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NOS1 Gene

protein-coding GIFtS: 71
GCID: GC12M117636

Nitric Oxide Synthase 1 (Neuronal)

(Previous symbol: NOS)

See NOS1-related diseases
at

MalaCards

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, ¹²H-InvDB, ¹³NCBI, ¹⁴NONCODE, and/or ¹⁵RNAdb)
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Aliases
Nitric Oxide Synthase 1 (Neuronal)¹ ²		bNOS² ³
NOS¹ ²		nNOS² ³
Constitutive NOS² ³		NOS Type I² ³
Neuronal NOS² ³		EC 1.14.13.39³ ⁸
Peptidyl-Cysteine S-Nitrosylase NOS1² ³		IHPS1²
N-NOS² ³		Nitric Oxide Synthase, Brain²
NC-NOS² ³

External Ids:	HGNC: 7872¹	Entrez Gene: 4842²	Ensembl: ENSG00000089250⁷	OMIM: 163731⁵	UniProtKB: P29475³

Export aliases for NOS1 gene to outside databases

Previous GC identifers: GC12M116666 GC12M117169 GC12M117431 GC12M116060 GC12M116111 GC12M114660

(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for NOS1 Gene:

The protein encoded by this gene belongs to the family of nitric oxide synthases, which synthesize nitric oxide

from L-arginine. Nitric oxide is a reactive free radical, which acts as a biologic mediator in several processes,

including neurotransmission, and antimicrobial and antitumoral activities. In the brain and peripheral nervous

system, nitric oxide displays many properties of a neurotransmitter, and has been implicated in neurotoxicity

associated with stroke and neurodegenerative diseases, neural regulation of smooth muscle, including peristalsis,

and penile erection. This protein is ubiquitously expressed, with high level of expression in skeletal muscle.

Multiple transcript variants that differ in the 5' UTR have been described for this gene but the full-length

nature of these transcripts is not known. Additionally, alternatively spliced transcript variants encoding

different isoforms (some testis-specific) have been found for this gene.(provided by RefSeq, Feb 2011)

GeneCards Summary for NOS1 Gene:

NOS1 (nitric oxide synthase 1 (neuronal)) is a protein-coding gene. Diseases associated with NOS1 include factitious disorder, and pyloric stenosis. GO annotations related to this gene include calmodulin binding and heme binding. An important paralog of this gene is NOS3.

UniProtKB/Swiss-Prot: NOS1_HUMAN, P29475

Function: Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In

the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Probably has

nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR

summary for NOS1 Gene:

Neuronal nitric oxide synthase (nNOS), along with inducible nitric oxide synthase (iNOS) and endothelial

nitric oxide synthase (eNOS), catalyze the generation of nitric oxide and L-citrulline from L-arginine and

molecular oxygen. It is activated at concentrations of calcium greater than 100 nM and requires co-factors

of tetrahydrobiopterin, flavin adenine dinucleotide, flavin mononucleotide and NADPH for catalytic activity.

Transcriptional regulation of nNOS is very complex and the nNOS gene produces multiple mRNA transcripts

using alternate promoters, alternative splicing, cassette insertions/deletions, and varied sites for 3'-UTR

cleavage and polyadenylation. Some of these alterations lead to variation in amino acid sequence,

translating into nNOS isoforms with altered structural and functional properties. nNOS has been implicated

in a wide variety of physiological and pathological processes, including neurotransmission, neurotoxicity,

skeletal muscle contraction, sexual function, body fluid homeostasis and atherosclerosis. Consistent with

such wide involvement, nNOS is expressed in numerous tissues. The human gene encoding nNOS is localized to

chromosome 12q14.

Gene Wiki entry for NOS1 Gene

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:

NC_000012.11 NT_029419.13 NC_018923.2

Regulatory elements:

Regulatory transcription factor binding sites in the NOS1 gene promoter:
CREB AP-1 ATF-2 deltaCREB c-Jun STAT5A Nkx2-5
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: NOS1 promoter sequence

Search Chromatin IP Primers for NOS1

Epigenetics:

DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat NOS1

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 12q24.22 Ensembl cytogenetic band: 12q24.22 HGNC cytogenetic band: 12q24.22

NOS1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
NOS1 gene location

GeneLoc information about chromosome 12 GeneLoc Exon Structure

GeneLoc location for GC12M117636: view genomic region (about GC identifiers)

Start:	117,645,947 bp from pter	End:	117,889,975 bp from pter
Size:	244,029 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, ²neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: NOS1_HUMAN, P29475 (See protein sequence)

Recommended Name: Nitric oxide synthase, brain

Size: 1434 amino acids; 160970 Da

Cofactor: Heme group

Cofactor: Binds 1 FAD

Cofactor: Binds 1 FMN

Cofactor: Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme

Subunit: Homodimer. Interacts with DLG4; the interaction possibly being prevented by the association between NOS1

and CAPON. Forms a ternary complex with CAPON and RASD1. Forms a ternary complex with CAPON and SYN1. Interacts

with ZDHHC23. Interacts with NOSIP; which may impair its synaptic location (By similarity). Interacts with HTR4.

