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Protein

Forkhead box protein P1

Gene

Foxp1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcriptional repressor. Can act with CTBP1 to synergistically repress transcription but CTPBP1 is not essential (PubMed:11358962, PubMed:14701752). Plays an important role in the specification and differentiation of lung epithelium. Acts cooperatively with FOXP4 to regulate lung secretory epithelial cell fate and regeneration by restricting the goblet cell lineage program; the function may involve regulation of AGR2 (PubMed:11358962, PubMed:22675208). Essential transcriptional regulator of B-cell development (PubMed:16819554). Involved in regulation of cardiac muscle cell proliferation (PubMed:20713518). Involved in the columnar organization of spinal motor neurons. Promotes the formation of the lateral motor neuron column (LMC) and the preganglionic motor column (PGC) and is required for respective appropriate motor axon projections. The segment-appropriate generation of spinal chord motor columns requires cooperation with other Hox proteins (PubMed:18667151, PubMed:18662545). Can regulate PITX3 promoter activity; may promote midbrain identity in embryonic stem cell-derived dopamine neurons by regulating PITX3 (PubMed:20175877). Negatively regulates the differentiation of T follicular helper cells T(FH)s (PubMed:24859450). Involved in maintainance of hair follicle stem cell quiescence; the function probably involves regulation of FGF18 (PubMed:23946441). Represses transcription of various pro-apoptotic genes and cooperates with NF-kappa B-signaling in promoting B-cell expansion by inhibition of caspase-dependent apoptosis. Binds to CSF1R promoter elements and is involved in regulation of monocyte differentiation and macrophage functions; repression of CSF1R in monocytes seems to involve NCOR2 as corepressor. Involved in endothelial cell proliferation, tube formation and migration indicative for a role in angiogenesis; the role in neovascularization seems to implicate suppression of SEMA5B. Can negatively regulate androgen receptor signaling (By similarity).By similarity3 Publications9 Publications
Isoform 5: Involved in transcriptional regulation in embryonic stem cells (ESCs). Stimulates expression of transcription factors that are required for pluripotency and decreases expression of differentiation-associated genes. Has distinct DNA-binding specifities as compared to the canonical form and preferentially binds DNA with the sequence 5'-CGATACAA-3' (or closely related sequences) (By similarity). Promotes ESC self-renewal and pluripotency (PubMed:21924763).By similarity1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri334 – 35926C2H2-typeAdd
BLAST
DNA bindingi493 – 58391Fork-headPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • chromatin binding Source: MGI
  • DNA binding Source: MGI
  • metal ion binding Source: UniProtKB-KW
  • protein heterodimerization activity Source: MGI
  • protein homodimerization activity Source: MGI
  • protein self-association Source: UniProtKB
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
  • transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: NTNU_SB
  • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding Source: MGI
  • transcription factor activity, sequence-specific DNA binding Source: MGI

GO - Biological processi

  • cardiac muscle cell differentiation Source: MGI
  • cardiovascular system development Source: MGI
  • chemokine (C-C motif) ligand 2 secretion Source: UniProtKB
  • endothelial cell activation Source: UniProtKB
  • heart development Source: MGI
  • immunoglobulin V(D)J recombination Source: MGI
  • interleukin-21 secretion Source: UniProtKB
  • in utero embryonic development Source: MGI
  • lung development Source: MGI
  • lung secretory cell differentiation Source: MGI
  • macrophage activation Source: UniProtKB
  • monocyte activation Source: UniProtKB
  • motor neuron axon guidance Source: UniProtKB
  • negative regulation of androgen receptor signaling pathway Source: UniProtKB
  • negative regulation of B cell apoptotic process Source: UniProtKB
  • negative regulation of lung goblet cell differentiation Source: MGI
  • negative regulation of transcription, DNA-templated Source: MGI
  • negative regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
  • osteoclast development Source: UniProtKB
  • osteoclast differentiation Source: UniProtKB
  • positive regulation of cardiac muscle cell differentiation Source: MGI
  • positive regulation of endothelial cell migration Source: UniProtKB
  • positive regulation of epithelial cell proliferation Source: MGI
  • positive regulation of immunoglobulin production Source: MGI
  • positive regulation of mesenchymal cell proliferation Source: MGI
  • positive regulation of smooth muscle cell proliferation Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • pre-B cell differentiation Source: MGI
  • regulation of cardiac muscle cell proliferation Source: MGI
  • regulation of defense response to bacterium Source: UniProtKB
  • regulation of lung goblet cell differentiation Source: MGI
  • regulation of macrophage colony-stimulating factor production Source: UniProtKB
  • regulation of monocyte differentiation Source: UniProtKB
  • regulation of tumor necrosis factor production Source: UniProtKB
  • response to lipopolysaccharide Source: UniProtKB
  • sarcomere organization Source: MGI
  • skeletal muscle tissue development Source: MGI
  • smooth muscle tissue development Source: MGI
  • T follicular helper cell differentiation Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
  • ventral spinal cord development Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Forkhead box protein P1
Alternative name(s):
Forkhead-related transcription factor 1
Gene namesi
Name:Foxp1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:1914004. Foxp1.

