Centaurin, alpha 1

Arf-GAP with dual PH domain-containing protein 1 is a protein that in humans is encoded by the ADAP1 gene.[5][6]

ADAP1
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 3FEH, 3FM8, 3LJU, 3MDB
Identifiers
Aliases	ADAP1, CENTA1, GCS1L, p42IP4, Centaurin, alpha 1, ArfGAP with dual PH domains 1
External IDs	OMIM: 608114 MGI: 2442201 HomoloGene: 55997 GeneCards: ADAP1
Gene location (Human) Chr. Chromosome 7 (human)[1] Band 7p22.3 Start 897,900 bp[1] End 955,407 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5|5 G2 Start 139,271,876 bp[2] End 139,325,622 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GO:0001948 protein binding • metal ion binding • GO:0005097, GO:0005099, GO:0005100 GTPase activator activity • inositol 1,3,4,5 tetrakisphosphate binding • phosphatidylinositol-3,4,5-trisphosphate binding • phosphatidylinositol bisphosphate binding Cellular component • cytoplasm • cell membrane • cell nucleus • cytosol Biological process • GO:0043087, GO:0032313, GO:0032319, GO:0032314, GO:0043088 regulation of GTPase activity • cell surface receptor signaling pathway • GO:0032320, GO:0032321, GO:0032855, GO:0043089, GO:0032854 positive regulation of GTPase activity Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	11033	231821
Ensembl	ENSG00000105963	ENSMUSG00000056413
UniProt	O75689	n/a
RefSeq (mRNA)	NM_006869 NM_001284308 NM_001284309 NM_001284310 NM_001284311	NM_172723
RefSeq (protein)	NP_001271237 NP_001271238 NP_001271239 NP_001271240 NP_006860	n/a
Location (UCSC)	Chr 7: 0.9 – 0.96 Mb	Chr 5: 139.27 – 139.33 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Interactions

Centaurin, alpha 1 has been shown to interact with:

• Casein kinase 1, alpha 1[7][8]
• Nucleolin,[9]
• P110α,[10]
• PRKCI,[10]
• Protein kinase D1,[10] and
• Protein kinase Mζ.[10]

Model organisms

Model organisms have been used in the study of ADAP1 function. A conditional knockout mouse line called Adap1^{tm1a(EUCOMM)Wtsi} was generated at the Wellcome Trust Sanger Institute.[11] Male and female animals underwent a standardized phenotypic screen[12] to determine the effects of deletion.[13][14][15][16] Additional screens performed:

• In-depth immunological phenotyping[17]
• in-depth bone and cartilage phenotyping[18]

Adap1 knockout mouse phenotype

Characteristic	Phenotype
All data available at.[12][17][18]
Insulin	Normal
Homozygous viability at P14	Normal
Homozygous Fertility	Normal
Body weight	Normal
Neurological assessment	Normal
Grip strength	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology 16 Weeks	Normal
Peripheral blood leukocytes 16 Weeks	Normal
Salmonella infection	Normal
Epidermal Immune Composition	Normal
Influenza Challenge	Abnormal

References

1. GRCh38: Ensembl release 89: ENSG00000105963 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000056413 - 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. Venkateswarlu K, Oatey PB, Tavaré JM, Jackson TR, Cullen PJ (Jun 1999). "Identification of centaurin-alpha1 as a potential in vivo phosphatidylinositol 3,4,5-trisphosphate-binding protein that is functionally homologous to the yeast ADP-ribosylation factor (ARF) GTPase-activating protein, Gcs1". The Biochemical Journal. 340 (2): 359–63. doi:10.1042/0264-6021:3400359. PMC 1220257. PMID 10333475.
6. "Entrez Gene: CENTA1 centaurin, alpha 1".
7. Dubois T, Howell S, Zemlickova E, Aitken A (Apr 2002). "Identification of casein kinase Ialpha interacting protein partners". FEBS Letters. 517 (1–3): 167–71. doi:10.1016/s0014-5793(02)02614-5. PMID 12062430.
8. Dubois T, Kerai P, Zemlickova E, Howell S, Jackson TR, Venkateswarlu K, Cullen PJ, Theibert AB, Larose L, Roach PJ, Aitken A (Jun 2001). "Casein kinase I associates with members of the centaurin-alpha family of phosphatidylinositol 3,4,5-trisphosphate-binding proteins". The Journal of Biological Chemistry. 276 (22): 18757–64. doi:10.1074/jbc.M010005200. PMID 11278595.
9. Dubois T, Zemlickova E, Howell S, Aitken A (Feb 2003). "Centaurin-alpha 1 associates in vitro and in vivo with nucleolin". Biochemical and Biophysical Research Communications. 301 (2): 502–8. doi:10.1016/s0006-291x(02)03010-3. PMID 12565890.
10. Zemlickova E, Dubois T, Kerai P, Clokie S, Cronshaw AD, Wakefield RI, Johannes FJ, Aitken A (Aug 2003). "Centaurin-alpha(1) associates with and is phosphorylated by isoforms of protein kinase C". Biochemical and Biophysical Research Communications. 307 (3): 459–65. doi:10.1016/s0006-291x(03)01187-2. PMID 12893243.
11. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
12. "International Mouse Phenotyping Consortium".
13. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
14. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
15. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
16. White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Sanger Institute Mouse Genetics Project, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
17. "Infection and Immunity Immunophenotyping (3i) Consortium".
18. "OBCD Consortium".

