Gene Report

Basic Information

Approved Symbol	NOS1
Approved Name	nitric oxide synthase 1 (neuronal)
Previous Symbol	NOS
Symbol Alias	nNOS
Location	12q24.22
Position	chr12:117799317-117799607 (-)
External Links	Entrez Gene: 4842 Ensembl: ENSG00000089250 UCSC: uc001twn.2 HGNC ID: 7872
No. of Studies (Positive/Negative)	1(0/1)
Type	Literature-origin; Protein mapped

Positive relationships between NOS1 and MDD (count: 0)

Positive relationships between NOS1 and other components at different levels (count: 0)

Positive relationship network of NOS1 in MK4MDD

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Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between NOS1 and MDD (count: 1)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
NOS1	Okumura T, 2010	Patients and nomal controls		We did not detect a significant association between NOS1 and...... We did not detect a significant association between NOS1 and MDD, BP or the fluvoxamine therapeutic response in MDD in allele/genotype-wise analysis. More...

Negative relationships between NOS1 and other components at different levels (count: 0)

NOS1 related SNPs in MK4MDD (count: 0)

NOS1 related proteins in MK4MDD (count: 1)

Approved Name	UniportKB	No. of Studies (Positive/Negative)	Source
Nitric oxide synthase, brain	P29475	2(2/0)	Literature-origin

NOS1 related GO terms (count: 96)

ID	Name	Type	Evidence
Literature-origin GO terms
GO:0043197	dendritic spine	cellular component	IEA
GO:0014069	postsynaptic density	cellular component	IEA
GO:0005856	cytoskeleton	cellular component	ISS[7545544]

