Full text data of GFI1B
GFI1B
[Confidence: low (only semi-automatic identification from reviews)]
Zinc finger protein Gfi-1b (Growth factor independent protein 1B; Potential regulator of CDKN1A translocated in CML)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Zinc finger protein Gfi-1b (Growth factor independent protein 1B; Potential regulator of CDKN1A translocated in CML)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q5VTD9
ID GFI1B_HUMAN Reviewed; 330 AA.
AC Q5VTD9; O95270; Q5VTD8; Q6FHZ2; Q6T888;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
read moreDT 07-DEC-2004, sequence version 1.
DT 22-JAN-2014, entry version 100.
DE RecName: Full=Zinc finger protein Gfi-1b;
DE AltName: Full=Growth factor independent protein 1B;
DE AltName: Full=Potential regulator of CDKN1A translocated in CML;
GN Name=GFI1B;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Umbilical cord blood;
RX PubMed=9878267; DOI=10.1006/geno.1998.5601;
RA Roedel B., Wagner T., Zoernig M., Niessing J., Moeroey T.;
RT "The human homologue (GFI1B) of the chicken GFI gene maps to
RT chromosome 9q34.13-A locus frequently altered in hematopoietic
RT diseases.";
RL Genomics 54:580-582(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INDUCTION BY GATA1.
RX PubMed=15280509; DOI=10.1093/nar/gkh719;
RA Huang D.Y., Kuo Y.Y., Lai J.S., Suzuki Y., Sugano S., Chang Z.F.;
RT "GATA-1 and NF-Y cooperate to mediate erythroid-specific transcription
RT of Gfi-1B gene.";
RL Nucleic Acids Res. 32:3935-3946(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION, 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
RT in normal hematopoiesis.";
RL Blood 100:2769-2777(2002).
RN [8]
RP INTERACTION WITH RUNX1T1.
RX PubMed=12874834; DOI=10.1002/jcb.10548;
RA McGhee L., Bryan J., Elliott L., Grimes H.L., Kazanjian A.,
RA Davis J.N., Meyers S.;
RT "Gfi-1 attaches to the nuclear matrix, associates with ETO (MTG8) and
RT histone deacetylase proteins, and represses transcription using a TSA-
RT sensitive mechanism.";
RL J. Cell. Biochem. 89:1005-1018(2003).
RN [9]
RP FUNCTION, DNA-BINDING, AND INTERACTION WITH GATA1.
RX PubMed=16177182; DOI=10.1093/nar/gki838;
RA Huang D.-Y., Kuo Y.-Y., Chang Z.-F.;
RT "GATA-1 mediates auto-regulation of Gfi-1B transcription in K562
RT cells.";
RL Nucleic Acids Res. 33:5331-5342(2005).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH EHMT2 AND
RP SUV39H1.
RX PubMed=16688220; DOI=10.1038/sj.emboj.7601124;
RA Vassen L., Fiolka K., Moeroey T.;
RT "Gfi1b alters histone methylation at target gene promoters and sites
RT of gamma-satellite containing heterochromatin.";
RL EMBO J. 25:2409-2419(2006).
RN [11]
RP FUNCTION.
RX PubMed=16782810; DOI=10.1073/pnas.0603728103;
RA Schwartz R., Engel I., Fallahi-Sichani M., Petrie H.T., Murre C.;
RT "Gene expression patterns define novel roles for E47 in cell cycle
RT progression, cytokine-mediated signaling, and T lineage development.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:9976-9981(2006).
RN [12]
RP INTERACTION WITH ARIH2.
RX PubMed=17646546; DOI=10.1182/blood-2006-11-058602;
RA Marteijn J.A., van der Meer L.T., van Emst L., van Reijmersdal S.,
RA Wissink W., de Witte T., Jansen J.H., Van der Reijden B.A.;
RT "Gfi1 ubiquitination and proteasomal degradation is inhibited by the
RT ubiquitin ligase Triad1.";
RL Blood 110:3128-3135(2007).
RN [13]
RP FUNCTION, DNA-BINDING, AND MUTAGENESIS OF ASN-290.
RX PubMed=17272506; DOI=10.1182/blood-2006-08-043331;
RA Wei X., Kee B.L.;
RT "Growth factor independent 1B (Gfi1b) is an E2A target gene that
RT modulates Gata3 in T-cell lymphomas.";
RL Blood 109:4406-4414(2007).
RN [14]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=17156408; DOI=10.1111/j.1365-2141.2006.06407.x;
RA Elmaagacli A.H., Koldehoff M., Zakrzewski J.L., Steckel N.K.,
RA Ottinger H., Beelen D.W.;
RT "Growth factor-independent 1B gene (GFI1B) is overexpressed in
RT erythropoietic and megakaryocytic malignancies and increases their
RT proliferation rate.";
RL Br. J. Haematol. 136:212-219(2007).
RN [15]
RP FUNCTION, AND INTERACTION WITH GATA1.
RX PubMed=17420275; DOI=10.1128/MCB.02212-06;
RA Kuo Y.-Y., Chang Z.-F.;
RT "GATA-1 and Gfi-1B interplay to regulate Bcl-xL transcription.";
RL Mol. Cell. Biol. 27:4261-4272(2007).
RN [16]
RP FUNCTION (ISOFORM 2), AND METHYLATION AT LYS-8.
RX PubMed=22399799; DOI=10.1242/jcs.095877;
RA Laurent B., Randrianarison-Huetz V., Frisan E., Andrieu-Soler C.,
RA Soler E., Fontenay M., Dusanter-Fourt I., Dumenil D.;
RT "A short Gfi-1B isoform controls erythroid differentiation by
RT recruiting the LSD1-CoREST complex through the dimethylation of its
RT SNAG domain.";
RL J. Cell Sci. 125:993-1002(2012).
RN [17]
RP VARIANT [LARGE SCALE ANALYSIS] HIS-231.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Essential proto-oncogenic transcriptional regulator
CC necessary for development and differentiation of erythroid and
CC megakaryocytic lineages. Component of a RCOR-GFI-KDM1A-HDAC
CC complex that suppresses, via histone deacetylase (HDAC)
CC recruitment, a number of genes implicated in multilineage blood
CC cell development and controls hematopoietic differentiation.
CC Transcriptional repressor or activator depending on both promoter
CC and cell type context; represses promoter activity of SOCS1 and
CC SOCS3 and thus, may regulate cytokine signaling pathways.
CC Cooperates with GATA1 to repress target gene transcription, such
CC as the apoptosis regulator BCL2L1; GFI1B silencing in leukemic
CC cell lines markedly increase apoptosis rate. Inhibits down-
CC regulation of MYC and MYB as well as the cyclin-dependent kinase
CC inhibitor CDKN1A/P21WAF1 in IL6-treated myelomonocytic cells.
CC Represses expression of GATA3 in T-cell lymphomas and inhibits
CC GATA1-mediated transcription; as GATA1 also mediates erythroid
CC GFI1B transcription, both GATA1 and GFI1B participate in a
CC feedback regulatory pathway controlling the expression of GFI1B
CC gene in erythroid cells. Suppresses GATA1-mediated stimulation of
CC GFI1B promoter through protein interaction. Binds to gamma-
CC satellite DNA and to its own promoter, auto-repressing its own
CC expression. Alters histone methylation by recruiting histone
CC methyltransferase to target genes promoters. Plays a role in
CC heterochromatin formation.
CC -!- SUBUNIT: Component of a RCOR-GFI-KDM1A-HDAC complex. Interacts
CC directly with RCOR1, KDM1A and HDAC2 (By similarity). Forms a
CC complex with GATA1. Interacts with histone methyltransferases
CC EHMT2 and SUV39H1. Interacts with ARIH2 (via RING-type 2).
CC Interacts with RUNX1T1.
CC -!- INTERACTION:
CC Q9HC77:CENPJ; NbExp=2; IntAct=EBI-946212, EBI-946194;
CC Q9Y219:JAG2; NbExp=2; IntAct=EBI-946212, EBI-946223;
CC Q99435:NELL2; NbExp=2; IntAct=EBI-946212, EBI-946274;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=p37;
CC IsoId=Q5VTD9-1; Sequence=Displayed;
CC Name=2; Synonyms=p32;
CC IsoId=Q5VTD9-2; Sequence=VSP_028459;
CC Note=Essential for erythroid differentiation. Binds to target
CC gene promoters and associates with the LSD1-CoREST repressor
CC complex more efficiently than the major isoform 1;
CC -!- TISSUE SPECIFICITY: Expressed in bone marrow and fetal liver, but
CC also detectable in fetal spleen, fetal thymus, and testes.
CC Detected in hematopoietic stem cells, erythroblasts, and
CC megakaryocytes. Overexpressed in bone marrow of patients with
CC erythroleukemia and megakaryocytic leukemia as well as in their
CC corresponding leukemic cell lines, and markedly repressed in
CC severe aplastic anemia (SAA).
CC -!- INDUCTION: By GATA1 which binds to GFI1B promoter in cooperation
CC with the transcription factor NFYA. Target gene of transcription
CC factor E2-alpha/TCF3 that promotes growth arrest and apoptosis in
CC lymphomas.
CC -!- DOMAIN: The zinc finger domains are essential for erythroid
CC expansion and acts as an activation domain whereas non finger
CC domain serves as repression domain (By similarity).
CC -!- DOMAIN: The SNAG domain of GFIs is required for nuclear location
CC and for interaction with some corepressors (By similarity).
CC -!- PTM: Methylation at Lys-8 in the SNAG domain seems required for
CC the recruitment of the corepressor complex.
CC -!- SIMILARITY: Contains 6 C2H2-type zinc fingers.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/GFI1BID40707ch9q34.html";
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DR EMBL; AF081946; AAD08672.1; -; mRNA.
DR EMBL; AY428733; AAR06639.1; -; mRNA.
DR EMBL; CR536546; CAG38783.1; -; mRNA.
DR EMBL; AL593851; CAH73618.1; -; Genomic_DNA.
DR EMBL; AL593851; CAH73619.1; -; Genomic_DNA.
DR EMBL; CH471090; EAW88025.1; -; Genomic_DNA.
DR EMBL; BC043371; AAH43371.1; -; mRNA.
DR EMBL; BC035626; -; NOT_ANNOTATED_CDS; mRNA.
DR RefSeq; NP_001128503.1; NM_001135031.1.
DR RefSeq; NP_004179.3; NM_004188.4.
DR RefSeq; XP_005272278.1; XM_005272221.1.
DR RefSeq; XP_005272279.1; XM_005272222.1.
DR RefSeq; XP_005272280.1; XM_005272223.1.
DR UniGene; Hs.553160; -.
DR ProteinModelPortal; Q5VTD9; -.
DR SMR; Q5VTD9; 163-327.
DR IntAct; Q5VTD9; 71.
DR MINT; MINT-2798741; -.
DR STRING; 9606.ENSP00000344782; -.
DR PhosphoSite; Q5VTD9; -.
DR DMDM; 74756792; -.
DR PaxDb; Q5VTD9; -.
DR PRIDE; Q5VTD9; -.
DR Ensembl; ENST00000339463; ENSP00000344782; ENSG00000165702.
DR Ensembl; ENST00000372122; ENSP00000361195; ENSG00000165702.
DR Ensembl; ENST00000372123; ENSP00000361196; ENSG00000165702.
DR Ensembl; ENST00000372124; ENSP00000361197; ENSG00000165702.
DR Ensembl; ENST00000450530; ENSP00000409546; ENSG00000165702.
DR Ensembl; ENST00000534944; ENSP00000446134; ENSG00000165702.
DR GeneID; 8328; -.
DR KEGG; hsa:8328; -.
DR UCSC; uc004ccg.3; human.
DR CTD; 8328; -.
DR GeneCards; GC09P135821; -.
DR HGNC; HGNC:4238; GFI1B.
DR HPA; HPA007012; -.
DR MIM; 604383; gene.
DR neXtProt; NX_Q5VTD9; -.
DR PharmGKB; PA28649; -.
DR eggNOG; COG5048; -.
DR HOGENOM; HOG000067832; -.
DR HOVERGEN; HBG106655; -.
DR InParanoid; Q5VTD9; -.
DR KO; K09223; -.
DR OMA; YGHSYRQ; -.
DR OrthoDB; EOG72RN05; -.
DR PhylomeDB; Q5VTD9; -.
DR SignaLink; Q5VTD9; -.
DR GeneWiki; GFI1B; -.
DR GenomeRNAi; 8328; -.
DR NextBio; 31186; -.
DR PRO; PR:Q5VTD9; -.
DR Bgee; Q5VTD9; -.
DR CleanEx; HS_GFI1B; -.
DR Genevestigator; Q5VTD9; -.
DR GO; GO:0016363; C:nuclear matrix; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription factor complex; IDA:BHF-UCL.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008283; P:cell proliferation; TAS:ProtInc.
DR GO; GO:0016568; P:chromatin modification; IEA:UniProtKB-KW.
DR GO; GO:0007275; P:multicellular organismal development; IEA:UniProtKB-KW.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; TAS:ProtInc.
DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; TAS:ProtInc.
DR Gene3D; 3.30.160.60; -; 6.
DR InterPro; IPR007087; Znf_C2H2.
DR InterPro; IPR015880; Znf_C2H2-like.
DR InterPro; IPR013087; Znf_C2H2/integrase_DNA-bd.