Interacts with VAC14 (By similarity). Interacts with SLC6A4 (By similarity). Interacts (via N-terminus domain)

with DLG4 (via N-terminus tandem pair of PDZ domains) (By similarity)

Secondary accessions: E9PH30 O75713

Alternative splicing: 5 isoforms: P29475-1 P29475-2 P29475-3 P29475-4 P29475-5

Explore the universe of human proteins at neXtProt for NOS1: NX_P29475

Explore proteomics data for NOS1 at MOPED

Post-translational modifications:

Ubiquitinated; mediated by STUB1/CHIP in the presence of Hsp70 and Hsp40 (in vitro) (By similarity)¹

Modification sites at neXtProt

Modification sites at PhosphoSitePlus

Selected DME Specific Peptides for NOS1 (P29475) (see all 38)

VLEEFPS

GWYMGTE

LDITTPP

VFGLGSR

See NOS1 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins (4 alternative transcripts):

NP_000611.1 NP_001191142.1 NP_001191143.1 NP_001191147.1

ENSEMBL proteins:

ENSP00000320758 ENSP00000337459 ENSP00000339862

Reactome Protein details: P29475

NOS1 Human Recombinant Protein Products:

	Browse Purified and Recombinant Proteins at EMD Millipore
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	Enzo Life Sciences proteins for NOS1
	OriGene Purified Protein for NOS1 OriGene Protein Over-expression Lysate for NOS1 OriGene MassSpec for NOS1 OriGene Custom Protein Services for NOS1
	GenScript Custom Purified and Recombinant Proteins Services for NOS1
	Novus Biologicals NOS1 Protein Novus Biologicals NOS1 Lysate
	Browse Sino Biological Recombinant Proteins Browse Sino Biological Cell Lysates
	Browse ProSpec Recombinant Proteins
	Cloud-Clone Corp. Proteins for NOS1
	Search eBioscience for Proteins for NOS1
	antibodies-online proteins for NOS1 (20 products)
	antibodies-online peptides for NOS1

NOS1 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of NOS1
	R&D Systems Antibodies for NOS1 (nNOS)
	Cell Signaling Technology (CST) Antibodies for NOS1 (nNOS)
	OriGene Antibodies for NOS1 OriGene Custom Antibody Services for NOS1
	Novus Biologicals NOS1 Antibodies
	Abcam antibodies for NOS1 (P29475, P35228)
	Cloud-Clone Corp. Antibodies for NOS1
	ThermoFisher Antibody for NOS1
	antibodies-online antibodies for NOS1 (160 products)

NOS1 Assay Products:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Assay Services for NOS1
	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for NOS1
	Enzo Life Sciences assays for NOS1
	Cloud-Clone Corp. ELISAs for NOS1 Cloud-Clone Corp. CLIAs for NOS1
	Search eBioscience for ELISAs for NOS1
	antibodies-online kits for NOS1 (34 products)

(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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IUPHAR Guide to PHARMACOLOGY protein family classification: Neuronal NOS

Nitric oxide synthases

Selected InterPro protein domains (see all 11):

IPR017927 Fd_Rdtase_FAD-bd

IPR001094 Flavdoxin

IPR001478 PDZ

IPR008254 Flavodoxin/NO_synth

IPR012144 NOS_euk

Graphical View of Domain Structure for InterPro Entry P29475

ProtoNet protein and cluster: P29475

Selected Blocks protein domains (see all 6):

IPB001094 Flavodoxin signature

IPB001433 Oxidoreductase FAD/NAD(P)-binding

IPB001478 PDZ/DHR/GLGF domain

IPB001709 Flavoprotein pyridine nucleotide cytochrome reductase signature

IPB003097 FAD-binding

UniProtKB/Swiss-Prot: NOS1_HUMAN, P29475

Domain: The PDZ domain in the N-terminal part of the neuronal isoform participates in protein-protein interaction,

and is responsible for targeting nNos to synaptic membranes in muscles. Mediates interaction with VAC14 (By

similarity)

Similarity: Belongs to the NOS family

Similarity: Contains 1 FAD-binding FR-type domain

Similarity: Contains 1 flavodoxin-like domain

Similarity: Contains 1 PDZ (DHR) domain

Find genes that share domains with NOS1 About GenesLikeMe

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Molecular Function:

