ID   ZNRF4_MACFA             Reviewed;         429 AA.
AC   Q4R6Y5;
DT   20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT   19-JUL-2005, sequence version 1.
DT   03-AUG-2022, entry version 73.
DE   RecName: Full=E3 ubiquitin-protein ligase ZNRF4 {ECO:0000250|UniProtKB:Q8WWF5};
DE            EC=2.3.2.27 {ECO:0000250|UniProtKB:Q8WWF5};
DE   AltName: Full=RING-type E3 ubiquitin transferase ZNRF4;
DE   AltName: Full=Zinc/RING finger protein 4 {ECO:0000250|UniProtKB:Q8WWF5};
DE   Flags: Precursor;
GN   Name=ZNRF4; ORFNames=QtsA-16853 {ECO:0000303|Ref.1};
OS   Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC   Cercopithecidae; Cercopithecinae; Macaca.
OX   NCBI_TaxID=9541;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Testis;
RG   International consortium for macaque cDNA sequencing and analysis;
RT   "DNA sequences of macaque genes expressed in brain or testis and its
RT   evolutionary implications.";
RL   Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
CC       of NOD2 signaling by mediating ubiquitination and degradation of RIPK2.
CC       Also catalyzes ubiquitination and proteasomal degradation of CANX
CC       within the endoplasmic reticulum (By similarity). Could have a role in
CC       spermatogenesis (By similarity). {ECO:0000250|UniProtKB:Q8WWF5,
CC       ECO:0000250|UniProtKB:Q9DAH2}.
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:0000250|UniProtKB:Q8WWF5};
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC       {ECO:0000250|UniProtKB:Q8WWF5}.
CC   -!- SUBUNIT: Interacts with CANX. {ECO:0000250|UniProtKB:Q8WWF5}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000250|UniProtKB:Q8WWF5}; Single-pass type I membrane protein
CC       {ECO:0000255}.
CC   -!- DOMAIN: The RING-type zinc finger is involved in CANX ubiquitination
CC       and degradation, but is not required for interaction with CANX.
CC       {ECO:0000250|UniProtKB:Q8WWF5}.
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DR   EMBL; AB169045; BAE01139.1; -; mRNA.
DR   RefSeq; NP_001270551.1; NM_001283622.1.
DR   AlphaFoldDB; Q4R6Y5; -.
DR   SMR; Q4R6Y5; -.
DR   STRING; 9541.XP_005587667.1; -.
DR   PRIDE; Q4R6Y5; -.
DR   GeneID; 101864779; -.
DR   CTD; 148066; -.
DR   eggNOG; KOG4628; Eukaryota.
DR   OrthoDB; 1487241at2759; -.
DR   UniPathway; UPA00143; -.
DR   Proteomes; UP000233100; Unplaced.
DR   GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0061630; F:ubiquitin protein ligase activity; ISS:UniProtKB.
DR   CDD; cd02123; PA_C_RZF_like; 1.
DR   Gene3D; 3.30.40.10; -; 1.
DR   InterPro; IPR003137; PA_domain.
DR   InterPro; IPR001841; Znf_RING.
DR   InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR   InterPro; IPR044744; ZNRF4/RNF13/RNF167_PA.
DR   Pfam; PF02225; PA; 1.
DR   Pfam; PF13639; zf-RING_2; 1.
DR   SMART; SM00184; RING; 1.
DR   PROSITE; PS50089; ZF_RING_2; 1.
PE   2: Evidence at transcript level;
KW   Endoplasmic reticulum; Glycoprotein; Membrane; Metal-binding;
KW   Reference proteome; Signal; Transferase; Transmembrane;
KW   Transmembrane helix; Zinc; Zinc-finger.
FT   SIGNAL          1..27
FT                   /evidence="ECO:0000255"
FT   CHAIN           28..429
FT                   /note="E3 ubiquitin-protein ligase ZNRF4"
FT                   /id="PRO_0000277862"
FT   TOPO_DOM        28..250
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        251..271
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        272..429
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   DOMAIN          152..223
FT                   /note="PA"
FT                   /evidence="ECO:0000255"
FT   ZN_FING         309..352
FT                   /note="RING-type; atypical"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT   REGION          30..64
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          358..381
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          409..429
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        358..372
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        152
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   429 AA;  46799 MW;  149671ECB405413A CRC64;
     MLRCRPEPLM PRATRVAVAV SLPLSHAVIP TQLPSHPGHR PSGRPRRCPK APCLPSPVGL
     SSTQPAKRVT MGWPRPGQAL VAVKALLVLS VLQVPAQAVV RAMLEDISSS VDFADLPALF
     GVPLAPEGIR GYLMEVKPAN ACHPVEAPRL GNRSLGAIAL IRRYDCTFDL KVLNAQRAGF
     EAAIVHNVHS DDLVSMTHVS EDLRGQIAIP SVFVGEAASQ DLRVILGCDK SAHVLLLPDD
     PPCRDLDCHP VLTVSWALGR TLALVVSTLF VLNRLWLWAQ ACCSHRRLVK TSTCQKAQVR
     TFTRRNDLCA ICLDEYEEGD QLKILPCSHT YHCKCIDPWF SQAPRRSCPV CKQSVAGTED
     SFDSTTDSFS DEDPSLPGHR PPIWAIQARL RSRRLELLGR ASPHCHCSTT SLEAEDTTVS
     PAPPEAPGQ