P58462 (FOXP1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Forkhead box protein P1

Alternative name(s):
Forkhead-related transcription factor 1

Gene names

Name:

Foxp1

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 › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	705 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcriptional repressor that plays an important role in the specification and differentiation of lung epithelium. Can act with CTBP1 to synergistically repress transcription but CTPBP1 is not essential. Essential transcriptional regulator of B-cell development. Ref.5 Ref.6
Subunit structure	Forms homodimers and heterodimers with FOXP2 and FOXP4. Dimerization is required for DNA-binding. Interacts with CTBP1. Ref.5
Subcellular location	Nucleus Probable.
Tissue specificity	Highest expression in the lung, brain, and spleen. Lower expression in heart, skeletal muscle, kidney, small intestine (isoform 3 not present) and liver.
Developmental stage	Expressed in developing lung, neural, intestinal and cardiovascular tissues. Expressed in both the airway epithelium of the forming lung as well as in the surrounding mesenchyme. By 16.5 dpc, expressed throughout the conducting airway epithelium, with highest expression in the distal alveolar regions. Also expressed in the endotheial cells of the pulmonary vasculature. During intestinal development, expressed in the mucosal layer but absent from the epithelium at 12.5 dpc. By 16.5 dpc, expressed in both the inner circular and outer longitudinal muscular layers of the intestine as well as in the epithelium of the intestine and developing stomach. Ref.4
Domain	The leucine-zipper is required for dimerization and transcriptional repression. Ref.5
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 initiation 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	cardiac muscle cell differentiation Inferred from mutant phenotype PubMed 15342473. Source: MGI immunoglobulin V(D)J recombination Inferred from mutant phenotype Ref.6. Source: MGI in utero embryonic development Inferred from mutant phenotype PubMed 20457810. Source: MGI lung secretory cell differentiation Inferred from genetic interaction PubMed 22675208. Source: MGI motor neuron axon guidance Inferred from mutant phenotype PubMed 20711475. Source: UniProtKB negative regulation of lung goblet cell differentiation Inferred from genetic interaction PubMed 22675208. Source: MGI negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.5PubMed 17428829PubMed 20713518. Source: MGI pattern specification process Inferred from Biological aspect of Ancestor. Source: RefGenome positive regulation of cardiac muscle cell differentiation Inferred from mutant phenotype PubMed 20713518. Source: MGI positive regulation of epithelial cell proliferation Inferred from genetic interaction PubMed 17428829. Source: MGI positive regulation of immunoglobulin production Inferred from mutant phenotype Ref.6. Source: MGI positive regulation of mesenchymal cell proliferation Inferred from genetic interaction PubMed 17428829. Source: MGI positive regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype PubMed 20713518. Source: MGI pre-B cell differentiation Inferred from mutant phenotype Ref.6. Source: MGI regulation of cardiac muscle cell proliferation Inferred from mutant phenotype PubMed 20713518. Source: MGI sarcomere organization Inferred from genetic interaction PubMed 20457810. 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 ventral spinal cord development Inferred from expression pattern PubMed 20711475. Source: UniProtKB
Cellular_component	cytoplasm Inferred from Biological aspect of Ancestor. Source: RefGenome nucleus Inferred from direct assay Ref.6PubMed 19797899PubMed 23610558. Source: MGI
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 direct assay Ref.6. Source: MGI chromatin binding Inferred from direct assay PubMed 18347093. Source: MGI metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing and alternative initiation. [Align] [Select]

Isoform 1 (identifier: P58462-1)

Also known as: A;

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: P58462-2)

Also known as: B;

The sequence of this isoform differs from the canonical sequence as follows:
     539-602: Missing.

Isoform 3 (identifier: P58462-3)

Also known as: C;

The sequence of this isoform differs from the canonical sequence as follows:
     1-250: Missing.

Note: Produced by alternative initiation at Met-251 of isoform 1.

Isoform 4 (identifier: P58462-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-130: Missing.

