Reviewed,
UniProtKB/Swiss-Prot P29475 (NOS1_HUMAN)
Last modified
October 13, 2009.
Version 113.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Nitric oxide synthase, brain EC=1.14.13.39 Alternative name(s): bNOS NOS type I Neuronal NOS Short name=N-NOS Short name=nNOS Constitutive NOS NC-NOS | ||
| Gene names |
| ||
| Organism | Homo sapiens (Human) [Complete proteome] | ||
| Taxonomic identifier | 9606 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 1434 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| 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. |
| Catalytic activity | L-arginine + n NADPH + n H+ + m O2 = citrulline + nitric oxide + n NADP+. |
| Cofactor | Heme group. Binds 1 FAD. Binds 1 FMN. Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme. |
| Enzyme regulation | Stimulated by calcium/calmodulin. Inhibited by n-Nos-inhibiting protein (PIN) which may prevent the dimerization of the protein. Inhibited by NOSIP. |
| Subunit structure | 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. |
| 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. |
| 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. |
| 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. |
| Involvement in disease | Genetic variations in NOS1 gene are associated with susceptibility to infantile hypertrophic pyloric stenosis type 1 (IHPS1) [MIM:179010]. IHPS has an incidence of 1-5 per 1'000 live births in whites and a marked preponderance of males to females (4:1). IHPS is the most frequent disorder requiring surgery in the first year of life. The disorder is characterized by hypertrophy and hyperplasia of the circular muscle layer of the pylorus, leading to persistent vomiting 2-12 weeks after birth. Defective pyloric relaxation and increased pyloric smooth muscle mass have been suggested to be responsible for gastric-outlet obstruction. Ref.7 |
| Sequence similarities | Belongs to the NOS family. Contains 1 FAD-binding FR-type domain. Contains 1 flavodoxin-like domain. Contains 1 PDZ (DHR) domain. |
Ontologies
Alternative products
| This entry describes 4 isoforms produced by alternative splicing. [Align] [Select] Note: Isoform 3 is produced by different alternative splicing events implicating either the untranslated exons TEX1 (TN-NOS) or TEX1B (TN-NOSB) leading to a N-terminus truncated protein which possesses enzymatic activity comparable to that of isoform 1. The C-terminal truncated isoform 4 is produced by insertion of the TEX2 exon between exons 3 and 4 of isoform 1, leading to a frameshift and a premature stop codon. | ||||||
| Isoform 1 (identifier: P29475-1) Also known as: N-NOS-1; This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: P29475-2) Also known as: N-NOS-2; The sequence of this isoform differs from the canonical sequence as follows: 509-613: Missing. | ||||||
| Isoform 3 (identifier: P29475-3) Also known as: TN-NOS; TN-NOSB; The sequence of this isoform differs from the canonical sequence as follows: 1-336: Missing. | ||||||
| Isoform 4 (identifier: P29475-4) Also known as: TEX2-insertion; The sequence of this isoform differs from the canonical sequence as follows: 285-407: PPTSGKQSPT...TYQLKDTELI → MRKLRITEGF...PKPTWKGWKR 408-1434: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1434 | 1434 | Nitric oxide synthase, brain | PRO_0000170921 | |||||
Regions | |||||||||
| Domain | 17 – 99 | 83 | PDZ | ||||||
| Domain | 760 – 940 | 181 | Flavodoxin-like | ||||||
| Domain | 995 – 1242 | 248 | FAD-binding FR-type | ||||||
| Nucleotide binding | 886 – 917 | 32 | FMN By similarity | ||||||
