GATA1
Encyclopedia
Erythroid transcription factor also known as GATA-binding factor 1 or GATA-1 is a protein
that in humans is encoded by the GATA1 gene
.
GATA-1 is a member of the GATA transcription factor
family and is involved in cell growth
and cancer
. This protein plays a role in erythroid development by regulating the switch of fetal hemoglobin
to adult hemoglobin. Mutations in this gene have been associated with X-linked dyserythropoietic anemia
and thrombocytopenia
.
(platelet
producing cell) development and mice without GATA1 die as embryos. It helps transcribe the α-spectrin
structural protein which is critical for the shape of red blood cells.
GATA-1 has been found to enhance the transcription rates of the α-spectrin
gene by up to 100 fold in humans.
DNA binding domain. The N-finger, named for being near the N-terminal also binds DNA and a cofactor
named FOG1 (friend of GATA). The Activation Domain is responsible for GATA1's strong transcriptional activation. The gene for GATA1 is on the X-chromosome.
(DS)-associated acute megakaryoblastic leukemia
(AMKL). While AMKL is typically associated with the (1;22) translocation and expression of a mutant fusion protein, the genetic alterations that promote individuals with DS-AMKL are related to the GATA1 mutations, and the formation of a truncated transcription factor (GATA1s).
The same mutations in exon 2 of GATA1 present in almost all Down Syndrome-associated transient myeloproliferative disorder (TMD) or transient leukemia (TL), a precursor condition that evolves into AMKL in 30% of patients, that as many as 10% of Down Syndrome children may develop. The encidence for the GATA1 mutation in about 4% of Down Syndrome patients, but less than 10% of those with the mutation developed AMKL. This mutation is present in the fetus, suggesting an early role in leukemogenesis. In addition to screening for TL, a GATA1 mutation at birth might serve as a bio-marker for an increased risk of DS-related AMKL.
with HDAC1
, Histone deacetylase 5
, Zinc finger and BTB domain-containing protein 16
, LMO2
, HDAC4
, HDAC3
, FLI1
, ZFPM2
and TAL1
.
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...
that in humans is encoded by the GATA1 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...
.
GATA-1 is a member of the GATA transcription factor
GATA transcription factor
GATA transcription factors are a family of transcription factors characterized by their ability to bind to the DNA sequence "GATA".-Genes:* GATA1 * GATA2 * GATA3 * GATA4 * GATA5 * GATA6...
family and is involved in cell growth
Cell growth
The term cell growth is used in the contexts of cell development and cell division . When used in the context of cell division, it refers to growth of cell populations, where one cell grows and divides to produce two "daughter cells"...
and cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
. This protein plays a role in erythroid development by regulating the switch of fetal hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
to adult hemoglobin. Mutations in this gene have been associated with X-linked dyserythropoietic anemia
Congenital dyserythropoietic anemia
Congenital dyserythropoietic anemia is a rare blood disorder, similar to the thalassemias. CDA is one of many types of anemia, characterized by ineffective erythropoiesis, and resulting from a decrease in the number of red blood cells in the body and a less than normal quantity of hemoglobin in...
and thrombocytopenia
Thrombocytopenia
Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
.
Function
GATA-1 is essential for erythroid (red blood cell) and megakaryocyticMegakaryocyte
The megakaryocyte is a bone marrow cell responsible for the production of blood thrombocytes , which are necessary for normal blood clotting...
(platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
producing cell) development and mice without GATA1 die as embryos. It helps transcribe the α-spectrin
Spectrin
Spectrin is a cytoskeletal protein that lines the intracellular side of the plasma membrane of many cell types in pentagonal or hexagonal arrangements, forming a scaffolding and playing an important role in maintenance of plasma membrane integrity and cytoskeletal structure...
structural protein which is critical for the shape of red blood cells.
GATA-1 has been found to enhance the transcription rates of the α-spectrin
Spectrin
Spectrin is a cytoskeletal protein that lines the intracellular side of the plasma membrane of many cell types in pentagonal or hexagonal arrangements, forming a scaffolding and playing an important role in maintenance of plasma membrane integrity and cytoskeletal structure...
gene by up to 100 fold in humans.
Structure
The molecule contains three domains: the C-finger, the N-finger, and the Activation Domain. The C-finger, named for being near the C-terminal, has a Zinc fingerZinc finger
Zinc fingers are small protein structural motifs that can coordinate one or more zinc ions to help stabilize their folds. They can be classified into several different structural families and typically function as interaction modules that bind DNA, RNA, proteins, or small molecules...