DR Pfam; PF00096; zf-C2H2; 1.
DR SMART; SM00355; ZnF_C2H2; 6.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 6.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 6.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; Chromatin regulator;
KW Complete proteome; Developmental protein; DNA-binding; Metal-binding;
KW Methylation; Nucleus; Polymorphism; Proto-oncogene;
KW Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1 330 Zinc finger protein Gfi-1b.
FT /FTId=PRO_0000306327.
FT ZN_FING 163 186 C2H2-type 1.
FT ZN_FING 192 214 C2H2-type 2.
FT ZN_FING 220 242 C2H2-type 3.
FT ZN_FING 248 270 C2H2-type 4.
FT ZN_FING 276 298 C2H2-type 5.
FT ZN_FING 304 327 C2H2-type 6.
FT REGION 1 20 SNAG domain.
FT REGION 91 330 Interaction with ARIH2.
FT REGION 164 330 Mediates interaction with GATA1.
FT MOD_RES 8 8 N6,N6-dimethyllysine.
FT VAR_SEQ 171 216 Missing (in isoform 2).
FT /FTId=VSP_028459.
FT VARIANT 231 231 R -> H (in a colorectal cancer sample;
FT somatic mutation).
FT /FTId=VAR_035556.
FT MUTAGEN 290 290 N->S: Prevents DNA-binding.
FT CONFLICT 11 11 K -> M (in Ref. 2; AAR06639).
FT CONFLICT 27 27 W -> R (in Ref. 3; CAG38783).
FT CONFLICT 29 29 P -> H (in Ref. 1; AAD08672).
FT CONFLICT 190 190 R -> W (in Ref. 2; AAR06639).
FT CONFLICT 219 219 S -> N (in Ref. 1; AAD08672).
SQ SEQUENCE 330 AA; 37492 MW; 947DD9C34B5BD962 CRC64;
MPRSFLVKSK KAHTYHQPRV QEDEPLWPPA LTPVPRDQAP SNSPVLSTLF PNQCLDWTNL
KREPELEQDQ NLARMAPAPE GPIVLSRPQD GDSPLSDSPP FYKPSFSWDT LATTYGHSYR
QAPSTMQSAF LEHSVSLYGS PLVPSTEPAL DFSLRYSPGM DAYHCVKCNK VFSTPHGLEV
HVRRSHSGTR PFACDICGKT FGHAVSLEQH THVHSQERSF ECRMCGKAFK RSSTLSTHLL
IHSDTRPYPC QFCGKRFHQK SDMKKHTYIH TGEKPHKCQV CGKAFSQSSN LITHSRKHTG
FKPFSCELCT KGFQRKVDLR RHRESQHNLK
//
ID GFI1B_HUMAN Reviewed; 330 AA.
AC Q5VTD9; O95270; Q5VTD8; Q6FHZ2; Q6T888;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
read moreDT 07-DEC-2004, sequence version 1.
DT 22-JAN-2014, entry version 100.
DE RecName: Full=Zinc finger protein Gfi-1b;
DE AltName: Full=Growth factor independent protein 1B;
DE AltName: Full=Potential regulator of CDKN1A translocated in CML;
GN Name=GFI1B;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Umbilical cord blood;
RX PubMed=9878267; DOI=10.1006/geno.1998.5601;
RA Roedel B., Wagner T., Zoernig M., Niessing J., Moeroey T.;
RT "The human homologue (GFI1B) of the chicken GFI gene maps to
RT chromosome 9q34.13-A locus frequently altered in hematopoietic
RT diseases.";
RL Genomics 54:580-582(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INDUCTION BY GATA1.
RX PubMed=15280509; DOI=10.1093/nar/gkh719;
RA Huang D.Y., Kuo Y.Y., Lai J.S., Suzuki Y., Sugano S., Chang Z.F.;
RT "GATA-1 and NF-Y cooperate to mediate erythroid-specific transcription
RT of Gfi-1B gene.";
RL Nucleic Acids Res. 32:3935-3946(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION, 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
RT in normal hematopoiesis.";
RL Blood 100:2769-2777(2002).
RN [8]
RP INTERACTION WITH RUNX1T1.
RX PubMed=12874834; DOI=10.1002/jcb.10548;
RA McGhee L., Bryan J., Elliott L., Grimes H.L., Kazanjian A.,
RA Davis J.N., Meyers S.;
RT "Gfi-1 attaches to the nuclear matrix, associates with ETO (MTG8) and
RT histone deacetylase proteins, and represses transcription using a TSA-
RT sensitive mechanism.";
RL J. Cell. Biochem. 89:1005-1018(2003).
RN [9]
RP FUNCTION, DNA-BINDING, AND INTERACTION WITH GATA1.
RX PubMed=16177182; DOI=10.1093/nar/gki838;
RA Huang D.-Y., Kuo Y.-Y., Chang Z.-F.;
RT "GATA-1 mediates auto-regulation of Gfi-1B transcription in K562
RT cells.";
RL Nucleic Acids Res. 33:5331-5342(2005).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH EHMT2 AND
RP SUV39H1.
RX PubMed=16688220; DOI=10.1038/sj.emboj.7601124;
RA Vassen L., Fiolka K., Moeroey T.;
RT "Gfi1b alters histone methylation at target gene promoters and sites
RT of gamma-satellite containing heterochromatin.";
RL EMBO J. 25:2409-2419(2006).
RN [11]
RP FUNCTION.
RX PubMed=16782810; DOI=10.1073/pnas.0603728103;
RA Schwartz R., Engel I., Fallahi-Sichani M., Petrie H.T., Murre C.;
RT "Gene expression patterns define novel roles for E47 in cell cycle
RT progression, cytokine-mediated signaling, and T lineage development.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:9976-9981(2006).
RN [12]
RP INTERACTION WITH ARIH2.
RX PubMed=17646546; DOI=10.1182/blood-2006-11-058602;
RA Marteijn J.A., van der Meer L.T., van Emst L., van Reijmersdal S.,
RA Wissink W., de Witte T., Jansen J.H., Van der Reijden B.A.;
RT "Gfi1 ubiquitination and proteasomal degradation is inhibited by the
RT ubiquitin ligase Triad1.";
RL Blood 110:3128-3135(2007).
RN [13]
RP FUNCTION, DNA-BINDING, AND MUTAGENESIS OF ASN-290.
RX PubMed=17272506; DOI=10.1182/blood-2006-08-043331;
RA Wei X., Kee B.L.;
RT "Growth factor independent 1B (Gfi1b) is an E2A target gene that
RT modulates Gata3 in T-cell lymphomas.";
RL Blood 109:4406-4414(2007).
