SHRM3 — Shroom Family Member 3

SHRM3 — Shroom Family Member 3

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#f8f9fa;text-align:center;font-size:1.1em;">SHRM3</th></tr>
<tr><th>Symbol</th><td>SHRM3</td></tr>
<tr><th>Full Name</th><td>Shroom Family Member 3</td></tr>
<tr><th>Chromosome</th><td>19q13.42</td></tr>
<tr><th>NCBI Gene ID</th><td>[63967](https://www.ncbi.nlm.nih.gov/gene/63967)</td></tr>
<tr><th>OMIM</th><td>[610595](https://www.omim.org/entry/610595)</td></tr>
<tr><th>Ensembl</th><td>[ENSG00000104892](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000104892)</td></tr>
<tr><th>UniProt</th><td>[Q9NWB5](https://www.uniprot.org/uniprot/Q9NWB5)</td></tr>
<tr><th>Associated Diseases</th><td>[Alzheimer's disease](/diseases/alzheimers-disease), [Parkinson's disease](/diseases/parkinsons-disease), [Neural tube defects](/diseases/neural-tube-defects)</td></tr>
</table>
</div>

Overview

SHRM3 (Shroom Family Member 3), also known as Shroom3, is an actin-binding protein that plays critical roles in cellular morphogenesis and tissue development [simic2018](https://pubmed.ncbi.nlm.nih.gov/29476772/). Originally identified for its essential function in neural tube closure, SHRM3 regulates apical constriction through direct binding to non-muscle myosin II and the actin cytoskeleton [riedl2008](https://pubmed.ncbi.nlm.nih.gov/18818081/).

SHRM3 — Shroom Family Member 3

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#f8f9fa;text-align:center;font-size:1.1em;">SHRM3</th></tr>
<tr><th>Symbol</th><td>SHRM3</td></tr>
<tr><th>Full Name</th><td>Shroom Family Member 3</td></tr>
<tr><th>Chromosome</th><td>19q13.42</td></tr>
<tr><th>NCBI Gene ID</th><td>[63967](https://www.ncbi.nlm.nih.gov/gene/63967)</td></tr>
<tr><th>OMIM</th><td>[610595](https://www.omim.org/entry/610595)</td></tr>
<tr><th>Ensembl</th><td>[ENSG00000104892](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000104892)</td></tr>
<tr><th>UniProt</th><td>[Q9NWB5](https://www.uniprot.org/uniprot/Q9NWB5)</td></tr>
<tr><th>Associated Diseases</th><td>[Alzheimer's disease](/diseases/alzheimers-disease), [Parkinson's disease](/diseases/parkinsons-disease), [Neural tube defects](/diseases/neural-tube-defects)</td></tr>
</table>
</div>

Overview

SHRM3 (Shroom Family Member 3), also known as Shroom3, is an actin-binding protein that plays critical roles in cellular morphogenesis and tissue development [simic2018](https://pubmed.ncbi.nlm.nih.gov/29476772/). Originally identified for its essential function in neural tube closure, SHRM3 regulates apical constriction through direct binding to non-muscle myosin II and the actin cytoskeleton [riedl2008](https://pubmed.ncbi.nlm.nih.gov/18818081/).

The Shroom family consists of four members (SHRM1-4) that share conserved domains involved in actin binding and regulation. SHRM3 is expressed in both developing and adult tissues, with particularly high expression in the nervous system and kidney [hatano2020](https://pubmed.ncbi.nlm.nih.gov/32006699/). While primarily studied in developmental contexts, SHRM3's role in actin dynamics has significant implications for synaptic plasticity and neurodegenerative diseases [pollard2017](https://pubmed.ncbi.nlm.nih.gov/28460230/).

Gene and Protein Structure

Gene Organization

The SHRM3 gene is located on chromosome 19q13.42 and encodes a protein of 1934 amino acids with a molecular weight of approximately 210 kDa. The gene contains multiple exons and undergoes alternative splicing to produce variant isoforms.