Note: Produced by alternative splicing. No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 705	705	Forkhead box protein P1		PRO_0000009336
Regions
	Zinc finger	334 – 359	26	C2H2-type
	DNA binding	493 – 583	91	Fork-head
	Region	376 – 397	22	Leucine-zipper
	Region	410 – 414	5	CTBP1-binding
	Compositional bias	55 – 258	204	Gln-rich
Natural variations
	Alternative sequence	1 – 250	250	Missing in isoform 3.		VSP_018732
	Alternative sequence	1 – 130	130	Missing in isoform 4.		VSP_026670
	Alternative sequence	539 – 602	64	Missing in isoform 2.		VSP_001557
Experimental info
	Mutagenesis	388	1	Missing: Loss of dimerization. Almost complete loss of DNA-binding. Reduced transcriptional repression activity. Ref.5
	Mutagenesis	410 – 414	5	PLNLV → AANAA: No significant effect on transcriptional repression activity. Ref.5
	Sequence conflict	61 – 92	32	Missing in AAH64764. Ref.3
	Sequence conflict	199	1	E → EQ in BAC28249. Ref.2
	Sequence conflict	199	1	E → EQ in BAC36586. Ref.2
	Sequence conflict	281	1	D → H in BAC28249. Ref.2
	Sequence conflict	353	1	K → T in BAC28249. Ref.2
	Sequence conflict	597	1	L → F in BAC28249. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (A) [UniParc]. Last modified December 5, 2001. Version 1. Checksum: 92962B82917CC79D	FASTA	705	78,833
	10 20 30 40 50 60 MMQESGSETK SNGSAIQNGS SGGNHLLECG ALRDTRSNGE APAVDLGAAD LAHVQQQQQQ 70 80 90 100 110 120 ALQVARQLLL QQQQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ QQQQQQQVSG LKSPKRNDKQ 130 140 150 160 170 180 PALQVPVSVA MMTPQVITPQ QMQQILQQQV LSPQQLQVLL QQQQALMLQQ QLQEFYKKQQ 190 200 210 220 230 240 EQLQLQLLQQ QHAGKQPKEQ QVATQQLAFQ QQLLQMQQLQ QQHLLSLQRQ GLLTIQPGQP 250 260 270 280 290 300 ALPLQPLAQG MIPTELQQLW KEVTSAHTAE ETTSSNHSSL DLTSTCVSSS APSKSSLIMN 310 320 330 340 350 360 PHASTNGQLS VHTPKRESLS HEEHPHSHPL YGHGVCKWPG CEAVCDDFPA FLKHLNSEHA 370 380 390 400 410 420 LDDRSTAQCR VQMQVVQQLE LQLAKDKERL QAMMTHLHVK STEPKAAPQP LNLVSSVTLS 430 440 450 460 470 480 KSASEASPQS LPHTPTTPTA PLTPVTQGPS VITTTSMHTV GPIRRRYSDK YNVPISSADI 490 500 510 520 530 540 AQNQEFYKNA EVRPPFTYAS LIRQAILESP EKQLTLNEIY NWFTRMFAYF RRNAATWKNA 550 560 570 580 590 600 VRHNLSLHKC FVRVENVKGA VWTVDEVEFQ KRRPQKISGN PSLIKNMQSS HAYCTPLNAA 610 620 630 640 650 660 LQASMAENSI PLYTTASMGN PTLGSLASAI REELNGAMEH TNSNESDSSP GRSPMQAVHP 670 680 690 700 IHVKEEPLDP EEAEGPLSLV TTANHSPDFD HDRDYEDEPV NEDME
	Isoform 2 (B) [UniParc]. Checksum: 8B898F9AC3BB917C	FASTA	641	71,591
