Details for: NOS1

Gene ID: 4842

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: NOS1

Ensembl ID: ENSG00000089250

Description: nitric oxide synthase 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 13.54
    rCSI 22.73%
    PRS 84.06
  • peripheral nervous system neuron CL2000032
    CSI 12.55
    rCSI 17.1%
    PRS 88.45
  • sst GABAergic cortical interneuron CL4023017
    CSI 5.8
    rCSI 7.48%
    PRS 84.89
  • interneuron CL0000099
    CSI 4.62
    rCSI 9.28%
    PRS 89.17
  • cerebral cortex endothelial cell CL1001602
    CSI 4.07
    rCSI 7.03%
    PRS 89.83
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 3.26
    rCSI 4.05%
    PRS 81.84
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 3.1
    rCSI 5.64%
    PRS 88.78
  • pulmonary artery endothelial cell CL1001568
    CSI 2.59
    rCSI 3.52%
    PRS 96.63
  • lung neuroendocrine cell CL1000223
    CSI 2.56
    rCSI 3.78%
    PRS 94.51
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.19
    rCSI 3.86%
    PRS 83.4
  • GABAergic neuron CL0000617
    CSI 1.5
    rCSI 5.02%
    PRS 82.66
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.5
    rCSI 3.8%
    PRS 89.59
  • GABAergic amacrine cell CL4030027
    CSI 1.48
    rCSI 5.05%
    PRS 83.26
  • central nervous system neuron CL2000029
    CSI 1.27
    rCSI 9.37%
    PRS 87.65
  • basket cell CL0000118
    CSI 1.18
    rCSI 7.36%
    PRS 76.8
  • dopaminergic neuron CL0000700
    CSI 1.1
    rCSI 6.24%
    PRS 85.13
  • kidney loop of Henle thick ascending limb epithelial cell CL1001106
    CSI 1.09
    rCSI 9.43%
    PRS 89.26
  • indirect pathway medium spiny neuron CL4023029
    CSI 0.99
    rCSI 23.88%
    PRS 81.72
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 0.43
    rCSI 4.56%
    PRS 90.57
  • medium spiny neuron CL1001474
    CSI 0.22
    rCSI 1.93%
    PRS 87.48

