GFI1_RAT
ID GFI1_RAT Reviewed; 423 AA.
AC Q07120;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1994, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Zinc finger protein Gfi-1;
DE AltName: Full=Growth factor independent protein 1;
GN Name=Gfi1; Synonyms=Gfi-1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
RX PubMed=8441411; DOI=10.1128/mcb.13.3.1759-1768.1993;
RA Gilks C.B., Bear S.E., Grimes H.L., Tsichlis P.N.;
RT "Progression of interleukin-2 (IL-2)-dependent rat T cell lymphoma lines to
RT IL-2-independent growth following activation of a gene (Gfi-1) encoding a
RT novel zinc finger protein.";
RL Mol. Cell. Biol. 13:1759-1768(1993).
RN [2]
RP INTERACTION WITH ZBTB17, AND FUNCTION.
RX PubMed=20190815; DOI=10.1038/onc.2010.48;
RA Liu Q., Basu S., Qiu Y., Tang F., Dong F.;
RT "A role of Miz-1 in Gfi-1-mediated transcriptional repression of CDKN1A.";
RL Oncogene 29:2843-2852(2010).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20 AND SER-57, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [4]
RP STRUCTURE BY NMR OF 312-393 IN COMPLEX WITH DNA.
RX PubMed=20153336; DOI=10.1016/j.jmb.2010.02.006;
RA Lee S., Doddapaneni K., Hogue A., McGhee L., Meyers S., Wu Z.;
RT "Solution structure of Gfi-1 zinc domain bound to consensus DNA.";
RL J. Mol. Biol. 397:1055-1066(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 promoter region.
CC Implicated in the maintenance of inner ear hair cells (By similarity).
CC {ECO:0000250, ECO:0000269|PubMed:20190815}.
CC -!- SUBUNIT: Interacts with U2AF1L4. Component of RCOR-GFI-KDM1A-HDAC
CC complexes. Interacts directly with RCOR1, KDM1A and HDAC2. Also
CC interacts with HDAC1. regions. Interacts (via the zinc-finger domain)
CC with ARIH2; the interaction prevents GFI1 ubiquitination and
CC proteasomal degradation. Interacts with PIAS3; the interaction relieves
CC the inhibitory effect of PIAS3 on STAT3-mediated transcriptional
CC activity. Forms a complex with EHMT2 and HDAC1 to promote 'Lys-9'
CC dimethylation of H3 (H3K9Me2) and repress expression of target genes.
CC Interacts directly with EHMT2. 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 independent 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 RUNX1T1;
CC the interaction represses HDAC-mediated transcriptional activity.
CC Interacts with RELA; the interaction occurs on liposaccharide (LPS)
CC stimulation controls RELA DNA binding activity and regulates endotoxin-
CC mediated TOLL-like receptor inflammatory response (By similarity).
CC Interacts (via the C-terminal zinc fingers) with ZBTB17; the
CC interaction results in the recruitment of GFI1 to the CDKN1A/p21
CC promoter and repression of CDKN1A/p21 transcription. {ECO:0000250,
CC ECO:0000269|PubMed:20153336, ECO:0000269|PubMed:20190815}.
CC -!- INTERACTION:
CC Q07120; Q96KQ7: EHMT2; Xeno; NbExp=3; IntAct=EBI-4289236, EBI-744366;
CC Q07120; Q13105-1: ZBTB17; Xeno; NbExp=2; IntAct=EBI-4289236, EBI-15753185;
CC Q07120; Q60821: Zbtb17; Xeno; NbExp=3; IntAct=EBI-4289236, EBI-11598394;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Note=Colocalizes with
CC PIAS3 and RUNX1T1 in nuclear dots. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Restricted to lymphoid tissues and testes in adult
CC animals. {ECO:0000269|PubMed:8441411}.
CC -!- DEVELOPMENTAL STAGE: Expression enhanced late after interaction of IL-2
CC with its receptor, approximately when cells enter S phase.
CC {ECO:0000269|PubMed:8441411}.
CC -!- DOMAIN: Zinc fingers 3,4 and 5 are required for DNA binding and for
CC interaction with SPI1.
CC -!- DOMAIN: The SNAG domain of GFIs is required for nuclear location and
CC for interaction with some corepressors. {ECO:0000250}.
CC -!- PTM: Ubiquitinated. {ECO:0000250}.
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DR EMBL; L06986; AAA41212.1; -; mRNA.
DR PIR; A48152; A48152.
DR RefSeq; NP_036698.1; NM_012566.1.
DR RefSeq; XP_008768139.1; XM_008769917.2.
DR RefSeq; XP_008768140.1; XM_008769918.2.
DR RefSeq; XP_017454563.1; XM_017599074.1.
DR PDB; 2KMK; NMR; -; A=312-393.
