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Protein

Zinc finger and BTB domain-containing protein 7A

Gene

Zbtb7a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Transcription factor that represses the transcription of a wide range of genes involved in cell proliferation and differentiation (PubMed:15337766, PubMed:15662416, PubMed:17495164, PubMed:26816381, PubMed:29813070). Directly and specifically binds to the consensus sequence 5'-[GA][CA]GACCCCCCCCC-3' and represses transcription both by regulating the organization of chromatin and through the direct recruitment of transcription factors to gene regulatory regions (PubMed:15337766, PubMed:15662416, PubMed:26816381, PubMed:29813070). Negatively regulates SMAD4 transcriptional activity in the TGF-beta signaling pathway through these two mechanisms (By similarity). That is, recruits the chromatin regulator HDAC1 to the SMAD4-DNA complex and in parallel prevents the recruitment of the transcriptional activators CREBBP and EP300 (By similarity). Collaborates with transcription factors like RELA to modify the accessibility of gene transcription regulatory regions to secondary transcription factors (PubMed:29813070). Also directly interacts with transcription factors like SP1 to prevent their binding to DNA (By similarity). Functions as an androgen receptor/AR transcriptional corepressor by recruiting NCOR1 and NCOR2 to the androgen response elements/ARE on target genes (By similarity). Thereby, negatively regulates androgen receptor signaling and androgen-induced cell proliferation (By similarity). Involved in the switch between fetal and adult globin expression during erythroid cells maturation (PubMed:26816381). Through its interaction with the NuRD complex regulates chromatin at the fetal globin genes to repress their transcription (PubMed:26816381). Specifically represses the transcription of the tumor suppressor ARF isoform from the CDKN2A gene (PubMed:15662416). Efficiently abrogates E2F1-dependent CDKN2A transactivation (PubMed:15662416). Regulates chondrogenesis through the transcriptional repression of specific genes via a mechanism that also requires histone deacetylation (PubMed:15337766). Regulates cell proliferation through the transcriptional regulation of genes involved in glycolysis (By similarity). Involved in adipogenesis through the regulation of genes involved in adipocyte differentiation (By similarity). Plays a key role in the differentiation of lymphoid progenitors into B and T lineages (PubMed:17495164). Promotes differentiation towards the B lineage by inhibiting the T-cell instructive Notch signaling pathway through the specific transcriptional repression of Notch downstream target genes (PubMed:17495164). Also regulates osteoclast differentiation (By similarity). May also play a role, independently of its transcriptional activity, in double-strand break repair via classical non-homologous end joining/cNHEJ (PubMed:26446488). Recruited to double-strand break sites on damage DNA, interacts with the DNA-dependent protein kinase complex and directly regulates its stability and activity in DNA repair (PubMed:26446488). May also modulate the splicing activity of KHDRBS1 toward BCL2L1 in a mechanism which is histone deacetylase-dependent and thereby negatively regulates the pro-apoptotic effect of KHDRBS1 (By similarity).By similarity6 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri376 – 398C2H2-type 1PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri404 – 426C2H2-type 2PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri432 – 454C2H2-type 3PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri460 – 484C2H2-type 4; atypicalPROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, DNA-binding, Repressor
Biological processDifferentiation, DNA damage, DNA repair, Transcription, Transcription regulation
LigandMetal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Zinc finger and BTB domain-containing protein 7ACurated
Alternative name(s):
Leukemia/lymphoma-related factor1 Publication
POZ and Krueppel erythroid myeloid ontogenic factor1 Publication
Short name:
POK erythroid myeloid ontogenic factor1 Publication
Short name:
Pokemon1 Publication
Gene namesi
Name:Zbtb7aImported
Synonyms:Lrf1 Publication, Zbtb7
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1335091 Zbtb7a

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

Death around 16.5 dpc because of severe anemia with a profound block in early B-cell development (PubMed:17495164). Conditional knockout in erythroid cells, leads to the expression of fetal globin in peripheral blood of adult mice and inefficient erythroid terminal differentiation (PubMed:26816381).2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000477161 – 569Zinc finger and BTB domain-containing protein 7AAdd BLAST569

