CENTD2

Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 1 is a protein that in humans is encoded by the ARAP1 gene.

Official Symbol: ARAP1.

Chromosomal location of human Ortholog: Chromosome:11, Band:11q13.4

Molecular weight: 162,192 Da

CENTD2: Centaurin, Delta 2

Organism: Homo sapiens (Human)

Overview

CENTD2 Phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating protein that modulates actin cytoskeleton remodeling by regulating ARF and RHO family members. Is activated by phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) binding. Can be activated by phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding, albeit with lower efficiency. Has a preference for ARF1 and ARF5. Detected in heart, skeletal muscle, spleen, kidney, liver, placenta, lung, peripheral blood leukocytes, adrenal gland, bone marrow, brain, lymph node, mammary gland, prostate, spinal cord, stomach, thyroid and trachea. 7 alternatively spliced human isoforms have been reported.

Function

The protein encoded by this gene contains ARF-GAP, RHO-GAP, ankyrin repeat, RAS-associating, and pleckstrin homology domains. In vitro, this protein displays RHO-GAP and phosphatidylinositol (3,4,5) trisphosphate (PIP3)-dependent ARF-GAP activity. The encoded protein associates with the Golgi, and the ARF-GAP activity mediates changes in the Golgi and the formation of filopodia. The RHO-GAP activity may mediate cell rounding and loss of stress fibers. At least three transcript variants encoding different isoforms have been found for this gene, but the full-length natures of all variants have not been determined.

Phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating protein that modulates actin cytoskeleton remodeling by regulating ARF and RHO family members, has a preference for ARF1 and ARF5, Positively regulates the ring size of circular dorsal ruffles and promotes macropinocytosis, acts as a bridging factor in osteoclasts to control actin and membrane dynamics, regulates the condensing of osteoclast podosomes into sealing zones which segregate the bone-facing membrane from other membrane domains and are required for osteoclast resorption activity, also regulates recruitment of the AP-3 complex to endosomal membranes and trafficking of lysosomal membrane proteins to the ruffled membrane border of osteoclasts to modulate bone resorption, regulates the endocytic trafficking of EGFR, regulates the incorporation of CD63 and CD9 into multivesicular bodies , and required in the retinal pigment epithelium (RPE) for photoreceptor survival due to its role in promoting RPE phagocytosis.

Protein attributes

Size: 1450 Amino acids

Protein existence level: PE1

Gene ontology

Enables GTPase activator activity, enables protein binding, enables phosphatidylinositol-3,4,5-trisphosphate binding, enable zinc ion binding, enables type 1 angiotensin receptor binding.

Disease association

Genome-wide association studies in populations of European ancestry have identified nine SNP's (single nuclear polymorphisms) on chromosome 11 that contributes to an independent as well as cumulative effect on the risk of developing type II diabetes mellitus. CENTD2 is significantly associated with decreased glucose-stimulated insulin release and increased plasma glucose values, suggesting that an impaired pancreatic beta cell function is the mediator to the diabetogenic effect of this locus.

External links

• Human ARAP1 genome location and ARAP1 gene details page in the UCSC Genome Browser.