ZBED3_MOUSE
ID ZBED3_MOUSE Reviewed; 228 AA.
AC Q9D0L1;
DT 06-MAR-2013, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Zinc finger BED domain-containing protein 3;
DE AltName: Full=Axin-interacting protein;
GN Name=Zbed3;
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].
RC STRAIN=C57BL/6J; TISSUE=Egg, and Embryo;
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 [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Embryonic brain, and Salivary gland;
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, INTERACTION WITH AXIN1, SUBCELLULAR LOCATION, MOTIF, AND
RP MUTAGENESIS OF SER-111 AND THR-113.
RX PubMed=19141611; DOI=10.1074/jbc.m807753200;
RA Chen T., Li M., Ding Y., Zhang L.S., Xi Y., Pan W.J., Tao D.L., Wang J.Y.,
RA Li L.;
RT "Identification of zinc-finger BED domain-containing 3 (Zbed3) as a novel
RT Axin-interacting protein that activates Wnt/beta-catenin signaling.";
RL J. Biol. Chem. 284:6683-6689(2009).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=24283382; DOI=10.1111/joim.12170;
RA Jia Y., Yuan L., Hu W., Luo Y., Suo L., Yang M., Chen S., Wang Y., Liu H.,
RA Yang G., Li L.;
RT "Zinc-finger BED domain-containing 3 (Zbed3) is a novel secreted protein
RT associated with insulin resistance in humans.";
RL J. Intern. Med. 275:522-533(2014).
RN [7]
RP FUNCTION, INTERACTION WITH NLRP5, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=28992324; DOI=10.1093/jmcb/mjx035;
RA Gao Z., Zhang X., Yu X., Qin D., Xiao Y., Yu Y., Xiang Y., Nie X., Lu X.,
RA Liu W., Yi Z., Li L.;
RT "Zbed3 participates in the subcortical maternal complex and regulates the
RT distribution of organelles.";
RL J. Mol. Cell Biol. 10:74-88(2018).
RN [8]
RP INTERACTION WITH TLE6, AND DEVELOPMENTAL STAGE.
RX PubMed=31575650; DOI=10.1242/dev.183616;
RA Qin D., Gao Z., Xiao Y., Zhang X., Ma H., Yu X., Nie X., Fan N., Wang X.,
RA Ouyang Y., Sun Q.Y., Yi Z., Li L.;
RT "The subcortical maternal complex protein Nlrp4f is involved in cytoplasmic
RT lattice formation and organelle distribution.";
RL Development 146:0-0(2019).
CC -!- FUNCTION: Acts as a positive regulator in the activation of the
CC canonical Wnt/beta-catenin signaling pathway by stabilizing cytoplasmic
CC beta-catenin (PubMed:19141611). Involved in transcription activation of
CC Wnt target gene expression (PubMed:19141611). Plays a role in symmetric
CC division of blastomeres in the early stages of embryogenesis via
CC regulation of mitotic spindle central positioning and organization of
CC the F-actin filament network (PubMed:28992324). Plays a role in
CC regulating the distribution of cellular organelles, via modulation of
CC cytoskeletal dynamics and cytoplasmic lattice formation
CC (PubMed:28992324). {ECO:0000269|PubMed:19141611,
CC ECO:0000269|PubMed:28992324}.
CC -!- SUBUNIT: Associates with the subcortical maternal complex (SCMC)
CC composed of at least NLRP5, KHDC3, OOEP, and TLE6 via interaction with
CC NLRP5 and TLE6 (PubMed:28992324, PubMed:31575650). Interacts (via PPPSP
CC motif) with AXIN1; the interaction is direct, enhanced by protein
CC kinase GSK3B and casein kinase CSNK1E activities and decreases GSK3B-
CC induced beta-catenin serine and threonine phosphorylations
CC (PubMed:19141611). {ECO:0000269|PubMed:19141611,
CC ECO:0000269|PubMed:28992324, ECO:0000269|PubMed:31575650}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19141611,
CC ECO:0000269|PubMed:28992324}. Membrane {ECO:0000269|PubMed:19141611}.
