PZRN3_MOUSE
ID PZRN3_MOUSE Reviewed; 1063 AA.
AC Q69ZS0; Q91Z03; Q9QY54; Q9QY55;
DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 3.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=E3 ubiquitin-protein ligase PDZRN3;
DE EC=2.3.2.27 {ECO:0000269|PubMed:17576800};
DE AltName: Full=PDZ domain-containing RING finger protein 3;
DE AltName: Full=RING-type E3 ubiquitin transferase PDZRN3 {ECO:0000305};
DE AltName: Full=Semaphorin cytoplasmic domain-associated protein 3;
DE Short=Protein SEMACAP3;
GN Name=Pdzrn3; Synonyms=Kiaa1095, Semcap3;
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 [MRNA] (ISOFORM 3), FUNCTION, CATALYTIC ACTIVITY,
RP PATHWAY, INTERACTION WITH MUSK AND UBE2D2, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, DOMAIN, AUTOUBIQUITINATION, AND
RP MUTAGENESIS OF CYS-18 AND CYS-38.
RX PubMed=17576800; DOI=10.1083/jcb.200610060;
RA Lu Z., Je H.S., Young P., Gross J., Lu B., Feng G.;
RT "Regulation of synaptic growth and maturation by a synapse-associated E3
RT ubiquitin ligase at the neuromuscular junction.";
RL J. Cell Biol. 177:1077-1089(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RA Wang L.-H., Strittmatter S.M.;
RT "Cloning and characterization of a novel PDZ domain containing protein
RT interacting with the transmembrane semaphorin, M-semF.";
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 12-1063 (ISOFORM 1).
RC TISSUE=Fetal brain;
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 392-1063.
RC STRAIN=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 [5]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=17118964; DOI=10.1242/jcs.03290;
RA Ko J.A., Kimura Y., Matsuura K., Yamamoto H., Gondo T., Inui M.;
RT "PDZRN3 (LNX3, SEMCAP3) is required for the differentiation of C2C12
RT myoblasts into myotubes.";
RL J. Cell Sci. 119:5106-5113(2006).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-427, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: E3 ubiquitin-protein ligase. Plays an important role in
CC regulating the surface level of MUSK on myotubes. Mediates the
CC ubiquitination of MUSK, promoting its endocytosis and lysosomal
CC degradation. Might contribute to terminal myogenic differentiation.
CC {ECO:0000269|PubMed:17118964, ECO:0000269|PubMed:17576800}.
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; Evidence={ECO:0000269|PubMed:17576800};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:17576800}.
CC -!- SUBUNIT: Interacts with NLGN1 and EFNB2 (By similarity). Interacts with
CC UBE2D2 and with MUSK via the first PDZ domain. In myotubes, the
CC interaction between PDZRN3 and MUSK is enhanced upon agrin stimulation.
CC {ECO:0000250, ECO:0000269|PubMed:17576800}.
CC -!- SUBCELLULAR LOCATION: Synapse {ECO:0000269|PubMed:17576800}. Cytoplasm
CC {ECO:0000250|UniProtKB:E7FDW2}. Note=Localizes to the postsynaptic
CC region of neuromuscular junctions. {ECO:0000269|PubMed:17576800}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=SEMCAP-3A, PDZRN3B;
CC IsoId=Q69ZS0-1; Sequence=Displayed;
CC Name=2; Synonyms=SEMCAP-3B;
CC IsoId=Q69ZS0-2; Sequence=VSP_012610;
CC Name=3; Synonyms=PDZRN3A;
CC IsoId=Q69ZS0-3; Sequence=VSP_039769;
CC -!- TISSUE SPECIFICITY: Highly expressed in skeletal and cardiac muscle and
CC at lower levels in spinal cord and brain (at protein level). Also
CC expressed in kidney and lung. In muscles, concentrated at the
CC neuromuscular junction (NMJ). {ECO:0000269|PubMed:17576800}.
CC -!- DEVELOPMENTAL STAGE: First detected at the NMJ at approximately 16.5
CC dpc, when NMJs have just formed. As the NMJ grows and matures,
CC expression levels increase in concert with that of acetylcholine
CC receptors. Levels stay relatively high until 14 days after birth, but
CC decrease significantly by 21 days. Up-regulated during myogenic
CC differentiation in C2C12 cells and during injury-induced muscle
CC regeneration. {ECO:0000269|PubMed:17118964,
CC ECO:0000269|PubMed:17576800}.
