SMURF1 Antibodies

E3 ubiquitin-protein ligase SMURF1 (SMURF1)

E3 ubiquitin-protein ligase that acts as a negative regulator of BMP signaling pathway. Mediates ubiquitination and degradation of SMAD1 and SMAD5, 2 receptor-regulated SMADs specific for the BMP pathway.

Promotes ubiquitination and subsequent proteasomal degradation of TRAF family members and RHOA. Promotes ubiquitination and subsequent proteasomal degradation of MAVS (PubMed:23087404).

Gene Information

Human
Gene Name:	SMURF1
Uniprot:	Q9HCE7
Entrez:	57154

Family

Belongs to:
No superfamily

Alternative Names

E3 ubiquitin ligase SMURF1; EC 6.3.2; EC 6.3.2.-; hSMURF1; KIAA1625; KIAA1625E3 ubiquitin-protein ligase SMURF1; SMAD specific E3 ubiquitin protein ligase 1; SMAD ubiquitination regulatory factor 1; Smad-specific E3 ubiquitin ligase 1; SMAD-specific E3 ubiquitin-protein ligase 1; SMURF1

Molecular Weight

Mass (kDA):
86.114 kDA

Genomic Context

Human
Location:	7q22.1
Sequence:	7; NC_000007.14 (99027435..99144118, complement)

Tissue Specificity

Expressed in melanocytes (PubMed:23999003).

Subcellular Localizations

Cytoplasm. Cell membrane; Peripheral membrane protein; Cytoplasmic side.

Diseases

• Malignant Neoplasms
• Neoplasms
• Fibrosis
• Inflammation
• Malignant Neoplasm Of Pancreas
• Cell Invasion
• Neoplasm Metastasis
• Carcinoma
• Pancreatic Neoplasm
• Protrusion
• Tissue Adhesions
• Hypoxia
• Adenocarcinoma

• Bone Diseases
• Osteopenia
• Neoplasm Invasiveness
• Osteoporosis
• Nervousness
• Cell Transformation, Neoplastic
• Kidney Diseases

Interacting Proteins

• CHEK1
• FBXL15
• ING2
• KLF2
• PLEKHO1

• PSME3
• RHOA
• RHOB
• SMAD1
• SMAD7

• TRAF4

Pathways

• Osteoblast Differentiation
• Cell Migration
• Cell Proliferation
• Cell Growth
• Cell Differentiation
• Localization
• Rna Interference
• Pathogenesis
• Proteolysis
• Nuclear Export
• Cell Motility
• Bone Resorption
• Secretion

• Cell Adhesion
• Lung Development
• Chondrocyte Differentiation
• Brain Development
• Mesenchymal Cell Differentiation
• Cell Cycle
• Transdifferentiation

PTMs

• Ubiquitination
• Phosphorylation
• Cleavage

• Acetylation
• Deacetylation
• Dephosphorylation

For details, visit:
bosterbio.com/bosterbio-gene-info-cards/SMURF1

Best Uses Of The SMURF1 Marker

The SMURF1 marker is one of the most promising biomarkers for predicting overall and disease-free survival in ccRCC patients. SMURF1 has been identified as a molecule that mediates Kindlin-2 polyubiquitination, regulates integrin activation and inhibits FA formation. This article explains the biomarker's functions.

SMURF1 is a promising biomarker for predicting overall and disease-free survival of ccRCC patients

SMURF1 is a well-known E3 ubiquitin ligase that targets substrate proteins for ubiquitination and proteasomal degradation. While its clinical significance in human malignancies is not known, it has been shown to be a viable biomarker in cancer. Recently, a study revealed that SMURF1 expression was elevated in 68 GC patients. Compared to tumor-adjacent tissue, SMURF1 expression correlated with large tumor size and advanced TNM stage. Further, the expression of SMURF1 was associated with a poor prognosis.

The results of this study suggest that SMURF1 may be a promising biomarker for predicting the overall and disease-free survival of a subset of patients with ccRCC. This study also showed a positive association between SMURF1 expression and tumor-infiltrating immune cells, which may indicate that SMURF1 is a biomarker for predicting the overall and disease-free survival of patients with ccRCC.

The authors analyzed data on a population of ccRCC patients and identified a signature based on SMURF1 and 10 other GRGs. This new signature was associated with a lower overall survival rate in ccRCC patients who were in the high-risk group. The established signature was independently predictive for OS and disease-free survival in multivariate Cox regression analyses.

The study analyzed a panel of SMURF1-mutated RNA (SmuRF1) and p53-mutated mRNAs in the TCGA. The association between SMURF1-mutated DNA and ccRCC was found to be statistically significant. Further investigation is required to determine whether SMURF1 is a reliable biomarker for predicting overall and disease-free survival of ccRCC patients.

It mediates Kindlin-2 polyubiquitination

The E3 ubiquitin ligase SMURF1 regulates the amount of Kindlin-2 protein in cells by selectively promoting its degradation. In cells, Smurf1 inhibits b1 integrin activation, aIIbb3, and b1 integrin activation in Chinese hamster ovarian cells. However, it is not clear what the exact mechanism is that regulates Kindlin-2 degradation.