Protein Domains

SHRM3 contains several functional domains [dos Remedios2015](https://pubmed.ncbi.nlm.nih.gov/26507252/):

Protein-Protein Interactions

Biological Functions

Apical Constriction

SHRM3 is a master regulator of apical constriction [zagora2020](https://pubmed.ncbi.nlm.nih.gov/32439325/), a fundamental process in tissue morphogenesis:

Neural Tube Formation

During embryogenesis, SHRM3 is essential for neural tube closure [shen2019](https://pubmed.ncbi.nlm.nih.gov/30626716/), [ek2010](https://pubmed.ncbi.nlm.nih.gov/20034178/):

• Neural plate bending: Initiates folding of the neural plate
• Neural fold elevation: Promotes elevation of neural folds
• Fusion of folds: Facilitates closure at the midline
• Spina bifida prevention: Proper SHRM3 function prevents neural tube defects

Actin Cytoskeleton Regulation

SHRM3 modulates the actin cytoskeleton through multiple mechanisms [kalman2018](https://pubmed.ncbi.nlm.nih.gov/29395626/):

• F-actin bundling: Organizes actin filaments into parallel bundles
• Actin polymerization: Regulates actin dynamics
• Cell shape control: Controls epithelial cell morphology
• Tissue integrity: Maintains tissue architecture

Role in the Nervous System

Synaptic Plasticity

SHRM3 plays important roles in synaptic function [pollard2017](https://pubmed.ncbi.nlm.nih.gov/28460230/), [morita2019](https://pubmed.ncbi.nlm.nih.gov/31749844/):

Dendritic Spines

• Spine morphology: Regulates spine shape and size
• Actin dynamics: Controls spine actin cytoskeleton
• Plasticity mechanisms: Involved in LTP and LTD
• Receptor trafficking: May affect AMPA and NMDA receptor localization

Synaptic Signaling

• Post-synaptic density: Localizes to synaptic complexes
• Signal transduction: Interfaces with synaptic signaling pathways
• Neuromuscular junctions: Important for peripheral synapses

Neuronal Development

• Axon guidance: May influence axonal pathfinding
• Dendritic arborization: Regulates dendrite branching
• Synapse formation: Contributes to synaptogenesis

Role in Neurodegenerative Diseases

Alzheimer's Disease

Actin cytoskeletal alterations are early events in AD pathogenesis [halabi2021](https://pubmed.ncbi.nlm.nih.gov/34536082/):

• Dendritic spine loss: Actin dysfunction contributes to spine elimination
• Tau pathology: Tau affects actin-binding proteins
• Synaptic failure: Actin dynamics are disrupted in early AD
• Amyloid effects: Aβ alters actin cytoskeleton

• Altered expression in AD brain
• Dysregulated actin signaling
• Impaired spine plasticity

Parkinson's Disease

Actin cytoskeletal changes also contribute to [Parkinson's disease](/diseases/parkinsons-disease) [boehm2021](https://pubmed.ncbi.nlm.nih.gov/34312945/):

• Dendritic complexity: Loss of dopaminergic neuron dendrites
• Axonal transport: Actin-based transport disruption
• Synaptic dysfunction: Dopamine release abnormalities
• Lewy body formation: Cytoskeletal components in inclusions

Amyotrophic Lateral Sclerosis

Cytoskeletal abnormalities are prominent in [ALS](/diseases/als) [yang2017](https://pubmed.ncbi.nlm.nih.gov/28781370/):

• Motor neuron cytoskeleton: Disrupted actin/microtubule networks
• Axonal transport: Cargo movement impaired
• Synaptic terminals: Nerve terminal dysfunction

Disease Associations

Neural Tube Defects

SHRM3 mutations are associated with neural tube defects [steghaus2020](https://pubmed.ncbi.nlm.nih.gov/32662567/):

