ZBED6_HUMAN
ID ZBED6_HUMAN Reviewed; 979 AA.
AC P86452;
DT 23-MAR-2010, integrated into UniProtKB/Swiss-Prot.
DT 23-MAR-2010, sequence version 1.
DT 03-AUG-2022, entry version 84.
DE RecName: Full=Zinc finger BED domain-containing protein 6 {ECO:0000303|PubMed:20016685};
GN Name=ZBED6 {ECO:0000303|PubMed:20016685};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [2] {ECO:0000305}
RP IDENTIFICATION.
RX PubMed=20016685; DOI=10.1371/journal.pbio.1000256;
RA Markljung E., Jiang L., Jaffe J.D., Mikkelsen T.S., Wallerman O.,
RA Larhammar M., Zhang X., Wang L., Saenz-Vash V., Gnirke A., Lindroth A.M.,
RA Barres R., Yan J., Stromberg S., De S., Ponten F., Lander E.S., Carr S.A.,
RA Zierath J.R., Kullander K., Wadelius C., Lindblad-Toh K., Andersson G.,
RA Hjalm G., Andersson L.;
RT "ZBED6, a novel transcription factor derived from a domesticated DNA
RT transposon regulates IGF2 expression and muscle growth.";
RL PLoS Biol. 7:E1000256-E1000256(2009).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=24043816; DOI=10.1073/pnas.1303625110;
RA Wang X., Jiang L., Wallerman O., Engstroem U., Ameur A., Gupta R.K., Qi Y.,
RA Andersson L., Welsh N.;
RT "Transcription factor ZBED6 affects gene expression, proliferation, and
RT cell death in pancreatic beta cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:15997-16002(2013).
CC -!- FUNCTION: Transcriptional repressor which binds to the consensus
CC sequence 5'-GCTCGC-3', transcription regulation may be tissue-specific
CC (By similarity). Regulates the expression of target genes such as:
CC IGF2, PGAP6/TMEM8, ENHO, and PIANP (By similarity). Acts as a
CC transcriptional repressor of growth factor IGF2, thereby negatively
CC regulating postnatal growth of muscles and internal organs, especially
CC in females (By similarity). Negatively regulates myoblast
CC differentiation and myoblast mitochondrial activity via its regulation
CC of IGF2 transcription (By similarity). Negatively regulates the cell
CC cycle of myoblasts, potentially via transcriptional regulation of the
CC E2F family of transcription factors such as: E2F1 and E2F2 (By
CC similarity). Positively regulates the cell cycle and survival of
CC pancreatic beta cells (PubMed:24043816). Binds to the CDH2 gene and may
CC directly repress CDH2 transcription (By similarity). Probably by
CC controlling CDH2 expression, regulates pancreatic beta cell adhesion,
CC and formation of cell-to-cell junctions between pancreatic beta cells
CC and neural crest stem cells (By similarity). May also play a role in
CC embryonic beta cell differentiation (By similarity). May play a role in
CC insulin sensitivity and glucose clearance (By similarity).
CC {ECO:0000250|UniProtKB:D2EAC2, ECO:0000269|PubMed:24043816}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:24043816}. Nucleus,
CC nucleolus {ECO:0000250|UniProtKB:D2EAC2}. Cytoplasm
CC {ECO:0000269|PubMed:24043816}. Note=Located predominantly in the
CC nucleolus but is also dispersed throughout the nucleus (By similarity).
CC Mainly cytoplasmic in insulin- and glucagon-positive islet pancreatic
CC cells, however nuclear localization is evidence in some pancreatic
CC endocrine cells (PubMed:24043816). {ECO:0000250|UniProtKB:D2EAC2,
CC ECO:0000269|PubMed:24043816}.
CC -!- TISSUE SPECIFICITY: Expressed in pancreatic islet cells (at protein
CC level). {ECO:0000269|PubMed:24043816}.
CC -!- MISCELLANEOUS: Encoded by an exapted DNA transposon located in an
CC intron of the ZC3H11A gene. {ECO:0000269|PubMed:20016685}.
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DR EMBL; AC114402; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS55673.1; -.
DR RefSeq; NP_001167579.1; NM_001174108.2.
DR AlphaFoldDB; P86452; -.
DR BioGRID; 1147772; 8.
DR IntAct; P86452; 5.
DR STRING; 9606.ENSP00000447879; -.
DR iPTMnet; P86452; -.
DR PhosphoSitePlus; P86452; -.
DR BioMuta; ZBED6; -.
DR DMDM; 292495573; -.
DR EPD; P86452; -.
DR jPOST; P86452; -.
DR MassIVE; P86452; -.
DR MaxQB; P86452; -.
DR PaxDb; P86452; -.
DR PeptideAtlas; P86452; -.
DR PRIDE; P86452; -.
DR ProteomicsDB; 57774; -.
DR Antibodypedia; 77040; 9 antibodies from 6 providers.
DR DNASU; 100381270; -.
DR Ensembl; ENST00000550078.2; ENSP00000447879.1; ENSG00000257315.3.
DR GeneID; 100381270; -.
DR KEGG; hsa:100381270; -.
DR MANE-Select; ENST00000550078.3; ENSP00000447879.1; NM_001395895.1; NP_001382824.1.
DR UCSC; uc021phs.2; human.
DR CTD; 100381270; -.
DR DisGeNET; 100381270; -.
DR GeneCards; ZBED6; -.
DR HGNC; HGNC:33273; ZBED6.
