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Q99684 (GFI1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·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
Zinc finger protein 163
Gene names
Name:GFI1
Synonyms:ZNF163
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length422 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.3 Ref.4 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14

Subunit structure

Interacts with U2AF1L4. Component of RCOR-GFI-KDM1A-HDAC complexes. Interacts directly with RCOR1, KDM1A and HDAC2 By similarity. Also interacts with HDAC1. Interacts (via the zinc-finger domain) with ARIH2; the interaction prevents GFI1 ubiquitination and proteasomal degradation. Interacts with PIAS3; the interaction relieves the inhibitory effect of PIAS3 on STAT3-mediated transcriptional activity. 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. 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 RUNX1T1; the interaction represses HDAC-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. Interacts (via the C-terminal zinc fingers) with ZBTB17; the interaction results in the recruitment of GFI1 to the CDKN1A/p21 and CDKN1B promoters and repression of transcription. Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.11 Ref.12 Ref.13

Subcellular location

Nucleus. Note: Colocalizes with PIAS3 and RUNX1T1 in nuclear dots. Ref.3 Ref.4 Ref.5 Ref.9 Ref.12

Induction

Down-regulated by TGFB1. Ref.12 Ref.13

Domain

Zinc fingers 3, 4 and 5 are required for DNA-binding and for interaction with SPI1. Ref.8

The SNAG domain of GFIs is required for nuclear location and for interaction with some corepressors By similarity. Ref.8

Post-translational modification

Ubiquitinated. Ubiquitination and degradation by the proteasome is inhibited by the ubiquitin ligase, ARIH2. Ref.7

Involvement in disease

Neutropenia, severe congenital 2, autosomal dominant (SCN2) [MIM:613107]: A disorder of hematopoiesis characterized by maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.14

Dominant nonimmune chronic idiopathic neutropenia of adults (NI-CINA) [MIM:607847]: Relatively mild form of neutropenia diagnosed in adults, but predisposing to leukemia in a subset of patients.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.14

Sequence similarities

Contains 6 C2H2-type zinc fingers.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   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 electronic annotation. Source: Ensembl

cell fate commitment

Inferred from electronic annotation. Source: Ensembl

cellular response to lipopolysaccharide

Inferred from expression pattern Ref.12. Source: UniProtKB

inner ear morphogenesis

Inferred from electronic annotation. Source: Ensembl

mechanosensory behavior

Inferred from electronic annotation. Source: Ensembl

negative regulation of NF-kappaB transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of calcidiol 1-monooxygenase activity

Inferred from direct assay PubMed 15947108. Source: BHF-UCL

negative regulation of cell fate specification

Inferred from electronic annotation. Source: Ensembl

negative regulation of neuron projection development

Inferred from direct assay Ref.10. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 15947108. Source: BHF-UCL

negative regulation of transcription, DNA-templated

Inferred from direct assay Ref.5. Source: UniProtKB

negative regulation of vitamin D biosynthetic process

Inferred by curator PubMed 15947108. Source: BHF-UCL

positive regulation of cell fate specification

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-6-mediated signaling pathway

Inferred from direct assay Ref.4. Source: UniProtKB

regulation of toll-like receptor signaling pathway

Inferred from direct assay Ref.12. Source: UniProtKB

regulation of transcription involved in G1/S transition of mitotic cell cycle

Traceable author statement PubMed 8441411. Source: ProtInc

viral process

Traceable author statement PubMed 8441411. Source: ProtInc

   Cellular_componentnuclear body

Inferred from direct assay Ref.4. Source: UniProtKB

nuclear matrix

Inferred from direct assay Ref.5. Source: UniProtKB

nucleus

Inferred from direct assay Ref.5Ref.12. Source: UniProtKB

transcriptional repressor complex

Inferred from direct assay Ref.5. Source: UniProtKB

   Molecular_functionRNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription

Inferred from direct assay PubMed 19506020. Source: UniProt

protein binding

Inferred from physical interaction Ref.4Ref.5PubMed 17636019Ref.9Ref.13Ref.12. Source: UniProtKB

transcription regulatory region DNA binding

Inferred from direct assay PubMed 15947108. Source: BHF-UCL

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 – 422422Zinc finger protein Gfi-1
PRO_0000047193

Regions

Zinc finger255 – 27824C2H2-type 1
Zinc finger284 – 30623C2H2-type 2
Zinc finger312 – 33423C2H2-type 3
Zinc finger340 – 36223C2H2-type 4
Zinc finger368 – 39023C2H2-type 5
Zinc finger396 – 41924C2H2-type 6
Region1 – 2020SNAG domain By similarity
Region140 – 257118Required for interaction with RELA
Compositional bias158 – 20952Ala/Gly-rich

