GATAD2A

Fig1. Schematic description of the NuRD complex. (Morgan P Torchy, 2015)

What is GATAD2A protein?

GATAD2A gene (GATA zinc finger domain containing 2A) is a protein coding gene which situated on the short arm of chromosome 19 at locus 19p13. GATAD2A is a protein associated with nucleosome remodeling and deacetylation (NuRD) complex. This NuRD complex plays an important role in regulating gene expression by altering the structure of chromatin to promote or inhibit transcription of specific genes. By interacting with MBD2, GATAD2A helps the NuRD complex to locate specific genomic regions, thereby regulating the expression of downstream target genes. GATAD2A active motifs refer to its functional domains that enable it to perform its role within the NuRD complex including GATA Zinc Finger Domai, Proline-Rich PPPLφ Motifs, CR1&2. The GATAD2A protein is consisted of 633 amino acids and GATAD2A molecular weight is approximately 68.1 kDa.

What is the function of GATAD2A protein?

GATAD2A protein is a protein associated with NuRD complex. It plays an important role in regulating gene expression, chromatin remodeling, DNA repair, and induced pluripotent stem cell (iPSC) formation. By interacting with MBD2, GATAD2A helps the NuRD complex to locate specific genomic regions, thereby regulating the expression of downstream target genes. In addition, GATAD2A is also involved in cell cycle control, cell differentiation and cell metabolism.

GATAD2A Related Signaling Pathway

GATAD2A protein is involved in several key signaling pathways, including as part of NuRD complex, affecting gene expression regulation and chromatin remodeling; Participate in HDAC signaling pathway, regulate chromatin status through histone deacetylation; Involved in cell cycle and proliferation regulation; It plays a role in immune response and may affect immune-related signaling pathways. Signaling pathway involved in cell fate determination with GATA transcription factor family members; Heterochromatin status and pluripotent gene expression are affected by kinases such as MAP2K6 in MAPK signaling pathway. As well as sharing chromatin regions with TRPS1, hinting at its role in specific signaling pathways.

GATAD2A Related Diseases

GATAD2A deficiency can lead to beta-thalassemia by affecting the formation of NuRD complexes contained in methyl-binding domain protein 2 (MBD2). GATAD2A is associated with neurodevelopmental disorders, and mutations in it may lead to neurodevelopment-related diseases. The mutation of GATA2 gene is associated with primary MDS in children, which is manifested by changes in clinical characteristics and molecular biological characteristics. Mutations in the GATA2 gene have been linked to a variety of immune disorders, including GATA2 deficiency syndrome (G2DS), a rare autosomal dominant disorder that presents with myeloid malignancy and immune deficiency symptoms. Related blood diseases also include acute myeloid leukemia (AML).

Bioapplications of GATAD2A

GATAD2A antibodies can be used in immunoprecipitation experiments to study GATAD2A's interactions with other proteins and its function within cells. Similarly, other G antibodies can be developed for Western Blot, immunohistochemistry (IHC), immunofluorescence (IF), etc. The study of GATAD2A-related diseases is helpful to develop clinical diagnostic markers and therapeutic targets, and provide basis for early diagnosis and treatment of diseases.

Case Study 1: Tianqi Yu, 2019

Circular RNAs (circRNAs) play critical roles in various diseases. However, whether and how circular RNA regulates influenza A virus (IAV) infection is unknown. Here, researchers studied the role of circular RNA GATA Zinc Finger Domain Containing 2A (circ-GATAD2A) in the replication of IAV H1N1 in A549 cells. Circ-GATAD2A was formed upon H1N1 infection. Knockdown of circ-GATAD2A in A549 cells enhanced autophagy and inhibited H1N1 replication. By contrast, overexpression of circ-GATAD2A impaired autophagy and promoted H1N1 replication. Similarly, knockout of vacuolar protein sorting 34 (VPS34) blocked autophagy and increased H1N1 replication. However, the expression of circ-GATAD2A could not further enhance H1N1 replication in VPS34 knockout cells.

Fig1. Detection of circ-GATAD2A by real-time PCR in H1N1-infected A549 cells at different doses.

Fig2. Impacts of H1N1 infection on autophagy in several cells.

Case Study 2: Nofar Mor, 2018

Mbd3 was previously identified as an inhibitor for deterministic induced pluripotent stem cell (iPSC) reprogramming. NuRD can assume multiple mutually exclusive conformations, and it remains unclear whether this deterministic phenotype can be attributed to a specific Mbd3/NuRD subcomplex. Moreover, since complete ablation of Mbd3 blocks somatic cell proliferation, researchers aimed to explore functionally relevant alternative ways to neutralize Mbd3-dependent NuRD activity. They identify Gatad2a, a NuRD-specific subunit, whose complete deletion specifically disrupts Mbd3/NuRD repressive activity on the pluripotency circuitry during iPSC differentiation and reprogramming without ablating somatic cell proliferation. Inhibition of Gatad2a facilitates deterministic murine iPSC reprogramming within 8 days. They validate a distinct molecular axis, Gatad2a-Chd4-Mbd3, within Mbd3/NuRD as being critical for blocking reestablishment of naive pluripotency and further highlight signaling-dependent and post-translational modifications of Mbd3/NuRD that influence its interactions and assembly.

Fig3. Representative flow cytometry measurements of ΔPE-Oct4-GFP reactivation dynamics.

Fig4. Flag-Mbd3 CoIP in Gatad2a-WT and Gatad2a-KO cells.

GATAD2A has several biochemical functions, for example, contributes_to RNA polymerase II regulatory region sequence-specific DNA binding,protein binding,protein binding, bridging. Some of the functions are cooperated with other proteins, some of the functions could acted by GATAD2A itself. We selected most functions GATAD2A had, and list some proteins which have the same functions with GATAD2A. You can find most of the proteins on our site.

GATAD2A has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with GATAD2A here. Most of them are supplied by our site. Hope this information will be useful for your research of GATAD2A.

HDAC1;CDK2AP1;HDAC2;His2B:CG33868;His3:CG33857;His4:CG33869;His2A:CG33808;KAT2B;MBD2;PAK4;q99ib8-pro_0000045599;Cdk2ap1;PTBP3;MBD3;KRAS;Junb