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0060314	regulation of ryanodine-sensitive calcium-release channel activity	biological process	TAS[21536106]
GO:0051346	negative regulation of hydrolase activity	biological process	ISS
GO:0033197	response to vitamin E	biological process	IEA
GO:0007596	blood coagulation	biological process	TAS
GO:0006527	arginine catabolic process	biological process	IC[7545544]
GO:1900273	positive regulation of long-term synaptic potentiation	biological process	IEA
GO:0009408	response to heat	biological process	IDA[18048451]
GO:1901206	positive regulation of adrenergic receptor signaling pathway involved in heart process	biological process	IEA
GO:0055117	regulation of cardiac muscle contraction	biological process	TAS[9892689]
GO:1901216	positive regulation of neuron death	biological process	IEA
GO:0044325	ion channel binding	molecular function	ISS; TAS[21536106]
GO:0042803	protein homodimerization activity	molecular function	IEA
GO:0045909	positive regulation of vasodilation	biological process	IDA[18048451]; IMP[18391107]
GO:0035066	positive regulation of histone acetylation	biological process	ISS
GO:0046676	negative regulation of insulin secretion	biological process	IEA
GO:0001917	photoreceptor inner segment	cellular component	ISS[17027776]
GO:0048148	behavioral response to cocaine	biological process	IEA
GO:0050767	regulation of neurogenesis	biological process	IEA
GO:0043234	protein complex	cellular component	ISS
GO:0005737	cytoplasm	cellular component	TAS[17892502]
GO:0030315	T-tubule	cellular component	IEA
GO:0005515	protein binding	molecular function	IPI[11149895\|17161399]
GO:0045906	negative regulation of vasoconstriction	biological process	IEA
GO:0045471	response to ethanol	biological process	IEA
GO:0042582	azurophil granule	cellular component	IEA
GO:0051930	regulation of sensory perception of pain	biological process	IEA
GO:0061337	cardiac conduction	biological process	TAS
GO:0030018	Z disc	cellular component	IEA
GO:0005901	caveola	cellular component	IEA
GO:0010288	response to lead ion	biological process	IEA
GO:0071731	response to nitric oxide	biological process	IEA
GO:0005516	calmodulin binding	molecular function	IEA
GO:0016529	sarcoplasmic reticulum	cellular component	IDA[9892689]
GO:0035094	response to nicotine	biological process	IEA
GO:0010523	negative regulation of calcium ion transport into cytosol	biological process	TAS[17568574]
GO:0007520	myoblast fusion	biological process	TAS[7545544]
GO:0006809	nitric oxide biosynthetic process	biological process	ISS[7545544]
GO:0034618	arginine binding	molecular function	TAS[17029414]
GO:0098735	positive regulation of the force of heart contraction	biological process	ISS
GO:0007565	female pregnancy	biological process	IEA
GO:0004517	nitric-oxide synthase activity	molecular function	IDA[1689048]; ISS[7545544]
GO:0055114	oxidation-reduction process	biological process	IEA
GO:0020037	heme binding	molecular function	ISS
GO:0048471	perinuclear region of cytoplasm	cellular component	ISS[17027776]
GO:0032496	response to lipopolysaccharide	biological process	IEA
GO:0045776	negative regulation of blood pressure	biological process	IBA
GO:0007568	aging	biological process	IEA
GO:0045121	membrane raft	cellular component	ISS
GO:0012506	vesicle membrane	cellular component	IEA
GO:0005739	mitochondrion	cellular component	ISS
GO:0045202	synapse	cellular component	ISS
GO:0017080	sodium channel regulator activity	molecular function	ISS
GO:0018119	peptidyl-cysteine S-nitrosylation	biological process	ISS
GO:1902307	positive regulation of sodium ion transmembrane transport	biological process	ISS
GO:0033555	multicellular organismal response to stress	biological process	IMP[18391107]
GO:0042383	sarcolemma	cellular component	IDA[7545544]
GO:0031965	nuclear membrane	cellular component	IEA
GO:0010181	FMN binding	molecular function	ISS
GO:0005829	cytosol	cellular component	TAS
GO:0043434	response to peptide hormone	biological process	IEA
GO:0034617	tetrahydrobiopterin binding	molecular function	NAS[7488039]
GO:0071260	cellular response to mechanical stimulus	biological process	IEA
GO:0045822	negative regulation of heart contraction	biological process	IEA
GO:0071363	cellular response to growth factor stimulus	biological process	ISS
GO:0045893	positive regulation of transcription, DNA-templated	biological process	ISS
GO:0051926	negative regulation of calcium ion transport	biological process	ISS
GO:0001666	response to hypoxia	biological process	IEP[16276418]
GO:0042738	exogenous drug catabolic process	biological process	ISS
GO:0045454	cell redox homeostasis	biological process	TAS
GO:0005741	mitochondrial outer membrane	cellular component	IEA
GO:1903779	regulation of cardiac conduction	biological process	TAS
GO:0002028	regulation of sodium ion transport	biological process	ISS
GO:0043066	negative regulation of apoptotic process	biological process	IEA
GO:0043627	response to estrogen	biological process	IEA
GO:0005506	iron ion binding	molecular function	IEA
GO:0007263	nitric oxide mediated signal transduction	biological process	IBA
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	biological process	ISS
GO:0043267	negative regulation of potassium ion transport	biological process	ISS
GO:0097110	scaffold protein binding	molecular function	ISS
GO:1902514	regulation of generation of L-type calcium current	biological process	TAS[21536106]
GO:0019899	enzyme binding	molecular function	IEA
GO:0014823	response to activity	biological process	IEA
GO:0051612	negative regulation of serotonin uptake	biological process	ISS
GO:0031284	positive regulation of guanylate cyclase activity	biological process	IBA
GO:0008285	negative regulation of cell proliferation	biological process	IEA
GO:0050660	flavin adenine dinucleotide binding	molecular function	ISS
GO:0050661	NADP binding	molecular function	ISS
GO:0051481	negative regulation of cytosolic calcium ion concentration	biological process	IEA
GO:0042136	neurotransmitter biosynthetic process	biological process	TAS[7545544]
GO:0006941	striated muscle contraction	biological process	ISS
GO:1990425	ryanodine receptor complex	cellular component	TAS[21536106]
GO:1901205	negative regulation of adrenergic receptor signaling pathway involved in heart process	biological process	TAS[21536106]
GO:0046870	cadmium ion binding	molecular function	ISS

NOS1 related KEGG pathways (count: 5)

