Homeobox
Encyclopedia
A homeobox is a DNA sequence found within gene
s that are involved in the regulation of patterns of anatomical development (morphogenesis
) in animal
s, fungi
and plant
s.
working in the lab of Walter Jakob Gehring
at the University of Basel
, Switzerland
; and by Matthew P. Scott
and Amy Weiner, who were then working with Thomas Kaufman at Indiana University in Bloomington
.
s long. It encodes a protein
domain (the homeodomain
) which when expressed (i.e. as protein) can bind DNA
. The following shows the consensus 60-residue chain corresponding to homeobox domain, with typical intron positions noted with dashes:
Homeobox genes encode transcription factor
s that typically switch on cascades of other genes. The homeodomain binds DNA in a sequence-specific manner. However, the specificity of a single homeodomain protein is usually not enough to recognize only its desired target genes. Most of the time, homeodomain proteins act in the promoter region of their target genes as complexes with other transcription factors. Such complexes have a much higher target specificity than a single homeodomain protein. Homeodomains are encoded both by genes of the Hox gene clusters and by other genes throughout the genome.
The homeobox domain was first identified in a number of drosophila homeotic and segmentation proteins, but is now known to be well-conserved in many other animals, including vertebrates. Hox genes encode homeodomain-containing transcriptional regulators that operate differential genetic programs along the anterior-posterior axis of animal bodies. The domain binds DNA through a helix-turn-helix (HTH)
structure. The HTH motif is characterised by two alpha-helices, which make intimate contacts with the DNA and are joined by a short turn. The second helix binds to DNA via a number of hydrogen bonds and hydrophobic interactions, which occur between specific side chains and the exposed bases and thymine methyl groups within the major groove of the DNA. The first helix helps to stabilise the structure.
The motif is very similar in sequence and structure in a wide range of DNA-binding proteins (e.g., cro and repressor proteins, homeotic proteins, etc.). One of the principal differences between HTH motifs in these different proteins arises from the stereo-chemical requirement for glycine in the turn which is needed to avoid steric interference of the beta-carbon with the main chain: for cro and repressor proteins the glycine appears to be mandatory, while for many of the homeotic and other DNA-binding proteins the requirement is relaxed.
They are essential metazoan genes as they determine the identity of embryonic regions along the anterio-posterior axis. The first vertebrate Hox gene was isolated in Xenopus
by Eddy De Robertis and colleagues in 1984, marking the beginning of the young science of Evo-devo
.
In vertebrates, the four paralog
clusters are partially redundant in function, but have also acquired several derived functions. In particular, HoxA and HoxD specify segment identity along the limb
axis.
The main interest in this set of genes stems from their unique behaviour. They are typically found in an organized cluster. The linear order of the genes within a cluster is directly correlated to the order of the regions they affect as well as the timing in which they are affected. This phenomenon is called colinearity. Due to this linear relationship, changes in the gene cluster due to mutations generally result in similar changes in the affected regions.
For example, when one gene is lost the segment develops into a more anterior one, while a mutation that leads to a gain of function causes a segment to develop into a more posterior one. This is called ectopia
. Famous examples are Antennapedia
and bithorax in Drosophila, which can cause the development of legs instead of antennae and the development of a duplicated thorax, respectively.
Molecular evidence shows that some limited number of Hox genes have existed in the Cnidaria
since before the earliest true Bilatera
, making these genes pre-Paleozoic
.
and have subsequently been identified in many other species, from insect
s to reptile
s and mammal
s.
Homeobox genes were previously only identified in bilateria
but more recently cnidaria
have also been found to contain homeobox domains and the "missing link" in the evolution between the two has been identified.
Homeobox genes have even been found in fungi
, for example the unicellular
yeast
s, and in plants.
genes in plants (MADS-box
genes) are not homologous
to Hox genes in animals. Plants and animals do not share the same homeotic genes, and this suggests that homeotic genes arose independently in the early evolution of animals and plants.
There is also a "distal-less homeobox" family: DLX1
, DLX2
, DLX3
, DLX4
, DLX5
, and DLX6
.
"HESX homeobox 1" is also known as HESX1
.
Short stature homeobox gene
is also known as SHOX
.
Additional human proteins containing this domain per UniProt
annotation:
changes.
Two examples of homeobox mutations in the above-mentioned fruit fly are legs where the antennae should be (antennapedia
), and a second pair of wings.
Duplication of homeobox genes can produce new body segments, and such duplications are likely to have been important in the evolution
of segmented animals. However, Hox genes typically determine the identity of body segments.
Interestingly, there is one insect
family, the xyelid sawflies
, in which both the antennae
and mouthparts are remarkably leg-like in structure. This is not uncommon in arthropods as all arthropod appendages are homologous.
is known to use the Polycomb
and Trithorax Complexes to maintain the expression of Hox genes after the down-regulation of the pair-rule and gap genes that occurs during larval development. Polycomb-group proteins
can silence the HOX genes by modulation of chromatin
structure.
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 that are involved in the regulation of patterns of anatomical development (morphogenesis
Morphogenesis
Morphogenesis , is the biological process that causes an organism to develop its shape...
) in animal
Animal
Animals are a major group of multicellular, eukaryotic organisms of the kingdom Animalia or Metazoa. Their body plan eventually becomes fixed as they develop, although some undergo a process of metamorphosis later on in their life. Most animals are motile, meaning they can move spontaneously and...
s, fungi
Fungus
A fungus is a member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds , as well as the more familiar mushrooms. These organisms are classified as a kingdom, Fungi, which is separate from plants, animals, and bacteria...
and plant
Plant
Plants are living organisms belonging to the kingdom Plantae. Precise definitions of the kingdom vary, but as the term is used here, plants include familiar organisms such as trees, flowers, herbs, bushes, grasses, vines, ferns, mosses, and green algae. The group is also called green plants or...
s.
