O35615 (FOG1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Zinc finger protein ZFPM1

Alternative name(s):
Friend of GATA protein 1
Short name=FOG-1
Short name=Friend of GATA 1
Zinc finger protein multitype 1

Gene names

Name:	Zfpm1
Synonyms:	Fog, Fog1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	995 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcription regulator that plays an essential role in erythroid and megakaryocytic cell differentiation. Essential cofactor that acts via the formation of a heterodimer with transcription factors of the GATA family GATA1, GATA2 and GATA3. Such heterodimer can both activate or repress transcriptional activity, depending on the cell and promoter context. The heterodimer formed with GATA proteins is essential to activate expression of genes such as NFE2, ITGA2B, alpha- and beta-globin, while it represses expression of KLF1. May be involved in regulation of some genes in gonads. May also be involved in cardiac development, in a non-redundant way with ZFPM2/FOG2. Ref.1 Ref.2 Ref.4 Ref.5 Ref.6 Ref.7 Ref.8
Subunit structure	Interacts with the N-terminal zinc-finger of GATA1, GATA2 and GATA3. Interacts with corepressor CTBP2; this interaction is however not essential for corepressor activity in erythropoiesis. Interacts with TACC3. Ref.1 Ref.3 Ref.5 Ref.6 Ref.11
Subcellular location	Nucleus Ref.1.
Tissue specificity	Mainly expressed in hematopoietic tissues. Expressed in the spleen, a primary site of hematopoiesis in the adult mouse, as well as in the liver and testis, but not in the heart, brain, lung, kidney, or skeletal muscle. Among hematopoietic cell lines, it is strongly expressed in erythroid and megakaryocytic cell lines. Expressed at low level in several lymphoid and early myeloid cell lines. Not expressed in mast cell and macrophage lines. Expressed in the heart, where it colocalizes with GATA4, GATA5 and GATA6. Ref.1 Ref.8
Developmental stage	First expressed in two extraembryonic mesodermal derivatives, the yolk sac and the allantois in E8.5 embryos. Localized to the embryonic red blood cells within the yolk sac blood islands. Ref.1
Domain	The CCHC-type zinc fingers 1, 5, 6 and 9 bind directly to GATA-type zinc fingers. The Tyr residue adjacent to the last Cys of the CCHC-type zinc finger is essential for the interaction with GATA-type zinc fingers.
Sequence similarities	Belongs to the FOG (Friend of GATA) family. Contains 4 C2H2-type zinc fingers. Contains 5 C2HC-type zinc fingers.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator Repressor
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	atrial septum morphogenesis Inferred from mutant phenotype Ref.8. Source: BHF-UCL atrioventricular valve morphogenesis Inferred from mutant phenotype Ref.8. Source: BHF-UCL cardiac muscle tissue morphogenesis Inferred from mutant phenotype Ref.8. Source: BHF-UCL definitive erythrocyte differentiation Inferred from mutant phenotype Ref.2. Source: MGI granulocyte differentiation Inferred from mutant phenotype PubMed 20010697. Source: MGI megakaryocyte development Inferred from mutant phenotype PubMed 20010697. Source: MGI mitral valve formation Inferred from mutant phenotype Ref.8. Source: BHF-UCL negative regulation of fat cell differentiation Inferred from mutant phenotype PubMed 20705609. Source: UniProtKB negative regulation of interleukin-4 biosynthetic process Inferred from electronic annotation. Source: Compara negative regulation of mast cell differentiation Inferred from direct assay PubMed 18063754. Source: BHF-UCL negative regulation of protein binding Inferred from direct assay PubMed 18063754. Source: BHF-UCL negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 2906112. Source: MGI outflow tract morphogenesis Inferred from mutant phenotype Ref.8. Source: BHF-UCL platelet formation Inferred from electronic annotation. Source: Compara positive regulation of interferon-gamma biosynthetic process Inferred from electronic annotation. Source: Compara primitive erythrocyte differentiation Inferred from mutant phenotype Ref.2. Source: MGI regulation of chemokine production Inferred from mutant phenotype PubMed 20643340. Source: MGI regulation of definitive erythrocyte differentiation Inferred from electronic annotation. Source: Compara transcriptional activation by promoter-enhancer looping Inferred from direct assay PubMed 15644435. Source: BHF-UCL tricuspid valve formation Inferred from mutant phenotype Ref.8. Source: BHF-UCL ventricular septum morphogenesis Inferred from mutant phenotype Ref.8. Source: BHF-UCL
Cellular_component	cytoplasm Inferred from direct assay PubMed 19654328. Source: MGI nucleus Inferred from direct assay PubMed 12213678PubMed 12923059PubMed 19654328. Source: MGI transcription factor complex Inferred from electronic annotation. Source: Compara transcriptional repressor complex Inferred from electronic annotation. Source: Compara
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW RNA polymerase II activating transcription factor binding Inferred from direct assay Ref.1. Source: MGI RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription Inferred from electronic annotation. Source: Compara transcription corepressor activity Traceable author statement PubMed 12923059. Source: MGI zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Tacc3	Q9JJ11	7	EBI-4394596,EBI-2553611

