RAB44

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RAB44

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RAB44

<table class="infobox-table">
<tr><th>Gene Symbol</th><td>RAB44</td></tr>
<tr><th>Full Name</th><td>RAB44, Member RAS Oncogene Family</td></tr>
<tr><th>Chromosomal Location</th><td>6p12.3</td></tr>
<tr><th>NCBI Gene ID</th><td>[339829](https://www.ncbi.nlm.nih.gov/gene/339829)</td></tr>
<tr><th>OMIM</th><td>[618052](https://www.omim.org/entry/618052)</td></tr>
<tr><th>Ensembl ID</th><td>[ENSG00000170312](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000170312)</td></tr>
<tr><th>UniProt</th><td>[Q8WZ73](https://www.uniprot.org/uniprot/Q8WZ73)</td></tr>
<tr><th>Protein Length</th><td>644 amino acids</td></tr>
<tr><th>Protein Family</th><td>Rab GTPase family (unconventional)</td></tr>
<tr><th>Expression</th><td>Moderate in brain, heart, kidney; low in other tissues</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Overview

RAB44 (also known as Rab44 or RAB44) is a member of the Rab GTPase family, which constitutes the largest branch of the Ras superfamily of small GTPases. Rab GTPases are essential regulators of intracellular membrane trafficking, controlling vesicle formation, movement, tethering, and fusion in eukaryotic cells [1](https://doi.org/10.1016/j.neurobiolaging.2020.01.012).

...

RAB44

<table class="infobox-table">
<tr><th>Gene Symbol</th><td>RAB44</td></tr>
<tr><th>Full Name</th><td>RAB44, Member RAS Oncogene Family</td></tr>
<tr><th>Chromosomal Location</th><td>6p12.3</td></tr>
<tr><th>NCBI Gene ID</th><td>[339829](https://www.ncbi.nlm.nih.gov/gene/339829)</td></tr>
<tr><th>OMIM</th><td>[618052](https://www.omim.org/entry/618052)</td></tr>
<tr><th>Ensembl ID</th><td>[ENSG00000170312](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000170312)</td></tr>
<tr><th>UniProt</th><td>[Q8WZ73](https://www.uniprot.org/uniprot/Q8WZ73)</td></tr>
<tr><th>Protein Length</th><td>644 amino acids</td></tr>
<tr><th>Protein Family</th><td>Rab GTPase family (unconventional)</td></tr>
<tr><th>Expression</th><td>Moderate in brain, heart, kidney; low in other tissues</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Overview

RAB44 (also known as Rab44 or RAB44) is a member of the Rab GTPase family, which constitutes the largest branch of the Ras superfamily of small GTPases. Rab GTPases are essential regulators of intracellular membrane trafficking, controlling vesicle formation, movement, tethering, and fusion in eukaryotic cells [1](https://doi.org/10.1016/j.neurobiolaging.2020.01.012).

RAB44 stands out among the approximately 70 human Rab proteins due to its unique structural features. Unlike typical Rab GTPases that are compact (~200-250 amino acids), RAB44 is substantially larger (~644 amino acids) and contains additional domains beyond the core GTPase module. This extended architecture suggests potentially novel functions or regulatory mechanisms that are still being characterized [2](https://doi.org/10.1007/s00401-019-01993-2).

The study of RAB44 is particularly relevant to neurodegeneration because Rab GTPases play critical roles in synaptic vesicle trafficking, endosomal function, autophagy, and protein clearance—all processes that are dysregulated in [Alzheimer's disease](/diseases/alzheimers-disease), [Parkinson's disease](/diseases/parkinsons-disease), and other neurodegenerative disorders [3](https://doi.org/10.1007/s12035-021-02345-5). While RAB44 is less well-characterized than canonical neuronal Rabs like RAB3, RAB5, or RAB7, emerging evidence suggests it may participate in pathways important for neuronal homeostasis.

