ZNRF4_MOUSE
ID ZNRF4_MOUSE Reviewed; 327 AA.
AC Q9DAH2; Q9WTN2;
DT 17-FEB-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 152.
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=Sperizin {ECO:0000303|PubMed:10191088};
DE AltName: Full=Zinc/RING finger protein 4 {ECO:0000250|UniProtKB:Q8WWF5};
DE Flags: Precursor;
GN Name=Znrf4 {ECO:0000312|MGI:MGI:1341258};
GN Synonyms=Spzn {ECO:0000303|PubMed:10191088};
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] {ECO:0000312|EMBL:BAA77407.1}
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC STRAIN=C57BL/6J {ECO:0000303|PubMed:10191088};
RC TISSUE=Testis {ECO:0000303|PubMed:10191088};
RX PubMed=10191088; DOI=10.1006/geno.1998.5738;
RA Fujii T., Tamura K., Copeland N.G., Gilbert D.J., Jenkins N.A.,
RA Yomogida K., Tanaka H., Nishimune Y., Nojima H., Abiko Y.;
RT "Sperizin is a murine RING zinc-finger protein specifically expressed in
RT haploid germ cells.";
RL Genomics 57:94-101(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Testis;
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 that acts as a negative regulator
CC of NOD2 signaling by mediating ubiquitination and degradation of RIPK2
CC (By similarity). Also catalyzes ubiquitination and proteasomal
CC degradation of CANX within the endoplasmic reticulum (By similarity).
CC Could have a role in spermatogenesis (PubMed:10191088).
CC {ECO:0000250|UniProtKB:Q8WWF5, ECO:0000305|PubMed:10191088}.
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:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed exclusively in spermatids (at protein
CC level). {ECO:0000269|PubMed:10191088}.
CC -!- DEVELOPMENTAL STAGE: Detected in the testis from the postpubertal stage
CC (23 days) onwards, with highest expression at 29 days.
CC {ECO:0000269|PubMed:10191088}.
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; AB016984; BAA77407.1; -; mRNA.
DR EMBL; AK005843; BAB24269.1; -; mRNA.
DR EMBL; CT485788; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC140986; AAI40987.1; -; mRNA.
DR CCDS; CCDS28906.1; -.
DR RefSeq; NP_035613.2; NM_011483.2.
DR AlphaFoldDB; Q9DAH2; -.
DR SMR; Q9DAH2; -.
DR STRING; 10090.ENSMUSP00000059715; -.
DR GlyGen; Q9DAH2; 1 site.
DR PhosphoSitePlus; Q9DAH2; -.
DR PaxDb; Q9DAH2; -.
DR PRIDE; Q9DAH2; -.
DR ProteomicsDB; 275307; -.
DR Antibodypedia; 2299; 113 antibodies from 19 providers.
DR DNASU; 20834; -.
DR Ensembl; ENSMUST00000052211; ENSMUSP00000059715; ENSMUSG00000044526.
DR GeneID; 20834; -.
DR KEGG; mmu:20834; -.
DR UCSC; uc008dce.1; mouse.
DR CTD; 148066; -.
DR MGI; MGI:1341258; Znrf4.
DR VEuPathDB; HostDB:ENSMUSG00000044526; -.
DR eggNOG; KOG4628; Eukaryota.
DR GeneTree; ENSGT00940000163061; -.
DR HOGENOM; CLU_035275_1_0_1; -.
DR InParanoid; Q9DAH2; -.
DR OMA; CDKSAHV; -.
DR OrthoDB; 1487241at2759; -.
DR PhylomeDB; Q9DAH2; -.
DR TreeFam; TF317486; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 20834; 2 hits in 74 CRISPR screens.
DR PRO; PR:Q9DAH2; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q9DAH2; protein.
DR Bgee; ENSMUSG00000044526; Expressed in spermatid and 5 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:MGI.
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 GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISO:MGI.
DR CDD; cd02123; PA_C_RZF_like; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR044744; ZNRF4/RNF13/RNF167_PA.
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 Endoplasmic reticulum; Glycoprotein; Membrane; Metal-binding;
KW Reference proteome; Signal; Transferase; Transmembrane;
KW Transmembrane helix; Zinc; Zinc-finger.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT CHAIN 29..327
FT /note="E3 ubiquitin-protein ligase ZNRF4"
FT /id="PRO_5004325102"
FT TOPO_DOM 29..150
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 151..171
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 172..327
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT ZN_FING 209..252
FT /note="RING-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 256..279
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 31
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 73
FT /note="W -> G (in Ref. 1; BAA77407)"
FT /evidence="ECO:0000305"
FT CONFLICT 244..246
FT /note="AQR -> GA (in Ref. 1; BAA77407)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 327 AA; 35628 MW; 5F8D34ABFE394193 CRC64;
MARFAWTRVA PVALVTFWLV LSLSPTDAQV NLSSVDFLDL PALLGVPVDP KRARGYLLVA
RPADACHAIE GPWPDNHSLD PLVLVRPLGC SWEQTGRRAQ RAGATAASVG PEAPGQLREF
EDLEVTVRCD QPARVLLPHA EPCPDPECHP VVVASWALAR ALALAASTLF VLRQLWPWVR
GLGSRGTAVK TQTCQKAQVR TFTRLSDLCA ICLDDYEEGE RLKILPCAHA YHCRCIDPWF
SRAAQRSCPL CKQSVASTHD GSTDGSVGGE EPPLPGHRPP IWAIQARLRS RRLELLARTV
PCRRCSSTTS LGVAENVAQS EATSELS
