P58463 (FOXP2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Forkhead box protein P2

Gene names

Name:

Foxp2

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	714 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcriptional repressor that may play a role in the specification and differentiation of lung epithelium. May also play a role in developing neural, gastrointestinal and cardiovascular tissues. Can act with CTBP1 to synergistically repress transcription but CTPBP1 is not essential. Ref.6
Subunit structure	Forms homodimers and heterodimers with FOXP1 and FOXP4. Dimerization is required for DNA-binding. Interacts with CTBP1. Ref.6
Subcellular location	Nucleus Probable.
Tissue specificity	Highest expression in lung. Lower expression in spleen, skeletal muscle, brain, kidney and small intestine.
Developmental stage	Expressed in developing lung, neural, intestinal and cardiovascular tissues. Expressed at a high level in the distal airway epithelium and at a low level in the proximal airway epithelium at 12.5 dpc, and restricted to the distal airway epithelium by 14.5 dpc. In the spinal cord, at 12.5 dpc, expressed in a subset of interneurons dorsal to motor neurons. At 16.5 dpc, expression in the brain is observed in the inner intermediate zone of the neopallial cortex and in the developing cerebral hemispheres. In the gastrointestinal system, at 12.5 expressed in the outer mesodermal layer and in the intestinal epithelium. By 16.5 dpc, expression is restricted to the outer longitudinal muscle layer of the intestine and stomach. In the cardiovascular system, at 14.5 dpc, expressed in the outflow tract region of the developing heart. By 16.5 dpc, observed in the outflow tract and atrium, but not in the ventricles. Ref.1 Ref.5
Domain	The leucine-zipper is required for dimerization and transcriptional repression. Ref.6
Sequence similarities	Contains 1 C2H2-type zinc finger. Contains 1 fork-head DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Repressor
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	camera-type eye development Inferred from mutant phenotype PubMed 17619227. Source: MGI caudate nucleus development Inferred from sequence or structural similarity. Source: UniProtKB cerebellum development Inferred from mutant phenotype PubMed 15983371PubMed 17619227. Source: MGI cerebral cortex development Inferred from Biological aspect of Ancestor. Source: RefGenome embryo development Inferred from genetic interaction PubMed 17428829. Source: MGI growth Inferred from mutant phenotype PubMed 17619227. Source: MGI lung alveolus development Inferred from mutant phenotype PubMed 17428829. Source: MGI negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.6PubMed 17428829. Source: MGI pattern specification process Inferred from Biological aspect of Ancestor. Source: RefGenome positive regulation of epithelial cell proliferation involved in lung morphogenesis Inferred from genetic interaction PubMed 17428829. Source: MGI positive regulation of mesenchymal cell proliferation Inferred from genetic interaction PubMed 17428829. Source: MGI post-embryonic development Inferred from mutant phenotype PubMed 17619227. Source: MGI putamen development Inferred from sequence or structural similarity. Source: UniProtKB regulation of sequence-specific DNA binding transcription factor activity Inferred from Biological aspect of Ancestor. Source: RefGenome righting reflex Inferred from mutant phenotype PubMed 17619227. Source: MGI skeletal muscle tissue development Inferred from genetic interaction PubMed 17428829. Source: MGI smooth muscle tissue development Inferred from genetic interaction PubMed 17428829. Source: MGI vocal learning Inferred from mutant phenotype PubMed 15983371. Source: MGI
Cellular_component	cytoplasm Inferred from Biological aspect of Ancestor. Source: RefGenome transcription factor complex Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	DNA binding, bending Inferred from Biological aspect of Ancestor. Source: RefGenome RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Inferred from Biological aspect of Ancestor. Source: RefGenome chromatin binding Inferred from Biological aspect of Ancestor. Source: RefGenome double-stranded DNA binding Inferred from Biological aspect of Ancestor. Source: RefGenome protein homodimerization activity Inferred from sequence or structural similarity. Source: UniProtKB sequence-specific DNA binding Inferred from electronic annotation. Source: Compara transcription factor binding Inferred from Biological aspect of Ancestor. Source: RefGenome zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: P58463-1)

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: P58463-2)

The sequence of this isoform differs from the canonical sequence as follows:
     134-154: Missing.