Subcellular locationi

  • Nucleus By similarity

  • Note: Not found in the nucleolus.By similarity

GO - Cellular componenti

  • nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi388 – 3881Missing : Loss of dimerization. Almost complete loss of DNA-binding. Reduced transcriptional repression activity. 1 Publication
Mutagenesisi410 – 4145PLNLV → AANAA: No significant effect on transcriptional repression activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 705705Forkhead box protein P1PRO_0000009336Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei113 – 1131PhosphoserineBy similarity
Modified residuei681 – 6811PhosphothreonineBy similarity
Modified residuei686 – 6861PhosphoserineBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP58462.
MaxQBiP58462.
PaxDbiP58462.
PeptideAtlasiP58462.
PRIDEiP58462.

PTM databases

iPTMnetiP58462.
PhosphoSiteiP58462.

Expressioni

Tissue specificityi

Isoform 5 is specifically expressed in embryonic stem cells (PubMed:21924763). Highest expression in the lung, brain, and spleen. Lower expression in heart, skeletal muscle, kidney, small intestine (isoform 3 not present) and liver.1 Publication

Developmental stagei

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 (PubMed:14516685). Expressed in E12.5 midbrain dopaminergic neurons (PubMed:20175877).2 Publications

Gene expression databases

BgeeiENSMUSG00000030067.
CleanExiMM_FOXP1.
ExpressionAtlasiP58462. baseline and differential.
GenevisibleiP58462. MM.

Interactioni

Subunit structurei

Forms homodimers and heterodimers with FOXP2 and FOXP4. Dimerization is required for DNA-binding. Self-associates (By similarity). Interacts with CTBP1 (PubMed:14701752). Interacts with NCOR2 and AR. Interacts with FOXP2 (By similarity).By similarity1 Publication

GO - Molecular functioni

  • protein heterodimerization activity Source: MGI
  • protein homodimerization activity Source: MGI
  • protein self-association Source: UniProtKB

Protein-protein interaction databases

BioGridi224357. 10 interactions.
STRINGi10090.ENSMUSP00000073953.

Structurei

3D structure databases

ProteinModelPortaliP58462.
SMRiP58462. Positions 339-397, 490-576.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni376 – 39722Leucine-zipperAdd
BLAST
Regioni410 – 4145CTBP1-binding

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi55 – 258204Gln-richAdd
BLAST

Domaini

The leucine-zipper is required for dimerization and transcriptional repression.1 Publication

Sequence similaritiesi

Contains 1 C2H2-type zinc finger.Curated
Contains 1 fork-head DNA-binding domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri334 – 35926C2H2-typeAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG4385. Eukaryota.
COG5025. LUCA.
GeneTreeiENSGT00800000124014.
HOGENOMiHOG000092089.
HOVERGENiHBG051657.
InParanoidiP58462.
KOiK09409.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR001766. Fork_head_dom.
IPR032354. FOXP-CC.
IPR030456. TF_fork_head_CS_2.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00250. Forkhead. 1 hit.
PF16159. FOXP-CC. 1 hit.
[Graphical view]
PRINTSiPR00053. FORKHEAD.
SMARTiSM00339. FH. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
PROSITEiPS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. 1 hit.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing and alternative initiation. AlignAdd to basket

