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Protein

Zinc finger protein Gfi-1b

Gene

GFI1B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.7 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri163 – 186C2H2-type 1PROSITE-ProRule annotationAdd BLAST24
Zinc fingeri192 – 214C2H2-type 2PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri220 – 242C2H2-type 3PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri248 – 270C2H2-type 4PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri276 – 298C2H2-type 5PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri304 – 327C2H2-type 6PROSITE-ProRule annotationAdd BLAST24

GO - Molecular functioni

GO - Biological processi

  • cell proliferation Source: ProtInc
  • chromatin organization Source: UniProtKB-KW
  • multicellular organism development Source: UniProtKB-KW
  • negative regulation of transcription by RNA polymerase II Source: ProtInc
  • transcription by RNA polymerase II Source: ProtInc

Keywordsi

Molecular functionActivator, Chromatin regulator, Developmental protein, DNA-binding, Repressor
Biological processTranscription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

SignaLinkiQ5VTD9
SIGNORiQ5VTD9

Names & Taxonomyi

Protein namesi
Recommended name:
Zinc finger protein Gfi-1b
Alternative name(s):
Growth factor independent protein 1B
Potential regulator of CDKN1A translocated in CML
Gene namesi
Name:GFI1B
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000165702.12
HGNCiHGNC:4238 GFI1B
MIMi604383 gene
neXtProtiNX_Q5VTD9

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Bleeding disorder, platelet-type 17 (BDPLT17)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease 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 also OMIM:187900

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi290N → S: Prevents DNA-binding. 1 Publication1

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNETi8328
MalaCardsiGFI1B
MIMi187900 phenotype
OpenTargetsiENSG00000165702
Orphaneti721 Gray platelet syndrome
PharmGKBiPA28649

Polymorphism and mutation databases

BioMutaiGFI1B
DMDMi74756792

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003063271 – 330Zinc finger protein Gfi-1bAdd BLAST330

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei8N6,N6-dimethyllysine1 Publication1

Post-translational modificationi

Methylation at Lys-8 in the SNAG domain seems required for the recruitment of the corepressor complex.1 Publication

Keywords - PTMi

Methylation

Proteomic databases

PaxDbiQ5VTD9
PeptideAtlasiQ5VTD9
PRIDEiQ5VTD9
ProteomicsDBi65320
65321 [Q5VTD9-2]

PTM databases

iPTMnetiQ5VTD9
PhosphoSitePlusiQ5VTD9

Expressioni

Tissue specificityi

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).3 Publications

Inductioni

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.1 Publication

Gene expression databases

BgeeiENSG00000165702
CleanExiHS_GFI1B
ExpressionAtlasiQ5VTD9 baseline and differential
GenevisibleiQ5VTD9 HS

Organism-specific databases

HPAiCAB004420

Interactioni

Subunit structurei

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.By similarity5 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • RNA polymerase II transcription factor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi113924, 76 interactors
IntActiQ5VTD9, 71 interactors
STRINGi9606.ENSP00000344782

Structurei

3D structure databases

ProteinModelPortaliQ5VTD9
SMRiQ5VTD9
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 20SNAG domainAdd BLAST20
Regioni91 – 330Interaction with ARIH21 PublicationAdd BLAST240
Regioni164 – 330Mediates interaction with GATA1Add BLAST167

Domaini

The zinc finger domains are essential for erythroid expansion and acts as an activation domain whereas non finger domain serves as repression domain.By similarity
The SNAG domain of GFIs is required for nuclear location and for interaction with some corepressors.By similarity

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri163 – 186C2H2-type 1PROSITE-ProRule annotationAdd BLAST24
Zinc fingeri192 – 214C2H2-type 2PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri220 – 242C2H2-type 3PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri248 – 270C2H2-type 4PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri276 – 298C2H2-type 5PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri304 – 327C2H2-type 6PROSITE-ProRule annotationAdd BLAST24

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1721 Eukaryota
COG5048 LUCA
GeneTreeiENSGT00740000115096
HOGENOMiHOG000067832
HOVERGENiHBG106655
InParanoidiQ5VTD9
KOiK09223
OrthoDBiEOG091G0NDD
PhylomeDBiQ5VTD9
TreeFamiTF350784