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 995

995

Zinc finger protein ZFPM1

PRO_0000221042

Regions

Zinc finger

255 – 278

24

C2HC-type 1

Zinc finger

303 – 327

25

C2H2-type 1

Zinc finger

333 – 355

23

C2H2-type 2

Zinc finger

361 – 384

24

C2H2-type 3

Zinc finger

590 – 613

24

C2HC-type 2

Zinc finger

696 – 719

24

C2HC-type 3

Zinc finger

836 – 859

24

C2HC-type 4

Zinc finger

868 – 891

24

C2H2-type 4

Zinc finger

963 – 986

24

C2HC-type 5

Region

343 – 354

12

Interaction with TACC3

Region

811 – 817

7

Interaction with CTBP2

Amino acid modifications

Modified residue

497

1

Phosphoserine Ref.10

Modified residue

500

1

Phosphoserine Ref.10

Modified residue

651

1

Phosphoserine Ref.10

Modified residue

666

1

Phosphothreonine Ref.9

Modified residue

803

1

Phosphoserine By similarity

Modified residue

925

1

Phosphoserine Ref.10

Modified residue

927

1

Phosphoserine Ref.10

Experimental info

Mutagenesis

254

1

V → A: Does not affect the interaction with GATA1. Ref.5 Ref.6

Mutagenesis

255

1

F → A: Impairs interaction with GATA1. Ref.5 Ref.6

Mutagenesis

256

1

P → A: Does not affect the interaction with GATA1. Ref.5 Ref.6

Mutagenesis

258

1

K → A: Does not affect the interaction with GATA1. Ref.5 Ref.6

Mutagenesis

259

1

D → A: Does not affect the interaction with GATA1. Ref.5 Ref.6

Mutagenesis

261

1

G → A: Slightly affects the interaction with GATA1. Ref.5 Ref.6

Mutagenesis

262

1

I → A: Impairs interaction with GATA1. Ref.5 Ref.6

Mutagenesis

263

1

W → A: Does not affect the interaction with GATA1. Ref.5 Ref.6

Mutagenesis

265

1

R → A: Slightly affects the interaction with GATA1. Ref.5 Ref.6

Mutagenesis

266

1

S → A: Does not affect the interaction with GATA1. Ref.5 Ref.6

Mutagenesis

267

1

E → A: Slightly affects the interaction with GATA1. Ref.5 Ref.6

Mutagenesis

268

1

R → A: Does not affect the interaction with GATA1. Ref.5 Ref.6

Mutagenesis

269

1

N → A: Impairs interaction with GATA1. Ref.5 Ref.6

Mutagenesis

271

1

Q → A: Does not affect the interaction with GATA1. Ref.5 Ref.6

Mutagenesis

274

1

L → A: Slightly affects the interaction with GATA1. Ref.5 Ref.6

Mutagenesis

275

1

L → A: Does not affect the interaction with GATA1. Ref.5 Ref.6

Mutagenesis

276

1

Y → A: Slightly affects the interaction with GATA1. Ref.5 Ref.6

Mutagenesis

277

1

Y → A: Impairs interaction with GATA1. Strongly impairs interaction with GATA1; when associated with A-612; A-718 and/or A-985. Ref.5 Ref.6

