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Protein

Zinc finger protein Gfi-1b

Gene

Gfi1b

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

Functioni

Essential proto-oncogenic transcriptional regulator necessary for development and differentiation of erythroid and megakaryocytic lineages. Component of a RCOR-GFI-KDM1A-HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development and controls hematopoietic differentiation. Transcriptional repressor or activator depending on both promoter and cell type context; represses promoter activity of SOCS1 and SOCS3 and thus, may regulate cytokine signaling pathways. Cooperates with GATA1 to repress target gene transcription, such as the apoptosis regulator BCL2L1; GFI1B silencing in leukemic cell lines markedly increase apoptosis rate. Inhibits down-regulation of MYC and MYB as well as the cyclin-dependent kinase inhibitor CDKN1A/P21WAF1 in IL6-treated myelomonocytic cells. Represses expression of GATA3 in T-cell lymphomas and inhibits GATA1-mediated transcription; as GATA1 also mediates erythroid GFI1B transcription, both GATA1 and GFI1B participate in a feedback regulatory pathway controlling the expression of GFI1B gene in erythroid cells. Suppresses GATA1-mediated stimulation of GFI1B promoter through protein interaction. Binds to gamma-satellite DNA and to its own promoter, auto-repressing its own expression. Alters histone methylation by recruiting histone methyltransferase to target genes promoters. Plays a role in heterochromatin formation.6 Publications

Miscellaneous

Transgenic mice with insertion of green fluorescence protein (GFP) cDNA in Gfi1b gene allowed to show up-regulation of Gfi1b in early stage of B-cell and in a subset of early thymic pre-T-cell. Mice overexpressing Gfi1b display peripheral T-lymphopenia and a profound defect in activation after CD3 cross-linking. Spleen cells show reduction in the numbers of CD4 and CD8 T-cells. Thymocyte lineage commitment and maturation are altered.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri163 – 186C2H2-type 1PROSITE-ProRule annotationAdd BLAST24
Zinc fingeri192 – 214C2H2-type 2PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri220 – 242C2H2-type 3PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri248 – 270C2H2-type 4PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri276 – 298C2H2-type 5PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri304 – 327C2H2-type 6PROSITE-ProRule annotationAdd BLAST24

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, Developmental protein, DNA-binding, Repressor
Biological processTranscription, Transcription regulation
LigandMetal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Zinc finger protein Gfi-1b
Alternative name(s):
Growth factor independent protein 1B
Gene namesi
Name:Gfi1b
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1276578 Gfi1b

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

Mice are not viable and embryos die by E15 during the transition from primitive to definitive hematopoiesis. They exhibit delayed maturation of primitive erythrocytes and subsequently die with failure to produce enucleated erythrocytes. Their fetal liver contains erythroid and megakaryocytic precursor arrested in their development.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi2P → A: Abrogates interaction with NCOR1 and KDM1A. Greatly diminished interaction with HDAC2. Loss of ability to promote erythrocyte and granulocyte differentiation. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003063281 – 330Zinc finger protein Gfi-1bAdd BLAST330

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei8N6,N6-dimethyllysineBy similarity1

Post-translational modificationi

Methylation at Lys-8 in the SNAG domain seems required for the recruitment of the corepressor complex.By similarity

Keywords - PTMi

Methylation

Proteomic databases

PRIDEiO70237

PTM databases

PhosphoSitePlusiO70237

Expressioni

Tissue specificityi

Expressed in bone marrow and in spleen. Detected in hematopoietic stem cells, erythroblasts, and megakaryocytes. Expressed in thymocytes.4 Publications

Inductioni

Down-regulated by IL6 treatment in myelomonocytic cells, and in response to EPO in myeloid cells; EPO-induced down-regulation of Gfi1b is STAT5-dependent.1 Publication

Gene expression databases

BgeeiENSMUSG00000026815 Expressed in 62 organ(s), highest expression level in blood
CleanExiMM_GFI1B
ExpressionAtlasiO70237 baseline and differential
GenevisibleiO70237 MM

Interactioni

Subunit structurei

Interacts with histone methyltransferases EHMT2 and SUV39H1. Interacts with ARIH2 (via RING-type 2) and with RUNX1T1 (By similarity). Forms a complex with GATA1. Component of a RCOR-GFI-KDM1A-HDAC complex. Interacts directly with RCOR1, KDM1A and HDAC2.By similarity2 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi199901, 6 interactors
CORUMiO70237
IntActiO70237, 11 interactors
MINTiO70237

Structurei

3D structure databases

ProteinModelPortaliO70237
SMRiO70237
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 20SNAG domainAdd BLAST20
Regioni91 – 330Interaction with ARIH2By similarityAdd BLAST240
Regioni164 – 330Mediates interaction with GATA1By similarityAdd BLAST167

Domaini

The zinc finger domain is essential for erythroid expansion and acts as an activation domain whereas non finger domain serves as repression domain.1 Publication
The SNAG domain of GFIs is required for nuclear location and for interaction with some corepressors.By similarity

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri163 – 186C2H2-type 1PROSITE-ProRule annotationAdd BLAST24
Zinc fingeri192 – 214C2H2-type 2PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri220 – 242C2H2-type 3PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri248 – 270C2H2-type 4PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri276 – 298C2H2-type 5PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri304 – 327C2H2-type 6PROSITE-ProRule annotationAdd BLAST24