Isoform 1 (identifier: P58462-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MMQESGSETK SNGSAIQNGS SGGNHLLECG ALRDTRSNGE APAVDLGAAD
60 70 80 90 100
LAHVQQQQQQ ALQVARQLLL QQQQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ
110 120 130 140 150
QQQQQQQVSG LKSPKRNDKQ PALQVPVSVA MMTPQVITPQ QMQQILQQQV
160 170 180 190 200
LSPQQLQVLL QQQQALMLQQ QLQEFYKKQQ EQLQLQLLQQ QHAGKQPKEQ
210 220 230 240 250
QVATQQLAFQ QQLLQMQQLQ QQHLLSLQRQ GLLTIQPGQP ALPLQPLAQG
260 270 280 290 300
MIPTELQQLW KEVTSAHTAE ETTSSNHSSL DLTSTCVSSS APSKSSLIMN
310 320 330 340 350
PHASTNGQLS VHTPKRESLS HEEHPHSHPL YGHGVCKWPG CEAVCDDFPA
360 370 380 390 400
FLKHLNSEHA LDDRSTAQCR VQMQVVQQLE LQLAKDKERL QAMMTHLHVK
410 420 430 440 450
STEPKAAPQP LNLVSSVTLS KSASEASPQS LPHTPTTPTA PLTPVTQGPS
460 470 480 490 500
VITTTSMHTV GPIRRRYSDK YNVPISSADI AQNQEFYKNA EVRPPFTYAS
510 520 530 540 550
LIRQAILESP EKQLTLNEIY NWFTRMFAYF RRNAATWKNA VRHNLSLHKC
560 570 580 590 600
FVRVENVKGA VWTVDEVEFQ KRRPQKISGN PSLIKNMQSS HAYCTPLNAA
610 620 630 640 650
LQASMAENSI PLYTTASMGN PTLGSLASAI REELNGAMEH TNSNESDSSP
660 670 680 690 700
GRSPMQAVHP IHVKEEPLDP EEAEGPLSLV TTANHSPDFD HDRDYEDEPV

NEDME
Length:705
Mass (Da):78,833
Last modified:December 5, 2001 - v1
Checksum:i92962B82917CC79D
GO
Isoform 2 (identifier: P58462-2) [UniParc]FASTAAdd to basket
Also known as: B

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

Show »
Length:641
Mass (Da):71,591
Checksum:i8B898F9AC3BB917C
GO
Isoform 3 (identifier: P58462-3) [UniParc]FASTAAdd to basket
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.
Show »
Length:455
Mass (Da):50,493
Checksum:iEA5EC089D4DB8168
GO
Isoform 4 (identifier: P58462-4) [UniParc]FASTAAdd to basket

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

Note: Produced by alternative splicing. No experimental confirmation available.
Show »
Length:575
Mass (Da):64,422
Checksum:i381CAA8E3720A7F0
GO
Isoform 5 (identifier: P58462-5) [UniParc]FASTAAdd to basket
Also known as: FOXP1-ES

The sequence of this isoform differs from the canonical sequence as follows:
     540-579: AVRHNLSLHK...QKRRPQKISG → GAIRTLSLHK...DENSDELGAH