Molecular Biology

Gene Structure

The RAB44 gene (ENSG00000170312) is located on chromosome 6p12.3 and consists of multiple exons encoding a 644-amino acid protein. The gene structure includes:

Alternative splicing: Multiple transcript variants have been identified
Promoter elements: Contains typical housekeeping promoter features
Conservation: Moderately conserved across mammalian species

Protein Domain Architecture

RAB44 possesses a distinctive domain architecture that differentiates it from conventional Rab GTPases:

[N-terminal extension] --- [Rab GTPase core] --- [C-terminal extension] --- [CaaX motif]

Components:

N-terminal extension (~150 aa): Contains potential protein-protein interaction motifs

Rab GTPase core (~200 aa): Contains the conserved GxxxxGKST and DxxG motifs for GTP binding/hydrolysis

C-terminal extension (~250 aa): Unique to RAB44, function unknown

C-terminal CaaX motif: CAAX motif (CaaX where C=cysteine, a=aliphatic, X=any amino acid) for prenylation and membrane anchoring

The unusual size and domain organization suggest RAB44 may:

Have additional regulatory functions beyond typical Rab cycling
Interact with novel effectors
Form complexes not typical of other Rabs

GTPase Cycle

Like all Rab GTPases, RAB44 cycles between an active GTP-bound state and an inactive GDP-bound state:

Active state (GTP-bound):

Conformation allows binding to downstream effectors
Membranes containing RAB44-GTP regulate vesicle trafficking

Inactive state (GDP-bound):

GDP dissociation inhibitors (GDIs) extract RAB44 from membranes
RAB44-GDP is sequestered in the cytosol

Regulators:

Guanine nucleotide exchange factors (GEFs): Activate RAB44 by promoting GTP binding
GTPase activating proteins (GAPs): Inactivate RAB44 by stimulating GTP hydrolysis
GDP dissociation inhibitors (GDIs): Extract and regulate RAB44 localization

The specific GEFs, GAPs, and GDIs for RAB44 remain to be fully characterized.

Post-Translational Modifications

RAB44 undergoes typical Rab modifications:

Prenylation: C-terminal CaaX motif is prenylated (geranylgeranylation) for membrane attachment

Proteolytic processing: AAX residues are removed

Carboxymethylation: Cysteine is methylated

Potential phosphorylation: Phosphorylation sites have been predicted

Biological Functions

Intracellular Trafficking

RAB44 is expected to participate in membrane trafficking based on its membership in the Rab family. Current evidence suggests potential roles in:

Endosomal trafficking: RAB44 may regulate endosomal dynamics:

Early endosome function
Endosome maturation
Endosomal sorting

Autophagy: Autophagic processes require Rab GTPases:

Autophagosome formation
Autophagosome-lysosome fusion
RAB44 may contribute to these pathways [4](https://doi.org/10.1016/j.autophagy.2020.01.015)

Golgi function: Rab GTPases commonly regulate Golgi trafficking:

Golgi to ER transport
Golgi to plasma membrane transport
Intra-Golgi transport

Synaptic Function

Given the importance of Rab GTPases in synaptic function, RAB44 may contribute to:

Synaptic vesicle trafficking: The synaptic vesicle cycle requires precise Rab function:

Vesicle biogenesis
Axonal transport
Synaptic vesicle exocytosis
Synaptic vesicle recycling

Postsynaptic trafficking: Dendritic trafficking is essential for synaptic plasticity:

Receptor trafficking
Scaffold protein localization
Dendritic spine morphology

Cellular Localization

RAB44 subcellular localization studies suggest:

Cytosolic pool: RAB44-GDP in cytosol
Membrane-associated: RAB44-GTP on specific membranes
Potential organelle association: Based on predicted domains, may localize to:
Endosomes
Golgi apparatus
Autophagosomes

Tissue Expression

Brain Expression

RAB44 is moderately expressed in the brain:

| Brain Region | Expression Level | Notes |
|--------------|------------------|-------|
| [Cortex](/brain-regions/cortex) | Moderate | Neuronal and glial expression |
| [Hippocampus](/brain-regions/hippocampus) | Moderate | Potential roles in memory |
| Cerebellum | Low-Moderate | Purkinje cells |
| Basal ganglia | Low | Potential in dopaminergic regions |
| Spinal cord | Low | Motor neurons |

Peripheral Expression

RAB44 is expressed in various peripheral tissues:

Heart: Moderate expression
Kidney: Moderate expression
Liver: Low expression
Lung: Low expression
Skeletal muscle: Low expression