CC -!- DOMAIN: The RING-type zinc finger domain is required for E3 ligase
CC activity. {ECO:0000269|PubMed:17576800}.
CC -!- PTM: Auto-ubiquitinated. {ECO:0000269|PubMed:17576800}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH10329.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
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DR EMBL; HM560981; ADK56111.1; -; mRNA.
DR EMBL; AF127084; AAF22131.1; -; mRNA.
DR EMBL; AF127085; AAF22132.1; -; mRNA.
DR EMBL; AK173098; BAD32376.1; -; mRNA.
DR EMBL; BC010329; AAH10329.1; ALT_SEQ; mRNA.
DR CCDS; CCDS20392.1; -. [Q69ZS0-1]
DR RefSeq; NP_061372.2; NM_018884.2. [Q69ZS0-1]
DR AlphaFoldDB; Q69ZS0; -.
DR BMRB; Q69ZS0; -.
DR SMR; Q69ZS0; -.
DR BioGRID; 207755; 6.
DR IntAct; Q69ZS0; 1.
DR STRING; 10090.ENSMUSP00000075376; -.
DR iPTMnet; Q69ZS0; -.
DR PhosphoSitePlus; Q69ZS0; -.
DR jPOST; Q69ZS0; -.
DR MaxQB; Q69ZS0; -.
DR PaxDb; Q69ZS0; -.
DR PeptideAtlas; Q69ZS0; -.
DR PRIDE; Q69ZS0; -.
DR ProteomicsDB; 300217; -. [Q69ZS0-1]
DR ProteomicsDB; 300218; -. [Q69ZS0-2]
DR ProteomicsDB; 300219; -. [Q69ZS0-3]
DR Antibodypedia; 31945; 110 antibodies from 16 providers.
DR DNASU; 55983; -.
DR Ensembl; ENSMUST00000075994; ENSMUSP00000075376; ENSMUSG00000035357. [Q69ZS0-1]
DR GeneID; 55983; -.
DR KEGG; mmu:55983; -.
DR UCSC; uc009dcd.2; mouse. [Q69ZS0-1]
DR UCSC; uc012eps.1; mouse. [Q69ZS0-3]
DR CTD; 23024; -.
DR MGI; MGI:1933157; Pdzrn3.
DR VEuPathDB; HostDB:ENSMUSG00000035357; -.
DR eggNOG; KOG0297; Eukaryota.
DR eggNOG; KOG0312; Eukaryota.
DR GeneTree; ENSGT00950000183062; -.
DR HOGENOM; CLU_011096_0_0_1; -.
DR InParanoid; Q69ZS0; -.
DR OMA; HAGCGQL; -.
DR PhylomeDB; Q69ZS0; -.
DR TreeFam; TF315909; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 55983; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Pdzrn3; mouse.
DR PRO; PR:Q69ZS0; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q69ZS0; protein.
DR Bgee; ENSMUSG00000035357; Expressed in humerus cartilage element and 239 other tissues.
DR ExpressionAtlas; Q69ZS0; baseline and differential.
DR Genevisible; Q69ZS0; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0031594; C:neuromuscular junction; IDA:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0007528; P:neuromuscular junction development; IMP:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR Gene3D; 2.30.42.10; -; 2.
DR Gene3D; 3.30.40.10; -; 2.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR041489; PDZ_6.
DR InterPro; IPR036034; PDZ_sf.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR InterPro; IPR001293; Znf_TRAF.
DR Pfam; PF00595; PDZ; 1.
DR Pfam; PF17820; PDZ_6; 1.
DR SMART; SM00228; PDZ; 2.
DR SMART; SM00184; RING; 1.
DR SUPFAM; SSF50156; SSF50156; 2.
