DAAM2

Official Full Name

dishevelled associated activator of morphogenesis 2

Organism

Homo sapiens

GeneID

23500

Background

Predicted to enable actin binding activity and small GTPase binding activity. Involved in several processes, including podocyte cell migration; regulation of actin filament polymerization; and regulation of filopodium assembly. Located in extracellular exosome. Implicated in familial nephrotic syndrome. [provided by Alliance of Genome Resources, Feb 2025]

Synonyms

NPHS24; dJ90A20A.1;

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Detailed Information

Derangement-associated activator of morphogenesis 2 (DAAM2) is a key regulator of cytoskeletal dynamics and cellular morphogenesis. DAAM2 plays a critical role in various cellular processes such as cell migration, adhesion and tissue morphogenesis. In addition, DAAM2 dysregulation affects diseases such as cancer and neurological disorders.

DAAM2 Is Involved in Cytoskeletal Remodeling

The DAAM2 gene is a crucial player in cell biology, with a significant role in cell skeleton remodeling. Cell skeleton, composed of microfilaments and microtubules, is a dynamic network that shapes cell architecture and participates in various cellular processes such as cell division, migration, and polarization. DAAM2 participates in cell skeleton remodeling through its interaction with multiple proteins involved in cytoskeletal dynamics. It binds to and activates the RhoGTPase family member RhoA, which plays a pivotal role in regulating actin cytoskeleton. Activation of RhoA leads to the formation of actin stress fibers and focal adhesions, promoting cell contractility and migration. Additionally, DAAM2 interacts with the regulatory protein phosphatidylinositol 3-kinase (PI3K), which is involved in the formation of lamellipodia and filopodia. These protrusions facilitate cell movement and exploration of the extracellular environment. DAAM2 also interacts with the tumor suppressor protein APC (adenomatous polyposis coli), promoting the assembly of microtubules and enhancing cell polarization. DAAM2 plays a key role in cell skeleton remodeling by regulating the activity of Rho GTPases and PI3K, as well as interacting with other proteins involved in cytoskeletal organization. This involvement in cell skeleton remodeling allows cells to adapt to their environment and execute diverse biological functions.

DAAM2-related Signaling Pathways

DAAM2 functions as a scaffold protein that interacts with multiple signaling molecules and effector proteins to regulate signaling pathways involved in tissue development and homeostasis. One of its key roles is in the activation of the Wnt signaling pathway, a crucial pathway responsible for embryonic development and adult tissue maintenance. By modulating Wnt signaling, DAAM2 contributes to the regulation of cell fate decisions, tissue patterning, and cell differentiation.

In addition, DAAM2 is involved in the regulation of other signaling pathways, such as Notch and Hedgehog, which further expands its functional repertoire. Notch signaling, for instance, plays a vital role in cell fate determination, cell proliferation, and tissue repair, while Hedgehog signaling is essential for cell proliferation and differentiation in various tissues.

DAAM2 and Tumors

(DAAM2) gene has recently emerged as a potential player in cancer development. This gene is involved in the regulation of cell morphology and motility, playing a crucial role in tissue development and homeostasis. Alterations in DAAM2 expression have been linked to various cancers, including breast, colon, and pancreatic cancer. DAAM2 can promote cancer cell invasion and metastasis by regulating cell polarity and cytoskeletal dynamics. It interacts with other signaling molecules like Wnt, Notch, and Hedgehog, influencing the transcription of target genes that control cell growth and differentiation. Inhibition of DAAM2 expression or activity has been demonstrated to suppress tumorigenesis and tumor progression.Aberrant DAAM2 expression has been associated with cancer stem cell properties, which contribute to treatment resistance and relapse. As such, DAAM2 represents a promising therapeutic target for the prevention and treatment of cancer. Researchers are currently exploring novel DAAM2-targeting strategies, including small molecules and antibodies, to interfere with its function and halt cancer progression.

References:

Wang CY, Zuo Z, Jo J, Kim KI, Madamba C, Ye Q, Jung SY, Bellen HJ, Lee HK. Daam2 phosphorylation by CK2α negatively regulates Wnt activity during white matter development and injury. Proc Natl Acad Sci U S A. 2023 Aug 29;120(35):e2304112120. doi: 10.1073/pnas.2304112120. Epub 2023 Aug 22. PMID: 37607236; PMCID: PMC10469030.
Cristobal CD, Wang CY, Zuo Z, Smith JA, Lindeke-Myers A, Bellen HJ, Lee HK. Daam2 Regulates Myelin Structure and the Oligodendrocyte Actin Cytoskeleton through Rac1 and Gelsolin. J Neurosci. 2022 Mar 2;42(9):1679-1691. doi: 10.1523/JNEUROSCI.1517-21.2022. Epub 2022 Jan 31. PMID: 35101966; PMCID: PMC8896627.

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