GFI1B_MOUSE
ID GFI1B_MOUSE Reviewed; 330 AA.
AC O70237; Q3U039;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Zinc finger protein Gfi-1b;
DE AltName: Full=Growth factor independent protein 1B;
GN Name=Gfi1b;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, REGION, AND TISSUE SPECIFICITY.
RC TISSUE=Bone marrow;
RX PubMed=9566867; DOI=10.1128/mcb.18.5.2462;
RA Tong B., Grimes H.L., Yang T.-Y., Bear S.E., Qin Z., Du K., El-Deiry W.S.,
RA Tsichlis P.N.;
RT "The Gfi-1B proto-oncoprotein represses p21WAF1 and inhibits myeloid cell
RT differentiation.";
RL Mol. Cell. Biol. 18:2462-2473(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=NOD; TISSUE=Spleen;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6NCr; TISSUE=Brain, and Hematopoietic stem cell;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=11825872; DOI=10.1101/gad.959102;
RA Saleque S., Cameron S., Orkin S.H.;
RT "The zinc-finger proto-oncogene Gfi-1b is essential for development of the
RT erythroid and megakaryocytic lineages.";
RL Genes Dev. 16:301-306(2002).
RN [6]
RP FUNCTION, AND INDUCTION.
RX PubMed=11696536; DOI=10.1074/jbc.m105575200;
RA Jegalian A.G., Wu H.;
RT "Regulation of Socs gene expression by the proto-oncoprotein GFI-1B: two
RT routes for STAT5 target gene induction by erythropoietin.";
RL J. Biol. Chem. 277:2345-2352(2002).
RN [7]
RP FUNCTION, DOMAIN, AND TISSUE SPECIFICITY.
RX PubMed=12351384; DOI=10.1182/blood-2002-01-0182;
RA Osawa M., Yamaguchi T., Nakamura Y., Kaneko S., Onodera M., Sawada K.,
RA Jegalian A., Wu H., Nakauchi H., Iwama A.;
RT "Erythroid expansion mediated by the Gfi-1B zinc finger protein: role in
RT normal hematopoiesis.";
RL Blood 100:2769-2777(2002).
RN [8]
RP FUNCTION, TRANSGENIC MICE, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=12594258; DOI=10.4049/jimmunol.170.5.2356;
RA Doan L.L., Kitay M.K., Yu Q., Singer A., Herblot S., Hoang T., Bear S.E.,
RA Morse H.C. III, Tsichlis P.N., Grimes H.L.;
RT "Growth factor independence-1B expression leads to defects in T cell
RT activation, IL-7 receptor alpha expression, and T cell lineage
RT commitment.";
RL J. Immunol. 170:2356-2366(2003).
RN [9]
RP INTERACTION WITH GATA1.
RX PubMed=15920471; DOI=10.1038/sj.emboj.7600702;
RA Rodriguez P., Bonte E., Krijgsveld J., Kolodziej K.E., Guyot B.,
RA Heck A.J.R., Vyas P., de Boer E., Grosveld F., Strouboulis J.;
RT "GATA-1 forms distinct activating and repressive complexes in erythroid
RT cells.";
RL EMBO J. 24:2354-2366(2005).
RN [10]
RP FUNCTION.
RX PubMed=15718298; DOI=10.1093/nar/gki243;
RA Vassen L., Fiolka K., Mahlmann S., Moeroey T.;
RT "Direct transcriptional repression of the genes encoding the zinc-finger
RT proteins Gfi1b and Gfi1 by Gfi1b.";
RL Nucleic Acids Res. 33:987-998(2005).
RN [11]
RP TRANSGENIC MICE, AND TISSUE SPECIFICITY.
RX PubMed=17095621; DOI=10.1182/blood-2006-06-030031;
RA Vassen L., Okayama T., Moeroey T.;
RT "Gfi1b:green fluorescent protein knock-in mice reveal a dynamic expression
RT pattern of Gfi1b during hematopoiesis that is largely complementary to
RT Gfi1.";
RL Blood 109:2356-2364(2007).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY AS A COMPONENT OF A GFI/RCOR/KDM1A/HDAC
RP COMPLEX, INTERACTION WITH RCOR1; HDAC1; HDAC2 AND KDM1A, FUNCTION, AND
RP MUTAGENESIS OF PRO-2.
