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Q5VTD9 · GFI1B_HUMAN

  • Protein
    Zinc finger protein Gfi-1b
  • Gene
    GFI1B
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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 annotationsall molecular functionvirus receptor activitydna bindingrna bindingcytoskeletal motor activitycatalytic activitygtpase activitystructural molecule activitytransporter activitycytoskeletal protein bindinglipid bindingcyclase activityantioxidant activityoxidoreductase activitytransferase activityhydrolase activitylyase activityisomerase activityligase activityprotein tag activitycargo receptor activityhistone bindingprotein folding chaperonetranslation regulator activitynutrient reservoir activityreceptor ligand activitymolecular transducer activitymolecular adaptor activitytoxin activitycell adhesion mediator activitymolecular function regulator activityvirus coreceptor activitycatalytic activity, acting on a proteincatalytic activity, acting on dnacatalytic activity, acting on rnamolecular carrier activitytranscription regulator activitygeneral transcription initiation factor activitymolecular sensor activitymolecular sequestering activityatp-dependent activityother molecular functionall biological processmitotic cell cyclecytokinesiscytoplasmic translationimmune system processmuscle system processcirculatory system processrenal system processrespiratory system processcarbohydrate metabolic processgeneration of precursor metabolites and energydna replicationdna repairdna recombinationchromatin organizationdna-templated transcriptionregulation of dna-templated transcriptiontrna metabolic processprotein foldingprotein glycosylationamino acid metabolic processmodified amino acid metabolic processlipid metabolic processvitamin metabolic processsulfur compound metabolic processintracellular protein transportnucleocytoplasmic transportautophagyinflammatory responsemitochondrion organizationcytoskeleton organizationmicrotubule-based movementperoxisome organizationlysosome organizationchromosome segregationcell adhesionestablishment or maintenance of cell polarityprogrammed cell deathphotosynthesismrna metabolic processsnrna metabolic processvesicle-mediated transportreproductive processdigestive system processsignalingcell differentiationprotein catabolic processextracellular matrix organizationregulatory ncrna-mediated gene silencingtelomere organizationcell junction organizationwound healingribosome biogenesiscilium organizationanatomical structure developmentcell motilitynervous system processendocrine processprotein maturationtransmembrane transportnucleobase-containing small molecule metabolic processhepaticobiliary system processmembrane organizationprotein-containing complex assemblycell wall organization or biogenesisnitrogen cycle metabolic processprotein localization to plasma membranedefense response to other organismdetoxificationmeiotic nuclear divisionmitotic nuclear divisionmitochondrial gene expressioncarbohydrate derivative metabolic processother biological processall cellular componentnuclear chromosomeextracellular regionextracellular spacecell wallnucleusnuclear envelopenucleoplasmchromosomenucleolusmitochondrionlysosomeendosomevacuoleperoxisomeendoplasmic reticulumgolgi apparatuslipid dropletmicrotubule organizing centercytosolribosomecytoskeletonplasma membraneciliumplastidthylakoidexternal encapsulating structureextracellular matrixcytoplasmic vesicleorganelleother cellular component
Cell color indicative of number of GO terms
AspectTerm
Cellular Componentnuclear matrix
Cellular Componentnucleoplasm
Cellular Componentnucleus
Cellular Componentplasma membrane
Cellular Componenttranscription regulator complex
Molecular FunctionDNA-binding transcription activator activity, RNA polymerase II-specific
Molecular FunctionDNA-binding transcription factor activity, RNA polymerase II-specific
Molecular Functionmetal ion binding
Molecular FunctionRNA polymerase II cis-regulatory region sequence-specific DNA binding
Molecular FunctionRNA polymerase II-specific DNA-binding transcription factor binding
Molecular Functionsequence-specific double-stranded DNA binding
Biological Processchromatin organization
Biological Processnegative regulation of G1/S transition of mitotic cell cycle
Biological Processnegative regulation of transcription by RNA polymerase II
Biological Processregulation of hemopoiesis
Biological Processregulation of transcription by RNA polymerase II

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Zinc finger protein Gfi-1b
  • Alternative names
    • Growth factor independent protein 1B
    • Potential regulator of CDKN1A translocated in CML

Gene names

    • Name
      GFI1B

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    Q5VTD9
  • Secondary accessions
    • O95270
    • Q5VTD8
    • Q6FHZ2
    • Q6T888

Proteomes

Organism-specific databases

Subcellular Location

Disease & Variants

Involvement in disease

Bleeding disorder, platelet-type, 17 (BDPLT17)

  • Note
    • The disease is caused by variants affecting the gene represented in this entry
  • Description
    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.
  • See also
    MIM:187900

Features

Showing features for natural variant, mutagenesis.