	10 20 30 40 50 60 MMQESGSETK SNGSAIQNGS SGGNHLLECG ALRDTRSNGE APAVDLGAAD LAHVQQQQQQ 70 80 90 100 110 120 ALQVARQLLL QQQQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ QQQQQQQVSG LKSPKRNDKQ 130 140 150 160 170 180 PALQVPVSVA MMTPQVITPQ QMQQILQQQV LSPQQLQVLL QQQQALMLQQ QLQEFYKKQQ 190 200 210 220 230 240 EQLQLQLLQQ QHAGKQPKEQ QVATQQLAFQ QQLLQMQQLQ QQHLLSLQRQ GLLTIQPGQP 250 260 270 280 290 300 ALPLQPLAQG MIPTELQQLW KEVTSAHTAE ETTSSNHSSL DLTSTCVSSS APSKSSLIMN 310 320 330 340 350 360 PHASTNGQLS VHTPKRESLS HEEHPHSHPL YGHGVCKWPG CEAVCDDFPA FLKHLNSEHA 370 380 390 400 410 420 LDDRSTAQCR VQMQVVQQLE LQLAKDKERL QAMMTHLHVK STEPKAAPQP LNLVSSVTLS 430 440 450 460 470 480 KSASEASPQS LPHTPTTPTA PLTPVTQGPS VITTTSMHTV GPIRRRYSDK YNVPISSADI 490 500 510 520 530 540 AQNQEFYKNA EVRPPFTYAS LIRQAILESP EKQLTLNEIY NWFTRMFAYF RRNAATWKAS 550 560 570 580 590 600 MAENSIPLYT TASMGNPTLG SLASAIREEL NGAMEHTNSN ESDSSPGRSP MQAVHPIHVK 610 620 630 640 EEPLDPEEAE GPLSLVTTAN HSPDFDHDRD YEDEPVNEDM E
	Isoform 3 (C) [UniParc]. Checksum: EA5EC089D4DB8168	FASTA	455	50,493
	10 20 30 40 50 60 MIPTELQQLW KEVTSAHTAE ETTSSNHSSL DLTSTCVSSS APSKSSLIMN PHASTNGQLS 70 80 90 100 110 120 VHTPKRESLS HEEHPHSHPL YGHGVCKWPG CEAVCDDFPA FLKHLNSEHA LDDRSTAQCR 130 140 150 160 170 180 VQMQVVQQLE LQLAKDKERL QAMMTHLHVK STEPKAAPQP LNLVSSVTLS KSASEASPQS 190 200 210 220 230 240 LPHTPTTPTA PLTPVTQGPS VITTTSMHTV GPIRRRYSDK YNVPISSADI AQNQEFYKNA 250 260 270 280 290 300 EVRPPFTYAS LIRQAILESP EKQLTLNEIY NWFTRMFAYF RRNAATWKNA VRHNLSLHKC 310 320 330 340 350 360 FVRVENVKGA VWTVDEVEFQ KRRPQKISGN PSLIKNMQSS HAYCTPLNAA LQASMAENSI 370 380 390 400 410 420 PLYTTASMGN PTLGSLASAI REELNGAMEH TNSNESDSSP GRSPMQAVHP IHVKEEPLDP 430 440 450 EEAEGPLSLV TTANHSPDFD HDRDYEDEPV NEDME
	Isoform 4 [UniParc]. Checksum: 381CAA8E3720A7F0	FASTA	575	64,422
	10 20 30 40 50 60 MMTPQVITPQ QMQQILQQQV LSPQQLQVLL QQQQALMLQQ QLQEFYKKQQ EQLQLQLLQQ 70 80 90 100 110 120 QHAGKQPKEQ QVATQQLAFQ QQLLQMQQLQ QQHLLSLQRQ GLLTIQPGQP ALPLQPLAQG 130 140 150 160 170 180 MIPTELQQLW KEVTSAHTAE ETTSSNHSSL DLTSTCVSSS APSKSSLIMN PHASTNGQLS 190 200 210 220 230 240 VHTPKRESLS HEEHPHSHPL YGHGVCKWPG CEAVCDDFPA FLKHLNSEHA LDDRSTAQCR 250 260 270 280 290 300 VQMQVVQQLE LQLAKDKERL QAMMTHLHVK STEPKAAPQP LNLVSSVTLS KSASEASPQS 310 320 330 340 350 360 LPHTPTTPTA PLTPVTQGPS VITTTSMHTV GPIRRRYSDK YNVPISSADI AQNQEFYKNA 370 380 390 400 410 420 EVRPPFTYAS LIRQAILESP EKQLTLNEIY NWFTRMFAYF RRNAATWKNA VRHNLSLHKC 430 440 450 460 470 480 FVRVENVKGA VWTVDEVEFQ KRRPQKISGN PSLIKNMQSS HAYCTPLNAA LQASMAENSI 490 500 510 520 530 540 PLYTTASMGN PTLGSLASAI REELNGAMEH TNSNESDSSP GRSPMQAVHP IHVKEEPLDP 550 560 570 EEAEGPLSLV TTANHSPDFD HDRDYEDEPV NEDME

