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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

NOS1 Gene

protein-coding GIFtS: 72
GCID: GC12M117636

nitric oxide synthase 1 (neuronal)

(Previous symbol: NOS)

Explore 179 diseases affiliated with
NOS1 via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Nitric Oxide Synthase 1 (Neuronal)¹ ²		NC-NOS² ³
NNOS¹		BNOS¹
NOS¹ ²		NOS Type I² ³
Constitutive NOS² ³		EC 1.14.13.39³ ⁸
Neuronal NOS² ³		IHPS1²
Peptidyl-Cysteine S-Nitrosylase NOS1² ³		Nitric Oxide Synthase, Brain²
N-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, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for NOS1:

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)

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:

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

(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 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000012.11 NC_018923.1 NT_009775.17

Regulatory elements:

SABiosciences 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 SABiosciences Chromatin IP Primers for NOS1

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat NOS1

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

Entrez Gene cytogenetic band: 12q24.2-q24.31 Ensembl cytogenetic band: 12q24.22 HGNC cytogenetic band: 12q14-qter

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, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, 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, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

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)

Subcellular location: 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)

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

Post-translational modifications:

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

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P29475

4/38 DME Specific Peptides for NOS1 (P29475) (see all 38)

VLEEFPS

GWYMGTE

LDITTPP

VFGLGSR

NOS1 Protein expression data from MOPED and PaxDb: About this image

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
Human Recombinant Protein Products for NOS1:

	Browse Purified and Recombinant Proteins at EMD Millipore
	Browse R&D Systems for human recombinant proteins
	Enzo Life Sciences proteins for NOS1
	OriGene Purified Protein: NOS1 OriGene Protein Over-expression Lysate: NOS1 OriGene Custom Protein Services for NOS1
	GenScript Custom Purified and Recombinant Proteins Services for NOS1
	Novus Biologicals NOS1 Proteins Novus Biologicals NOS1 Lysate
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for NOS1

Gene Ontology (GO): 5/9 cellular component terms (GO ID links to tree view) (see all 9): 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

NOS1 for ontologies About GeneDecksing

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 (see all 2): NOS1 OriGene Custom Antibody Services for NOS1
	GenScript Custom Superior Antibodies Services for NOS1
	Novus Biologicals NOS1 Antibodies
	Abcam antibodies for NOS1
	Uscn Antibodies for NOS1
	ThermoFisher Antibody for NOS1

Assay Products for NOS1:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for NOS1
	Enzo Life Sciences assays for NOS1
	Uscn ELISAs and CLIAs for NOS1

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

NOS1 for domains About GeneDecksing

5/12 InterPro domains/families (see all 12):

IPR026009 NOS

IPR017927 Fd_Rdtase_FAD-bd

IPR001094 Flavdoxin

IPR001478 PDZ

IPR008254 Flavodoxin/NO_synth

Graphical View of Domain Structure for InterPro Entry P29475

ProtoNet protein and cluster: P29475

5/6 Blocks protein families (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

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, Sirion Biotech, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, Sirion Biotech, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

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): 5/13 molecular function terms (GO ID links to tree view) (see all 13): 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	7545544
GO:0005506	iron ion binding	IEA	--
GO:0005515	protein binding	IPI	11149895
GO:0005516	calmodulin binding	IEA	--

NOS1 for ontologies About GeneDecksing

Phenotypes:
1 GenomeRNAi human phenotype for NOS1:

Decreased viability after Chla

15/21 MGI mutant phenotypes (inferred from 5 alleles) (MGI details for Nos1) (see all 21):

adipose tissue	behavior/neurological	cardiovascular system	cellular	digestive/alimentary
endocrine/exocrine gland	growth/size	hematopoietic system	homeostasis/metabolism	immune system
liver/biliary system	mortality/aging	muscle	nervous system	normal

NOS1 for phenotypes About GeneDecksing

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

inGenious Targeting Laboratory - Customizable classic, inducible, and humanized mouse model solutions for NOS1

miRNA Products:		OriGene 3'-UTR Clone: NOS1 Browse MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat NOS1
		8/74 QIAGEN miScript miRNA 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:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for NOS1 (see all 7) OriGene shRNA RFP: NOS1 OriGene siRNA: NOS1
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat NOS1
		Sirion Biotech Custom design and validation of potent shRNA sequences against NOS1