UniProtKB/Swiss-Prot Summary: NOS1_HUMAN, P29475

Function: Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In

the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Probably has

nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR

Catalytic activity: 2 L-arginine + 3 NADPH + 4 O(2) = 2 L-citrulline + 2 nitric oxide + 3 NADP(+) + 4 H(2)O

Enzyme regulation: Stimulated by calcium/calmodulin. Inhibited by n-Nos-inhibiting protein (PIN) which may prevent

the dimerization of the protein. Inhibited by NOSIP

Genatlas biochemistry entry for NOS1:

nitric oxide synthase 1,constitutive by expressed,neuronal,putative susceptibility gene for infantile pyloric

stenosis,widely expressed with a high expression in skeletal muscle

Enzyme Number (IUBMB): EC 1.14.13.39¹ ²

Gene Ontology (GO): Selected molecular function terms (see all 16): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0003958	NADPH-hemoprotein reductase activity	IBA	--
GO:0004517	nitric-oxide synthase activity	ISS	--
GO:0005506	iron ion binding	IEA	--
GO:0005515	protein binding	IPI	11149895
GO:0005516	calmodulin binding	IEA	--

Find genes that share ontologies with NOS1 About GenesLikeMe

Phenotypes:
1 GenomeRNAi human phenotype for NOS1:

Decreased viability after Chla

Selected MGI mutant phenotypes (inferred from 6 alleles) (MGI details for Nos1) (see all 22):

adipose tissue	behavior/neurological	cardiovascular system	cellular	digestive/alimentary
endocrine/exocrine gland	growth/size/body	hematopoietic system	homeostasis/metabolism	immune system
liver/biliary system	mortality/aging	muscle	nervous system	no phenotypic analysis

Find genes that share phenotypes with NOS1 About GenesLikeMe

Animal Models:
MGI mouse knock-outs for NOS1: Nos1^tm1Plh Nos1^tm1Enik Nos1^tm2Plh

genOway: Develop your customized and physiologically relevant rodent model for NOS1

miRNA Products:		Block miRNA regulation of human, mouse, rat NOS1 using miScript Target Protectors
		Selected qRT-PCR Assays for microRNAs that regulate NOS1 (see all 74):
		hsa-miR-4254 hsa-miR-146a hsa-miR-15a hsa-miR-938 hsa-miR-371-5p hsa-miR-502-3p hsa-miR-149 hsa-miR-3116

		SwitchGear 3'UTR luciferase reporter plasmid: NOS1 3' UTR sequence

Inhib. RNA Products:		OriGene RNAi products in human, mouse, rat for NOS1
		Predesigned siRNA for gene silencing in human, mouse, rat NOS1

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for NOS1

Clone Products:		OriGene clones in human, mouse for NOS1 (see all 7) OriGene ORF clones in mouse, rat for NOS1 OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector (see all 4): NOS1 (NM_000620)
		Browse Sino Biological Human cDNA Clones
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for NOS1
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat NOS1

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for NOS1
		Browse ESI BIO Cell Lines and PureStem Progenitors for NOS1

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NOS1

Flow Cytometry
Products:

eBioscience FlowRNA Probe Sets ( VA1-11704) for NOS1

(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Subcellular locations from UniProtKB/Swiss-Prot

NOS1_HUMAN, P29475: Cell membrane, sarcolemma; Peripheral membrane protein. Cell projection, dendritic spine (By

similarity). Note=In skeletal muscle, it is localized beneath the sarcolemma of fast-twitch muscle fiber by

associating with the dystrophin glycoprotein complex. In neurons, enriched in dendritic spines (By similarity)

Subcellular locations from COMPARTMENTS:

Compartment	Confidence
plasma membrane	5
cytosol	4
endoplasmic reticulum	4
cytoskeleton	3
mitochondrion	2
nucleus	2
extracellular	1

About this image

Gene Ontology (GO): Selected cellular component terms (see all 10): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001917	photoreceptor inner segment	ISS	17027776
GO:0005737	cytoplasm	TAS	17892502
GO:0005829	cytosol	TAS	--
GO:0005856	cytoskeleton	ISS	7545544
GO:0016529	sarcoplasmic reticulum	IDA	9892689

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(SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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SuperPaths for NOS1 About (see all 33)

See pathways by source

Powered
by

SuperPath

Contained pathways About

Arginine and proline metabolism

	superpathway of citrulline metabolism	0.00			Arginine and proline metabolism
	citrulline-nitric oxide cycle	0.00

Amyotrophic lateral sclerosis (ALS)

Amyotrophic lateral sclerosis (ALS)