Mutagenesis

280

1

S → A: Does not affect the interaction with GATA1. Ref.5 Ref.6

Mutagenesis

281

1

R → A: Does not affect the interaction with GATA1. Ref.5 Ref.6

Mutagenesis

334

1

V → A: No effect on interaction with TACC3. Ref.6 Ref.11

Mutagenesis

336

1

L → A: No effect on interaction with TACC3. Ref.6 Ref.11

Mutagenesis

339

1

L → A: No effect on interaction with TACC3. Ref.6 Ref.11

Mutagenesis

340

1

S → A: No effect on interaction with TACC3. Ref.6 Ref.11

Mutagenesis

343

1

T → A: Impairs interaction with TACC3. Ref.6 Ref.11

Mutagenesis

344

1

T → A: Abolishes interaction with TACC3. Ref.6 Ref.11

Mutagenesis

345

1

K → A: No effect on interaction with TACC3. Ref.6 Ref.11

Mutagenesis

346

1

A → D: No effect on interaction with TACC3. Ref.6 Ref.11

Mutagenesis

347

1

N → A: Abolishes interaction with TACC3. Ref.6 Ref.11

Mutagenesis

349

1

E → A: No effect on interaction with TACC3. Ref.6 Ref.11

Mutagenesis

350

1

R → A: Abolishes interaction with TACC3. Ref.6 Ref.11

Mutagenesis

352

1

L → A: No effect on interaction with TACC3. Ref.6 Ref.11

Mutagenesis

353

1

K → A: No effect on interaction with TACC3. Ref.6 Ref.11

Mutagenesis

354

1

V → A: Abolishes interaction with TACC3. Ref.6 Ref.11

Mutagenesis

356

1

T → A: No effect on interaction with TACC3. Ref.6 Ref.11

Mutagenesis

357

1

D → A: No effect on interaction with TACC3. Ref.6 Ref.11

Mutagenesis

612

1

Y → A: Impairs interaction with GATA1. Strongly impairs interaction with GATA1; when associated with A-277; A-718 and/or A-985. Ref.5 Ref.6

Mutagenesis

698

1

C → A: Abolishes interaction with GATA1. Ref.3 Ref.6

Mutagenesis

706

1

S → R: Able to partially restore the interaction with the G-205 GATA1 mutant, which is usually unable to interact with ZFPM1. Ref.4 Ref.6

Mutagenesis

718

1

Y → A: Impairs interaction with GATA1. Strongly impairs interaction with GATA1; when associated with A-277; A-612 and/or A-985. Ref.5 Ref.6

Mutagenesis

719

1

C → A: Abolishes interaction with GATA1. Ref.3 Ref.6

Mutagenesis

719

1

C → H: Transforms the C2HC-type zinc finger into a C2H2-type, leading to abolition of interaction with GATA1. Ref.3 Ref.6

Mutagenesis

811 – 814

4

PIDL → AIAA: Abolishes interaction with CTBP2. Ref.5 Ref.6

Mutagenesis

813 – 814

2

DL → AS: Abolishes interaction with CTBP2; it however does not abolish the corepressor activity in erythropoiesis. Ref.6

Mutagenesis

985

1

Y → A: Slightly affects the interaction with GATA1. Strongly impairs interaction with GATA1; when associated with A-277; A-612 and/or A-718. Ref.5 Ref.6

Secondary structure

1

.

.

.

.

.

.

.

995

Helix Strand Turn

Details...