RN [14]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=17156408; DOI=10.1111/j.1365-2141.2006.06407.x;
RA Elmaagacli A.H., Koldehoff M., Zakrzewski J.L., Steckel N.K.,
RA Ottinger H., Beelen D.W.;
RT "Growth factor-independent 1B gene (GFI1B) is overexpressed in
RT erythropoietic and megakaryocytic malignancies and increases their
RT proliferation rate.";
RL Br. J. Haematol. 136:212-219(2007).
RN [15]
RP FUNCTION, AND INTERACTION WITH GATA1.
RX PubMed=17420275; DOI=10.1128/MCB.02212-06;
RA Kuo Y.-Y., Chang Z.-F.;
RT "GATA-1 and Gfi-1B interplay to regulate Bcl-xL transcription.";
RL Mol. Cell. Biol. 27:4261-4272(2007).
RN [16]
RP FUNCTION (ISOFORM 2), AND METHYLATION AT LYS-8.
RX PubMed=22399799; DOI=10.1242/jcs.095877;
RA Laurent B., Randrianarison-Huetz V., Frisan E., Andrieu-Soler C.,
RA Soler E., Fontenay M., Dusanter-Fourt I., Dumenil D.;
RT "A short Gfi-1B isoform controls erythroid differentiation by
RT recruiting the LSD1-CoREST complex through the dimethylation of its
RT SNAG domain.";
RL J. Cell Sci. 125:993-1002(2012).
RN [17]
RP VARIANT [LARGE SCALE ANALYSIS] HIS-231.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Essential proto-oncogenic transcriptional regulator
CC necessary for development and differentiation of erythroid and
CC megakaryocytic lineages. Component of a RCOR-GFI-KDM1A-HDAC
CC complex that suppresses, via histone deacetylase (HDAC)
CC recruitment, a number of genes implicated in multilineage blood
CC cell development and controls hematopoietic differentiation.
CC Transcriptional repressor or activator depending on both promoter
CC and cell type context; represses promoter activity of SOCS1 and
CC SOCS3 and thus, may regulate cytokine signaling pathways.
CC Cooperates with GATA1 to repress target gene transcription, such
CC as the apoptosis regulator BCL2L1; GFI1B silencing in leukemic
CC cell lines markedly increase apoptosis rate. Inhibits down-
CC regulation of MYC and MYB as well as the cyclin-dependent kinase
CC inhibitor CDKN1A/P21WAF1 in IL6-treated myelomonocytic cells.
CC Represses expression of GATA3 in T-cell lymphomas and inhibits
CC GATA1-mediated transcription; as GATA1 also mediates erythroid
CC GFI1B transcription, both GATA1 and GFI1B participate in a
CC feedback regulatory pathway controlling the expression of GFI1B
CC gene in erythroid cells. Suppresses GATA1-mediated stimulation of
CC GFI1B promoter through protein interaction. Binds to gamma-
CC satellite DNA and to its own promoter, auto-repressing its own
CC expression. Alters histone methylation by recruiting histone
CC methyltransferase to target genes promoters. Plays a role in
CC heterochromatin formation.
CC -!- SUBUNIT: Component of a RCOR-GFI-KDM1A-HDAC complex. Interacts
CC directly with RCOR1, KDM1A and HDAC2 (By similarity). Forms a
CC complex with GATA1. Interacts with histone methyltransferases
CC EHMT2 and SUV39H1. Interacts with ARIH2 (via RING-type 2).
CC Interacts with RUNX1T1.
CC -!- INTERACTION:
CC Q9HC77:CENPJ; NbExp=2; IntAct=EBI-946212, EBI-946194;
CC Q9Y219:JAG2; NbExp=2; IntAct=EBI-946212, EBI-946223;
CC Q99435:NELL2; NbExp=2; IntAct=EBI-946212, EBI-946274;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=p37;
CC IsoId=Q5VTD9-1; Sequence=Displayed;
CC Name=2; Synonyms=p32;
CC IsoId=Q5VTD9-2; Sequence=VSP_028459;
CC Note=Essential for erythroid differentiation. Binds to target
CC gene promoters and associates with the LSD1-CoREST repressor
CC complex more efficiently than the major isoform 1;
CC -!- TISSUE SPECIFICITY: Expressed in bone marrow and fetal liver, but
CC also detectable in fetal spleen, fetal thymus, and testes.
CC Detected in hematopoietic stem cells, erythroblasts, and
CC megakaryocytes. Overexpressed in bone marrow of patients with
CC erythroleukemia and megakaryocytic leukemia as well as in their
CC corresponding leukemic cell lines, and markedly repressed in
CC severe aplastic anemia (SAA).
CC -!- INDUCTION: By GATA1 which binds to GFI1B promoter in cooperation
CC with the transcription factor NFYA. Target gene of transcription
CC factor E2-alpha/TCF3 that promotes growth arrest and apoptosis in
CC lymphomas.
CC -!- DOMAIN: The zinc finger domains are essential for erythroid
CC expansion and acts as an activation domain whereas non finger
CC domain serves as repression domain (By similarity).
CC -!- DOMAIN: The SNAG domain of GFIs is required for nuclear location
CC and for interaction with some corepressors (By similarity).
CC -!- PTM: Methylation at Lys-8 in the SNAG domain seems required for
CC the recruitment of the corepressor complex.
CC -!- SIMILARITY: Contains 6 C2H2-type zinc fingers.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/GFI1BID40707ch9q34.html";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; AF081946; AAD08672.1; -; mRNA.
DR EMBL; AY428733; AAR06639.1; -; mRNA.
DR EMBL; CR536546; CAG38783.1; -; mRNA.
DR EMBL; AL593851; CAH73618.1; -; Genomic_DNA.
DR EMBL; AL593851; CAH73619.1; -; Genomic_DNA.
DR EMBL; CH471090; EAW88025.1; -; Genomic_DNA.
DR EMBL; BC043371; AAH43371.1; -; mRNA.
DR EMBL; BC035626; -; NOT_ANNOTATED_CDS; mRNA.
DR RefSeq; NP_001128503.1; NM_001135031.1.
DR RefSeq; NP_004179.3; NM_004188.4.
DR RefSeq; XP_005272278.1; XM_005272221.1.
DR RefSeq; XP_005272279.1; XM_005272222.1.
DR RefSeq; XP_005272280.1; XM_005272223.1.
DR UniGene; Hs.553160; -.
DR ProteinModelPortal; Q5VTD9; -.
DR SMR; Q5VTD9; 163-327.
DR IntAct; Q5VTD9; 71.
DR MINT; MINT-2798741; -.
DR STRING; 9606.ENSP00000344782; -.
DR PhosphoSite; Q5VTD9; -.
DR DMDM; 74756792; -.
DR PaxDb; Q5VTD9; -.
DR PRIDE; Q5VTD9; -.
DR Ensembl; ENST00000339463; ENSP00000344782; ENSG00000165702.