Show »
Length:721
Mass (Da):80,762
Checksum:i17D1A90C996E9227
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti61 – 9232Missing in AAH64764 (PubMed:15489334).CuratedAdd
BLAST
Sequence conflicti199 – 1991E → EQ in BAC28249 (PubMed:16141072).Curated
Sequence conflicti199 – 1991E → EQ in BAC36586 (PubMed:16141072).Curated
Sequence conflicti281 – 2811D → H in BAC28249 (PubMed:16141072).Curated
Sequence conflicti353 – 3531K → T in BAC28249 (PubMed:16141072).Curated
Sequence conflicti597 – 5971L → F in BAC28249 (PubMed:16141072).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 250250Missing in isoform 3. 1 PublicationVSP_018732Add
BLAST
Alternative sequencei1 – 130130Missing in isoform 4. 1 PublicationVSP_026670Add
BLAST
Alternative sequencei539 – 60264Missing in isoform 2. 1 PublicationVSP_001557Add
BLAST
Alternative sequencei540 – 57940AVRHN…QKISG → GAIRTLSLHKCFIRVEDEFG SFWTVDDEEFLRGRHIQRGR PRKYCPDENSDELGAH in isoform 5. 1 PublicationVSP_057342Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS39578.1. [P58462-1]
RefSeqiNP_001184250.1. NM_001197321.1.
NP_001184251.1. NM_001197322.1.
NP_444432.1. NM_053202.2. [P58462-1]
XP_006505385.1. XM_006505322.1.
XP_006505386.1. XM_006505323.2.
XP_011239423.1. XM_011241121.1. [P58462-1]
XP_011239428.1. XM_011241126.1. [P58462-4]
UniGeneiMm.234965.
Mm.392884.
Mm.485266.
Mm.487716.

Genome annotation databases

EnsembliENSMUST00000074346; ENSMUSP00000073953; ENSMUSG00000030067. [P58462-1]
ENSMUST00000113322; ENSMUSP00000108948; ENSMUSG00000030067. [P58462-1]
ENSMUST00000113329; ENSMUSP00000108955; ENSMUSG00000030067. [P58462-2]
GeneIDi108655.
KEGGimmu:108655.
UCSCiuc009dbi.2. mouse. [P58462-1]
uc009dbl.2. mouse. [P58462-2]

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS39578.1. [P58462-1]
RefSeqiNP_001184250.1. NM_001197321.1.
NP_001184251.1. NM_001197322.1.
NP_444432.1. NM_053202.2. [P58462-1]
XP_006505385.1. XM_006505322.1.
XP_006505386.1. XM_006505323.2.
XP_011239423.1. XM_011241121.1. [P58462-1]
XP_011239428.1. XM_011241126.1. [P58462-4]
UniGeneiMm.234965.
Mm.392884.
Mm.485266.
Mm.487716.

3D structure databases

ProteinModelPortaliP58462.
SMRiP58462. Positions 339-397, 490-576.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi224357. 10 interactions.
STRINGi10090.ENSMUSP00000073953.

PTM databases

iPTMnetiP58462.
PhosphoSiteiP58462.

Proteomic databases

EPDiP58462.
MaxQBiP58462.
PaxDbiP58462.
PeptideAtlasiP58462.
PRIDEiP58462.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000074346; ENSMUSP00000073953; ENSMUSG00000030067. [P58462-1]
ENSMUST00000113322; ENSMUSP00000108948; ENSMUSG00000030067. [P58462-1]
ENSMUST00000113329; ENSMUSP00000108955; ENSMUSG00000030067. [P58462-2]
GeneIDi108655.
KEGGimmu:108655.
UCSCiuc009dbi.2. mouse. [P58462-1]
uc009dbl.2. mouse. [P58462-2]

Organism-specific databases

CTDi27086.
MGIiMGI:1914004. Foxp1.

Phylogenomic databases

eggNOGiKOG4385. Eukaryota.
COG5025. LUCA.
GeneTreeiENSGT00800000124014.
HOGENOMiHOG000092089.
HOVERGENiHBG051657.
InParanoidiP58462.
KOiK09409.

Miscellaneous databases

ChiTaRSiFoxp1. mouse.
PROiP58462.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000030067.
CleanExiMM_FOXP1.
ExpressionAtlasiP58462. baseline and differential.
GenevisibleiP58462. MM.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR001766. Fork_head_dom.
IPR032354. FOXP-CC.
IPR030456. TF_fork_head_CS_2.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00250. Forkhead. 1 hit.
PF16159. FOXP-CC. 1 hit.
[Graphical view]
PRINTSiPR00053. FORKHEAD.
SMARTiSM00339. FH. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
PROSITEiPS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFOXP1_MOUSE
AccessioniPrimary (citable) accession number: P58462
Secondary accession number(s): Q6P221, Q8C5V2, Q8CCD9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: December 5, 2001
Last modified: September 7, 2016
This is version 140 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.