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Protein

Zinc finger protein Gfi-1b

Gene

Gfi1b

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri163 – 18624C2H2-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri192 – 21423C2H2-type 2PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri220 – 24223C2H2-type 3PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri248 – 27023C2H2-type 4PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri276 – 29823C2H2-type 5PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri304 – 32724C2H2-type 6PROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

  • hemopoiesis Source: InterPro
  • negative regulation of histone H3-K4 methylation Source: UniProtKB
  • positive regulation of granulocyte differentiation Source: UniProtKB
  • positive regulation of histone H3-K9 methylation Source: UniProtKB
  • regulation of erythrocyte differentiation Source: UniProtKB
  • regulation of transcription, DNA-templated Source: UniProtKB-KW
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator, Developmental protein, Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1276578. Gfi1b.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi2 – 21P → A: Abrogates interaction with NCOR1 and KDM1A. Greatly diminished interaction with HDAC2. Loss of ability to promote erythrocyte and granulocyte differentiation. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 330330Zinc finger protein Gfi-1bPRO_0000306328Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei8 – 81N6,N6-dimethyllysineBy similarity

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

iPTMnetiO70237.
PhosphoSiteiO70237.

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

BgeeiO70237.
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

WithEntry#Exp.IntActNotes
Ehmt2Q9Z1482EBI-4287943,EBI-444966
Suv39h1O548642EBI-4287943,EBI-302230

GO - Molecular functioni

Protein-protein interaction databases

BioGridi199901. 6 interactions.
IntActiO70237. 11 interactions.
MINTiMINT-2736285.

Structurei

3D structure databases

ProteinModelPortaliO70237.
SMRiO70237. Positions 163-327.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 2020SNAG domainAdd
BLAST
Regioni91 – 330240Interaction with ARIH2By similarityAdd
BLAST
Regioni164 – 330167Mediates interaction with GATA1By similarityAdd
BLAST

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

Sequence similaritiesi

Contains 6 C2H2-type zinc fingers.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri163 – 18624C2H2-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri192 – 21423C2H2-type 2PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri220 – 24223C2H2-type 3PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri248 – 27023C2H2-type 4PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri276 – 29823C2H2-type 5PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri304 – 32724C2H2-type 6PROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

GeneTreeiENSGT00740000115096.
HOGENOMiHOG000067832.
HOVERGENiHBG106655.
InParanoidiO70237.
KOiK09223.
OrthoDBiEOG72RN05.
TreeFamiTF350784.

Family and domain databases

Gene3Di3.30.160.60. 6 hits.
InterProiIPR029840. GFI1/1B.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PANTHERiPTHR19303:SF239. PTHR19303:SF239. 1 hit.
PfamiPF00096. zf-C2H2. 1 hit.
PF13912. zf-C2H2_6. 1 hit.
[Graphical view]
SMARTiSM00355. ZnF_C2H2. 6 hits.
[Graphical view]
PROSITEiPS00028. ZINC_FINGER_C2H2_1. 6 hits.
PS50157. ZINC_FINGER_C2H2_2. 6 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti37 – 371E → G in BAE34016 (PubMed:16141072).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF017275 mRNA. Translation: AAC40088.1.
AK157262 mRNA. Translation: BAE34016.1.
AL731851 Genomic DNA. Translation: CAM22291.1.
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.

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. Translation: CAM22291.1.
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. Positions 163-327.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199901. 6 interactions.
IntActiO70237. 11 interactions.
MINTiMINT-2736285.

PTM databases

iPTMnetiO70237.
PhosphoSiteiO70237.

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.
OrthoDBiEOG72RN05.
TreeFamiTF350784.

Miscellaneous databases

PROiO70237.
SOURCEiSearch...

Gene expression databases

BgeeiO70237.
CleanExiMM_GFI1B.
ExpressionAtlasiO70237. baseline and differential.
GenevisibleiO70237. MM.