0.63

Amyotrophic lateral sclerosis (ALS)

0.63

Alzheimer's disease

Alzheimers Disease

0.44

Alzheimer's disease

0.44

Monoamine Transport

Monoamine Transport

Serotonin Transporter Activity

0.00

Neuropathic Pain-Signaling in Dorsal Horn Neurons

Neuropathic Pain-Signaling in Dorsal Horn Neurons

0.47

Find genes that share SuperPaths with NOS1 About GenesLikeMe

Pathways by source See SuperPaths
Show all pathways

Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for NOS1 (see all 9)

	Cellular Effects of Sildenafil
	Muscular Dystrophies and Dystrophin-Glycoprotein Complex
	Neuropathic Pain-Signaling in Dorsal Horn Neurons
	Sertoli-Sertoli Cell Junction Dynamics
	Endothelin-1 Signaling Pathway

2 Cell Signaling Technology (CST) Pathways for NOS1

	Neuroscience
	PI3K / Akt Signaling

3 GeneGo (Thomson Reuters) Pathways for NOS1

	Mechanisms of CFTR activation by S-nitrosoglutathione (normal and CF)
	Apoptosis and survival Anti-apoptotic action of nuclear ESR1 and ESR2
	NO-dependent CFTR activation (normal and CF)

Selected BioSystems Pathways for NOS1 (see all 9)

	Myometrial Relaxation and Contraction Pathways
	Spinal Cord Injury
	Amyotrophic lateral sclerosis (ALS)
	Effects of nitric oxide
	Monoamine Transport

2 Reactome Pathways for NOS1

	Phagosomal maturation (early endosomal stage)
	Nitric oxide stimulates guanylate cyclase

2 PharmGKB Pathways for NOS1

	Doxorubicin Pathway (Cardiomyocyte Cell), Pharmacodynamics
	Doxorubicin Pathway, Pharmacokinetics

Selected Kegg Pathways (Kegg details for NOS1) (see all 9):

	Arginine and proline metabolism
	Metabolic pathways
	Calcium signaling pathway
	Phagosome
	Circadian entrainment

Pathway & Disease-focused RT² Profiler PCR Arrays including NOS1:

Nitric Oxide Signaling Pathway in human mouse rat

Synaptic Plasticity in human mouse rat

Interactions:

GeneGlobe Interaction Network for NOS1

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

Selected Interacting proteins for NOS1 (P29475^{1, 2, 3} ENSP00000320758⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 89)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
VAC14	Q08AM6¹^,²^,³, ENSP00000261776⁴	EBI-7164065,EBI-2107455 MINT-3999924 MINT-3999953 MINT-3999982 MINT-3999902 MINT-3999876 I2D: score=3 STRING: ENSP00000261776
CALM1	P62158³, ENSP00000349467⁴	I2D: score=1 STRING: ENSP00000349467
CALM2	P62158³	I2D: score=1
CALM3	P62158³	I2D: score=1
ADRA1A	P35348³, ENSP00000369960⁴	I2D: score=2 STRING: ENSP00000369960

About this table

Gene Ontology (GO): Selected biological process terms (see all 30): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001666	response to hypoxia	IEP	16276418
GO:0002028	regulation of sodium ion transport	--	--
GO:0006527	arginine catabolic process	IC	7545544
GO:0006809	nitric oxide biosynthetic process	ISS	7545544
GO:0006941	striated muscle contraction	IEA	--

Find genes that share ontologies with NOS1 About GenesLikeMe

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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Browse Small Molecules at EMD Millipore

Enzo Life Sciences drugs & compounds for NOS1

Browse compounds at ApexBio

Compounds for NOS1 available from Tocris Bioscience About this table

Compound	Action	CAS #
3-Bromo-7-nitroindazole	Selective nNOS inhibitor	[74209-34-0]
Nomega-Propyl-L-arginine hydrochloride	Highly selective inhibitor of nNOS	[137361-05-8]
ARL 17477 dihydrochloride	Selective nNOS inhibitor	[180983-17-9]

