InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: GFI1

Summary

InnateDB Protein

IDBP-100284.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

GFI1

Protein Name

growth factor independent 1 transcription repressor

Synonyms

GFI-1; GFI1A; SCN2; ZNF163;

Species

Homo sapiens

Ensembl Protein

ENSP00000294702

InnateDB Gene

IDBG-100280 (GFI1)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:11060035, ECO:0000269PubMed:12778173, ECO:0000269PubMed:16287849, ECO:0000269PubMed:17197705, ECO:0000269PubMed:17646546, ECO:0000269PubMed:18805794, ECO:0000269PubMed:19026687, ECO:0000269PubMed:19164764, ECO:0000269PubMed:20190815, ECO:0000269PubMed:20547752, ECO:0000269PubMed:8754800}.

Subcellular Localization

Nucleus {ECO:0000269PubMed:11060035, ECO:0000269PubMed:12874834, ECO:0000269PubMed:18805794, ECO:0000269PubMed:20547752, ECO:0000269PubMed:8754800}. Note=Colocalizes with PIAS3 and RUNX1T1 in nuclear dots.

Disease Associations

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. {ECO:0000269PubMed:12778173}. Note=The disease is caused by mutations affecting the gene represented in this entry.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. {ECO:0000269PubMed:12778173}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 59 experimentally validated interaction(s) in this database.
They are also associated with 17 interaction(s) predicted by orthology.

Experimentally validated
Total	59 [view]
Protein-Protein	50 [view]
Protein-DNA	9 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	17 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001078	RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription
GO:0005515	protein binding
GO:0008270	zinc ion binding
GO:0044212	transcription regulatory region DNA binding
GO:0046872	metal ion binding

Biological Process

GO:0000083	regulation of transcription involved in G1/S transition of mitotic cell cycle
GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0006351	transcription, DNA-templated
GO:0010956	negative regulation of calcidiol 1-monooxygenase activity
GO:0010957	negative regulation of vitamin D biosynthetic process
GO:0010977	negative regulation of neuron projection development
GO:0016032	viral process
GO:0032088	negative regulation of NF-kappaB transcription factor activity
GO:0034121	regulation of toll-like receptor signaling pathway
GO:0045892	negative regulation of transcription, DNA-templated
GO:0070105	positive regulation of interleukin-6-mediated signaling pathway
GO:0071222	cellular response to lipopolysaccharide