Discovery
They were discovered independently in 1983 by Ernst Hafen, Michael Levine and William McGinnisWilliam McGinnis
William "Bill" McGinnis, Ph.D. is a molecular biologist and professor of biology at the University of California, San Diego . At UCSD he has also served as the Chairman of the Department of Biology from July 1998 - June 1999, as Associate Dean of the Division of Natural Sciences from July 1, 1999...
working in the lab of Walter Jakob Gehring
Walter Jakob Gehring
Walter Jakob Gehring is Professor at the Biozentrum of the University of Basel, Switzerland. He obtained his Ph.D...
at the University of Basel
University of Basel
The University of Basel is located in Basel, Switzerland, and is considered to be one of leading universities in the country...
, Switzerland
Switzerland
Switzerland name of one of the Swiss cantons. ; ; ; or ), in its full name the Swiss Confederation , is a federal republic consisting of 26 cantons, with Bern as the seat of the federal authorities. The country is situated in Western Europe,Or Central Europe depending on the definition....
; and by Matthew P. Scott
Matthew P. Scott
Matthew P. Scott is a developmental biologist and HHMI investigator at Stanford University studying how embryonic and later development is governed by proteins that control gene activity and cell signaling processes....
and Amy Weiner, who were then working with Thomas Kaufman at Indiana University in Bloomington
Bloomington, Indiana
Bloomington is a city in and the county seat of Monroe County in the southern region of the U.S. state of Indiana. The population was 80,405 at the 2010 census....
.
Homeodomain
A homeobox is about 180 base pairBase pair
In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...
s long. It encodes a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
domain (the homeodomain
Homeodomain fold
The homeodomain fold is a protein structural domain that binds DNA or RNA and is thus commonly found in transcription factors. The fold consists of a 60-amino acid helix-turn-helix structure in which three alpha helices are connected by short loop regions...
) which when expressed (i.e. as protein) can bind 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...
. The following shows the consensus 60-residue chain corresponding to homeobox domain, with typical intron positions noted with dashes:
RRRKRTA-YTRYQLLE-LEKEFLF-NRYLTRRRRIELAHSL-NLTERHIKIWFQN-RRMK-WKKEN
Homeobox genes encode 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...
s that typically switch on cascades of other genes. The homeodomain binds DNA in a sequence-specific manner. However, the specificity of a single homeodomain protein is usually not enough to recognize only its desired target genes. Most of the time, homeodomain proteins act in the promoter region of their target genes as complexes with other transcription factors. Such complexes have a much higher target specificity than a single homeodomain protein. Homeodomains are encoded both by genes of the Hox gene clusters and by other genes throughout the genome.
The homeobox domain was first identified in a number of drosophila homeotic and segmentation proteins, but is now known to be well-conserved in many other animals, including vertebrates. Hox genes encode homeodomain-containing transcriptional regulators that operate differential genetic programs along the anterior-posterior axis of animal bodies. The domain binds DNA through a helix-turn-helix (HTH)
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...
structure. The HTH motif is characterised by two alpha-helices, which make intimate contacts with the DNA and are joined by a short turn. The second helix binds to DNA via a number of hydrogen bonds and hydrophobic interactions, which occur between specific side chains and the exposed bases and thymine methyl groups within the major groove of the DNA. The first helix helps to stabilise the structure.
The motif is very similar in sequence and structure in a wide range of DNA-binding proteins (e.g., cro and repressor proteins, homeotic proteins, etc.). One of the principal differences between HTH motifs in these different proteins arises from the stereo-chemical requirement for glycine in the turn which is needed to avoid steric interference of the beta-carbon with the main chain: for cro and repressor proteins the glycine appears to be mandatory, while for many of the homeotic and other DNA-binding proteins the requirement is relaxed.
Hox genes
Xenopus
Xenopus is a genus of highly aquatic frogs native to Sub-Saharan Africa. There are 19 species in the Xenopus genus...
by Eddy De Robertis and colleagues in 1984, marking the beginning of the young science of Evo-devo
Evolutionary developmental biology
Evolutionary developmental biology is a field of biology that compares the developmental processes of different organisms to determine the ancestral relationship between them, and to discover how developmental processes evolved...
.
In vertebrates, the four paralog
Homology (biology)
Homology forms the basis of organization for comparative biology. In 1843, Richard Owen defined homology as "the same organ in different animals under every variety of form and function". Organs as different as a bat's wing, a seal's flipper, a cat's paw and a human hand have a common underlying...
clusters are partially redundant in function, but have also acquired several derived functions. In particular, HoxA and HoxD specify segment identity along the limb
Limb (anatomy)
A limb is a jointed, or prehensile , appendage of the human or other animal body....
axis.
The main interest in this set of genes stems from their unique behaviour. They are typically found in an organized cluster. The linear order of the genes within a cluster is directly correlated to the order of the regions they affect as well as the timing in which they are affected. This phenomenon is called colinearity. Due to this linear relationship, changes in the gene cluster due to mutations generally result in similar changes in the affected regions.
For example, when one gene is lost the segment develops into a more anterior one, while a mutation that leads to a gain of function causes a segment to develop into a more posterior one. This is called ectopia
Ectopic expression
Ectopic expression is the expression of a gene in an abnormal place in an organism. This can be caused by a disease, or it can be artificially produced as a way to help determine what the function of that gene is....
. Famous examples are Antennapedia
Antennapedia
Antennapedia is a HOM-C gene first discovered in Drosophila which controls the formation of legs during development. Loss-of-function mutations in the regulatory region of this gene result in the development of the second leg pair into ectopic antennae...
and bithorax in Drosophila, which can cause the development of legs instead of antennae and the development of a duplicated thorax, respectively.