14 HMDB Compounds for NOS1 (see first 10) About this table

Compound	Synonyms	CAS #	PubMed Ids
Dihydrobiopterin	(S-(R,S))-2-amino-6-(1,2-dihydroxypropyl)-7,8-dihydro-4(1H)-Pteridinone (see all 15)	6779-87-9	16804678
Tetrahydrobiopterin	(1R,2S)-(2-Amino-3,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)-1,2-propandiol (see all 11)	17528-72-2	16216381
Calcium	Ca (see all 2)	7440-70-2	--
Citrulline	(2S)-2-amino-5-(carbamoylamino)pentanoic acid (see all 55)	372-75-8	--
FAD	1H-Purin-6-amine flavin dinucleotide (see all 21)	146-14-5	--
Flavin Mononucleotide	FMN (see all 19)	146-17-8	--
Heme	(protoporphyrinato)iron (see all 19)	14875-96-8	--
L-Arginine	(S)-2-Amino-5-[(aminoiminomethyl)amino]pentanoate (see all 14)	74-79-3	--
N-(o)-Hydroxyarginine	N-(G)-Hydroxyarginine (see all 2)	--	--
NADP	Adenine-nicotinamide dinucleotide phosphate (see all 18)	53-59-8	--
NADPH	2'-(dihydrogen phosphate) 5'-(trihydrogen pyrophosphate) Adenosine 5'-ester with 1,4-dihydro-1-b-D-ribofuranosylnicotinamide (see all 23)	53-57-6	--
Nitric oxide	Mononitrogen monoxide (see all 9)	10102-43-9	--
Oxygen	Oxygen (see all 5)	7782-44-7	--
Water	Dihydrogen oxide (see all 2)	7732-18-5	--

Selected DrugBank Compounds for NOS1 (see all 26) About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
L-Citrulline	2-Amino-5-uredovaleric acid (see all 8)	372-75-8	target	--	10681601 10502685 10962148 10945985 10799481
(6r,1'r,2's)-5,6,7,8 Tetrahydrobiopterin	--	--	target	--	17139284 17016423 10592235
2'-Monophosphoadenosine 5'-Diphosphoribose	--	--	target	--	17139284 17016423 10592235
3-Bromo-7-Nitroindazole	--	--	target	--	17139284 17016423 10592235
5-N-Allyl-Arginine	--	--	target	--	17139284 17016423 10592235
Alpha-D-Mannose	--	3458-28-4	target	--	17139284 17016423 10592235
Flavin-Adenine Dinucleotide	--	146-14-5	target	--	17139284 17016423 10592235
Heme	--	--	target	--	17139284 17016423 10592235
L-N(Omega)-Nitroarginine-(4r)-Amino-L-Proline Amide	--	--	target	--	17139284 17016423 10592235
L-N(Omega)-Nitroarginine-2,4-L-Diaminobutyric Amide	--	--	target	--	17139284 17016423 10592235

2 IUPHAR Ligands for NOS1 (Neuronal NOS) About this table

Ligand	Type	Action	Affinity	Pubmed IDs
3-bromo-7NI	Inhibitor	Inhibition	6.1 - 6.5	7544863
7NI	Inhibitor	Inhibition	5.3	7693279

Selected Novoseek inferred chemical compound relationships for NOS1 gene (see all 127) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
nitric oxide	94.2	3522	18580182 (7), 16581191 (7), 17320763 (6), 7524095 (6) (see all 99)
tetrahydrobiopterin	92.1	193	16216381 (6), 7691806 (5), 9858648 (4), 7514193 (2) (see all 99)
citrulline	87.1	144	12586539 (4), 14725962 (3), 17110176 (3), 8962079 (2) (see all 91)
7-nitroindazole	85.1	167	7542758 (3), 11448483 (3), 12322787 (3), 15138761 (2) (see all 70)
arginine	84.3	472	7519607 (9), 14602725 (5), 15007014 (5), 8955074 (4) (see all 99)
n(g)-hydroxy-l-arginine	81.7	27	9398165 (4), 19128180 (3), 11481035 (2), 9735327 (1) (see all 12)
nadph	81.2	265	10847600 (6), 7528212 (5), 12429187 (4), 8690302 (4) (see all 99)
dihydrobiopterin	78.6	14	8626754 (3), 16804678 (1), 15476407 (1), 16118486 (1) (see all 6)
peroxynitrite	75.9	47	8839053 (4), 11085318 (3), 12208472 (2), 9398256 (2) (see all 28)
n-omega-propyl-l-arginine	75	21	15160393 (2), 16423462 (1), 17572695 (1), 19019012 (1) (see all 8)

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(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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REFSEQ mRNAs for NOS1 gene (4 alternative transcripts):

NM_000620.4 NM_001204213.1 NM_001204214.1 NM_001204218.1

Unigene Cluster for NOS1:

Nitric oxide synthase 1 (neuronal)

Hs.654410 [show with all ESTs]

Unigene Representative Sequence: NM_001204218

5 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000317775(uc021ren.1 uc021reo.1 uc001twn.2 uc001twm.2)

ENST00000338101 ENST00000549189 ENST00000477584 ENST00000344089

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Flow Cytometry
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eBioscience FlowRNA Probe Sets ( VA1-11704) for NOS1

