ENSMUSP00000105493.

Structurei

Secondary structure

1
913
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi55 – 6410Combined sources
Beta strandi67 – 693Combined sources
Beta strandi72 – 8211Combined sources
Beta strandi91 – 977Combined sources
Helixi100 – 1034Combined sources
Beta strandi104 – 1074Combined sources
Helixi109 – 1113Combined sources
Beta strandi115 – 1228Combined sources
Helixi126 – 1283Combined sources
Beta strandi129 – 1313Combined sources
Helixi136 – 14510Combined sources
Beta strandi148 – 1547Combined sources
Helixi161 – 1655Combined sources
Turni167 – 1704Combined sources
Beta strandi173 – 1753Combined sources
Beta strandi177 – 1804Combined sources
Helixi182 – 19211Combined sources
Beta strandi194 – 1963Combined sources
Beta strandi198 – 2047Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4C86X-ray2.00A/B53-205[»]
4C8AX-ray2.70A/B/C53-205[»]
4C8CX-ray2.40A/B53-205[»]
4C8FX-ray2.69A/B/C/D53-205[»]
4C8PX-ray2.10A53-205[»]
4C99X-ray2.80A/C53-205[»]
4C9AX-ray2.40A/C53-205[»]
4C9EX-ray3.00A/C/E/G53-205[»]
4CDJX-ray1.50A/B53-205[»]
4CDKX-ray2.80A/B/C/D53-205[»]
4UFSX-ray4.80C53-205[»]
ProteinModelPortaliQ5SSZ7.
SMRiQ5SSZ7. Positions 53-205, 289-335.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi2 – 2726Arg-richAdd
BLAST

Sequence similaritiesi

Belongs to the ZNRF3 family.Curated
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri290 – 33142RING-type; atypicalPROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix, Zinc-finger

Phylogenomic databases

eggNOGiKOG0800. Eukaryota.
ENOG41121N2. LUCA.
GeneTreeiENSGT00760000119057.
HOGENOMiHOG000155811.
HOVERGENiHBG082538.
InParanoidiQ5SSZ7.
KOiK16273.
OMAiCYTEDYS.
OrthoDBiEOG7P5T06.
PhylomeDBiQ5SSZ7.
TreeFamiTF317074.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF13639. zf-RING_2. 1 hit.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
[Graphical view]
PROSITEiPS50089. ZF_RING_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q5SSZ7-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MRPRSGGRPG APGRRRRRLR RGPRGRRLPP PPPLPLLLGL LLAAAGPGAA
60 70 80 90 100
RAKETAFVEV VLFESSPSGD YTTHTTGLTG RFSRAGAMLS AEGEIVQMHP
110 120 130 140 150
LGLCNNNDEE DLYEYGWVGV VKLEQPELDP KPCLTVLGKA KRAVQRGATA
160 170 180 190 200
VIFDVSENPE AIDQLNQGSE DPLKRPVVYV KGADAIKLMN IVNKQKVARA
210 220 230 240 250
RIQHLPPRQP TEYFDMGIFL AFFVVVSLVC LILLVKIKLK QRRSQNSMNR
260 270 280 290 300
LAVQALEKME TRKFNSKSKG RREGSCGALD TLSSGSTSDC AICLEKYIDG
310 320 330 340 350
EELRVIPCTH RFHRKCVDPW LLQHHTCPHC RHNIIEQKGN PGAVCVETSN
360 370 380 390 400
LTRGRQPRVT LPVHYPGRVH RTNAIPAYPT RTSMDSHGNP VTLLTMDRHG
410 420 430 440 450
EQNLYSPQTP TYVRGYPPLH LDHTLAPHRC SLEHRAYSPA HPFRRPKFSS
460 470 480 490 500
RSFSKAACFS QYETMYQHYY FQGLSYPEQE GQTIPSVTPR GQSRAFPPSG
510 520 530 540 550
ASSLLFPTMV HVAPPTHVES GSTSSFSCYH GHRSVCSGYL ADCPGSDSSS
560 570 580 590 600
NSSGQCRCSS SDSVVDCTEV SNQGVYGSCS TFRSSLSSDY DPFIYRSRGP
610 620 630 640 650
AVHLEGSPPP EELPAGHSQS AGRGEPWLGP ASPSGDQLST CSLEMNYSSN
660 670 680 690 700
SSLEPRGPNS STSEVGLEVS PGAALDLRRT WKGGPEGPSC ACCFEPQPFP
710 720 730 740 750
PGSGIETSAG GSSLFLGPRL LEDCNPPSGE PQLGSSQGLY GLHSDHYPRT
760 770 780 790 800
DGVKYEGLPC CFYEEKQVAH SAGRGNGCYT EDYSVSVQYT LTEEPPPSCY
810 820 830 840 850
AGPRDLSQRI PIIPEDVDCD LGLPQDCHGM HNHSPWGGAL SLDVPRLHWS
860 870 880 890 900
LGTTREEEQA PCYQAEVQPG CSPEEAGASR ASLSSAPQDT QESHALAAEA
910
SGPGSGPGIG TGA
Length:913
Mass (Da):98,967
Last modified:December 21, 2004 - v1
Checksum:iD57C8EF69AAE5C0F
GO
Isoform 2 (identifier: Q5SSZ7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-96: Missing.
     97-97: Q → M
     903-913: PGSGPGIGTGA → ENR