Gene Editing Products:			DNA2.0 Custom Protein Engineering Service for NOS1
			Sirion Biotech Customized adenovirus for overexpression of NOS1 Sirion Biotech Customized adenovirus for potent knockdown of NOS1

Clone Products:		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for NOS1 (see all 3) OriGene untagged cDNA clones in CMV expression vector in human, 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
		Search LifeMap BioReagents cell lines for NOS1
		Sirion Biotech Customized stable knockdown cell line services for NOS1 Sirion Biotech Customized inducible knockdown cell line services for NOS1 Sirion Biotech Customized stable overexpressing cell line services for NOS1 Sirion Biotech Customized inducible overexpressing cell line services for NOS1

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NOS1

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, 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 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/31 super-pathways (see all 31) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Nitric oxide stimulates guanylate cyclase

Nitric oxide stimulates guanylate cyclase

1.00

Platelet homeostasis

0.34

superpathway of citrulline metabolism

superpathway of citrulline metabolism

1.00

citrulline-nitric oxide cycle

0.40

Insulin receptor recycling

Phagosomal maturation (early endosomal stage)

0.64

Latent infection of Homo sapiens with Mycobacterium tuberculosis

0.64

Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.

Alzheimer's disease

0.43

Alzheimers Disease

0.00

Development HGF signaling pathway

Apoptosis and survival_Anti-apoptotic action of nuclear ESR1 and ESR2

0.15

Apoptosis and survival Anti-apoptotic action of nuclear ESR1 and ESR2

0.15

Pathway sources
See GeneCards unified pathways
Show all pathways

1 EMD Millipore Pathway for NOS1

Apoptosis and survival Anti-apoptotic action of nuclear ESR1 and ESR2

5/9 Downloadable PowerPoint Slides of QIAGEN 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)

5 BioSystems Pathways for NOS1

	Myometrial Relaxation and Contraction Pathways
	citrulline-nitric oxide cycle
	Monoamine Transport
	Alzheimers Disease
	superpathway of citrulline metabolism

5/6 Reactome Pathways for NOS1 (see all 6)

	Hemostasis
	Phagosomal maturation (early endosomal stage)
	Latent infection of Homo sapiens with Mycobacterium tuberculosis
	Platelet homeostasis
	Nitric oxide stimulates guanylate cyclase

2 PharmGKB Pathways for NOS1

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

5/8 Kegg Pathways (Kegg details for NOS1) (see all 8):

	Arginine and proline metabolism
	Metabolic pathways
	Calcium signaling pathway
	Phagosome
	Long-term depression

NOS1 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for NOS1

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

5/62 Interacting proteins for NOS1 (P29475^{2, 3} ENSP00000320758⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 62)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
VAC14	Q08AM6²^,³, ENSP00000261776⁴	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
DLG4	P78352³, ENSP00000293813⁴	I2D: score=4 STRING: ENSP00000293813

About this table

Gene Ontology (GO): 5/27 biological process terms (GO ID links to tree view) (see all 27): 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	--	--

NOS1 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

NOS1 for compounds About GeneDecksing

EMD Millipore small molecules for NOS1:
Small Molecule - inhibitor

Enzo Life Sciences drugs & compounds for NOS1

Compounds for NOS1 available from Tocris Bioscience About this table

Compound	Action	CAS #
TRIM	nNOS/iNOS inhibitor	[25371-96-4]
3-Bromo-7-nitroindazole	Selective nNOS inhibitor	[74209-34-0]
L-NNA	NOS inhibitor (nNOS = eNOS >> iNOS)	[2149-70-4]
Nomega-Propyl-L-arginine hydrochloride	Highly selective inhibitor of nNOS	[137361-05-8]

10/14 HMDB Compounds for NOS1 (see all 14) 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	--

10/25 DrugBank Compounds for NOS1 (see all 25) 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