Molecular evidence shows that some limited number of Hox genes have existed in the Cnidaria
Cnidaria
Cnidaria is a phylum containing over 9,000 species of animals found exclusively in aquatic and mostly marine environments. Their distinguishing feature is cnidocytes, specialized cells that they use mainly for capturing prey. Their bodies consist of mesoglea, a non-living jelly-like substance,...
since before the earliest true Bilatera
Bilateria
The bilateria are all animals having a bilateral symmetry, i.e. they have a front and a back end, as well as an upside and downside. Radially symmetrical animals like jellyfish have a topside and downside, but no front and back...
, making these genes pre-Paleozoic
Paleozoic
The Paleozoic era is the earliest of three geologic eras of the Phanerozoic eon, spanning from roughly...
.
Diversity
The homeobox genes were first found in the fruit fly Drosophila melanogasterDrosophila 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...
and have subsequently been identified in many other species, from insect
Insect
Insects are a class of living creatures within the arthropods that have a chitinous exoskeleton, a three-part body , three pairs of jointed legs, compound eyes, and two antennae...
s to reptile
Reptile
Reptiles are members of a class of air-breathing, ectothermic vertebrates which are characterized by laying shelled eggs , and having skin covered in scales and/or scutes. They are tetrapods, either having four limbs or being descended from four-limbed ancestors...
s and mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
s.
Homeobox genes were previously only identified in bilateria
Bilateria
The bilateria are all animals having a bilateral symmetry, i.e. they have a front and a back end, as well as an upside and downside. Radially symmetrical animals like jellyfish have a topside and downside, but no front and back...
but more recently cnidaria
Cnidaria
Cnidaria is a phylum containing over 9,000 species of animals found exclusively in aquatic and mostly marine environments. Their distinguishing feature is cnidocytes, specialized cells that they use mainly for capturing prey. Their bodies consist of mesoglea, a non-living jelly-like substance,...
have also been found to contain homeobox domains and the "missing link" in the evolution between the two has been identified.
Homeobox genes have even been found in fungi
Fungus
A fungus is a member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds , as well as the more familiar mushrooms. These organisms are classified as a kingdom, Fungi, which is separate from plants, animals, and bacteria...
, for example the unicellular
Microorganism
A microorganism or microbe is a microscopic organism that comprises either a single cell , cell clusters, or no cell at all...
yeast
Yeast
Yeasts are eukaryotic micro-organisms classified in the kingdom Fungi, with 1,500 species currently described estimated to be only 1% of all fungal species. Most reproduce asexually by mitosis, and many do so by an asymmetric division process called budding...
s, and in plants.
Plants
The well known homeoticHomeosis
Homeosis is the transformation of one body part into another, arising from mutation in or misexpression of specific developmentally critical genes. It may be caused by mutations in Hox genes, found in animals, or others such as the MADS-box family in plants...
genes in plants (MADS-box
MADS-box
The MADS box is a conserved sequence motif found in genes which comprise the MADS-box gene family. The MADS box encodes the DNA-binding MADS domain. The MADS domain binds to DNA sequences of high similarity to the motif CC[A/T]6GG termed the CArG-box. MADS-domain proteins are generally...
genes) are not homologous
Homology (biology)
Homology forms the basis of organization for comparative biology. In 1843, Richard Owen defined homology as "the same organ in different animals under every variety of form and function". Organs as different as a bat's wing, a seal's flipper, a cat's paw and a human hand have a common underlying...
to Hox genes in animals. Plants and animals do not share the same homeotic genes, and this suggests that homeotic genes arose independently in the early evolution of animals and plants.
Human genes
Humans generally contain Hox genes in four clusters:| name | chromosome Chromosome A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes... |
gene |
| HOXA (or sometimes HOX1) - | chromosome 7 Chromosome 7 (human) Chromosome 7 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 7 spans more than 158 million base pairs and represents between 5 and 5.5 percent of the total DNA in cells.Identifying genes on each chromosome is an active area of genetic... |
HOXA1, HOXA2 HOXA2 Homeobox protein Hox-A2 is a protein that in humans is encoded by the HOXA2 gene.- Function :In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially... , HOXA3 HOXA3 Homeobox protein Hox-A3 is a protein that in humans is encoded by the HOXA3 gene.- Regulation :The HOXA3 gene is repressed by the microRNA miR-10a.... , HOXA4 HOXA4 Homeobox A4, also known as HOXA4, is a protein which in humans is encoded by the HOXA4 gene.- Function :In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins... , HOXA5 HOXA5 Homeobox protein Hox-A5 is a protein that in humans is encoded by the HOXA5 gene.-Further reading:- External links :... , HOXA6 HOXA6 Homeobox protein Hox-A6 is a protein that in humans is encoded by the HOXA6 gene.-Further reading:... , HOXA7 HOXA7 Homeobox protein Hox-A7 is a protein that in humans is encoded by the HOXA7 gene.-Further reading:... , HOXA9 HOXA9 Homeobox protein Hox-A9 is a protein that in humans is encoded by the HOXA9 gene.-Interactions:HOXA9 has been shown to interact with PBX2, TRIP6 and MEIS1.-Further reading:... , HOXA10, HOXA11 HOXA11 Homeobox protein Hox-A11 is a protein that in humans is encoded by the HOXA11 gene.... , HOXA13 HOXA13 Homeobox protein Hox-A13 is a protein that in humans is encoded by the HOXA13 gene.- Function :In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is... |
| HOXB - | chromosome 17 | HOXB1 HOXB1 Homeobox protein Hox-B1 is a protein that in humans is encoded by the HOXB1 gene.-Further reading:... , HOXB2 HOXB2 Homeobox protein Hox-B2 is a protein that in humans is encoded by the HOXB2 gene.... , HOXB3 HOXB3 Homeobox protein Hox-B3 is a protein that in humans is encoded by the HOXB3 gene.... , HOXB4 HOXB4 Homeobox protein Hox-B4 is a protein that in humans is encoded by the HOXB4 gene.... , HOXB5 HOXB5 Homeobox protein Hox-B5 is a protein that in humans is encoded by the HOXB5 gene.-Further reading:... , HOXB6 HOXB6 Homeobox protein Hox-B6 is a protein that in humans is encoded by the HOXB6 gene.-Further reading:... , HOXB7 HOXB7 Homeobox protein Hox-B7 is a protein that in humans is encoded by the HOXB7 gene.-Interactions:HOXB7 has been shown to interact with PBX1 and CREB-binding protein.-Further reading:... , HOXB8 HOXB8 Homeobox protein Hox-B8 is a protein that in humans is encoded by the HOXB8 gene.Transplantation of normal bone marrow into a Hoxb8 mutant mouse results is a reduction of compulsive grooming.... , HOXB9 HOXB9 Homeobox protein Hox-B9 is a protein that in humans is encoded by the HOXB9 gene.-Interactions:HOXB9 has been shown to interact with BTG2 and BTG1.... , HOXB13 HOXB13 Homeobox protein Hox-B13 is a protein that in humans is encoded by the HOXB13 gene.-Further reading:... |
| HOXC - | chromosome 12 | HOXC4 HOXC4 Homeobox protein Hox-C4 is a protein that in humans is encoded by the HOXC4 gene.... , HOXC5 HOXC5 Homeobox protein Hox-C5 is a protein that in humans is encoded by the HOXC5 gene.... , HOXC6 HOXC6 Homeobox protein Hox-C6 is a protein that in humans is encoded by the HOXC6 gene.-Further reading:... , HOXC8 HOXC8 Homeobox protein Hox-C8 is a protein that in humans is encoded by the HOXC8 gene.-Interactions:HOXC8 has been shown to interact with Mothers against decapentaplegic homolog 6 and Mothers against decapentaplegic homolog 1.... , HOXC9 HOXC9 Homeobox protein Hox-C9 is a protein that in humans is encoded by the HOXC9 gene.... , HOXC10 HOXC10 Homeobox protein Hox-C10 is a protein that in humans is encoded by the HOXC10 gene.... , HOXC11 HOXC11 Homeobox protein Hox-C11 is a protein that in humans is encoded by the HOXC11 gene.... , HOXC12 HOXC12 Homeobox C12 is a protein that in humans is encoded by the HOXC12 gene.This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms... , HOXC13 HOXC13 Homeobox protein Hox-C13 is a protein that in humans is encoded by the HOXC13 gene.... |
| HOXD - | chromosome 2 | HOXD1 HOXD1 Homeobox protein Hox-D1 is a protein that in humans is encoded by the HOXD1 gene.- External links :... , HOXD3 HOXD3 Homeobox protein Hox-D3 is a protein that in humans is encoded by the HOXD3 gene.- External links :... , HOXD4 HOXD4 Homeobox protein Hox-D4 is a protein that in humans is encoded by the HOXD4 gene.- External links :... , HOXD8 HOXD8 Homeobox protein Hox-D8 is a protein that in humans is encoded by the HOXD8 gene.- External links :... , HOXD9 HOXD9 Homeobox protein Hox-D9 is a protein that in humans is encoded by the HOXD9 gene.-Further reading:- External links :... , HOXD10 HOXD10 Homeobox D10, also known as HOXD10, is a protein which in humans is encoded by the HOXD10 gene.- Function :This gene is a member of the Abd-B homeobox family and encodes a protein with a homeobox DNA-binding domain. It is included in a cluster of homeobox D genes located on chromosome 2... , HOXD11 HOXD11 Homeobox protein Hox-D11 is a protein that in humans is encoded by the HOXD11 gene.This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms... , HOXD12 HOXD12 Homeobox protein Hox-D12 is a protein that in humans is encoded by the HOXD12 gene.This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms... , HOXD13 HOXD13 Homeobox protein Hox-D13 is a protein that in humans is encoded by the HOXD13 gene.This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms... |
There is also a "distal-less homeobox" family: DLX1
DLX1
Homeobox protein DLX-1 is a protein that in humans is encoded by the DLX1 gene.- Function :This gene encodes a member of a homeobox transcription factor gene family similar to the Drosophila distal-less gene. The encoded protein is localized to the nucleus where it may function as a transcriptional...
, DLX2
DLX2
Homeobox protein DLX-2 is a protein that in humans is encoded by the DLX2 gene.-Interactions:DLX2 has been shown to interact with DLX5, MSX1 and Msh homeobox 2.-Further reading:...
, DLX3
DLX3 (gene)
Homeobox protein DLX-3 is a protein that in humans is encoded by the DLX3 gene....
, DLX4
DLX4
Homeobox protein DLX-4 is a protein that in humans is encoded by the DLX4 gene.- External links :...
, DLX5
DLX5
Homeobox protein DLX-5 is a protein that in humans is encoded by the DLX5 gene.- Function :This gene encodes a member of a homeobox transcription factor gene family similar to the Drosophila distal-less gene. The encoded protein may play a role in bone development and fracture healing...
, and DLX6
DLX6
Homeobox protein DLX-6 is a protein that in humans is encoded by the DLX6 gene.-Further reading:...
.
"HESX homeobox 1" is also known as HESX1
HESX1
Homeobox expressed in ES cells 1, also known as homeobox protein ANF, is a homeobox protein that in humans is encoded by the HESX1 gene.Expression of HEX1 and HESX1 marks the anterior visceral endoderm of the embryo...
.
Short stature homeobox gene
Short stature homeobox gene
Short stature homeobox gene or SHOX is a gene on the X chromosome and Y chromosome which is associated with short stature in humans if mutated or present in only one copy .-Pathology:...
is also known as SHOX
Shox
Shox is an arcade, rally game, it is available on the PlayStation 2 console in the USA and Europe.-Gameplay:Shox is based around the concept of a shockwave that appears in front of the player's car if they successfully pass, within the time limit, through three points on a track...
.
Additional human proteins containing this domain per UniProt
UniProt
UniProt is a comprehensive, high-quality and freely accessible database of protein sequence and functional information, many of which are derived from genome sequencing projects...
annotation:
- ADNP; ALX1ALX1ALX homeobox protein 1 is a protein that in humans is encoded by the ALX1 gene.-Further reading:...
; ALX3; ALX4ALX4Homeobox protein aristaless-like 4 is a protein that in humans is encoded by the ALX4 gene.-Interactions:ALX4 has been shown to interact with Lymphoid enhancer-binding factor 1.-External links:*...
; ARGFX; ARXAristaless related homeoboxAristaless related homeobox, also known as ARX is a protein associated with mental retardation and lissencephaly.... - BARHL1; BARHL2; BARX1; BARX2; BSX
- CDX1CDX1Homeobox protein CDX-1 is a protein that in humans is encoded by the CDX1 gene....
; CDX2CDX2Homeobox protein CDX-2 is a protein that in humans is encoded by the CDX2 gene. The protein encoded by this gene is a homeobox transcription factor.-Function:...
; CDX4; CRXCRX (gene)Cone-rod homeobox protein is a protein that in humans is encoded by the CRX gene.-External links:*...
; CUTL1CUTL1Cux1 is a homeodomain protein that in humans is encoded by the CUX1 gene.-Interactions:Cux1 has been shown to interact with CREB binding protein, SATB1 and Retinoblastoma protein....
; CUTL2 - DBX1DBX1Homeobox protein DBX1, also known as developing brain homeobox protein 1, is a protein that in humans is encoded by the DBX1 gene....
; DBX2DBX2Homeobox protein DBX2, also known as developing brain homeobox protein 2, is a protein that in humans is encoded by the DBX2 gene....
; DLX1DLX1Homeobox protein DLX-1 is a protein that in humans is encoded by the DLX1 gene.- Function :This gene encodes a member of a homeobox transcription factor gene family similar to the Drosophila distal-less gene. The encoded protein is localized to the nucleus where it may function as a transcriptional...
; DLX2DLX2Homeobox protein DLX-2 is a protein that in humans is encoded by the DLX2 gene.-Interactions:DLX2 has been shown to interact with DLX5, MSX1 and Msh homeobox 2.-Further reading:...
; DLX3DLX3 (gene)Homeobox protein DLX-3 is a protein that in humans is encoded by the DLX3 gene....
; DLX4DLX4Homeobox protein DLX-4 is a protein that in humans is encoded by the DLX4 gene.- External links :...
; DLX5DLX5Homeobox protein DLX-5 is a protein that in humans is encoded by the DLX5 gene.- Function :This gene encodes a member of a homeobox transcription factor gene family similar to the Drosophila distal-less gene. The encoded protein may play a role in bone development and fracture healing...
; DLX6DLX6Homeobox protein DLX-6 is a protein that in humans is encoded by the DLX6 gene.-Further reading:...
; DMBX1; DPRX; DRGX; DUX1; DUX2; DUX3; DUX4DUX4Double homeobox, 4 also known as DUX4 is a protein which in humans is encoded by the DUX4 gene.-Gene:This gene is located within a D4Z4 repeat array in the subtelomeric region of chromosome 4q. The D4Z4 repeat is polymorphic in length; a similar D4Z4 repeat array has been identified on chromosome 10...
; DUX4L2; DUX4L3; DUX4L4; DUX4L5; DUX4L6; DUX4L7; DUX4L9; DUX5; DUXA - EMX1EMX1Homeobox protein EMX1 is a protein that in humans is encoded by the EMX1 gene.-Further reading:...
; EMX2EMX2Homeobox protein EMX2 is a protein that in humans is encoded by the EMX2 gene....
; EN1EN1 (gene)Homeobox protein engrailed-1 is a protein that in humans is encoded by the EN1 gene....
; EN2EN2 (gene)Homeobox protein engrailed-2 is a protein that in humans is encoded by the EN2 gene.-In cancer diagnosis:A promising method of diagnosing prostate cancer is to detect EN2 in urine...
; ESX1L; EVX1; EVX2 - GBX1; GBX2GBX2Homeobox protein GBX-2 is a protein that in humans is encoded by the GBX2 gene.-Further reading:...
; GSCGSC (gene)Homeobox protein goosecoid is a protein that in humans is encoded by the GSC gene.-Further reading:-External links:*...
; GSC2; GSX1; GSX2 - HDX; HESX1HESX1Homeobox expressed in ES cells 1, also known as homeobox protein ANF, is a homeobox protein that in humans is encoded by the HESX1 gene.Expression of HEX1 and HESX1 marks the anterior visceral endoderm of the embryo...
; HHEXHHEXHematopoietically-expressed homeobox protein HHEX is a protein that in humans is encoded by the HHEX gene.-Interactions:HHEX has been shown to interact with Promyelocytic leukemia protein.-Further reading:...
; HLX1HLX (gene)H2.0-like homeobox protein is a protein that in humans is encoded by the HLX gene....
; HMBOX1; HMX1; HMX2; HMX3; HNF1A; HNF1B; HOMEZ; HOPXHOPXHomeodomain-only protein is a protein that in humans is encoded by the HOPX gene.-Further reading:... - IRX1IRX1Iroquois-class homeodomain protein IRX-1, also known as Iroquois homeobox protein 1, is a protein that in humans is encoded by the IRX1 gene.- Function :...
; IRX2IRX2Iroquois-class homeodomain protein IRX-2, also known as Iroquois homeobox protein 2, is a protein that in humans is encoded by the IRX2 gene.- Function :...
; IRX3IRX3Iroquois-class homeodomain protein IRX-3, also known as Iroquois homeobox protein 3, is a protein that in humans is encoded by the IRX3 gene.- Function :...
; IRX4IRX4Iroquois-class homeodomain protein IRX-4, also known as Iroquois homeobox protein 4, is a protein that in humans is encoded by the IRX4 gene.- Function :...
; IRX5IRX5Iroquois-class homeodomain protein IRX-5, also known as Iroquois homeobox protein 5, is a protein that in humans is encoded by the IRX5 gene.- Function :...
; IRX6IRX6Iroquois-class homeodomain protein IRX-6, also known as Iroquois homeobox protein 6, is a protein that in humans is encoded by the IRX6 gene.- Function :...
; ISL1ISL1Insulin gene enhancer protein ISL-1 is a protein that in humans is encoded by the ISL1 gene.- Interactions :ISL1 has been shown to interact with Estrogen receptor alpha.-Role in cardiac development:...
; ISL2; ISX - LASS2LASS2LAG1 longevity assurance homolog 2 is a protein that in humans is encoded by the LASS2 gene.-Further reading:...
; LASS3; LASS4; LASS5; LASS6; LBX1LBX1Transcription factor LBX1 is a protein that in humans is encoded by the LBX1 gene.-Further reading:...
; LBX2; LHX1LHX1LIM homeobox 1, also known as LHX1, is a gene.-Further reading:...
; LHX2LHX2LIM/homeobox protein Lhx2 is a protein that in humans is encoded by the LHX2 gene.-Further reading:...
; LHX3LHX3LIM/homeobox protein Lhx3 is a protein that in humans is encoded by the LHX3 gene.- Function :LHX3 encodes a protein of a large protein family, members of which carry the LIM domain, a unique cysteine-rich zinc-binding domain. The encoded protein is a transcription factor that is required for...
; LHX4LHX4LIM/homeobox protein Lhx4 is a protein that in humans is encoded by the LHX4 gene.-Further reading:...
; LHX5; LHX6LHX6LIM/homeobox protein Lhx6 is a protein that in humans is encoded by the LHX6 gene.-Further reading:...
; LHX8; LHX9; LMX1ALMX1ALIM homeobox transcription factor 1, alpha, also known as LMX1A, is a protein which in humans is encoded by the LMX1A gene.- Function :Insulin is produced exclusively by the beta cells in the islets of Langerhans in the pancreas...
; LMX1BLMX1BLIM homeobox transcription factor 1-beta, also known as LMX1B, is a protein which in humans is encoded by the LMX1B gene.- Function :... - MEIS1MEIS1Homeobox protein Meis1 is a protein that in humans is encoded by the MEIS1 gene.-Interactions:MEIS1 has been shown to interact with PBX1 and HOXA9.- External links :...
; MEIS2MEIS2Homeobox protein Meis2 is a protein that in humans is encoded by the MEIS2 gene....
; MEIS3; MEOX1MEOX1Homeobox protein MOX-1 is a protein that in humans is encoded by the MEOX1 gene.-Interactions:MEOX1 has been shown to interact with PAX1 and PAX3.-Further reading:...
; MEOX2MEOX2Homeobox protein MOX-2 is a protein that in humans is encoded by the MEOX2 gene.-Interactions:MEOX2 has been shown to interact with PAX1 and PAX3....
; MIXL1; MKXMKXHomeobox protein Mohawk, also known as iroquois homeobox protein-like 1, is a protein that in humans is encoded by the MKX gene.- Function :...
; MNX1MNX1Motor neuron and pancreas homeobox 1 also known as Homeobox HB9 , is a human gene.It can be associated with Currarino syndrome....
; MSX1MSX1Msh homeobox 1, also known as MSX1, is a protein that in humans is encoded by the MSX1 gene. MSX1 transcripts are not only found in thyrotrope-derived TSH cells, but also in the TtT97 thyrotropic tumor, which is a well differentiated hyperplastic tissue that produces both TSHß- and a-subunits and...
; MSX2 - NANOG; NANOGP1; NANOGP8; NKX2-1; NKX2-2NKX2-2Homeobox protein Nkx-2.2 is a protein that in humans is encoded by the NKX2-2 gene.Homeobox protein Nkx-2.2 contains a homeobox domain and may be involved in the morphogenesis of the central nervous system. This gene is found on chromosome 20 near NKX2-4, and these two genes appear to be duplicated...
; NKX2-3NKX2-3Homeobox protein Nkx-2.3 is a protein that in humans is encoded by the NKX2-3 gene.-Further reading:...
; NKX2-4; NKX2-5NKX2-5Homeobox protein Nkx-2.5 is a protein that in humans is encoded by the NKX2-5 gene.-Interactions:NKX2-5 has been shown to interact with GATA4 and TBX5....
; NKX2-8; NKX3-1NKX3-1Homeobox protein Nkx-3.1 is a protein that in humans is encoded by the NKX3-1 gene.- External links :...
; NKX3-2NKX3-2NK3 homeobox 2 also known as NKX3-2 is a human gene. It is a homolog of bagpipe in Drosophila and therefore also known as Bapx1 . The protein encoded by this gene is a homeo domain containing transcription factor.-Function:NKX3-2 plays a role in the development of the skeleton...
; NKX6-1NKX6-1Homeobox protein Nkx-6.1 is a protein that in humans is encoded by the NKX6-1 gene.- Function :In the pancreas, NKX6.1 is required for the development of beta cells and is a potent bifunctional transcription regulator that binds to AT-rich sequences within the promoter region of target...
; NKX6-2NKX6-2Homeobox protein Nkx-6.2 is a protein that in humans is encoded by the NKX6-2 gene.-Further reading:...
; NKX6-3; NOBOXNOBOXHomeobox protein NOBOX, also known as newborn ovary homeobox protein, is a protein that in humans is encoded by the NOBOX gene.- Function :NOBOX is a homeobox gene that is preferentially expressed in oocytes...
