ARAP3: ArfGAP with RhoGAP Domain, Ankyrin Repeat and PH Domain 3

A multi-domain GTPase-activating protein involved in cell adhesion, migration, and phosphoinositide signaling.

Gene Information Card

Symbol ARAP3
Full Name ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 3
Gene Type Protein coding
Chromosomal Location 5q31.3
NCBI Gene ID 64411 ncbi.nlm.nih.gov/gene/64411
Ensembl ID ENSG00000113580
UniProt ID Q8WWN8
OMIM ID 606647
HGNC ID 24058
Aliases CENTD3, DRAG1, KIAA0702, centaurin-delta-3

Description

ARAP3 encodes a multi-domain protein that functions as a GTPase-activating protein (GAP) for both Arf and Rho family small GTPases. It contains an N-terminal ArfGAP domain, a RhoGAP domain, ankyrin repeats, and a pleckstrin homology (PH) domain. ARAP3 is involved in regulating cell adhesion, cytoskeletal dynamics, and cell migration, particularly in response to phosphoinositide 3-kinase (PI3K) signaling. It is widely expressed and plays roles in vascular development and immune cell function.

Disease Associations

Disease category Pathophysiological mechanism Genomic evidence
Cancer (various types) Dysregulation of ARAP3 expression and mutations may alter cell migration and invasion through Rho/Arf signaling pathways. COSMIC database reports somatic mutations in multiple cancer types; limited functional validation.
Thrombocytopenia ARAP3 knockout mice exhibit platelet defects; human relevance not fully established. OMIM #606647; mouse model studies.

Expression Profile

Tissue Expression
Tissue nTPM level
Brain 12.5 Medium
Lung 8.3 Low
Heart 6.1 Low
Liver 4.2 Low
Kidney 7.8 Low
Testis 15.2 Medium
Spleen 10.1 Medium
Placenta 9.4 Low
Cell Line Expression
Cell Line nTPM Notes
HEK 293 11.3 Embryonic kidney cells
HeLa 9.8 Cervical cancer cells
K562 7.2 Leukemia cells
A549 8.5 Lung cancer cells
HepG2 6.0 Liver cancer cells
Data source:Human Protein Atlas(proteinatlas.org)

Mutations & Variants

Hotspot Mutations
Variant Type Frequency Functional Description
p.Gly111Arg Missense <0.1% Unknown; reported in COSMIC
p.Arg422* Nonsense <0.1% Predicted loss of function
p.Leu567Phe Missense <0.1% Unknown; reported in COSMIC
Mutation functional classification

Loss of Function (LOF)

Nonsense mutations (e.g., p.Arg422*) likely result in truncated protein and loss of GAP activity.

Gain of Function (GOF)

No well-characterized gain-of-function mutations reported.

Dominant Negative (DN)

Not established for ARAP3.

Pathways

• PI3K-Akt signaling pathway
• Rho GTPase cycle
• Arf GTPase cycle
• Regulation of actin cytoskeleton
• Focal adhesion

Protein Summary

ARAP3 is a 1504-amino acid protein that integrates signals from phosphoinositides and small GTPases. It contains an ArfGAP domain that inactivates Arf6, and a RhoGAP domain that inactivates RhoA and Cdc42. The PH domain binds phosphatidylinositol (3,4,5)-trisphosphate (PIP3), linking ARAP3 to PI3K signaling. Through its GAP activities, ARAP3 modulates cell adhesion, spreading, and migration. It is implicated in vascular development and cancer cell invasion.

Related Products

Product name Cat.No. Species Gene ID
ARAP3 Knockout HEK293 Cell Line EDJ-KQ1336 Human 64411 Details Get a Quote
ARAP3 Knockout A-549 Cell Line EDJ-KQ20788 Human 64411 Details Get a Quote
ARAP3 Knockout HCT 116 Cell Line EDJ-KQ20789 Human 64411 Details Get a Quote
ARAP3 Knockout HeLa Cell Line EDJ-KQ20790 Human 64411 Details Get a Quote
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