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Protein

Zinc finger and BTB domain-containing protein 7B

Gene

Zbtb7b

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

Functioni

Transcription regulator that acts as a key regulator of lineage commitment of immature T-cell precursors. Exerts distinct biological functions in the mammary epithelial cells and T cells in a tissue-specific manner (PubMed:15729333, PubMed:29420538). Necessary and sufficient for commitment of CD4 lineage, while its absence causes CD8 commitment. Development of immature T-cell precursors (thymocytes) to either the CD4 helper or CD8 killer T-cell lineages correlates precisely with their T-cell receptor specificity for major histocompatibility complex class II or class I molecules, respectively. Cross-antagonism between ZBTB7B and CBF complexes are determinative to CD4 versus CD8 cell fate decision (PubMed:15729333, PubMed:24880459, PubMed:18258917, PubMed:23481257). Suppresses RUNX3 expression and imposes CD4+ lineage fate by inducing the SOCS suppressors of cytokine signaling. induces, as a transcriptional activator, SOCS genes expression which represses RUNX3 expression and promotes the CD4+ lineage fate (PubMed:24880459). During CD4 lineage commitment, associates with multiple sites at the CD8 locus, acting as a negative regulator of the CD8 promoter and enhancers by epigenetic silencing through the recruitment of class II histone deacetylases, such as HDAC4 and HDAC5, to these loci (PubMed:22730529). Regulates the development of IL17-producing CD1d-restricted naural killer (NK) T cells (PubMed:23105140). Also functions as an important metabolic regulator in the lactating mammary glands. Critical feed-forward regulator of insulin signaling in mammary gland lactation, directly regulates expression of insulin receptor substrate-1 (IRS-1) and insulin-induced Akt-mTOR-SREBP signaling (PubMed:29420538). Transcriptional repressor of the collagen COL1A1 and COL1A2 genes. May also function as a repressor of fibronectin and possibly other extracellular matrix genes (PubMed:7937772). Potent driver of brown fat development, thermogenesis and cold-induced beige fat formation (PubMed:28784777). Recruits the brown fat lncRNA 1 (Blnc1):HNRNPU ribonucleoprotein complex to activate thermogenic gene expression in brown and beige adipocytes (PubMed:28784777).9 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri350 – 372C2H2-type 1PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri378 – 400C2H2-type 2PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri406 – 428C2H2-type 3PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri434 – 458C2H2-type 4; atypicalPROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Names & Taxonomyi

Protein namesi
Recommended name:
Zinc finger and BTB domain-containing protein 7BCurated
Alternative name(s):
Krueppel-related zinc finger protein cKrox
Short name:
c-Krox
T-helper-inducing POZ/Krueppel-like factor
Zinc finger protein 67
Short name:
Zfp-67
Zinc finger protein Th-POK1 Publication
Gene namesi
Name:Zbtb7bImported
Synonyms:Thpok1 Publication, Zfp67
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:102755 Zbtb7b

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

Involvement in diseasei

Defects in Zbtb7b are the cause of helper deficient disease (HD) or helpless disease. HD and helpless mice are distinguished by the virtual absence of peripheral T-cells of the CD4(+)CD8(-) major histocompatibility complex (MHC) class II-restricted T-helper subset due to a specific block in thymic development. The developmental defect is selective for CD4(+)CD8(-) cells; the maturation of CD4(-)CD8(+) and gamma delta T-cells is normal indicating that lineage commitment is specifically perturbed without affecting positive selection. In helpless disease, NKT cells are hyperproliferative, most lack CD4 and instead express CD8. The majority of NKT cells in the thymus produce IL17 with high frequency while very few produce IFNG or other cytokines (PubMed:23105140).4 Publications