ID	Name	Brief Description	Full Description
Literature-origin KEGG pathway
hsa04020	calcium signaling_pathway	Calcium signaling pathway	Ca2+ that enters the cell from the outside is a principal so...... Ca2+ that enters the cell from the outside is a principal source of signal Ca2+. Entry of Ca2+ is driven by the presence of a large electrochemical gradient across the plasma membrane. Cells use this external source of signal Ca2+ by activating various entry channels with widely different properties. The voltage-operated channels (VOCs) are found in excitable cells and generate the rapid Ca2+ fluxes that control fast cellular processes. There are many other Ca2+-entry channels, such as the receptor-operated channels (ROCs), for example the NMDA (N-methyl-D-aspartate) receptors (NMDARs) that respond to glutamate. There also are second-messenger-operated channels (SMOCs) and store-operated channels (SOCs). The other principal source of Ca2+ for signalling is the internal stores that are located primarily in the endoplasmic/sarcoplasmic reticulum (ER/SR), in which inositol-1,4,5-trisphosphate receptors (IP3Rs) or ryanodine receptors (RYRs) regulate the release of Ca2+. The principal activator of these channels is Ca2+ itself and this process of Ca2+-induced Ca2+ release is central to the mechanism of Ca2+ signalling. Various second messengers or modulators also control the release of Ca2+. IP3, which is generated by pathways using different isoforms of phospholipase C (PLCbeta, delta, epsilon, gamma and zeta), regulates the IP3Rs. Cyclic ADP-ribose (cADPR) releases Ca2+ via RYRs. Nicotinic acid adenine dinucleotide phosphate (NAADP) may activate a distinct Ca2+ release mechanism on separate acidic Ca2+ stores. Ca2+ release via the NAADP-sensitive mechanism may also feedback onto either RYRs or IP3Rs. cADPR and NAADP are generated by CD38. This enzyme might be sensitive to the cellular metabolism, as ATP and NADH inhibit it. The influx of Ca2+ from the environment or release from internal stores causes a very rapid and dramatic increase in cytoplasmic calcium concentration, which has been widely exploited for signal transduction. Some proteins, such as troponin C (TnC) involved in muscle contraction, directly bind to and sense Ca2+. However, in other cases Ca2+ is sensed through intermediate calcium sensors such as calmodulin (CALM). More...
hsa04730	long term_depression	Long-term depression	Cerebellar long-term depression (LTD), thought to be a molec...... Cerebellar long-term depression (LTD), thought to be a molecular and cellular basis for cerebellar learning, is a process involving a decrease in the synaptic strength between parallel fiber (PF) and Purkinje cells (PCs) induced by the conjunctive activation of PFs and climbing fiber (CF). Multiple signal transduction pathways have been shown to be involved in this process. Activation of PFs terminating on spines in dendritic branchlets leads to glutamate release and activation of both AMPA and mGluRs. Activation of CFs, which make multiple synaptic contacts on proximal dendrites, also via AMPA receptors, opens voltage-gated calcium channels (VGCCs) and causes a generalized influx of calcium. These cellular signals, generated from two different synaptic origins, trigger a cascade of events culminating in a phosphorylation-dependent, long-term reduction in AMPA receptor sensitivity at the PF-PC synapse. This may take place either through receptor internalization and/or through receptor desensitization. More...

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
hsa00330	arginine and_proline_metabolism	Arginine and proline metabolism
hsa05010	alzheimers disease	Alzheimer's disease	Alzheimer's disease (AD) is a chronic disorder that slowly d...... Alzheimer's disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-beta (Abeta), a major component of senile plaques, has various pathological effects on cell and organelle function. The extracellular Abeta oligomers may activate caspases through activation of cell surface death receptors. Alternatively, intracellular Abeta may contribute to pathology by facilitating tau hyper-phosphorylation, disrupting mitochondria function, and triggering calcium dysfunction. To date genetic studies have revealed four genes that may be linked to autosomal dominant or familial early onset AD (FAD). These four genes include: amyloid precursor protein (APP), presenilin 1 (PS1), presenilin 2 (PS2) and apolipoprotein E (ApoE). All mutations associated with APP and PS proteins can lead to an increase in the production of Abeta peptides, specifically the more amyloidogenic form, Abeta42. FAD-linked PS1 mutation downregulates the unfolded protein response and leads to vulnerability to ER stress. More...
hsa05014	amyotrophic lateral_sclerosis_als	Amyotrophic lateral sclerosis (ALS)	Amyotrophic lateral sclerosis (ALS) is a progressive, lethal...... Amyotrophic lateral sclerosis (ALS) is a progressive, lethal, degenerative disorder of motor neurons. The hallmark of this disease is the selective death of motor neurons in the brain and spinal cord, leading to paralysis of voluntary muscles. Mutant superoxide dismutase 1 (SOD1), as seen in some familial amyotrophic lateral sclerosis (FALS) cases, may be toxic because it is unstable, forming aggregates in the motor neuron cytoplasm, axoplasm and mitochondria. Within mitochondria, mutant SOD1 may interfere with the anti-apoptotic function of Bcl-2, affect mitochondrial import by interfering with the translocation machinery (TOM/TIM), and generate toxic free radicals (ROS) via aberrant superoxide chemistry. These changes may then result in abnormal mitochondrial energy metabolism, Ca2+ handling, and release of pro-apoptotic factors. Reactive oxygen species (ROS), produced within mitochondria, inhibit the function of EAAT2, the main glial glutamate transporter protein, responsible for most of the reuptake of synaptically released glutamate. Glutamate excess causes neurotoxicity by increasing intracellular calcium, which enhances oxidative stress and mitochondrial damage. Mutant SOD1 can also trigger oxidative reactions by various means including by increasing levels of peroxynitrite, which can then cause damage through the formation of hydroxyl radicals or via nitration of tyrosine residues on proteins. Nitration may target neurofilament proteins, disrupting their phosphorylation and affecting axonal transport. Collectively, these mechanisms (or a combination thereof) are predicted to disturb cellular homeostasis (within glial and/or motor neurons), ultimately triggering motor neuron death. More...