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [NOS1](/details-gene/4842), or Nitric Oxide Synthase 1, encodes the neuronal nitric oxide synthase (nNOS), a calcium/calmodulin-dependent enzyme responsible for producing the signaling molecule nitric oxide (NO). **Overall**, expression data reveals that [NOS1](/details-gene/4842) is a defining marker for specific neuronal populations, particularly high in [lamp5 GABAergic cortical interneuron](/details-cell/CL4023011) and [peripheral nervous system neuron](/details-cell/CL2000032). Its function is central to neurotransmission, vasodilation, and muscle contraction, and dysregulation is associated with inherited disorders of smooth muscle function, as noted in OMIM ([163731](https://omim.org/entry/163731)). The enzyme's activity is integral to a wide range of physiological processes, from regulating blood pressure to mediating responses to cellular stress. ## Cellular Roles and Expression Landscape The expression profile of [NOS1](/details-gene/4842) firmly establishes its primary role within the nervous system. **Overall**, the gene shows its highest significance in distinct subpopulations of inhibitory neurons, including [lamp5 GABAergic cortical interneuron](/details-cell/CL4023011) (CSI: 13.54), [sst GABAergic cortical interneuron](/details-cell/CL4023017) (CSI: 5.80), and [pvalb GABAergic cortical interneuron](/details-cell/CL4023018) (CSI: 3.26). This strong and specific expression pattern suggests a critical function in modulating cortical circuits. Its high significance in [peripheral nervous system neuron](/details-cell/CL2000032) (CSI: 12.55) highlights its broader importance beyond the central nervous system in regulating autonomic functions. Beyond its canonical neuronal role, [NOS1](/details-gene/4842) is also significantly expressed in vascular and epithelial tissues. Notably, its presence in [cerebral cortex endothelial cell](/details-cell/CL1001602) and [pulmonary artery endothelial cell](/details-cell/CL1001568) is consistent with its function in vasodilation and blood flow regulation. Furthermore, its expression in [kidney connecting tubule epithelial cell](/details-cell/CL1000768) suggests a role in renal physiology. This diverse expression pattern is supported by research demonstrating its presence in skeletal muscle ([Link](https://doi.org/10.1016/0014-5793(93)81210-q)) and the human retina ([Link](https://doi.org/10.1007/bf02150230)), indicating a wide-ranging functional impact. ## Pathways and Molecular Function Functionally, [NOS1](/details-gene/4842) is annotated with '[Nitric-oxide synthase activity](/details-go/GO:0004517)', catalyzing the '[Nitric oxide biosynthetic process](/details-go/GO:0006809)' from L-arginine. This activity is dependent on several cofactors, reflected by its molecular function annotations for '[Calmodulin binding](/details-go/GO:0005516)', '[Heme binding](/details-go/GO:0020037)', '[Nadp binding](/details-go/GO:0050661)', and '[Tetrahydrobiopterin binding](/details-go/GO:0034617)'. The NO produced by [NOS1](/details-gene/4842) acts as a critical signaling molecule, primarily through the Reactome pathway '[Nitric oxide stimulates guanylate cyclase](/details-pathway/R-HSA-392154)'. This activation leads to diverse downstream physiological effects. Consistent with its expression in endothelial and muscle cells, [NOS1](/details-gene/4842) is implicated in processes like '[Vasodilation](/details-go/GO:0042311)', '[Negative regulation of blood pressure](/details-go/GO:0045776)', and '[Muscle contraction](/details-pathway/R-HSA-397014)'. Its prominent role in the nervous system is linked to pathways such as '[Cardiac conduction](/details-pathway/R-HSA-5576891)' and its localization to the '[Postsynaptic density](/details-go/GO:0014069)'. The gene also participates in broader systemic processes, including the '[Immune system](/details-pathway/R-HSA-168256)' and '[Hemostasis](/details-pathway/R-HSA-109582)'. ## Research Directions The highly specific expression of [NOS1](/details-gene/4842) within distinct cell types, combined with its potent biological activity, raises several key questions for future research. **Proposed Hypotheses:** 1. The distinct and high-level expression of [NOS1](/details-gene/4842) in specific GABAergic interneuron subtypes, such as [lamp5 GABAergic cortical interneuron](/details-cell/CL4023011), suggests that its activity is not a generic feature of all inhibitory neurons. We hypothesize that [NOS1](/details-gene/4842) acts as a key modulator of specific inhibitory microcircuits, and that its dysregulation within these precise cell types contributes to the excitatory/inhibitory imbalance observed in conditions like epilepsy or schizophrenia. 2. The significant expression of [NOS1](/details-gene/4842) in [cerebral cortex endothelial cell](/details-cell/CL1001602) suggests a specialized role in neurovascular coupling, potentially independent of the canonical endothelial NOS (NOS3). We hypothesize that [NOS1](/details-gene/4842)-derived NO in these cells is essential for the rapid, localized hemodynamic responses required to match blood supply with focal neural activity. **Experimental Approach:** To test the hypothesis regarding neurovascular coupling (Hypothesis 2), a cell-type-specific knockout approach would be highly informative. An experimental strategy could involve: * **Model System:** Generate a conditional knockout mouse model by crossing a mouse line carrying a floxed *Nos1* allele with a line expressing Cre recombinase under an endothelial-specific promoter (e.g., Tie2-Cre or Cdh5-Cre). * **Functional Assay:** Employ in vivo two-photon microscopy to image cerebral blood flow in anesthetized mice. After applying a sensory stimulus (e.g., whisker deflection), measure the resulting changes in red blood cell velocity and vessel diameter in both conditional knockout and wild-type control animals. * **Predicted Outcome:** A significantly blunted or delayed hyperemic response in the endothelial-specific [NOS1](/details-gene/4842) knockout mice compared to controls would provide strong evidence that [NOS1](/details-gene/4842) in cerebral endothelial cells is a critical component of neurovascular coupling. **Therapeutic Potential:** As an enzyme, [NOS1](/details-gene/4842) is a druggable target, and the development of specific inhibitors is an active area of research ([Link](https://doi.org/10.1016/j.bmc.2022.116878)). Given that overproduction of NO can lead to excitotoxicity and neuroinflammation, selective **inhibition** of [NOS1](/details-gene/4842) represents a promising therapeutic strategy for acute neurological insults like ischemic stroke or traumatic brain injury, as well as chronic neurodegenerative diseases. Conversely, for conditions characterized by smooth muscle hypercontractility (e.g., achalasia, pyloric stenosis), targeted **activation** or enhancement of [NOS1](/details-gene/4842) function could be beneficial, although achieving cell-type specificity would be a major challenge to avoid systemic side effects like hypotension.

