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P70338

- GFI1_MOUSE

UniProt

P70338 - GFI1_MOUSE

Protein

Zinc finger protein Gfi-1

Gene

Gfi1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 117 (01 Oct 2014)
      Sequence version 2 (03 Oct 2012)
      Previous versions | rss
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    Functioni

    Transcription repressor essential for hematopoiesis. Functions in a cell-context and development-specific manner. Binds to 5'-TAAATCAC[AT]GCA-3' in the promoter region of a large number of genes. Component of several complexes, including the EHMT2-GFI1-HDAC1, AJUBA-GFI1-HDAC1 and RCOR-GFI-KDM1A-HDAC complexes, that suppress, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Regulates neutrophil differentiation, promotes proliferation of lymphoid cells, and is required for granulocyte development. Mediates, together with U2AF1L4, the alternative splicing of CD45 and controls T-cell receptor signaling. Regulates the endotoxin-mediated Toll-like receptor (TLR) inflammatory response by antagonizing RELA. Cooperates with CBFA2T2 to regulate ITGB1-dependent neurite growth. Controls cell-cycle progression by repressing CDKNIA/p21 transcription in response to TGFB1 via recruitment of GFI1 by ZBTB17 to the CDKNIA/p21 and CDKNIB promoters. Required for the maintenance of inner ear hair cells.5 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri256 – 27924C2H2-type 1PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri285 – 30723C2H2-type 2PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri313 – 33523C2H2-type 3PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri341 – 36323C2H2-type 4PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri369 – 39123C2H2-type 5PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri397 – 42024C2H2-type 6PROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. DNA binding Source: UniProtKB-KW
    2. protein binding Source: UniProtKB
    3. zinc ion binding Source: InterPro

    GO - Biological processi

    1. auditory receptor cell differentiation Source: MGI
    2. cell fate commitment Source: MGI
    3. cellular response to lipopolysaccharide Source: UniProtKB
    4. inner ear morphogenesis Source: MGI
    5. mechanosensory behavior Source: MGI
    6. negative regulation of cell fate specification Source: MGI
    7. negative regulation of neuron projection development Source: UniProtKB
    8. negative regulation of NF-kappaB transcription factor activity Source: UniProtKB
    9. negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    10. positive regulation of cell fate specification Source: MGI
    11. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding, Metal-binding, Zinc

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Zinc finger protein Gfi-1
    Alternative name(s):
    Growth factor independent protein 1
    Gene namesi
    Name:Gfi1
    Synonyms:Gfi-1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 5

    Organism-specific databases

    MGIiMGI:103170. Gfi1.

    Subcellular locationi

    Nucleus
    Note: Colocalizes with PIAS3 and RUNX1T1 in nuclear dots.By similarity

    GO - Cellular componenti

    1. nucleus Source: UniProtKB-SubCell
    2. transcriptional repressor complex Source: UniProtKB

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Disruption phenotypei

    Null mice exhibit neutropenia, characterized by absence of neutrophils. This results in growth retardation, susceptibility to bacterial infection and early lethality. Immature granulocytes and macrophage precursors accumulate in bone marrow. Mice have inner ear anomalies, as they are ataxic, circle, display head tilting behavior and do not respond to noise. In the inner ear, hair cells are disorganized in both vestibule and cochlea. Outer hair cells of the cochlea are initially improperly innervated, and just before birth, mice lose all cochlear hair cells due to apoptosis. By 5 months there is a dramatic reduction in the number of cochlear neurons.2 Publications

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi2 – 21P → A: Abrogates transcriptional repression. No change in nuclear location. 1 Publication
    Mutagenesisi3 – 31R → A: Partial loss of transcription repression. No change in nuclear location. 1 Publication
    Mutagenesisi4 – 41S → A: Partial loss of transcription repression. No change in nuclear location. 1 Publication
    Mutagenesisi10 – 101K → A: Abolishes most of the nuclear localization and reduces transcriptional repressor activity; when associated with A-11. 1 Publication
    Mutagenesisi11 – 111K → A: Abolishes most of the nuclear localization and reduces transcriptional repressor activity; when associated with A-10. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 423423Zinc finger protein Gfi-1PRO_0000047194Add
    BLAST

    Post-translational modificationi

    Ubiquitinated.By similarity

    Keywords - PTMi

    Ubl conjugation

    Proteomic databases

    PRIDEiP70338.

