PLR1_CAEEL
ID PLR1_CAEEL Reviewed; 487 AA.
AC Q9U2B7;
DT 30-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 2.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Probable E3 ubiquitin-protein ligase plr-1 {ECO:0000305};
DE EC=2.3.2.- {ECO:0000305};
DE AltName: Full=Probable E3 ubiquitin-protein transferase plr-1 {ECO:0000305};
DE Flags: Precursor;
GN Name=plr-1 {ECO:0000303|PubMed:24401370, ECO:0000312|WormBase:Y47D3B.11};
GN ORFNames=Y47D3B.11 {ECO:0000312|WormBase:Y47D3B.11};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP DOMAIN, AND MUTAGENESIS OF CYS-317.
RX PubMed=24401370; DOI=10.1242/dev.101600;
RA Moffat L.L., Robinson R.E., Bakoulis A., Clark S.G.;
RT "The conserved transmembrane RING finger protein PLR-1 downregulates Wnt
RT signaling by reducing Frizzled, Ror and Ryk cell-surface levels in C.
RT elegans.";
RL Development 141:617-628(2014).
RN [3] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=25448694; DOI=10.1016/j.ydbio.2014.11.008;
RA Bhat J.M., Pan J., Hutter H.;
RT "PLR-1, a putative E3 ubiquitin ligase, controls cell polarity and axonal
RT extensions in C. elegans.";
RL Dev. Biol. 398:44-56(2015).
CC -!- FUNCTION: Probable E3 ubiquitin-protein ligase that acts as a negative
CC regulator of the Wnt signaling pathway by mediating the ubiquitination,
CC endocytosis and subsequent degradation of Wnt receptor complex
CC components Frizzled (By similarity). Acts on both canonical and non-
CC canonical Wnt signaling pathway (By similarity). Plays a role in the
CC migration and axon guidance of different neuronal cell types including
CC CAN, HSN, AVK and AVG (PubMed:24401370, PubMed:25448694). Promotes the
CC differentiation and regulates the anteroposterior polarity of AVG
CC unpaired interneurons by sequestering the Wnt signaling proteins cfz-2,
CC mig-1 and mom-5 to endosomes which thereby reduces their cell surface
CC expression and negatively regulates Wnt signaling (PubMed:24401370).
CC May also regulate AVG polarity and axon guidance through Wnt-
CC independent mechanisms involving unc-53/Nav2, unc-73/Trio and cytosolic
CC protein vab-8 (PubMed:25448694). {ECO:0000250|UniProtKB:Q68DV7,
CC ECO:0000269|PubMed:24401370, ECO:0000269|PubMed:25448694}.
CC -!- PATHWAY: Protein modification; protein ubiquitination. {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9ULT6};
CC Single-pass membrane protein {ECO:0000255}. Early endosome
CC {ECO:0000269|PubMed:24401370, ECO:0000269|PubMed:25448694}. Late
CC endosome {ECO:0000269|PubMed:24401370}. Perikaryon
CC {ECO:0000269|PubMed:25448694}. Cell projection, axon
CC {ECO:0000269|PubMed:25448694}.
CC -!- TISSUE SPECIFICITY: Expressed in a subset of head, ventral nerve cord
CC and tail neurons, the excretory canal and tail epidermis.
CC {ECO:0000269|PubMed:24401370, ECO:0000269|PubMed:25448694}.
CC -!- DEVELOPMENTAL STAGE: First expressed during the late gastrulation stage
CC of embryogenesis with high expression in the tail region
CC (PubMed:25448694). In the comma stage of embryogenesis, expression is
CC prominent in the body wall muscle cells (PubMed:25448694). In early
CC larval development, expressed in hypodermal cells, muscle, the pharynx,
CC intestine and in anal depressor and stomatointestinal muscle
CC (PubMed:25448694). In the nervous system, transiently expressed in late
CC embryogenesis and early larval development in AVG unpaired interneurons
CC and during larval development, expressed in neurons in the head and
CC tail ganglia and ventral cord motor neurons (PubMed:24401370,
CC PubMed:25448694). In the late stages of larval development, expressed
CC in the distal tip cell, the vulva, uterine muscle cells and the VC4 and
CC VC5 neurons that flank the vulva (PubMed:25448694).
CC {ECO:0000269|PubMed:24401370, ECO:0000269|PubMed:25448694}.
