protein
Active breakpoint cluster region-related protein
Gene
ABR
Organism
Homo sapiens(9606)
Length
859 aa
Mass
97,598 Da
Active breakpoint cluster region-related protein (ABR) is a dual-function regulator of small GTPases that contains both a Dbl homology (DH) guanine nucleotide exchange factor domain and a C-terminal GTPase-activating protein (GAP) domain (UniProt: Q12979). The DH domain promotes GTP loading of CDC42, RHOA, and RAC1, while the GAP domain stimulates GTP hydrolysis, particularly of RAC1 and CDC42, thereby providing opposing regulatory activities. ABR functions as a negative regulator of neuronal RAC1 activity and modulates macrophage motility and phagocytosis through RAC1 modulation (UniProt: Q12979).
No tissue-specific or pathway annotations are detailed in UniProt for ABR. The protein shows no baseline curated disease associations in the reference database (UniProt: Q12979).
ABR is associated with Alzheimer's Disease in this dataset and is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of −0.45 across measured subcellular fractions. This reduction may reflect altered regulation of RAC1-dependent signaling pathways implicated in neuronal integrity and synaptic dysfunction in AD pathology.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↓ Down in ADP3
-0.452
P2
not detected
S2
not detected
S3
not detected
Mean log₂FC across detected fractions: -0.4521 (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
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
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
Protein with a unique structure having two opposing regulatory activities toward small GTP-binding proteins. The C-terminus is a GTPase-activating protein domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. Accelerates the intrinsic rate of GTP hydrolysis of RAC1 or CDC42, leading to down-regulation of the active GTP-bound form (PubMed:17116687, PubMed:7479768). The central Dbl homology (DH) domain functions as a guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to the GTP-bound form (PubMed:7479768). Functions as an important negative regulator of neuronal RAC1 activity (By similarity). Regulates macrophage functions such as CSF-1 directed motility and phagocytosis through the modulation of RAC1 activity (By similarity)
Sources
Last updated 5/8/2026, 6:38:27 AM