| Nucleotide binding | 1032 – 1043 | 12 | FAD By similarity | ||||||
| Nucleotide binding | 1175 – 1185 | 11 | FAD By similarity | ||||||
| Nucleotide binding | 1250 – 1268 | 19 | NADP By similarity | ||||||
| Nucleotide binding | 1348 – 1363 | 16 | NADP By similarity | ||||||
| Region | 1 – 205 | 205 | Interaction with NOSIP By similarity | ||||||
| Region | 163 – 245 | 83 | PIN (nNOS-inhibiting protein) binding | ||||||
| Region | 730 – 750 | 21 | Calmodulin-binding Potential | ||||||
| Region | 755 – 774 | 20 | Tetrahydrobiopterin-binding By similarity | ||||||
Sites | |||||||||
| Metal binding | 420 | 1 | Iron (heme axial ligand) By similarity | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 336 | 336 | Missing in isoform 3. | VSP_003571 | |||||
| Alternative sequence | 285 – 407 | 123 | PPTSG…DTELI → MRKLRITEGFGVQRGSHNHP PPQENSPPQRMAAPPSVHAS SRSRTGRLRWFSLTPSTLRA HWKRDALSTSAWAPSCILLS MQGGLKTSAQKDSSSLSPKS LLINTIHQLKDLAPKPTWKG WKR in isoform 4. | VSP_003572 | |||||
| Alternative sequence | 408 – 1434 | 1027 | Missing in isoform 4. | VSP_003573 | |||||
| Alternative sequence | 509 – 613 | 105 | Missing in isoform 2. | VSP_003574 | |||||
| Natural variant | 228 | 1 | P → S: dbSNP rs9658279. Ref.6 | VAR_018948 | |||||
| Natural variant | 394 | 1 | D → A: dbSNP rs9658356. Ref.6 | VAR_018949 | |||||
| Natural variant | 725 | 1 | N → D: dbSNP rs9658403. Ref.6 | VAR_018950 | |||||
| Natural variant | 864 | 1 | G → D: dbSNP rs9658445. Ref.6 | VAR_018951 | |||||
| Natural variant | 1064 | 1 | Q → R: dbSNP rs9658482. Ref.6 | VAR_018952 | |||||
Experimental info | |||||||||
| Sequence conflict | 131 | 1 | K → E in AAB49040. Ref.4 | ||||||
| Sequence conflict | 178 – 184 | 7 | LAPRPPG → WPQAPR Ref.3 | ||||||
| Sequence conflict | 178 – 184 | 7 | LAPRPPG → WPQAPR Ref.4 | ||||||
| Sequence conflict | 492 – 493 | 2 | QP → HR in AAA36376. Ref.3 | ||||||
| Sequence conflict | 549 | 1 | V → L in AAA36376. Ref.3 | ||||||
| Sequence conflict | 563 | 1 | G → A in AAA36376. Ref.3 | ||||||
| Sequence conflict | 1407 | 1 | Y → I in AAA36376. Ref.3 | ||||||
Sequences
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References
| [1] | "Structural organization of the human neuronal nitric oxide synthase gene (NOS1)." Hall A.V., Antoniou H., Wang Y., Cheung A.H., Arbus A.M., Olson S.L., Lu W.C., Kau C.-L., Marsden P.A. J. Biol. Chem. 269:33082-33090(1994) [PubMed: 7528745] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). |
| [2] | "Expression of two types of nitric oxide synthase mRNA in human neuroblastoma cell lines." Fujisawa H., Ogura T., Kurashima Y., Yokoyama T., Yamashita J., Esumi H. J. Neurochem. 63:140-145(1994) [PubMed: 7515942] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). Tissue: Cerebellum. |
| [3] | "Cloned human brain nitric oxide synthase is highly expressed in skeletal muscle." Nakane M., Schmidt H.H.H.W., Pollock J.S., Foerstermann U., Murad F. FEBS Lett. 316:175-180(1993) [PubMed: 7678401] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Brain. |
| [4] | "Neuronal isoform of nitric oxide synthase is expressed at low levels in human retina." Park C.-S., Gianotti C., Park R., Krishna G. Cell. Mol. Neurobiol. 16:499-515(1996) [PubMed: 8879752] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Retina. |
| [5] | "A novel, testis-specific mRNA transcript encoding an NH2-terminal truncated nitric-oxide synthase." Wang Y., Goligorsky M.S., Lin M., Wilcox J.N., Marsden P.A. J. Biol. Chem. 272:11392-11401(1997) [PubMed: 9111048] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 3 AND 4). Tissue: Testis. |