10/127 Novoseek 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)

Search CenterWatch for drugs/clinical trials and news about NOS1

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 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,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, Sirion Biotech, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for NOS1 gene (4 alternative transcripts):

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

Unigene Clusters for NOS1:

Nitric oxide synthase 1 (neuronal)

Hs.654410 [show with all ESTs], Hs.684465 , Hs.684466 , Hs.684467 , Hs.735734 [show with all ESTs]

Unigene Representative Sequences: NM_001204218, AF446137, AF446133, AF446132, DA522461

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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Additional cDNA sequence:

AF446131.1 AF446135.1

7 DOTS entries:

DT.209591 DT.430999 DT.40118528 DT.91668000 DT.121200078 DT.87046327 DT.91658756

24/49 AceView cDNA sequences (see all 49):

AF446131 U17327 BX115063 AA935529 AI914145 BE744153 BC010126 BX105805

NM_000620 AI299150 AI793292 AJ004918 BE669690 CD609196 BE741353 AA923118

AF446135 BF447723 BE326294 AI791677 BC033208 D16408 U31466 AI302351

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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

NOS1 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: ATGGGCTTCT

About this image

NOS1 expression in embryonic tissues and stem cells
Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

10/13 LifeMap In Vivo Development Anatomical Compartments/Cells (see all 13)

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Gut Tube

Midgut

Midgut Endoderm Cells

Endoderm

Spinal Cord

Spinal Dorsal Columns

Dorsal Spinal Cord Progenitor Cells

Spinal Cord

Spinal Ventral Columns

Ventral Spinal Cord Progenitor Cells

Motor Neurons

Brain

Brain

Brain

Brain

Gut Tube

Neural Tube

Neural Tube

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

See NOS1 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for NOS1

SOURCE GeneReport for Unigene clusters: Hs.654410 Hs.684465 Hs.684466 Hs.684467 Hs.735734

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

SABiosciences Expression via Pathway-Focused 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)
About This Section

This gene was present in the last universal common ancestor (LUCA).

Orthologs for NOS1 gene from 9/31 species (see all 31) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	NOS1¹	nitric oxide synthase 1 (neuronal)	79.98(n) 84.32(a)		427721 XM_425296.2 XP_425296.2
lizard (Anolis carolinensis)	Reptilia	NOS1⁶ NDOR1⁶	--	82(a) 23(a)	1 ↔ 1 possible ortholog	LGb(2418671-2462979) GL344097.1(1892-21914)
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 53.9(n)¹ 48.33(a)¹		2 32B1³ 34495¹ NM_078817.3¹ NP_523541.2¹
worm (Caenorhabditis elegans)	Secernentea	fre-1⁶	Flavin REductase family member (fre-1)	21(a)	possible ortholog	V(20075890-20087702)
thale cress (Arabidopsis thaliana)	eudicotyledons	AT3G02280⁶ ATLFNR1⁶ (see all 5)	ferredoxin--NADP+ reductase (see all 5)	24(a) 18(a) (see all 5)	possible ortholog possible ortholog (see all 5)	3(453421-457841) 5(26450964-26453199)
rice (Oryza sativa)	Liliopsida	-- -- (see all 5)	NADPH reductase, putative, expressed ferredoxin--NADP reductase, chloroplast precursor,... (see all 5)	23(a) 17(a) (see all 5)	possible ortholog possible ortholog (see all 5)	1(30592390-30597478) 3(32559330-32562489)
E. coli (Escherichia coli)	Gamma proteobacteria	cysJ⁶	sulfite reductase, alpha subunit, flavoprotein	26(a)	possible ortholog	Chromosome(2888121-2889920)

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)
About This Section

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

NOS1 for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, 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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