Family and domain databases

Gene3Di3.30.160.60. 6 hits.
InterProiIPR029840. GFI1/1B.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PANTHERiPTHR19303:SF239. PTHR19303:SF239. 1 hit.
PfamiPF00096. zf-C2H2. 1 hit.
PF13912. zf-C2H2_6. 1 hit.
[Graphical view]
SMARTiSM00355. ZnF_C2H2. 6 hits.
[Graphical view]
PROSITEiPS00028. ZINC_FINGER_C2H2_1. 6 hits.
PS50157. ZINC_FINGER_C2H2_2. 6 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The Gfi-1B proto-oncoprotein represses p21WAF1 and inhibits myeloid cell differentiation."
    Tong B., Grimes H.L., Yang T.-Y., Bear S.E., Qin Z., Du K., El-Deiry W.S., Tsichlis P.N.
    Mol. Cell. Biol. 18:2462-2473(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, REGION, TISSUE SPECIFICITY.
    Tissue: Bone marrow.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: NOD.
    Tissue: Spleen.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6NCr.
    Tissue: Brain and Hematopoietic stem cell.
  5. "The zinc-finger proto-oncogene Gfi-1b is essential for development of the erythroid and megakaryocytic lineages."
    Saleque S., Cameron S., Orkin S.H.
    Genes Dev. 16:301-306(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.
  6. "Regulation of Socs gene expression by the proto-oncoprotein GFI-1B: two routes for STAT5 target gene induction by erythropoietin."
    Jegalian A.G., Wu H.
    J. Biol. Chem. 277:2345-2352(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INDUCTION.
  7. "Erythroid expansion mediated by the Gfi-1B zinc finger protein: role in normal hematopoiesis."
    Osawa M., Yamaguchi T., Nakamura Y., Kaneko S., Onodera M., Sawada K., Jegalian A., Wu H., Nakauchi H., Iwama A.
    Blood 100:2769-2777(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DOMAIN, TISSUE SPECIFICITY.
  8. "Growth factor independence-1B expression leads to defects in T cell activation, IL-7 receptor alpha expression, and T cell lineage commitment."
    Doan L.L., Kitay M.K., Yu Q., Singer A., Herblot S., Hoang T., Bear S.E., Morse H.C. III, Tsichlis P.N., Grimes H.L.
    J. Immunol. 170:2356-2366(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TRANSGENIC MICE, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
  9. "GATA-1 forms distinct activating and repressive complexes in erythroid cells."
    Rodriguez P., Bonte E., Krijgsveld J., Kolodziej K.E., Guyot B., Heck A.J.R., Vyas P., de Boer E., Grosveld F., Strouboulis J.
    EMBO J. 24:2354-2366(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH GATA1.
  10. "Direct transcriptional repression of the genes encoding the zinc-finger proteins Gfi1b and Gfi1 by Gfi1b."
    Vassen L., Fiolka K., Mahlmann S., Moeroey T.
    Nucleic Acids Res. 33:987-998(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  11. "Gfi1b:green fluorescent protein knock-in mice reveal a dynamic expression pattern of Gfi1b during hematopoiesis that is largely complementary to Gfi1."
    Vassen L., Okayama T., Moeroey T.
    Blood 109:2356-2364(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: TRANSGENIC MICE, TISSUE SPECIFICITY.
  12. "Epigenetic regulation of hematopoietic differentiation by Gfi-1 and Gfi-1b is mediated by the cofactors CoREST and LSD1."
    Saleque S., Kim J., Rooke H.M., Orkin S.H.
    Mol. Cell 27:562-572(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY AS A COMPONENT OF A GFI/RCOR/KDM1A/HDAC COMPLEX, INTERACTION WITH RCOR1; HDAC1; HDAC2 AND KDM1A, FUNCTION, MUTAGENESIS OF PRO-2.
  13. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Spleen.

Entry informationi

Entry nameiGFI1B_MOUSE
AccessioniPrimary (citable) accession number: O70237
Secondary accession number(s): Q3U039
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 2, 2007
Last sequence update: August 1, 1998
Last modified: June 8, 2016
This is version 130 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.