FOX proteins
Encyclopedia
FOX proteins are a family of transcription factor
s that play important roles in regulating the expression of gene
s involved in cell growth, proliferation, differentiation, and longevity
. Many FOX proteins are important to embryonic development.
The defining feature of FOX proteins is the forkhead box
, a sequence of 80 to 100 amino acids forming a motif that binds to DNA
. This forkhead motif is also known as the winged helix
due to the butterfly-like appearance of the loops in the protein structure of the domain. Forkhead genes are a subgroup of the helix-turn-helix
class of proteins.
the FOXF2 gene encodes forkhead box F2, one of many human homologues of the Drosophila melanogaster
transcription factor
forkhead. FOXF2 is expressed in lung and placenta
.
Some FOX genes are downstream targets of the hedgehog signaling pathway
, which plays a role in the development of basal cell carcinoma
s.
Members of the class O regulate metabolism, cellular proliferation, stress tolerance and possibly lifespan. The activity of FoxO is controlled by post-translational modifications, including phosphorylation, acetylation and ubiquitination.
, discovered by Detlef Weigel
and Herbert Jäckle. Since then a large number of family members have been discovered, especially in vertebrate
s. Originally they were given vastly different names (such as HFH, FREAC, and fkh), but in 2000 a unified nomenclature was introduced that grouped the FOX proteins into subclasses (FOXA-FOXS) based on sequence conservation.
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
s that play important roles in regulating the expression of gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s involved in cell growth, proliferation, differentiation, and longevity
Longevity
The word "longevity" is sometimes used as a synonym for "life expectancy" in demography or known as "long life", especially when it concerns someone or something lasting longer than expected ....
. Many FOX proteins are important to embryonic development.
The defining feature of FOX proteins is the forkhead box
Fork head domain
The fork head domain is a type of protein domain which is often found in transcription factors and whose purpose is to bind DNA.- Function :...
, a sequence of 80 to 100 amino acids forming a motif that binds to DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
. This forkhead motif is also known as the winged helix
Winged-helix transcription factors
Consisting of about 110 amino acids, the domain in winged-helix transcription factors has four helices and a two-strand beta-sheet.These proteins are classified into 17 families called FoxA-FoxQ....
due to the butterfly-like appearance of the loops in the protein structure of the domain. Forkhead genes are a subgroup of the helix-turn-helix
Helix-turn-helix
In proteins, the helix-turn-helix is a major structural motif capable of binding DNA. It is composed of two α helices joined by a short strand of amino acids and is found in many proteins that regulate gene expression...
class of proteins.
Biological roles
Many genes encoding FOX proteins have been identified. For example,the FOXF2 gene encodes forkhead box F2, one of many human homologues of the Drosophila melanogaster
Drosophila melanogaster
Drosophila melanogaster is a species of Diptera, or the order of flies, in the family Drosophilidae. The species is known generally as the common fruit fly or vinegar fly. Starting from Charles W...
transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
forkhead. FOXF2 is expressed in lung and placenta
Placenta
The placenta is an organ that connects the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother's blood supply. "True" placentas are a defining characteristic of eutherian or "placental" mammals, but are also found in some snakes and...
.
Some FOX genes are downstream targets of the hedgehog signaling pathway
Hedgehog signaling pathway
In a growing embryo, cells develop differently in the head or tail end of the embryo, the left or right, and other positions. They also form segments which develop into different body parts. The hedgehog signaling pathway gives cells information that they need to make the embryo develop properly....
, which plays a role in the development of basal cell carcinoma
Carcinoma
Carcinoma is the medical term for the most common type of cancer occurring in humans. Put simply, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that generally arises from cells originating in the endodermal or ectodermal germ layer during...
s.
Members of the class O regulate metabolism, cellular proliferation, stress tolerance and possibly lifespan. The activity of FoxO is controlled by post-translational modifications, including phosphorylation, acetylation and ubiquitination.
Discovery
The founding member and namesake of the FOX family is the fork head transcription factor in DrosophilaDrosophila
Drosophila is a genus of small flies, belonging to the family Drosophilidae, whose members are often called "fruit flies" or more appropriately pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit...
, discovered by Detlef Weigel
Detlef Weigel
Detlef Weigel is a German American scientist working at the interface of developmental and evolutionary biology.-Scientific career:...
and Herbert Jäckle. Since then a large number of family members have been discovered, especially in vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...
s. Originally they were given vastly different names (such as HFH, FREAC, and fkh), but in 2000 a unified nomenclature was introduced that grouped the FOX proteins into subclasses (FOXA-FOXS) based on sequence conservation.
Genes
- FOXA1FOXA1Forkhead box protein A1 , also known as hepatocyte nuclear factor 3-alpha , is a protein that in humans is encoded by the FOXA1 gene.- Function :FOXA1 is a member of the forkhead class of DNA-binding proteins...