Additional mRNA sequence:

AF446135.1 AJ004918.1 AK294435.1 AK307481.1 BC010126.2 BC033208.1 D16408.1 EU753241.1

L02881.1 U17327.1 U31466.1

5 DOTS entries:

DT.209591 DT.430999 DT.40118528 DT.121200078 DT.87046327

Selected AceView cDNA sequences (see all 49):

NM_000620 AI793292 BX115063 BC010126 AA935529 BE744153 AI914145 BX105805

AI299150 U17327 AJ004918 AF446131 AI791677 BE669690 BE297602 BF433556

AF446135 U31466 D16408 BC033208 AI302351 BE741353 BE326294 L02881

GeneLoc Exon Structure

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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NOS1 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>^2/3
CGAP TAG: ATGGGCTTCT

About this image

NOS1 expression in embryonic tissues and stem cells About this table

Data from LifeMap, the Embryonic Development and Stem Cells Database
selected tissues (see all 7) fully expand


Neural Tube (Nervous System) fully expand to see all 5 entries
Metencephalon

Brain (Nervous System) fully expand to see all 4 entries
Adult Endothelial Cells Blood Brain Barrier
Midbrain tegmentum

Inner Cell Mass (Early Embryonic Tissues) fully expand to see all 2 entries
Human embryonic stem cells (family)

Epithelial Cells
Mature Choroid Plexus Cells Choroid Plexus

Gut Tube (Gastrointestinal Tract)
Midgut

NOS1 Protein expression data from MOPED¹, PaxDb² and MaxQB³:

About this image

NOS1 Protein Expression

SOURCE GeneReport for Unigene cluster: Hs.654410

UniProtKB/Swiss-Prot: NOS1_HUMAN, P29475

Tissue specificity: Isoform 1 is ubiquitously expressed: detected in skeletal muscle and brain, also in testis,

lung and kidney, and at low levels in heart, adrenal gland and retina. Not detected in the platelets. Isoform 3

is expressed only in testis. Isoform 4 is detected in testis, skeletal muscle, lung, and kidney, at low levels in

the brain, but not in the heart and adrenal gland

Pathway & Disease-focused RT² Profiler PCR Arrays including NOS1:

Nitric Oxide Signaling Pathway in human mouse rat

Synaptic Plasticity in human mouse rat

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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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This gene was present in the common ancestor of animals and fungi.

Orthologs for NOS1 gene from Selected species (see all 17) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Nos1^{1 , 5}	nitric oxide synthase 1, neuronal^{1, 5}	87.05(n)¹ 94.05(a)¹		5 (57.29 cM)⁵ 18125¹ NM_008712.2¹ NP_032738.1¹ 117781032⁵
chicken (Gallus gallus)	Aves	NOS1¹	nitric oxide synthase 1 (neuronal)	80.04(n) 84.36(a)		427721 XM_004934480.1 XP_004934537.1
lizard (Anolis carolinensis)	Reptilia	NOS1⁶	nitric oxide synthase 1 (neuronal)	81(a)	1 ↔ 1	LGb(2413952-2463375)
African clawed frog (Xenopus laevis)	Amphibia	nos1-A²	neuronal nitric oxide synthase 1	76.45(n)		AF053935.2
zebrafish (Danio rerio)	Actinopterygii	nos1²	nitric oxide synthase 1 (neuronal)	74.9(n)		60658 AY211528.1
fruit fly (Drosophila melanogaster)	Insecta	Nos^{1 , 3}	imaginal disc development calmodulin binding³ Nitric oxide synthase¹	49(a)³ 56.44(n)¹ 51.37(a)¹		2 32B1³ 34495¹ NM_078817.3¹ NP_523541.2¹
baker's yeast (Saccharomyces cerevisiae)	Saccharomycetes	NCP1⁶	NADP-cytochrome P450 reductase; involved in ergost...	25(a)	1 → many	VIII(190543-192618) YHR042W

ENSEMBL Gene Tree for NOS1 (if available)
TreeFam Gene Tree for NOS1 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
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Paralogs for NOS1 gene