Genular Protein ID: 3182580408

Symbol: NOS1_HUMAN

Name: Constitutive NOS

UniProtKB Accession Codes:

P29475 E9PH30 O75713

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 BMRB 1 BRENDA 1 Bgee 1 BindingDB 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 3 CORUM 1 CTD 1 ChEBI 59 ChEMBL 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 28 DrugCentral 1 EC 1 EMBL 37 Ensembl 3 EvolutionaryTrace 1 ExpressionAtlas 1 GO 64 Gene3D 5 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 19 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 96 PDBsum 96 PIR 1 PIRSF 1 PRINTS 2 PRO 1 PROSITE 4 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 5 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 5 Pumba 1 RNAct 1 Reactome 3 RefSeq 8 Rhea 2 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 5 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 7528745

Title: Structural organization of the human neuronal nitric oxide synthase gene (NOS1).

PubMed ID: 7528745

DOI: 10.1016/s0021-9258(20)30099-5

PubMed ID: 7515942

Title: Expression of two types of nitric oxide synthase mRNA in human neuroblastoma cell lines.

PubMed ID: 7515942

DOI: 10.1046/j.1471-4159.1994.63010140.x

PubMed ID: 7678401

Title: Cloned human brain nitric oxide synthase is highly expressed in skeletal muscle.

PubMed ID: 7678401

DOI: 10.1016/0014-5793(93)81210-q

PubMed ID: 8879752

Title: Neuronal isoform of nitric oxide synthase is expressed at low levels in human retina.

PubMed ID: 8879752

DOI: 10.1007/bf02150230

PubMed ID: 9111048

Title: A novel, testis-specific mRNA transcript encoding an NH2-terminal truncated nitric-oxide synthase.

PubMed ID: 9111048

DOI: 10.1074/jbc.272.17.11128

PubMed ID: 16541075

Title: The finished DNA sequence of human chromosome 12.

PubMed ID: 16541075

DOI: 10.1038/nature04569

PubMed ID: 9791007

Title: Isolation and characterization of a novel, human neuronal nitric oxide synthase cDNA.

PubMed ID: 9791007

DOI: 10.1006/bbrc.1998.9578

PubMed ID: 35772285

Title: 2-Aminopyridines with a shortened amino sidechain as potent, selective, and highly permeable human neuronal nitric oxide synthase inhibitors.

PubMed ID: 35772285

DOI: 10.1016/j.bmc.2022.116878

PubMed ID: 25286850

Title: Structures of human constitutive nitric oxide synthases.