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] (ISOFORMS 1; 2 AND 3). Strain: C57BL/6. Tissue: Lung.
[2]	"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 4). Strain: C57BL/6J. Tissue: Lung and Testis.
[3]	"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] (ISOFORM 1). Strain: C57BL/6J. Tissue: Embryo.
[4]	"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.
[5]	"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-388 AND 410-PRO--VAL-414.
[6]	"Foxp1 is an essential transcriptional regulator of B cell development." Hu H., Wang B., Borde M., Nardone J., Maika S., Allred L., Tucker P.W., Rao A. Nat. Immunol. 7:819-826(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF339103 mRNA. Translation: AAK69648.1. AF339104 mRNA. Translation: AAK69649.1. AF339105 mRNA. Translation: AAK69650.1. AK033368 mRNA. Translation: BAC28249.1. AK077062 mRNA. Translation: BAC36586.1. BC064764 mRNA. Translation: AAH64764.1.
RefSeq	NP_001184250.1. NM_001197321.1. NP_001184251.1. NM_001197322.1. NP_444432.1. NM_053202.2.
UniGene	Mm.234965. Mm.392884. Mm.485266.
3D structure databases
ProteinModelPortal	P58462.
SMR	P58462. Positions 339-397, 490-576.
ModBase	Search...
MobiDB	Search...
Protein-protein interaction databases
BioGrid	224357. 9 interactions.
PTM databases
PhosphoSite	P58462.
Proteomic databases
PaxDb	P58462.
PRIDE	P58462.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000074346; ENSMUSP00000073953; ENSMUSG00000030067. ENSMUST00000113322; ENSMUSP00000108948; ENSMUSG00000030067. ENSMUST00000113326; ENSMUSP00000108952; ENSMUSG00000030067. ENSMUST00000113329; ENSMUSP00000108955; ENSMUSG00000030067. ENSMUST00000177437; ENSMUSP00000135809; ENSMUSG00000030067.
GeneID	108655.
KEGG	mmu:108655.
UCSC	uc009dbi.2. mouse.
Organism-specific databases
CTD	27086.
MGI	MGI:1914004. Foxp1.
Phylogenomic databases
eggNOG	COG5025.
GeneTree	ENSGT00740000114886.
HOGENOM	HOG000092089.
HOVERGEN	HBG051657.
KO	K09409.
OrthoDB	EOG7M6D7G.
Gene expression databases
ArrayExpress	P58462.
Bgee	P58462.
CleanEx	MM_FOXP1.
Genevestigator	P58462.
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	PS00658. FORK_HEAD_2. 1 hit. PS50039. FORK_HEAD_3. 1 hit. PS00028. ZINC_FINGER_C2H2_1. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	FOXP1. mouse.
NextBio	361173.
PRO	P58462.
SOURCE	Search...

Entry information

Entry name

FOXP1_MOUSE

Accession

Primary (citable) accession number: P58462
Secondary accession number(s): Q6P221, Q8C5V2, Q8CCD9

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 5, 2001
Last sequence update:	December 5, 2001
Last modified:	February 19, 2014
This is version 115 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program