NOS3² POR² NOS2² MTRR²

2 SIMAP similar genes for NOS1 using alignment to 5 protein entries: NOS1_HUMAN (see all proteins):

NOS3 NOS2

Find genes that share paralogs with NOS1 About GenesLikeMe

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, ⁴UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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SNP ID	Valid	Clinical significance	Chr 12 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs149551400^1,2		--	114654634(+)	`TTCCCC/TTCCCC`	4	--	ds500¹		0	--	--	--	--
rs77934895^1,2	C,F	--	114654681(+)	`TCTTTT/CCCTCT`	4	--	ds500¹		1		EA	120
rs73206086^1,2	C,F	--	114654699(+)	`CTTTCC/TCTCCT`	4	--	ds500¹		1		NA	120
rs187869116^1,2		--	114654871(+)	`CCTCCC/TCTCTC`	4	--	ds500¹		0	--	--	--	--
rs56055739^1,2	C	--	114655039(+)	`TCTGGA/GGCACC`	4	--	ds500¹		0	--	--	--	--
rs71444610^1,2	C	--	114655364(+)	`ACAGC-/GT/GTG TGTGTGTGTGTGTG`	8	--	ut3¹ cds¹		1		NA	2
rs66886445^1,2	C	--	114655365(+)	`CAGCG-/GT/GTGTG TGTGTGTGTGTTGTGT`	8	--	ut3¹		0	--	--	--	--
rs58714999^1,2	C	--	114655395(+)	`GTGTG-/TGT/TGTGT/TGTGTGTGT GTGT/TGTGTGTGTGTGTGTGGTGAG`	16	--	cds¹ ut3¹		0	--	--	--	--
rs191867506^1,2		--	114655723(+)	`ACAGGG/TTCTCA`	4	--	ut3¹		0	--	--	--	--
rs7308150^1,2	C,F,A	--	114655764(+)	`CATCTC/TGGCTC`	4	--	ut3¹		2		WA CSA	4

HapMap Linkage Disequilibrium report for NOS1 (117645947 - 117889975 bp)

Structural Variations
Database of Genomic Variants (DGV) 7 variations for NOS1: About this table

Variant ID	Type	Subtype	PubMed ID
esv2746436	CNV	Deletion	23290073
esv2746435	CNV	Deletion	23290073
nsv901	CNV	Insertion	18451855
nsv509478	CNV	Insertion	20534489
nsv832526	CNV	Loss	17160897
nsv53465	CNV	Loss	16902084
nsv510592	CNV	Loss	20534489

Human Gene Mutation Database (HGMD): NOS1
Locus Specific Mutation Databases (LSDB): NOS1

1 Site Specific Mutation Identification with PCR Assay for NOS1:

Cosmic Id	AA Change
110337	p.S771L

SeqTarget long-range PCR primers for resequencing NOS1

DNA2.0 Custom Variant and Variant Library Synthesis for NOS1

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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OMIM gene information: 163731 OMIM disorders: --

Selected diseases for NOS1 (see all 22):
About MalaCards

factitious disorder pyloric stenosis hypertrophic pyloric stenosis impotence

cerebral hypoxia intestinal perforation gastroschisis acute chest syndrome

hyperphenylalaninemia gastroparesis brain injury sepiapterin reductase deficiency

atherosclerosis childhood-onset schizophrenia spermatogenic failure 12 psychotic disorder

schizophrenia achalasia tetrahydrobiopterin deficiency brain ischemia

1 inferred disease relationship from the University of Copenhagen DISEASES database for NOS1:

Vascular disease

Find genes that share disorders with NOS1 About GenesLikeMe

Selected Novoseek inferred disease relationships for NOS1 gene (see all 92) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
pyloric stenosis	59	21	11283889 (3), 14757827 (2), 9354728 (1), 15361336 (1) (see all 14)
diabetic gastroparesis	54	6	12768383 (1), 17161551 (1), 17160518 (1), 20185690 (1) (see all 5)
muscular dystrophy duchenne	51.2	20	17313973 (2), 11745948 (2), 9536265 (1), 9398448 (1) (see all 16)
pyloric stenosis, infantile	50.5	4	8571963 (2)
neurodegenerative diseases	49.3	23	7523410 (2), 19268602 (1), 20337441 (1), 9847056 (1) (see all 13)
erectile dysfunction	47.9	4	9284206 (1), 9631946 (1), 7588327 (1), 8562693 (1)
schizophrenia	45.5	85	19513863 (6), 12140778 (4), 19200422 (4), 18544180 (3) (see all 46)
brain ischemia	43.5	3	16141535 (1), 10320673 (1)
schizoaffective disorder	42.7	12	9988837 (1), 17665305 (1), 8483645 (1), 17267179 (1) (see all 11)
neurodegeneration	41.9	15	15579064 (1), 16095570 (1), 16179512 (1), 18805011 (1) (see all 11)

Genetic Association Database (GAD): NOS1
Human Genome Epidemiology (HuGE) Navigator: NOS1 (103 documents)

Export disorders for NOS1 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
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PubMed articles for NOS1 gene, integrated from 10 sources (see all 1622):
(articles sorted by number of sources associating them with NOS1)