DR PDBsum; 2KMK; -.
DR AlphaFoldDB; Q07120; -.
DR SMR; Q07120; -.
DR DIP; DIP-48689N; -.
DR IntAct; Q07120; 5.
DR STRING; 10116.ENSRNOP00000002807; -.
DR iPTMnet; Q07120; -.
DR PhosphoSitePlus; Q07120; -.
DR PaxDb; Q07120; -.
DR PRIDE; Q07120; -.
DR Ensembl; ENSRNOT00000002807; ENSRNOP00000002807; ENSRNOG00000002042.
DR GeneID; 24388; -.
DR KEGG; rno:24388; -.
DR UCSC; RGD:2680; rat.
DR CTD; 2672; -.
DR RGD; 2680; Gfi1.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000156166; -.
DR HOGENOM; CLU_002678_94_9_1; -.
DR InParanoid; Q07120; -.
DR OMA; KPYMWNS; -.
DR OrthoDB; 1318335at2759; -.
DR PhylomeDB; Q07120; -.
DR TreeFam; TF350784; -.
DR EvolutionaryTrace; Q07120; -.
DR PRO; PR:Q07120; -.
DR Proteomes; UP000002494; Chromosome 14.
DR Bgee; ENSRNOG00000002042; Expressed in thymus and 8 other tissues.
DR Genevisible; Q07120; RN.
DR GO; GO:0016604; C:nuclear body; ISO:RGD.
DR GO; GO:0016363; C:nuclear matrix; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
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:RGD.
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:RGD.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:RGD.
DR GO; GO:0045165; P:cell fate commitment; ISO:RGD.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISO:RGD.
DR GO; GO:0030097; P:hemopoiesis; IEA:InterPro.
DR GO; GO:0042491; P:inner ear auditory receptor cell differentiation; ISO:RGD.
DR GO; GO:0042472; P:inner ear morphogenesis; ISO:RGD.
DR GO; GO:0007638; P:mechanosensory behavior; ISO:RGD.
DR GO; GO:0010956; P:negative regulation of calcidiol 1-monooxygenase activity; ISO:RGD.
DR GO; GO:0009996; P:negative regulation of cell fate specification; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0042660; P:positive regulation of cell fate specification; ISO:RGD.
DR GO; GO:0070105; P:positive regulation of interleukin-6-mediated signaling pathway; ISO:RGD.
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:RGD.
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 3D-structure; DNA-binding; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Transcription; Transcription regulation;
KW Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..423
FT /note="Zinc finger protein Gfi-1"
FT /id="PRO_0000047195"
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..102
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1..20
FT /note="SNAG domain"
FT /evidence="ECO:0000250"
FT REGION 141..258
FT /note="Required for interaction with RELA"
FT /evidence="ECO:0000250"
FT COMPBIAS 63..81
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 20
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 57
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT STRAND 316..318
FT /evidence="ECO:0007829|PDB:2KMK"
FT STRAND 321..324
FT /evidence="ECO:0007829|PDB:2KMK"
FT HELIX 325..336
FT /evidence="ECO:0007829|PDB:2KMK"
FT STRAND 344..346
FT /evidence="ECO:0007829|PDB:2KMK"
FT STRAND 349..352
FT /evidence="ECO:0007829|PDB:2KMK"
FT HELIX 353..364
FT /evidence="ECO:0007829|PDB:2KMK"
FT TURN 372..374
FT /evidence="ECO:0007829|PDB:2KMK"
FT STRAND 377..380
FT /evidence="ECO:0007829|PDB:2KMK"
FT HELIX 381..391
FT /evidence="ECO:0007829|PDB:2KMK"
SQ SEQUENCE 423 AA; 45858 MW; FC39B6100D684D14 CRC64;
MPRSFLVKSK KAHSYHQPRS PGPDYSLRLE TVPVPGRADG GAVSAGESKM EPRERLSPES
QLTEAPDRAS ASPNSCEGSV CDPSSEFEDY WRPPSPSVSP ASEKSLCRSL DEAQPYTLPF
KPYAWSGLAG SDLRHLVQSY RQCSALERSA GLSLFCERGA ESGRPAARYG SEQAAGGAGA
GQPGSCGAAS GATSAGGLGL YGDFAPAAAG LFERPSTAAG RLYQDRGHEL HADKSVGVKV
ESELLCTRLL LGGGSYKCIK CSKVFSTPHG LEVHVRRSHS GTRPFACEMC GKTFGHAVSL
EQHKAVHSQE RSFDCKICGK SFKRSSTLST HLLIHSDTRP YPCQYCGKRF HQKSDMKKHT
FIHTGEKPHK CQVCGKAFSQ SSNLITHSRK HTGFKPFGCD LCGKGFQRKV DLRRHRETQH
GLK