RX PubMed=17707228; DOI=10.1016/j.molcel.2007.06.039;
RA Saleque S., Kim J., Rooke H.M., Orkin S.H.;
RT "Epigenetic regulation of hematopoietic differentiation by Gfi-1 and Gfi-1b
RT is mediated by the cofactors CoREST and LSD1.";
RL Mol. Cell 27:562-572(2007).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Essential proto-oncogenic transcriptional regulator necessary
CC for development and differentiation of erythroid and megakaryocytic
CC lineages. Component of a RCOR-GFI-KDM1A-HDAC complex that suppresses,
CC via histone deacetylase (HDAC) recruitment, a number of genes
CC implicated in multilineage blood cell development and controls
CC hematopoietic differentiation. Transcriptional repressor or activator
CC depending on both promoter and cell type context; represses promoter
CC activity of SOCS1 and SOCS3 and thus, may regulate cytokine signaling
CC pathways. Cooperates with GATA1 to repress target gene transcription,
CC such as the apoptosis regulator BCL2L1; GFI1B silencing in leukemic
CC cell lines markedly increase apoptosis rate. Inhibits down-regulation
CC of MYC and MYB as well as the cyclin-dependent kinase inhibitor
CC CDKN1A/P21WAF1 in IL6-treated myelomonocytic cells. Represses
CC expression of GATA3 in T-cell lymphomas and inhibits GATA1-mediated
CC transcription; as GATA1 also mediates erythroid GFI1B transcription,
CC both GATA1 and GFI1B participate in a feedback regulatory pathway
CC controlling the expression of GFI1B gene in erythroid cells. Suppresses
CC GATA1-mediated stimulation of GFI1B promoter through protein
CC interaction. Binds to gamma-satellite DNA and to its own promoter,
CC auto-repressing its own expression. Alters histone methylation by
CC recruiting histone methyltransferase to target genes promoters. Plays a
CC role in heterochromatin formation. {ECO:0000269|PubMed:11696536,
CC ECO:0000269|PubMed:12351384, ECO:0000269|PubMed:12594258,
CC ECO:0000269|PubMed:15718298, ECO:0000269|PubMed:17707228,
CC ECO:0000269|PubMed:9566867}.
CC -!- SUBUNIT: Interacts with histone methyltransferases EHMT2 and SUV39H1.
CC Interacts with ARIH2 (via RING-type 2) and with RUNX1T1 (By
CC similarity). Forms a complex with GATA1. Component of a RCOR-GFI-KDM1A-
CC HDAC complex. Interacts directly with RCOR1, KDM1A and HDAC2.
CC {ECO:0000250, ECO:0000269|PubMed:15920471,
CC ECO:0000269|PubMed:17707228}.
CC -!- INTERACTION:
CC O70237; Q9Z148: Ehmt2; NbExp=2; IntAct=EBI-4287943, EBI-444966;
CC O70237; O54864: Suv39h1; NbExp=2; IntAct=EBI-4287943, EBI-302230;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12594258}.
CC Note=Localized at foci of pericentric heterochromatin.
CC -!- TISSUE SPECIFICITY: Expressed in bone marrow and in spleen. Detected in
CC hematopoietic stem cells, erythroblasts, and megakaryocytes. Expressed
CC in thymocytes. {ECO:0000269|PubMed:12351384,
CC ECO:0000269|PubMed:12594258, ECO:0000269|PubMed:17095621,
CC ECO:0000269|PubMed:9566867}.
CC -!- INDUCTION: Down-regulated by IL6 treatment in myelomonocytic cells, and
CC in response to EPO in myeloid cells; EPO-induced down-regulation of
CC Gfi1b is STAT5-dependent. {ECO:0000269|PubMed:11696536}.
CC -!- DOMAIN: The zinc finger domain is essential for erythroid expansion and
CC acts as an activation domain whereas non finger domain serves as
CC repression domain. {ECO:0000269|PubMed:12351384}.
CC -!- DOMAIN: The SNAG domain of GFIs is required for nuclear location and
CC for interaction with some corepressors. {ECO:0000250}.
CC -!- PTM: Methylation at Lys-8 in the SNAG domain seems required for the
CC recruitment of the corepressor complex. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice are not viable and embryos die by 15 dpc
CC during the transition from primitive to definitive hematopoiesis. They
CC exhibit delayed maturation of primitive erythrocytes and subsequently
CC die with failure to produce enucleated erythrocytes. Their fetal liver
CC contains erythroid and megakaryocytic precursor arrested in their
CC development. {ECO:0000269|PubMed:11825872}.
CC -!- MISCELLANEOUS: Transgenic mice with insertion of green fluorescence
CC protein (GFP) cDNA in Gfi1b gene allowed to show up-regulation of Gfi1b
CC in early stage of B-cell and in a subset of early thymic pre-T-cell.
CC Mice overexpressing Gfi1b display peripheral T-lymphopenia and a
CC profound defect in activation after CD3 cross-linking. Spleen cells
CC show reduction in the numbers of CD4 and CD8 T-cells. Thymocyte lineage
CC commitment and maturation are altered.
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DR EMBL; AF017275; AAC40088.1; -; mRNA.
