P70338 (GFI1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Zinc finger protein Gfi-1

Alternative name(s):
Growth factor independent protein 1

Gene names

Name:	Gfi1
Synonyms:	Gfi-1

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	423 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcription repressor essential for hematopoiesis. Functions in a cell-context and development-specific manner. Binds to 5'-TAAATCAC[AT]GCA-3' in the promoter region of a large number of genes. Component of several complexes, including the EHMT2-GFI1-HDAC1, AJUBA-GFI1-HDAC1 and RCOR-GFI-KDM1A-HDAC complexes, that suppress, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Regulates neutrophil differentiation, promotes proliferation of lymphoid cells, and is required for granulocyte development. Mediates, together with U2AF1L4, the alternative splicing of CD45 and controls T-cell receptor signaling. Regulates the endotoxin-mediated Toll-like receptor (TLR) inflammatory response by antagonizing RELA. Cooperates with CBFA2T2 to regulate ITGB1-dependent neurite growth. Controls cell-cycle progression by repressing CDKNIA/p21 transcription in response to TGFB1 via recruitment of GFI1 by ZBTB17 to the CDKNIA/p21 promoter. Required for the maintenance of inner ear hair cells. Ref.2 Ref.4 Ref.6 Ref.7 Ref.8
Subunit structure	Interacts (via the zinc-finger domain) with ARIH2; the interaction prevents GFI1 ubiquitination and proteasomal degradation. Forms a complex with EHMT2 and HDAC1 to promote 'Lys-9' dimethylation of H3 (H3K9Me2) and repress expression of target genes. Interacts directly with EHMT2. Interacts with RUNX1T1; the interaction represses HDAC-mediated transcriptional activity. Interacts (via the C-terminal zinc fingers) with ZBTB17; the interaction results in the recruitment of GFI1 to the CDKN1A/p21 promoter and repression of CDKN1A/p21 transcription By similarity. Interacts with U2AF1L4. Component of RCOR-GFI-KDM1A-HDAC complexes. Interacts directly with RCOR1, KDM1A and HDAC2. Also interacts with HDAC1. Component of the GFI1-AJUBA-HDAC1 repressor complex. Interacts directly with AJUBA (via its LIM domains); the interaction results in the HDAC-dependent corepression of a subset of GFI1 target genes and, occurs independently of the SNAG domain. Interacts with SPI1; the interaction inhibits SPI1 transcriptional activity and represses SPI1-regulated macrophage-specific genes required for proper granulocyte developmment. Interacts with PIAS3; the interaction relieves the inhibitory effect of PIAS3 on STAT3-mediated transcriptional activity. Interacts with RELA; the interaction occurs on liposaccharide (LPS) stimulation and controls RELA DNA binding activity and regulates endotoxin-mediated TOLL-like receptor inflammatory response. Ref.5 Ref.6 Ref.7
Subcellular location	Nucleus. Note: Colocalizes with PIAS3 and RUNX1T1 in nuclear dots By similarity.
Induction	By IL2 and CSF3. Induced by the endotoxin bacterial lipopolysaccharide (LPS) in primary bone marrow macrophages (BMDMs). Ref.8
Domain	Zinc fingers 3,4 and 5 are required for DNA binding and for interaction with SPI1 By similarity. Ref.3 Ref.6 The SNAG domain of GFIs is required for nuclear location and for interaction with some corepressors. Ref.3 Ref.6
Post-translational modification	Ubiquitinated By similarity.
Disruption phenotype	Null mice exhibit neutropenia, characterized by absence of neutrophils. This results in growth retardation, susceptibility to bacterial infection and early lethality. Immature granulocytes and macrophage precursors accumulate in bone marrow. Mice have inner ear anomalies, as they are ataxic, circle, display head tilting behavior and do not respond to noise. In the inner ear, hair cells are disorganized in both vestibule and cochlea. Outer hair cells of the cochlea are initially improperly innervated, and just before birth, mice lose all cochlear hair cells due to apoptosis. By 5 months there is a dramatic reduction in the number of cochlear neurons. Ref.4 Ref.6
Sequence similarities	Contains 6 C2H2-type zinc fingers.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	auditory receptor cell differentiation Inferred from mutant phenotype Ref.4. Source: MGI cell fate commitment Inferred from mutant phenotype. Source: MGI cellular response to lipopolysaccharide Inferred from expression pattern Ref.8. Source: UniProtKB inner ear morphogenesis Inferred from mutant phenotype Ref.4. Source: MGI mechanosensory behavior Inferred from mutant phenotype Ref.4. Source: MGI negative regulation of NF-kappaB transcription factor activity Inferred from mutant phenotype Ref.8. Source: UniProtKB negative regulation of cell fate specification Inferred from mutant phenotype. Source: MGI negative regulation of neuron projection development Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype Ref.8. Source: UniProtKB positive regulation of cell fate specification Inferred from mutant phenotype. Source: MGI transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	transcriptional repressor complex Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction Ref.7. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Chaf1a	Q9QWF0	5	EBI-3954754,EBI-639217
Pias3	O54714	6	EBI-3954754,EBI-927969
Spi1	P17433	2	EBI-3954754,EBI-607588
U2af1l4	Q8BGJ9	5	EBI-3954754,EBI-4288480

