ID   GFI1B_HUMAN             Reviewed;         330 AA.
AC   Q5VTD9; O95270; Q5VTD8; Q6FHZ2; Q6T888;
DT   02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT   07-DEC-2004, sequence version 1.
DT   05-OCT-2010, entry version 67.
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   MEDLINE=99097364; 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   FUNCTION, REGION, 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   [9]
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   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-261, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Cervix carcinoma;
RX   PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA   Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA   Mann M.;
RT   "Global, in vivo, and site-specific phosphorylation dynamics in
RT   signaling networks.";
RL   Cell 127:635-648(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   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. Transcriptional repressor or activator
CC       depending on both promoter and cell type context; represses
CC       promoter activity of SOCS1 and SOCS3 and thus, may regulate
CC       cytokine signaling pathways. Cooperates with GATA1 to repress
CC       target gene transcription, such as the apoptosis regulator BCL2L1;
CC       GFI1B silencing in leukemic cell lines markedly increase apoptosis
CC       rate. Inhibits down-regulation of MYC and MYB as well as the
CC       cyclin-dependent kinase inhibitor CDKN1A/P21WAF1 in IL6-treated
CC       myelomonocytic cells. Represses expression of GATA3 in T-cell
CC       lymphomas and inhibits GATA1-mediated transcription; as GATA1 also
CC       mediates erythroid GFI1B transcription, both GATA1 and GFI1B
CC       participate in a feedback regulatory pathway controlling the
CC       expression of GFI1B gene in erythroid cells. Suppresses GATA1-
CC       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.
CC       Plays a role in heterochromatin formation.
CC   -!- SUBUNIT: Forms a complex with GATA1. Interacts with histone
CC       methyltransferases EHMT2 and SUV39H1. Interacts with ARIH2 (via
CC       RING-type 2).
CC   -!- INTERACTION:
CC       Q9HC77:CENPJ; NbExp=1; IntAct=EBI-946212, EBI-946194;
CC       Q9Y219:JAG2; NbExp=1; IntAct=EBI-946212, EBI-946223;
CC       Q99435:NELL2; NbExp=1; IntAct=EBI-946212, EBI-946274;
CC   -!- SUBCELLULAR LOCATION: Nucleus.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q5VTD9-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q5VTD9-2; Sequence=VSP_028459;
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, amd 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   -!- SIMILARITY: Contains 6 C2H2-type zinc fingers.
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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   IPI; IPI00003110; -.
DR   IPI; IPI00479652; -.
DR   RefSeq; NP_001128503.1; -.
DR   RefSeq; NP_004179.3; -.
DR   UniGene; Hs.553160; -.
DR   HSSP; Q9H4T2; 2COT.
DR   ProteinModelPortal; Q5VTD9; -.
DR   SMR; Q5VTD9; 162-327.
DR   IntAct; Q5VTD9; 81.
DR   MINT; MINT-2798741; -.
DR   STRING; Q5VTD9; -.
DR   PhosphoSite; Q5VTD9; -.
DR   PRIDE; Q5VTD9; -.
DR   Ensembl; ENST00000339463; ENSP00000344782; ENSG00000165702.
DR   Ensembl; ENST00000372122; ENSP00000361195; ENSG00000165702.
DR   Ensembl; ENST00000450530; ENSP00000409546; ENSG00000165702.
DR   GeneID; 8328; -.
DR   KEGG; hsa:8328; -.
DR   NMPDR; fig|9606.3.peg.32132; -.
DR   UCSC; uc004ccg.1; human.
DR   UCSC; uc010mzy.1; human.
DR   CTD; 8328; -.
DR   GeneCards; GC09P135821; -.
DR   HGNC; HGNC:4238; GFI1B.
DR   HPA; HPA007012; -.
DR   MIM; 604383; gene.
DR   PharmGKB; PA28649; -.
DR   eggNOG; prNOG10531; -.
DR   HOGENOM; HBG713941; -.
DR   HOVERGEN; HBG106655; -.
DR   InParanoid; Q5VTD9; -.
DR   OMA; LRYSPGM; -.
DR   OrthoDB; EOG9STVQG; -.
DR   PhylomeDB; Q5VTD9; -.
DR   NextBio; 31186; -.
DR   ArrayExpress; Q5VTD9; -.
DR   Bgee; Q5VTD9; -.
DR   CleanEx; HS_GFI1B; -.
DR   Genevestigator; Q5VTD9; -.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0005515; F:protein binding; IPI:IntAct.
DR   GO; GO:0003704; F:specific RNA polymerase II transcription fa...; TAS:ProtInc.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
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 R...; TAS:ProtInc.
DR   GO; GO:0000114; P:regulation of transcription involved in G1 ...; TAS:ProtInc.
DR   GO; GO:0006350; P:transcription; IEA:UniProtKB-KW.
DR   InterPro; IPR007087; Znf_C2H2.
DR   InterPro; IPR015880; Znf_C2H2-like.
DR   InterPro; IPR013087; Znf_C2H2/integrase_DNA-bd.
DR   Gene3D; G3DSA:3.30.160.60; Znf_C2H2/integrase_DNA-bd; 4.
DR   Pfam; PF00096; zf-C2H2; 3.
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   Nucleus; Phosphoprotein; Polymorphism; Proto-oncogene; Repeat;
KW   Repressor; Transcription; 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       Mediates repression of transcription.
FT   REGION       91    330       Interaction with ARIH2.
FT   REGION      164    330       Mediates interaction with GATA1.
FT   MOD_RES     261    261       Phosphoserine.
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
//