Q5VTD9 · GFI1B_HUMAN
- ProteinZinc finger protein Gfi-1b
- GeneGFI1B
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids330 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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.
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | nuclear matrix | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleus | |
Cellular Component | plasma membrane | |
Cellular Component | transcription regulator complex | |
Molecular Function | DNA-binding transcription activator activity, RNA polymerase II-specific | |
Molecular Function | DNA-binding transcription factor activity, RNA polymerase II-specific | |
Molecular Function | metal ion binding | |
Molecular Function | RNA polymerase II cis-regulatory region sequence-specific DNA binding | |
Molecular Function | RNA polymerase II-specific DNA-binding transcription factor binding | |
Molecular Function | sequence-specific double-stranded DNA binding | |
Biological Process | chromatin organization | |
Biological Process | negative regulation of G1/S transition of mitotic cell cycle | |
Biological Process | negative regulation of transcription by RNA polymerase II | |
Biological Process | regulation of hemopoiesis | |
Biological Process | regulation of transcription by RNA polymerase II |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameZinc finger protein Gfi-1b
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ5VTD9
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Bleeding disorder, platelet-type, 17 (BDPLT17)
- Note
- DescriptionAn 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.
- See alsoMIM:187900
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Natural variant | VAR_035556 | 231 | in a colorectal cancer sample; somatic mutation; dbSNP:rs761044764 | ||
Mutagenesis | 290 | Prevents DNA-binding. | |||
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 451 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Chain | PRO_0000306327 | 1-330 | Zinc finger protein Gfi-1b | ||
Modified residue | 8 | N6,N6-dimethyllysine | |||
Post-translational modification
Methylation at Lys-8 in the SNAG domain seems required for the recruitment of the corepressor complex.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
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).
Induction
By GATA1 which binds to GFI1B promoter in cooperation with the transcription factor NFYA. Target gene of transcription factor E2-alpha/TCF3 that promotes growth arrest and apoptosis in lymphomas.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Component of a RCOR-GFI-KDM1A-HDAC complex. Interacts directly with RCOR1, KDM1A and HDAC2 (By similarity).
Forms a complex with GATA1. Interacts with histone methyltransferases EHMT2 and SUV39H1. Interacts with ARIH2 (via RING-type 2). Interacts with RUNX1T1
Forms a complex with GATA1. Interacts with histone methyltransferases EHMT2 and SUV39H1. Interacts with ARIH2 (via RING-type 2). Interacts with RUNX1T1
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | IntAct | |
---|---|---|---|---|---|
BINARY | Q5VTD9 | CENPJ Q9HC77 | 2 | EBI-946212, EBI-946194 | |
BINARY | Q5VTD9 | JAG2 Q9Y219 | 2 | EBI-946212, EBI-946223 | |
BINARY | Q5VTD9 | NELL2 Q99435 | 2 | EBI-946212, EBI-946274 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, zinc finger.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Region | 1-20 | SNAG domain | |||
Region | 1-42 | Disordered | |||
Region | 91-330 | Interaction with ARIH2 | |||
Zinc finger | 163-186 | C2H2-type 1 | |||
Region | 164-330 | Mediates interaction with GATA1 | |||
Zinc finger | 192-214 | C2H2-type 2 | |||
Zinc finger | 220-242 | C2H2-type 3 | |||
Zinc finger | 248-270 | C2H2-type 4 | |||
Zinc finger | 276-298 | C2H2-type 5 | |||
Zinc finger | 304-327 | C2H2-type 6 | |||
Domain
The zinc finger domains are essential for erythroid expansion and acts as an activation domain whereas non finger domain serves as repression domain.
The SNAG domain of GFIs is required for nuclear location and for interaction with some corepressors.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q5VTD9-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Synonymsp37
- Length330
- Mass (Da)37,492
- Last updated2004-12-07 v1
- MD5 ChecksumEDAF3F96D097FC491F71BFD1909AF6A5
Q5VTD9-2
- Name2
- Synonymsp32
- NoteEssential for erythroid differentiation. Binds to target gene promoters and associates with the LSD1-CoREST repressor complex more efficiently than the major isoform 1.
- Differences from canonical
- 171-216: Missing
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A1B0GTD0 | A0A1B0GTD0_HUMAN | GFI1B | 362 | ||
A0A024R8F3 | A0A024R8F3_HUMAN | GFI1B | 352 |
Features
Showing features for sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Sequence conflict | 11 | in Ref. 2; AAR06639 | |||
Sequence conflict | 27 | in Ref. 3; CAG38783 | |||
Sequence conflict | 29 | in Ref. 1; AAD08672 | |||
Alternative sequence | VSP_028459 | 171-216 | in isoform 2 | ||
Sequence conflict | 190 | in Ref. 2; AAR06639 | |||
Sequence conflict | 219 | in Ref. 1; AAD08672 | |||
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF081946 EMBL· GenBank· DDBJ | AAD08672.1 EMBL· GenBank· DDBJ | mRNA | ||
AY428733 EMBL· GenBank· DDBJ | AAR06639.1 EMBL· GenBank· DDBJ | mRNA | ||
CR536546 EMBL· GenBank· DDBJ | CAG38783.1 EMBL· GenBank· DDBJ | mRNA | ||
AL593851 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471090 EMBL· GenBank· DDBJ | EAW88025.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC043371 EMBL· GenBank· DDBJ | AAH43371.1 EMBL· GenBank· DDBJ | mRNA | ||
BC035626 EMBL· GenBank· DDBJ | - | mRNA | No translation available. |