Target intelligence / Profile preview

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 1 (ARAP1)

Target
ARAP1
Molecular classification
Enzyme (specifically, GTPase-activating protein/GAP), Adapter/scaffolding protein (multi-domain, participates in membrane and cytoskeletal remodeling), Other (multi-domain protein with ArfGAP, RhoGAP, ankyrin repeat, PH, and SAM domains)
01

Overview

ARAP1 (ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 1) is a large multifunctional protein containing ArfGAP, RhoGAP, ankyrin repeats, SAM, and multiple pleckstrin homology (PH) domains[1][4]. It functions as a phosphoinositide-activated GTPase-activating protein (GAP), regulating both Arf and Rho family small GTPases, with a role in actin cytoskeleton remodeling, intracellular trafficking, and the assembly of actin-rich structures such as podosomes and sealing zones in osteoclasts[1][2][4]. ARAP1 is essential for the regulated trafficking of lysosomal membrane proteins and maintenance of proper bone resorption, and alterations in its activity are linked to bone, metabolic, and retinal diseases[1][2][6]. It acts as a molecular bridge between F-actin dynamics and membrane trafficking, affecting cell shape, movement, and specialized membrane domains[2][4]. Multiple alternative transcripts and isoforms exist, and homologs are found in mammalian species.

Other names
CENTD2KIAA0782Centaurin-delta-2Cnt-d2ARF-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 1ARF-GAP, RHO-GAP, ankyrin repeat, and pleckstrin homology domains-containing protein 1centaurin, delta 2
02

Biological functions

Regulation of actin cytoskeleton dynamicsSignal transductionMembrane trafficking, particularly trafficking of lysosomal membrane proteinsRegulation of bone resorption by osteoclastsReceptor trafficking (including involvement in apoptosis)
03

Disease associations

Cancer (e.g., gastric cancer)Bone homeostasis disorders (e.g., osteoporosis; experimentally linked to osteoclast dysfunction)Diabetes (e.g., maturity-onset diabetes of the young)Wolfram syndrome 2Retinal pigment epithelium dysfunction/retinal disease
04

Safety considerations

Potential safety concerns around modulating actin cytoskeleton and membrane trafficking in critical tissues (such as bone, retina, endocrine pancreas); off-target effects could disrupt essential cellular architecture or signaling
05

Biomarkers

Potential biomarker for bone resorption disorders and certain metabolic diseases, but not clinically established

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