Show »
Length:809
Mass (Da):88,383
Checksum:iF8044D6232F7354B
GO

Sequence cautioni

The sequence AAI51081.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAI51084.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti683 – 6831G → W in BAE21609 (PubMed:16141072).Curated
Sequence conflicti708 – 7081S → T in AAI51084 (PubMed:15489334).Curated
Sequence conflicti708 – 7081S → T in AAI51081 (PubMed:15489334).Curated
Sequence conflicti798 – 7981S → T in AAI51084 (PubMed:15489334).Curated
Sequence conflicti798 – 7981S → T in AAI51081 (PubMed:15489334).Curated
Sequence conflicti903 – 9053PGS → ENR in AAI51084 (PubMed:15489334).Curated
Sequence conflicti903 – 9053PGS → ENR in AAI51081 (PubMed:15489334).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 9696Missing in isoform 2. 2 PublicationsVSP_023089Add
BLAST
Alternative sequencei97 – 971Q → M in isoform 2. 2 PublicationsVSP_023090
Alternative sequencei903 – 91311PGSGPGIGTGA → ENR in isoform 2. 2 PublicationsVSP_023091Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK133342 mRNA. Translation: BAE21609.1.
AL662876, AL662853 Genomic DNA. Translation: CAI24933.1.
AL662853, AL662876 Genomic DNA. Translation: CAI24978.1.
BC151080 mRNA. Translation: AAI51081.1. Different initiation.
BC151083 mRNA. Translation: AAI51084.1. Different initiation.
CCDSiCCDS36102.1. [Q5SSZ7-1]
CCDS70134.1. [Q5SSZ7-2]
RefSeqiNP_001074393.1. NM_001080924.2. [Q5SSZ7-1]
NP_001277430.1. NM_001290501.1. [Q5SSZ7-2]
UniGeneiMm.216313.

Genome annotation databases

EnsembliENSMUST00000109867; ENSMUSP00000105493; ENSMUSG00000041961. [Q5SSZ7-1]
ENSMUST00000172492; ENSMUSP00000134698; ENSMUSG00000041961. [Q5SSZ7-2]
GeneIDi407821.
KEGGimmu:407821.
UCSCiuc007hwj.2. mouse. [Q5SSZ7-1]
uc007hwk.4. mouse. [Q5SSZ7-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK133342 mRNA. Translation: BAE21609.1.
AL662876, AL662853 Genomic DNA. Translation: CAI24933.1.
AL662853, AL662876 Genomic DNA. Translation: CAI24978.1.
BC151080 mRNA. Translation: AAI51081.1. Different initiation.
BC151083 mRNA. Translation: AAI51084.1. Different initiation.
CCDSiCCDS36102.1. [Q5SSZ7-1]
CCDS70134.1. [Q5SSZ7-2]
RefSeqiNP_001074393.1. NM_001080924.2. [Q5SSZ7-1]
NP_001277430.1. NM_001290501.1. [Q5SSZ7-2]
UniGeneiMm.216313.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4C86X-ray2.00A/B53-205[»]
4C8AX-ray2.70A/B/C53-205[»]
4C8CX-ray2.40A/B53-205[»]
4C8FX-ray2.69A/B/C/D53-205[»]
4C8PX-ray2.10A53-205[»]
4C99X-ray2.80A/C53-205[»]
4C9AX-ray2.40A/C53-205[»]
4C9EX-ray3.00A/C/E/G53-205[»]
4CDJX-ray1.50A/B53-205[»]
4CDKX-ray2.80A/B/C/D53-205[»]
4UFSX-ray4.80C53-205[»]
ProteinModelPortaliQ5SSZ7.
SMRiQ5SSZ7. Positions 53-205, 289-335.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi240468. 5 interactions.
STRINGi10090.ENSMUSP00000105493.

PTM databases

iPTMnetiQ5SSZ7.
PhosphoSiteiQ5SSZ7.

Proteomic databases

PaxDbiQ5SSZ7.
PRIDEiQ5SSZ7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000109867; ENSMUSP00000105493; ENSMUSG00000041961. [Q5SSZ7-1]
ENSMUST00000172492; ENSMUSP00000134698; ENSMUSG00000041961. [Q5SSZ7-2]
GeneIDi407821.
KEGGimmu:407821.
UCSCiuc007hwj.2. mouse. [Q5SSZ7-1]
uc007hwk.4. mouse. [Q5SSZ7-2]

Organism-specific databases

CTDi84133.
MGIiMGI:3039616. Znrf3.

Phylogenomic databases

eggNOGiKOG0800. Eukaryota.
ENOG41121N2. LUCA.
GeneTreeiENSGT00760000119057.
HOGENOMiHOG000155811.
HOVERGENiHBG082538.
InParanoidiQ5SSZ7.
KOiK16273.
OMAiCYTEDYS.
OrthoDBiEOG7P5T06.
PhylomeDBiQ5SSZ7.
TreeFamiTF317074.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-MMU-4641263. Regulation of FZD by ubiquitination.

Miscellaneous databases

PROiQ5SSZ7.
SOURCEiSearch...

Gene expression databases

BgeeiQ5SSZ7.
CleanExiMM_ZNRF3.
ExpressionAtlasiQ5SSZ7. baseline and differential.
GenevisibleiQ5SSZ7. MM.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF13639. zf-RING_2. 1 hit.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
[Graphical view]
PROSITEiPS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Strain: C57BL/6J.
    Tissue: Testis.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Brain.
  4. Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  5. "Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors."
    Koo B.K., Spit M., Jordens I., Low T.Y., Stange D.E., van de Wetering M., van Es J.H., Mohammed S., Heck A.J., Maurice M.M., Clevers H.
    Nature 488:665-669(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.

Entry informationi

Entry nameiZNRF3_MOUSE
AccessioniPrimary (citable) accession number: Q5SSZ7
Secondary accession number(s): B2RXA5, Q3V095
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: December 21, 2004
Last modified: June 8, 2016
This is version 103 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.