InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: GFI1B

Summary

InnateDB Protein

IDBP-603143.3

Last Modified

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

Gene Symbol

GFI1B

Protein Name

growth factor independent 1B transcription repressor

Synonyms

BDPLT17;

Species

Homo sapiens

Ensembl Protein

ENSP00000446134

InnateDB Gene

IDBG-90485 (GFI1B)

Protein Structure

UniProt Annotation

Function

Essential proto-oncogenic transcriptional regulator necessary for development and differentiation of erythroid and megakaryocytic lineages. Component of a RCOR-GFI-KDM1A-HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development and controls hematopoietic differentiation. Transcriptional repressor or activator depending on both promoter and cell type context; represses promoter activity of SOCS1 and SOCS3 and thus, may regulate cytokine signaling pathways. Cooperates with GATA1 to repress target gene transcription, such as the apoptosis regulator BCL2L1; GFI1B silencing in leukemic cell lines markedly increase apoptosis rate. Inhibits down- regulation of MYC and MYB as well as the cyclin-dependent kinase inhibitor CDKN1A/P21WAF1 in IL6-treated myelomonocytic cells. Represses expression of GATA3 in T-cell lymphomas and inhibits GATA1-mediated transcription; as GATA1 also mediates erythroid GFI1B transcription, both GATA1 and GFI1B participate in a feedback regulatory pathway controlling the expression of GFI1B gene in erythroid cells. Suppresses GATA1-mediated stimulation of GFI1B promoter through protein interaction. Binds to gamma- satellite DNA and to its own promoter, auto-repressing its own expression. Alters histone methylation by recruiting histone methyltransferase to target genes promoters. Plays a role in heterochromatin formation. {ECO:0000269PubMed:12351384, ECO:0000269PubMed:16177182, ECO:0000269PubMed:16688220, ECO:0000269PubMed:16782810, ECO:0000269PubMed:17156408, ECO:0000269PubMed:17272506, ECO:0000269PubMed:17420275}.

Subcellular Localization

Nucleus {ECO:0000269PubMed:16688220}.

Disease Associations

Bleeding disorder, platelet-type 17 (BDPLT17) [MIM:187900]: An autosomal dominant disorder characterized by increased bleeding tendency due to platelet dysfunction, and associated with macrothrombocytopenia and red cell anisopoikilocytosis. Platelets appear abnormal on light microscopy, while electron microscopy shows a heterogeneous decrease of alpha granules within platelets. Bone marrow biopsy shows increased numbers of abnormal megakaryocytes, suggesting a defect in megakaryopoiesis and platelet production. The severity of bleeding is variable with some affected individuals experiencing spontaneous bleeding while other exhibit only abnormal bleeding with surgery. {ECO:0000269PubMed:23927492, ECO:0000269PubMed:24325358}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Expressed in bone marrow and fetal liver, but also detectable in fetal spleen, fetal thymus, and testes. Detected in hematopoietic stem cells, erythroblasts, and megakaryocytes. Overexpressed in bone marrow of patients with erythroleukemia and megakaryocytic leukemia as well as in their corresponding leukemic cell lines, and markedly repressed in severe aplastic anemia (SAA). {ECO:0000269PubMed:12351384, ECO:0000269PubMed:17156408, ECO:0000269PubMed:9878267}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 80 experimentally validated interaction(s) in this database.
They are also associated with 9 interaction(s) predicted by orthology.

Experimentally validated
Total	80 [view]
Protein-Protein	80 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	9 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001085	RNA polymerase II transcription factor binding
GO:0003677	DNA binding
GO:0005515	protein binding
GO:0046872	metal ion binding

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0006366	transcription from RNA polymerase II promoter
GO:0007275	multicellular organismal development
GO:0008283	cell proliferation
GO:0016568	chromatin modification