ZBT7A_RAT
ID ZBT7A_RAT Reviewed; 569 AA.
AC Q9QZ48;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Zinc finger and BTB domain-containing protein 7A {ECO:0000305};
DE AltName: Full=Leukemia/lymphoma-related factor;
DE AltName: Full=Osteoclast-derived zinc finger protein {ECO:0000303|PubMed:10477728};
GN Name=Zbtb7a {ECO:0000312|RGD:620946};
GN Synonyms=Lrf, Oczf {ECO:0000303|PubMed:10477728}, Zbtb7;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC STRAIN=Sprague-Dawley;
RX PubMed=10477728;
RA Kukita A., Kukita T., Ouchida M., Maeda H., Yatsuki H., Kohashi O.;
RT "Osteoclast-derived zinc finger (OCZF) protein with POZ domain, a possible
RT transcriptional repressor, is involved in osteoclastogenesis.";
RL Blood 94:1987-1997(1999).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-331, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Transcription factor that represses the transcription of a
CC wide range of genes involved in cell proliferation and differentiation
CC (By similarity) (PubMed:10477728). Directly and specifically binds to
CC the consensus sequence 5'-[GA][CA]GACCCCCCCCC-3' and represses
CC transcription both by regulating the organization of chromatin and
CC through the direct recruitment of transcription factors to gene
CC regulatory regions (By similarity) (PubMed:10477728). Negatively
CC regulates SMAD4 transcriptional activity in the TGF-beta signaling
CC pathway through these two mechanisms. That is, recruits the chromatin
CC regulator HDAC1 to the SMAD4-DNA complex and in parallel prevents the
CC recruitment of the transcriptional activators CREBBP and EP300 (By
CC similarity). Collaborates with transcription factors like RELA to
CC modify the accessibility of gene transcription regulatory regions to
CC secondary transcription factors (By similarity). Also directly
CC interacts with transcription factors like SP1 to prevent their binding
CC to DNA. Functions as an androgen receptor/AR transcriptional
CC corepressor by recruiting NCOR1 and NCOR2 to the androgen response
CC elements/ARE on target genes. Thereby, negatively regulates androgen
CC receptor signaling and androgen-induced cell proliferation. Involved in
CC the switch between fetal and adult globin expression during erythroid
CC cells maturation. Through its interaction with the NuRD complex
CC regulates chromatin at the fetal globin genes to repress their
CC transcription (By similarity). Specifically represses the transcription
CC of the tumor suppressor ARF isoform from the CDKN2A gene. Efficiently
CC abrogates E2F1-dependent CDKN2A transactivation. Regulates
CC chondrogenesis through the transcriptional repression of specific genes
CC via a mechanism that also requires histone deacetylation (By
CC similarity). Regulates cell proliferation through the transcriptional
CC regulation of genes involved in glycolysis. Involved in adipogenesis
CC through the regulation of genes involved in adipocyte differentiation
CC (By similarity). Plays a key role in the differentiation of lymphoid
CC progenitors into B and T lineages. Promotes differentiation towards the
CC B lineage by inhibiting the T-cell instructive Notch signaling pathway
CC through the specific transcriptional repression of Notch downstream
CC target genes (By similarity). Also regulates osteoclast differentiation
CC (PubMed:10477728). May also play a role, independently of its
CC transcriptional activity, in double-strand break repair via classical
CC non-homologous end joining/cNHEJ. Recruited to double-strand break
CC sites on damage DNA, interacts with the DNA-dependent protein kinase
CC complex and directly regulates its stability and activity in DNA repair
CC (By similarity). May also modulate the splicing activity of KHDRBS1
CC toward BCL2L1 in a mechanism which is histone deacetylase-dependent and
CC thereby negatively regulates the pro-apoptotic effect of KHDRBS1 (By
CC similarity). {ECO:0000250|UniProtKB:O88939,
CC ECO:0000250|UniProtKB:O95365, ECO:0000269|PubMed:10477728}.
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with BCL6 (By
CC similarity). Interacts with RELA; involved in the control by RELA of
CC the accessibility of target gene promoters (By similarity). Interacts
CC with AR (via NR LBD domain); the interaction is direct and androgen-
CC dependent (By similarity). Interacts with NCOR1 (By similarity).
CC Interacts with NCOR2 (By similarity). Interacts with SMAD4; the
CC interaction is direct and stimulated by TGFB1 (By similarity).
CC Interacts with HDAC1 (By similarity). Interacts with SP1; ZBTB7A
CC prevents the binding to GC-rich motifs in promoters and represses the
CC transcriptional activity of SP1 (By similarity). Interacts with the
CC DNA-dependent protein kinase complex/DNA-PKc (By similarity). Interacts
CC with KHDRBS1; negatively regulates KHDRBS1 splicing activity (By
CC similarity). {ECO:0000250|UniProtKB:O88939,
CC ECO:0000250|UniProtKB:O95365}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10477728}.
CC Note=Recruited to double-strand break sites of damaged DNA.
CC {ECO:0000250|UniProtKB:O88939}.
CC -!- TISSUE SPECIFICITY: Expressed in osteoclasts and kidney cells.
CC {ECO:0000269|PubMed:10477728}.
CC -!- DOMAIN: The BTB domain mediates the interaction with the androgen
CC receptor/AR and HDAC1. Also mediates the interaction with SP1.
CC {ECO:0000250|UniProtKB:O95365}.
CC -!- PTM: Sumoylated. Undergoes sumoylation with SUMO1 that may regulate its
CC transcriptional activity. {ECO:0000250|UniProtKB:O95365}.
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DR EMBL; D88450; BAA86393.1; -; mRNA.
DR RefSeq; NP_446454.1; NM_054002.1.
DR AlphaFoldDB; Q9QZ48; -.
DR SMR; Q9QZ48; -.
DR STRING; 10116.ENSRNOP00000027323; -.
DR iPTMnet; Q9QZ48; -.
DR PhosphoSitePlus; Q9QZ48; -.
DR PaxDb; Q9QZ48; -.
DR PRIDE; Q9QZ48; -.
DR GeneID; 117107; -.
DR KEGG; rno:117107; -.
DR UCSC; RGD:620946; rat.
DR CTD; 51341; -.
DR RGD; 620946; Zbtb7a.
DR eggNOG; KOG1721; Eukaryota.
DR InParanoid; Q9QZ48; -.
DR OrthoDB; 1318335at2759; -.
DR PhylomeDB; Q9QZ48; -.
DR PRO; PR:Q9QZ48; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0070418; C:DNA-dependent protein kinase complex; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:RGD.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0035035; F:histone acetyltransferase binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0050681; F:nuclear androgen receptor binding; ISS:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISO:RGD.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:RGD.
DR GO; GO:0046332; F:SMAD binding; ISS:UniProtKB.
DR GO; GO:0001222; F:transcription corepressor binding; ISS:UniProtKB.
DR GO; GO:0030183; P:B cell differentiation; ISS:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; ISO:RGD.
DR GO; GO:0006338; P:chromatin remodeling; ISS:UniProtKB.
DR GO; GO:0097680; P:double-strand break repair via classical nonhomologous end joining; ISS:UniProtKB.
DR GO; GO:0043249; P:erythrocyte maturation; ISS:UniProtKB.
DR GO; GO:0045444; P:fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0060766; P:negative regulation of androgen receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; 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:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0034504; P:protein localization to nucleus; ISO:RGD.
DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; ISS:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0051090; P:regulation of DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0006110; P:regulation of glycolytic process; ISS:UniProtKB.
DR GO; GO:0045670; P:regulation of osteoclast differentiation; IDA:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:2000677; P:regulation of transcription regulatory region DNA binding; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:RGD.
DR GO; GO:0006351; P:transcription, DNA-templated; ISO:RGD.
DR Gene3D; 3.30.710.10; -; 1.
DR InterPro; IPR000210; BTB/POZ_dom.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR Pfam; PF00651; BTB; 1.
DR Pfam; PF00096; zf-C2H2; 2.
DR SMART; SM00225; BTB; 1.
DR SMART; SM00355; ZnF_C2H2; 4.
DR SUPFAM; SSF54695; SSF54695; 1.
DR SUPFAM; SSF57667; SSF57667; 2.
DR PROSITE; PS50097; BTB; 1.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 3.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 4.
PE 1: Evidence at protein level;
KW Developmental protein; Differentiation; DNA-binding; Isopeptide bond;
KW Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Repressor; Transcription; Transcription regulation; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1..569
FT /note="Zinc finger and BTB domain-containing protein 7A"
FT /id="PRO_0000047717"
FT DOMAIN 34..101
FT /note="BTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT ZN_FING 376..398
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 404..426
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 432..454
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 460..484
FT /note="C2H2-type 4; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 214..306
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 275..569
FT /note="Mediates interaction with KHDRBS1"
FT /evidence="ECO:0000250|UniProtKB:O95365"
FT REGION 343..569
FT /note="Mediates interaction with RELA"
FT /evidence="ECO:0000250|UniProtKB:O88939"
FT REGION 371..569
FT /note="Mediates interaction with SMAD4"
FT /evidence="ECO:0000250|UniProtKB:O95365"
FT REGION 480..569
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 331
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 335
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95365"
FT MOD_RES 537
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95365"
FT CROSSLNK 430
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O95365"
FT CROSSLNK 527
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O95365"
SQ SEQUENCE 569 AA; 60543 MW; C1114B303B0D0F0D CRC64;
MAGGVDGPIG IPFPDHSSDI LSGLNEQRTQ GLLCDVVILV EGREFPTHRS VLAACSQYFK
KLFTSGAVVD QQNVYEIDFV SAEALTALMD FAYTATLTVS TANVGDILSA ARLLEIPAVS
RVCTDLLERQ ILAADDVGDA GQPDGAGPTD QRNLLRAKEY LEFFRSNPMN SLPPTAFQWP
GFSAPDDDLD ATKEAVAAAV AAVAAGDCNG LDFYGPGPPA DRPPTGDGEE GDSTPGLWPE
RDEDAPPGGL FPPPTAPPAT TQNGHYGRAG ASTGEEEAVA LSEAAPEPGD SPGFLSGAAE
GEDGDAADVD GLAASTLLQQ MMSSVGRAGD SDEESRPDDK GVMDYYLKYF SGAHEGDVYP
AWSQKGEKKI RAKAFQKCPI CEKVIQGAGK LPRHIRTHTG EKPYECNICK VRFTRQDKLK
VHMRKHTGEK PYLCQQCGAA FAHNYDLKNH MRVHTGLRPY QCDSCCKTFV RSDHLHRHLK
KDGCNGVPSR RGRKPRVRGV PPDVPSGAGA PPGLPDAPRN GQEKHFKDEE DDEEEASLDG
LGRLNVAGSG GDDGAGGPTV AATEGNFAT