DR Ensembl; ENST00000372122; ENSP00000361195; ENSG00000165702.
DR Ensembl; ENST00000372123; ENSP00000361196; ENSG00000165702.
DR Ensembl; ENST00000372124; ENSP00000361197; ENSG00000165702.
DR Ensembl; ENST00000450530; ENSP00000409546; ENSG00000165702.
DR Ensembl; ENST00000534944; ENSP00000446134; ENSG00000165702.
DR GeneID; 8328; -.
DR KEGG; hsa:8328; -.
DR UCSC; uc004ccg.3; human.
DR CTD; 8328; -.
DR GeneCards; GC09P135821; -.
DR HGNC; HGNC:4238; GFI1B.
DR HPA; HPA007012; -.
DR MIM; 604383; gene.
DR neXtProt; NX_Q5VTD9; -.
DR PharmGKB; PA28649; -.
DR eggNOG; COG5048; -.
DR HOGENOM; HOG000067832; -.
DR HOVERGEN; HBG106655; -.
DR InParanoid; Q5VTD9; -.
DR KO; K09223; -.
DR OMA; YGHSYRQ; -.
DR OrthoDB; EOG72RN05; -.
DR PhylomeDB; Q5VTD9; -.
DR SignaLink; Q5VTD9; -.
DR GeneWiki; GFI1B; -.
DR GenomeRNAi; 8328; -.
DR NextBio; 31186; -.
DR PRO; PR:Q5VTD9; -.
DR Bgee; Q5VTD9; -.
DR CleanEx; HS_GFI1B; -.
DR Genevestigator; Q5VTD9; -.
DR GO; GO:0016363; C:nuclear matrix; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription factor complex; IDA:BHF-UCL.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008283; P:cell proliferation; TAS:ProtInc.
DR GO; GO:0016568; P:chromatin modification; IEA:UniProtKB-KW.
DR GO; GO:0007275; P:multicellular organismal development; IEA:UniProtKB-KW.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; TAS:ProtInc.
DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; TAS:ProtInc.
DR Gene3D; 3.30.160.60; -; 6.
DR InterPro; IPR007087; Znf_C2H2.
DR InterPro; IPR015880; Znf_C2H2-like.
DR InterPro; IPR013087; Znf_C2H2/integrase_DNA-bd.
DR Pfam; PF00096; zf-C2H2; 1.
DR SMART; SM00355; ZnF_C2H2; 6.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 6.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 6.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; Chromatin regulator;
KW Complete proteome; Developmental protein; DNA-binding; Metal-binding;
KW Methylation; Nucleus; Polymorphism; Proto-oncogene;
KW Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1 330 Zinc finger protein Gfi-1b.
FT /FTId=PRO_0000306327.
FT ZN_FING 163 186 C2H2-type 1.
FT ZN_FING 192 214 C2H2-type 2.
FT ZN_FING 220 242 C2H2-type 3.
FT ZN_FING 248 270 C2H2-type 4.
FT ZN_FING 276 298 C2H2-type 5.
FT ZN_FING 304 327 C2H2-type 6.
FT REGION 1 20 SNAG domain.
FT REGION 91 330 Interaction with ARIH2.
FT REGION 164 330 Mediates interaction with GATA1.
FT MOD_RES 8 8 N6,N6-dimethyllysine.
FT VAR_SEQ 171 216 Missing (in isoform 2).
FT /FTId=VSP_028459.
FT VARIANT 231 231 R -> H (in a colorectal cancer sample;
FT somatic mutation).
FT /FTId=VAR_035556.
FT MUTAGEN 290 290 N->S: Prevents DNA-binding.
FT CONFLICT 11 11 K -> M (in Ref. 2; AAR06639).
FT CONFLICT 27 27 W -> R (in Ref. 3; CAG38783).
FT CONFLICT 29 29 P -> H (in Ref. 1; AAD08672).
FT CONFLICT 190 190 R -> W (in Ref. 2; AAR06639).
FT CONFLICT 219 219 S -> N (in Ref. 1; AAD08672).
SQ SEQUENCE 330 AA; 37492 MW; 947DD9C34B5BD962 CRC64;
MPRSFLVKSK KAHTYHQPRV QEDEPLWPPA LTPVPRDQAP SNSPVLSTLF PNQCLDWTNL
KREPELEQDQ NLARMAPAPE GPIVLSRPQD GDSPLSDSPP FYKPSFSWDT LATTYGHSYR
QAPSTMQSAF LEHSVSLYGS PLVPSTEPAL DFSLRYSPGM DAYHCVKCNK VFSTPHGLEV
HVRRSHSGTR PFACDICGKT FGHAVSLEQH THVHSQERSF ECRMCGKAFK RSSTLSTHLL
IHSDTRPYPC QFCGKRFHQK SDMKKHTYIH TGEKPHKCQV CGKAFSQSSN LITHSRKHTG
FKPFSCELCT KGFQRKVDLR RHRESQHNLK
//
MIM
604383
*RECORD*
*FIELD* NO
604383
*FIELD* TI
*604383 GROWTH FACTOR-INDEPENDENT 1B; GFI1B
*FIELD* TX
DESCRIPTION
The GFI1B gene encodes a transcriptional repressor important for
read morehematopoiesis and megakaryopoiesis (summary by Monteferrario et al.,
2014).
CLONING
Tong et al. (1998) isolated a full-length cDNA clone of a novel gene,
which they designated Gfi1b, from a murine spleen cDNA library. They
found that Gfi1b encodes a 330-amino acid zinc finger protein with a
SNAG repressor domain. Gfi1b is 97% identical in the zinc finger domain
and 95% identical in the SNAG domain to Gfi1 (600871). Northern blot
analysis showed that Gfi1b is expressed in bone marrow and spleen but
not in kidney, liver, lung, heart, or brain. In contrast, Gfi1 is
expressed primarily in bone marrow and thymus.
Rodel et al. (1998) screened a cDNA library from human umbilical cord
mononuclear cells with a conserved sequence from chicken Gfi and used
PCR to generate a 1.1-kb cDNA fragment of GFI1B. Northern blot analysis
showed that human GFI1B expression was highest in bone marrow and fetal
liver as well as in the chronic myeloid leukemia cell line K562. It was
expressed at lower levels in other hematopoietic precursor cells.
GENE FUNCTION
Tong et al. (1998) found that Gfi1b was downregulated in myelomonocytic
M1 cells in the presence of interleukin-6 (IL6; 147620). However, forced
expression of Gfi1b inhibited IL6-induced cell cycle arrest and
differentiation and inhibited expression of the p21(WAF1) (CDKN1A;
116899) promoter. The inhibition was attributed to a transcriptional
repressor contained in the Gfi1b SNAG domain.
