Q5VTD9 (GFI1B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Zinc finger protein Gfi-1b

Alternative name(s):
Growth factor independent protein 1B
Potential regulator of CDKN1A translocated in CML

Gene names

Name:

GFI1B

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	330 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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. Ref.7 Ref.9 Ref.10 Ref.11 Ref.13 Ref.14 Ref.15 Ref.16
Subunit structure	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. Ref.8 Ref.9 Ref.10 Ref.12 Ref.15
Subcellular location	Nucleus Ref.10.
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). Ref.1 Ref.7 Ref.14
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. Ref.2
Domain	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.
Post-translational modification	Methylation at Lys-8 in the SNAG domain seems required for the recruitment of the corepressor complex. Ref.16
Sequence similarities	Contains 6 C2H2-type zinc fingers.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Proto-oncogene
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator Chromatin regulator Developmental protein Repressor
PTM	Methylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell proliferation Traceable author statement PubMed 9566867. Source: ProtInc chromatin modification Inferred from electronic annotation. Source: UniProtKB-KW multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of transcription from RNA polymerase II promoter Traceable author statement PubMed 9566867. Source: ProtInc regulation of transcription involved in G1 phase of mitotic cell cycle Traceable author statement PubMed 9566867. Source: ProtInc transcription from RNA polymerase II promoter Traceable author statement PubMed 9566867. Source: ProtInc
Cellular_component	nuclear matrix Inferred from direct assay Ref.8. Source: UniProtKB transcription factor complex Inferred from direct assay PubMed 15920471. Source: BHF-UCL
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CENPJ	Q9HC77	2	EBI-946212,EBI-946194
JAG2	Q9Y219	2	EBI-946212,EBI-946223
NELL2	Q99435	2	EBI-946212,EBI-946274

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q5VTD9-1)

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.

Isoform 2 (identifier: Q5VTD9-2)

