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Protein

Nitric oxide synthase

Gene

Nos

Organism
Drosophila melanogaster (Fruit fly)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. Truncated isoforms (isoform 3-isoform 6) are able to form intracellular complexes with the full length protein and serve as dominant negative inhibitors of the enzyme activity.3 Publications

Catalytic activityi

2 L-arginine + 3 NADPH + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O.

Cofactori

Protein has several cofactor binding sites:
  • hemeBy similarity
  • FADBy similarityNote: Binds 1 FAD.By similarity
  • FMNBy similarityNote: Binds 1 FMN.By similarity

Enzyme regulationi

Stimulated by calcium/calmodulin.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi328Iron (heme axial ligand)By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi814 – 845FMNPROSITE-ProRule annotationAdd BLAST32
Nucleotide bindingi957 – 968FADBy similarityAdd BLAST12
Nucleotide bindingi1100 – 1110FADBy similarityAdd BLAST11
Nucleotide bindingi1175 – 1193NADPBy similarityAdd BLAST19
Nucleotide bindingi1273 – 1287NADPBy similarityAdd BLAST15

GO - Molecular functioni

  • calmodulin binding Source: FlyBase
  • flavin adenine dinucleotide binding Source: InterPro
  • FMN binding Source: InterPro
  • heme binding Source: FlyBase
  • iron ion binding Source: InterPro
  • NADP binding Source: InterPro
  • nitric-oxide synthase activity Source: UniProtKB

GO - Biological processi

  • imaginal disc development Source: FlyBase
  • negative regulation of cell proliferation Source: FlyBase
  • negative regulation of DNA replication Source: FlyBase
  • nervous system development Source: FlyBase
  • nitric oxide biosynthetic process Source: UniProtKB
  • nitric oxide mediated signal transduction Source: GO_Central
  • positive regulation of guanylate cyclase activity Source: GO_Central
  • regulation of heart rate Source: FlyBase
  • regulation of organ growth Source: FlyBase
  • synapse assembly Source: FlyBase
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

Calmodulin-binding, FAD, Flavoprotein, FMN, Heme, Iron, Metal-binding, NADP

Enzyme and pathway databases

ReactomeiR-DME-1222556. ROS, RNS production in response to bacteria.
R-DME-1474151. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
R-DME-203615. eNOS activation.
R-DME-203641. NOSTRIN mediated eNOS trafficking.
R-DME-203754. NOSIP mediated eNOS trafficking.
R-DME-392154. Nitric oxide stimulates guanylate cyclase.
R-DME-5218920. VEGFR2 mediated vascular permeability.
R-DME-5578775. Ion homeostasis.

Names & Taxonomyi

Protein namesi
Recommended name:
Nitric oxide synthase (EC:1.14.13.39)
Alternative name(s):
dNOS
Gene namesi
Name:Nos
ORF Names:CG6713
OrganismiDrosophila melanogaster (Fruit fly)
Taxonomic identifieri7227 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraEndopterygotaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora
Proteomesi
  • UP000000803 Componenti: Chromosome 2L

Organism-specific databases

FlyBaseiFBgn0011676. Nos.

Subcellular locationi

GO - Cellular componenti

  • peroxisome Source: FlyBase
Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001709511 – 1349Nitric oxide synthaseAdd BLAST1349

Proteomic databases

PaxDbiQ27571.
PRIDEiQ27571.

Expressioni

Developmental stagei

Isoform 3 is expressed in larvae only. Isoform 4, isoform 5, isoform 6 and isoform 10 are expressed throughout development from embryos to adults.1 Publication

Gene expression databases

BgeeiFBgn0011676.
GenevisibleiQ27571. DM.

