GFI1_MOUSE
ID GFI1_MOUSE Reviewed; 423 AA.
AC P70338; O09063;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 2.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Zinc finger protein Gfi-1;
DE AltName: Full=Growth factor independent protein 1;
GN Name=Gfi1; Synonyms=Gfi-1;
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].
RC STRAIN=BALB/cJ; TISSUE=Thymus;
RX PubMed=8985317; DOI=10.1128/jvi.71.1.9-16.1997;
RA Scheijen B., Jonkers J., Acton D., Berns A.;
RT "Characterization of pal-1, a common proviral insertion site in murine
RT leukemia virus-induced lymphomas of c-myc and Pim-1 transgenic mice.";
RL J. Virol. 71:9-16(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=8622900;
RA Zornig M., Schmidt T., Karsunky H., Grzeschiczek A., Moroy T.;
RT "Zinc finger protein GFI-1 cooperates with myc and pim-1 in T-cell
RT lymphomagenesis by reducing the requirements for IL-2.";
RL Oncogene 12:1789-1801(1996).
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 DOMAIN SNAG, AND MUTAGENESIS OF PRO-2; ARG-3; SER-4; LYS-10 AND LYS-11.
RX PubMed=8887656; DOI=10.1128/mcb.16.11.6263;
RA Grimes H.L., Chan T.O., Zweidler-McKay P.A., Tong B., Tsichlis P.N.;
RT "The Gfi-1 proto-oncoprotein contains a novel transcriptional repressor
RT domain, SNAG, and inhibits G1 arrest induced by interleukin-2 withdrawal.";
RL Mol. Cell. Biol. 16:6263-6272(1996).
RN [5]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=12441305; DOI=10.1242/dev.00190;
RA Wallis D., Hamblen M., Zhou Y., Venken K.J., Schumacher A., Grimes H.L.,
RA Zoghbi H.Y., Orkin S.H., Bellen H.J.;
RT "The zinc finger transcription factor Gfi1, implicated in lymphomagenesis,
RT is required for inner ear hair cell differentiation and survival.";
RL Development 130:221-232(2003).
RN [6]
RP INTERACTION WITH U2AF1L4.
RX PubMed=16819553; DOI=10.1038/ni1361;
RA Heyd F., ten Dam G., Moeroey T.;
RT "Auxiliary splice factor U2AF26 and transcription factor Gfi1 cooperate
RT directly in regulating CD45 alternative splicing.";
RL Nat. Immunol. 7:859-867(2006).
RN [7]
RP INTERACTION WITH SPI1, DOMAIN ZINC-FINGER, FUNCTION, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=17197705; DOI=10.1074/jbc.m607613200;
RA Dahl R., Iyer S.R., Owens K.S., Cuylear D.D., Simon M.C.;
RT "The transcriptional repressor GFI-1 antagonizes PU.1 activity through
RT protein-protein interaction.";
RL J. Biol. Chem. 282:6473-6483(2007).
RN [8]
RP IDENTIFICATION AS A COMPONENT OF A GFI-COR-KDM1A-HDAC COMPLEX, INTERACTION
RP WITH RCOR1; HDAC1; HDAC2 AND KDM1A, AND FUNCTION.
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 [9]
RP INDUCTION, AND FUNCTION.
RX PubMed=20547752; DOI=10.1128/mcb.00087-10;
RA Sharif-Askari E., Vassen L., Kosan C., Khandanpour C., Gaudreau M.C.,
RA Heyd F., Okayama T., Jin J., Rojas M.E., Grimes H.L., Zeng H., Moroy T.;
RT "Zinc finger protein Gfi1 controls the endotoxin-mediated Toll-like
RT receptor inflammatory response by antagonizing NF-kappaB p65.";
RL Mol. Cell. Biol. 30:3929-3942(2010).
CC -!- FUNCTION: Transcription repressor essential for hematopoiesis.
CC Functions in a cell-context and development-specific manner. Binds to
CC 5'-TAAATCAC[AT]GCA-3' in the promoter region of a large number of
CC genes. Component of several complexes, including the EHMT2-GFI1-HDAC1,
CC AJUBA-GFI1-HDAC1 and RCOR-GFI-KDM1A-HDAC complexes, that suppress, via
CC histone deacetylase (HDAC) recruitment, a number of genes implicated in
CC multilineage blood cell development. Regulates neutrophil
CC differentiation, promotes proliferation of lymphoid cells, and is
CC required for granulocyte development. Mediates, together with U2AF1L4,
CC the alternative splicing of CD45 and controls T-cell receptor
CC signaling. Regulates the endotoxin-mediated Toll-like receptor (TLR)
CC inflammatory response by antagonizing RELA. Cooperates with CBFA2T2 to
CC regulate ITGB1-dependent neurite growth. Controls cell-cycle
CC progression by repressing CDKNIA/p21 transcription in response to TGFB1
CC via recruitment of GFI1 by ZBTB17 to the CDKNIA/p21 and CDKNIB
CC promoters. Required for the maintenance of inner ear hair cells.
CC {ECO:0000269|PubMed:12441305, ECO:0000269|PubMed:17197705,
CC ECO:0000269|PubMed:17707228, ECO:0000269|PubMed:20547752,
CC ECO:0000269|PubMed:8622900}.
CC -!- SUBUNIT: Interacts (via the zinc-finger domain) with ARIH2; the
CC interaction prevents GFI1 ubiquitination and proteasomal degradation.
CC Forms a complex with EHMT2 and HDAC1 to promote 'Lys-9' dimethylation
CC of H3 (H3K9Me2) and repress expression of target genes. Interacts
CC directly with EHMT2. Interacts with RUNX1T1; the interaction represses
CC HDAC-mediated transcriptional activity. Interacts (via the C-terminal
CC zinc fingers) with ZBTB17; the interaction results in the recruitment
CC of GFI1 to the CDKN1A/p21 and CDKNIB promoters and repression of
CC transcription (By similarity). Interacts with U2AF1L4. Component of
CC RCOR-GFI-KDM1A-HDAC complexes. Interacts directly with RCOR1, KDM1A and
CC HDAC2. Also interacts with HDAC1. Component of the GFI1-AJUBA-HDAC1
CC repressor complex. Interacts directly with AJUBA (via its LIM domains);
CC the interaction results in the HDAC-dependent corepression of a subset
CC of GFI1 target genes and, occurs independently of the SNAG domain.
CC Interacts with SPI1; the interaction inhibits SPI1 transcriptional
CC activity and represses SPI1-regulated macrophage-specific genes
CC required for proper granulocyte development. Interacts with PIAS3; the
CC interaction relieves the inhibitory effect of PIAS3 on STAT3-mediated
CC transcriptional activity. Interacts with RELA; the interaction occurs
CC on liposaccharide (LPS) stimulation and controls RELA DNA binding
CC activity and regulates endotoxin-mediated TOLL-like receptor
CC inflammatory response. {ECO:0000250, ECO:0000269|PubMed:16819553,
CC ECO:0000269|PubMed:17197705, ECO:0000269|PubMed:17707228}.
CC -!- INTERACTION:
CC P70338; Q9QWF0: Chaf1a; NbExp=5; IntAct=EBI-3954754, EBI-639217;
CC P70338; O54714: Pias3; NbExp=6; IntAct=EBI-3954754, EBI-927969;
CC P70338; P17433: Spi1; NbExp=2; IntAct=EBI-3954754, EBI-607588;
CC P70338; Q8BGJ9: U2af1l4; NbExp=5; IntAct=EBI-3954754, EBI-4288480;
CC P70338; P14921: ETS1; Xeno; NbExp=2; IntAct=EBI-3954754, EBI-913209;
CC -!- SUBCELLULAR LOCATION: Nucleus. Note=Colocalizes with PIAS3 and RUNX1T1
CC in nuclear dots. {ECO:0000250}.
CC -!- INDUCTION: By IL2 and CSF3. Induced by the endotoxin bacterial
CC lipopolysaccharide (LPS) in primary bone marrow macrophages (BMDMs).
CC {ECO:0000269|PubMed:20547752}.
CC -!- DOMAIN: Zinc fingers 3,4 and 5 are required for DNA binding and for
CC interaction with SPI1. {ECO:0000250}.
CC -!- DOMAIN: The SNAG domain of GFIs is required for nuclear location and
CC for interaction with some corepressors. {ECO:0000269|PubMed:17197705,
CC ECO:0000269|PubMed:8887656}.
CC -!- PTM: Ubiquitinated. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Null mice exhibit neutropenia, characterized by
CC absence of neutrophils. This results in growth retardation,
CC susceptibility to bacterial infection and early lethality. Immature
CC granulocytes and macrophage precursors accumulate in bone marrow. Mice
CC have inner ear anomalies, as they are ataxic, circle, display head
CC tilting behavior and do not respond to noise. In the inner ear, hair
CC cells are disorganized in both vestibule and cochlea. Outer hair cells
CC of the cochlea are initially improperly innervated, and just before
CC birth, mice lose all cochlear hair cells due to apoptosis. By 5 months
CC there is a dramatic reduction in the number of cochlear neurons.
CC {ECO:0000269|PubMed:12441305, ECO:0000269|PubMed:17197705}.
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DR EMBL; U58973; AAC52960.1; -; mRNA.
DR EMBL; U58972; AAC52959.1; -; mRNA.
DR EMBL; U78312; AAB36829.1; -; mRNA.
DR EMBL; AC117574; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS57371.1; -.
DR RefSeq; NP_034408.1; NM_010278.2.
DR RefSeq; XP_006534854.2; XM_006534791.2.
DR RefSeq; XP_006534855.1; XM_006534792.1.
DR RefSeq; XP_006534856.1; XM_006534793.3.
DR RefSeq; XP_006534857.1; XM_006534794.1.
DR RefSeq; XP_011247711.1; XM_011249409.2.
DR AlphaFoldDB; P70338; -.
DR SMR; P70338; -.
DR BioGRID; 199900; 2.
DR IntAct; P70338; 13.
DR STRING; 10090.ENSMUSP00000135884; -.