; NOTONotoNoto is a city and comune in the Province of Syracuse, Sicily . Its located 32 km southwest of the city of Syracuse at the foot of the Iblean Mountains and gives its name to the surrounding valley, Val di Noto... - ONECUT1; ONECUT2; ONECUT3; OTP; OTX1OTX1Homeobox protein OTX1 is a protein that in humans is encoded by the OTX1 gene....
; OTX2 - PAX3PAX3PAX3 is a gene that belongs to the paired box family of transcription factors. This gene was formerly known as splotch. PAX3 has been identified with ear, eye and facial development. Mutations in it can cause Waardenburg syndrome types 1 and 3...
; PAX4PAX4Paired box gene 4, also known as PAX4, is a protein which in humans is encoded by the PAX4 gene.- Function :This gene is a member of the paired box family of transcription factors. Members of this gene family typically contain a paired box domain, an octapeptide, and a paired-type homeodomain...
; PAX6PAX6Paired box protein Pax-6 also known as aniridia type II protein or oculorhombin is a protein that in humans is encoded by the PAX6 gene.- Function :PAX6 is a member of the Pax gene family...
; PAX7PAX7Paired box protein Pax-7 is a protein that in humans is encoded by the PAX7 gene.- Function :Pax-7 plays a role in neural crest development and gastrulation, and it is an important factor in the expression of neural crest markers such as Slug, Sox9, Sox10 and HNK-1....
; PBX1PBX1Pre-B-cell leukemia transcription factor 1 is a protein that in humans is encoded by the PBX1 gene.-Interactions:PBX1 has been shown to interact with HOXB1, MEIS1 and HOXB7.-Further reading:...
; PBX2PBX2Pre-B-cell leukemia transcription factor 2 is a protein that in humans is encoded by the PBX2 gene.-Further reading:...
; PBX3PBX3Pre-B-cell leukemia transcription factor 3 is a protein that in humans is encoded by the PBX3 gene.-Further reading:...
; PBX4; PDX1Pdx1Pdx1 , also known as insulin promoter factor 1, is a transcription factor necessary for pancreatic development and β-cell maturation...
; PHOX2APHOX2APaired mesoderm homeobox protein 2A is a protein that in humans is encoded by the PHOX2A gene.- External links :* * *...
; PHOX2BPHOX2BPaired-like homeobox 2b , also known as neuroblastoma Phox , is a protein that in humans is encoded by the PHOX2B gene located on chromosome 4....
; PITX1PITX1Pituitary homeobox 1 is a protein that in humans is encoded by the PITX1 gene.-Interactions:PITX1 has been shown to interact with Pituitary-specific positive transcription factor 1.-Further reading:...
; PITX2PITX2Paired-like homeodomain transcription factor 2 also known as pituitary homeobox 2 is a protein that in humans is encoded by the PITX2 gene.- Function :...
; PITX3PITX3Pituitary homeobox 3 is a protein that in humans is encoded by the PITX3 gene.-Further reading:...
; PKNOX1PKNOX1Homeobox protein PKNOX1 is a protein that in humans is encoded by the PKNOX1 gene.-Further reading:...
; PKNOX2; POU1F1; POU2F1POU2F1POU domain, class 2, transcription factor 1 is a protein that in humans is encoded by the POU2F1 gene.-Interactions:POU2F1 has been shown to interact with SNAPC4, Ku80, Glucocorticoid receptor, Sp1 transcription factor, NPAT, POU2AF1, Host cell factor C1, TATA binding protein, RELA, Nuclear...
; POU2F2; POU2F3POU2F3POU domain, class 2, transcription factor 3 is a protein that in humans is encoded by the POU2F3 gene.-Further reading:...
; POU3F1POU3F1POU domain, class 3, transcription factor 1 is a protein that in humans is encoded by the POU3F1 gene....
; POU3F2POU3F2POU domain, class 3, transcription factor 2 is a protein that in humans is encoded by the POU3F2 gene....
; POU3F3; POU3F4POU3F4POU domain, class 3, transcription factor 4 is a protein that in humans is encoded by the POU3F4 gene. Mutations in POU3F4, located on the X chromosome, may cause deafness. The role of POU3F4 in the hypothalamus where it was originally described remains unknown....
; POU4F1POU4F1POU domain, class 4, transcription factor 1 also known as brain-specific homeobox/POU domain protein 3A , homeobox/POU domain protein RDC-1 or Oct-T1 is a protein that in humans is encoded by the POU4F1 gene....
; POU4F2POU4F2POU domain, class 4, transcription factor 2 is a protein that in humans is encoded by the POU4F2 gene.-Interactions:POU4F2 has been shown to interact with Estrogen receptor alpha....
; POU4F3POU4F3POU domain, class 4, transcription factor 3 is a protein that in humans is encoded by the POU4F3 gene....
; POU5F1; POU5F1P1; POU5F1P4; POU5F2; POU6F1; POU6F2; PROP1PROP1Homeobox protein prophet of Pit-1 is a protein that in humans is encoded by the PROP1 gene.- External links :*...
; PRRX1PRRX1Paired mesoderm homeobox protein 1 is a protein that in humans is encoded by the PRRX1 gene....
; PRRX2PRRX2Paired mesoderm homeobox protein 2 is a protein that in humans is encoded by the PRRX2 gene.-Further reading:... - RAX; RAX2; RHOXF1RHOXF1Rhox homeobox family member 1 is a protein that in humans is encoded by the RHOXF1 gene.-Further reading:...
; RHOXF2 - SATB1SATB1SATB1 is a protein which in humans is encoded by the SATB1 gene.- Function :SATB1, the global chromatin organizer and transcription factor, has emerged as a key factor integrating higher-order chromatin architecture with gene regulation...
; SATB2SATB2Special AT-rich sequence-binding protein 2 also known as DNA-binding protein SATB2 is a protein that in humans is encoded by the SATB2 gene. SATB2 is a DNA-binding protein that specifically binds nuclear matrix attachment regions and is involved in transcriptional regulation and chromatin...