Note: May be due to a competing acceptor splice site. No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 714	714	Forkhead box protein P2		PRO_0000091882
Regions
	Zinc finger	345 – 370	26	C2H2-type
	DNA binding	503 – 593	91	Fork-head
	Region	387 – 408	22	Leucine-zipper
	Region	421 – 425	5	CTBP1-binding
	Compositional bias	53 – 267	215	Gln-rich
Natural variations
	Alternative sequence	134 – 154	21	Missing in isoform 2.		VSP_011540
Experimental info
	Mutagenesis	399	1	Missing: Loss of dimerization. Almost complete loss of DNA-binding. Reduced transcriptional repression activity. Ref.6
	Mutagenesis	407 – 408	2	HL → AA: Severely reduced transcriptional repression activity. Ref.6
	Mutagenesis	408	1	L → A: Severely reduced transcriptional repression activity. Ref.6
	Mutagenesis	421 – 425	5	PLNLV → AANAA: No significant effect on transcriptional repression activity. Ref.6
	Sequence conflict	6	1	A → V in AAK69651. Ref.1
	Sequence conflict	543	1	N → S in AAK69651. Ref.1
	Sequence conflict	663	1	P → R in BAC38477. Ref.3
	Sequence conflict	675	1	E → D in BAC38477. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified August 31, 2004. Version 2. Checksum: EB02D66B5AA452D0	FASTA	714	79,819
	10 20 30 40 50 60 MMQESATETI SNSSMNQNGM STLSSQLDAG SRDGRSSGDT SSEVSTVELL HLQQQQALQA 70 80 90 100 110 120 ARQLLLQQQT SGLKSPKSSE KQRPLQVPVS VAMMTPQVIT PQQMQQILQQ QVLSPQQLQA 130 140 150 160 170 180 LLQQQQAVML QQQQLQEFYK KQQEQLHLQL LQQQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ 190 200 210 220 230 240 QQQQQQQQQQ QHPGKQAKEQ QQQQQQQQLA AQQLVFQQQL LQMQQLQQQQ HLLSLQRQGL 250 260 270 280 290 300 ISIPPGQAAL PVQSLPQAGL SPAEIQQLWK EVTGVHSMED NGIKHGGLDL TTNNSSSTTS 310 320 330 340 350 360 STTSKASPPI THHSIVNGQS SVLNARRDSS SHEETGASHT LYGHGVCKWP GCESICEDFG 370 380 390 400 410 420 QFLKHLNNEH ALDDRSTAQC RVQMQVVQQL EIQLSKERER LQAMMTHLHM RPSEPKPSPK 430 440 450 460 470 480 PLNLVSSVTM SKNMLETSPQ SLPQTPTTPT APVTPITQGP SVITPASVPN VGAIRRRHSD 490 500 510 520 530 540 KYNIPMSSEI APNYEFYKNA DVRPPFTYAT LIRQAIMESS DRQLTLNEIY SWFTRTFAYF 550 560 570 580 590 600 RRNAATWKNA VRHNLSLHKC FVRVENVKGA VWTVDEVEYQ KRRSQKITGS PTLVKNIPTS 610 620 630 640 650 660 LGYGAALNAS LQAALAESSL PLLSNPGLIN NASSGLLQAV HEDLNGSLDH IDSNGNSSPG 670 680 690 700 710 CSPQPHIHSI HVKEEPVIAE DEDCPMSLVT TANHSPELED DREIEEEPLS EDLE
	Isoform 2 [UniParc]. Checksum: 5A9582A3C4DB2E09	FASTA	693	77,138
	10 20 30 40 50 60 MMQESATETI SNSSMNQNGM STLSSQLDAG SRDGRSSGDT SSEVSTVELL HLQQQQALQA 70 80 90 100 110 120 ARQLLLQQQT SGLKSPKSSE KQRPLQVPVS VAMMTPQVIT PQQMQQILQQ QVLSPQQLQA 130 140 150 160 170 180 LLQQQQAVML QQQQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ HPGKQAKEQQ 190 200 210 220 230 240 QQQQQQQLAA QQLVFQQQLL QMQQLQQQQH LLSLQRQGLI SIPPGQAALP VQSLPQAGLS 250 260 270 280 290 300 PAEIQQLWKE VTGVHSMEDN GIKHGGLDLT TNNSSSTTSS TTSKASPPIT HHSIVNGQSS 310 320 330 340 350 360 VLNARRDSSS HEETGASHTL YGHGVCKWPG CESICEDFGQ FLKHLNNEHA LDDRSTAQCR 370 380 390 400 410 420 VQMQVVQQLE IQLSKERERL QAMMTHLHMR PSEPKPSPKP LNLVSSVTMS KNMLETSPQS 430 440 450 460 470 480 LPQTPTTPTA PVTPITQGPS VITPASVPNV GAIRRRHSDK YNIPMSSEIA PNYEFYKNAD 490 500 510 520 530 540 VRPPFTYATL IRQAIMESSD RQLTLNEIYS WFTRTFAYFR RNAATWKNAV RHNLSLHKCF 550 560 570 580 590 600 VRVENVKGAV WTVDEVEYQK RRSQKITGSP TLVKNIPTSL GYGAALNASL QAALAESSLP 610 620 630 640 650 660 LLSNPGLINN ASSGLLQAVH EDLNGSLDHI DSNGNSSPGC SPQPHIHSIH VKEEPVIAED 670 680 690 EDCPMSLVTT ANHSPELEDD REIEEEPLSE DLE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of a new subfamily of winged-helix/forkhead (Fox) genes that are expressed in the lung and act as transcriptional repressors." Shu W., Yang H., Zhang L., Lu M.M., Morrisey E.E. J. Biol. Chem. 276:27488-27497(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), DEVELOPMENTAL STAGE. Strain: C57BL/6. Tissue: Lung.
