NOS1

Protein identityUniProt · HPA

UniProt accession

P29475

Gene

NOS1

Ensembl

ENSG00000089250

Chromosome

12

Canonical length

1434 aa

Protein class

Cancer-related genes, Enzymes, FDA approved drug targets, Metabolic proteins, Plasma proteins, Predicted intracellular proteins, Transporters

Subcellular location

Nucleoplasm,Plasma membrane

Quaternary structure

Homodimer

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

1434 residues, UniProt reviewed canonical sequence.

>P29475|NOS1
     1  MEDHMFGVQQ IQPNVISVRL FKRKVGGLGF LVKERVSKPP VIISDLIRGG AAEQSGLIQA
    61  GDIILAVNGR PLVDLSYDSA LEVLRGIASE THVVLILRGP EGFTTHLETT FTGDGTPKTI
   121  RVTQPLGPPT KAVDLSHQPP AGKEQPLAVD GASGPGNGPQ HAYDDGQEAG SLPHANGLAP
   181  RPPGQDPAKK ATRVSLQGRG ENNELLKEIE PVLSLLTSGS RGVKGGAPAK AEMKDMGIQV
   241  DRDLDGKSHK PLPLGVENDR VFNDLWGKGN VPVVLNNPYS EKEQPPTSGK QSPTKNGSPS
   301  KCPRFLKVKN WETEVVLTDT LHLKSTLETG CTEYICMGSI MHPSQHARRP EDVRTKGQLF
   361  PLAKEFIDQY YSSIKRFGSK AHMERLEEVN KEIDTTSTYQ LKDTELIYGA KHAWRNASRC
   421  VGRIQWSKLQ VFDARDCTTA HGMFNYICNH VKYATNKGNL RSAITIFPQR TDGKHDFRVW
   481  NSQLIRYAGY KQPDGSTLGD PANVQFTEIC IQQGWKPPRG RFDVLPLLLQ ANGNDPELFQ
   541  IPPELVLEVP IRHPKFEWFK DLGLKWYGLP AVSNMLLEIG GLEFSACPFS GWYMGTEIGV
   601  RDYCDNSRYN ILEEVAKKMN LDMRKTSSLW KDQALVEINI AVLYSFQSDK VTIVDHHSAT
   661  ESFIKHMENE YRCRGGCPAD WVWIVPPMSG SITPVFHQEM LNYRLTPSFE YQPDPWNTHV
   721  WKGTNGTPTK RRAIGFKKLA EAVKFSAKLM GQAMAKRVKA TILYATETGK SQAYAKTLCE
   781  IFKHAFDAKV MSMEEYDIVH LEHETLVLVV TSTFGNGDPP ENGEKFGCAL MEMRHPNSVQ
   841  EERKSYKVRF NSVSSYSDSQ KSSGDGPDLR DNFESAGPLA NVRFSVFGLG SRAYPHFCAF
   901  GHAVDTLLEE LGGERILKMR EGDELCGQEE AFRTWAKKVF KAACDVFCVG DDVNIEKANN
   961  SLISNDRSWK RNKFRLTFVA EAPELTQGLS NVHKKRVSAA RLLSRQNLQS PKSSRSTIFV
  1021  RLHTNGSQEL QYQPGDHLGV FPGNHEDLVN ALIERLEDAP PVNQMVKVEL LEERNTALGV
  1081  ISNWTDELRL PPCTIFQAFK YYLDITTPPT PLQLQQFASL ATSEKEKQRL LVLSKGLQEY
  1141  EEWKWGKNPT IVEVLEEFPS IQMPATLLLT QLSLLQPRYY SISSSPDMYP DEVHLTVAIV
  1201  SYRTRDGEGP IHHGVCSSWL NRIQADELVP CFVRGAPSFH LPRNPQVPCI LVGPGTGIAP
  1261  FRSFWQQRQF DIQHKGMNPC PMVLVFGCRQ SKIDHIYREE TLQAKNKGVF RELYTAYSRE
  1321  PDKPKKYVQD ILQEQLAESV YRALKEQGGH IYVCGDVTMA ADVLKAIQRI MTQQGKLSAE
  1381  DAGVFISRMR DDNRYHEDIF GVTLRTYEVT NRLRSESIAF IEESKKDTDE VFSS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NOS1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.31