    PTM databases

    PhosphoSiteiP70338.

    Expressioni

    Inductioni

    By IL2 and CSF3. Induced by the endotoxin bacterial lipopolysaccharide (LPS) in primary bone marrow macrophages (BMDMs).1 Publication

    Gene expression databases

    ArrayExpressiP70338.
    BgeeiP70338.
    CleanExiMM_GFI1.
    GenevestigatoriP70338.

    Interactioni

    Subunit structurei

    Interacts (via the zinc-finger domain) with ARIH2; the interaction prevents GFI1 ubiquitination and proteasomal degradation. Forms a complex with EHMT2 and HDAC1 to promote 'Lys-9' dimethylation of H3 (H3K9Me2) and repress expression of target genes. Interacts directly with EHMT2. Interacts with RUNX1T1; the interaction represses HDAC-mediated transcriptional activity. Interacts (via the C-terminal zinc fingers) with ZBTB17; the interaction results in the recruitment of GFI1 to the CDKN1A/p21 and CDKNIB promoters and repression of transcription By similarity. Interacts with U2AF1L4. Component of RCOR-GFI-KDM1A-HDAC complexes. Interacts directly with RCOR1, KDM1A and HDAC2. Also interacts with HDAC1. Component of the GFI1-AJUBA-HDAC1 repressor complex. Interacts directly with AJUBA (via its LIM domains); the interaction results in the HDAC-dependent corepression of a subset of GFI1 target genes and, occurs independently of the SNAG domain. Interacts with SPI1; the interaction inhibits SPI1 transcriptional activity and represses SPI1-regulated macrophage-specific genes required for proper granulocyte development. Interacts with PIAS3; the interaction relieves the inhibitory effect of PIAS3 on STAT3-mediated transcriptional activity. Interacts with RELA; the interaction occurs on liposaccharide (LPS) stimulation and controls RELA DNA binding activity and regulates endotoxin-mediated TOLL-like receptor inflammatory response.By similarity3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Chaf1aQ9QWF05EBI-3954754,EBI-639217
    ETS1P149212EBI-3954754,EBI-913209From a different organism.
    Pias3O547146EBI-3954754,EBI-927969
    Spi1P174332EBI-3954754,EBI-607588
    U2af1l4Q8BGJ95EBI-3954754,EBI-4288480

    Protein-protein interaction databases

    BioGridi199900. 2 interactions.
    IntActiP70338. 12 interactions.

    Structurei

    3D structure databases

    ProteinModelPortaliP70338.
    SMRiP70338. Positions 235-423.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 2020SNAG domainAdd
    BLAST
    Regioni141 – 258118Required for interaction with RELABy similarityAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi159 – 21052Ala/Gly-richAdd
    BLAST

    Domaini

    Zinc fingers 3,4 and 5 are required for DNA binding and for interaction with SPI1.By similarity
    The SNAG domain of GFIs is required for nuclear location and for interaction with some corepressors.2 Publications

    Sequence similaritiesi

    Contains 6 C2H2-type zinc fingers.PROSITE-ProRule annotation

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri256 – 27924C2H2-type 1PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri285 – 30723C2H2-type 2PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri313 – 33523C2H2-type 3PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri341 – 36323C2H2-type 4PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri369 – 39123C2H2-type 5PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri397 – 42024C2H2-type 6PROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Repeat, Zinc-finger

    Phylogenomic databases

    eggNOGiCOG5048.
    GeneTreeiENSGT00740000115096.
    HOVERGENiHBG006967.
    InParanoidiP70338.
    KOiK09223.
    OrthoDBiEOG72RN05.
    TreeFamiTF350784.