Interactioni

GO - Molecular functioni

  • calmodulin binding Source: FlyBase

Protein-protein interaction databases

BioGridi60568. 1 interactor.
IntActiQ27571. 2 interactors.
MINTiMINT-964951.
STRINGi7227.FBpp0099922.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2I86model-@217-629[»]
ProteinModelPortaliQ27571.
SMRiQ27571.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini671 – 868Flavodoxin-likePROSITE-ProRule annotationAdd BLAST198
Domaini928 – 1167FAD-binding FR-typePROSITE-ProRule annotationAdd BLAST240

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni641 – 661Calmodulin-bindingSequence analysisAdd BLAST21

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi24 – 51Gln-richAdd BLAST28
Compositional biasi76 – 79Poly-Gly4
Compositional biasi145 – 156Poly-GlyAdd BLAST12

Sequence similaritiesi

Belongs to the NOS family.Curated
Contains 1 FAD-binding FR-type domain.PROSITE-ProRule annotation
Contains 1 flavodoxin-like domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG1158. Eukaryota.
COG0369. LUCA.
COG4362. LUCA.
GeneTreeiENSGT00840000129757.
InParanoidiQ27571.
KOiK13240.
OMAiQFTEICI.
OrthoDBiEOG091G10Z0.
PhylomeDBiQ27571.

Family and domain databases

Gene3Di1.20.990.10. 1 hit.
3.40.50.360. 2 hits.
3.90.340.10. 1 hit.
InterProiIPR003097. FAD-binding_1.
IPR017927. Fd_Rdtase_FAD-bd.
IPR001094. Flavdoxin-like.
IPR008254. Flavodoxin/NO_synth.
IPR001709. Flavoprot_Pyr_Nucl_cyt_Rdtase.
IPR029039. Flavoprotein-like_dom.
IPR023173. NADPH_Cyt_P450_Rdtase_dom3.
IPR012144. NOS_euk.
IPR004030. NOS_N.
IPR001433. OxRdtase_FAD/NAD-bd.
IPR017938. Riboflavin_synthase-like_b-brl.
[Graphical view]
PfamiPF00667. FAD_binding_1. 1 hit.
PF00258. Flavodoxin_1. 1 hit.
PF00175. NAD_binding_1. 1 hit.
PF02898. NO_synthase. 1 hit.
[Graphical view]
PIRSFiPIRSF000333. NOS. 1 hit.
PRINTSiPR00369. FLAVODOXIN.
PR00371. FPNCR.
SUPFAMiSSF52218. SSF52218. 1 hit.
SSF56512. SSF56512. 1 hit.
SSF63380. SSF63380. 1 hit.
PROSITEiPS51384. FAD_FR. 1 hit.
PS50902. FLAVODOXIN_LIKE. 1 hit.
PS60001. NOS. 1 hit.
[Graphical view]

Sequences (7)i

Sequence statusi: Complete.

This entry describes 7 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1Curated (identifier: Q27571-1) [UniParc]FASTAAdd to basket
Also known as: AImported, dNOS-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.