Natural variations

Natural variant361S → N.
Corresponds to variant rs34631763 [ dbSNP | Ensembl ].
VAR_052722
Natural variant3821N → S in SCN2; zero neutrophil count. marked monocytosis and reduced T- and B-lymphocyte number leading to recurrent infectious complications. Abolishes recognition of DNA binding site of zinc finger. Diminished repression activity and elevated ELA2 expression. No effect on repression of CDKN1A/p21 transcription. Ref.13 Ref.14
Corresponds to variant rs28936381 [ dbSNP | Ensembl ].
VAR_016212
Natural variant4031K → R in NI-CINA; Neutropenic and elevated monocytosis but no history of infectious complications. No effect on DNA binding but diminished GFI1 repression activity. Ref.14
Corresponds to variant rs28936382 [ dbSNP | Ensembl ].
VAR_016213

Experimental info

Mutagenesis21P → A: Abrogates transcriptional repression. Ref.8
Sequence conflict73 – 775DSCEG → RQLRS in AAB37272. Ref.1
Sequence conflict184 – 1863SCS → NCI in AAB37272. Ref.1
Sequence conflict2131R → K in AAB37272. Ref.1
Sequence conflict2281G → R in AAB37272. Ref.1
Sequence conflict2321D → N in AAB37272. Ref.1
Sequence conflict3671P → L in AAB37272. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q99684 [UniParc].

Last modified August 15, 2003. Version 2.
Checksum: 740A466F72C5FC72

FASTA42245,297
        10         20         30         40         50         60 
MPRSFLVKSK KAHSYHQPRS PGPDYSLRLE NVPAPSRADS TSNAGGAKAE PRDRLSPESQ 

        70         80         90        100        110        120 
LTEAPDRASA SPDSCEGSVC ERSSEFEDFW RPPSPSASPA SEKSMCPSLD EAQPFPLPFK 

       130        140        150        160        170        180 
PYSWSGLAGS DLRHLVQSYR PCGALERGAG LGLFCEPAPE PGHPAALYGP KRAAGGAGAG 

       190        200        210        220        230        240 
APGSCSAGAG ATAGPGLGLY GDFGSAAAGL YERPTAAAGL LYPERGHGLH ADKGAGVKVE 

       250        260        270        280        290        300 
SELLCTRLLL GGGSYKCIKC SKVFSTPHGL EVHVRRSHSG TRPFACEMCG KTFGHAVSLE 

       310        320        330        340        350        360 
QHKAVHSQER SFDCKICGKS FKRSSTLSTH LLIHSDTRPY PCQYCGKRFH QKSDMKKHTF 

       370        380        390        400        410        420 
IHTGEKPHKC QVCGKAFSQS SNLITHSRKH TGFKPFGCDL CGKGFQRKVD LRRHRETQHG 


