NOSIP Gene

Name	nitric oxide synthase interacting protein
Description	The protein encoded by this gene may modulate the activity and localization of nitric oxide synthase (endothelial and neuronal) and thus nitric oxide production. Alternative splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Aug 2012]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNOSIP (nitric oxide synthase interacting protein) has been identified as a key modulator of endothelial nitric oxide synthase (eNOS) activity. Early studies revealed that NOSIP binds to the carboxyl‐terminal region of the eNOS oxygenase domain and sequesters eNOS from plasma membrane caveolae, thereby inhibiting NO synthesis. Subsequent work further demonstrated that endogenous NOSIP reduces the enzymatic capacity of eNOS in a cell cycle–dependent manner by targeting eNOS to the actin cytoskeleton during G2, an effect that is tightly coupled to NOSIP’s regulated nucleocytoplasmic shuttling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional investigations have highlighted the pathophysiological relevance of NOSIP. In the context of gastrointestinal disorders such as Hirschsprung’s associated enterocolitis, NOSIP has been implicated in the modulation of NO-mediated intestinal homeostasis, suggesting that altered expression may contribute to disease. Moreover, during neutrophil differentiation, a sustained decrease in NOSIP levels coincides with enhanced nNOS-driven NO production, an observation that underlines its role in granulopoiesis and myeloid cell function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nBiochemical analyses have further unraveled the intracellular dynamics of NOSIP, demonstrating that it functions as an E3‐ubiquitin ligase. Its subcellular localization is predominantly nuclear under basal conditions, but NOSIP is actively imported into the nucleus by transportin 1 and subsequently redistributes to the cytoplasm, particularly during the G2 phase. This dynamic nucleocytoplasmic shuttling of NOSIP is critical for its interaction with eNOS and may constitute an additional regulatory layer in the control of nitric oxide signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "J Dedio, P König, P Wohlfart, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NOSIP, a novel modulator of endothelial nitric oxide synthase activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.00-0078com"}], "href": "https://doi.org/10.1096/fj.00-0078com"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11149895"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11149895"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Michael Schleicher, Fredrik Brundin, Steffen Gross, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cell cycle-regulated inactivation of endothelial NO synthase through NOSIP-dependent targeting to the cytoskeleton."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.25.18.8251-8258.2005"}], "href": "https://doi.org/10.1128/MCB.25.18.8251-8258.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16135813"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16135813"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Christian Tomuschat, Anne-Marie O'Donnell, David Coyle, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NOS-interacting protein (NOSIP) is increased in the colon of patients with Hirschsprungs's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Pediatr Surg (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jpedsurg.2017.01.046"}], "href": "https://doi.org/10.1016/j.jpedsurg.2017.01.046"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28196663"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28196663"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Samreen Sadaf, Sheela Nagarkoti, Deepika Awasthi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "nNOS induction and NOSIP interaction impact granulopoiesis and neutrophil differentiation by modulating nitric oxide generation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Mol Cell Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamcr.2021.119018"}], "href": "https://doi.org/10.1016/j.bbamcr.2021.119018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33771575"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33771575"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Marius Pörschke, Inés Rodríguez-González, Iwan Parfentev, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transportin 1 is a major nuclear import receptor of the nitric oxide synthase interacting protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jbc.2023.102932"}], "href": "https://doi.org/10.1016/j.jbc.2023.102932"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36690276"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36690276"}]}]}]}
Synonyms	CGI-25
Proteins	NOSIP_HUMAN
NCBI Gene ID	51070
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

NOSIP has 7,231 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 120 datasets.

Click the + buttons to view associations for NOSIP from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

NOSIP Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of NOSIP gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of NOSIP gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of NOSIP gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of NOSIP gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of NOSIP gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of NOSIP gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of NOSIP gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of NOSIP gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of NOSIP gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of NOSIP gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of NOSIP gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with NOSIP protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with NOSIP gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of NOSIP gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of NOSIP gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of NOSIP gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of NOSIP gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of NOSIP gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing NOSIP protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing NOSIP protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing NOSIP protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing NOSIP protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with NOSIP protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with NOSIP protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of NOSIP gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with NOSIP gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with NOSIP gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of NOSIP protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by NOSIP gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with NOSIP gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with NOSIP gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with NOSIP gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with NOSIP gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with NOSIP gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at NOSIP gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of NOSIP gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of NOSIP gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing NOSIP from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of NOSIP gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with NOSIP gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.