DR PROSITE; PS50106; PDZ; 2.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
DR PROSITE; PS50145; ZF_TRAF; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Coiled coil; Cytoplasm; Metal-binding;
KW Phosphoprotein; Reference proteome; Repeat; Synapse; Transferase;
KW Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..1063
FT /note="E3 ubiquitin-protein ligase PDZRN3"
FT /id="PRO_0000055918"
FT DOMAIN 249..339
FT /note="PDZ 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 419..503
FT /note="PDZ 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT ZN_FING 18..56
FT /note="RING-type; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 100..158
FT /note="TRAF-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00207"
FT REGION 545..602
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 746..798
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 COILED 680..705
FT /evidence="ECO:0000255"
FT COMPBIAS 568..586
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 754..775
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 427
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 82..133
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_012610"
FT VAR_SEQ 419..451
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17576800"
FT /id="VSP_039769"
FT MUTAGEN 18
FT /note="C->A: Loss of E3 ligase activity."
FT /evidence="ECO:0000269|PubMed:17576800"
FT MUTAGEN 38
FT /note="C->A: Loss of E3 ligase activity."
FT /evidence="ECO:0000269|PubMed:17576800"
FT CONFLICT 82
FT /note="C -> R (in Ref. 3; BAD32376)"
FT /evidence="ECO:0000305"
FT CONFLICT 199
FT /note="V -> L (in Ref. 2; AAF22131/AAF22132)"
FT /evidence="ECO:0000305"
FT CONFLICT 596
FT /note="S -> Y (in Ref. 2; AAF22131/AAF22132)"
FT /evidence="ECO:0000305"
FT CONFLICT 731
FT /note="N -> Y (in Ref. 2; AAF22131/AAF22132)"
FT /evidence="ECO:0000305"
FT CONFLICT 823
FT /note="A -> S (in Ref. 4; AAH10329)"
FT /evidence="ECO:0000305"
FT CONFLICT 912
FT /note="V -> A (in Ref. 4; AAH10329)"
FT /evidence="ECO:0000305"
FT CONFLICT 938
FT /note="R -> K (in Ref. 2; AAF22131/AAF22132)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1063 AA; 119401 MW; AC87470326242BED CRC64;
MGFELDRFDG DVDPDLKCAL CHKVLEDPLT TPCGHVFCAG CVLPWVVQEG SCPARCRGRL
SAKELNHVLP LKRLILKLDI KCAHAARGCG RVVKLQDLPE HLERCDFAPA RCRHAGCGQL
LLRRDVEAHM RDACDARPVG RCQEGCGLPL THGEQRAGGH CCARALRAHN GALQARLGAL
HKALKKEALR AGKREKSLVA QLAAAQLELQ MTALRYQKKF TEYSARLDSL SRCVAAPPGG
KGEETKSLTL VLHRDSGSLG FNIIGGRPCV DNQDGSSSEG IFVSKIVDSG PAAKEGGLQI
HDRIIEVNGK DLSRATHDQA VEAFKTAKEP IVVQVLRRTP RTKMFTPASE SQLVDTGTQT
DITFEHIMAL TKMSSPSPPV LDPYLLPEEH PASHDYYDPN DYMGDIHQDM DREELELEEV
GLYRMNSQDK LGLTVCYRTD DEDDIGIYIS EIDPNSIAAK DGRIREGDRI IQINGIEVQN
REEAVALLTS EENKNFSLLI ARPELQLDEG WMDDDRNDFL DDLHMDMLEE QHHQAMQFTA
SVLQQKKHEE DGGTTDTATI LSNQHEKDSG VGRTDESTRN DESSEQENNG EDATASANPL
AGQRKLTCSQ DTLGSGDLPF SNESFISADC TDVDYLGIPE DECERFRELL ELKCQVQSAS
PYSLYYPSSP LDAAGKSDPE SVDKELELLN EELRSIELEC LSIVRAHKMQ QLKEQYRESW
MLHHSGFRNY NTSVDVRRHE LSDITELPEK SDKDSSSAYN TGESCRSTPL TLEISPDNSL
RRVAEGSSEG ATANIEAYRP SPKNLLAITE DPEVSTPSYN PSAKELDPSQ ALEIKERRGS
DGSRSPTASP KLGNAYLPSY HHSPYKHAHI PAHAQHYQSY MHLIQQKSAV EYAQSQMSLV
SMCKDLNSSN SVEPRMEWKV KIRSDGTRYI TKRPVRDRLL RERALKIREE RSGLTTDDDA
MSEMKMGRYW SKEERKQHLV KAKEQRRRRE FMMQSRLDCL KEQQASDDRK EMNILELSHK
KMMKKRNKKI FDNWMTIQEL LTHGTKSPDG TRVYNSFLSV TTV