Highest tissue expression

54 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.19

gnomAD pLI

1

gnomAD missense Z

3.68

DepMap mean gene effect

-0.15

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• calcium ion transport
• cell redox homeostasis
• cellular response to growth factor stimulus
• establishment of localization in cell
• L-arginine catabolic process
• multicellular organismal response to stress
• myoblast fusion
• negative regulation of blood pressure
• negative regulation of calcium ion transport
• negative regulation of calcium ion transport into cytosol
• negative regulation of potassium ion transport
• negative regulation of serotonin uptake
• nitric oxide biosynthetic process
• nitric oxide mediated signal transduction
• positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway
• positive regulation of DNA-templated transcription
• positive regulation of membrane repolarization during ventricular cardiac muscle cell action potential
• positive regulation of neuron apoptotic process
• positive regulation of the force of heart contraction
• positive regulation of transcription by RNA polymerase II
• potassium ion transport
• regulation of calcium ion transmembrane transport via high voltage-gated calcium channel
• regulation of cardiac muscle contraction
• regulation of cardiac muscle contraction by calcium ion signaling
• regulation of neurogenesis
• regulation of postsynaptic membrane potential
• regulation of sodium ion transport
• response to heat
• response to hormone
• response to hypoxia
• response to lipopolysaccharide
• striated muscle contraction
• vasodilation
• xenobiotic catabolic process
• positive regulation of sodium ion transmembrane transport
• synaptic signaling by nitric oxide

Molecular functions

• arginine binding
• cadmium ion binding
• calcium channel regulator activity
• calcium-dependent protein binding
• calmodulin binding
• flavin adenine dinucleotide binding
• FMN binding
• heme binding
• NADP binding
• nitric-oxide synthase activity
• peptidyl-cysteine S-nitrosylase activity
• scaffold protein binding
• sodium channel regulator activity
• tetrahydrobiopterin binding
• transmembrane transporter binding

Cellular components

• calyx of Held
• caveola
• cell periphery
• cytoplasm
• cytoskeleton
• cytosol
• dendritic spine
• membrane raft
• mitochondrion
• nucleoplasm
• nucleus
• perinuclear region of cytoplasm
• photoreceptor inner segment
• plasma membrane
• postsynaptic density
• protein-containing complex
• sarcolemma
• sarcoplasmic reticulum
• sarcoplasmic reticulum membrane
• synapse
• T-tubule
• Z disc

Protein domainsUniProt · Pfam · InterPro

• Flavodoxin-like
• Oxidoreductase FAD/NAD(P)-binding
• PDZ domain
• Flavoprotein pyridine nucleotide cytochrome reductase
• Sulfite reductase [NADPH] flavoprotein alpha-component-like, FAD-binding
• Nitric oxide synthase, N-terminal
• Flavodoxin/nitric oxide synthase
• Nitric-oxide synthase, eukaryote
• FAD-binding domain, ferredoxin reductase-type
• Riboflavin synthase-like beta-barrel
• NADPH-cytochrome p450 reductase, FAD-binding, alpha-helical domain superfamily
• Flavoprotein-like superfamily
• PDZ superfamily
• Nitric oxide synthase, N-terminal domain superfamily
• Ferredoxin-NADP reductase (FNR), nucleotide-binding domain
• Nitric oxide synthase, domain 2 superfamily
• Nitric oxide synthase, domain 1 superfamily
• Nitric oxide synthase, domain 3 superfamily
• Nitric Oxide Synthase (NOS)
• Oxidoreductase NAD-binding domain
• Flavodoxin
• PDZ domain
• FAD binding domain
• Nitric oxide synthase, oxygenase domain

KeywordsUniProt

• Calmodulin-binding
• Cell membrane
• Cell projection
• FAD
• Flavoprotein
• FMN
• Heme
• Iron
• Membrane
• Metal-binding
• NADP
• Oxidoreductase
• Phosphoprotein
• Synapse
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of NOS1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• DLG4
• DMD
• DYNLL1
• HTR4
• NOSIP
• SLC6A4
• VAC14
• ZDHHC23