FOXP1

FOXP1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
Aliases FOXP1, 12CC4, HSPC215, MFH, QRF1, hFKH1B, forkhead box P1
External IDs OMIM: 605515 MGI: 1914004 HomoloGene: 136512 GeneCards: FOXP1
Genetically Related Diseases
attention deficit hyperactivity disorder[1]
Orthologs
Species Human Mouse
Entrez

27086

108655

Ensembl

ENSG00000114861

ENSMUSG00000030067

UniProt

Q9H334

P58462

RefSeq (mRNA)

NM_001197321
NM_001197322
NM_053202

RefSeq (protein)

NP_001184250.1
NP_001184251.1
NP_444432.1

Location (UCSC) Chr 3: 70.95 – 71.58 Mb Chr 6: 98.93 – 99.52 Mb
PubMed search [2] [3]
Wikidata
View/Edit HumanView/Edit Mouse

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.

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.[4]

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.[5]

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.[6]

The expression of FOXP1 was also implicated in the biology of B cell malignancies, and is regulated by non-coding RNA (miRNA) termed miR-150.[7]

See also

References

  1. "Diseases that are genetically associated with FOXP1 view/edit references on wikidata".
  2. "Human PubMed Reference:".
  3. "Mouse PubMed Reference:".
  4. "Entrez Gene: FOXP1 forkhead box P1".
  5. 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 3470686Freely accessible. PMID 22736078.
  6. 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.
  7. Mraz M, Chen L, Rassenti LZ, Ghia EM, Li H, Jepsen K, Smith EN, Messer K, Frazer KA, Kipps TJ (2014). "MiR-150 influences B-cell receptor signaling in chronic lymphocytic leukemia by regulating expression of GAB1 and FOXP1". Blood. 124 (1): 84–95. doi:10.1182/blood-2013-09-527234. PMID 24787006.

Further reading

External links

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

This article is issued from Wikipedia - version of the 8/10/2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.