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei331PhosphoserineCombined sources1
Modified residuei335PhosphoserineBy similarity1
Cross-linki430Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki527Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei537PhosphoserineCombined sources1

Post-translational modificationi

Sumoylated. Undergoes sumoylation with SUMO1 that may regulate its transcriptional activity.By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO88939
MaxQBiO88939
PaxDbiO88939
PeptideAtlasiO88939
PRIDEiO88939

PTM databases

iPTMnetiO88939
PhosphoSitePlusiO88939

Expressioni

Tissue specificityi

Widely expressed (PubMed:9927193). In normal thymus, expressed in medullary epithelial cells and Hassle's corpuscles (at protein level) (PubMed:15662416). In the spleen, mainly expressed in the white pulp germinal centers (at protein level) (PubMed:15662416). Up-regulated in thymic lymphomas (PubMed:15662416).2 Publications

Developmental stagei

Expressed at E9.5-E10.0 day in limb buds, pharyngeal arches, tail bud, placenta and neural tube (PubMed:9927193). Up-regulated during adipocyte differentiation (PubMed:14701838).2 Publications

Gene expression databases

BgeeiENSMUSG00000035011 Expressed in 276 organ(s), highest expression level in ascending aorta
CleanExiMM_ZBTB7A
ExpressionAtlasiO88939 baseline and differential
GenevisibleiO88939 MM

Interactioni

Subunit structurei

Homodimer (By similarity). Interacts with BCL6 (PubMed:9927193). Interacts with RELA; involved in the control by RELA of the accessibility of target gene promoters (PubMed:29813070). Interacts with AR (via NR LBD domain); the interaction is direct and androgen-dependent (By similarity). Interacts with NCOR1 (By similarity). Interacts with NCOR2 (By similarity). Interacts with SMAD4; the interaction is direct and stimulated by TGFB1 (By similarity). Interacts with HDAC1 (By similarity). Interacts with SP1; ZBTB7A prevents the binding to GC-rich motifs in promoters and represses the transcriptional activity of SP1 (By similarity). Interacts with the DNA-dependent protein kinase complex/DNA-PKc (PubMed:26446488). Interacts with KHDRBS1; negatively regulates KHDRBS1 splicing activity (By similarity).By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Hdac1O091063EBI-595063,EBI-301912

GO - Molecular functioni

Protein-protein interaction databases

BioGridi201199, 8 interactors
DIPiDIP-33318N
IntActiO88939, 10 interactors
MINTiO88939
STRINGi10090.ENSMUSP00000047333

Structurei

3D structure databases

ProteinModelPortaliO88939
SMRiO88939
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini34 – 101BTBPROSITE-ProRule annotationAdd BLAST68

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni275 – 569Mediates interaction with KHDRBS1By similarityAdd BLAST295
Regioni343 – 569Mediates interaction with RELA1 PublicationAdd BLAST227
Regioni371 – 569Mediates interaction with SMAD4By similarityAdd BLAST199

Domaini

The BTB domain mediates the interaction with the androgen receptor/AR and HDAC1. Also mediates the interaction with SP1.By similarity

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri376 – 398C2H2-type 1PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri404 – 426C2H2-type 2PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri432 – 454C2H2-type 3PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri460 – 484C2H2-type 4; atypicalPROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1721 Eukaryota
COG5048 LUCA
GeneTreeiENSGT00920000148950
HOGENOMiHOG000082521
HOVERGENiHBG106747
InParanoidiO88939
KOiK10494
OMAiIDQRNHL
OrthoDBiEOG091G057O
PhylomeDBiO88939
TreeFamiTF331824