[2]	"Molecular evolution of FOXP2, a gene involved in speech and language." Enard W., Przeworski M., Fisher S.E., Lai C.S.L., Wiebe V., Kitano T., Monaco A.P., Paeaebo S. Nature 418:869-872(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Strain: BALB/c.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: C57BL/6J. Tissue: Cerebellum.
[4]	"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). Strain: C57BL/6. Tissue: Brain.
[5]	"Foxp4: a novel member of the Foxp subfamily of winged-helix genes co-expressed with Foxp1 and Foxp2 in pulmonary and gut tissues." Lu M.M., Li S., Yang H., Morrisey E.E. Mech. Dev. 119:S197-S202(2002) [PubMed] [Europe PMC] [Abstract] Cited for: DEVELOPMENTAL STAGE.
[6]	"Transcriptional and DNA binding activity of the Foxp1/2/4 family is modulated by heterotypic and homotypic protein interactions." Li S., Weidenfeld J., Morrisey E.E. Mol. Cell. Biol. 24:809-822(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DIMERIZATION, INTERACTION WITH CTBP1, DOMAIN, MUTAGENESIS OF GLU-399; 407-HIS-LEU-408; LEU-408 AND 421-PRO--VAL-425.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF339106 mRNA. Translation: AAK69651.1. AY079003 mRNA. Translation: AAL85482.1. AK082361 mRNA. Translation: BAC38477.1. BC058960 mRNA. Translation: AAH58960.1. BC062926 mRNA. Translation: AAH62926.1.
IPI	IPI00276962. IPI00463757.
RefSeq	NP_444472.2. NM_053242.4. NP_997600.1. NM_212435.1.
UniGene	Mm.332919.
3D structure databases
ProteinModelPortal	P58463.
SMR	P58463. Positions 350-408, 502-583.
ModBase	Search...
PTM databases
PhosphoSite	P58463.
Proteomic databases
PRIDE	P58463.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000031545; ENSMUSP00000031545; ENSMUSG00000029563. ENSMUST00000115472; ENSMUSP00000111132; ENSMUSG00000029563. ENSMUST00000115477; ENSMUSP00000111137; ENSMUSG00000029563.
GeneID	114142.
KEGG	mmu:114142.
UCSC	uc009ayy.1. mouse. uc012eie.1. mouse.
Organism-specific databases
CTD	93986.
MGI	MGI:2148705. Foxp2.
Phylogenomic databases
eggNOG	COG5025.
GeneTree	ENSGT00690000101938.
HOGENOM	HOG000092089.
HOVERGEN	HBG051657.
KO	K09409.
OrthoDB	EOG402WS7.
Gene expression databases
ArrayExpress	P58463.
Bgee	P58463.
CleanEx	MM_FOXP2.
Genevestigator	P58463.
GermOnline	ENSMUSG00000029563. Mus musculus.
Family and domain databases
Gene3D	1.10.10.10. 1 hit.
InterPro	IPR001766. TF_fork_head. IPR018122. TF_fork_head_CS. IPR011991. WHTH_DNA-bd_dom. IPR015880. Znf_C2H2-like. [Graphical view]
Pfam	PF00250. Fork_head. 1 hit. [Graphical view]
PRINTS	PR00053. FORKHEAD.
SMART	SM00339. FH. 1 hit. SM00355. ZnF_C2H2. 1 hit. [Graphical view]
PROSITE	PS00657. FORK_HEAD_1. False negative. PS00658. FORK_HEAD_2. 1 hit. PS50039. FORK_HEAD_3. 1 hit. PS00028. ZINC_FINGER_C2H2_1. 1 hit. PS50157. ZINC_FINGER_C2H2_2. False negative. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	FOXP2. mouse.
NextBio	368137.
SOURCE	Search...

Entry information

Entry name

FOXP2_MOUSE

Accession

Primary (citable) accession number: P58463
Secondary accession number(s): Q6PD37, Q8C4F0, Q8R441

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 5, 2001
Last sequence update:	August 31, 2004
Last modified:	May 1, 2013
This is version 108 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program