NOS1AP

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.^[3][4][5]

NOS1AP
Identifiers
Aliases	NOS1AP, 6330408P19Rik, CAPON, nitric oxide synthase 1 adaptor protein, NPHS22
External IDs	OMIM: 605551; HomoloGene: 136252; GeneCards: NOS1AP; OMA:NOS1AP - orthologs
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1q23.3 Start 162,069,691 bp[1] End 162,370,475 bp[1]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Region I of hippocampus proper cerebellar vermis frontal pole orbitofrontal cortex prefrontal cortex paraflocculus of cerebellum right hemisphere of cerebellum superior frontal gyrus Brodmann area 46 parietal lobe n/a More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding nitric-oxide synthase binding Cellular component L-type voltage-gated calcium channel complex cytosol nuclear membrane inward rectifier potassium channel complex perinuclear region of cytoplasm sarcolemma nucleus mitochondrion caveola Z discdkac T-tubule sarcoplasmic reticulum membrane glutamatergic synapse Biological process positive regulation of peptidyl-cysteine S-nitrosylation regulation of cardiac muscle cell action potential positive regulation of nitric oxide biosynthetic process regulation of nitric-oxide synthase activity positive regulation of delayed rectifier potassium channel activity positive regulation of gene expression positive regulation of nitric oxide mediated signal transduction positive regulation of nitric-oxide synthase activity regulation of high voltage-gated calcium channel activity positive regulation of potassium ion transmembrane transport regulation of heart rate by chemical signal positive regulation of voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization regulation of nitric oxide biosynthetic process regulation of calcium ion transmembrane transport via high voltage-gated calcium channel regulation of ventricular cardiac muscle cell membrane repolarization postsynaptic actin cytoskeleton organization Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 9722 n/a Ensembl ENSG00000198929 n/a UniProt O75052 n/a RefSeq (mRNA) NM_014697 NM_001126060 NM_001164757 n/a RefSeq (protein) NP_001119532 NP_001158229 NP_055512 n/a Location (UCSC) Chr 1: 162.07 – 162.37 Mb n/a PubMed search [2] n/a
Wikidata
View/Edit Human

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.^[5] NOS1AP polymorphisms has been associated with the QT interval length.^[6]

Interactions

NOS1AP has been shown to interact with:

• LRP1,^[7]
• LRP2,^[7]
• NOS1,^[4]
• RASD1,^[8]
• SYN1^[9]

References

1. GRCh38: Ensembl release 89: ENSG00000198929 – Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. Seki N, Ohira M, Nagase T, Ishikawa K, Miyajima N, Nakajima D, Nomura N, Ohara O (February 1998). "Characterization of cDNA clones in size-fractionated cDNA libraries from human brain". DNA Res. 4 (5): 345–9. doi:10.1093/dnares/4.5.345. PMID 9455484. S2CID 263410587.
4. Jaffrey SR, Snowman AM, Eliasson MJ, Cohen NA, Snyder SH (Mar 1998). "CAPON: a protein associated with neuronal nitric oxide synthase that regulates its interactions with PSD95". Neuron. 20 (1): 115–24. doi:10.1016/S0896-6273(00)80439-0. PMID 9459447. S2CID 14613261.
5. "Entrez Gene: NOS1AP nitric oxide synthase 1 (neuronal) adaptor protein".
6. 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 (2006). "A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization". Nat. Genet. 38 (6): 644–51. doi:10.1038/ng1790. PMID 16648850. S2CID 12942685.
7. Gotthardt M, Trommsdorff M, Nevitt MF, Shelton J, Richardson JA, Stockinger W, Nimpf J, Herz J (August 2000). "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. doi:10.1074/jbc.M000955200. PMID 10827173.
8. Fang M, Jaffrey SR, Sawa A, Ye K, Luo X, Snyder SH (October 2000). "Dexras1: a G protein specifically coupled to neuronal nitric oxide synthase via CAPON". Neuron. 28 (1): 183–93. doi:10.1016/S0896-6273(00)00095-7. PMID 11086993. S2CID 10533464.
9. Jaffrey SR, Benfenati F, Snowman AM, Czernik AJ, Snyder SH (March 2002). "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. Bibcode:2002PNAS...99.3199J. doi:10.1073/pnas.261705799. PMC 122496. PMID 11867766.

Further reading

• Gotthardt M, Trommsdorff M, Nevitt MF, Shelton J, Richardson JA, Stockinger W, Nimpf J, Herz J (2000). "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. doi:10.1074/jbc.M000955200. PMID 10827173.
• Hartley JL, Temple GF, Brasch MA (2000). "DNA cloning using in vitro site-specific recombination". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
• Zheng Y, Li H, Qin W, Chen W, Duan Y, Xiao Y, Li C, Zhang J, Li X, Feng G, He L (2005). "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. doi:10.1016/j.bbrc.2005.01.037. PMID 15707951.
• Xu B, Wratten N, Charych EI, Buyske S, Firestein BL, Brzustowicz LM (2005). "Increased expression in dorsolateral prefrontal cortex of CAPON in schizophrenia and bipolar disorder". PLOS Med. 2 (10): e263. doi:10.1371/journal.pmed.0020263. PMC 1201690. PMID 16146415.
• 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 (2006). "Failure to confirm allelic association between markers at the CAPON gene locus and schizophrenia in a British sample". Biol. Psychiatry. 59 (2): 195–7. doi:10.1016/j.biopsych.2005.08.015. PMID 16202394. S2CID 29114143.
• Post W, Shen H, Damcott C, Arking DE, Kao WH, Sack PA, Ryan KA, Chakravarti A, Mitchell BD, Shuldiner AR (2007). "Associations between genetic variants in the NOS1AP (CAPON) gene and cardiac repolarization in the old order Amish". Hum. Hered. 64 (4): 214–9. doi:10.1159/000103630. PMC 2880727. PMID 17565224.