By coimmunoprecipitation assays with mouse and human cells, Saleque et
al. (2007) showed that LSD1 (AOF2; 609132), COREST (RCOR; 607675), HDAC1
(601241), and HDAC2 (605164) interacted with both GFI1 and GFI1B in
endogenous complexes. The N-terminal SNAG repression domain of GFI1 and
GFI1B was required for their association with COREST and LSD1. Mouse
Gfi1b recruited these cofactors to the majority of target gene promoters
in vivo. Inhibition of Corest and Lsd1 perturbed differentiation of
mouse erythroid, megakaryocytic, and granulocytic cells, as well as
primary erythroid progenitors. Lsd1 depletion derepressed GFI targets in
lineage-specific patterns, accompanied by enhanced histone-3 (see
602810) lys4 methylation at the respective promoters. Saleque et al.
(2007) concluded that GFI complexes catalyze serial histone modification
of their targets, leading to their graded silencing.
GENE STRUCTURE
Rodel et al. (1998) determined that the coding region of human GFI1B is
spread over 5 kb and contains 6 coding exons.
MAPPING
By sequence comparison within a mapped cosmid (GenBank GENBANK
AC000393), Rodel et al. (1998) mapped the human GFI1B gene to chromosome
9q34.13, distal of ABL1 (189980). This chromosomal region is
translocated to chromosome 22q11 in chronic myeloid leukemia (151410).
MOLECULAR GENETICS
In affected members of a family with platelet-type bleeding disorder-17
(BDPLT17; 187900), originally reported by Kurstjens et al. (1968),
Monteferrario et al. (2014) identified a heterozygous truncating
mutation in the GFI1B gene (Q287X; 604383.0001). The mutation was found
by linkage analysis followed by candidate gene sequencing. The patients
had moderate recurrent bleeding and thrombocytopenia associated with
decreased platelet alpha-granules and abnormal megakaryocytes on bone
marrow biopsy. Myeloid and erythroid lineages were unaffected. The
surface expression of several platelet markers, including alpha-2-beta
integrin (ITGA2B; 607759), was normal, but 5 of 6 affected individuals
had a marked decrease in the expression of platelet glycoprotein
Ib-alpha (CD42B, GP1BA; 606672). Patient platelets also showed increased
expression of CD34 (142230). In vitro functional expression studies
showed that the mutant protein lacked transcriptional repression
activity and acted in a dominant-negative manner when coexpressed with
the wildtype protein. Expression of the mutation in mouse bone marrow
cells resulted in dysplastic megakaryocytes with hypolobulated nuclei,
irregular contours, and multiple separated nuclei, similar to the
features observed in patient cells. The findings indicated that GFI1B
has an important role in megakaryopoiesis and normal platelet
production.
In affected members of a large family with BDPLT17, originally reported
by Ardlie et al. (1976), Stevenson et al. (2013) identified a
heterozygous truncating mutation in the GFI1B gene (604383.0002). In
vitro cellular functional expression assays showed that the mutant
protein was unable to repress the transcription of the target gene
TGFBR3 (600742) or of itself, even when expressed with wildtype GFI1B.
Patient platelets had decreased levels of the alpha-granule-related
protein P-selectin (SELP; 173610), with smaller reductions in ITGB3
(173470) and GP1BA, compared to controls. These findings were associated
with decreased alpha-granules observed by electron microscopy in patient
platelets.
ANIMAL MODEL
Saleque et al. (2002) found that Gfi1b +/- mice appeared normal, but
Gfi1b -/- embryos exhibited embryonic lethality. Livers of Gfi1b -/-
embryos contained erythroid and megakaryocytic precursors arrested in
their development, and many primitive erythrocytes were characterized by
extensive membrane blebbing and ruffling. Myelopoiesis was normal. Gfi1b
-/- embryos appeared to die during the transition from primitive to
definitive hematopoiesis, with failure to produce enucleated
erythrocytes. Saleque et al. (2002) concluded that GFI1B is an essential
transcriptional regulator of erythroid and megakaryocyte development.
*FIELD* AV
.0001
BLEEDING DISORDER, PLATELET-TYPE, 17
GFI1B, GLN287TER
In affected members of a large family with autosomal dominant
platelet-type bleeding disorder-17 (BDPLT17; 187900), originally
reported by Kurstjens et al. (1968), Monteferrario et al. (2014)
identified a heterozygous c.859C-T transition in exon 6 of the GFI1B
gene, resulting in a gln287-to-ter (Q287X) substitution in zinc finger
5, which is required for DNA binding. The mutation was found by linkage
analysis followed by candidate gene sequencing and segregated with the
disorder in the family. A mutant transcript was detected in patient
cells, indicating that the mutation did not cause nonsense-mediated mRNA
decay. In vitro functional expression studies showed that the mutant
protein lacked transcriptional repression activity and acted in a
dominant-negative manner when coexpressed with the wildtype protein.
Expression of the mutation in mouse bone marrow cells resulted in
dysplastic megakaryocytes with hypolobulated nuclei, irregular contours,
and multiple separated nuclei, similar to the features observed in
patient cells.
.0002
BLEEDING DISORDER, PLATELET-TYPE, 17
GFI1B, 1-BP INS, 880C
In affected members of a large family with BDPLT17 (187900) originally
reported by Ardlie et al. (1976), Stevenson et al. (2013) identified a
heterozygous 1-bp insertion (c.880_881insC) in exon 7 of the GFI1B gene,
resulting in a frameshift and premature termination (His294fsTer307)
predicted to disrupt the fifth and sixth zinc finger DNA-binding
domains. The mutation segregated with the disorder in the family and was
not present in the 1000 Genomes Project database. Both wildtype and
mutant transcript were detected in patient cells and platelets. In vitro
cellular functional expression assays showed that the mutant protein was
unable to repress the transcription of the target gene TGFBR3 (600742)
or of itself, even when expressed with wildtype GFI1B. Patient platelets
had decreased levels of the alpha-granule-related protein P-selectin
(SELP; 173610), with smaller reductions in ITGB3 (173470) and GP1BA
(606672), compared to controls. These findings were associated with
decreased alpha-granules observed by electron microscopy in patient
platelets.
*FIELD* RF
1. Ardlie, N. G.; Coupland, W. W.; Schoefl, G. I.: Hereditary thrombocytopathy:
a familial bleeding disorder due to impaired platelet coagulant activity. Aust.
New Zeal. J. Med. 6: 37-45, 1976.
2. Kurstjens, R.; Bolt, C.; Vossen, M.; Haanen, C.: Familial thrombopathic
thrombocytopenia. Brit. J. Haemat. 15: 305-317, 1968.