    Family and domain databases

    Gene3Di3.30.160.60. 6 hits.
    InterProiIPR007087. Znf_C2H2.
    IPR015880. Znf_C2H2-like.
    IPR013087. Znf_C2H2/integrase_DNA-bd.
    IPR001878. Znf_CCHC.
    [Graphical view]
    PfamiPF00096. zf-C2H2. 1 hit.
    [Graphical view]
    SMARTiSM00355. ZnF_C2H2. 6 hits.
    SM00343. ZnF_C2HC. 1 hit.
    [Graphical view]
    PROSITEiPS00028. ZINC_FINGER_C2H2_1. 6 hits.
    PS50157. ZINC_FINGER_C2H2_2. 6 hits.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P70338-1 [UniParc]FASTAAdd to Basket

    « Hide

    MPRSFLVKSK KAHSYHQPRS PGPDYSLRLE TVPAPGRAEG GAVSAGESKM    50
    EPRERLSPDS QLTEAPDRAS ASPNSCEGSV CDPCSEFEDF WRPPSPSVSP 100
    ASEKSLCRSL DEAQPYTLPF KPYAWSGLAG SDLRHLVQSY RQCSALERSA 150
    GLSLFCERGS EPGRPAARYG PEQAAGGAGA GQPGRCGVAG GATSAAGLGL 200
    YGDFAPAAAG LYERPSTAAG RLYQDHGHEL HADKSVGVKV ESELLCTRLL 250
    LGGGSYKCIK CSKVFSTPHG LEVHVRRSHS GTRPFACEMC GKTFGHAVSL 300
    EQHKAVHSQE RSFDCKICGK SFKRSSTLST HLLIHSDTRP YPCQYCGKRF 350
    HQKSDMKKHT FIHTGEKPHK CQVCGKAFSQ SSNLITHSRK HTGFKPFGCD 400
    LCGKGFQRKV DLRRHRETQH GLK 423
    Length:423
    Mass (Da):45,944
    Last modified:October 3, 2012 - v2
    Checksum:i63AB726025300B6B
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti185 – 1851R → S in AAC52959. (PubMed:8985317)Curated
    Sequence conflicti185 – 1851R → S in AAB36829. (PubMed:8622900)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U58973 mRNA. Translation: AAC52960.1.
    U58972 mRNA. Translation: AAC52959.1.
    U78312 mRNA. Translation: AAB36829.1.
    AC117574 Genomic DNA. No translation available.
    CCDSiCCDS57371.1.
    RefSeqiNP_034408.1. NM_010278.2.
    XP_006534855.1. XM_006534792.1.
    XP_006534856.1. XM_006534793.1.
    XP_006534857.1. XM_006534794.1.
    UniGeneiMm.2078.
    Mm.453139.

    Genome annotation databases

    EnsembliENSMUST00000031205; ENSMUSP00000135884; ENSMUSG00000029275.
    ENSMUST00000159164; ENSMUSP00000137229; ENSMUSG00000029275.
    GeneIDi14581.
    KEGGimmu:14581.
    UCSCiuc029vkg.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U58973 mRNA. Translation: AAC52960.1 .
    U58972 mRNA. Translation: AAC52959.1 .
    U78312 mRNA. Translation: AAB36829.1 .
    AC117574 Genomic DNA. No translation available.
    CCDSi CCDS57371.1.
    RefSeqi NP_034408.1. NM_010278.2.
    XP_006534855.1. XM_006534792.1.
    XP_006534856.1. XM_006534793.1.
    XP_006534857.1. XM_006534794.1.
    UniGenei Mm.2078.
    Mm.453139.

    3D structure databases

    ProteinModelPortali P70338.
    SMRi P70338. Positions 235-423.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 199900. 2 interactions.
    IntActi P70338. 12 interactions.

    PTM databases

    PhosphoSitei P70338.

    Proteomic databases

    PRIDEi P70338.

    Protocols and materials databases

    DNASUi 14581.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000031205 ; ENSMUSP00000135884 ; ENSMUSG00000029275 .
    ENSMUST00000159164 ; ENSMUSP00000137229 ; ENSMUSG00000029275 .
    GeneIDi 14581.
    KEGGi mmu:14581.
    UCSCi uc029vkg.1. mouse.

    Organism-specific databases

    CTDi 2672.
    MGIi MGI:103170. Gfi1.

    Phylogenomic databases

    eggNOGi COG5048.
    GeneTreei ENSGT00740000115096.
    HOVERGENi HBG006967.
    InParanoidi P70338.
    KOi K09223.
    OrthoDBi EOG72RN05.
    TreeFami TF350784.

