protein
Rho GTPase-activating protein 44
Gene
ARHGAP44
Organism
Homo sapiens(9606)
Length
818 aa
Mass
89,247 Da
ARHGAP44 (Rho GTPase-activating protein 44) is a GAP protein that regulates Rho-type GTPases, particularly CDC42 and RAC1, by stimulating their GTPase activity and controlling their cycling between active GTP-bound and inactive GDP-bound states (UniProt: Q17R89). In neurons, the protein plays a role in dendritic spine formation and synaptic plasticity through RAC1-GAP activity, limiting exploratory dendritic filopodia initiation and regulating actin polymerization at the plasma membrane. ARHGAP44 also associates with SHANK3 to promote GRIA1 exocytosis and spine morphological changes linked to long-term potentiation (UniProt: Q17R89).
In Alzheimer's Disease, ARHGAP44 is downregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.47 (Chaparral AD proteomics). This reduction was observed in human post-mortem AD brain samples analyzed by TMT-labeled proteomics across four subcellular fractions. The downregulation of this synaptic plasticity-related protein may contribute to the dendritic spine loss and cognitive dysfunction characteristic of AD pathology.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↓ Down in ADP3
-0.470
P2
not detected
S2
not detected
S3
not detected
Mean log₂FC across detected fractions: -0.4699 (1 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Related Publications
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Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772
Function
GTPase-activating protein (GAP) that stimulates the GTPase activity of Rho-type GTPases. Thereby, controls Rho-type GTPases cycling between their active GTP-bound and inactive GDP-bound states. Acts as a GAP at least for CDC42 and RAC1 (PubMed:11431473). In neurons, is involved in dendritic spine formation and synaptic plasticity in a specific RAC1-GAP activity (By similarity). Limits the initiation of exploratory dendritic filopodia. Recruited to actin-patches that seed filopodia, binds specifically to plasma membrane sections that are deformed inward by acto-myosin mediated contractile forces. Acts through GAP activity on RAC1 to reduce actin polymerization necessary for filopodia formation (By similarity). In association with SHANK3, promotes GRIA1 exocytosis from recycling endosomes and spine morphological changes associated to long-term potentiation (By similarity)
Sources
Last updated 5/8/2026, 6:30:23 AM