Further reading

• Venkateswarlu K, Cullen PJ (Aug 1999). "Molecular cloning and functional characterization of a human homologue of centaurin-alpha". Biochemical and Biophysical Research Communications. 262 (1): 237–44. doi:10.1006/bbrc.1999.1065. PMID 10448098.
• Dubois T, Kerai P, Zemlickova E, Howell S, Jackson TR, Venkateswarlu K, Cullen PJ, Theibert AB, Larose L, Roach PJ, Aitken A (Jun 2001). "Casein kinase I associates with members of the centaurin-alpha family of phosphatidylinositol 3,4,5-trisphosphate-binding proteins". The Journal of Biological Chemistry. 276 (22): 18757–64. doi:10.1074/jbc.M010005200. PMID 11278595.
• Sedehizade F, Hanck T, Stricker R, Horstmayer A, Bernstein HG, Reiser G (Feb 2002). "Cellular expression and subcellular localization of the human Ins(1,3,4,5)P(4)-binding protein, p42(IP4), in human brain and in neuronal cells". Brain Research. Molecular Brain Research. 99 (1): 1–11. doi:10.1016/S0169-328X(01)00335-7. PMID 11869802.
• Whitley P, Gibbard AM, Koumanov F, Oldfield S, Kilgour EE, Prestwich GD, Holman GD (Apr 2002). "Identification of centaurin-alpha2: a phosphatidylinositide-binding protein present in fat, heart and skeletal muscle". European Journal of Cell Biology. 81 (4): 222–30. doi:10.1078/0171-9335-00242. PMID 12018390.
• Reiser G, Bernstein HG (Dec 2002). "Neurons and plaques of Alzheimer's disease patients highly express the neuronal membrane docking protein p42IP4/centaurin alpha". NeuroReport. 13 (18): 2417–9. doi:10.1097/00001756-200212200-00008. PMID 12499840.
• Dubois T, Zemlickova E, Howell S, Aitken A (Feb 2003). "Centaurin-alpha 1 associates in vitro and in vivo with nucleolin". Biochemical and Biophysical Research Communications. 301 (2): 502–8. doi:10.1016/S0006-291X(02)03010-3. PMID 12565890.
• Matsuda A, Suzuki Y, Honda G, Muramatsu S, Matsuzaki O, Nagano Y, Doi T, Shimotohno K, Harada T, Nishida E, Hayashi H, Sugano S (May 2003). "Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways". Oncogene. 22 (21): 3307–18. doi:10.1038/sj.onc.1206406. PMID 12761501.
• Zemlickova E, Dubois T, Kerai P, Clokie S, Cronshaw AD, Wakefield RI, Johannes FJ, Aitken A (Aug 2003). "Centaurin-alpha(1) associates with and is phosphorylated by isoforms of protein kinase C". Biochemical and Biophysical Research Communications. 307 (3): 459–65. doi:10.1016/S0006-291X(03)01187-2. PMID 12893243.
• Venkateswarlu K, Brandom KG, Lawrence JL (Feb 2004). "Centaurin-alpha1 is an in vivo phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating protein for ARF6 that is involved in actin cytoskeleton organization" (PDF). The Journal of Biological Chemistry. 279 (8): 6205–8. doi:10.1074/jbc.C300482200. PMID 14625293.
• Hanck T, Stricker R, Sedehizade F, Reiser G (Jan 2004). "Identification of gene structure and subcellular localization of human centaurin alpha 2, and p42IP4, a family of two highly homologous, Ins 1,3,4,5-P4-/PtdIns 3,4,5-P3-binding, adapter proteins". Journal of Neurochemistry. 88 (2): 326–36. doi:10.1046/j.1471-4159.2003.02143.x. PMID 14690521.
• Reiser G, Bernstein HG (Jan 2004). "Altered expression of protein p42IP4/centaurin-alpha 1 in Alzheimer's disease brains and possible interaction of p42IP4 with nucleolin". NeuroReport. 15 (1): 147–8. doi:10.1097/00001756-200401190-00028. PMID 15106847.
• Thacker E, Kearns B, Chapman C, Hammond J, Howell A, Theibert A (Oct 2004). "The arf6 GAP centaurin alpha-1 is a neuronal actin-binding protein which also functions via GAP-independent activity to regulate the actin cytoskeleton". European Journal of Cell Biology. 83 (10): 541–54. doi:10.1078/0171-9335-00416. PMID 15679100.
• Lawrence J, Mundell SJ, Yun H, Kelly E, Venkateswarlu K (Jun 2005). "Centaurin-alpha 1, an ADP-ribosylation factor 6 GTPase activating protein, inhibits beta 2-adrenoceptor internalization". Molecular Pharmacology. 67 (6): 1822–8. doi:10.1124/mol.105.011338. PMID 15778454.
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
• Hayashi H, Matsuzaki O, Muramatsu S, Tsuchiya Y, Harada T, Suzuki Y, Sugano S, Matsuda A, Nishida E (Jan 2006). "Centaurin-alpha1 is a phosphatidylinositol 3-kinase-dependent activator of ERK1/2 mitogen-activated protein kinases". The Journal of Biological Chemistry. 281 (3): 1332–7. doi:10.1074/jbc.M505905200. PMID 16287813.
• Sedehizade F, von Klot C, Hanck T, Reiser G (Oct 2005). "p42(IP4)/centaurin alpha1, a brain-specific PtdIns(3,4,5)P3/Ins(1,3,4,5)P4-binding protein: membrane trafficking induced by epidermal growth factor is inhibited by stimulation of phospholipase C-coupled thrombin receptor". Neurochemical Research. 30 (10): 1319–30. doi:10.1007/s11064-005-8804-1. PMID 16341594.