LK 

« Hide

References

« Hide 'large scale' references
[1]"Cloning of the human Gfi-1 gene and its mapping to chromosome region 1p22."
Roberts T., Cowell J.K.
Oncogene 14:1003-1005(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Bone marrow.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lung and Testis.
[3]"Gfi-1 encodes a nuclear zinc finger protein that binds DNA and functions as a transcriptional repressor."
Zweidler-Mckay P.A., Grimes H.L., Flubacher M.M., Tsichlis P.N.
Mol. Cell. Biol. 16:4024-4034(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: DNA-BINDING, SUBCELLULAR LOCATION, FUNCTION.
[4]"The zinc finger protein Gfi-1 can enhance STAT3 signaling by interacting with the STAT3 inhibitor PIAS3."
Roedel B., Tavassoli K., Karsunky H., Schmidt T., Bachmann M., Schaper F., Heinrich P., Shuai K., Elsaesser H.-P., Moeroey T.
EMBO J. 19:5845-5855(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PIAS3, SUBCELLULAR LOCATION, FUNCTION.
[5]"Gfi-1 attaches to the nuclear matrix, associates with ETO (MTG8) and histone deacetylase proteins, and represses transcription using a TSA-sensitive mechanism."
McGhee L., Bryan J., Elliott L., Grimes H.L., Kazanjian A., Davis J.N., Meyers S.
J. Cell. Biochem. 89:1005-1018(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH RUNX1T1; HDAC1; HDAC2 AND HDAC3, INTERACTION WITH RUNX1T1, SUBCELLULAR LOCATION.
[6]"Gfi1 coordinates epigenetic repression of p21Cip/WAF1 by recruitment of histone lysine methyltransferase G9a and histone deacetylase 1."
Duan Z., Zarebski A., Montoya-Durango D., Grimes H.L., Horwitz M.
Mol. Cell. Biol. 25:10338-10351(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH EHMT2 AND HDAC1, INTERACTION WITH EHMT2 AND HDAC1, FUNCTION.
[7]"Gfi1 ubiquitination and proteasomal degradation is inhibited by the ubiquitin ligase Triad1."
Marteijn J.A., van der Meer L.T., van Emst L., van Reijmersdal S., Wissink W., de Witte T., Jansen J.H., Van der Reijden B.A.
Blood 110:3128-3135(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ARIH2, UBIQUITINATION.
[8]"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, MUTAGENESIS OF PRO-2.
[9]"Ajuba functions as a histone deacetylase-dependent co-repressor for autoregulation of the growth factor-independent-1 transcription factor."
Montoya-Durango D.E., Velu C.S., Kazanjian A., Rojas M.E., Jay C.M., Longmore G.D., Grimes H.L.
J. Biol. Chem. 283:32056-32065(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH AJUBA IN THE GFI1-AJUBA-HDAC COMPLEX, SUBCELLULAR LOCATION, FUNCTION.
[10]"Loss of function genetic screens reveal MTGR1 as an intracellular repressor of beta1 integrin-dependent neurite outgrowth."
Ossovskaya V.S., Dolganov G., Basbaum A.I.
J. Neurosci. Methods 177:322-333(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"Gfi-1 represses CDKN2B encoding p15INK4B through interaction with Miz-1."
Basu S., Liu Q., Qiu Y., Dong F.
Proc. Natl. Acad. Sci. U.S.A. 106:1433-1438(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ZBTB17.
[12]"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: INTERACTION WITH RELA, SUBCELLULAR LOCATION, INDUCTION, FUNCTION.
[13]"A role of Miz-1 in Gfi-1-mediated transcriptional repression of CDKN1A."
Liu Q., Basu S., Qiu Y., Tang F., Dong F.
Oncogene 29:2843-2852(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ZBTB17, FUNCTION, INDUCTION, CHARACTERIZATION OF VARIANT SER-382.
[14]"Mutations in proto-oncogene GFI1 cause human neutropenia and target ELA2."
Person R.E., Li F.-Q., Duan Z., Benson K.F., Wechsler J., Papadaki H.A., Eliopoulos G., Kaufman C., Bertolone S.J., Nakamoto B., Papayannopoulou T., Grimes H.L., Horwitz M.
Nat. Genet. 34:308-312(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NI-CINA ARG-403, VARIANT SCN2 SER-382, CHARACTERIZATION OF VARIANTS NI-CINA ARG-403 AND SCN2 SER-382, FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U67369 mRNA. Translation: AAB37272.1.
BC032751 mRNA. Translation: AAH32751.1.
BC074866 mRNA. Translation: AAH74866.1.
BC074867 mRNA. Translation: AAH74867.1.
CCDSCCDS30773.1.
RefSeqNP_001120687.1. NM_001127215.1.
NP_001120688.1. NM_001127216.1.
NP_005254.2. NM_005263.3.
XP_005270806.1. XM_005270749.2.
UniGeneHs.73172.

3D structure databases

ProteinModelPortalQ99684.
SMRQ99684. Positions 255-422.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108940. 15 interactions.
DIPDIP-38452N.
IntActQ99684. 15 interactions.
MINTMINT-149356.
STRING9606.ENSP00000294702.

PTM databases

PhosphoSiteQ99684.

Polymorphism databases

DMDM33860154.

Proteomic databases

PaxDbQ99684.
PRIDEQ99684.

Protocols and materials databases

DNASU2672.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000294702; ENSP00000294702; ENSG00000162676.
ENST00000370332; ENSP00000359357; ENSG00000162676.
ENST00000427103; ENSP00000399719; ENSG00000162676.
GeneID2672.
KEGGhsa:2672.
UCSCuc001dou.4. human.

Organism-specific databases

CTD2672.
GeneCardsGC01M092940.
HGNCHGNC:4237. GFI1.
HPACAB011197.
MIM600871. gene.
607847. phenotype.
613107. phenotype.
neXtProtNX_Q99684.
Orphanet486. Autosomal dominant severe congenital neutropenia.
PharmGKBPA24344.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5048.
HOVERGENHBG006967.
InParanoidQ99684.
KOK09223.
OMAPFPLPFK.
OrthoDBEOG72RN05.
PhylomeDBQ99684.
TreeFamTF350784.

Enzyme and pathway databases

SignaLinkQ99684.

Gene expression databases

ArrayExpressQ99684.
BgeeQ99684.
CleanExHS_GFI1.
GenevestigatorQ99684.

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

GeneWikiGFI1.
GenomeRNAi2672.
NextBio10546.
PROQ99684.
SOURCESearch...

Entry information

Entry nameGFI1_HUMAN
AccessionPrimary (citable) accession number: Q99684
Secondary accession number(s): Q8N564
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: August 15, 2003
Last modified: July 9, 2014
This is version 132 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM