CENTB1

ACAP1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3JUE, 3T9K, 4CKG, 4CKH, 4F1P, 4NSW
Identifiers
Aliases	ACAP1, CENTB1, ArfGAP with coiled-coil, ankyrin repeat and PH domains 1
External IDs	OMIM: 607763; MGI: 2388270; HomoloGene: 22835; GeneCards: ACAP1; OMA:ACAP1 - orthologs
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17p13.1 Start 7,336,529 bp[1] End 7,351,477 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11|11 B3 Start 69,772,393 bp[2] End 69,786,365 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in granulocyte blood lymph node spleen bone marrow cell left testis right testis appendix nucleus accumbens pituitary gland Top expressed in granulocyte thymus blood lymph node mesenteric lymph nodes spleen pharynx bone marrow subcutaneous adipose tissue embryo More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding metal ion binding GTPase activator activity Cellular component endosome recycling endosome membrane membrane intracellular membrane-bounded organelle Biological process protein transport positive regulation of GTPase activity transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 9744 216859 Ensembl ENSG00000072818 ENSG00000288169 ENSMUSG00000001588 UniProt Q15027 Q8K2H4 RefSeq (mRNA) NM_014716 NM_153788 RefSeq (protein) NP_055531 NP_722483 Location (UCSC) Chr 17: 7.34 – 7.35 Mb Chr 11: 69.77 – 69.79 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Centaurin β1 (CENTB1), also known as ACAP1,^[5] is a GTPase-activating protein (GAP) for ADP-ribosylation factor (ARF) 6 belonging to the ADP-ribosylation factor family.^[6] It also contains a coiled-coil structural motif, ankyrin repeat (ANK), and a PH domain. CENTB1 is encoded by a gene located on the short arm of human chromosome 17.^[7] CENTB1 is also located in mouse chromosome 11. The expression of CENTB1 is tissue-specific, with the highest levels observed in the lung and spleen, while the lower levels are found in the heart, kidney, liver, and pancreas.^[8]

Structure

CENTB1, also known as ACAP1, is composed of several distinct domains. Its structure includes an Arf-GAP domain with coiled-coil region, along with an ankyrin (ANK) repeat and a pleckstrin homology (PH) domain-containing protein.^[9][8][6]

It has a length of 740 amino acids and a molecular mass of 81,536 Da.^[10] As for its quaternary structure, the CENTB1 protein has a banana-structure homodimer configuration. These homodimers laterally assemble into tetramers, which further pack helically onto the membrane.^[10]

Interactions

CENTB1 interacts with GTP-bound ARF6, regulating polymerization of the actin cytoskeleton around the plasma membrane.^[5] CENTB1 also interacts with the third cytoplasmic loop of SLC2A4/GLUT4: it anchors GLUT4 within specific intercellular compartments of facilitate its sorting into the correct vesicles for transport.^[11] CENTB1 may also function as an adaptor protein by binding to clathrin heavy chain, linking specific cargo to the clathrin coat during the formation of a vesicle.^[11] Other proteins known to interact with CENTB1 include GULP1 and the integrin β1 chain; in both cases CENTB1 regulates the sorting and recycling of vesicle traffic.^[12][13]

Function

CENTB1 is a cytoplasmic protein that is able to down-regulate the NF-κB activity through NOD-1 and NOD-2 signaling pathways.^[14] Which can be in response to γ-D-glutamyl-meso-diaminopimelic acid (iE-DAP) and muramyl dipeptide (MDP-LD) stimulation in intestinal epithelial cells.^[15] CENTB1 is a component of a novel clathrin coat complex involved in endocytic recycling, with initial evidence from studies in HeLa cells.^[6]

Regulation

With the regulation of ARF6, the CENTB1 containing clathrin coat complex functions in two physiological contexts requiring endocytic recycling. Which is integrin recycling, vital for cell migration, and Glut4 recycling, essential for glucose homeostasis.^[6] The CENTB1 protein plays an important role in regulating integrin β1 (ITGB1) by facilitating its export from recycling endosomes to the cell surface and ITGB1-dependent cell migration.^[8]

CENTB1 protein regulates endocytic recycling, which is a process that is essential for diverse cellular function such as nutrient uptake, cell polarity, cell motility, signal transduction, and phagocytosis.^[16] As well, CENTB1 facilitates TfR recycling and establishes its role in cargo sorting.^[16] It was also found that CENTB1 is a component of a novel clathrin coat complex that regulates stimulation-dependent integrin recycling and insulin-stimulated Glut4 recycling.^[6]

Clinical significance

CENTB1 was found to be an example of a protein that was initially characterized in human neutrophils.^[14] CENTB1 could be regarded as beneficial in treating chronic inflammatory disorders dominated by neutrophils, by functioning as a specific modulator of NF-κB activity.^[14]

Ulcerative colitis

CENTB1 gene and protein expression were investigated in patients with ulcerative colitis (UC). CENTB1 gene expression was measured from colonic biopsies of UC patients and was detected by using immunohistochemistry. Its findings indicated that the expression of CENTB1 gene was significantly up-regulated in colonic mucosa from patients with active UC compared to remission UC and the healthy patients.^[15] CENTB1 cells were primarily localized within inflammatory infiltrates and dominated by polymorphonuclear cells. As well, extending from the adventitia to the mucosa, with higher abundance observed in epithelial cells and the adventitia. Therefore, it suggest that CENTB1 is involved in the inflammatory process in patients with UC.^[15]

References

1. ENSG00000288169 GRCh38: Ensembl release 89: ENSG00000072818, ENSG00000288169 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000001588 – 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. Jackson TR, Brown FD, Nie Z, Miura K, Foroni L, Sun J, et al. (October 2000). "ACAPs are arf6 GTPase-activating proteins that function in the cell periphery". The Journal of Cell Biology. 151 (3): 627–638. doi:10.1083/jcb.151.3.627. PMC 2185579. PMID 11062263.
6. Li J, Peters PJ, Bai M, Dai J, Bos E, Kirchhausen T, et al. (July 2007). "An ACAP1-containing clathrin coat complex for endocytic recycling". The Journal of Cell Biology. 178 (3): 453–464. doi:10.1083/jcb.200608033. PMC 2064835. PMID 17664335.
7. Yamamoto-Furusho JK, Barnich N, Xavier R, Hisamatsu T, Podolsky DK (November 2006). "Centaurin beta1 down-regulates nucleotide-binding oligomerization domains 1- and 2-dependent NF-kappaB activation". The Journal of Biological Chemistry. 281 (47): 36060–36070. doi:10.1074/jbc.M602383200. PMID 17005562.
8. "CENTB1 (human)". www.phosphosite.org. Retrieved 2025-12-02.
9. "Protein structure - ACAP1 - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2025-12-02.
10. GeneCards Human Gene Database. "ACAP1 Gene - GeneCards | ACAP1 Protein | ACAP1 Antibody". www.genecards.org. Archived from the original on 2025-08-14. Retrieved 2025-12-03.
11. Li J, Peters PJ, Bai M, Dai J, Bos E, Kirchhausen T, et al. (July 2007). "An ACAP1-containing clathrin coat complex for endocytic recycling". The Journal of Cell Biology. 178 (3): 453–464. doi:10.1083/jcb.200608033. PMC 2064835. PMID 17664335.
12. Ma Z, Nie Z, Luo R, Casanova JE, Ravichandran KS (April 2007). "Regulation of Arf6 and ACAP1 signaling by the PTB-domain-containing adaptor protein GULP". Current Biology. 17 (8): 722–727. doi:10.1016/j.cub.2007.03.014. PMC 1930157. PMID 17398097.
13. Li J, Ballif BA, Powelka AM, Dai J, Gygi SP, Hsu VW (November 2005). "Phosphorylation of ACAP1 by Akt regulates the stimulation-dependent recycling of integrin beta1 to control cell migration". Developmental Cell. 9 (5): 663–673. doi:10.1016/j.devcel.2005.09.012. PMID 16256741.
14. Tomazella GG, da Silva I, Laure HJ, Rosa JC, Chammas R, Wiker HG, et al. (August 2009). "Proteomic analysis of total cellular proteins of human neutrophils". Proteome Science. 7 (1): 32. doi:10.1186/1477-5956-7-32. PMC 3224919. PMID 19719850.
15. Yamamoto-Furusho JK, Furuzawa-Carballeda J, Fonseca-Camarillo G (July 2013). "Gene and protein expression of centaurin beta 1 (CENTB1) are up-regulated in patients with ulcerative colitis". Journal of Crohn's & Colitis. 7 (6): e238–e239. doi:10.1016/j.crohns.2012.12.004. PMID 23317930.
16. Dai J, Li J, Bos E, Porcionatto M, Premont RT, Bourgoin S, et al. (November 2004). "ACAP1 promotes endocytic recycling by recognizing recycling sorting signals". Developmental Cell. 7 (5): 771–776. doi:10.1016/j.devcel.2004.10.002. PMID 15525538.

Further reading

• Nomura N, Nagase T, Miyajima N, Sazuka T, Tanaka A, Sato S, et al. (1995). "Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1". DNA Research. 1 (5): 223–229. doi:10.1093/dnares/1.5.223. PMID 7584044.
• Dai J, Li J, Bos E, Porcionatto M, Premont RT, Bourgoin S, et al. (November 2004). "ACAP1 promotes endocytic recycling by recognizing recycling sorting signals". Developmental Cell. 7 (5): 771–776. doi:10.1016/j.devcel.2004.10.002. PMID 15525538.
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–1178. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
• Zhan X, Desiderio DM (July 2006). "Nitroproteins from a human pituitary adenoma tissue discovered with a nitrotyrosine affinity column and tandem mass spectrometry". Analytical Biochemistry. 354 (2): 279–289. doi:10.1016/j.ab.2006.05.024. PMID 16777052.
• Yamamoto-Furusho JK, Barnich N, Xavier R, Hisamatsu T, Podolsky DK (November 2006). "Centaurin beta1 down-regulates nucleotide-binding oligomerization domains 1- and 2-dependent NF-kappaB activation". The Journal of Biological Chemistry. 281 (47): 36060–36070. doi:10.1074/jbc.M602383200. PMID 17005562.
• Shinozaki-Narikawa N, Kodama T, Shibasaki Y (November 2006). "Cooperation of phosphoinositides and BAR domain proteins in endosomal tubulation". Traffic. 7 (11): 1539–1550. doi:10.1111/j.1600-0854.2006.00480.x. PMID 17010122. S2CID 39282089.
• Li J, Peters PJ, Bai M, Dai J, Bos E, Kirchhausen T, et al. (July 2007). "An ACAP1-containing clathrin coat complex for endocytic recycling". The Journal of Cell Biology. 178 (3): 453–464. doi:10.1083/jcb.200608033. PMC 2064835. PMID 17664335.

External links

• Human ACAP1 genome location and ACAP1 gene details page in the UCSC Genome Browser.