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.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 330	330	Zinc finger protein Gfi-1b		PRO_0000306327
Regions
	Zinc finger	163 – 186	24	C2H2-type 1
	Zinc finger	192 – 214	23	C2H2-type 2
	Zinc finger	220 – 242	23	C2H2-type 3
	Zinc finger	248 – 270	23	C2H2-type 4
	Zinc finger	276 – 298	23	C2H2-type 5
	Zinc finger	304 – 327	24	C2H2-type 6
	Region	1 – 20	20	SNAG domain
	Region	91 – 330	240	Interaction with ARIH2
	Region	164 – 330	167	Mediates interaction with GATA1
Amino acid modifications
	Modified residue	8	1	N6,N6-dimethyllysine Ref.16
Natural variations
	Alternative sequence	171 – 216	46	Missing in isoform 2.		VSP_028459
	Natural variant	231	1	R → H in a colorectal cancer sample; somatic mutation. Ref.17		VAR_035556
Experimental info
	Mutagenesis	290	1	N → S: Prevents DNA-binding. Ref.13
	Sequence conflict	11	1	K → M in AAR06639. Ref.2
	Sequence conflict	27	1	W → R in CAG38783. Ref.3
	Sequence conflict	29	1	P → H in AAD08672. Ref.1
	Sequence conflict	190	1	R → W in AAR06639. Ref.2
	Sequence conflict	219	1	S → N in AAD08672. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (p37) [UniParc]. Last modified December 7, 2004. Version 1. Checksum: 947DD9C34B5BD962	FASTA	330	37,492
	10 20 30 40 50 60 MPRSFLVKSK KAHTYHQPRV QEDEPLWPPA LTPVPRDQAP SNSPVLSTLF PNQCLDWTNL 70 80 90 100 110 120 KREPELEQDQ NLARMAPAPE GPIVLSRPQD GDSPLSDSPP FYKPSFSWDT LATTYGHSYR 130 140 150 160 170 180 QAPSTMQSAF LEHSVSLYGS PLVPSTEPAL DFSLRYSPGM DAYHCVKCNK VFSTPHGLEV 190 200 210 220 230 240 HVRRSHSGTR PFACDICGKT FGHAVSLEQH THVHSQERSF ECRMCGKAFK RSSTLSTHLL 250 260 270 280 290 300 IHSDTRPYPC QFCGKRFHQK SDMKKHTYIH TGEKPHKCQV CGKAFSQSSN LITHSRKHTG 310 320 330 FKPFSCELCT KGFQRKVDLR RHRESQHNLK
	Isoform 2 (p32) [UniParc]. Checksum: 36498895611B0E20	FASTA	284	32,419
	10 20 30 40 50 60 MPRSFLVKSK KAHTYHQPRV QEDEPLWPPA LTPVPRDQAP SNSPVLSTLF PNQCLDWTNL 70 80 90 100 110 120 KREPELEQDQ NLARMAPAPE GPIVLSRPQD GDSPLSDSPP FYKPSFSWDT LATTYGHSYR 130 140 150 160 170 180 QAPSTMQSAF LEHSVSLYGS PLVPSTEPAL DFSLRYSPGM DAYHCVKCNK ERSFECRMCG 190 200 210 220 230 240 KAFKRSSTLS THLLIHSDTR PYPCQFCGKR FHQKSDMKKH TYIHTGEKPH KCQVCGKAFS 250 260 270 280 QSSNLITHSR KHTGFKPFSC ELCTKGFQRK VDLRRHRESQ HNLK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The human homologue (GFI1B) of the chicken GFI gene maps to chromosome 9q34.13-A locus frequently altered in hematopoietic diseases." Roedel B., Wagner T., Zoernig M., Niessing J., Moeroey T. Genomics 54:580-582(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY. Tissue: Umbilical cord blood.
[2]	"GATA-1 and NF-Y cooperate to mediate erythroid-specific transcription of Gfi-1B gene." Huang D.Y., Kuo Y.Y., Lai J.S., Suzuki Y., Sugano S., Chang Z.F. Nucleic Acids Res. 32:3935-3946(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INDUCTION BY GATA1.
[3]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Brain.
[7]	"Erythroid expansion mediated by the Gfi-1B zinc finger protein: role in normal hematopoiesis." Osawa M., Yamaguchi T., Nakamura Y., Kaneko S., Onodera M., Sawada K., Jegalian A., Wu H., Nakauchi H., Iwama A. Blood 100:2769-2777(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[8]	"Gfi-1 attaches to the nuclear matrix, associates with ETO (MTG8) and histone deacetylase proteins, and represses transcription using a TSA-sensitive mechanism." McGhee L., Bryan J., Elliott L., Grimes H.L., Kazanjian A., Davis J.N., Meyers S. J. Cell. Biochem. 89:1005-1018(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RUNX1T1.
[9]	"GATA-1 mediates auto-regulation of Gfi-1B transcription in K562 cells." Huang D.-Y., Kuo Y.-Y., Chang Z.-F. Nucleic Acids Res. 33:5331-5342(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DNA-BINDING, INTERACTION WITH GATA1.
[10]	"Gfi1b alters histone methylation at target gene promoters and sites of gamma-satellite containing heterochromatin." Vassen L., Fiolka K., Moeroey T. EMBO J. 25:2409-2419(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH EHMT2 AND SUV39H1.