Family and domain databases

InterProiView protein in InterPro
IPR037044 Gfi-1b
IPR036236 Znf_C2H2_sf
IPR013087 Znf_C2H2_type
PANTHERiPTHR44643 PTHR44643, 1 hit
SMARTiView protein in SMART
SM00355 ZnF_C2H2, 6 hits
SUPFAMiSSF57667 SSF57667, 3 hits
PROSITEiView protein in PROSITE
PS00028 ZINC_FINGER_C2H2_1, 6 hits
PS50157 ZINC_FINGER_C2H2_2, 6 hits

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q5VTD9-1) [UniParc]FASTAAdd to basket
Also known as: p37

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.

« Hide

        10         20         30         40         50
MPRSFLVKSK KAHTYHQPRV QEDEPLWPPA LTPVPRDQAP SNSPVLSTLF
60 70 80 90 100
PNQCLDWTNL KREPELEQDQ NLARMAPAPE GPIVLSRPQD GDSPLSDSPP
110 120 130 140 150
FYKPSFSWDT LATTYGHSYR QAPSTMQSAF LEHSVSLYGS PLVPSTEPAL
160 170 180 190 200
DFSLRYSPGM DAYHCVKCNK VFSTPHGLEV HVRRSHSGTR PFACDICGKT
210 220 230 240 250
FGHAVSLEQH THVHSQERSF ECRMCGKAFK RSSTLSTHLL IHSDTRPYPC
260 270 280 290 300
QFCGKRFHQK SDMKKHTYIH TGEKPHKCQV CGKAFSQSSN LITHSRKHTG
310 320 330
FKPFSCELCT KGFQRKVDLR RHRESQHNLK
Length:330
Mass (Da):37,492
Last modified:December 7, 2004 - v1
Checksum:i947DD9C34B5BD962
GO
Isoform 2 (identifier: Q5VTD9-2) [UniParc]FASTAAdd to basket
Also known as: p32

The sequence of this isoform differs from the canonical sequence as follows:
     171-216: Missing.

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.
Show »
Length:284
Mass (Da):32,419
Checksum:i36498895611B0E20
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti11K → M in AAR06639 (PubMed:15280509).Curated1
Sequence conflicti27W → R in CAG38783 (Ref. 3) Curated1
Sequence conflicti29P → H in AAD08672 (PubMed:9878267).Curated1
Sequence conflicti190R → W in AAR06639 (PubMed:15280509).Curated1
Sequence conflicti219S → N in AAD08672 (PubMed:9878267).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_035556231R → H in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs761044764Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_028459171 – 216Missing in isoform 2. 1 PublicationAdd BLAST46

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF081946 mRNA Translation: AAD08672.1
AY428733 mRNA Translation: AAR06639.1
CR536546 mRNA Translation: CAG38783.1
AL593851 Genomic DNA No translation available.
CH471090 Genomic DNA Translation: EAW88025.1
BC043371 mRNA Translation: AAH43371.1
BC035626 mRNA No translation available.
CCDSiCCDS48049.1 [Q5VTD9-2]
CCDS6957.1 [Q5VTD9-1]
RefSeqiNP_001128503.1, NM_001135031.1 [Q5VTD9-2]
NP_004179.3, NM_004188.6 [Q5VTD9-1]
XP_011517372.1, XM_011519070.2 [Q5VTD9-1]
XP_016870665.1, XM_017015176.1 [Q5VTD9-2]
UniGeneiHs.553160

Genome annotation databases

EnsembliENST00000339463; ENSP00000344782; ENSG00000165702 [Q5VTD9-1]
ENST00000372122; ENSP00000361195; ENSG00000165702 [Q5VTD9-1]
ENST00000372123; ENSP00000361196; ENSG00000165702 [Q5VTD9-2]
GeneIDi8328
KEGGihsa:8328
UCSCiuc004ccg.4 human [Q5VTD9-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiGFI1B_HUMAN
AccessioniPrimary (citable) accession number: Q5VTD9
Secondary accession number(s): O95270
, Q5VTD8, Q6FHZ2, Q6T888
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 2, 2007
Last sequence update: December 7, 2004
Last modified: June 20, 2018
This is version 140 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

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