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P70338 (GFI1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 116. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Zinc finger protein Gfi-1
Alternative name(s):
Growth factor independent protein 1
Gene names
Name:Gfi1
Synonyms:Gfi-1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length423 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.2 Ref.5 Ref.7 Ref.8 Ref.9

Subunit structure

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. Ref.6 Ref.7 Ref.8

Subcellular location

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

Induction

By IL2 and CSF3. Induced by the endotoxin bacterial lipopolysaccharide (LPS) in primary bone marrow macrophages (BMDMs). Ref.9

Domain

Zinc fingers 3,4 and 5 are required for DNA binding and for interaction with SPI1 By similarity. Ref.4 Ref.7

The SNAG domain of GFIs is required for nuclear location and for interaction with some corepressors. Ref.4 Ref.7

Post-translational modification

Ubiquitinated By similarity.

Disruption phenotype

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. Ref.5 Ref.7

Sequence similarities

Contains 6 C2H2-type zinc fingers.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   DomainRepeat
Zinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   PTMUbl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processauditory receptor cell differentiation

Inferred from mutant phenotype Ref.5. Source: MGI

cell fate commitment

Inferred from mutant phenotype PubMed 16230531. Source: MGI

cellular response to lipopolysaccharide

Inferred from expression pattern Ref.9. Source: UniProtKB

inner ear morphogenesis

Inferred from mutant phenotype Ref.5. Source: MGI

mechanosensory behavior

Inferred from mutant phenotype Ref.5. Source: MGI

negative regulation of NF-kappaB transcription factor activity

Inferred from mutant phenotype Ref.9. Source: UniProtKB

negative regulation of cell fate specification

Inferred from mutant phenotype PubMed 16230531. Source: MGI

negative regulation of neuron projection development

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype Ref.9. Source: UniProtKB

positive regulation of cell fate specification

Inferred from mutant phenotype PubMed 16230531. Source: MGI

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentnucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

transcriptional repressor complex

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionDNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction Ref.8. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 423423Zinc finger protein Gfi-1
PRO_0000047194

Regions

Zinc finger256 – 27924C2H2-type 1
Zinc finger285 – 30723C2H2-type 2
Zinc finger313 – 33523C2H2-type 3
Zinc finger341 – 36323C2H2-type 4
Zinc finger369 – 39123C2H2-type 5
Zinc finger397 – 42024C2H2-type 6
Region1 – 2020SNAG domain
Region141 – 258118Required for interaction with RELA By similarity
Compositional bias159 – 21052Ala/Gly-rich

Experimental info

Mutagenesis21P → A: Abrogates transcriptional repression. No change in nuclear location. Ref.4
Mutagenesis31R → A: Partial loss of transcription repression. No change in nuclear location. Ref.4
Mutagenesis41S → A: Partial loss of transcription repression. No change in nuclear location. Ref.4
Mutagenesis101K → A: Abolishes most of the nuclear localization and reduces transcriptional repressor activity; when associated with A-11. Ref.4
Mutagenesis111K → A: Abolishes most of the nuclear localization and reduces transcriptional repressor activity; when associated with A-10. Ref.4
Sequence conflict1851R → S in AAC52959. Ref.1
Sequence conflict1851R → S in AAB36829. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P70338 [UniParc].

Last modified October 3, 2012. Version 2.
Checksum: 63AB726025300B6B

FASTA42345,944
        10         20         30         40         50         60 
MPRSFLVKSK KAHSYHQPRS PGPDYSLRLE TVPAPGRAEG GAVSAGESKM EPRERLSPDS 

        70         80         90        100        110        120 
QLTEAPDRAS ASPNSCEGSV CDPCSEFEDF WRPPSPSVSP ASEKSLCRSL DEAQPYTLPF 

       130        140        150        160        170        180 
KPYAWSGLAG SDLRHLVQSY RQCSALERSA GLSLFCERGS EPGRPAARYG PEQAAGGAGA 

       190        200        210        220        230        240 
GQPGRCGVAG GATSAAGLGL YGDFAPAAAG LYERPSTAAG RLYQDHGHEL HADKSVGVKV 

       250        260        270        280        290        300 
ESELLCTRLL LGGGSYKCIK CSKVFSTPHG LEVHVRRSHS GTRPFACEMC GKTFGHAVSL 

       310        320        330        340        350        360 
EQHKAVHSQE RSFDCKICGK SFKRSSTLST HLLIHSDTRP YPCQYCGKRF HQKSDMKKHT 

       370        380        390        400        410        420 
FIHTGEKPHK CQVCGKAFSQ SSNLITHSRK HTGFKPFGCD LCGKGFQRKV DLRRHRETQH 


GLK 

« Hide

References

« Hide 'large scale' references
[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]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U58973 mRNA. Translation: AAC52960.1.
U58972 mRNA. Translation: AAC52959.1.
U78312 mRNA. Translation: AAB36829.1.
AC117574 Genomic DNA. No translation available.
CCDSCCDS57371.1.
RefSeqNP_034408.1. NM_010278.2.
XP_006534855.1. XM_006534792.1.
XP_006534856.1. XM_006534793.1.
XP_006534857.1. XM_006534794.1.
UniGeneMm.2078.
Mm.453139.

3D structure databases

ProteinModelPortalP70338.
SMRP70338. Positions 235-423.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid199900. 2 interactions.
IntActP70338. 12 interactions.

PTM databases

PhosphoSiteP70338.

Proteomic databases

PRIDEP70338.

Protocols and materials databases

DNASU14581.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000031205; ENSMUSP00000135884; ENSMUSG00000029275.
ENSMUST00000159164; ENSMUSP00000137229; ENSMUSG00000029275.
GeneID14581.
KEGGmmu:14581.
UCSCuc029vkg.1. mouse.

Organism-specific databases

CTD2672.
MGIMGI:103170. Gfi1.

Phylogenomic databases

eggNOGCOG5048.
GeneTreeENSGT00740000115096.
HOVERGENHBG006967.
InParanoidP70338.
KOK09223.
OrthoDBEOG72RN05.
TreeFamTF350784.

Gene expression databases

ArrayExpressP70338.
BgeeP70338.
CleanExMM_GFI1.
GenevestigatorP70338.

Family and domain databases

Gene3D3.30.160.60. 6 hits.
InterProIPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
IPR001878. Znf_CCHC.
[Graphical view]
PfamPF00096. zf-C2H2. 1 hit.
[Graphical view]
SMARTSM00355. ZnF_C2H2. 6 hits.
SM00343. ZnF_C2HC. 1 hit.
[Graphical view]
PROSITEPS00028. ZINC_FINGER_C2H2_1. 6 hits.
PS50157. ZINC_FINGER_C2H2_2. 6 hits.
[Graphical view]
ProtoNetSearch...

Other

NextBio286310.
PROP70338.
SOURCESearch...

Entry information

Entry nameGFI1_MOUSE
AccessionPrimary (citable) accession number: P70338
Secondary accession number(s): O09063
Entry history
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 statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot