P55316 (FOXG1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Forkhead box protein G1

Alternative name(s):
Brain factor 1
Short name=BF-1
Short name=BF1
Brain factor 2
Short name=BF-2
Short name=BF2
Short name=hBF-2
Forkhead box protein G1A
Forkhead box protein G1B
Forkhead box protein G1C
Forkhead-related protein FKHL1
Short name=HFK1
Forkhead-related protein FKHL2
Short name=HFK2
Forkhead-related protein FKHL3
Short name=HFK3

Gene names

Name:	FOXG1
Synonyms:	FKH2, FKHL1, FKHL2, FKHL3, FKHL4, FOXG1A, FOXG1B, FOXG1C

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	489 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcription repression factor which plays an important role in the establishment of the regional subdivision of the developing brain and in the development of the telencephalon. Ref.6
Subunit structure	Interacts with KDM5B. Ref.6
Subcellular location	Nucleus Ref.8.
Tissue specificity	Expression is restricted to the neurons of the developing telencephalon. Ref.1
Involvement in disease	Defects in FOXG1 are the cause of congenital variant of Rett syndrome (RTTCV) [MIM:613454]. RTTCV is a severe neurodevelopmental disorder with features of classic Rett syndrome but earlier onset in the first months of life. Clinical features include progressive microcephaly, hypotonia, irresponsiveness and irritability in the neonatal period, mental retardation, psychomotor regression and stereotypical movements. Ref.8 Ref.9
Sequence similarities	Contains 1 fork-head DNA-binding domain.
Caution	Ref.1 claims that there are 3 different FOXG1 proteins, FOXG1A, FOXG1B, and FOXG1C. It was latter found that there is only one gene and the differences between these three may be sequencing errors since the protein is coded in a unique exon.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation Mental retardation
Ligand	DNA-binding
Molecular function	Developmental protein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Uncategorized	promoter binding Inferred from Biological aspect of Ancestor. Source: RefGenome specific RNA polymerase II transcription factor activity Inferred from Biological aspect of Ancestor. Source: RefGenome specific transcriptional repressor activity Inferred from Biological aspect of Ancestor. Source: RefGenome transcription activator activity Inferred from Biological aspect of Ancestor. Source: RefGenome
Biological process	axon midline choice point recognition Inferred from Biological aspect of Ancestor. Source: RefGenome central nervous system neuron development Inferred from Biological aspect of Ancestor. Source: RefGenome dorsal/ventral pattern formation Inferred from Biological aspect of Ancestor. Source: RefGenome embryo development ending in birth or egg hatching Inferred from Biological aspect of Ancestor. Source: RefGenome hindbrain development Inferred from Biological aspect of Ancestor. Source: RefGenome inner ear morphogenesis Inferred from Biological aspect of Ancestor. Source: RefGenome negative regulation of neuron differentiation Inferred from Biological aspect of Ancestor. Source: RefGenome negative regulation of transcription, DNA-dependent Inferred from direct assay Ref.6. Source: UniProtKB nonmotile primary cilium assembly Inferred from Biological aspect of Ancestor. Source: RefGenome nose development Inferred from Biological aspect of Ancestor. Source: RefGenome positive regulation of cell cycle Inferred from Biological aspect of Ancestor. Source: RefGenome positive regulation of neuroblast proliferation Inferred from Biological aspect of Ancestor. Source: RefGenome positive regulation of transcription from RNA polymerase II promoter Inferred from Biological aspect of Ancestor. Source: RefGenome regulation of mitotic cell cycle Inferred from Biological aspect of Ancestor. Source: RefGenome regulation of sequence-specific DNA binding transcription factor activity Inferred from Biological aspect of Ancestor. Source: RefGenome tissue development Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular component	transcription factor complex Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular function	DNA binding, bending Inferred from Biological aspect of Ancestor. Source: RefGenome double-stranded DNA binding Inferred from Biological aspect of Ancestor. Source: RefGenome sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro sequence-specific distal enhancer binding RNA polymerase II transcription factor activity Inferred from Biological aspect of Ancestor. Source: RefGenome transcription factor binding Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 489	489	Forkhead box protein G1		PRO_0000091835
Regions
	DNA binding	181 – 275	95	Fork-head
	Region	383 – 406	24	Interaction with KDM5B
	Compositional bias	33 – 57	25	His-rich
	Compositional bias	58 – 112	55	Pro-rich
	Compositional bias	118 – 177	60	Gly-rich
Natural variations
	Natural variant	109	1	P → L. Ref.8		VAR_064395
	Natural variant	215	1	F → L in RTTCV. Ref.9		VAR_063885
	Natural variant	244	1	R → C in RTTCV; the mutant protein extensively, although not fully, localizes in nuclear speckles, while the wild-type is more widely dispersed throughout the nucleus. Ref.8		VAR_064396
Experimental info
	Mutagenesis	388 – 389	2	VP → AA: Abolishes interaction with KDM5B.
	Mutagenesis	394 – 395	2	VP → AA: Abolishes interaction with KDM5B.
	Mutagenesis	404	1	P → A: Abolishes interaction with KDM5B. Ref.6
	Sequence conflict	27 – 28	2	AV → GL in CAA52239. Ref.1
	Sequence conflict	27 – 28	2	AV → GL in CAA52240. Ref.1
	Sequence conflict	27 – 28	2	AV → GL in CAA55038. Ref.2
	Sequence conflict	69 – 75	7	PQQQQPP → RAAQQQQ in CAA52239. Ref.1
	Sequence conflict	79 – 138	60	PPAPQ…PGELA → RRGARRRRRRGPSSCCSAAH AHGAPEGQRQLAQGDRRGRG IC in CAA52240. Ref.1
	Sequence conflict	79 – 138	60	PPAPQ…PGELA → RRGARRRRRRGPSSCCSAAH AHGAPEGQRQLAQGDRRGRG IC in CAA55038. Ref.2
	Sequence conflict	81 – 96	16	APQPP…AADDD → LAPQAGGAAQSNDE in CAA52239. Ref.1
	Sequence conflict	101	1	Q → L in CAA52239. Ref.1
	Sequence conflict	107 – 117	11	PPPPPPAAALD → TDHHRPPS in CAA52239. Ref.1
	Sequence conflict	122 – 133	12	DGLGG…EPGGG → GGCCR in CAA52239. Ref.1
	Sequence conflict	122	1	D → V in AAH50072. Ref.5
	Sequence conflict	138	1	A → G in CAA52239. Ref.1
	Sequence conflict	148 – 150	3	GAG → AR in CAA52240. Ref.1
	Sequence conflict	148 – 150	3	GAG → AR in CAA55038. Ref.2
	Sequence conflict	183	1	P → PP in CAA52241. Ref.1
	Sequence conflict	194	1	I → M in CAA52240. Ref.1
	Sequence conflict	194	1	I → M in CAA55038. Ref.2
	Sequence conflict	226	1	Q → H in CAA52241. Ref.1
	Sequence conflict	231	1	H → D in CAA52241. Ref.1
	Sequence conflict	237	1	K → M in AAH50072. Ref.5
	Sequence conflict	274	1	Missing in CAA52240. Ref.1
	Sequence conflict	274	1	Missing in CAA55038. Ref.2
	Sequence conflict	276	1	Missing in CAA52240. Ref.1
	Sequence conflict	276	1	Missing in CAA55038. Ref.2
	Sequence conflict	281	1	R → P in CAA52239. Ref.1
	Sequence conflict	281	1	R → P in CAA52240. Ref.1
	Sequence conflict	281	1	R → P in CAA55038. Ref.2
	Sequence conflict	284	1	L → P in CAA52240. Ref.1
	Sequence conflict	284	1	L → P in CAA55038. Ref.2
	Sequence conflict	286 – 291	6	FKRGAR → AFRWCA in CAA52241. Ref.1
	Sequence conflict	291	1	R → A in CAA52239. Ref.1
	Sequence conflict	291	1	R → A in CAA52240. Ref.1
	Sequence conflict	291	1	R → A in CAA55038. Ref.2
	Sequence conflict	302 – 320	19	RAGSL…LHHPR → APAPSTGPCRPSCPCTTP in CAA52240. Ref.1
	Sequence conflict	302 – 320	19	RAGSL…LHHPR → APAPSTGPCRPSCPCTTP in CAA55038. Ref.2
	Sequence conflict	356	1	F → S in CAA52240. Ref.1
	Sequence conflict	356	1	F → S in CAA55038. Ref.2
	Sequence conflict	371	1	E → G in CAA52240. Ref.1
	Sequence conflict	371	1	E → G in CAA55038. Ref.2
	Sequence conflict	385	1	A → T in CAA52240. Ref.1
	Sequence conflict	385	1	A → T in CAA55038. Ref.2
	Sequence conflict	393	1	S → L in CAA52240. Ref.1
	Sequence conflict	393	1	S → L in CAA55038. Ref.2
	Sequence conflict	439	1	A → T in AAH50072. Ref.5
	Sequence conflict	446 – 450	5	QAPST → AGPPRP in CAA52240. Ref.1
	Sequence conflict	446 – 450	5	QAPST → AGPPRP in CAA55038. Ref.2
	Sequence conflict	446	1	Q → P in CAA52239. Ref.1
	Sequence conflict	449 – 450	2	ST → RP in CAA52239. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P55316 [UniParc]. Last modified July 10, 2007. Version 2. Checksum: 897945F9CE4F2A71	FASTA	489	52,352
	10 20 30 40 50 60 MLDMGDRKEV KMIPKSSFSI NSLVPEAVQN DNHHASHGHH NSHHPQHHHH HHHHHHHPPP 70 80 90 100 110 120 PAPQPPPPPQ QQQPPPPPPP APQPPQTRGA PAADDDKGPQ QLLLPPPPPP PPAAALDGAK 130 140 150 160 170 180 ADGLGGKGEP GGGPGELAPV GPDEKEKGAG AGGEEKKGAG EGGKDGEGGK EGEKKNGKYE 190 200 210 220 230 240 KPPFSYNALI MMAIRQSPEK RLTLNGIYEF IMKNFPYYRE NKQGWQNSIR HNLSLNKCFV 250 260 270 280 290 300 KVPRHYDDPG KGNYWMLDPS SDDVFIGGTT GKLRRRSTTS RAKLAFKRGA RLTSTGLTFM 310 320 330 340 350 360 DRAGSLYWPM SPFLSLHHPR ASSTLSYNGT TSAYPSHPMP YSSVLTQNSL GNNHSFSTAN 370 380 390 400 410 420 GLSVDRLVNG EIPYATHHLT AAALAASVPC GLSVPCSGTY SLNPCSVNLL AGQTSYFFPH 430 440 450 460 470 480 VPHPSMTSQS STSMSARAAS SSTSPQAPST LPCESLRPSL PSFTTGLSGG LSDYFTHQNQ GSSSNPLIH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human brain factor 1, a new member of the fork head gene family." Murphy D.B., Wiese S., Burfeind P., Schmundt D., Mattei M.-G., Schulz-Schaeffer W., Thies U. Genomics 21:551-557(1994) [PubMed: 7959731] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Fetal brain.
[2]	"The genes for human brain factor 1 and 2, members of the fork head gene family, are clustered on chromosome 14q." Wiese S., Murphy D.B., Schlung A., Burfeind P., Schmundt D., Schnulle V., Mattei M.-G., Thies U. Biochim. Biophys. Acta 1262:105-112(1995) [PubMed: 7599184] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"The DNA sequence and analysis of human chromosome 14." Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J. Nature 421:601-607(2003) [PubMed: 12508121] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[6]	"Human PLU-1 has transcriptional repression properties and interacts with the developmental transcription factors BF-1 and PAX9." Tan K., Shaw A.L., Madsen B., Jensen K., Taylor-Papadimitriou J., Freemont P.S. J. Biol. Chem. 278:20507-20513(2003) [PubMed: 12657635] [Abstract] Cited for: INTERACTION WITH KDM5B, MUTAGENESIS OF 388-VAL-PRO-389; 394-VAL-PRO-395 AND PRO-404, FUNCTION.
[7]	"Comparative evolutionary analysis of the FoxG1 transcription factor from diverse vertebrates identifies conserved recognition sites for microRNA regulation." Bredenkamp N., Seoighe C., Illing N. Dev. Genes Evol. 217:227-233(2007) [PubMed: 17260156] [Abstract] Cited for: IDENTIFICATION OF FOXG1 AS A SINGLE-COPY GENE.
[8]	"A missense mutation within the fork-head domain of the forkhead box G1 Gene (FOXG1) affects its nuclear localization." Guen T.L., Fichou Y., Nectoux J., Bahi-Buisson N., Rivier F., Boddaert N., Diebold B., Heron D., Chelly J., Bienvenu T. Hum. Mutat. 0:0-0(2010) [PubMed: 21140463] [Abstract] Cited for: SUBCELLULAR LOCATION, VARIANT RTTCV CYS-244, VARIANT LEU-109, CHARACTERIZATION OF VARIANT RTTCV CYS-244.
[9]	"Novel FOXG1 mutations associated with the congenital variant of Rett syndrome." Mencarelli M.A., Spanhol-Rosseto A., Artuso R., Rondinella D., De Filippis R., Bahi-Buisson N., Nectoux J., Rubinsztajn R., Bienvenu T., Moncla A., Chabrol B., Villard L., Krumina Z., Armstrong J., Roche A., Pineda M., Gak E., Mari F., Ariani F., Renieri A. J. Med. Genet. 47:49-53(2010) [PubMed: 19578037] [Abstract] Cited for: VARIANT RTTCV LEU-215.
+	Additional computationally mapped references.

Web resources

Wikipedia

FOXG1 entry

Cross-references

Sequence databases
EMBL GenBank DDBJ	X74142 mRNA. Translation: CAA52239.1. X74143 mRNA. Translation: CAA52240.1. X74144 mRNA. Translation: CAA52241.1. X78202 Genomic DNA. Translation: CAA55038.1. AL049777 Genomic DNA. No translation available. CH471078 Genomic DNA. Translation: EAW65978.1. BC050072 mRNA. Translation: AAH50072.1.
IPI	IPI00024386.
PIR	B54743. I37451.
RefSeq	NP_005240.3. NM_005249.3.
UniGene	Hs.695962. Hs.708841.
3D structure databases
ProteinModelPortal	P55316.
SMR	P55316. Positions 181-269.
ModBase	Search...
Protein-protein interaction databases
IntAct	P55316. 2 interactions.
MINT	MINT-1407364.
STRING	P55316.
PTM databases
PhosphoSite	P55316.
Polymorphism databases
DMDM	152031604.
Proteomic databases
PRIDE	P55316.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000313071; ENSP00000339004; ENSG00000176165. ENST00000382535; ENSP00000371975; ENSG00000176165.
GeneID	2290.
KEGG	hsa:2290.
UCSC	uc001wqe.1. human.
Organism-specific databases
CTD	2290.
GeneCards	GC14P029235.
HGNC	HGNC:3811. FOXG1.
MIM	164874. gene. 613454. phenotype.
neXtProt	NX_P55316.
Orphanet	261144. 14q12 microdeletion syndrome. 3095. Atypical Rett syndrome.
PharmGKB	PA162388806. PA28228.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG17308.
GeneTree	ENSGT00600000084188.
HOGENOM	HBG717442.
HOVERGEN	HBG051645.
InParanoid	P55316.
OMA	LPYATHH.
OrthoDB	EOG4M0F2T.
PhylomeDB	P55316.
Enzyme and pathway databases
Pathway_Interaction_DB	smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling.
Gene expression databases
ArrayExpress	P55316.
Bgee	P55316.
CleanEx	HS_FOXG1.
Genevestigator	P55316.
GermOnline	ENSG00000176165. Homo sapiens.
Family and domain databases
InterPro	IPR001766. TF_fork_head. IPR018122. TF_fork_head_CS. IPR011991. WHTH_trsnscrt_rep_DNA-bd. [Graphical view]
Gene3D	G3DSA:1.10.10.10. Wing_hlx_DNA_bd. 1 hit.
KO	K09385.
Pfam	PF00250. Fork_head. 1 hit. [Graphical view]
PRINTS	PR00053. FORKHEAD.
SMART	SM00339. FH. 1 hit. [Graphical view]
PROSITE	PS00657. FORK_HEAD_1. 1 hit. PS00658. FORK_HEAD_2. 1 hit. PS50039. FORK_HEAD_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	9307.
SOURCE	Search...

Entry information

Entry name

FOXG1_HUMAN

Accession

Primary (citable) accession number: P55316
Secondary accession number(s): A6NFY2 , P55315, Q14488, Q86XT7

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	July 10, 2007
Last modified:	January 25, 2012
This is version 98 of the entry and version 2 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.