    Miscellaneous databases

    NextBioi 286310.
    PROi P70338.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P70338.
    Bgeei P70338.
    CleanExi MM_GFI1.
    Genevestigatori P70338.

    Family and domain databases

    Gene3Di 3.30.160.60. 6 hits.
    InterProi IPR007087. Znf_C2H2.
    IPR015880. Znf_C2H2-like.
    IPR013087. Znf_C2H2/integrase_DNA-bd.
    IPR001878. Znf_CCHC.
    [Graphical view ]
    Pfami PF00096. zf-C2H2. 1 hit.
    [Graphical view ]
    SMARTi SM00355. ZnF_C2H2. 6 hits.
    SM00343. ZnF_C2HC. 1 hit.
    [Graphical view ]
    PROSITEi PS00028. ZINC_FINGER_C2H2_1. 6 hits.
    PS50157. ZINC_FINGER_C2H2_2. 6 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Characterization of pal-1, a common proviral insertion site in murine leukemia virus-induced lymphomas of c-myc and Pim-1 transgenic mice."
      Scheijen B., Jonkers J., Acton D., Berns A.
      J. Virol. 71:9-16(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: BALB/c.
      Tissue: Thymus.
    2. "Zinc finger protein GFI-1 cooperates with myc and pim-1 in T-cell lymphomagenesis by reducing the requirements for IL-2."
      Zornig M., Schmidt T., Karsunky H., Grzeschiczek A., Moroy T.
      Oncogene 12:1789-1801(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    4. "The Gfi-1 proto-oncoprotein contains a novel transcriptional repressor domain, SNAG, and inhibits G1 arrest induced by interleukin-2 withdrawal."
      Grimes H.L., Chan T.O., Zweidler-McKay P.A., Tong B., Tsichlis P.N.
      Mol. Cell. Biol. 16:6263-6272(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: DOMAIN SNAG, MUTAGENESIS OF PRO-2; ARG-3; SER-4; LYS-10 AND LYS-11.
    5. "The zinc finger transcription factor Gfi1, implicated in lymphomagenesis, is required for inner ear hair cell differentiation and survival."
      Wallis D., Hamblen M., Zhou Y., Venken K.J., Schumacher A., Grimes H.L., Zoghbi H.Y., Orkin S.H., Bellen H.J.
      Development 130:221-232(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION.
    6. "Auxiliary splice factor U2AF26 and transcription factor Gfi1 cooperate directly in regulating CD45 alternative splicing."
      Heyd F., ten Dam G., Moeroey T.
      Nat. Immunol. 7:859-867(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH U2AF1L4.
    7. "The transcriptional repressor GFI-1 antagonizes PU.1 activity through protein-protein interaction."
      Dahl R., Iyer S.R., Owens K.S., Cuylear D.D., Simon M.C.
      J. Biol. Chem. 282:6473-6483(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SPI1, DOMAIN ZINC-FINGER, FUNCTION, DISRUPTION PHENOTYPE.
    8. "Epigenetic regulation of hematopoietic differentiation by Gfi-1 and Gfi-1b is mediated by the cofactors CoREST and LSD1."
      Saleque S., Kim J., Rooke H.M., Orkin S.H.
      Mol. Cell 27:562-572(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION AS A COMPONENT OF A GFI-COR-KDM1A-HDAC COMPLEX, INTERACTION WITH RCOR1; HDAC1; HDAC2 AND KDM1A, FUNCTION.
    9. "Zinc finger protein Gfi1 controls the endotoxin-mediated Toll-like receptor inflammatory response by antagonizing NF-kappaB p65."
      Sharif-Askari E., Vassen L., Kosan C., Khandanpour C., Gaudreau M.C., Heyd F., Okayama T., Jin J., Rojas M.E., Grimes H.L., Zeng H., Moroy T.
      Mol. Cell. Biol. 30:3929-3942(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION, FUNCTION.

    Entry informationi

    Entry nameiGFI1_MOUSE
    AccessioniPrimary (citable) accession number: P70338
    Secondary accession number(s): O09063
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1999
    Last sequence update: October 3, 2012
    Last modified: October 1, 2014
    This is version 117 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3