Utopia: connect your pdf to the dynamic
world of online information

Genetic association analysis of functional polymorphisms in neuronal nitric oxide synthase 1 gene (NOS1) and mood disorders and fluvoxamine response in major depressive disorder in the Japanese population. (PubMed id 20016223)^{1, 4, 9} Okumura T....Iwata N. (Neuropsychobiology 2010)
Nasal nitric oxide levels in cystic fibrosis patients are associated with a neuronal NO synthase (NOS1) gene polymorphism. (PubMed id 11890749)^{1, 4, 9} Grasemann H....Ratjen F. (Nitric Oxide 2002)
Variants in the neuronal nitric oxide synthase (nNOS, NOS1) gene are associated with restless legs syndrome. (PubMed id 18058820)^{1, 4, 9} Winkelmann J....MA1ller-Myhsok B. (Mov. Disord. 2008)
Single-nucleotide promoter polymorphism alters transcription of neuronal nitric oxide synthase exon 1c in infantile hypertrophic pyloric stenosis. (PubMed id 14757827)^{1, 4, 9} Saur D....Allescher H.D. (Proc. Natl. Acad. Sci. U.S.A. 2004)
Expression of two types of nitric oxide synthase mRNA in human neuroblastoma cell lines. (PubMed id 7515942)^{1, 2, 9} Fujisawa H....Esumi H. (J. Neurochem. 1994)
Association between achalasia and nitric oxide synthase gene polymorphisms. (PubMed id 16848803)^{1, 4, 9} Mearin F....Lanas A. (Am. J. Gastroenterol. 2006)
Effects of sex and of gene variants in constitutive nitric oxide synthases on exhaled nitric oxide. (PubMed id 12531780)^{1, 4, 9} Grasemann H....Ratjen F. (Am. J. Respir. Crit. Care Med. 2003)
Allelic association of the neuronal nitric oxide synthase (NOS1) gene with schizophrenia. (PubMed id 12140778)^{1, 4, 9} Shinkai T....Nakamura J. (Mol. Psychiatry 2002)
Influence of NOS1 on verbal intelligence and working memory in both patients with schizophrenia and healthy control subjects. (PubMed id 19805695)^{1, 4, 9} Donohoe G....Corvin A. (Arch. Gen. Psychiatry 2009)
Environmental exposures, nitric oxide synthase genes, and exhaled nitric oxide in asthmatic children. (PubMed id 19603529)^{1, 4, 9} Spanier A.J....Lanphear B.P. (Pediatr. Pulmonol. 2009)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 4842	HGNC: 7872	AceView: NOS1	Ensembl:ENSG00000089250	euGenes: HUgn4842
ECgene: NOS1	Kegg: 4842	H-InvDB: NOS1

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for NOS1	Pharmacogenomics, SNPs, Pathways
NIEHS-SNPs	http://egp.gs.washington.edu/data/nos1/
Wikipedia	http://en.wikipedia.org/wiki/Nitric_oxide_synthase

Intellectual Property for NOS1 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for NOS1 gene:
Search GeneIP for patents involving NOS1

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

(Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, eBioscience, antibodies-online, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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Nitric Oxide Synthase 1 (Neuronal)

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Limb girdle
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NOS1 Gene

Nitric Oxide Synthase 1 (Neuronal)

Aliasesfor NOS1 gene

Summariesfor NOS1 gene

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Proteinsfor NOS1 gene

NOS1 Human Recombinant Protein Products:

NOS1 Antibody Products:

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Domains /Familiesfor NOS1 gene

Functionfor NOS1 gene

Localizationfor NOS1 gene

Pathways & Interactionsfor NOS1 gene

Drugs & Compoundsfor NOS1 gene

Transcriptsfor NOS1 gene

Expression for NOS1 gene

Orthologsfor NOS1 gene

Paralogsfor NOS1 gene

Genomic Variantsfor NOS1 gene

Disorders / Diseasesfor NOS1 gene

Publicationsfor NOS1 gene

External Searches for NOS1 gene

Genome Databases showing NOS1 gene

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Aliases
for NOS1 gene

Summaries
for NOS1 gene

Genomic Views
for NOS1 gene

Proteins
for NOS1 gene

Domains /
Families
for NOS1 gene

Function
for NOS1 gene

Localization
for NOS1 gene

Pathways & Interactions
for NOS1 gene

Drugs & Compounds
for NOS1 gene

Transcripts
for NOS1 gene

Expression
for NOS1 gene

Orthologs
for NOS1 gene

Paralogs
for NOS1 gene

Genomic Variants
for NOS1 gene

Disorders / Diseases
for NOS1 gene

Publications
for NOS1 gene

Intellectual Property
for NOS1 gene

Products
for NOS1 gene