[11]	"Gene expression patterns define novel roles for E47 in cell cycle progression, cytokine-mediated signaling, and T lineage development." Schwartz R., Engel I., Fallahi-Sichani M., Petrie H.T., Murre C. Proc. Natl. Acad. Sci. U.S.A. 103:9976-9981(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[12]	"Gfi1 ubiquitination and proteasomal degradation is inhibited by the ubiquitin ligase Triad1." Marteijn J.A., van der Meer L.T., van Emst L., van Reijmersdal S., Wissink W., de Witte T., Jansen J.H., Van der Reijden B.A. Blood 110:3128-3135(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ARIH2.
[13]	"Growth factor independent 1B (Gfi1b) is an E2A target gene that modulates Gata3 in T-cell lymphomas." Wei X., Kee B.L. Blood 109:4406-4414(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DNA-BINDING, MUTAGENESIS OF ASN-290.
[14]	"Growth factor-independent 1B gene (GFI1B) is overexpressed in erythropoietic and megakaryocytic malignancies and increases their proliferation rate." Elmaagacli A.H., Koldehoff M., Zakrzewski J.L., Steckel N.K., Ottinger H., Beelen D.W. Br. J. Haematol. 136:212-219(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[15]	"GATA-1 and Gfi-1B interplay to regulate Bcl-xL transcription." Kuo Y.-Y., Chang Z.-F. Mol. Cell. Biol. 27:4261-4272(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH GATA1.
[16]	"A short Gfi-1B isoform controls erythroid differentiation by recruiting the LSD1-CoREST complex through the dimethylation of its SNAG domain." Laurent B., Randrianarison-Huetz V., Frisan E., Andrieu-Soler C., Soler E., Fontenay M., Dusanter-Fourt I., Dumenil D. J. Cell Sci. 125:993-1002(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION (ISOFORM 2), METHYLATION AT LYS-8.
[17]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] HIS-231.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF081946 mRNA. Translation: AAD08672.1. AY428733 mRNA. Translation: AAR06639.1. CR536546 mRNA. Translation: CAG38783.1. AL593851 Genomic DNA. Translation: CAH73618.1. AL593851 Genomic DNA. Translation: CAH73619.1. CH471090 Genomic DNA. Translation: EAW88025.1. BC043371 mRNA. Translation: AAH43371.1. BC035626 mRNA. No translation available.
IPI	IPI00003110. IPI00479652.
RefSeq	NP_001128503.1. NM_001135031.1. NP_004179.3. NM_004188.4.
UniGene	Hs.553160.
3D structure databases
HSSP	HSSP built from PDB template 2COT based on UniProtKB Q9H4T2.
ProteinModelPortal	Q5VTD9.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q5VTD9. 71 interactions.
MINT	MINT-2798741.
STRING	9606.ENSP00000344782.
PTM databases
PhosphoSite	Q5VTD9.
Polymorphism databases
DMDM	74756792.
Proteomic databases
PaxDb	Q5VTD9.
PRIDE	Q5VTD9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000339463; ENSP00000344782; ENSG00000165702. ENST00000372122; ENSP00000361195; ENSG00000165702. ENST00000372123; ENSP00000361196; ENSG00000165702. ENST00000372124; ENSP00000361197; ENSG00000165702. ENST00000450530; ENSP00000409546; ENSG00000165702. ENST00000534944; ENSP00000446134; ENSG00000165702.
GeneID	8328.
KEGG	hsa:8328.
UCSC	uc004ccg.3. human. uc010mzy.3. human.
Organism-specific databases
CTD	8328.
GeneCards	GC09P135821.
HGNC	HGNC:4238. GFI1B.
HPA	HPA007012.
MIM	604383. gene.
neXtProt	NX_Q5VTD9.
PharmGKB	PA28649.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5048.
HOGENOM	HOG000067832.
HOVERGEN	HBG106655.
InParanoid	Q5VTD9.
KO	K09223.
OMA	YGHSYRQ.
PhylomeDB	Q5VTD9.
Gene expression databases
Bgee	Q5VTD9.
CleanEx	HS_GFI1B.
Genevestigator	Q5VTD9.
Family and domain databases
Gene3D	3.30.160.60. 6 hits.
InterPro	IPR007087. Znf_C2H2. IPR015880. Znf_C2H2-like. IPR013087. Znf_C2H2/integrase_DNA-bd. [Graphical view]
Pfam	PF00096. zf-C2H2. 1 hit. [Graphical view]
SMART	SM00355. ZnF_C2H2. 6 hits. [Graphical view]
PROSITE	PS00028. ZINC_FINGER_C2H2_1. 6 hits. PS50157. ZINC_FINGER_C2H2_2. 6 hits. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	8328.
NextBio	31186.
SOURCE	Search...

Entry information

Entry name

GFI1B_HUMAN

Accession

Primary (citable) accession number: Q5VTD9
Secondary accession number(s): O95270 , Q5VTD8, Q6FHZ2, Q6T888

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 2, 2007
Last sequence update:	December 7, 2004
Last modified:	May 1, 2013
This is version 93 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.