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

GeneTreeiENSGT00740000115096
HOGENOMiHOG000067832
HOVERGENiHBG106655
InParanoidiO70237
KOiK09223
TreeFamiTF350784

Family and domain databases

InterProiView protein in InterPro
IPR037044 Gfi-1b
IPR036236 Znf_C2H2_sf
IPR013087 Znf_C2H2_type
PANTHERiPTHR44643 PTHR44643, 1 hit
PfamiView protein in Pfam
PF00096 zf-C2H2, 6 hits
SMARTiView protein in SMART
SM00355 ZnF_C2H2, 6 hits
SUPFAMiSSF57667 SSF57667, 3 hits
PROSITEiView protein in PROSITE
PS00028 ZINC_FINGER_C2H2_1, 6 hits
PS50157 ZINC_FINGER_C2H2_2, 6 hits

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

O70237-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MPRSFLVKSK KAHTYHQPRA QGDELVWPPA VIPVAKEHSQ SASPLLSTPL
60 70 80 90 100
PSQTLDWNTI KQEREMLLNQ SLPKMASAPE GPLVTPQPQD GESPLSESPP
110 120 130 140 150
FYKPSFSWDT LASSYSHSYT QTPSTMQSAF LERSVRLYGS PLVPSTESPL
160 170 180 190 200
DFRLRYSPGM DTYHCVKCNK VFSTPHGLEV HVRRSHSGTR PFACDVCGKT
210 220 230 240 250
FGHAVSLEQH THVHSQERSF ECRMCGKAFK RSSTLSTHLL IHSDTRPYPC
260 270 280 290 300
QFCGKRFHQK SDMKKHTYIH TGEKPHKCQV CGKAFSQSSN LITHSRKHTG
310 320 330
FKPFSCELCT KGFQRKVDLR RHRESQHNLK
Length:330
Mass (Da):37,443
Last modified:August 1, 1998 - v1
Checksum:i6194D1972112E6FC
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B7ZNH2B7ZNH2_MOUSE
Gfi1b protein
Gfi1b
363Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti37E → G in BAE34016 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF017275 mRNA Translation: AAC40088.1
AK157262 mRNA Translation: BAE34016.1
AL731851 Genomic DNA No translation available.
BC052654 mRNA Translation: AAH52654.1
BC132365 mRNA Translation: AAI32366.1
BC132367 mRNA Translation: AAI32368.1
CCDSiCCDS15843.1
RefSeqiNP_032140.1, NM_008114.3
UniGeneiMm.373385

Genome annotation databases

EnsembliENSMUST00000028156; ENSMUSP00000028156; ENSMUSG00000026815
GeneIDi14582
KEGGimmu:14582
UCSCiuc008iyu.2 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF017275 mRNA Translation: AAC40088.1
AK157262 mRNA Translation: BAE34016.1
AL731851 Genomic DNA No translation available.
BC052654 mRNA Translation: AAH52654.1
BC132365 mRNA Translation: AAI32366.1
BC132367 mRNA Translation: AAI32368.1
CCDSiCCDS15843.1
RefSeqiNP_032140.1, NM_008114.3
UniGeneiMm.373385

3D structure databases

ProteinModelPortaliO70237
SMRiO70237
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199901, 6 interactors
CORUMiO70237
IntActiO70237, 11 interactors
MINTiO70237

PTM databases

PhosphoSitePlusiO70237

Proteomic databases

PRIDEiO70237

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000028156; ENSMUSP00000028156; ENSMUSG00000026815
GeneIDi14582
KEGGimmu:14582
UCSCiuc008iyu.2 mouse

Organism-specific databases

CTDi8328
MGIiMGI:1276578 Gfi1b

Phylogenomic databases

GeneTreeiENSGT00740000115096
HOGENOMiHOG000067832
HOVERGENiHBG106655
InParanoidiO70237
KOiK09223
TreeFamiTF350784

Miscellaneous databases

PROiPR:O70237
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000026815 Expressed in 62 organ(s), highest expression level in blood
CleanExiMM_GFI1B
ExpressionAtlasiO70237 baseline and differential
GenevisibleiO70237 MM

Family and domain databases

InterProiView protein in InterPro
IPR037044 Gfi-1b
IPR036236 Znf_C2H2_sf
IPR013087 Znf_C2H2_type
PANTHERiPTHR44643 PTHR44643, 1 hit
PfamiView protein in Pfam
PF00096 zf-C2H2, 6 hits
SMARTiView protein in SMART
SM00355 ZnF_C2H2, 6 hits
SUPFAMiSSF57667 SSF57667, 3 hits
PROSITEiView protein in PROSITE
PS00028 ZINC_FINGER_C2H2_1, 6 hits
PS50157 ZINC_FINGER_C2H2_2, 6 hits
ProtoNetiSearch...

Entry informationi

Entry nameiGFI1B_MOUSE
AccessioniPrimary (citable) accession number: O70237
Secondary accession number(s): Q3U039
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 2, 2007
Last sequence update: August 1, 1998
Last modified: November 7, 2018
This is version 144 of the entry and version 1 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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