, FOXA2FOXA2Hepatocyte nuclear factor 3-beta , also known as forkhead box protein A2 or transcription factor 3B is a protein that in humans is encoded by the FOXA2 gene.- Function :...
, FOXA3FOXA3Hepatocyte nuclear factor 3-gamma , also known as forkhead box protein A3 or transcription factor 3G is a protein that in humans is encoded by the FOXA3 gene.- Function :...
(See also Hepatocyte nuclear factorsHepatocyte nuclear factorsHepatocyte nuclear factors are a group of phylogenetically unrelated transcription factors that regulate the transcription of a diverse group of genes into proteins...
) - FOXB1, FOXB2
- FOXC1, FOXC2FOXC2Forkhead box protein C2 also known as forkhead-related protein FKHL14 , transcription factor FKH-14, or mesenchyme fork head protein 1 is a protein that in humans is encoded by the FOXC2 gene...
- FOXD1, FOXD2, FOXD3FOXD3Forkhead box D3 also known as FOXD3 is a forkhead protein that in humans is encoded by the FOXD3 gene.- Function :This gene belongs to the forkhead family of transcription factors which is characterized by a distinct forkhead domain....
, FOXD4FOXD4Forkhead box protein D4 is a protein that in humans is encoded by the FOXD4 gene.-Further reading:...
, FOXD5, FOXD6 - FOXE1FOXE1Forkhead box protein E1 is a protein that in humans is encoded by the FOXE1 gene.- Function :This intronless gene belongs to the forkhead family of transcription factors, which is characterized by a distinct forkhead domain...
, FOXE2, FOXE3FOXE3Forkhead box protein E3 also known as forkhead-related transcription factor 8 is a protein that in humans is encoded by the FOXE3 gene located on the short arm of chromosome 1.- Function :... - FOXF1FOXF1Forkhead box protein F1 is a protein that in humans is encoded by the FOXF1 gene....
, FOXF2 - FOXG1FOXG1Forkhead box protein G1 is a protein that in humans is encoded by the FOXG1 gene....
- FOXH1FOXH1Forkhead box protein H1 is a protein that in humans is encoded by the FOXH1 gene.-Interactions:FOXH1 has been shown to interact with DRAP1 and Mothers against decapentaplegic homolog 2....
- FOXI1FOXI1FOXI1 is a human gene.It can be associated with enlarged vestibular aqueduct....
, FOXI2 - FOXJ1FOXJ1Forkhead box protein J1 is a protein that in humans is encoded by the FOXJ1 gene. It has been shown that this gene is a transcription factor involved in ciliogenesis.- Function :This gene encodes a member of the forkhead family of transcription factors...
, FOXJ2FOXJ2Forkhead box protein J2 is a protein that in humans is encoded by the FOXJ2 gene.-Further reading:...
, FOXJ3 - FOXK1FOXK1Forkhead box protein K1 is a protein that in humans is encoded by the FOXK1 gene.-Further reading:...
, FOXK2FOXK2Forkhead box protein K2 is a protein that in humans is encoded by the FOXK2 gene.-Further reading:... - FOXL1, FOXL2
- FOXM1FOXM1Forkhead box protein M1 is a protein that in humans is encoded by the FOXM1 gene. The protein encoded by this gene is a member of the FOX family of transcription factors...
- FOXN1FOXN1Forkhead box protein N1 is a protein that in humans is encoded by the FOXN1 gene.-Further reading:...
, FOXN2, FOXN3FOXN3Forkhead box protein N3 is a protein that in humans is encoded by the FOXN3 gene....
, FOXN4 - FOXO1, FOXO3FOXO3AForkhead box O3, also known as FOXO3 or FOXO3a, is a human protein encoded by the FOXO3 gene.- Function :FOXO3 belongs to the O subclass of the forkhead family of transcription factors which are characterized by a distinct fork head DNA binding domain. There are three other FoxO family members in...
, FOXO4FOXO4Forkhead box protein O4 is a protein that in humans is encoded by the FOXO4 gene.-Interactions:FOXO4 has been shown to interact with PIN1 and Mdm2.-Further reading:...
, FOXO6 - FOXP1FOXP1FOXP1 is a gene that is necessary for the proper development of the brain and lung in mammals. It is a member of the large FOX family of transcription factors....
, FOXP2FOXP2Forkhead box protein P2 also known as FOXP2 is a protein that in humans is encoded by the FOXP2 gene, located on human chromosome 7 . FOXP2 orthologs have also been identified in all mammals for which complete genome data are available...
, FOXP3FOXP3FOXP3 is a protein involved in immune system responses. A member of the FOX protein family, FOXP3 appears to function as a master regulator in the development and function of regulatory T cells....
, FOXP4FOXP4Forkhead box protein P4 is a protein that in humans is encoded by the FOXP4 gene.-Further reading:... - FOXQ1
- FOXR1, FOXR2