FOXP1

Forkhead box protein P1 is a protein that in humans is encoded by the FOXP1 gene. FOXP1 is necessary for the proper development of the brain, heart, and lung in mammals. It is a member of the large FOX family of transcription factors.

FOXP1
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 2KIU
Identifiers
Aliases	FOXP1, 12CC4, HSPC215, MFH, QRF1, hFKH1B, forkhead box P1
External IDs	OMIM: 605515 HomoloGene: 136512 GeneCards: FOXP1
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3p13 Start 70,952,817 bp[1] End 71,583,993 bp[1]
Gene ontology Molecular function • metal ion binding • sequence-specific DNA binding • protein self-association • androgen receptor binding • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity • DNA binding • GO:0001948 protein binding • identical protein binding • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding • chromatin binding • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding • transcription factor binding • protein homodimerization activity • protein heterodimerization activity Cellular component • cell nucleus • nucleoplasm • cytoplasm Biological process • regulation of monocyte differentiation • negative regulation of androgen receptor signaling pathway • negative regulation of B cell apoptotic process • positive regulation of endothelial cell migration • transcription, DNA-templated • response to lipopolysaccharide • regulation of defense response to bacterium • regulation of interleukin-12 secretion • endothelial cell activation • regulation of interleukin-1 beta secretion • regulation of endothelial tube morphogenesis • macrophage activation • osteoclast development • positive regulation of smooth muscle cell proliferation • T follicular helper cell differentiation • interleukin-21 secretion • regulation of macrophage colony-stimulating factor production • regulation of tumor necrosis factor production • regulation of inflammatory response • osteoclast differentiation • monocyte activation • regulation of transcription, DNA-templated • chemokine (C-C motif) ligand 2 secretion • negative regulation of transcription, DNA-templated • regulation of transcription from RNA polymerase II promoter • somatic stem cell population maintenance • negative regulation of transcription from RNA polymerase II promoter • in utero embryonic development • positive regulation of mesenchymal cell proliferation • pre-B cell differentiation • positive regulation of immunoglobulin production • heart development • skeletal muscle tissue development • motor neuron axon guidance • ventral spinal cord development • striatum development • lung development • forebrain development • immunoglobulin V(D)J recombination • response to testosterone • sarcomere organization • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • smooth muscle tissue development • positive regulation of epithelial cell proliferation • cardiac muscle cell differentiation • regulation of cardiac muscle cell proliferation • negative regulation of cell growth involved in cardiac muscle cell development • lung secretory cell differentiation • cellular response to tumor necrosis factor • cardiovascular system development • innate vocalization behavior • regulation of action potential • regulation of lung goblet cell differentiation • negative regulation of lung goblet cell differentiation • cellular response to ionomycin • positive regulation of hydrogen peroxide-induced cell death • positive regulation of cardiac muscle cell differentiation • cellular response to DNA damage stimulus • negative regulation of gene expression • positive regulation of B cell receptor signaling pathway Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	27086	n/a
Ensembl	ENSG00000114861	n/a
UniProt	Q9H334	n/a
RefSeq (mRNA)	NM_001012505 NM_001244808 NM_001244810 NM_001244812 NM_001244813 NM_001244814 NM_001244815 NM_001244816 NM_032682 NM_001349338 NM_001349340 NM_001349341 NM_001349342 NM_001349343 NM_001349344 NM_001349337 NM_001370548	n/a
RefSeq (protein)	NP_001012523 NP_001231737 NP_001231739 NP_001231741 NP_001231742 NP_001231743 NP_001231744 NP_001231745 NP_116071 NP_001336267 NP_001336269 NP_001336270 NP_001336271 NP_001336272 NP_001336273 NP_001336266	n/a
Location (UCSC)	Chr 3: 70.95 – 71.58 Mb	n/a
PubMed search	[2]	n/a
Wikidata
View/Edit Human

Function

This gene belongs to subfamily P of the forkhead box (FOX) transcription factor family. Forkhead box transcription factors play important roles in the regulation of tissue- and cell type-specific gene transcription during both development and adulthood. Forkhead box P1 protein contains both DNA-binding- and protein-protein binding-domains. This gene may act as a tumor suppressor as it is lost in several tumor types and maps to a chromosomal region (3p14.1) reported to contain a tumor suppressor gene(s). Alternative splicing results in multiple transcript variants encoding different isoforms.[3]