3. Monteferrario, D.; Bolar, N. A.; Marneth, A. E.; Hebeda, K. M.;
Bergevoet, S. M.; Veenstra, H.; Laros-van Gorkom, B. A. P.; MacKenzie,
M. A.; Khandanpour, C.; Botezatu, L.; Fransen, E.; Van Camp, G.; and
11 others: A dominant-negative GFI1B mutation in the gray platelet
syndrome. New Eng. J. Med. 370: 245-253, 2014.
4. Rodel, B.; Wagner, T.; Zornig, M.; Niessing, J.; Moroy, T.: The
human homologue (GFI1B) of the chicken GFI gene maps to chromosome
9q34.13--a locus frequently altered in hematopoietic diseases. Genomics 54:
580-582, 1998.
5. Saleque, S.; Cameron, S.; Orkin, S. H.: The zinc-finger proto-oncogene
Gfi-1b is essential for development of the erythroid and megakaryocytic
lineages. Genes Dev. 16: 301-306, 2002.
6. Saleque, S.; Kim, J.; Rooke, H. M.; Orkin, S. H.: Epigenetic regulation
of hematopoietic differentiation by Gfi-1 and Gfi-1b is mediated by
the cofactors CoREST and LSD1. Molec. Cell 27: 562-572, 2007.
7. Stevenson, W. S.; Morel-Kopp, M.-C.; Chen, Q.; Liang, H. P.; Bromhead,
C. J.; Wright, S.; Turakulov, R.; Ng, A. P.; Roberts, A. W.; Bahlo,
M..; Ward, C. M.: GFI1B mutation causes a bleeding disorder with
abnormal platelet function. J. Thromb. Haemost. 11: 2039-2047, 2013.
8. Tong, B.; Grimes, H. L.; Yang, T.-Y.; Bear, S. E.; Qin, Z.; Du,
K.; El-Deiry, W. S.; Tsichlis, P. N.: The Gfi-1B proto-oncoprotein
represses p21(WAF1) and inhibits myeloid cell differentiation. Molec.
Cell. Biol. 18: 2462-2473, 1998.
*FIELD* CN
Cassandra L. Kniffin - updated: 1/27/2014
Patricia A. Hartz - updated: 10/28/2008
Patricia A. Hartz - updated: 9/26/2007
*FIELD* CD
Paul J. Converse: 12/29/1999
*FIELD* ED
carol: 01/28/2014
carol: 1/28/2014
ckniffin: 1/27/2014
mgross: 2/5/2013
mgross: 10/28/2008
terry: 10/28/2008
mgross: 10/2/2007
terry: 9/26/2007
alopez: 12/30/1999
carol: 12/29/1999
*RECORD*
*FIELD* NO
604383
*FIELD* TI
*604383 GROWTH FACTOR-INDEPENDENT 1B; GFI1B
*FIELD* TX
DESCRIPTION
The GFI1B gene encodes a transcriptional repressor important for
read morehematopoiesis and megakaryopoiesis (summary by Monteferrario et al.,
2014).
CLONING
Tong et al. (1998) isolated a full-length cDNA clone of a novel gene,
which they designated Gfi1b, from a murine spleen cDNA library. They
found that Gfi1b encodes a 330-amino acid zinc finger protein with a
SNAG repressor domain. Gfi1b is 97% identical in the zinc finger domain
and 95% identical in the SNAG domain to Gfi1 (600871). Northern blot
analysis showed that Gfi1b is expressed in bone marrow and spleen but
not in kidney, liver, lung, heart, or brain. In contrast, Gfi1 is
expressed primarily in bone marrow and thymus.
Rodel et al. (1998) screened a cDNA library from human umbilical cord
mononuclear cells with a conserved sequence from chicken Gfi and used
PCR to generate a 1.1-kb cDNA fragment of GFI1B. Northern blot analysis
showed that human GFI1B expression was highest in bone marrow and fetal
liver as well as in the chronic myeloid leukemia cell line K562. It was
expressed at lower levels in other hematopoietic precursor cells.
GENE FUNCTION
Tong et al. (1998) found that Gfi1b was downregulated in myelomonocytic
M1 cells in the presence of interleukin-6 (IL6; 147620). However, forced
expression of Gfi1b inhibited IL6-induced cell cycle arrest and
differentiation and inhibited expression of the p21(WAF1) (CDKN1A;
116899) promoter. The inhibition was attributed to a transcriptional
repressor contained in the Gfi1b SNAG domain.
By coimmunoprecipitation assays with mouse and human cells, Saleque et
al. (2007) showed that LSD1 (AOF2; 609132), COREST (RCOR; 607675), HDAC1
(601241), and HDAC2 (605164) interacted with both GFI1 and GFI1B in
endogenous complexes. The N-terminal SNAG repression domain of GFI1 and
GFI1B was required for their association with COREST and LSD1. Mouse
Gfi1b recruited these cofactors to the majority of target gene promoters
in vivo. Inhibition of Corest and Lsd1 perturbed differentiation of
mouse erythroid, megakaryocytic, and granulocytic cells, as well as
primary erythroid progenitors. Lsd1 depletion derepressed GFI targets in
lineage-specific patterns, accompanied by enhanced histone-3 (see
602810) lys4 methylation at the respective promoters. Saleque et al.
(2007) concluded that GFI complexes catalyze serial histone modification
of their targets, leading to their graded silencing.
GENE STRUCTURE
Rodel et al. (1998) determined that the coding region of human GFI1B is
spread over 5 kb and contains 6 coding exons.
MAPPING
By sequence comparison within a mapped cosmid (GenBank GENBANK
AC000393), Rodel et al. (1998) mapped the human GFI1B gene to chromosome
9q34.13, distal of ABL1 (189980). This chromosomal region is
translocated to chromosome 22q11 in chronic myeloid leukemia (151410).
MOLECULAR GENETICS
In affected members of a family with platelet-type bleeding disorder-17
(BDPLT17; 187900), originally reported by Kurstjens et al. (1968),
Monteferrario et al. (2014) identified a heterozygous truncating
mutation in the GFI1B gene (Q287X; 604383.0001). The mutation was found
by linkage analysis followed by candidate gene sequencing. The patients
had moderate recurrent bleeding and thrombocytopenia associated with
decreased platelet alpha-granules and abnormal megakaryocytes on bone
marrow biopsy. Myeloid and erythroid lineages were unaffected. The
surface expression of several platelet markers, including alpha-2-beta
integrin (ITGA2B; 607759), was normal, but 5 of 6 affected individuals
had a marked decrease in the expression of platelet glycoprotein
Ib-alpha (CD42B, GP1BA; 606672). Patient platelets also showed increased
expression of CD34 (142230). In vitro functional expression studies
showed that the mutant protein lacked transcriptional repression
activity and acted in a dominant-negative manner when coexpressed with
the wildtype protein. Expression of the mutation in mouse bone marrow
cells resulted in dysplastic megakaryocytes with hypolobulated nuclei,
irregular contours, and multiple separated nuclei, similar to the
features observed in patient cells. The findings indicated that GFI1B
has an important role in megakaryopoiesis and normal platelet
production.