NOS1 related BioCarta pathways (count: 1)

ID	Name	Brief Description	Full Description
Gene mapped BioCarta pathways
NOS1_PATHWAY	nos1 pathway	Nitric Oxide Signaling Pathway	Glutamatergic-mediated nitric oxide (NO) production occurs v...... Glutamatergic-mediated nitric oxide (NO) production occurs via the N-methyl-D-aspartic acid (NMDA) postsynaptic density protein 95 (PSD95)-neuronal nitric oxide synthase (NOS1) ternary complex. The increased intracellular Ca2+ stimulates the interaction of nNOS and calmodulin (CaM) and the translocaton of nNOS from the plasma membrane to the cytoplasm. The dephosphorylation of nNOS by Calcineurin catalyzes the conversion of arginine to citrulline and nitric oxide (NO), which turns on guanylate cyclase and the various cGMP regulated signaling pathways. More...

NOS1 related Reactome pathways (count: 0)

NOS1 related interactors from protein-protein interaction data in HPRD (count: 30)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
NOS1	ADRB2	Yes	in vivo	12184796
NOS1	ATP2B4	No	in vitro;in vivo	11591728
NOS1	DLGAP2	No	in vitro	10824095
NOS1	PRKACA	No	in vitro	10400690 , 10874031 , 12630910 , 1375933
NOS1	ARG1	No	in vivo	11849441
NOS1	DLG4	Yes	in vitro;in vivo;yeast 2-hybrid	8625413 , 10488080 , 9459447
NOS1	DLG2	Yes	in vitro;yeast 2-hybrid	8625413 , 8922396
NOS1	HMOX1	No	in vivo	11849436
NOS1	DYNLL1	No	in vitro;in vivo;yeast 2-hybrid	8864115 , 9837926 , 9808772
NOS1	ADRA1A	No	in vivo	12184796
NOS1	CAMK4	No	in vitro	10400690 , 10874031 , 12630910 , 1375933
NOS1	ADRB1	No	in vivo	12184796
NOS1	BDKRB2	No	in vivo	10681501
NOS1	SNTA1	No	in vitro;in vivo	11747091 , 10221915
NOS1	HSP90AA1	No	in vitro;in vivo	11284722 , 9880522
NOS1	NOS1AP	No	in vitro;in vivo;yeast 2-hybrid	9459447
NOS1	ADRA1D	No	in vivo	12184796
NOS1	CAMK2A	Yes	in vitro	10400690 , 10874031 , 12630910 , 1375933
NOS1	NOSIP	Yes	in vivo	15548660
NOS1	ZDHHC23	No	in vitro;in vivo	15105416
NOS1	CAV3	No	in vitro	9353265
NOS1	RASD1	No	in vivo	11086993
NOS1	CTBP1	No	in vitro;in vivo	11590170
NOS1	PTPN6	Yes	in vitro;in vivo	11511520
NOS1	ADRA1B	No	in vivo	12184796
NOS1	VAC14	No	in vitro;in vivo	17161399
NOS1	PTPRN	No	in vitro;in vivo	11043403
NOS1	CAMK1	No	in vitro;in vivo	10400690 , 10874031 , 12630910 , 1375933 , 15251453
NOS1	PRKCA	No	in vitro	10400690 , 10874031 , 12630910 , 1375933
NOS1	PFKM	No	in vitro	10187848

Gene Report

Literature-origin GO terms

Gene mapped GO terms

Literature-origin KEGG pathway

Gene mapped KEGG pathways

Gene mapped BioCarta pathways