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
				--	--	--		--	--
rs73206086^1,2	C	--	114654699(+)	`CTTTCC/TCTCCT`	4	--	ds500¹		1		NA	120
rs56055739^1,2	C	--	114655039(+)	`TCTGGA/GGCACC`	4	--	ds500¹		0	--	--	--	--
rs73393697^1,2	C	--	114656041(+)	`CCTCCC/ACCGGA`	4	--	ut3¹		2		WA	120
rs74567483^1,2		--	114656090(+)	`AACCAC/GTGGGC`	4	--	ut3¹		0	--	--	--	--
rs12425729^1,2	C,H	--	114656270(+)	`aggtaT/Ccttgt`	4	--	ut3¹		3		NA	124
rs111962507^1,2		--	114657143(+)	`GAGACG/AAGATT`	4	--	ut3¹		1		CSA	2
rs58982059^1,2		--	114657179(+)	`AAACTC/GCTGGC`	4	--	ut3¹		0	--	--	--	--
rs11068413^1,2	C	--	114657189(+)	`ccccaG/Agtgat`	4	--	ut3¹		1		NA	2
rs60695198^1,2	C	--	114657835(+)	`GCTGAC/TTATCA`	4	--	ut3¹		2		WA	120
rs113781886^1,2		--	114657900(+)	`CTCAGC/GTAGGG`	4	--	ut3¹		2		CSA WA	120

HapMap Linkage Disequilibrium report for NOS1 (117645947 - 117889975 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 2 variations for NOS1
2 CNVs: 5697 4789
Human Gene Mutation Database (HGMD): NOS1

Locus Specific Mutation Databases (LSDB): NOS1

1 SABiosciences Cancer Mutation PCR Assay for NOS1:

Cosmic Id	AA Change
110337	p.S771L

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(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.)
About This Section

NOS1 for disorders           About GeneDecksing

OMIM gene information: 163731    OMIM disorders: --

20/179 diseases for NOS1 (see all 179):    About MalaCards

neurodegenerative disease dopa-responsive dystonia pyloric stenosis alpha 1-antitrypsin deficiency

limb-girdle muscular dystrophy neuronitis sepiapterin reductase deficiency spinal cord injury

muscular dystrophy amyotrophic lateral sclerosis atherosclerosis attention deficit hyperactivity disorder

hypertrophic pyloric stenosis amyotrophic lateral sclerosis (als) childhood-onset schizophrenia non-small cell lung carcinoma

becker muscular dystrophy schizoaffective disorder aortic valve stenosis temporal lobe epilepsy

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

Vascular disease

10/92 Novoseek 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)
About This Section

PubMed articles for NOS1 gene, integrated from 9 sources (see all 1603):
(articles sorted by number of sources associating them with NOS1)

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

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. (2002)
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. (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. (1994)
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. (2003)
Allelic association of the neuronal nitric oxide synthase (NOS1) gene with schizophrenia. (PubMed id 12140778)^{1, 4, 9} Shinkai T....Nakamura J. (2002)
Nitric oxide synthase 1 as a potential modifier gene of decline in lung function in patients with cystic fibrosis. (PubMed id 14760158)^{1, 4, 9} Texereau J....Dinh-Xuan A.T. (2004)
Exhaled nitric oxide in patients with asthma: association with NOS1 genotype. (PubMed id 11112111)^{1, 4, 9} Wechsler M.E....Drazen J.M. (2000)
Localization of brain nitric oxide synthase (NOS) to human chromosome 12. (PubMed id 1385308)^{1, 3, 9} Kishimoto J....Xu W. (1992)
Nitric oxide synthase polymorphisms and asthma phenotypes in Chinese children. (PubMed id 16238787)^{1, 4, 9} Leung T.F....Wong G.W. (2005)
[Polymorphic markers of the NO synthase genes and genetic predisposition to diabetic polyneuropathy in patients with type 1 diabetes mellitus] (PubMed id 15856945)^{1, 4, 9} Zotova E.V....Nosikov V.V. (2005)

(in PubMed, OMIM, and NCBI Bookshelf)
About This Section

		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)
About This Section

Entrez Gene: 4842	HGNC: 7872	AceView: NOS1	Ensembl:ENSG00000089250	euGenes: HUgn4842
ECgene: NOS1	Kegg: 4842	H-InvDB: NOS1

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

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:
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NOS1 Gene

nitric oxide synthase 1 (neuronal)

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NOS1 Gene

nitric oxide synthase 1 (neuronal)

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