NOS1AP explained

Nitric oxide synthase 1 adaptor protein (NOS1AP) also known as carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase protein (CAPON) is a protein that in humans is encoded by the NOS1AP gene.^{[1] [2] [3]}

This gene encodes a cytosolic protein that binds to the signaling molecule, neuronal nitric oxide synthase (nNOS). This protein has a C-terminal PDZ-binding domain that mediates interactions with nNOS and an N-terminal phosphotyrosine binding (PTB) domain that binds to the small monomeric G protein, Dexras1. Studies of the related mouse and rat proteins have shown that this protein functions as an adapter protein linking nNOS to specific targets, such as Dexras1 and the synapsins. NOS1AP polymorphisms has been associated with the QT interval length.^[4]

Interactions

NOS1AP has been shown to interact with:

• LRP1,
• LRP2,^[5]
• NOS1,
• RASD1,^[6]
• SYN1^[7]

Further reading

• Gotthardt M, Trommsdorff M, Nevitt MF, Shelton J, Richardson JA, Stockinger W, Nimpf J, Herz J . Interactions of the low density lipoprotein receptor gene family with cytosolic adaptor and scaffold proteins suggest diverse biological functions in cellular communication and signal transduction . J. Biol. Chem. . 275 . 33 . 25616–24 . 2000 . 10827173 . 10.1074/jbc.M000955200 . free .
• Hartley JL, Temple GF, Brasch MA . DNA cloning using in vitro site-specific recombination . Genome Res. . 10 . 11 . 1788–95 . 2000 . 11076863 . 310948 . 10.1101/gr.143000 .
• Zheng Y, Li H, Qin W, Chen W, Duan Y, Xiao Y, Li C, Zhang J, Li X, Feng G, He L . Association of the carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase gene with schizophrenia in the Chinese Han population . Biochem. Biophys. Res. Commun. . 328 . 4 . 809–15 . 2005 . 15707951 . 10.1016/j.bbrc.2005.01.037 .
• Xu B, Wratten N, Charych EI, Buyske S, Firestein BL, Brzustowicz LM . Increased expression in dorsolateral prefrontal cortex of CAPON in schizophrenia and bipolar disorder . PLOS Med. . 2 . 10 . e263 . 2005 . 16146415 . 1201690 . 10.1371/journal.pmed.0020263 . free .
• Puri V, McQuillin A, Thirumalai S, Lawrence J, Krasucki R, Choudhury K, Datta S, Kerwin S, Quested D, Bass N, Pimm J, Lamb G, Moorey H, Kandasami G, Badacsonyi A, Kelly K, Morgan J, Punukollu B, Nadeem H, Curtis D, Gurling HM . Failure to confirm allelic association between markers at the CAPON gene locus and schizophrenia in a British sample . Biol. Psychiatry . 59 . 2 . 195–7 . 2006 . 16202394 . 10.1016/j.biopsych.2005.08.015 . 29114143 .
• Post W, Shen H, Damcott C, Arking DE, Kao WH, Sack PA, Ryan KA, Chakravarti A, Mitchell BD, Shuldiner AR . Associations between genetic variants in the NOS1AP (CAPON) gene and cardiac repolarization in the old order Amish . Hum. Hered. . 64 . 4 . 214–9 . 2007 . 17565224 . 2880727 . 10.1159/000103630 .

Notes and References

1. Seki N, Ohira M, Nagase T, Ishikawa K, Miyajima N, Nakajima D, Nomura N, Ohara O . Characterization of cDNA clones in size-fractionated cDNA libraries from human brain . DNA Res. . 4 . 5 . 345–9 . February 1998 . 9455484 . 10.1093/dnares/4.5.345 . free . 263410587 .
2. Jaffrey SR, Snowman AM, Eliasson MJ, Cohen NA, Snyder SH . CAPON: a protein associated with neuronal nitric oxide synthase that regulates its interactions with PSD95 . Neuron . 20 . 1 . 115–24 . Mar 1998 . 9459447 . 10.1016/S0896-6273(00)80439-0 . 14613261 . free .
3. Web site: Entrez Gene: NOS1AP nitric oxide synthase 1 (neuronal) adaptor protein.
4. Arking DE, Pfeufer A, Post W, Kao WH, Newton-Cheh C, Ikeda M, West K, Kashuk C, Akyol M, Perz S, Jalilzadeh S, Illig T, Gieger C, Guo CY, Larson MG, Wichmann HE, Marbán E, O'Donnell CJ, Hirschhorn JN, Kääb S, Spooner PM, Meitinger T, Chakravarti A . A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization . Nat. Genet. . 38 . 6 . 644–51 . 2006 . 16648850 . 10.1038/ng1790 . 12942685 .
5. Gotthardt M, Trommsdorff M, Nevitt MF, Shelton J, Richardson JA, Stockinger W, Nimpf J, Herz J . Interactions of the low density lipoprotein receptor gene family with cytosolic adaptor and scaffold proteins suggest diverse biological functions in cellular communication and signal transduction . J. Biol. Chem. . 275 . 33 . 25616–24 . August 2000 . 10827173 . 10.1074/jbc.M000955200 . free .
6. Fang M, Jaffrey SR, Sawa A, Ye K, Luo X, Snyder SH . Dexras1: a G protein specifically coupled to neuronal nitric oxide synthase via CAPON . Neuron . 28 . 1 . 183–93 . October 2000 . 11086993 . 10.1016/S0896-6273(00)00095-7 . 10533464 . free .
7. Jaffrey SR, Benfenati F, Snowman AM, Czernik AJ, Snyder SH . Neuronal nitric-oxide synthase localization mediated by a ternary complex with synapsin and CAPON . Proc. Natl. Acad. Sci. U.S.A. . 99 . 5 . 3199–204 . March 2002 . 11867766 . 122496 . 10.1073/pnas.261705799 . 2002PNAS...99.3199J . free .