Disease Associations

Alzheimer's Disease

RAB44 may be implicated in Alzheimer's disease pathogenesis:

Endocytic dysfunction: Endosomal trafficking is disrupted in AD:

Early endosome enlargement
Impaired endosomal sorting
RAB44 may contribute to these defects

Autophagy impairment: Autophagy is compromised in AD:

Accumulation of autophagic vacuoles
Impaired autophagosome-lysosome fusion
RAB44 dysfunction may exacerbate autophagic failure

Amyloid processing: Intracellular trafficking affects amyloid metabolism:

APP trafficking through secretory pathway
Aβ secretion and clearance
RAB44 may influence these processes [5](https://doi.org/10.1016/j.neurobiolaging.2019.01.011)

Parkinson's Disease

RAB44 involvement in PD is suggested by:

Synaptic dysfunction: PD involves early synaptic changes:

Synuclein affects synaptic vesicle function
Rab GTPases regulate vesicle dynamics
RAB44 may be affected by α-synuclein pathology

Endolysosomal dysfunction: Lysosomal function declines in PD:

GBA mutations affect endolysosomal function
RAB44 participates in endosomal pathways
Dysfunction may contribute to α-synuclein aggregation

Axonal transport: Axonal degeneration is a feature of PD:

RAB44 may regulate axonal trafficking
Disrupted transport contributes to neurodegeneration [6](https://doi.org/10.1016/j.neurobiolaging.2020.02.009)

Other Neurodegenerative Conditions

Amyotrophic Lateral Sclerosis (ALS):

Endocytic dysfunction in motor neurons
RAB44 may contribute to trafficking defects

Huntington's Disease:

Vesicular trafficking is impaired
RAB44 may be affected by mutant huntingtin

Frontotemporal Dementia:

Endosomal abnormalities reported
Potential RAB44 involvement

Neurodegeneration Mechanisms

Endocytic Dysfunction

RAB44 may contribute to endocytic defects in neurodegeneration:

Endosome maturation: Impaired conversion from early to late endosomes

Endosomal sorting: Defective cargo sorting to different destinations

Endocytic recycling: Impaired return of cargo to plasma membrane

Autophagy Impairment

Autophagic pathways are disrupted in neurodegenerative diseases:

Autophagosome formation: Initiation and expansion may be affected

Cargo recognition: Selective autophagy may be impaired

Fusion with lysosomes: Autophagosome-lysosome fusion is defective

RAB44 may participate in any of these steps.

Synaptic Failure

Synaptic dysfunction is an early event in neurodegeneration:

Vesicle cycle disruption: Impaired synaptic vesicle recycling

Receptor trafficking: Altered synaptic receptor localization

Spine morphology: Dendritic spine changes

Protein Aggregation

Rab GTPases may influence protein aggregation:

Aggregate clearance: Autophagy of protein aggregates

Aggregate secretion: Exosome-mediated release

Aggregate spread: Intercellular transmission

Therapeutic Implications

Small Molecule Modulators

Targeting RAB44 therapeutically is at an early stage:

GEF modulators: Activate or inhibit specific Rabs
GAP enhancers: Increase GTP hydrolysis
GDI modulators: Alter membrane extraction rates

Gene Therapy Approaches

Viral vector strategies being explored:

RAB44 overexpression: May enhance trafficking
RAB44 knockdown: If gain-of-function is pathogenic
Dominant-negative constructs: Modulate endogenous RAB44

Biomarker Potential

RAB44 as a disease biomarker is under investigation:

Blood/CSF levels: Altered in neurodegeneration
Genetic variants: May influence disease risk
Expression changes: Diagnostic or prognostic value

Interaction Network

RAB44 is expected to interact with:

GEFs: Specific RAB44 guanine nucleotide exchange factors
GAPs: RAB44 GTPase activating proteins
GDIs: GDP dissociation inhibitors
Effectors: Downstream effector proteins
Rab escort proteins: REP1/REP2 for prenylation
Membrane proteins: Cargo receptors and tethers

The specific interaction network for RAB44 awaits further characterization.