Foxp1 is a transcription factor; specifically it is a transcriptional repressor. Fox genes are part of a forkhead DNA-binding domain family. This domain binds to sequences in promoters and enhancers of many genes. Foxp1 regulates a variety of important aspects of development including tissue development of: the lungs, brain, thymus and heart. In the heart Foxp1 has 3 vital roles, these include the regulation of cardiac myocyte maturation and proliferation, outflow tract separation of the pulmonary artery and aorta, and expression of Sox4 in cushions and myocardium. Foxp1 is also an important gene in muscle development of the esophagus and esophageal epithelium. Foxp1 is also an important regulator of lung airway morphogenesis. Foxp1 knockout embryos display severe defects in cardiac morphogenesis. A few of these defects include myocyte maturation and proliferation defects that cause a thin ventricular myocardial compact zone, non-separation of the pulmonary artery and aorta, and cardiomyocyte proliferation increase and defective differentiation. These defects, caused by Foxp1 inactivation, lead to fetal death. Disruptions of FoxP1 have been identified in very rare human patients and – similarly to FoxP2 - lead to cognitive dysfunction, including intellectual disability and autism spectrum disorder, together with language impairment.[4]

It was shown that the embryonic stem cell (ESC)-specific isoform of FOXP1 stimulates the expression of transcription factor genes required for pluripotency, including OCT4, NANOG, NR5A2, and GDF3, while concomitantly repressing genes required for ESC differentiation. This isoform also promotes the maintenance of ESC pluripotency and contributes to efficient reprogramming of somatic cells into induced pluripotent stem cells. These results reveal a pivotal role for an Alternative splicing event in the regulation of pluripotency through the control of critical ESC-specific transcriptional programs.[5]

See also

• FOXP2
• FOXP3

References

1. GRCh38: Ensembl release 89: ENSG00000114861 - Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. "Entrez Gene: FOXP1 forkhead box P1".
4. Bacon C, Rappold GA (Nov 2012). "The distinct and overlapping phenotypic spectra of FOXP1 and FOXP2 in cognitive disorders". Human Genetics. 131 (11): 1687–98. doi:10.1007/s00439-012-1193-z. PMC 3470686. PMID 22736078.
5. Gabut M, Samavarchi-Tehrani P, Wang X, Slobodeniuc V, O'Hanlon D, Sung HK, Alvarez M, Talukder S, Pan Q, Mazzoni EO, Nedelec S, Wichterle H, Woltjen K, Hughes TR, Zandstra PW, Nagy A, Wrana JL, Blencowe BJ (September 2011). "An alternative splicing switch regulates embryonic stem cell pluripotency and reprogramming". Cell. 147 (1): 132–46. doi:10.1016/j.cell.2011.08.023. PMID 21924763.