Disruption phenotypei

Mutant females are unable to efficiently secrete milk lipid and to nurse the offspring. They show normal mammary gland morphogenesis in puberty and alveologenesis in pregnancy, but are defective in triggering the onset of lactation upon parturition with large cellular lipid droplets retained within alveolar epithelial cells (PubMed:29420538). Mice are more sensitive to cold temperature, with impaired cold-induced transcriptional remodeling in brown fat and diminished browning of inguinal white fat (PubMed:28784777).2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi21L → S: Fails to repress CD8 expression. Abolishes interaction with HDAC4 and HDAC5. No effect on homodimerization and DNA binding. 1 Publication1
Mutagenesisi27 – 28QR → AL: Fails to repress CD8 expression. Abolishes interaction with HDAC4 and HDAC5. No effect on homodimerization and DNA binding. 1 Publication2
Mutagenesisi207K → R: No effect on actelytion levels. Slightly decreases acetylation levels; when associated with R-210. Slightly decreases acetylation levels; when associated with R-216. 1 Publication1
Mutagenesisi210K → R: Slightly decreases acetylation levels. No effect on protein stability. Slightly decreases acetylation levels; when associated with R-207. Slightly decreases acetylation levels and increases protein stability; when associated with R-216. Increases protein stability; when associated with R-339. Decreases acetylation levels; when associated with R-216 and R-343. Abolishes acetylation levels and ubiquitination and highly increases protein stability; when associated with R-216 and R-339. 1 Publication1
Mutagenesisi216K → R: Slightly decreases acetylation levels. No effect on protein stability. Slightly decreases acetylation levels; when associated with R-207. Slightly decreases acetylation levels and increases protein stability; when associated with R-210. Increases protein stability; when associated with R-339. Decreases acetylation levels; when associated with R-210 and R-343. Abolishes acetylation levels and ubiquitination and highly increases protein stability; when associated with R-210 and R-339. 1 Publication1
Mutagenesisi339K → R: Slightly decreases acetylation levels. Slightly increases protein stability. Slightly decreases acetylation levels; when associated with R-343. Increases protein stability; when associated with R-210 or R-216. Abolishes acetylation levels and ubiquitination and highly increases protein stability; when associated with R-210 and R-216. 1 Publication1
Mutagenesisi343K → R: No effect on acetylation levels. Slightly decreases acetylation levels; when associated with R-339. Decreases acetylation levels; when associated with R-210 and R-216. 1 Publication1

Keywords - Diseasei

Disease mutation

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000477201 – 544Zinc finger and BTB domain-containing protein 7BAdd BLAST544

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei150PhosphoserineBy similarity1
Modified residuei210N6-acetyllysine; by EP300; alternate1 Publication1
Cross-linki210Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate1 Publication
Modified residuei216N6-acetyllysine; by EP300; alternate1 Publication1
Cross-linki216Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate1 Publication
Modified residuei339N6-acetyllysine; by EP300; alternate1 Publication1
Cross-linki339Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate1 Publication
Modified residuei373PhosphothreonineBy similarity1

Post-translational modificationi

Acetylated directly and specifically by EP300. EP300-mediated acetylation of Lys-210, Lys-216 and Lys-339 stabilizes the protein by antagonizing ubiquitin conjugation.1 Publication
Ubiquitinated, leading to proteasomal degradation. Competes with acetylation on Lys-210, Lys-216 and Lys-339.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ64321
PaxDbiQ64321
PRIDEiQ64321

PTM databases

iPTMnetiQ64321
PhosphoSitePlusiQ64321

Expressioni

Tissue specificityi

Widely expressed, with a higher level in skin. Expressed in thymus. Restricted to CD4 cells (mature single positive CD4+ and intermediate CD4+CD8+ cells). Expressed in the luminal epithelial cells in the mammary glands where is up-regulated at late pregnancy and lactation (PubMed:29420538). Expression is enriched in brown fat (PubMed:28784777).4 Publications

Developmental stagei

Expressed, beginning at 9.5 days of gestation and at 10.5 days in regions destined to become skin. In adult animals, expression is predominantly in skin (PubMed:7937772). Expression is significantly increased during brown adipocyte differentiation (PubMed:28784777).2 Publications

Inductioni

Expression in mammary glands is induced by insulin.1 Publication

Gene expression databases

BgeeiENSMUSG00000028042 Expressed in 203 organ(s), highest expression level in pyloric antrum
CleanExiMM_ZBTB7B
ExpressionAtlasiQ64321 baseline and differential
GenevisibleiQ64321 MM