DNA binding domain. The N-finger, named for being near the N-terminal also binds DNA and a cofactor
Cofactor (biochemistry)
A cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. These proteins are commonly enzymes, and cofactors can be considered "helper molecules" that assist in biochemical transformations....
named FOG1 (friend of GATA). The Activation Domain is responsible for GATA1's strong transcriptional activation. The gene for GATA1 is on the X-chromosome.
Disease linkage
Mutations in exon 2 of the GATA1 gene are present in almost all cases of Down syndromeDown syndrome
Down syndrome, or Down's syndrome, trisomy 21, is a chromosomal condition caused by the presence of all or part of an extra 21st chromosome. It is named after John Langdon Down, the British physician who described the syndrome in 1866. The condition was clinically described earlier in the 19th...
(DS)-associated acute megakaryoblastic leukemia
Acute megakaryoblastic leukemia
Acute megakaryoblastic leukemia is a form of leukemia where a majority of the blasts are megakaryoblastic.It is classified under M7 in the French-American-British classification....
(AMKL). While AMKL is typically associated with the (1;22) translocation and expression of a mutant fusion protein, the genetic alterations that promote individuals with DS-AMKL are related to the GATA1 mutations, and the formation of a truncated transcription factor (GATA1s).
The same mutations in exon 2 of GATA1 present in almost all Down Syndrome-associated transient myeloproliferative disorder (TMD) or transient leukemia (TL), a precursor condition that evolves into AMKL in 30% of patients, that as many as 10% of Down Syndrome children may develop. The encidence for the GATA1 mutation in about 4% of Down Syndrome patients, but less than 10% of those with the mutation developed AMKL. This mutation is present in the fetus, suggesting an early role in leukemogenesis. In addition to screening for TL, a GATA1 mutation at birth might serve as a bio-marker for an increased risk of DS-related AMKL.
Interactions
GATA1 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with HDAC1
HDAC1
Histone deacetylase 1 is an enzyme that in humans is encoded by the HDAC1 gene.-Interactions:HDAC1 has been shown to interact with RAD9A, DNMT3L, MTA1, FKBP3, CDC20, CDH1, Host cell factor C1, BUB3, Nuclear receptor co-repressor 2, IKZF1, Prohibitin, EVI1, DDX5, DNMT3A, Mothers against...
, Histone deacetylase 5
Histone deacetylase 5
Histone deacetylase 5 is an enzyme that in humans is encoded by the HDAC5 gene.-Interactions:Histone deacetylase 5 has been shown to interact with Zinc finger and BTB domain-containing protein 16, BCL6, CBX5, YWHAQ, Myocyte-specific enhancer factor 2A, Nuclear receptor co-repressor 1, IKZF1,...
, Zinc finger and BTB domain-containing protein 16
Zinc finger and BTB domain-containing protein 16
Zinc finger and BTB domain-containing protein 16 is a protein that in humans is encoded by the ZBTB16 gene.-Function:This gene is a member of the Krueppel C2H2-type zinc-finger protein family and encodes a zinc finger transcription factor that contains nine Kruppel-type zinc finger domains at the...
, LMO2
LMO2
LIM domain only 2 , also known as LMO2, is a protein which in humans is encoded by the LMO2 gene.- Function :LMO2 encodes a cysteine-rich, two LIM domain protein that is required for yolk sac erythropoiesis. The LMO2 protein has a central and crucial role in hematopoietic development and is highly...
, HDAC4
HDAC4
Histone deacetylase 4, also known as HDAC4, is a protein which in humans is encoded by the HDAC4 gene.- Function :Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects...
, HDAC3
HDAC3
Histone deacetylase 3 is an enzyme that in humans is encoded by the HDAC3 gene.-Interactions:HDAC3 has been shown to interact with HDAC9, HDAC7A, Retinoblastoma protein, RBBP4, Testicular receptor 2, MAP3K7IP2, Peroxisome proliferator-activated receptor delta, GTF2I, Histone deacetylase 5, RELA,...
, FLI1
FLI1
Friend leukemia integration 1 transcription factor , also known as proto-oncogene Fli-1 or transcription factor ERGB, is a protein that in humans is encoded by the human FLI1 gene. - Function :...
, ZFPM2
ZFPM2
Zinc finger protein ZFPM2 is a protein that in humans is encoded by the ZFPM2 gene.-Interactions:ZFPM2 has been shown to interact with GATA4, GATA1 and CTBP2.-Further reading:...
and TAL1
TAL1
T-cell acute lymphocytic leukemia protein 1 is a protein that in humans is encoded by the TAL1 gene.The protein encoded by TAL1 is a basic-helix-loop-helix transcription factor.-Interactions:...
.