CC Secreted {ECO:0000250|UniProtKB:Q96IU2}. Note=Colocalizes with AXIN1 in
CC the cytoplasm (PubMed:19141611). Colocalizes with NLRP5 in the oocyte
CC subcortex (PubMed:28992324). {ECO:0000269|PubMed:19141611,
CC ECO:0000269|PubMed:28992324}.
CC -!- TISSUE SPECIFICITY: Expressed in the liver (at protein level)
CC (PubMed:24283382). Abundantly expressed in muscle, with lower
CC expression in brain, fat, and heart (PubMed:24283382). Expressed in the
CC spleen, lungs and kidney (PubMed:24283382, PubMed:28992324). Abundantly
CC expressed in ovaries and testis, with lower expression in the uterus
CC (PubMed:28992324). {ECO:0000269|PubMed:24283382,
CC ECO:0000269|PubMed:28992324}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the cytoplasm of germinal vesicle
CC oocytes before becoming concentrated in the subcortex of metaphase 2
CC oocytes (PubMed:28992324). Expressed in ovaries at birth, expression
CC peaks at postnatal day 10 (P10), expression is then decreased at P17
CC and further decreased at P21 (PubMed:31575650).
CC {ECO:0000269|PubMed:28992324, ECO:0000269|PubMed:31575650}.
CC -!- PTM: Dual phosphorylation on serine and tyrosine residues of the
CC cytoplasmic PPPSP motif by GSK3 and CK1 may be required for AXIN1-
CC binding. {ECO:0000305|PubMed:19141611}.
CC -!- DISRUPTION PHENOTYPE: Males show normal fertility however females
CC produce smaller litters (PubMed:28992324). Increase in the number of 2-
CC cell embryos with asymmetric blastomeres as a result of impaired
CC central mitotic spindle position and therefore an increase in the
CC distance between the cellular center and the chromosomes
CC (PubMed:28992324). Disorganization of the F-actin filament network
CC around the mitotic spindle and loss of FMN2-expressing endoplasmic
CC reticulum localization to the mitotic spindle periphery in zygotes and
CC oocytes (PubMed:28992324). Mitochondria are mislocalized to the plus-
CC ends of elongated microtubules in the subcortical cytoplasm in oocytes
CC prior to nuclear envelope breakdown (PubMed:28992324). Loss of
CC cytoplasmic lattices and extension of the alpha-tubulin pool into the
CC subcortical region following microtubule-organizing center congression
CC in oocytes (PubMed:28992324). {ECO:0000269|PubMed:28992324}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK011319; BAB27542.1; -; mRNA.
DR EMBL; AK135692; BAE22613.1; -; mRNA.
DR EMBL; AK135797; BAE22666.1; -; mRNA.
DR EMBL; AK162256; BAE36818.1; -; mRNA.
DR EMBL; AK163367; BAE37318.1; -; mRNA.
DR EMBL; AC133188; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466567; EDL00907.1; -; Genomic_DNA.
DR EMBL; CH466567; EDL00908.1; -; Genomic_DNA.
DR EMBL; CH466567; EDL00909.1; -; Genomic_DNA.
DR EMBL; BC016263; AAH16263.1; -; mRNA.
DR EMBL; BC085478; AAH85478.1; -; mRNA.
DR CCDS; CCDS26696.1; -.
DR RefSeq; NP_001289467.1; NM_001302538.1.
DR RefSeq; NP_001289468.1; NM_001302539.1.
DR RefSeq; NP_082382.1; NM_028106.3.
DR AlphaFoldDB; Q9D0L1; -.
DR SMR; Q9D0L1; -.
DR BioGRID; 215161; 2.
DR IntAct; Q9D0L1; 2.
DR STRING; 10090.ENSMUSP00000044774; -.
DR iPTMnet; Q9D0L1; -.
DR PhosphoSitePlus; Q9D0L1; -.
DR REPRODUCTION-2DPAGE; Q9D0L1; -.
DR MaxQB; Q9D0L1; -.
DR PaxDb; Q9D0L1; -.
DR PRIDE; Q9D0L1; -.
DR ProteomicsDB; 298490; -.
DR Antibodypedia; 24479; 88 antibodies from 24 providers.
DR DNASU; 72114; -.
DR Ensembl; ENSMUST00000045909; ENSMUSP00000044774; ENSMUSG00000041995.