Beta strand

336 – 338

3

Beta strand

341 – 344

4

Helix

345 – 352

8

Helix

353 – 355

3

Sequences

	Sequence		Length	Mass (Da)
	O35615 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 293255B28151ECB8	FASTA	995	105,984
	10 20 30 40 50 60 MSRRKQSNPR QIKRSLRDME AGEEAKAMDS SPKEQEAPDP EAPAIEEPPS PPREDVSPPA 70 80 90 100 110 120 VPAPPESPED PEDMEGQELE MRPQDEEKEE KEEEAAMASP WSGPEELELA LQDGQRCVRA 130 140 150 160 170 180 RLSLTEGLSW GPFYGSIQTR ALSPEREEPG PAVTLMVDES CWLRMLPQVL TEEAANSEIY 190 200 210 220 230 240 RKDDALWCRV TKVVPSGGLL YVRLVTEPHG APRHPVQEPV EPGGLAPVHT DIQLLPQQAG 250 260 270 280 290 300 MASILATAVI NKDVFPCKDC GIWYRSERNL QAHLLYYCAS RQRAGSPVSA TEEKPKETYP 310 320 330 340 350 360 NERVCPFPQC RKSCPSASSL EIHMRSHSGE RPFVCLICLS AFTTKANCER HLKVHTDTLS 370 380 390 400 410 420 GVCHNCGFIS TTRDILYSHL VTNHMVCQPG SKGEIYSPGA GHPAAKLPPD SLAGFQQHSL 430 440 450 460 470 480 MHSPLVPADK APTPSSGLDS KAEVTNGETR VPPQNGGSSE SPAAPRTIKV EAAEEPEATR 490 500 510 520 530 540 ASGPGEPGPQ APSRTPSPHS PNPVRVKTEL SSPTPGSSPG PGELTMAGTL FLPQYVFSPD 550 560 570 580 590 600 AGTTTVPTAP QASEILAKMS ELVHNRLQQG AGSSGAAGTP TGLFSGTKGA TCFECEITFN 610 620 630 640 650 660 NINNFYVHKR LYCSGRRAPE DPPTVRRPKA ATGPARAPAG AAAEPDPSRS SPGPGPREEE 670 680 690 700 710 720 ASGTTTPEAE AAGRGSEGSQ SPGSSVDDAE DDPSRTLCEA CNIRFSRHET YTVHKRYYCA 730 740 750 760 770 780 SRHDPPPRRP PAPTTAPGPA APALTAPPVR TRRRRKLYEL PAAGAPPPAA GPAPVPVVPS 790 800 810 820 830 840 PTAELPSSPR PGSASAGPAP ALSPSPVPDG PIDLSKRPRR QSPDAPTALP ALADYHECTA 850 860 870 880 890 900 CRVSFHSLEA YLAHKKYSCP AAPLRTTALC PYCPPNGRVR GDLVEHLRQA HGLQVAKPAA 910 920 930 940 950 960 SPGAEPRTPA ERAPRDSPDG RAPRSPSPAP ENTPSDPADQ GARTPSKGPP APAPAPGGGG 970 980 990 GHRYCRLCNI RFSSLSTFIA HKKYYCSSHA AEHVK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"FOG, a multitype zinc finger protein, acts as a cofactor for transcription factor GATA-1 in erythroid and megakaryocytic differentiation." Tsang A.P., Visvader J.E., Turner C.A., Fujiwara Y., Yu C., Weiss M.J., Crossley M., Orkin S.H. Cell 90:109-119(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INTERACTION WITH GATA1; GATA2 AND GATA3. Tissue: Erythroleukemia.
[2]	"Failure of megakaryopoiesis and arrested erythropoiesis in mice lacking the GATA-1 transcriptional cofactor FOG." Tsang A.P., Fujiwara Y., Hom D.B., Orkin S.H. Genes Dev. 12:1176-1188(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[3]	"Key residues characteristic of GATA N-fingers are recognized by FOG." Fox A.H., Kowalski K., King G.F., Mackay J.P., Crossley M. J. Biol. Chem. 273:33595-33603(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GATA1, MUTAGENESIS OF CYS-698 AND CYS-719.
[4]	"Use of altered specificity mutants to probe a specific protein-protein interaction in differentiation: the GATA-1:FOG complex." Crispino J.D., Lodish M.B., MacKay J.P., Orkin S.H. Mol. Cell 3:219-228(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF SER-706.
[5]	"Transcriptional cofactors of the FOG family interact with GATA proteins by means of multiple zinc fingers." Fox A.H., Liew C., Holmes M., Kowalski K., Mackay J., Crossley M. EMBO J. 18:2812-2822(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH GATA1 AND CTBP2, MUTAGENESIS OF VAL-254; PHE-255; PRO-256; LYS-258; ASP-259; GLY-261; ILE-262; TRP-263; ARG-265; SER-266; GLU-267; ARG-268; ASN-269; GLN-271; LEU-274; LEU-275; TYR-276; TYR-277; SER-280; ARG-281; 811-PRO--LEU-814; TYR-612; TYR-718 AND TYR-985.
[6]	"Interaction between FOG-1 and the corepressor C-terminal binding protein is dispensable for normal erythropoiesis in vivo." Katz S.G., Cantor A.B., Orkin S.H. Mol. Cell. Biol. 22:3121-3128(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CTBP2, MUTAGENESIS OF 813-ASP-LEU-814.
[7]	"Control of megakaryocyte-specific gene expression by GATA-1 and FOG-1: role of Ets transcription factors." Wang X., Crispino J.D., Letting D.L., Nakazawa M., Poncz M., Blobel G.A. EMBO J. 21:5225-5234(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"Endothelial lineage-mediated loss of the GATA cofactor Friend of GATA 1 impairs cardiac development." Katz S.G., Williams A., Yang J., Fujiwara Y., Tsang A.P., Epstein J.A., Orkin S.H. Proc. Natl. Acad. Sci. U.S.A. 100:14030-14035(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[9]	"Protein phosphorylation and expression profiling by Yin-yang multidimensional liquid chromatography (Yin-yang MDLC) mass spectrometry." Dai J., Jin W.-H., Sheng Q.-H., Shieh C.-H., Wu J.-R., Zeng R. J. Proteome Res. 6:250-262(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-666, MASS SPECTROMETRY. Tissue: Liver.
[10]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-497; SER-500; SER-651; SER-925 AND SER-927, MASS SPECTROMETRY. Tissue: Liver.
[11]	"A classic zinc finger from Friend of GATA mediates an interaction with the coiled-coil of transforming acidic coiled-coil 3." Simpson R.J.Y., Yi Lee S.H., Bartle N., Sum E.Y., Visvader J.E., Matthews J.M., Mackay J.P., Crossley M. J. Biol. Chem. 279:39789-39797(2004) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 328-360, INTERACTION WITH TACC3, MUTAGENESIS OF VAL-334; LEU-336; LEU-339; SER-340; THR-343; THR-344; LYS-345; ALA-346; ASN-347; GLU-349; ARG-350; LEU-352; LYS-353; VAL-354; THR-356 AND ASP-357.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF006492 mRNA. Translation: AAC53292.1.

