ID ZBT16_HUMAN Reviewed; 673 AA. AC Q05516; Q8TAL4; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 07-MAR-2006, sequence version 2. DT 11-NOV-2015, entry version 172. DE RecName: Full=Zinc finger and BTB domain-containing protein 16; DE AltName: Full=Promyelocytic leukemia zinc finger protein; DE AltName: Full=Zinc finger protein 145; DE AltName: Full=Zinc finger protein PLZF; GN Name=ZBTB16; Synonyms=PLZF, ZNF145; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PLZFB), ALTERNATIVE SPLICING, AND RP CHROMOSOMAL TRANSLOCATION WITH RARA. RC TISSUE=Heart ventricle; RX PubMed=8384553; RA Chen Z., Brand N.J., Chen A., Chen S.-J., Tong J.-H., Wang Z.-Y., RA Waxman S., Zelent A.; RT "Fusion between a novel Kruppel-like zinc finger gene and the retinoic RT acid receptor-alpha locus due to a variant t(11;17) translocation RT associated with acute promyelocytic leukaemia."; RL EMBO J. 12:1161-1167(1993). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=10500192; DOI=10.1073/pnas.96.20.11422; RA Zhang T., Xiong H., Kan L.-X., Zhang C.-K., Jiao X.-F., Fu G., RA Zhang Q.-H., Lu L., Tong J.-H., Gu B.-W., Yu M., Liu J.-X., Licht J., RA Waxman S., Zelent A., Chen E., Chen S.-J.; RT "Genomic sequence, structural organization, molecular evolution, and RT aberrant rearrangement of promyelocytic leukemia zinc finger gene."; RL Proc. Natl. Acad. Sci. U.S.A. 96:11422-11427(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PLZFB). 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 424-455. RX PubMed=8387545; DOI=10.1172/JCI116453; RA Chen S.-J., Zelent A., Tong J.-H., Yu H.-Q., Wang Z.-Y., Derre J., RA Berger R., Waxman S., Chen Z.; RT "Rearrangements of the retinoic acid receptor alpha and promyelocytic RT leukemia zinc finger genes resulting from t(11;17)(q23;q21) in a RT patient with acute promyelocytic leukemia."; RL J. Clin. Invest. 91:2260-2267(1993). RN [5] RP INTERACTION WITH ZBTB32. RX PubMed=10572087; RA Hoatlin M.E., Zhi Y., Ball H., Silvey K., Melnick A., Stone S., RA Arai S., Hawe N., Owen G., Zelent A., Licht J.D.; RT "A novel BTB/POZ transcriptional repressor protein interacts with the RT Fanconi anemia group C protein and PLZF."; RL Blood 94:3737-3747(1999). RN [6] RP INTERACTION WITH EPN1. RX PubMed=11161217; DOI=10.1126/science.291.5506.1047; RA Itoh T., Koshiba S., Kigawa T., Kikuchi A., Yokoyama S., Takenawa T.; RT "Role of the ENTH domain in phosphatidylinositol-4,5-bisphosphate RT binding and endocytosis."; RL Science 291:1047-1051(2001). RN [7] RP FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE, AND INTERACTION WITH CUL3. RX PubMed=14528312; DOI=10.1038/ncb1056; RA Furukawa M., He Y.J., Borchers C., Xiong Y.; RT "Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin RT ligases."; RL Nat. Cell Biol. 5:1001-1007(2003). RN [8] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 6-126. RX PubMed=9770450; DOI=10.1073/pnas.95.21.12123; RA Ahmad K.F., Engel C.K., Prive G.G.; RT "Crystal structure of the BTB domain from PLZF."; RL Proc. Natl. Acad. Sci. U.S.A. 95:12123-12128(1998). RN [9] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 7-122. RX PubMed=10537309; RA Li X., Peng H., Schultz D.C., Lopez-Guisa J.M., Rauscher F.J. III, RA Marmorstein R.; RT "Structure-function studies of the BTB/POZ transcriptional repression RT domain from the promyelocytic leukemia zinc finger oncoprotein."; RL Cancer Res. 59:5275-5282(1999). RN [10] RP VARIANT SGYMR VAL-617. RX PubMed=18611983; DOI=10.1136/jmg.2008.059451; RA Fischer S., Kohlhase J., Boehm D., Schweiger B., Hoffmann D., RA Heitmann M., Horsthemke B., Wieczorek D.; RT "Biallelic loss of function of the promyelocytic leukaemia zinc finger RT (PLZF) gene causes severe skeletal defects and genital hypoplasia."; RL J. Med. Genet. 45:731-737(2008). CC -!- FUNCTION: Probable transcription factor. May play a role in CC myeloid maturation and in the development and/or maintenance of CC other differentiated tissues. Probable substrate-recognition CC component of an E3 ubiquitin-protein ligase complex which mediates CC the ubiquitination and subsequent proteasomal degradation of CC target proteins. {ECO:0000269|PubMed:14528312}. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC -!- SUBUNIT: Binds EPN1. Interacts with ZBTB32 and CUL3. CC {ECO:0000269|PubMed:10572087, ECO:0000269|PubMed:11161217, CC ECO:0000269|PubMed:14528312}. CC -!- INTERACTION: CC Self; NbExp=3; IntAct=EBI-711925, EBI-711925; CC P68104:EEF1A1; NbExp=4; IntAct=EBI-711925, EBI-352162; CC O35826:Gne (xeno); NbExp=2; IntAct=EBI-711925, EBI-7109445; CC Q08379:GOLGA2; NbExp=3; IntAct=EBI-711925, EBI-618309; CC P09022:Hoxa1 (xeno); NbExp=3; IntAct=EBI-711925, EBI-3957603; CC P05231:IL6; NbExp=2; IntAct=EBI-711925, EBI-720533; CC Q6A162:KRT40; NbExp=3; IntAct=EBI-711925, EBI-10171697; CC A0A0C4DGV4:LAMTOR5; NbExp=3; IntAct=EBI-711925, EBI-10173304; CC P29590:PML; NbExp=7; IntAct=EBI-711925, EBI-295890; CC P29590-5:PML; NbExp=2; IntAct=EBI-711925, EBI-304008; CC Q9H788-2:SH2D4A; NbExp=3; IntAct=EBI-711925, EBI-10308083; CC Q9NYJ8:TAB2; NbExp=3; IntAct=EBI-711925, EBI-358708; CC Q12933:TRAF2; NbExp=2; IntAct=EBI-711925, EBI-355744; CC Q9BYV2:TRIM54; NbExp=3; IntAct=EBI-711925, EBI-2130429; CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=PLZFB; CC IsoId=Q05516-1; Sequence=Displayed; CC Name=PLZFA; CC IsoId=Q05516-2; Sequence=VSP_006896; CC -!- TISSUE SPECIFICITY: Within the hematopoietic system, PLZF is CC expressed in bone marrow, early myeloid cell lines and peripheral CC blood mononuclear cells. Also expressed in the ovary, and at lower CC levels, in the kidney and lung. CC -!- INDUCTION: By retinoic acid. CC -!- DISEASE: Skeletal defects, genital hypoplasia, and mental CC retardation (SGYMR) [MIM:612447]: A disorder characterized by CC mental retardation, craniofacial dysmorphism, microcephaly and CC short stature. Additional features include absence of the thumbs, CC hypoplasia of the radii and ulnae, additional vertebrae and ribs, CC retarded bone age and genital hypoplasia. CC {ECO:0000269|PubMed:18611983}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- DISEASE: Note=A chromosomal aberration involving ZBTB16 may be a CC cause of acute promyelocytic leukemia (APL). Translocation CC t(11;17)(q32;q21) with RARA. CC -!- SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein CC family. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 BTB (POZ) domain. {ECO:0000255|PROSITE- CC ProRule:PRU00037}. CC -!- SIMILARITY: Contains 9 C2H2-type zinc fingers. CC {ECO:0000255|PROSITE-ProRule:PRU00042}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/PLZFID37.html"; 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; Z19002; CAA79489.1; -; mRNA. DR EMBL; AF060568; AAD03619.1; -; Genomic_DNA. DR EMBL; BC026902; AAH26902.1; -; mRNA. DR EMBL; BC029812; AAH29812.1; -; mRNA. DR EMBL; S60093; AAC60590.2; -; Genomic_DNA. DR CCDS; CCDS8367.1; -. [Q05516-1] DR PIR; S36336; S36336. DR RefSeq; NP_001018011.1; NM_001018011.1. [Q05516-1] DR RefSeq; NP_005997.2; NM_006006.4. [Q05516-1] DR UniGene; Hs.591945; -. DR UniGene; Hs.682144; -. DR PDB; 1BUO; X-ray; 1.90 A; A=6-126. DR PDB; 1CS3; X-ray; 2.00 A; A=7-122. DR PDBsum; 1BUO; -. DR PDBsum; 1CS3; -. DR ProteinModelPortal; Q05516; -. DR SMR; Q05516; 6-126, 405-656. DR BioGrid; 113498; 117. DR DIP; DIP-2654N; -. DR IntAct; Q05516; 75. DR MINT; MINT-158782; -. DR STRING; 9606.ENSP00000338157; -. DR PhosphoSite; Q05516; -. DR BioMuta; ZBTB16; -. DR DMDM; 90109930; -. DR PaxDb; Q05516; -. DR PRIDE; Q05516; -. DR DNASU; 7704; -. DR Ensembl; ENST00000335953; ENSP00000338157; ENSG00000109906. [Q05516-1] DR Ensembl; ENST00000392996; ENSP00000376721; ENSG00000109906. [Q05516-1] DR GeneID; 7704; -. DR KEGG; hsa:7704; -. DR UCSC; uc001poo.1; human. [Q05516-1] DR CTD; 7704; -. DR GeneCards; ZBTB16; -. DR HGNC; HGNC:12930; ZBTB16. DR HPA; CAB004540; -. DR HPA; HPA001499; -. DR MIM; 176797; gene. DR MIM; 612447; phenotype. DR neXtProt; NX_Q05516; -. DR Orphanet; 520; Acute promyelocytic leukemia. DR PharmGKB; PA37517; -. DR eggNOG; KOG1721; Eukaryota. DR eggNOG; COG5048; LUCA. DR GeneTree; ENSGT00530000063338; -. DR HOGENOM; HOG000130800; -. DR HOVERGEN; HBG057844; -. DR InParanoid; Q05516; -. DR KO; K10055; -. DR OMA; HKANQMR; -. DR OrthoDB; EOG7N8ZTX; -. DR PhylomeDB; Q05516; -. DR TreeFam; TF350825; -. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR SignaLink; Q05516; -. DR UniPathway; UPA00143; -. DR ChiTaRS; ZBTB16; human. DR EvolutionaryTrace; Q05516; -. DR GeneWiki; Zinc_finger_and_BTB_domain-containing_protein_16; -. DR GenomeRNAi; 7704; -. DR NextBio; 29862; -. DR PRO; PR:Q05516; -. DR Proteomes; UP000005640; Chromosome 11. DR Bgee; Q05516; -. DR CleanEx; HS_ZBTB16; -. DR ExpressionAtlas; Q05516; baseline and differential. DR Genevisible; Q05516; HS. DR GO; GO:0005829; C:cytosol; IEA:Ensembl. DR GO; GO:0016604; C:nuclear body; IDA:UniProtKB. DR GO; GO:0016607; C:nuclear speck; IDA:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl. DR GO; GO:0016605; C:PML body; IDA:UniProtKB. DR GO; GO:0017053; C:transcriptional repressor complex; IDA:MGI. DR GO; GO:0003677; F:DNA binding; NAS:UniProtKB. DR GO; GO:0003690; F:double-stranded DNA binding; IEA:Ensembl. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0000980; F:RNA polymerase II distal enhancer sequence-specific DNA binding; IDA:NTNU_SB. DR GO; GO:0001206; F:transcriptional repressor activity, RNA polymerase II distal enhancer sequence-specific binding; IDA:NTNU_SB. DR GO; GO:0009952; P:anterior/posterior pattern specification; IEA:Ensembl. DR GO; GO:0006915; P:apoptotic process; NAS:UniProtKB. DR GO; GO:0051216; P:cartilage development; IDA:UniProtKB. DR GO; GO:0007417; P:central nervous system development; ISS:UniProtKB. DR GO; GO:0042733; P:embryonic digit morphogenesis; IEA:Ensembl. DR GO; GO:0035116; P:embryonic hindlimb morphogenesis; IEA:Ensembl. DR GO; GO:0009880; P:embryonic pattern specification; IEA:Ensembl. DR GO; GO:0035136; P:forelimb morphogenesis; IEA:Ensembl. DR GO; GO:0030097; P:hemopoiesis; IDA:UniProtKB. DR GO; GO:0048133; P:male germ-line stem cell asymmetric division; IEA:Ensembl. DR GO; GO:0001823; P:mesonephros development; ISS:UniProtKB. DR GO; GO:0030099; P:myeloid cell differentiation; TAS:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell proliferation; IEA:Ensembl. DR GO; GO:0045638; P:negative regulation of myeloid cell differentiation; ISS:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:NTNU_SB. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; NAS:UniProtKB. DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl. DR GO; GO:0061036; P:positive regulation of cartilage development; IDA:UniProtKB. DR GO; GO:0032332; P:positive regulation of chondrocyte differentiation; IMP:UniProtKB. DR GO; GO:0045600; P:positive regulation of fat cell differentiation; IMP:UniProtKB. DR GO; GO:0051138; P:positive regulation of NK T cell differentiation; IEA:Ensembl. DR GO; GO:0045778; P:positive regulation of ossification; IDA:UniProtKB. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0034504; P:protein localization to nucleus; IEA:Ensembl. DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR Gene3D; 3.30.160.60; -; 8. DR InterPro; IPR000210; BTB/POZ_dom. DR InterPro; IPR011333; POZ_dom. DR InterPro; IPR007087; Znf_C2H2. DR InterPro; IPR015880; Znf_C2H2-like. DR InterPro; IPR013087; Znf_C2H2/integrase_DNA-bd. DR Pfam; PF00651; BTB; 1. DR SMART; SM00225; BTB; 1. DR SMART; SM00355; ZnF_C2H2; 9. DR SUPFAM; SSF54695; SSF54695; 1. DR PROSITE; PS50097; BTB; 1. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 8. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 9. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Chromosomal rearrangement; KW Complete proteome; Disease mutation; DNA-binding; Mental retardation; KW Metal-binding; Nucleus; Phosphoprotein; Proto-oncogene; KW Reference proteome; Repeat; Transcription; Transcription regulation; KW Ubl conjugation pathway; Zinc; Zinc-finger. FT CHAIN 1 673 Zinc finger and BTB domain-containing FT protein 16. FT /FTId=PRO_0000047729. FT DOMAIN 34 96 BTB. {ECO:0000255|PROSITE- FT ProRule:PRU00037}. FT ZN_FING 404 426 C2H2-type 1. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 432 454 C2H2-type 2. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 461 483 C2H2-type 3. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 490 512 C2H2-type 4. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 518 540 C2H2-type 5. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 546 568 C2H2-type 6. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 574 596 C2H2-type 7. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 602 624 C2H2-type 8. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 630 652 C2H2-type 9. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT SITE 394 395 Breakpoint for translocation to form FT PLZF-RAR-alpha oncogene. FT MOD_RES 76 76 Phosphoserine; by PDPK1. {ECO:0000255}. FT MOD_RES 184 184 Phosphoserine; by PDPK1. {ECO:0000255}. FT MOD_RES 197 197 Phosphoserine; by PDPK1. {ECO:0000255}. FT MOD_RES 256 256 Phosphoserine; by PDPK1. {ECO:0000255}. FT MOD_RES 282 282 Phosphothreonine; by PDPK1. FT {ECO:0000255}. FT MOD_RES 628 628 Phosphoserine; by PDPK1. {ECO:0000255}. FT VAR_SEQ 255 377 Missing (in isoform PLZFA). FT {ECO:0000305}. FT /FTId=VSP_006896. FT VARIANT 617 617 M -> V (in SGYMR). FT {ECO:0000269|PubMed:18611983}. FT /FTId=VAR_054912. FT CONFLICT 580 580 G -> D (in Ref. 1; CAA79489). FT {ECO:0000305}. FT HELIX 16 30 {ECO:0000244|PDB:1BUO}. FT TURN 31 33 {ECO:0000244|PDB:1BUO}. FT STRAND 36 42 {ECO:0000244|PDB:1BUO}. FT STRAND 44 47 {ECO:0000244|PDB:1BUO}. FT HELIX 49 55 {ECO:0000244|PDB:1BUO}. FT HELIX 57 62 {ECO:0000244|PDB:1BUO}. FT HELIX 63 65 {ECO:0000244|PDB:1CS3}. FT STRAND 68 72 {ECO:0000244|PDB:1BUO}. FT HELIX 77 89 {ECO:0000244|PDB:1BUO}. FT HELIX 96 98 {ECO:0000244|PDB:1BUO}. FT HELIX 99 109 {ECO:0000244|PDB:1BUO}. FT HELIX 112 125 {ECO:0000244|PDB:1BUO}. SQ SEQUENCE 673 AA; 74274 MW; 51F8E361FA31239E CRC64; MDLTKMGMIQ LQNPSHPTGL LCKANQMRLA GTLCDVVIMV DSQEFHAHRT VLACTSKMFE ILFHRNSQHY TLDFLSPKTF QQILEYAYTA TLQAKAEDLD DLLYAAEILE IEYLEEQCLK MLETIQASDD NDTEATMADG GAEEEEDRKA RYLKNIFISK HSSEESGYAS VAGQSLPGPM VDQSPSVSTS FGLSAMSPTK AAVDSLMTIG QSLLQGTLQP PAGPEEPTLA GGGRHPGVAE VKTEMMQVDE VPSQDSPGAA ESSISGGMGD KVEERGKEGP GTPTRSSVIT SARELHYGRE ESAEQVPPPA EAGQAPTGRP EHPAPPPEKH LGIYSVLPNH KADAVLSMPS SVTSGLHVQP ALAVSMDFST YGGLLPQGFI QRELFSKLGE LAVGMKSESR TIGEQCSVCG VELPDNEAVE QHRKLHSGMK TYGCELCGKR FLDSLRLRMH LLAHSAGAKA FVCDQCGAQF SKEDALETHR QTHTGTDMAV FCLLCGKRFQ AQSALQQHME VHAGVRSYIC SECNRTFPSH TALKRHLRSH TGDHPYECEF CGSCFRDEST LKSHKRIHTG EKPYECNGCG KKFSLKHQLE THYRVHTGEK PFECKLCHQR SRDYSAMIKH LRTHNGASPY QCTICTEYCP SLSSMQKHMK GHKPEEIPPD WRIEKTYLYL CYV //