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P70338

- GFI1_MOUSE

UniProt

P70338 - GFI1_MOUSE

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Protein

Zinc finger protein Gfi-1

Gene
Gfi1, Gfi-1
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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 1Add
BLAST
Zinc fingeri285 – 30723C2H2-type 2Add
BLAST
Zinc fingeri313 – 33523C2H2-type 3Add
BLAST
Zinc fingeri341 – 36323C2H2-type 4Add
BLAST
Zinc fingeri369 – 39123C2H2-type 5Add
BLAST
Zinc fingeri397 – 42024C2H2-type 6Add
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
Complete GO annotation...

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
Complete GO annotation...

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.3 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.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 2020SNAG domainAdd
BLAST
Regioni141 – 258118Required for interaction with RELA By 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.2 Publications
The SNAG domain of GFIs is required for nuclear location and for interaction with some corepressors.2 Publications

Sequence similaritiesi

Zinc finger

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

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti185 – 1851R → S in AAC52959. 1 Publication
Sequence conflicti185 – 1851R → S in AAB36829. 1 Publication

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

« Hide 'large scale' publications
  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: July 9, 2014
This is version 116 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

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