IPI

IPI00132648.

RefSeq

NP_033595.1. NM_009569.3.

UniGene

Mm.390068.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1SRK	NMR	-	A	328-360	[»]

ProteinModelPortal

O35615.

SMR

O35615. Positions 250-383, 581-619, 837-894, 956-992.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-48414N.

IntAct

O35615. 2 interactions.

STRING

10090.ENSMUSP00000058037.

PTM databases

PhosphoSite

O35615.

Proteomic databases

PaxDb

O35615.

PRIDE

O35615.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000054052; ENSMUSP00000058037; ENSMUSG00000049577.

GeneID

22761.

KEGG

mmu:22761.

UCSC

uc009nsj.1. mouse.

Organism-specific databases

CTD

161882.

MGI

MGI:1095400. Zfpm1.

Phylogenomic databases

eggNOG

NOG146797.

GeneTree

ENSGT00530000063823.

HOGENOM

HOG000112626.

HOVERGEN

HBG101018.

InParanoid

O35615.

OMA

CTACSIS.

OrthoDB

EOG4N5VZN.

Gene expression databases

ArrayExpress

O35615.

Bgee

O35615.

CleanEx

MM_ZFPM1.

Genevestigator

O35615.

GermOnline

ENSMUSG00000049577. Mus musculus.

Family and domain databases

Gene3D

3.30.160.60. 2 hits.

InterPro

IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]

SMART

SM00355. ZnF_C2H2. 9 hits.
[Graphical view]

PROSITE

PS00028. ZINC_FINGER_C2H2_1. 2 hits.
PS50157. ZINC_FINGER_C2H2_2. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

O35615.

NextBio

303277.

SOURCE

Search...

Entry information

Entry name

FOG1_MOUSE

Accession

Primary (citable) accession number: O35615

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2004
Last sequence update:	January 1, 1998
Last modified:	May 1, 2013
This is version 108 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program