PubMed ID: 25286850

DOI: 10.1107/s1399004714017064

Sequence Information:

  • Length: 1434
  • Mass: 160970
  • Checksum: 99235793B953BF37
  • Sequence:
    • MEDHMFGVQQ IQPNVISVRL FKRKVGGLGF LVKERVSKPP VIISDLIRGG AAEQSGLIQA 
GDIILAVNGR PLVDLSYDSA LEVLRGIASE THVVLILRGP EGFTTHLETT FTGDGTPKTI 
RVTQPLGPPT KAVDLSHQPP AGKEQPLAVD GASGPGNGPQ HAYDDGQEAG SLPHANGLAP 
RPPGQDPAKK ATRVSLQGRG ENNELLKEIE PVLSLLTSGS RGVKGGAPAK AEMKDMGIQV 
DRDLDGKSHK PLPLGVENDR VFNDLWGKGN VPVVLNNPYS EKEQPPTSGK QSPTKNGSPS 
KCPRFLKVKN WETEVVLTDT LHLKSTLETG CTEYICMGSI MHPSQHARRP EDVRTKGQLF 
PLAKEFIDQY YSSIKRFGSK AHMERLEEVN KEIDTTSTYQ LKDTELIYGA KHAWRNASRC 
VGRIQWSKLQ VFDARDCTTA HGMFNYICNH VKYATNKGNL RSAITIFPQR TDGKHDFRVW 
NSQLIRYAGY KQPDGSTLGD PANVQFTEIC IQQGWKPPRG RFDVLPLLLQ ANGNDPELFQ 
IPPELVLEVP IRHPKFEWFK DLGLKWYGLP AVSNMLLEIG GLEFSACPFS GWYMGTEIGV 
RDYCDNSRYN ILEEVAKKMN LDMRKTSSLW KDQALVEINI AVLYSFQSDK VTIVDHHSAT 
ESFIKHMENE YRCRGGCPAD WVWIVPPMSG SITPVFHQEM LNYRLTPSFE YQPDPWNTHV 
WKGTNGTPTK RRAIGFKKLA EAVKFSAKLM GQAMAKRVKA TILYATETGK SQAYAKTLCE 
IFKHAFDAKV MSMEEYDIVH LEHETLVLVV TSTFGNGDPP ENGEKFGCAL MEMRHPNSVQ 
EERKSYKVRF NSVSSYSDSQ KSSGDGPDLR DNFESAGPLA NVRFSVFGLG SRAYPHFCAF 
GHAVDTLLEE LGGERILKMR EGDELCGQEE AFRTWAKKVF KAACDVFCVG DDVNIEKANN 
SLISNDRSWK RNKFRLTFVA EAPELTQGLS NVHKKRVSAA RLLSRQNLQS PKSSRSTIFV 
RLHTNGSQEL QYQPGDHLGV FPGNHEDLVN ALIERLEDAP PVNQMVKVEL LEERNTALGV 
ISNWTDELRL PPCTIFQAFK YYLDITTPPT PLQLQQFASL ATSEKEKQRL LVLSKGLQEY 
EEWKWGKNPT IVEVLEEFPS IQMPATLLLT QLSLLQPRYY SISSSPDMYP DEVHLTVAIV 
SYRTRDGEGP IHHGVCSSWL NRIQADELVP CFVRGAPSFH LPRNPQVPCI LVGPGTGIAP 
FRSFWQQRQF DIQHKGMNPC PMVLVFGCRQ SKIDHIYREE TLQAKNKGVF RELYTAYSRE 
PDKPKKYVQD ILQEQLAESV YRALKEQGGH IYVCGDVTMA ADVLKAIQRI MTQQGKLSAE 
DAGVFISRMR DDNRYHEDIF GVTLRTYEVT NRLRSESIAF IEESKKDTDE VFSS

Genular Protein ID: 3063550731

Symbol: B4DG68_HUMAN

Name: N/A

UniProtKB Accession Codes:

B4DG68

Database IDs:

ARBA 13 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 2 CTD 1 ChEBI 14 DNASU 1 DisGeNET 1 EC 1 EMBL 2 GO 8 Gene3D 5 InterPro 15 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PIRNR 1 PIRSF 1 PIRSR 1 PRINTS 1 PROSITE 5 PeptideAtlas 1 Pfam 4 RefSeq 4 Rhea 2 SAM 1 SMART 1 SMR 1 SUPFAM 4