; SEBOX; SHOXShoxShox is an arcade, rally game, it is available on the PlayStation 2 console in the USA and Europe.-Gameplay:Shox is based around the concept of a shockwave that appears in front of the player's car if they successfully pass, within the time limit, through three points on a track...
; SHOX2SHOX2Short stature homeobox 2, also known as homeobox protein Og12X or paired-related homeobox protein SHOT, is a protein that in humans is encoded by the SHOX2 gene.- Function :...
; SIX1SIX1Homeobox protein SIX1 is a protein that in humans is encoded by the SIX1 gene.-Interactions:SIX1 has been shown to interact with EYA1 and MDFI.-Further reading:...
; SIX2SIX2Homeobox protein SIX2 is a protein that in humans is encoded by the SIX2 gene.-Further reading:...
; SIX3SIX3Homeobox protein SIX3 is a protein that in humans is encoded by the SIX3 gene.-Interactions:SIX3 has been shown to interact with TLE1 and Neuron-derived orphan receptor 1.-External links:*...
; SIX4SIX4Homeobox protein SIX4 is a protein that in humans is encoded by the SIX4 gene.-Further reading:...
; SIX5SIX5Homeodomain transcription factor is a protein that in humans is encoded by the SIX5 gene.-External links:...
; SIX6 - TGIF1; TGIF2TGIF2Homeobox protein TGIF2 is a protein that in humans is encoded by the TGIF2 gene.-Further reading:...
; TGIF2LX; TGIF2LY; TLX1TLX1T-cell leukemia homeobox protein 1 is a protein that in humans is encoded by the TLX1 gene.-Interactions:TLX1 has been shown to interact with PPP1CC, PPP2CB and PPP2CA.-Further reading:...
; TLX2TLX2T-cell leukemia homeobox protein 2 is a protein that in humans is encoded by the TLX2 gene.-Further reading:...
; TLX3TLX3T-cell leukemia homeobox protein 3 is a protein that in humans is encoded by the TLX3 gene.-Further reading:...
; TSHZ1; TSHZ2; TSHZ3TSHZ3Teashirt homolog 3 is a protein that in humans is encoded by the TSHZ3 gene. In mice, it is a necessary part of the neural circuitry that controls breathing... - UNCX; VAX1VAX1Ventral anterior homeobox 1 is a protein that in humans is encoded by the VAX1 gene.- Function :This gene appears to influence the development in humans of the forebrain...
; VAX2; VENTX; VSX1VSX1Visual system homeobox 1 is a protein that in humans is encoded by the VSX1 gene.The protein encoded by this gene contains a paired-like homeodomain and binds to the core of the locus control region of the red/green visual pigment gene cluster. The encoded protein may regulate expression of the...
; VSX2VSX2Visual system homeobox 2 is a protein that in humans is encoded by the VSX2 gene.-Further reading:... - ZEB1ZEB1Zinc finger E-box-binding homeobox 1 is a protein that in humans is encoded by the ZEB1 gene.TCF8 encodes a human zinc finger transcription factor that represses T-lymphocyte-specific IL2 gene expression by binding to a negative regulatory domain 100 nucleotides 5-prime of the IL2 transcription...
; ZEB2ZEB2Zinc finger E-box-binding homeobox 2 is a protein that in humans is encoded by the ZEB2 gene.-Function:The SMADIP1 gene is a member of the delta-EF1 /Zfh1 family of 2-handed zinc finger/homeodomain proteins...
; ZFHX2; ZFHX3; ZFHX4; ZHX1ZHX1Zinc fingers and homeoboxes protein 1 is a protein that in humans is encoded by the ZHX1 gene.-Further reading:...
Mutations
Mutations to homeobox genes can produce easily visible phenotypicPhenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
changes.
Two examples of homeobox mutations in the above-mentioned fruit fly are legs where the antennae should be (antennapedia
Antennapedia
Antennapedia is a HOM-C gene first discovered in Drosophila which controls the formation of legs during development. Loss-of-function mutations in the regulatory region of this gene result in the development of the second leg pair into ectopic antennae...
), and a second pair of wings.
Duplication of homeobox genes can produce new body segments, and such duplications are likely to have been important in the evolution
Evolution
Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...
of segmented animals. However, Hox genes typically determine the identity of body segments.
Interestingly, there is one insect
Insect
Insects are a class of living creatures within the arthropods that have a chitinous exoskeleton, a three-part body , three pairs of jointed legs, compound eyes, and two antennae...
family, the xyelid sawflies
Xyelidae
The Xyelidae is a small family of sawflies known from fewer than 50 extant species in 5 genera, but with an extensive fossil record; they are the oldest fossil Hymenoptera, dating back to the Triassic, some 200 million years ago. Most species occur in the Northern Hemisphere, especially in boreal...
, in which both the antennae
Antenna (biology)
Antennae in biology have historically been paired appendages used for sensing in arthropods. More recently, the term has also been applied to cilium structures present in most cell types of eukaryotes....
and mouthparts are remarkably leg-like in structure. This is not uncommon in arthropods as all arthropod appendages are homologous.
Regulation
The regulation of Hox genes is highly complex and involves reciprocal interactions, mostly inhibitory. 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...
is known to use the Polycomb
Polycomb-group proteins
Polycomb-group proteins are a family of proteins first discovered in fruit flies that can remodel chromatin such that epigenetic silencing of genes takes place...
and Trithorax Complexes to maintain the expression of Hox genes after the down-regulation of the pair-rule and gap genes that occurs during larval development. Polycomb-group proteins
Polycomb-group proteins
Polycomb-group proteins are a family of proteins first discovered in fruit flies that can remodel chromatin such that epigenetic silencing of genes takes place...
can silence the HOX genes by modulation of chromatin
Chromatin
Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...
structure.