• Spina bifida: Failure of spinal cord closure
• Anencephaly: Absence of cranial structures
• Encephalocele: Protrusion of brain tissue

Kidney Disorders

• Renal hypoplasia: Reduced kidney development
• Congenital kidney anomalies: Structural abnormalities

Potential Neurodegenerative Links

While not directly causative, SHRM3 may contribute to:

• Age-related neurodegeneration
• Synaptic failure in disease
• Cytoskeletal dysfunction

Expression Patterns

Tissue Distribution

SHRM3 shows distinct expression patterns:

• Kidney: High expression in renal tubules
• Brain: [Cortex](/brain-regions/cortex), [cerebellum](/brain-regions/cerebellum), [hippocampus](/brain-regions/hippampus)
• Lung: Bronchial epithelium
• Intestine: Epithelial cells
• Embryonic tissues: High during development

Brain Regional Distribution

Within the nervous system:

• Cerebral cortex: Pyramidal neurons
• Hippocampus: CA1-CA3 regions, dentate gyrus
• Cerebellum: Purkinje cells
• Spinal cord: Motor neurons

Cell Type Specificity

• Neurons: Expression in excitatory and inhibitory neurons
• Astrocytes: Lower expression
• Epithelial cells: High in transporting epithelia
• Endothelial cells: Moderate expression

Therapeutic Implications

Targeting Actin Dynamics

Modulating SHRM3 function offers therapeutic potential [kalman2018](https://pubmed.ncbi.nlm.nih.gov/29395626/):

Direct Approaches

• Small molecule modulators: Target SHRM3-actin interactions
• Peptide inhibitors: Block protein-protein interactions
• Gene therapy: Modulate SHRM3 expression

Indirect Strategies

• Myosin II inhibitors: Affect downstream effectors
• Actin polymerization modulators: Control actin dynamics
• Rho kinase inhibitors: Affect upstream signaling

Neurodegeneration Strategies

Drug Development Considerations

| Challenge | Approach |
|-----------|----------|
| Protein-protein interactions | Develop interface inhibitors |
| Cell type specificity | Target disease-specific isoforms |
| BBB penetration | Design CNS-penetrant molecules |
| Therapeutic window | Careful dosing strategies |

Animal Models

Genetic Models

• Shrm3 knockout mice: Neural tube defects, embryonic lethal
• Conditional knockouts: Tissue-specific phenotypes
• Transgenic models: Disease-relevant mutations

Phenotypes

• Exencephaly
• Spina bifida
• Kidney hypoplasia

Research Directions

Unresolved Questions

Emerging Areas

Cross-Links

Related Mechanisms

• [Actin Cytoskeleton in Neurodegeneration](/mechanisms/actin-cytoskeleton-neurodegeneration)
• [Synaptic Plasticity Mechanisms](/mechanisms/synaptic-plasticity)
• [Dendritic Spine Dynamics](/mechanisms/dendritic-spine-dynamics)
• [Apical Constriction Pathway](/mechanisms/apical-constriction)

Related Genes

• [SHRM2](/genes/shrm2) — Related Shroom family member
• [SHRM4](/genes/shrm4) — Related Shroom family member
• [MYH9](/genes/myh9) — Non-muscle myosin

Related Proteins

• [Beta-actin](/proteins/beta-actin) — Actin isoform
• [Myosin II](/proteins/myosin-ii) — Motor protein
• [Tau](/proteins/tau) — Microtubule-associated protein

Related Diseases

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Amyotrophic Lateral Sclerosis](/diseases/als)
• [Neural Tube Defects](/diseases/neural-tube-defects)

External Links

• [NCBI Gene: SHRM3](https://www.ncbi.nlm.nih.gov/gene/63967)
• [UniProt: Q9NWB5](https://www.uniprot.org/uniprot/Q9NWB5)
• [Ensembl: ENSG00000104892](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000104892)
• [HGNC: SHRM3](https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:14120)

References