DR iPTMnet; P70338; -.
DR PhosphoSitePlus; P70338; -.
DR EPD; P70338; -.
DR jPOST; P70338; -.
DR PaxDb; P70338; -.
DR PRIDE; P70338; -.
DR ProteomicsDB; 272956; -.
DR DNASU; 14581; -.
DR GeneID; 14581; -.
DR KEGG; mmu:14581; -.
DR CTD; 2672; -.
DR MGI; MGI:103170; Gfi1.
DR eggNOG; KOG1721; Eukaryota.
DR InParanoid; P70338; -.
DR TreeFam; TF350784; -.
DR BioGRID-ORCS; 14581; 3 hits in 77 CRISPR screens.
DR PRO; PR:P70338; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P70338; protein.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0016363; C:nuclear matrix; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0017053; C:transcription repressor complex; ISS:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IBA:GO_Central.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISO:MGI.
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:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:MGI.
DR GO; GO:0045165; P:cell fate commitment; IMP:MGI.
DR GO; GO:0001708; P:cell fate specification; IMP:MGI.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEP:UniProtKB.
DR GO; GO:0030097; P:hemopoiesis; IEA:InterPro.
DR GO; GO:0042491; P:inner ear auditory receptor cell differentiation; IMP:MGI.
DR GO; GO:0042472; P:inner ear morphogenesis; IMP:MGI.
DR GO; GO:0007638; P:mechanosensory behavior; IMP:MGI.
DR GO; GO:0010956; P:negative regulation of calcidiol 1-monooxygenase activity; ISO:MGI.
DR GO; GO:0009996; P:negative regulation of cell fate specification; IMP:MGI.
DR GO; GO:0010977; P:negative regulation of neuron projection development; ISS:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0042660; P:positive regulation of cell fate specification; IMP:MGI.
DR GO; GO:0070105; P:positive regulation of interleukin-6-mediated signaling pathway; ISO:MGI.
DR GO; GO:0051569; P:regulation of histone H3-K4 methylation; IEA:InterPro.
DR GO; GO:0034121; P:regulation of toll-like receptor signaling pathway; ISO:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR InterPro; IPR029840; GFI1/1B.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR PANTHER; PTHR24404:SF46; PTHR24404:SF46; 1.
DR Pfam; PF00096; zf-C2H2; 6.
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 DNA-binding; Metal-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; Transcription; Transcription regulation; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1..423
FT /note="Zinc finger protein Gfi-1"
FT /id="PRO_0000047194"
FT ZN_FING 256..279
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 285..307
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 313..335
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 341..363
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 369..391
FT /note="C2H2-type 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 397..420
FT /note="C2H2-type 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 1..76
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1..20
FT /note="SNAG domain"
FT REGION 141..258
FT /note="Required for interaction with RELA"
FT /evidence="ECO:0000250"
FT MOD_RES 20
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q07120"
FT MOD_RES 57
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q07120"
FT MUTAGEN 2
FT /note="P->A: Abrogates transcriptional repression. No
FT change in nuclear location."
FT /evidence="ECO:0000269|PubMed:8887656"
FT MUTAGEN 3
FT /note="R->A: Partial loss of transcription repression. No
FT change in nuclear location."
FT /evidence="ECO:0000269|PubMed:8887656"
FT MUTAGEN 4
FT /note="S->A: Partial loss of transcription repression. No
FT change in nuclear location."
FT /evidence="ECO:0000269|PubMed:8887656"
FT MUTAGEN 10
FT /note="K->A: Abolishes most of the nuclear localization and
FT reduces transcriptional repressor activity; when associated
FT with A-11."
FT /evidence="ECO:0000269|PubMed:8887656"
FT MUTAGEN 11
FT /note="K->A: Abolishes most of the nuclear localization and
FT reduces transcriptional repressor activity; when associated
FT with A-10."
FT /evidence="ECO:0000269|PubMed:8887656"
FT CONFLICT 185
FT /note="R -> S (in Ref. 1; AAC52959 and 2; AAB36829)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 423 AA; 45944 MW; 63AB726025300B6B CRC64;
MPRSFLVKSK KAHSYHQPRS PGPDYSLRLE TVPAPGRAEG GAVSAGESKM EPRERLSPDS
QLTEAPDRAS ASPNSCEGSV CDPCSEFEDF WRPPSPSVSP ASEKSLCRSL DEAQPYTLPF
KPYAWSGLAG SDLRHLVQSY RQCSALERSA GLSLFCERGS EPGRPAARYG PEQAAGGAGA
GQPGRCGVAG GATSAAGLGL YGDFAPAAAG LYERPSTAAG RLYQDHGHEL HADKSVGVKV
ESELLCTRLL LGGGSYKCIK CSKVFSTPHG LEVHVRRSHS GTRPFACEMC GKTFGHAVSL
EQHKAVHSQE RSFDCKICGK SFKRSSTLST HLLIHSDTRP YPCQYCGKRF HQKSDMKKHT
FIHTGEKPHK CQVCGKAFSQ SSNLITHSRK HTGFKPFGCD LCGKGFQRKV DLRRHRETQH
GLK