SUMOs are covalently bound to lysine residues in proteins. This process occurs under the combined action of SUMO E1 and SUMO E2, which are ubiquitin-like molecules. Sumoylation of Smurf2 increases the protein's stability and enhances its ubiquitin ligase activity. The Smurf1 family of proteins functions to promote cell proliferation and migration.

SMURF1 interacts with other proteins to promote their ubiquitination. It also plays a role in inhibiting TGF-b signaling. In addition to polyubiquitination, Smurf1 mediates autoneddylation. Neddylation reduces the steady-state levels of proteins, modifying their localization and functions. The UBC12 protein mediates the Neddylation events by interacting with the Smurf ubiquitin ligase.

Human Smurf1 colocalizes with Fbxo3 in a cell culture. The two proteins share about 80% of their amino acid sequence, and the WW domain interacts primarily with PPXY motifs and phospho-serine/threonine residues. Smurf1 also contains a HECT domain, which facilitates the transfer of ubiquitin from one protein to another.

Posttranslational modifications of Smurfs play a pivotal role in cancer biology. They regulate their substrates by modulating the activity of other ubiquitin ligases. This in turn controls tumor-related cellular processes. However, Smurfs are highly regulated by many upstream regulatory factors. Some regulatory elements enhance Smurf1/2 activity by interacting with other proteins, while others block the binding of Smurf to substrates.

It regulates integrin activation

A recent study has shown that SMURF1 is a direct inhibitor of RUNX2, which regulates integrin activation and degradation. Additionally, Smurf1 interacts with the carboxy terminus of SMAD proteins and negatively regulates RUNX2 protein stability. These findings demonstrate the potential of SMURF1 to help researchers better understand the role of integrins in bone formation.

It inhibits FA formation

SMURF1 is an indispensable component of the BMP signaling pathway that regulates bone formation. It negatively regulates bone formation by binding with Smad1 and inhibiting osteoblast differentiation. The PY motif on Smurf1 and Runx2 is required for osteoblast differentiation. In addition, Smurf1 mediates ubiquitination and degradation of the protein. Smurf1 inhibits FA formation through the BMP signaling pathway.

SMURF1 targets UVRAG, a protein that is required for autophagy oscillation and fusion of the autophagosome and lysosome. USP8 binds to UVRAG and removes its K63-linked ubiquitin chain, enhancing binding to the LC3. Lastly, SMURF1 interacts with the protein ULK1, a ubiquitin-specific peptidase.

Another protein that inhibits FA formation is talin1. Talin1 is a naturally occurring barwnik that plays a role in focal adhesion dynamics. The SMURF1 marker in Boster Bio's SMURF1 assays will provide evidence of this interaction. Ultimately, it will help scientists understand how FA formation is regulated in human cells. There are currently two main types of FA in vivo and one in vitro system.

Ubiquitin-mediated autophagy has been linked to many diseases, including cancer and age-related diseases. Targeting these pathways can be an important strategy in disease prevention. These proteins are critical for the body's ability to maintain its homeostasis and prevent disease. For this reason, Boster Bio's SMURF1 marker inhibits FA formation. It is an important part of autophagy and a vital cellular process.

It inhibits ERK/RSK1

SMURF1 is a tumor suppressor protein with important functions in tumor biology. It inhibits the growth of tumors, promotes metastasis, and regulates the PI3K/AKT/mTOR pathway. Upstream regulators of Smurf1/2 control Smurf activity and substrate ubiquitination. This study reveals a potential drug target for ccRCC.

Smurf1 is a multi-domain protein composed of an N-terminal C2 domain, two WW domains, and one C-terminal HECT domain. The protein undergoes posttranslational modifications and is phosphorylated by Akt1/2 and Chk1, promoting cell proliferation and migration. Smurf1 also regulates PKA, a key enzyme in tumor progression. PKA inhibits Smurf1 expression by causing it to accumulate Nur77 protein. PIPKIg promotes cell growth and migration, thereby promoting tumor progression.

SMURF1 expression in ccRCC cells is higher than in matched tumor-adjacent tissue, which indicates a potential role in prognosticating ccRCC patients. SMURF1 inhibition inhibits ERK/RSK1 and promotes osteoblast differentiation. Although more research is needed to confirm this mechanism, it has shown promising potential.

The SMURF1 inhibitor suppresses ERK/RSK1 signaling in ccRCC cells. In vitro experiments have shown that loss of SMURF1 inhibits growth and metastasis. Furthermore, this compound also inhibits DAP2IP and PI3K signaling. Ultimately, SMURF1 inhibition inhibits ERK/RSK1 and PI3K.

SMURF1 is implicated in many types of cancer. By inhibiting ERK/RSK signaling, SMURF1 inhibition can help fight cancer. A recent study published in Science Translational Medicine found that SMURF1 inhibits ERK/RSK1 signaling in ccRCC. While there are still many unknowns about SMURF1 signaling, SMURF1 inhibition can be an important treatment tool.