Type
IDPosition(s)Description
Natural variantVAR_035556231in a colorectal cancer sample; somatic mutation; dbSNP:rs761044764
Mutagenesis290Prevents 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.

Go to variant viewer

Keywords

Organism-specific databases

Miscellaneous

Genetic variation databases

PTM/Processing

Features

Showing features for chain, modified residue.

Type
IDPosition(s)Description
ChainPRO_00003063271-330Zinc finger protein Gfi-1b
Modified residue8N6,N6-dimethyllysine

Post-translational modification

Methylation at Lys-8 in the SNAG domain seems required for the recruitment of the corepressor complex.

Keywords

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

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntAct
BINARY Q5VTD9CENPJ Q9HC772EBI-946212, EBI-946194
BINARY Q5VTD9JAG2 Q9Y2192EBI-946212, EBI-946223
BINARY Q5VTD9NELL2 Q994352EBI-946212, EBI-946274

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Features

Showing features for region, zinc finger.

Type
IDPosition(s)Description
Region1-20SNAG domain
Region1-42Disordered
Region91-330Interaction with ARIH2
Zinc finger163-186C2H2-type 1
Region164-330Mediates interaction with GATA1
Zinc finger192-214C2H2-type 2
Zinc finger220-242C2H2-type 3
Zinc finger248-270C2H2-type 4
Zinc finger276-298C2H2-type 5
Zinc finger304-327C2H2-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

Phylogenomic databases

Family and domain databases

Sequence & Isoform

Align isoforms (2)
  • Sequence status
    Complete

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.

  • Name
    1
  • Synonyms
    p37
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Length
    330
  • Mass (Da)
    37,492
  • Last updated
    2004-12-07 v1
  • MD5 Checksum
    EDAF3F96D097FC491F71BFD1909AF6A5
MPRSFLVKSKKAHTYHQPRVQEDEPLWPPALTPVPRDQAPSNSPVLSTLFPNQCLDWTNLKREPELEQDQNLARMAPAPEGPIVLSRPQDGDSPLSDSPPFYKPSFSWDTLATTYGHSYRQAPSTMQSAFLEHSVSLYGSPLVPSTEPALDFSLRYSPGMDAYHCVKCNKVFSTPHGLEVHVRRSHSGTRPFACDICGKTFGHAVSLEQHTHVHSQERSFECRMCGKAFKRSSTLSTHLLIHSDTRPYPCQFCGKRFHQKSDMKKHTYIHTGEKPHKCQVCGKAFSQSSNLITHSRKHTGFKPFSCELCTKGFQRKVDLRRHRESQHNLK

Q5VTD9-2

  • Name
    2
  • Synonyms
    p32
  • Note
    Essential for erythroid differentiation. Binds to target gene promoters and associates with the LSD1-CoREST repressor complex more efficiently than the major isoform 1.
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Computationally mapped potential isoform sequences

There are 2 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A0A1B0GTD0A0A1B0GTD0_HUMANGFI1B362
A0A024R8F3A0A024R8F3_HUMANGFI1B352

Features

Showing features for sequence conflict, alternative sequence.

Type
IDPosition(s)Description
Sequence conflict11in Ref. 2; AAR06639
Sequence conflict27in Ref. 3; CAG38783
Sequence conflict29in Ref. 1; AAD08672
Alternative sequenceVSP_028459171-216in isoform 2
Sequence conflict190in Ref. 2; AAR06639
Sequence conflict219in Ref. 1; AAD08672

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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.

Genome annotation databases

Similar Proteins

Disclaimer

Any 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. Our staff consists of biologists and biochemists that are not trained to give medical advice.
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