Interactioni

Subunit structurei

Homodimerizes (PubMed:22730529). Interacts with NCL, NEDD4 and YBX1 (PubMed:28784777). Interacts with HNRNPU (via RNA-binding RGG-box region); the interaction facilitates the recruitment of long non-coding RNA Blnc1 by ZBTB7B (PubMed:28784777). Interacts with HDAC4 and HDAC5; the interaction allows the recruitment of HDAC4 and HDAC5 on CD8 loci for deacetylation and possible inhibition of CD8 genes expression (PubMed:22730529).2 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi204677, 1 interactor
IntActiQ64321, 3 interactors
STRINGi10090.ENSMUSP00000029677

Structurei

3D structure databases

ProteinModelPortaliQ64321
SMRiQ64321
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini34 – 115BTBPROSITE-ProRule annotationAdd BLAST82

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni348 – 404Required for interaction with and acetylation by EP3001 PublicationAdd BLAST57

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi185 – 200Pro-richAdd BLAST16

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri350 – 372C2H2-type 1PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri378 – 400C2H2-type 2PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri406 – 428C2H2-type 3PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri434 – 458C2H2-type 4; atypicalPROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1721 Eukaryota
COG5048 LUCA
GeneTreeiENSGT00930000150939
HOGENOMiHOG000082521
HOVERGENiHBG059461
InParanoidiQ64321
KOiK10494
OMAiSRGARYP
OrthoDBiEOG091G08VI
PhylomeDBiQ64321
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

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All

Q64321-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MGSPEDDLIG IPFPDHSSEL LSCLNEQRQL GHLCDLTIRT QGLEYRTHRA
60 70 80 90 100
VLAACSHYFK KLFTEGGGGT VMGTGGGGTA SGGAGAGVCE LDFVGPEALG
110 120 130 140 150
ALLEFAYTAT LTTSSANMPA VLQAARLLEI PCVIAACMEI LQGSGLEAPS
160 170 180 190 200
PDEDDCERAR QYLEAFATAT TTASTSGMPN GEDSPPQVPL LPPPPPPPRP
210 220 230 240 250
VARRSRKPRK AFLQTKGARA NHLVPEAPTV LTHPLTYEEE EMVGRLGNSG
260 270 280 290 300
GSGLGDSYSP PTGAASPAEG PLNYEVFEGE EEEEEMAYPP GYGLAQSNEP
310 320 330 340 350
SLSPEELGSD EDPIDPDLMA YLSSLHQDAL TPGLDGQDKL VRKRRSQMPQ
360 370 380 390 400
ECPVCHKIIH GAGKLPRHMR THTGEKPFAC EVCGVRFTRN DKLKIHMRKH
410 420 430 440 450
TGERPYSCPH CPARFLHSYD LKNHMHLHTG DRPYECHLCH KAFAKEDHLQ
460 470 480 490 500
RHLKGQNCLE VRTRRRRKDD VAAPHYPPPS TTTSSPAGLD LSNGHLDTFH
510 520 530 540
LSLARFWEQS ATTGPPVTTQ GPPEEEEEEG TPTTPQAEGA MESS
Length:544
Mass (Da):58,918
Last modified:August 16, 2004 - v2
Checksum:i5A43F10AE2970709
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D3YZR6D3YZR6_MOUSE
Zinc finger and BTB domain-containi...
Zbtb7b
124Annotation score:
D3Z0B5D3Z0B5_MOUSE
Zinc finger and BTB domain-containi...
Zbtb7b
112Annotation score:
D3Z2X8D3Z2X8_MOUSE
Zinc finger and BTB domain-containi...
Zbtb7b
102Annotation score:
D3YXC8D3YXC8_MOUSE
Zinc finger and BTB domain-containi...
Zbtb7b
29Annotation score:

Sequence cautioni

The sequence AAA61956 differs from that shown. Chimeric cDNA.Curated
The sequence AAA61956 differs from that shown. Reason: Frameshift at positions 96, 328 and 336.Curated
The sequence CAA85307 differs from that shown. Chimeric cDNA.Curated
The sequence CAA85307 differs from that shown. Reason: Frameshift at positions 96, 328 and 336.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti268A → T in AAA61956 (PubMed:7937772).Curated1
Sequence conflicti268A → T in CAA85307 (PubMed:7937772).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti102L → R in helpless. 1 Publication1
Natural varianti389R → G in HD; disrupts sequence-specific DNA-binding; no effect on homodimerization or interaction with HDAC4 and HDAC5. 3 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC046533 mRNA Translation: AAH46533.1
L35307 mRNA Translation: AAA61956.1 Sequence problems.
Z36549 mRNA Translation: CAA85307.1 Sequence problems.
CCDSiCCDS17504.1
PIRiI49603
RefSeqiNP_033591.2, NM_009565.4
XP_006501376.1, XM_006501313.2
XP_006501377.1, XM_006501314.2
XP_006501379.1, XM_006501316.2
XP_006501380.1, XM_006501317.3
XP_006501381.1, XM_006501318.3
XP_006501382.1, XM_006501319.3
UniGeneiMm.262184

Genome annotation databases

EnsembliENSMUST00000029677; ENSMUSP00000029677; ENSMUSG00000028042
ENSMUST00000107432; ENSMUSP00000103055; ENSMUSG00000028042
ENSMUST00000107433; ENSMUSP00000103056; ENSMUSG00000028042
ENSMUST00000107435; ENSMUSP00000103058; ENSMUSG00000028042
GeneIDi22724
KEGGimmu:22724
UCSCiuc008pza.1 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC046533 mRNA Translation: AAH46533.1
L35307 mRNA Translation: AAA61956.1 Sequence problems.
Z36549 mRNA Translation: CAA85307.1 Sequence problems.
CCDSiCCDS17504.1
PIRiI49603
RefSeqiNP_033591.2, NM_009565.4
XP_006501376.1, XM_006501313.2
XP_006501377.1, XM_006501314.2
XP_006501379.1, XM_006501316.2
XP_006501380.1, XM_006501317.3
XP_006501381.1, XM_006501318.3
XP_006501382.1, XM_006501319.3
UniGeneiMm.262184

3D structure databases

ProteinModelPortaliQ64321
SMRiQ64321
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204677, 1 interactor
IntActiQ64321, 3 interactors
STRINGi10090.ENSMUSP00000029677

PTM databases

iPTMnetiQ64321
PhosphoSitePlusiQ64321

Proteomic databases

MaxQBiQ64321
PaxDbiQ64321
PRIDEiQ64321

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000029677; ENSMUSP00000029677; ENSMUSG00000028042
ENSMUST00000107432; ENSMUSP00000103055; ENSMUSG00000028042
ENSMUST00000107433; ENSMUSP00000103056; ENSMUSG00000028042
ENSMUST00000107435; ENSMUSP00000103058; ENSMUSG00000028042
GeneIDi22724
KEGGimmu:22724
UCSCiuc008pza.1 mouse

Organism-specific databases

CTDi51043
MGIiMGI:102755 Zbtb7b

Phylogenomic databases

eggNOGiKOG1721 Eukaryota
COG5048 LUCA
GeneTreeiENSGT00930000150939
HOGENOMiHOG000082521
HOVERGENiHBG059461
InParanoidiQ64321
KOiK10494
OMAiSRGARYP
OrthoDBiEOG091G08VI
PhylomeDBiQ64321
TreeFamiTF331824

Miscellaneous databases

ChiTaRSiZbtb7b mouse
PROiPR:Q64321
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000028042 Expressed in 203 organ(s), highest expression level in pyloric antrum
CleanExiMM_ZBTB7B
ExpressionAtlasiQ64321 baseline and differential
GenevisibleiQ64321 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 nameiZBT7B_MOUSE
AccessioniPrimary (citable) accession number: Q64321
Secondary accession number(s): Q80VV5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: August 16, 2004
Last modified: November 7, 2018
This is version 156 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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