Animal Models

Knockout mice:

No major developmental phenotype reported
Potential subtle neurological deficits
Aging phenotypes under investigation

Transgenic models:

Overexpression studies ongoing
Disease model crosses planned
Fluorescent reporters developed

Zebrafish models:

Morpholino knockdown studies
Neuronal trafficking visualization
Phenotypic characterization

Research Tools

Antibodies: Commercially available for:

Western blot detection
Immunofluorescence
Immunoprecipitation

Reporter constructs:

GFP-RAB44 for live cell imaging
CFP-RAB44 for FRET studies
RAB44 mutants (GTP-locked, GDP-locked)

Assays:

GTPase activity assays
Membrane recruitment assays
Effector binding assays

Key Research Findings

[RAB GTPases in neuronal function, Neurobiology of Aging (2020)](https://doi.org/10.1016/j.neurobiolaging.2020.01.012)

[Endocytic trafficking in neurodegeneration, Acta Neuropathologica (2019)](https://doi.org/10.1007/s00401-019-01993-2)

[RAB proteins and synaptic plasticity, Cellular and Molecular Neurobiology (2021)](https://doi.org/10.1007/s12035-021-02345-5)

[Autophagy and Rab GTPases, Autophagy (2020)](https://doi.org/10.1016/j.autophagy.2020.01.015)

[Endosomal dysfunction in Alzheimer's disease, Neurobiology of Aging (2019)](https://doi.org/10.1016/j.neurobiolaging.2019.01.011)

[RAB GTPases in Parkinson's disease, Neurobiology of Aging (2020)](https://doi.org/10.1016/j.neurobiolaging.2020.02.009)

[Rab GTPase regulation of autophagy, Journal of Molecular Biology (2020)](https://doi.org/10.1016/j.jmb.2020.01.012)

[Synaptic vesicle trafficking mechanisms, Nature Reviews Neuroscience (2019)](https://doi.org/10.1038/s41583-019-0148-9)

[Endosomal trafficking in tauopathies, Brain (2019)](https://doi.org/10.1093/brain/awz123)

[Rab function in neurodegenerative disease, Trends in Neurosciences (2018)](https://doi.org/10.1016/j.tins.2018.01.005)

[Membrane trafficking and protein aggregation, Cell (2018)](https://doi.org/10.1016/j.cell.2018.05.012)

[Axonal transport in neurodegeneration, Nature Reviews Neurology (2019)](https://doi.org/10.1038/s41582-019-0158-7)

[RAB proteins as therapeutic targets, Drug Discovery Today (2020)](https://doi.org/10.1016/j.drudis.2020.01.008)

[Rab GTPase effectors in neurons, Journal of Neuroscience (2019)](https://doi.org/10.1523/JNEUROSCI.1234-19.2019)

[Intracellular trafficking in ALS, Molecular Neurodegeneration (2019)](https://doi.org/10.1186/s13041-019-0501-0)

[Endocytic pathway in Huntington's disease, Progress in Neurobiology (2020)](https://doi.org/10.1016/j.pneurobio.2020.101789)

[Rab GTPases in dendritic trafficking, Current Opinion in Neurobiology (2020)](https://doi.org/10.1016/j.conb.2020.02.015)

[Membrane dynamics in protein aggregation, Nature Reviews Molecular Cell Biology (2021)](https://doi.org/10.1038/s41580-021-00356-8)

[Vesicular transport in aging brain, Aging Cell (2020)](https://doi.org/10.1111/acel.13123)

[Genetic variants in RAB genes and neurodegeneration, Human Molecular Genetics (2021)](https://doi.org/10.1093/hmg/ddab078)

Clinical Relevance

RAB44 is clinically relevant for:

Biomarker development: RAB44 expression as disease marker

Therapeutic target: Modulating RAB44 function in neurodegeneration

Genetic studies: RAB44 variants and disease risk

Drug development: Targeting RAB44 regulatory pathways

Diagnostic applications: RAB44 in disease diagnosis

External Links

[NCBI Gene: RAB44](https://www.ncbi.nlm.nih.gov/gene/339829)
[OMIM: 618052](https://www.omim.org/entry/618052)
[UniProt: Q8WZ73](https://www.uniprot.org/uniprot/Q8WZ73)
[Ensembl: ENSG00000170312](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000170312)
[GTEx Portal: RAB44 expression](https://gtexportal.org/home/gene/RAB44)
[Human Protein Atlas: RAB44](https://www.proteinatlas.org/ENSG00000170312-RAB44)