DR HPA; ENSG00000257315; Low tissue specificity.
DR MIM; 613512; gene.
DR neXtProt; NX_P86452; -.
DR OpenTargets; ENSG00000257315; -.
DR PharmGKB; PA165752811; -.
DR VEuPathDB; HostDB:ENSG00000257315; -.
DR eggNOG; KOG1121; Eukaryota.
DR GeneTree; ENSGT00940000163411; -.
DR HOGENOM; CLU_303823_0_0_1; -.
DR InParanoid; P86452; -.
DR OMA; KTSAVWN; -.
DR OrthoDB; 223749at2759; -.
DR PhylomeDB; P86452; -.
DR TreeFam; TF322818; -.
DR PathwayCommons; P86452; -.
DR SignaLink; P86452; -.
DR BioGRID-ORCS; 100381270; 16 hits in 1077 CRISPR screens.
DR GeneWiki; ZBED6; -.
DR Pharos; P86452; Tdark.
DR PRO; PR:P86452; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P86452; protein.
DR Bgee; ENSG00000257315; Expressed in adrenal tissue and 106 other tissues.
DR Genevisible; P86452; HS.
DR GO; GO:0034451; C:centriolar satellite; IDA:HPA.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISS:ARUK-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISS:ARUK-UCL.
DR GO; GO:0060548; P:negative regulation of cell death; ISS:UniProtKB.
DR GO; GO:0051148; P:negative regulation of muscle cell differentiation; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0045787; P:positive regulation of cell cycle; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR InterPro; IPR008906; HATC_C_dom.
DR InterPro; IPR012337; RNaseH-like_sf.
DR InterPro; IPR003656; Znf_BED.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR Pfam; PF05699; Dimer_Tnp_hAT; 1.
DR Pfam; PF02892; zf-BED; 2.
DR SUPFAM; SSF53098; SSF53098; 1.
DR SUPFAM; SSF57667; SSF57667; 2.
DR PROSITE; PS50808; ZF_BED; 2.
PE 1: Evidence at protein level;
KW Cytoplasm; DNA-binding; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..979
FT /note="Zinc finger BED domain-containing protein 6"
FT /id="PRO_0000392573"
FT ZN_FING 130..187
FT /note="BED-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00027"
FT ZN_FING 264..321
FT /note="BED-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00027"
FT REGION 1..89
FT /note="Required for nucleolar localization"
FT /evidence="ECO:0000250|UniProtKB:D2EAC2"
FT REGION 207..232
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 333..383
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 866..948
FT /note="HATC (Hobo-Ac-Tam3) domain"
FT COMPBIAS 347..361
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 151
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00027"
FT BINDING 154
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00027"
FT BINDING 175
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00027"
FT BINDING 180
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00027"
FT BINDING 285
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00027"
FT BINDING 288
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00027"
FT BINDING 309
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00027"
FT BINDING 314
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00027"
FT MOD_RES 381
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:D2EAC2"
SQ SEQUENCE 979 AA; 109973 MW; 48D5B5EE9AFDC2A2 CRC64;
MSVCTLSVPV SSLSPGRRCN TFSDSGILGC VPINSNTDEE DVVEEKMVAE GVNKEAKQPA
KKKRKKGLRI KGKRRRKKLI LAKKFSKDLG SGRPVADAPA LLASNDPEQD EESLFESNIE
KQIYLPSTRA KTSIVWHFFH VDPQYTWRAI CNLCEKSVSR GKPGSHLGTS TLQRHLQARH
SPHWTRANKF GVASGEEDFT LDVSLSPSSG SNGSFEYIPT DPLDDNRMGK KHDKSASDAL
RAERGRFLIK SNIVKHALIP GTRAKTSAVW NFFYTDPQHI SRAVCNICKR SVSRGRPGSH
LGTSTLQRHL QATHPIHWAV ANKDSGAVAN GLDEAETERS DLLSDTLHGE KSTGSQDLTA
EDLSDSDSDE PMLEVENRSE SPIPVAEQGT LMRAQERETT CCGNPVSSHI SQAIIQMIVE
DMHPYNYFST PAFQRFMQIV APDYRLPSET YFFTKAVPQL YDCVREKIFL TLENVQSQKI
HLTVDIWTHD PSTDYFIVTV HWVSLETASF LNNGRIPDFR KWAVLCVTGL AKDCLITNIL
QELNDQIGLW LSPNFLIPSF IVSDNSSNVV HAIKDGGFTH VPCFLHCLNM VIQDFFCEHK
SIENMLVAAR KTCHHFSHSV KARQILQEFQ NDHQLPWKNL KQDETGHWIS TFYMLKWLLE
HCYSVHHSLG RASGVVLTSL QWTLMTYVCD ILKPFEEATQ KVSVKTAGLN QVLPLIHHLL
LSLQKLREDF QVRGITQALN LVDSLSLKLE TDTLLSAMLK SKPCILATLL DPCFKNSLED
FFPQGADLET YKQFLAEEVC NYMESSPEIC QIPTSEASCP SVTVGADSFT SSLKEGTSSS
GSVDSSAVDN VALGSKSFMF PSAVAVVDEY FKEKYSEFSG GDDPLIYWQR KISIWPALTQ
VAIQYLSCPM CSWQSECIFT KNSHFHPKQI MSLDFDNIEQ LMFLKMNLKN VNYDYSTLVL
SWDPEQNEVV QSSEKEILP
