ZNRF1_MOUSE
ID ZNRF1_MOUSE Reviewed; 227 AA.
AC Q91V17; Q8C5D7;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=E3 ubiquitin-protein ligase ZNRF1;
DE EC=2.3.2.27;
DE AltName: Full=Nerve injury-induced gene 283 protein;
DE AltName: Full=RING-type E3 ubiquitin transferase ZNRF1;
DE AltName: Full=Zinc/RING finger protein 1;
GN Name=Znrf1; Synonyms=Nin283;
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], AND SUBCELLULAR LOCATION.
RX PubMed=11427537; DOI=10.1074/jbc.m104271200;
RA Araki T., Nagarajan R., Milbrandt J.;
RT "Identification of genes induced in peripheral nerve after injury.
RT Expression profiling and novel gene discovery.";
RL J. Biol. Chem. 276:34131-34141(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Cerebellum, and Lung;
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 MRNA].
RC STRAIN=C57BL/6J, and 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 [4]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=14561866; DOI=10.1523/jneurosci.23-28-09385.2003;
RA Araki T., Milbrandt J.;
RT "ZNRF proteins constitute a family of presynaptic E3 ubiquitin ligases.";
RL J. Neurosci. 23:9385-9394(2003).
RN [5]
RP INTERACTION WITH TUBB2A.
RX PubMed=19737534; DOI=10.1016/j.bbrc.2009.09.011;
RA Yoshida K., Watanabe M., Hatakeyama S.;
RT "ZNRF1 interacts with tubulin and regulates cell morphogenesis.";
RL Biochem. Biophys. Res. Commun. 389:506-511(2009).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-52 AND SER-53, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung;
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).
RN [7]
RP FUNCTION, INTERACTION WITH GLUL, AND MUTAGENESIS OF CYS-184.
RX PubMed=20107048; DOI=10.1523/jneurosci.3591-09.2010;
RA Saitoh F., Araki T.;
RT "Proteasomal degradation of glutamine synthetase regulates schwann cell
RT differentiation.";
RL J. Neurosci. 30:1204-1212(2010).
RN [8]
RP FUNCTION, INTERACTION WITH AKT1, AND MUTAGENESIS OF CYS-145 AND CYS-184.
RX PubMed=22057101; DOI=10.1038/ncb2373;
RA Wakatsuki S., Saitoh F., Araki T.;
RT "ZNRF1 promotes Wallerian degeneration by degrading AKT to induce GSK3B-
RT dependent CRMP2 phosphorylation.";
RL Nat. Cell Biol. 13:1415-1423(2011).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that mediates the ubiquitination
CC of AKT1 and GLUL, thereby playing a role in neuron cells
CC differentiation. Plays a role in the establishment and maintenance of
CC neuronal transmission and plasticity. Regulates Schwann cells
CC differentiation by mediating ubiquitination of GLUL. Promotes Wallerian
CC degeneration, a neurodegeneration disorder, by mediating 'Lys-48'-
CC linked polyubiquitination and subsequent degradation of AKT1 in axons:
CC degradation of AKT1 prevents AKT1-mediated phosphorylation of GSK3B,
CC leading to GSK3B activation and phosphorylation of DPYSL2/CRMP2
CC followed by destabilization of microtubule assembly in axons.
CC {ECO:0000269|PubMed:20107048, ECO:0000269|PubMed:22057101}.
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;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with AKT1, GLUL and TUBB2A.
CC {ECO:0000269|PubMed:19737534, ECO:0000269|PubMed:20107048,
CC ECO:0000269|PubMed:22057101}.
CC -!- SUBCELLULAR LOCATION: Endosome. Lysosome. Membrane; Peripheral membrane
CC protein. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle
CC membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}.
CC Note=Associated with synaptic vesicle membranes in neurons.
CC -!- DOMAIN: The RING-type zinc finger domain is required for E3 ligase
CC activity. {ECO:0000250}.
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DR EMBL; AF378525; AAK69754.1; -; mRNA.
DR EMBL; AK078819; BAC37410.1; -; mRNA.
DR EMBL; AK079338; BAC37612.1; -; mRNA.
DR EMBL; BC006765; AAH06765.1; -; mRNA.
DR EMBL; BC086770; AAH86770.1; -; mRNA.
DR CCDS; CCDS22676.1; -.
DR RefSeq; NP_001162092.1; NM_001168621.1.