In affected members of a large family with BDPLT17, originally reported
by Ardlie et al. (1976), Stevenson et al. (2013) identified a
heterozygous truncating mutation in the GFI1B gene (604383.0002). In
vitro cellular functional expression assays showed that the mutant
protein was unable to repress the transcription of the target gene
TGFBR3 (600742) or of itself, even when expressed with wildtype GFI1B.
Patient platelets had decreased levels of the alpha-granule-related
protein P-selectin (SELP; 173610), with smaller reductions in ITGB3
(173470) and GP1BA, compared to controls. These findings were associated
with decreased alpha-granules observed by electron microscopy in patient
platelets.
ANIMAL MODEL
Saleque et al. (2002) found that Gfi1b +/- mice appeared normal, but
Gfi1b -/- embryos exhibited embryonic lethality. Livers of Gfi1b -/-
embryos contained erythroid and megakaryocytic precursors arrested in
their development, and many primitive erythrocytes were characterized by
extensive membrane blebbing and ruffling. Myelopoiesis was normal. Gfi1b
-/- embryos appeared to die during the transition from primitive to
definitive hematopoiesis, with failure to produce enucleated
erythrocytes. Saleque et al. (2002) concluded that GFI1B is an essential
transcriptional regulator of erythroid and megakaryocyte development.
*FIELD* AV
.0001
BLEEDING DISORDER, PLATELET-TYPE, 17
GFI1B, GLN287TER
In affected members of a large family with autosomal dominant
platelet-type bleeding disorder-17 (BDPLT17; 187900), originally
reported by Kurstjens et al. (1968), Monteferrario et al. (2014)
identified a heterozygous c.859C-T transition in exon 6 of the GFI1B
gene, resulting in a gln287-to-ter (Q287X) substitution in zinc finger
5, which is required for DNA binding. The mutation was found by linkage
analysis followed by candidate gene sequencing and segregated with the
disorder in the family. A mutant transcript was detected in patient
cells, indicating that the mutation did not cause nonsense-mediated mRNA
decay. In vitro functional expression studies showed that the mutant
protein lacked transcriptional repression activity and acted in a
dominant-negative manner when coexpressed with the wildtype protein.
Expression of the mutation in mouse bone marrow cells resulted in
dysplastic megakaryocytes with hypolobulated nuclei, irregular contours,
and multiple separated nuclei, similar to the features observed in
patient cells.
.0002
BLEEDING DISORDER, PLATELET-TYPE, 17
GFI1B, 1-BP INS, 880C
In affected members of a large family with BDPLT17 (187900) originally
reported by Ardlie et al. (1976), Stevenson et al. (2013) identified a
heterozygous 1-bp insertion (c.880_881insC) in exon 7 of the GFI1B gene,
resulting in a frameshift and premature termination (His294fsTer307)
predicted to disrupt the fifth and sixth zinc finger DNA-binding
domains. The mutation segregated with the disorder in the family and was
not present in the 1000 Genomes Project database. Both wildtype and
mutant transcript were detected in patient cells and platelets. In vitro
cellular functional expression assays showed that the mutant protein was
unable to repress the transcription of the target gene TGFBR3 (600742)
or of itself, even when expressed with wildtype GFI1B. Patient platelets
had decreased levels of the alpha-granule-related protein P-selectin
(SELP; 173610), with smaller reductions in ITGB3 (173470) and GP1BA
(606672), compared to controls. These findings were associated with
decreased alpha-granules observed by electron microscopy in patient
platelets.
*FIELD* RF
1. Ardlie, N. G.; Coupland, W. W.; Schoefl, G. I.: Hereditary thrombocytopathy:
a familial bleeding disorder due to impaired platelet coagulant activity. Aust.
New Zeal. J. Med. 6: 37-45, 1976.
2. Kurstjens, R.; Bolt, C.; Vossen, M.; Haanen, C.: Familial thrombopathic
thrombocytopenia. Brit. J. Haemat. 15: 305-317, 1968.
3. Monteferrario, D.; Bolar, N. A.; Marneth, A. E.; Hebeda, K. M.;
Bergevoet, S. M.; Veenstra, H.; Laros-van Gorkom, B. A. P.; MacKenzie,
M. A.; Khandanpour, C.; Botezatu, L.; Fransen, E.; Van Camp, G.; and
11 others: A dominant-negative GFI1B mutation in the gray platelet
syndrome. New Eng. J. Med. 370: 245-253, 2014.
4. Rodel, B.; Wagner, T.; Zornig, M.; Niessing, J.; Moroy, T.: The
human homologue (GFI1B) of the chicken GFI gene maps to chromosome
9q34.13--a locus frequently altered in hematopoietic diseases. Genomics 54:
580-582, 1998.
5. Saleque, S.; Cameron, S.; Orkin, S. H.: The zinc-finger proto-oncogene
Gfi-1b is essential for development of the erythroid and megakaryocytic
lineages. Genes Dev. 16: 301-306, 2002.
6. Saleque, S.; Kim, J.; Rooke, H. M.; Orkin, S. H.: Epigenetic regulation
of hematopoietic differentiation by Gfi-1 and Gfi-1b is mediated by
the cofactors CoREST and LSD1. Molec. Cell 27: 562-572, 2007.
7. Stevenson, W. S.; Morel-Kopp, M.-C.; Chen, Q.; Liang, H. P.; Bromhead,
C. J.; Wright, S.; Turakulov, R.; Ng, A. P.; Roberts, A. W.; Bahlo,
M..; Ward, C. M.: GFI1B mutation causes a bleeding disorder with
abnormal platelet function. J. Thromb. Haemost. 11: 2039-2047, 2013.
8. Tong, B.; Grimes, H. L.; Yang, T.-Y.; Bear, S. E.; Qin, Z.; Du,
K.; El-Deiry, W. S.; Tsichlis, P. N.: The Gfi-1B proto-oncoprotein
represses p21(WAF1) and inhibits myeloid cell differentiation. Molec.
Cell. Biol. 18: 2462-2473, 1998.
*FIELD* CN
Cassandra L. Kniffin - updated: 1/27/2014
Patricia A. Hartz - updated: 10/28/2008
Patricia A. Hartz - updated: 9/26/2007
*FIELD* CD
Paul J. Converse: 12/29/1999
*FIELD* ED
carol: 01/28/2014
carol: 1/28/2014
ckniffin: 1/27/2014
mgross: 2/5/2013
mgross: 10/28/2008
terry: 10/28/2008
mgross: 10/2/2007
terry: 9/26/2007
alopez: 12/30/1999
carol: 12/29/1999