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 423	423	Zinc finger protein Gfi-1		PRO_0000047194
Regions
	Zinc finger	256 – 279	24	C2H2-type 1
	Zinc finger	285 – 307	23	C2H2-type 2
	Zinc finger	313 – 335	23	C2H2-type 3
	Zinc finger	341 – 363	23	C2H2-type 4
	Zinc finger	369 – 391	23	C2H2-type 5
	Zinc finger	397 – 420	24	C2H2-type 6
	Region	1 – 20	20	SNAG domain
	Region	141 – 258	118	Required for interaction with RELA By similarity
	Compositional bias	159 – 210	52	Ala/Gly-rich
Amino acid modifications
	Modified residue	57	1	Phosphoserine By similarity
Experimental info
	Mutagenesis	2	1	P → A: Abrogates transcriptional repression. No change in nuclear location. Ref.3
	Mutagenesis	3	1	R → A: Partial loss of transcription repression. No change in nuclear location. Ref.3
	Mutagenesis	4	1	S → A: Partial loss of transcription repression. No change in nuclear location. Ref.3
	Mutagenesis	10	1	K → A: Abolishes most of the nuclear localization and reduces transcriptional repressor activity; when associated with A-11. Ref.3
	Mutagenesis	11	1	K → A: Abolishes most of the nuclear localization and reduces transcriptional repressor activity; when associated with A-10. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P70338 [UniParc]. Last modified February 1, 1997. Version 1. Checksum: 8FDAB5BB4886D056	FASTA	423	45,875
	10 20 30 40 50 60 MPRSFLVKSK KAHSYHQPRS PGPDYSLRLE TVPAPGRAEG GAVSAGESKM EPRERLSPDS 70 80 90 100 110 120 QLTEAPDRAS ASPNSCEGSV CDPCSEFEDF WRPPSPSVSP ASEKSLCRSL DEAQPYTLPF 130 140 150 160 170 180 KPYAWSGLAG SDLRHLVQSY RQCSALERSA GLSLFCERGS EPGRPAARYG PEQAAGGAGA 190 200 210 220 230 240 GQPGSCGVAG GATSAAGLGL YGDFAPAAAG LYERPSTAAG RLYQDHGHEL HADKSVGVKV 250 260 270 280 290 300 ESELLCTRLL LGGGSYKCIK CSKVFSTPHG LEVHVRRSHS GTRPFACEMC GKTFGHAVSL 310 320 330 340 350 360 EQHKAVHSQE RSFDCKICGK SFKRSSTLST HLLIHSDTRP YPCQYCGKRF HQKSDMKKHT 370 380 390 400 410 420 FIHTGEKPHK CQVCGKAFSQ SSNLITHSRK HTGFKPFGCD LCGKGFQRKV DLRRHRETQH GLK