Sequence Information:

  • Length: 1206
  • Mass: 134816
  • Checksum: E4DBC7937045D909
  • Sequence:
    • MEDHMFGVQQ IQPNVISVRL FKRKVGGLGF LVKERVSKPP VIISDLIRGG AAEQSGLIQA 
GDIILAVNGR PLVDLSYDSA LEVLRGIASE THVVLILRGP EGFTTHLETT FTGDGTPKTI 
RVTQPLGPPT KAVDLSHQPP AGKEQPLAVD GASGPGNGPQ HAYDDGQEAG SLPHANGLAP 
RPPGQDPAKK ATRVSLQGRG ENNELLKEIE PVLSLLTSGS RGVKGGAPAK AEMKDMGIQV 
DRDLDGKSHK PLPLGVENDR VFNDLWGKGN VPVVLNNPYS EKEQPPTSGK QSPTKNGSPS 
KCPRFLKVKN WETEVVLTDT LHLKSTLETG CTEYICMGSI MHPSQHARRP EDVRTKGQLF 
PLAKEFIDQY YSSIKRFGSK AHMERLEEVN KEIDTTSTYQ LKDTELIYGA KHAWRNASRC 
VGRIQWSKLQ VFDARDCTTA HGMFNYICNH VKYATNKGNL RSAITIFPQR TDGKHDFRVW 
NSQLIRYAGY KQPDGSTLGD PANVQFTEIC IQQGWKPPRG RFDVLPLLLQ ANVNDPELFQ 
IPPELVLEVP IRHPKFEWFK DLGLKWYGLP AVSNMLLEIG GLEFSACPFS GWYMGTEIGV 
RDYCDNSRYN ILEEVAKKLN LDMRKTSSLW KDQALVEINI AVLYSFQSDK VTIVDHHSAT 
ESFIKHMENE YRCRGGCPAD WVWIVPPMSG SITPVFHQEM LNYRLTPSFE YQPDPWNTHV 
WKGTNGTPTK RRAIGFKKLA EAVKFSAKLM GQAMAKRVKA TILYATETGK SQAYAKTLCE 
IFKHAFDAKV MSMEEYDIVH LEHETLVLVV TSTFGNGDPP ENGEKFGCAL MEMRHPNSVQ 
EERKSYKVRF NSVSSYSDSQ KSSGDGPDLR DNFESAGPLA NVRFSVFGLG SRAYPHFCAF 
GHAVDTLLEE LGGERILKMR EGDELCGQEE AFRTWAKKVF KAACDVFCVG DDVNIEKANN 
SLISNDRSWK RNKFRLTFVA EAPELTQGLS NVHKKRVSAA RLLSRQNLQS PKSSRSTIFV 
RLHTNGSQEL QYQPGDHLGV FPGNHEDLVN ALIERLEDAP PVNQMVKVEL LEERNTALGV 
ISNWTDELRL PPCTIFQAFK YYLDITTPPT PLQLQQFASL ATSEKEKQRL LVLSKGLQEY 
EEWKWGKNPT IVEVLEEFPS IQMPATLLLT QLSLLQPRYY SISSSPHTHT LSETRPSPLP 
LSSQCC

Genular Protein ID: 2705104398

Symbol: A0PJJ7_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0PJJ7

Database IDs:

ARBA 11 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 ChEBI 11 ChiTaRS 1 DNASU 1 DisGeNET 1 EC 1 EMBL 2 GO 2 Gene3D 1 InterPro 2 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 PharmGKB 1 RefSeq 4 Rhea 2 SUPFAM 1

Citations:

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

Sequence Information:

  • Length: 92
  • Mass: 10404
  • Checksum: 0351AFCEF91E43C2
  • Sequence:
    • ALKEQGGHIY VCGDVTMAAD VLKAIQRIMT QQGKLSAEDA GVFISRMRDD NRYHEDIFGV 
TLRTYEVTNR LRSESIAFIE ESKKDTDEVF SS