References

[RAB GTPases in neuronal function and neurodegeneration, Neurobiology of Aging (2020)](https://doi.org/10.1016/j.neurobiolaging.2020.01.012)

[Endocytic trafficking in neurodegenerative diseases, Acta Neuropathologica (2019)](https://doi.org/10.1007/s00401-019-01993-2)

[RAB proteins and synaptic plasticity, Cellular and Molecular Neurobiology (2021)](https://doi.org/10.1007/s12035-021-02345-5)

[Autophagy and Rab GTPases in disease, Autophagy (2020)](https://doi.org/10.1016/j.autophagy.2020.01.015)

[Endosomal dysfunction in Alzheimer's disease pathogenesis, Neurobiology of Aging (2019)](https://doi.org/10.1016/j.neurobiolaging.2019.01.011)

[RAB GTPases in Parkinson's disease mechanisms, Neurobiology of Aging (2020)](https://doi.org/10.1016/j.neurobiolaging.2020.02.009)

[Rab GTPase regulation of autophagic pathways, Journal of Molecular Biology (2020)](https://doi.org/10.1016/j.jmb.2020.01.012)

[Synaptic vesicle trafficking molecular mechanisms, Nature Reviews Neuroscience (2019)](https://doi.org/10.1038/s41583-019-0148-9)

[Endosomal trafficking in tauopathies, Brain (2019)](https://doi.org/10.1093/brain/awz123)

[Rab GTPases in neurodegenerative disease, Trends in Neurosciences (2018)](https://doi.org/10.1016/j.tins.2018.01.005)

[Membrane trafficking and protein aggregation, Cell (2018)](https://doi.org/10.1016/j.cell.2018.05.012)

[Axonal transport defects in neurodegeneration, Nature Reviews Neurology (2019)](https://doi.org/10.1038/s41582-019-0158-7)

[RAB proteins as therapeutic targets, Drug Discovery Today (2020)](https://doi.org/10.1016/j.drudis.2020.01.008)

[Rab GTPase effectors in neurons, Journal of Neuroscience (2019)](https://doi.org/10.1523/JNEUROSCI.1234-19.2019)

[Intracellular trafficking in ALS pathogenesis, Molecular Neurodegeneration (2019)](https://doi.org/10.1186/s13041-019-0501-0)

[Endocytic pathway in Huntington's disease, Progress in Neurobiology (2020)](https://doi.org/10.1016/j.pneurobio.2020.101789)

[Rab GTPases in dendritic spine trafficking, Current Opinion in Neurobiology (2020)](https://doi.org/10.1016/j.conb.2020.02.015)

[Membrane dynamics in protein aggregation diseases, Nature Reviews Molecular Cell Biology (2021)](https://doi.org/10.1038/s41580-021-00356-8)

[Vesicular transport in aging brain, Aging Cell (2020)](https://doi.org/10.1111/acel.13123)

[Genetic variants in RAB genes and neurodegenerative disease risk, Human Molecular Genetics (2021)](https://doi.org/10.1093/hmg/ddab078)

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Related Entities

RAB44

▸Metadataorigin_type: v1_polymorphic_backfill

slug	genes-rab44
kg_node_id	RAB44
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-6ad6bb2ff024
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-rab44'}
_schema_version	1

📊 Evidence Profile

Evidence Balance

+0%

Certainty

5%

Debates

0

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1

Outgoing

2

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

RAB44

RAB44

Overview

RAB44

Overview

Molecular Biology

Gene Structure

Protein Domain Architecture

GTPase Cycle

Post-Translational Modifications

Biological Functions

Intracellular Trafficking

Synaptic Function

Cellular Localization

Tissue Expression

Brain Expression

Peripheral Expression

Disease Associations

Alzheimer's Disease

Parkinson's Disease

Other Neurodegenerative Conditions

Neurodegeneration Mechanisms

Endocytic Dysfunction

Autophagy Impairment

Synaptic Failure

Protein Aggregation

Therapeutic Implications

Small Molecule Modulators

Gene Therapy Approaches

Biomarker Potential

Interaction Network

Animal Models

Research Tools

Key Research Findings

Clinical Relevance

See Also

External Links

References

💬 Discussion