« Hide

        10         20         30         40         50
MSQHFTSIFE NLRFVTIKRS TNAQQQQQQQ QQQLQQQQQQ LQQQKAQTQQ
60 70 80 90 100
QNSRKIKTQA TPTLNGNGLL SGNPNGGGGD SSPSHEVDHP GGAQGAQAAG
110 120 130 140 150
GLPSSSGTPL RHHKRASIST ASPPIRERRG TNTSIVVELD GSGSGSGSGG
160 170 180 190 200
GGVGVGQGAG CPPSGSCTAS GKSSRELSPS PKNQQQPRKM SQDYRSRAGS
210 220 230 240 250
FMHLDDEGRS LLMRKPMRLK NIEGRPEVYD TLHCKGREIL SCSKATCTSS
260 270 280 290 300
IMNIGNAAVE ARKSDLILEH AKDFLEQYFT SIKRTSSTAH ETRWKQVRQS
310 320 330 340 350
IETTGHYQLT ETELIYGAKL AWRNSSRCIG RIQWSKLQVF DCRYVTTTSG
360 370 380 390 400
MFEAICNHIK YATNKGNLRS AITIFPQRTD AKHDYRIWNN QLISYAGYKQ
410 420 430 440 450
ADGKIIGDPM NVEFTEVCTK LGWKSKGSEW DILPLVVSAN GHDPDYFDYP
460 470 480 490 500
PELILEVPLT HPKFEWFSDL GLRWYALPAV SSMLFDVGGI QFTATTFSGW
510 520 530 540 550
YMSTEIGSRN LCDTNRRNML ETVALKMQLD TRTPTSLWKD KAVVEMNIAV
560 570 580 590 600
LHSYQSRNVT IVDHHTASES FMKHFENESK LRNGCPADWI WIVPPLSGSI
610 620 630 640 650
TPVFHQEMAL YYLKPSFEYQ DPAWRTHVWK KGRGESKGKK PRRKFNFKQI
660 670 680 690 700
ARAVKFTSKL FGRALSKRIK ATVLYATETG KSEQYAKQLC ELLGHAFNAQ
710 720 730 740 750
IYCMSDYDIS SIEHEALLIV VASTFGNGDP PENGELFSQE LYAMRVQESS
760 770 780 790 800
EHGLQDSSIG SSKSFMKASS RQEFMKLPLQ QVKRIDRWDS LRGSTSDTFT
810 820 830 840 850
EETFGPLSNV RFAVFALGSS AYPNFCAFGQ YVDNILGELG GERLLRVAYG
860 870 880 890 900
DEMCGQEQSF RKWAPEVFKL ACETFCLDPE ESLSDASLAL QNDSLTVNTV
910 920 930 940 950
RLVPSANKGS LDSSLSKYHN KKVHCCKAKA KPHNLTRLSE GAKTTMLLEI
960 970 980 990 1000
CAPGLEYEPG DHVGIFPANR TELVDGLLNR LVGVDNPDEV LQLQLLKEKQ
1010 1020 1030 1040 1050
TSNGIFKCWE PHDKIPPDTL RNLLARFFDL TTPPSRQLLT LLAGFCEDTA
1060 1070 1080 1090 1100
DKERLELLVN DSSAYEDWRH WRLPHLLDVL EEFPSCRPPA PLLLAQLTPL
1110 1120 1130 1140 1150
QPRFYSISSS PRRVSDEIHL TVAIVKYRCE DGQGDERYGV CSNYLSGLRA
1160 1170 1180 1190 1200
DDELFMFVRS ALGFHLPSDR SRPIILIGPG TGIAPFRSFW QEFQVLSDLD
1210 1220 1230 1240 1250
PTAKLPKMWL FFGCRNRDVD LYAEEKAELQ KDQILDRVFL ALSREQAIPK
1260 1270 1280 1290 1300
TYVQDLIEQE FDSLYQLIVQ ERGHIYVCGD VTMAEHVYQT IRKCIAGKEQ
1310 1320 1330 1340
KSEAEVETFL LTLRDESRYH EDIFGITLRT AEIHTKSRAT ARIRMASQP
Length:1,349
Mass (Da):151,715
Last modified:June 10, 2008 - v3
Checksum:iE19D8CBAEFAF76FC
GO
Isoform 2Curated (identifier: Q27571-2) [UniParc]FASTAAdd to basket
Also known as: dNOS-21 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     417-521: Missing.

Show »
Length:1,244
Mass (Da):139,754
Checksum:iAD7AA548C03AE48F
GO
Isoform 3Curated (identifier: Q27571-3) [UniParc]FASTAAdd to basket
Also known as: dNOS-31 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     201-214: FMHLDDEGRSLLMR → RFFPARRPPVRAAL
     215-1349: Missing.

Show »
Length:214
Mass (Da):22,460
Checksum:iAA970488F5BFBF76
GO
Isoform 4Curated (identifier: Q27571-4) [UniParc]FASTAAdd to basket
Also known as: B, dNOS-41 Publication, FImported

The sequence of this isoform differs from the canonical sequence as follows:
     736-756: LFSQELYAMRVQESSEHGLQD → VSTPPRKDHTELINGLGPAAF
     757-1349: Missing.

Show »
Length:756
Mass (Da):84,261
Checksum:i1ABA7993149272D0
GO
Isoform 5Curated (identifier: Q27571-5) [UniParc]FASTAAdd to basket
Also known as: dNOS-51 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     701-704: IYCM → VSLT
     705-1349: Missing.