DR Ensembl; ENSMUST00000221807; ENSMUSP00000152153; ENSMUSG00000041995.
DR GeneID; 72114; -.
DR KEGG; mmu:72114; -.
DR UCSC; uc007rmg.2; mouse.
DR CTD; 84327; -.
DR MGI; MGI:1919364; Zbed3.
DR VEuPathDB; HostDB:ENSMUSG00000041995; -.
DR eggNOG; ENOG502SQ4N; Eukaryota.
DR GeneTree; ENSGT00940000164103; -.
DR HOGENOM; CLU_112726_0_0_1; -.
DR InParanoid; Q9D0L1; -.
DR OMA; TPMPHNK; -.
DR OrthoDB; 1464780at2759; -.
DR PhylomeDB; Q9D0L1; -.
DR TreeFam; TF338048; -.
DR BioGRID-ORCS; 72114; 3 hits in 71 CRISPR screens.
DR ChiTaRS; Zbed3; mouse.
DR PRO; PR:Q9D0L1; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; Q9D0L1; protein.
DR Bgee; ENSMUSG00000041995; Expressed in secondary oocyte and 192 other tissues.
DR ExpressionAtlas; Q9D0L1; baseline and differential.
DR Genevisible; Q9D0L1; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:MGI.
DR GO; GO:0007015; P:actin filament organization; IMP:UniProtKB.
DR GO; GO:0051643; P:endoplasmic reticulum localization; IMP:UniProtKB.
DR GO; GO:0051293; P:establishment of spindle localization; IMP:UniProtKB.
DR GO; GO:0051646; P:mitochondrion localization; IMP:UniProtKB.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IGI:MGI.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IDA:MGI.
DR GO; GO:0040019; P:positive regulation of embryonic development; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IDA:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0009749; P:response to glucose; ISS:UniProtKB.
DR GO; GO:0032868; P:response to insulin; ISS:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR043471; ZBED2/3.
DR InterPro; IPR033546; ZBED3.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR PANTHER; PTHR35827; PTHR35827; 1.
DR PANTHER; PTHR35827:SF2; PTHR35827:SF2; 1.
DR SUPFAM; SSF57667; SSF57667; 1.
PE 1: Evidence at protein level;
KW Coiled coil; Cytoplasm; Membrane; Metal-binding; Phosphoprotein;
KW Reference proteome; Secreted; Wnt signaling pathway; Zinc; Zinc-finger.
FT CHAIN 1..228
FT /note="Zinc finger BED domain-containing protein 3"
FT /id="PRO_0000421257"
FT ZN_FING 33..95
FT /note="BED-type"
FT REGION 95..114
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 183..228
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 132..185
FT /evidence="ECO:0000255"
FT MOTIF 108..112
FT /note="PPPSP motif; required for interaction with AXIN1"
FT /evidence="ECO:0000269|PubMed:19141611"
FT MUTAGEN 111
FT /note="S->A: Decreases the interaction with AXIN1, GSK3B-
FT mediated beta-catenin phosphorylation, cytoplasmic beta-
FT catenin accumulation and Wnt-mediated transcription
FT activation."
FT /evidence="ECO:0000269|PubMed:19141611"
FT MUTAGEN 113
FT /note="T->A: Decreases the interaction with AXIN1, GSK3B-
FT mediated beta-catenin phosphorylation, cytoplasmic beta-
FT catenin accumulation and Wnt-mediated transcription
FT activation."
FT /evidence="ECO:0000269|PubMed:19141611"
SQ SEQUENCE 228 AA; 25609 MW; 1CB44DD084B895A3 CRC64;
MKSKKPLKIT MEDSRRLNDP AEQGGLCPAP VGPSYSEAWG YFHLDPAQPR HRMMSAWATC
RLCGLQVGGL PNFQMWTRAL CQHLSDVHLP ELKKSAAPSS PTTMPCPPPP SPTMAAEGDW
ARLLEQMGEL AMRGSQRELE LERREAALMQ AELELERKRQ ALKQEAQSVE QERHQLQVER
EALSKWIKKQ SPGAQVPEPP SPLPLLPKED PDIHDNNSDN DMVTKVLL