CC -!- DOMAIN: The RING finger region is required to block Wnt signaling and
CC is also required for endosomal localization.
CC {ECO:0000269|PubMed:24401370}.
CC -!- PTM: Autoubiquitinated. {ECO:0000250|UniProtKB:Q68DV7}.
CC -!- DISRUPTION PHENOTYPE: Mutants exhibit cell migration and axon guidance
CC defects in HSN, AVK, CAN and AVG neurons, and also display excretory
CC canal elongation defects with premature termination of the canal.
CC Double knockout with either unc-53 or vab-8 results in premature
CC termination of the AVG axon and AVG polarity defects.
CC {ECO:0000269|PubMed:25448694}.
CC -!- SIMILARITY: Belongs to the ZNRF3 family. {ECO:0000305}.
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DR EMBL; BX284603; CAB54384.2; -; Genomic_DNA.
DR PIR; T26958; T26958.
DR RefSeq; NP_499473.2; NM_067072.4.
DR AlphaFoldDB; Q9U2B7; -.
DR SMR; Q9U2B7; -.
DR STRING; 6239.Y47D3B.11; -.
DR EPD; Q9U2B7; -.
DR PaxDb; Q9U2B7; -.
DR EnsemblMetazoa; Y47D3B.11.1; Y47D3B.11.1; WBGene00023404.
DR GeneID; 176575; -.
DR KEGG; cel:CELE_Y47D3B.11; -.
DR UCSC; Y47D3B.11; c. elegans.
DR CTD; 176575; -.
DR WormBase; Y47D3B.11; CE33946; WBGene00023404; plr-1.
DR eggNOG; KOG0800; Eukaryota.
DR HOGENOM; CLU_566506_0_0_1; -.
DR InParanoid; Q9U2B7; -.
DR OMA; SSFRACD; -.
DR OrthoDB; 1487241at2759; -.
DR UniPathway; UPA00143; -.
DR PRO; PR:Q9U2B7; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00023404; Expressed in embryo and 3 other tissues.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005769; C:early endosome; IDA:WormBase.
DR GO; GO:0005794; C:Golgi apparatus; IDA:WormBase.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005770; C:late endosome; IDA:WormBase.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
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:WormBase.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IMP:WormBase.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF13639; zf-RING_2; 1.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Endosome; Glycoprotein; Membrane;
KW Metal-binding; Reference proteome; Signal; Transferase; Transmembrane;
KW Transmembrane helix; Ubl conjugation; Ubl conjugation pathway;
KW Wnt signaling pathway; Zinc; Zinc-finger.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..487
FT /note="Probable E3 ubiquitin-protein ligase plr-1"
FT /evidence="ECO:0000305"
FT /id="PRO_5004334962"
FT TOPO_DOM 22..210
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 211..231
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 232..487
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT ZN_FING 317..358
FT /note="RING-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 370..487
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 378..407
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 413..439
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 452..487
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 10
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT MUTAGEN 317
FT /note="C->Y: In zd164; disrupted polarity of the unpaired
FT interneuron AVG."
FT /evidence="ECO:0000269|PubMed:24401370"
SQ SEQUENCE 487 AA; 54947 MW; 4A6D0F54FF31B71F CRC64;
MRLLLFILLN TTLLSTNYVH ARPSVSHTTL ASQFKFAEKA DIFVTHTNIN EDRTQDEKTI
KLSGTFSPVG SNYETGGDIV QVSSFRACDA RRKGLDNTVF EHVPVVFYDD VEKFLTGCVA
LDNQARFAEK SGAMALIVGP ASRVERTTRP MMIGGSKIPV IVLDDEQTER LRSELRSASE
RGAVTKLRIS FIDEKPTKVL KLQVFRPTVL NITLLGLLII LIVFVSLLVV VKIRCQPTMH
RELWLRALAR TALTKMEIRS FQKEKNVEAG QKKKTSSTFA RLKQHRSSSS RHSSYLAVFG
SLTSVAQSSS HSAQERCVIC LEEYEEGTEL RVLFCGHEFH PKCVDPWLLS KRRCPLCQFD
VVYKHYPKVD SPEKLSGRSD DTTSLLPRTS PSEDLPSAPS SRSTRLTRPY RTTHHLIPSS
TRPSSHQRPS LQPTAPRTRS CPRRRQLRSR NQIDFSIRIG GYSSDVSSSH AEQSRSFEIE
PRTSQQL