Family and domain databases

InterProiView protein in InterPro
IPR000210 BTB/POZ_dom
IPR011333 SKP1/BTB/POZ_sf
IPR036236 Znf_C2H2_sf
IPR013087 Znf_C2H2_type
PfamiView protein in Pfam
PF00651 BTB, 1 hit
PF00096 zf-C2H2, 2 hits
SMARTiView protein in SMART
SM00225 BTB, 1 hit
SM00355 ZnF_C2H2, 4 hits
SUPFAMiSSF54695 SSF54695, 1 hit
SSF57667 SSF57667, 2 hits
PROSITEiView protein in PROSITE
PS50097 BTB, 1 hit
PS00028 ZINC_FINGER_C2H2_1, 3 hits
PS50157 ZINC_FINGER_C2H2_2, 4 hits

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O88939-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MAGGVDGPIG IPFPDHSSDI LSGLNEQRTQ GLLCDVVILV EGREFPTHRS
60 70 80 90 100
VLAACSQYFK KLFTSGAVVD QQNVYEIDFV SAEALTALMD FAYTATLTVS
110 120 130 140 150
TANVGDILSA ARLLEIPAVS HVCADLLERQ ILAADDVGDA SQPDGAGPTD
160 170 180 190 200
QRNLLRAKEY LEFFRSNPMN SLPPTAFPWS GFGAPDDDLD ATKEAVAAAV
210 220 230 240 250
AAVAAGDCNG LDFYGPGPPA DRPPAGDGDE GDSTPGLWPE RDEDAPPGGL
260 270 280 290 300
FPPPTAPPAT TQNGHYGRAG AGTGEEEAAA LSEAAPEPGD SPGFLSGAAE
310 320 330 340 350
GEDGDAADVD GLAASTLLQQ MMSSVGRAGD SDEESRTDDK GVMDYYLKYF
360 370 380 390 400
SGAHEGDVYP AWSQKGEKKI RAKAFQKCPI CEKVIQGAGK LPRHIRTHTG
410 420 430 440 450
EKPYECNICK VRFTRQDKLK VHMRKHTGEK PYLCQQCGAA FAHNYDLKNH
460 470 480 490 500
MRVHTGLRPY QCDSCCKTFV RSDHLHRHLK KDGCNGVPSR RGRKPRVRGV
510 520 530 540 550
PPDVPAGAGA PPGLPDAPRN GQEKHFKDEE EDEEEASPDG SGRLNVAGSG
560
GDDGAGGPAV ATAEGNFAT
Length:569
Mass (Da):60,281
Last modified:September 2, 2008 - v2
Checksum:iB4F79FF89A88CBD5
GO
Isoform 2 (identifier: O88939-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     532-535: Missing.

Show »
Length:565
Mass (Da):59,778
Checksum:iB59CCA89D740DC70
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D3Z4C3D3Z4C3_MOUSE
Zinc finger and BTB domain-containi...
Zbtb7a
415Annotation score:
D3YVF8D3YVF8_MOUSE
Zinc finger and BTB domain-containi...
Zbtb7a
174Annotation score:
D3YZI8D3YZI8_MOUSE
Zinc finger and BTB domain-containi...
Zbtb7a
44Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti433L → M in BAB26897 (PubMed:16141072).Curated1
Sequence conflicti548G → D in BAE32917 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_035026532 – 535Missing in isoform 2. 1 Publication4

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF086830 mRNA Translation: AAC35367.1
AK010379 mRNA Translation: BAB26897.1
AK154907 mRNA Translation: BAE32917.1
CH466553 Genomic DNA Translation: EDL31455.1
BC057204 mRNA Translation: AAH57204.1
BC138524 mRNA Translation: AAI38525.1
BC145311 mRNA Translation: AAI45312.1
CCDSiCCDS35991.1 [O88939-1]
RefSeqiNP_034861.3, NM_010731.3 [O88939-1]
XP_006513342.2, XM_006513279.2 [O88939-1]
XP_006513343.2, XM_006513280.3 [O88939-1]
XP_006513345.1, XM_006513282.2 [O88939-1]
UniGeneiMm.20920
Mm.486315

Genome annotation databases

EnsembliENSMUST00000048128; ENSMUSP00000047333; ENSMUSG00000035011 [O88939-1]
ENSMUST00000117956; ENSMUSP00000113428; ENSMUSG00000035011 [O88939-1]
ENSMUST00000119606; ENSMUSP00000113612; ENSMUSG00000035011 [O88939-1]
GeneIDi16969
KEGGimmu:16969
UCSCiuc007gfz.1 mouse [O88939-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF086830 mRNA Translation: AAC35367.1
AK010379 mRNA Translation: BAB26897.1
AK154907 mRNA Translation: BAE32917.1
CH466553 Genomic DNA Translation: EDL31455.1
BC057204 mRNA Translation: AAH57204.1
BC138524 mRNA Translation: AAI38525.1
BC145311 mRNA Translation: AAI45312.1
CCDSiCCDS35991.1 [O88939-1]
RefSeqiNP_034861.3, NM_010731.3 [O88939-1]
XP_006513342.2, XM_006513279.2 [O88939-1]
XP_006513343.2, XM_006513280.3 [O88939-1]
XP_006513345.1, XM_006513282.2 [O88939-1]
UniGeneiMm.20920
Mm.486315

3D structure databases

ProteinModelPortaliO88939
SMRiO88939
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201199, 8 interactors
DIPiDIP-33318N
IntActiO88939, 10 interactors
MINTiO88939
STRINGi10090.ENSMUSP00000047333

PTM databases

iPTMnetiO88939
PhosphoSitePlusiO88939

Proteomic databases

EPDiO88939
MaxQBiO88939
PaxDbiO88939
PeptideAtlasiO88939
PRIDEiO88939

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000048128; ENSMUSP00000047333; ENSMUSG00000035011 [O88939-1]
ENSMUST00000117956; ENSMUSP00000113428; ENSMUSG00000035011 [O88939-1]
ENSMUST00000119606; ENSMUSP00000113612; ENSMUSG00000035011 [O88939-1]
GeneIDi16969
KEGGimmu:16969
UCSCiuc007gfz.1 mouse [O88939-1]

Organism-specific databases

CTDi51341
MGIiMGI:1335091 Zbtb7a

Phylogenomic databases

eggNOGiKOG1721 Eukaryota
COG5048 LUCA
GeneTreeiENSGT00920000148950
HOGENOMiHOG000082521
HOVERGENiHBG106747
InParanoidiO88939
KOiK10494
OMAiIDQRNHL
OrthoDBiEOG091G057O
PhylomeDBiO88939
TreeFamiTF331824

Miscellaneous databases

ChiTaRSiZbtb7a mouse
PROiPR:O88939
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000035011 Expressed in 276 organ(s), highest expression level in ascending aorta
CleanExiMM_ZBTB7A
ExpressionAtlasiO88939 baseline and differential
GenevisibleiO88939 MM

Family and domain databases

InterProiView protein in InterPro
IPR000210 BTB/POZ_dom
IPR011333 SKP1/BTB/POZ_sf
IPR036236 Znf_C2H2_sf
IPR013087 Znf_C2H2_type
PfamiView protein in Pfam
PF00651 BTB, 1 hit
PF00096 zf-C2H2, 2 hits
SMARTiView protein in SMART
SM00225 BTB, 1 hit
SM00355 ZnF_C2H2, 4 hits
SUPFAMiSSF54695 SSF54695, 1 hit
SSF57667 SSF57667, 2 hits
PROSITEiView protein in PROSITE
PS50097 BTB, 1 hit
PS00028 ZINC_FINGER_C2H2_1, 3 hits
PS50157 ZINC_FINGER_C2H2_2, 4 hits
ProtoNetiSearch...

Entry informationi

Entry nameiZBT7A_MOUSE
AccessioniPrimary (citable) accession number: O88939
Secondary accession number(s): B2RRP7
, B7ZNL6, Q3U372, Q9CRJ0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: September 2, 2008
Last modified: October 10, 2018
This is version 168 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health

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