CENTD2

ARAP1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4X1V
Identifiers
Aliases	ARAP1 , CENTD2, ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 1, cnt-d2
External IDs	OMIM: 606646; MGI: 1916960; HomoloGene: 12326; GeneCards: ARAP1; OMA:ARAP1 - orthologs
Gene location (Human) Chr. Chromosome 11 (human) [1] Band 11q13.4 Start 72,685,069 bp [1] End 72,793,599 bp [1]
Gene location (Mouse) Chr. Chromosome 7 (mouse) [2] Band 7|7 E2 Start 100,997,274 bp [2] End 101,061,793 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in granulocyte monocyte right uterine tube upper lobe of left lung right lung spleen right adrenal cortex left adrenal cortex anterior pituitary right lobe of thyroid gland Top expressed in granulocyte lip gastrula stroma of bone marrow efferent ductule tibiofemoral joint thymus lumbar spinal ganglion uterus spleen More reference expression data BioGPS n/a
Gene ontology Molecular function metal ion binding protein binding GTPase activator activity phosphatidylinositol-3,4,5-trisphosphate binding type 1 angiotensin receptor binding Cellular component cytoplasm Golgi apparatus membrane Golgi cisterna membrane trans-Golgi network cytoplasmic vesicle nucleoplasm cytosol plasma membrane intracellular membrane-bounded organelle Biological process actin filament reorganization involved in cell cycle regulation of cell shape negative regulation of stress fiber assembly regulation of small GTPase mediated signal transduction positive regulation of filopodium assembly signal transduction positive regulation of receptor recycling positive regulation of epidermal growth factor receptor signaling pathway positive regulation of GTPase activity Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 116985 69710 Ensembl ENSG00000186635 ENSMUSG00000032812 UniProt Q96P48 Q4LDD4 RefSeq (mRNA) NM_015242 NM_001040118 NM_001135190 NM_001369489 NM_001040111 NM_001040112 NM_027180 NM_198096 RefSeq (protein) NP_001035207 NP_001128662 NP_056057 NP_001356418 NP_001035200 NP_001035201 NP_081456 NP_932764 NP_001394730 NP_001394732 Location (UCSC) Chr 11: 72.69 – 72.79 Mb Chr 7: 101 – 101.06 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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. ^[5]

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. ^[6]

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. ^[5]

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. ^[7]

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. ^[8]

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. ^[9] 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. ^[10]

References

1. GRCh38: Ensembl release 89: ENSG00000186635 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000032812 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: CENTD2 centaurin, delta 2".
6. "CENTD2 (human)". www.phosphosite.org. Retrieved 2025-12-04.
7. "UniProt". UniProt. Retrieved 2025-12-04.
8. GeneCards Human Gene Database. "ARAP1 Gene - GeneCards | ARAP1 Protein | ARAP1 Antibody". www.genecards.org. Archived from the original on 2025-08-14. Retrieved 2025-12-04.
9. Qian Y, Dong M, Lu F, Li H, Jin G, Hu Z, et al. (2015-05-15). "Joint effect of CENTD2 and KCNQ1 polymorphisms on the risk of type 2 diabetes mellitus among Chinese Han population". Molecular and Cellular Endocrinology. 407: 46–51. doi:10.1016/j.mce.2015.02.026. ISSN   0303-7207.
10. Nielsen T, Sparsø T, Grarup N, Jørgensen T, Pisinger C, Witte DR, et al. (May 2011). "Type 2 diabetes risk allele near CENTD2 is associated with decreased glucose-stimulated insulin release". Diabetologia. 54 (5): 1052–1056. doi:10.1007/s00125-011-2054-3. ISSN   1432-0428. PMID   21267535.

External links

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

Further reading

• Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T (June 2002). "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones". DNA Research. 9 (3): 99–106. CiteSeerX   10.1.1.500.923 . doi:10.1093/dnares/9.3.99. PMID   12168954.
• Nagase T, Ishikawa K, Suyama M, Kikuno R, Miyajima N, Tanaka A, et al. (October 1998). "Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 5 (5): 277–286. doi: 10.1093/dnares/5.5.277 . PMID   9872452.
• Krugmann S, Anderson KE, Ridley SH, Risso N, McGregor A, Coadwell J, et al. (January 2002). "Identification of ARAP3, a novel PI3K effector regulating both Arf and Rho GTPases, by selective capture on phosphoinositide affinity matrices". Molecular Cell. 9 (1): 95–108. doi: 10.1016/S1097-2765(02)00434-3 . PMID   11804589.
• Miura K, Jacques KM, Stauffer S, Kubosaki A, Zhu K, Hirsch DS, et al. (January 2002). "ARAP1: a point of convergence for Arf and Rho signaling". Molecular Cell. 9 (1): 109–119. doi: 10.1016/S1097-2765(02)00428-8 . PMID   11804590.
• Ahn J, Chung KS, Kim DU, Won M, Kim L, Kim KS, et al. (November 2004). "Systematic identification of hepatocellular proteins interacting with NS5A of the hepatitis C virus". Journal of Biochemistry and Molecular Biology. 37 (6): 741–748. doi: 10.5483/bmbrep.2004.37.6.741 . PMID   15607035.
• Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, et al. (September 2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell. 122 (6): 957–968. Bibcode:2005Cell..122..957S. doi:10.1016/j.cell.2005.08.029. hdl: 11858/00-001M-0000-0010-8592-0 . PMID   16169070. S2CID   8235923.
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, et al. (November 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–648. doi: 10.1016/j.cell.2006.09.026 . PMID   17081983. S2CID   7827573.