References

[1]	"Characterization of pal-1, a common proviral insertion site in murine leukemia virus-induced lymphomas of c-myc and Pim-1 transgenic mice." Scheijen B., Jonkers J., Acton D., Berns A. J. Virol. 71:9-16(1997) [PubMed: 8985317] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: BALB/c. Tissue: Thymus.
[2]	"Zinc finger protein GFI-1 cooperates with myc and pim-1 in T-cell lymphomagenesis by reducing the requirements for IL-2." Zornig M., Schmidt T., Karsunky H., Grzeschiczek A., Moroy T. Oncogene 12:1789-1801(1996) [PubMed: 8622900] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
[3]	"The Gfi-1 proto-oncoprotein contains a novel transcriptional repressor domain, SNAG, and inhibits G1 arrest induced by interleukin-2 withdrawal." Grimes H.L., Chan T.O., Zweidler-McKay P.A., Tong B., Tsichlis P.N. Mol. Cell. Biol. 16:6263-6272(1996) [PubMed: 8887656] [Abstract] Cited for: DOMAIN SNAG, MUTAGENESIS OF PRO-2; ARG-3; SER-4; LYS-10 AND LYS-11.
[4]	"The zinc finger transcription factor Gfi1, implicated in lymphomagenesis, is required for inner ear hair cell differentiation and survival." Wallis D., Hamblen M., Zhou Y., Venken K.J., Schumacher A., Grimes H.L., Zoghbi H.Y., Orkin S.H., Bellen H.J. Development 130:221-232(2003) [PubMed: 12441305] [Abstract] Cited for: DISRUPTION PHENOTYPE, FUNCTION.
[5]	"Auxiliary splice factor U2AF26 and transcription factor Gfi1 cooperate directly in regulating CD45 alternative splicing." Heyd F., ten Dam G., Moeroey T. Nat. Immunol. 7:859-867(2006) [PubMed: 16819553] [Abstract] Cited for: INTERACTION WITH U2AF1L4.
[6]	"The transcriptional repressor GFI-1 antagonizes PU.1 activity through protein-protein interaction." Dahl R., Iyer S.R., Owens K.S., Cuylear D.D., Simon M.C. J. Biol. Chem. 282:6473-6483(2007) [PubMed: 17197705] [Abstract] Cited for: INTERACTION WITH SPI1, DOMAIN ZINC FINGER, FUNCTION, DISRUPTION PHENOTYPE.
[7]	"Epigenetic regulation of hematopoietic differentiation by Gfi-1 and Gfi-1b is mediated by the cofactors CoREST and LSD1." Saleque S., Kim J., Rooke H.M., Orkin S.H. Mol. Cell 27:562-572(2007) [PubMed: 17707228] [Abstract] Cited for: IDENTIFICATION AS A COMPONENT OF A GFI-COR-KDM1A-HDAC COMPLEX, INTERACTION WITH RCOR1; HDAC1; HDAC2 AND KDM1A, FUNCTION.
[8]	"Zinc finger protein Gfi1 controls the endotoxin-mediated Toll-like receptor inflammatory response by antagonizing NF-kappaB p65." Sharif-Askari E., Vassen L., Kosan C., Khandanpour C., Gaudreau M.C., Heyd F., Okayama T., Jin J., Rojas M.E., Grimes H.L., Zeng H., Moroy T. Mol. Cell. Biol. 30:3929-3942(2010) [PubMed: 20547752] [Abstract] Cited for: INDUCTION, FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U58973 mRNA. Translation: AAC52960.1. U58972 mRNA. Translation: AAC52959.1. U78312 mRNA. Translation: AAB36829.1.
IPI	IPI00108152.
RefSeq	NP_034408.1. NM_010278.2.
UniGene	Mm.2078. Mm.453139.
3D structure databases
ProteinModelPortal	P70338.
SMR	P70338. Positions 226-423.
ModBase	Search...
Protein-protein interaction databases
IntAct	P70338. 11 interactions.
STRING	P70338.
PTM databases
PhosphoSite	P70338.
Proteomic databases
PRIDE	P70338.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	14581.
KEGG	mmu:14581.
UCSC	uc008ymv.1. mouse.
Organism-specific databases
CTD	2672.
MGI	MGI:103170. Gfi1.
Phylogenomic databases
HOVERGEN	HBG006967.
InParanoid	P70338.
OrthoDB	EOG48PMK8.
Gene expression databases
ArrayExpress	P70338.
CleanEx	MM_GFI1.
Genevestigator	P70338.
GermOnline	ENSMUSG00000029275. Mus musculus.
Family and domain databases
InterPro	IPR007087. Znf_C2H2. IPR015880. Znf_C2H2-like. IPR013087. Znf_C2H2/integrase_DNA-bd. IPR001878. Znf_CCHC. [Graphical view]
Gene3D	G3DSA:3.30.160.60. Znf_C2H2/integrase_DNA-bd. 6 hits.
KO	K09223.
Pfam	PF00096. zf-C2H2. 6 hits. [Graphical view]
SMART	SM00355. ZnF_C2H2. 6 hits. SM00343. ZnF_C2HC. 1 hit. [Graphical view]
PROSITE	PS00028. ZINC_FINGER_C2H2_1. 6 hits. PS50157. ZINC_FINGER_C2H2_2. 6 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	286310.
SOURCE	Search...

Entry information

Entry name

GFI1_MOUSE

Accession

Primary (citable) accession number: P70338
Secondary accession number(s): O09063

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	February 1, 1997
Last modified:	January 25, 2012
This is version 95 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program