DR RefSeq; NP_001162093.1; NM_001168622.1.
DR RefSeq; NP_001162094.1; NM_001168623.1.
DR RefSeq; NP_573469.1; NM_133206.3.
DR RefSeq; XP_006530794.1; XM_006530731.2.
DR AlphaFoldDB; Q91V17; -.
DR SMR; Q91V17; -.
DR BioGRID; 228404; 1.
DR STRING; 10090.ENSMUSP00000092799; -.
DR iPTMnet; Q91V17; -.
DR PhosphoSitePlus; Q91V17; -.
DR EPD; Q91V17; -.
DR jPOST; Q91V17; -.
DR MaxQB; Q91V17; -.
DR PaxDb; Q91V17; -.
DR PRIDE; Q91V17; -.
DR ProteomicsDB; 275102; -.
DR Antibodypedia; 30290; 162 antibodies from 27 providers.
DR DNASU; 170737; -.
DR Ensembl; ENSMUST00000095176; ENSMUSP00000092799; ENSMUSG00000033545.
DR Ensembl; ENSMUST00000168428; ENSMUSP00000126684; ENSMUSG00000033545.
DR Ensembl; ENSMUST00000172856; ENSMUSP00000133309; ENSMUSG00000033545.
DR Ensembl; ENSMUST00000173506; ENSMUSP00000133993; ENSMUSG00000033545.
DR GeneID; 170737; -.
DR KEGG; mmu:170737; -.
DR UCSC; uc009nmk.2; mouse.
DR CTD; 84937; -.
DR MGI; MGI:2177308; Znrf1.
DR VEuPathDB; HostDB:ENSMUSG00000033545; -.
DR eggNOG; KOG0801; Eukaryota.
DR GeneTree; ENSGT00940000159278; -.
DR HOGENOM; CLU_062700_0_1_1; -.
DR InParanoid; Q91V17; -.
DR OMA; YNVRTQR; -.
DR OrthoDB; 1256682at2759; -.
DR PhylomeDB; Q91V17; -.
DR TreeFam; TF317681; -.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 170737; 1 hit in 70 CRISPR screens.
DR ChiTaRS; Znrf1; mouse.
DR PRO; PR:Q91V17; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q91V17; protein.
DR Bgee; ENSMUSG00000033545; Expressed in granulocyte and 264 other tissues.
DR ExpressionAtlas; Q91V17; baseline and differential.
DR Genevisible; Q91V17; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005768; C:endosome; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0030672; C:synaptic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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:0007010; P:cytoskeleton organization; TAS:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB.
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 Cytoplasmic vesicle; Endosome; Lipoprotein; Lysosome; Membrane;
KW Metal-binding; Myristate; Phosphoprotein; Reference proteome; Synapse;
KW Transferase; Ubl conjugation pathway; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000255"
FT CHAIN 2..227
FT /note="E3 ubiquitin-protein ligase ZNRF1"
FT /id="PRO_0000277800"
FT ZN_FING 184..225
FT /note="RING-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 1..42
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2..10
FT /note="Required for endosomal and lysosomal localization
FT and myristoylation"
FT /evidence="ECO:0000250"
FT REGION 65..105
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 86..102
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 52
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 53
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 123
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8ND25"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000255"
FT MUTAGEN 145
FT /note="C->A: Delays neurite degeneration and inhibits
FT DPYSL2/CRMP2 phosphorylation."
FT /evidence="ECO:0000269|PubMed:22057101"
FT MUTAGEN 184
FT /note="C->A: Dominant negative mutant; can prevent
FT Wallerian degeneration when overexpressed."
FT /evidence="ECO:0000269|PubMed:20107048,
FT ECO:0000269|PubMed:22057101"
SQ SEQUENCE 227 AA; 23843 MW; D8DD30B6F00858A0 CRC64;
MGGKQSTAAR SRGPFPGVST DDSAVPPPGG APHFGHYRTG GGAMGLRSRS VSSVAGMGMD
PSTAGGVPFS LYTPASRGTG DSERAPGGGG STSDSTYAHG NGYQETGGGH HRDGMLYLGS
RASLADALPL HIAPRWFSSH SGFKCPICSK SVASDEMEMH FIMCLSKPRL SYNDDVLTKD
AGECVICLEE LLQGDTIARL PCLCIYHKSC IDSWFEVNRS CPEHPAD