| [6] | NIEHS SNPs program Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-228; ALA-394; ASP-725; ASP-864 AND ARG-1064. |
| [7] | "Single-nucleotide promoter polymorphism alters transcription of neuronal nitric oxide synthase exon 1c in infantile hypertrophic pyloric stenosis." Saur D., Vanderwinden J.-M., Seidler B., Schmid R.M., De Laet M.-H., Allescher H.-D. Proc. Natl. Acad. Sci. U.S.A. 101:1662-1667(2004) [PubMed: 14757827] [Abstract] Cited for: INVOLVEMENT IN IHPS1 SUSCEPTIBILITY. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| U17327 mRNA. Translation: AAA62405.1. U17326 U17325 Genomic DNA. Translation: AAB60654.1. Sequence problems.D16408 mRNA. Translation: BAA03895.1. L02881 mRNA. Translation: AAA36376.1. U31466 mRNA. Translation: AAB49040.1. U66362 Genomic DNA. No translation available. AY445095 Genomic DNA. Translation: AAR07069.1. | |
| IPI | IPI00216232. IPI00217225. IPI00472618. IPI00746356. |
| PIR | G01946. |
| RefSeq | NP_000611.1. |
| UniGene | Hs.654410 |
3D structure databases | |
| HSSP | HSSP built from PDB template 1QAV based on UniProtKB P29476. |
| SMR | P29475. Positions 12-126, 304-723, 968-1402. |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | P29475. |
PTM databases | |
| PhosphoSite | P29475. |
Proteomic databases | |
| PRIDE | P29475. |
Genome annotation databases | |
| Ensembl | ENST00000317775; ENSP00000320758; ENSG00000089250; Homo sapiens. [Genome view] ENST00000338101; ENSP00000337459; ENSG00000089250; Homo sapiens. [Genome view] ENST00000344089; ENSP00000339862; ENSG00000089250; Homo sapiens. [Genome view] ENST00000397605; ENSP00000380730; ENSG00000089250; Homo sapiens. [Genome view] ENST00000397607; ENSP00000380732; ENSG00000089250; Homo sapiens. [Genome view] |
| GeneID | 4842. |
| KEGG | hsa:4842. |
| UCSC | uc001twm.1. human. |
Organism-specific databases | |
| CTD | 4842. |
| GeneCards | GC12M116111. |
| H-InvDB | HIX0036725. |
| HGNC | HGNC:7872. NOS1. |
| HPA | CAB002167. |
| MIM | 163731. gene. 179010. phenotype. |
| PharmGKB | PA134876543. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOGENOM | P29475. |
| HOVERGEN | P29475. |
Enzyme and pathway databases | |
| BioCyc | MetaCyc:MON-11229. |
| BRENDA | 1.14.13.39. 247. |
Gene expression databases | |
| ArrayExpress | P29475. |
| Bgee | P29475. |
| CleanEx | HS_NOS1. |
| Genevestigator | P29475. |
| GermOnline | ENSG00000089250. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR003097. FAD-binding_1. IPR017927. Fd_Rdtase_FAD-bd. IPR001094. Flavdoxin-like. IPR008254. Flavodoxin/NO_synth. IPR001709. Flavoprot_Pyr_Nucl_cyt_Rdtase. IPR012144. Nitric-oxide_synthase. IPR004030. NO_synthase_oxygenase_reg. IPR001433. OxRdtase_FAD/NAD_bd. IPR001478. PDZ/DHR/GLGF. [Graphical view] |
| Gene3D | G3DSA:3.90.340.10. NO_synthase_oxygenase_reg. 1 hit. |
| Pfam | PF00667. FAD_binding_1. 1 hit. PF00258. Flavodoxin_1. 1 hit. PF00175. NAD_binding_1. 1 hit. PF02898. NO_synthase. 1 hit. PF00595. PDZ. 1 hit. [Graphical view] |
| PIRSF | PIRSF000333. NOS. 1 hit. |
| PRINTS | PR00369. FLAVODOXIN. PR00371. FPNCR. |
| SMART | SM00228. PDZ. 1 hit. [Graphical view] |
| PROSITE | PS51384. FAD_FR. 1 hit. PS50902. FLAVODOXIN_LIKE. 1 hit. PS60001. NOS. 1 hit. PS50106. PDZ. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| DrugBank | DB00155. L-Citrulline. |
| NextBio | 18658. |
| PMAP-CutDB | P29475. |
| SOURCE | Search... |
Entry information
| Entry name | NOS1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P29475 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 12 Human chromosome 12: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