DR EMBL; AK157262; BAE34016.1; -; mRNA.
DR EMBL; AL731851; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC052654; AAH52654.1; -; mRNA.
DR EMBL; BC132365; AAI32366.1; -; mRNA.
DR EMBL; BC132367; AAI32368.1; -; mRNA.
DR CCDS; CCDS15843.1; -.
DR RefSeq; NP_032140.1; NM_008114.3.
DR AlphaFoldDB; O70237; -.
DR SMR; O70237; -.
DR BioGRID; 199901; 6.
DR CORUM; O70237; -.
DR IntAct; O70237; 11.
DR MINT; O70237; -.
DR STRING; 10090.ENSMUSP00000028156; -.
DR PhosphoSitePlus; O70237; -.
DR PRIDE; O70237; -.
DR ProteomicsDB; 263352; -.
DR Antibodypedia; 1815; 120 antibodies from 24 providers.
DR DNASU; 14582; -.
DR Ensembl; ENSMUST00000028156; ENSMUSP00000028156; ENSMUSG00000026815.
DR GeneID; 14582; -.
DR KEGG; mmu:14582; -.
DR UCSC; uc008iyu.2; mouse.
DR CTD; 8328; -.
DR MGI; MGI:1276578; Gfi1b.
DR VEuPathDB; HostDB:ENSMUSG00000026815; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000160010; -.
DR HOGENOM; CLU_002678_94_9_1; -.
DR InParanoid; O70237; -.
DR TreeFam; TF350784; -.
DR BioGRID-ORCS; 14582; 5 hits in 75 CRISPR screens.
DR ChiTaRS; Gfi1b; mouse.
DR PRO; PR:O70237; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; O70237; protein.
DR Bgee; ENSMUSG00000026815; Expressed in fetal liver hematopoietic progenitor cell and 46 other tissues.
DR ExpressionAtlas; O70237; baseline and differential.
DR Genevisible; O70237; MM.
DR GO; GO:0016363; C:nuclear matrix; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0005667; C:transcription regulator complex; ISO:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0051572; P:negative regulation of histone H3-K4 methylation; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0030854; P:positive regulation of granulocyte differentiation; IDA:UniProtKB.
DR GO; GO:0051574; P:positive regulation of histone H3-K9 methylation; IMP:UniProtKB.
DR GO; GO:0045646; P:regulation of erythrocyte differentiation; IMP:UniProtKB.
DR GO; GO:1903706; P:regulation of hemopoiesis; IBA:GO_Central.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR Pfam; PF00096; zf-C2H2; 5.
DR SMART; SM00355; ZnF_C2H2; 6.
DR SUPFAM; SSF57667; SSF57667; 3.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 6.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 6.
PE 1: Evidence at protein level;
KW Activator; Developmental protein; DNA-binding; Metal-binding; Methylation;
KW Nucleus; Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..330
FT /note="Zinc finger protein Gfi-1b"
FT /id="PRO_0000306328"
FT ZN_FING 163..186
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 192..214
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 220..242
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 248..270
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 276..298
FT /note="C2H2-type 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 304..327
FT /note="C2H2-type 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1..20
FT /note="SNAG domain"
FT REGION 75..99
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 91..330
FT /note="Interaction with ARIH2"
FT /evidence="ECO:0000250"
FT REGION 164..330
FT /note="Mediates interaction with GATA1"
FT /evidence="ECO:0000250"
FT MOD_RES 8
FT /note="N6,N6-dimethyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q5VTD9"
FT MUTAGEN 2
FT /note="P->A: Abrogates interaction with NCOR1 and KDM1A.
FT Greatly diminished interaction with HDAC2. Loss of ability
FT to promote erythrocyte and granulocyte differentiation."
FT /evidence="ECO:0000269|PubMed:17707228"
FT CONFLICT 37
FT /note="E -> G (in Ref. 2; BAE34016)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 330 AA; 37443 MW; 6194D1972112E6FC CRC64;
MPRSFLVKSK KAHTYHQPRA QGDELVWPPA VIPVAKEHSQ SASPLLSTPL PSQTLDWNTI
KQEREMLLNQ SLPKMASAPE GPLVTPQPQD GESPLSESPP FYKPSFSWDT LASSYSHSYT
QTPSTMQSAF LERSVRLYGS PLVPSTESPL DFRLRYSPGM DTYHCVKCNK VFSTPHGLEV
HVRRSHSGTR PFACDVCGKT FGHAVSLEQH THVHSQERSF ECRMCGKAFK RSSTLSTHLL
IHSDTRPYPC QFCGKRFHQK SDMKKHTYIH TGEKPHKCQV CGKAFSQSSN LITHSRKHTG
FKPFSCELCT KGFQRKVDLR RHRESQHNLK