Further reading

• Katoh M, Katoh M (2005). "Human FOX gene family (Review)". Int. J. Oncol. 25 (5): 1495–500. doi:10.3892/ijo.25.5.1495. PMID 15492844.
• Li C, Tucker PW (1994). "DNA-binding properties and secondary structural model of the hepatocyte nuclear factor 3/fork head domain". Proc. Natl. Acad. Sci. U.S.A. 90 (24): 11583–7. doi:10.1073/pnas.90.24.11583. PMC 48028. PMID 8265594.
• Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY, Lu G, Zhong M, Xu XR, Han ZG, Zhang JW, Tao J, Huang QH, Zhou J, Hu GX, Gu J, Chen SJ, Chen Z (2001). "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells". Genome Res. 10 (10): 1546–60. doi:10.1101/gr.140200. PMC 310934. PMID 11042152.
• Banham AH, Beasley N, Campo E, Fernandez PL, Fidler C, Gatter K, Jones M, Mason DY, Prime JE, Trougouboff P, Wood K, Cordell JL (2002). "The FOXP1 winged helix transcription factor is a novel candidate tumor suppressor gene on chromosome 3p". Cancer Res. 61 (24): 8820–9. PMID 11751404.
• Wolska MK, Bukowski K, Jakubczak A (2002). "[Occurrence of beta-lactamase type ESBL and IBL in Pseudomonas aeruginosa rods]". Medycyna doświadczalna i mikrobiologia. 53 (1): 45–51. PMID 11757404.
• Wang B, Lin D, Li C, Tucker P (2003). "Multiple domains define the expression and regulatory properties of Foxp1 forkhead transcriptional repressors". J. Biol. Chem. 278 (27): 24259–68. doi:10.1074/jbc.M207174200. PMID 12692134.
• Li S, Weidenfeld J, Morrisey EE (2004). "Transcriptional and DNA binding activity of the Foxp1/2/4 family is modulated by heterotypic and homotypic protein interactions". Mol. Cell. Biol. 24 (2): 809–22. doi:10.1128/MCB.24.2.809-822.2004. PMC 343786. PMID 14701752.
• Teramitsu I, Kudo LC, London SE, Geschwind DH, White SA (2004). "Parallel FoxP1 and FoxP2 expression in songbird and human brain predicts functional interaction". J. Neurosci. 24 (13): 3152–63. doi:10.1523/JNEUROSCI.5589-03.2004. PMC 6730014. PMID 15056695.
• Fox SB, Brown P, Han C, Ashe S, Leek RD, Harris AL, Banham AH (2004). "Expression of the forkhead transcription factor FOXP1 is associated with estrogen receptor alpha and improved survival in primary human breast carcinomas". Clin. Cancer Res. 10 (10): 3521–7. doi:10.1158/1078-0432.CCR-03-0461. PMID 15161711.
• Shi C, Zhang X, Chen Z, Sulaiman K, Feinberg MW, Ballantyne CM, Jain MK, Simon DI (2004). "Integrin engagement regulates monocyte differentiation through the forkhead transcription factor Foxp1". J. Clin. Invest. 114 (3): 408–18. doi:10.1172/JCI21100. PMC 484980. PMID 15286807.
• Streubel B, Vinatzer U, Lamprecht A, Raderer M, Chott A (2005). "T(3;14)(p14.1;q32) involving IGH and FOXP1 is a novel recurrent chromosomal aberration in MALT lymphoma". Leukemia. 19 (4): 652–8. doi:10.1038/sj.leu.2403644. PMID 15703784.
• Banham AH, Connors JM, Brown PJ, Cordell JL, Ott G, Sreenivasan G, Farinha P, Horsman DE, Gascoyne RD (2005). "Expression of the FOXP1 transcription factor is strongly associated with inferior survival in patients with diffuse large B-cell lymphoma". Clin. Cancer Res. 11 (3): 1065–72. PMID 15709173.
• Brown P, Marafioti T, Kusec R, Banham AH (2007). "The FOXP1 transcription factor is expressed in the majority of follicular lymphomas but is rarely expressed in classical and lymphocyte predominant Hodgkin's lymphoma". J. Mol. Histol. 36 (4): 249–56. doi:10.1007/s10735-005-6521-3. PMID 16200457.
• Giatromanolaki A, Koukourakis MI, Sivridis E, Gatter KC, Harris AL, Banham AH (2006). "Loss of expression and nuclear/cytoplasmic localization of the FOXP1 forkhead transcription factor are common events in early endometrial cancer: relationship with estrogen receptors and HIF-1alpha expression". Mod. Pathol. 19 (1): 9–16. doi:10.1038/modpathol.3800494. PMID 16258506.
• Sagaert X, de Paepe P, Libbrecht L, Vanhentenrijk V, Verhoef G, Thomas J, Wlodarska I, De Wolf-Peeters C (2006). "Forkhead box protein P1 expression in mucosa-associated lymphoid tissue lymphomas predicts poor prognosis and transformation to diffuse large B-cell lymphoma". J. Clin. Oncol. 24 (16): 2490–7. doi:10.1200/JCO.2006.05.6150. PMID 16636337.
• Haralambieva E, Adam P, Ventura R, Katzenberger T, Kalla J, Höller S, Hartmann M, Rosenwald A, Greiner A, Muller-Hermelink HK, Banham AH, Ott G (2007). "Genetic rearrangement of FOXP1 is predominantly detected in a subset of diffuse large B-cell lymphomas with extranodal presentation". Leukemia. 20 (7): 1300–3. doi:10.1038/sj.leu.2404244. PMID 16673020.
• Hannenhalli S, Putt ME, Gilmore JM, Wang J, Parmacek MS, Epstein JA, Morrisey EE, Margulies KB, Cappola TP (2006). "Transcriptional genomics associates FOX transcription factors with human heart failure". Circulation. 114 (12): 1269–76. doi:10.1161/CIRCULATIONAHA.106.632430. PMID 16952980.
• Shu W, Min Lu M, Zhang Y, Tucker PW, Zhou D, Morrisey EE (2007). "Foxp2 and Foxp1 cooperatively regulate lung and esophagus development". Development. 134 (10): 1991–2000. doi:10.1242/dev.02846. PMID 17428829.
• Wang B, Weidenfeld J, Min Lu M, Maika S, Kuziel WA, Morrisey EE, Tucker PW (2004). "Foxp1 regulates cardiac outflow tract, endocardial cushion morphogenesis and myocyte proliferation and maturation". Development. 131 (18): 4477–4487. doi:10.1242/dev.01287.

External links

• Further clinical details at OMIM Entry #613670 (Mental Retardation With Language Impairment and with or without Austistic Features)
• Additional information also at OMIM Entry #605515 (Forkhead Box P1)
• FOXP1+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
• Overview of all the structural information available in the PDB for UniProt: Q9H334 (Forkhead box protein P1) at the PDBe-KB.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.