Show »
Length:704
Mass (Da):78,690
Checksum:iEEF32F5F9BB8091E
GO
Isoform 6Curated (identifier: Q27571-6) [UniParc]FASTAAdd to basket
Also known as: dNOS-61 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     701-746: IYCMSDYDIS...FSQELYAMRV → CPVGSVSSDP...WQNKISCKHL
     747-1349: Missing.

Show »
Length:746
Mass (Da):83,144
Checksum:i8449B48E111D7132
GO
Isoform 10Curated (identifier: Q27571-7) [UniParc]FASTAAdd to basket
Also known as: dNOS-101 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     758-1291: Missing.

Show »
Length:815
Mass (Da):91,268
Checksum:i86C08065EBA6C062
GO

Sequence cautioni

The sequence AAZ66452 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti20S → A in AAC46882 (PubMed:7568075).Curated1
Sequence conflicti24Q → QQ in AAC46882 (PubMed:7568075).Curated1
Sequence conflicti105S → L in AAC46882 (PubMed:7568075).Curated1
Sequence conflicti287S → C in AAC46882 (PubMed:7568075).Curated1
Sequence conflicti373T → S in AAF25682 (PubMed:11526108).Curated1
Sequence conflicti1197S → R in AAC46882 (PubMed:7568075).Curated1
Sequence conflicti1197S → R in AAF25682 (PubMed:11526108).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_003585201 – 214FMHLD…SLLMR → RFFPARRPPVRAAL in isoform 3. CuratedAdd BLAST14
Alternative sequenceiVSP_003586215 – 1349Missing in isoform 3. CuratedAdd BLAST1135
Alternative sequenceiVSP_003587417 – 521Missing in isoform 2. 1 PublicationAdd BLAST105
Alternative sequenceiVSP_003590701 – 746IYCMS…YAMRV → CPVGSVSSDPQDPVQLGLVV VLVSSTCVCKKHLPAAWQNK ISCKHL in isoform 6. CuratedAdd BLAST46
Alternative sequenceiVSP_003588701 – 704IYCM → VSLT in isoform 5. Curated4
Alternative sequenceiVSP_003589705 – 1349Missing in isoform 5. CuratedAdd BLAST645
Alternative sequenceiVSP_003592736 – 756LFSQE…HGLQD → VSTPPRKDHTELINGLGPAA F in isoform 4. CuratedAdd BLAST21
Alternative sequenceiVSP_003591747 – 1349Missing in isoform 6. CuratedAdd BLAST603
Alternative sequenceiVSP_003593757 – 1349Missing in isoform 4. CuratedAdd BLAST593
Alternative sequenceiVSP_003594758 – 1291Missing in isoform 10. CuratedAdd BLAST534

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U25117 mRNA. Translation: AAC46882.1.
AF215700
, AF215691, AF215692, AF215693, AF215694, AF215695, AF215696, AF215697, AF215698, AF215699 Genomic DNA. Translation: AAF25682.1.
AE014134 Genomic DNA. Translation: AAF53014.1.
AE014134 Genomic DNA. Translation: AAZ66450.1.
AE014134 Genomic DNA. Translation: AAZ66451.1.
AE014134 Genomic DNA. Translation: AAZ66452.2. Sequence problems.
AE014134 Genomic DNA. Translation: AAZ66453.1.
AE014134 Genomic DNA. Translation: AAZ66454.1.
AE014134 Genomic DNA. Translation: AAZ66455.1.
AE014134 Genomic DNA. Translation: AAZ66456.1.
AE014134 Genomic DNA. Translation: AAZ66457.1.
BT010016 mRNA. Translation: AAQ22485.1.
PIRiT13254.
RefSeqiNP_001027240.1. NM_001032069.2. [Q27571-4]
NP_001027243.2. NM_001032072.2.
NP_523541.2. NM_078817.4. [Q27571-1]
UniGeneiDm.2707.

Genome annotation databases

EnsemblMetazoaiFBtr0080188; FBpp0079777; FBgn0011676. [Q27571-1]
GeneIDi34495.
KEGGidme:Dmel_CG6713.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U25117 mRNA. Translation: AAC46882.1.
AF215700
, AF215691, AF215692, AF215693, AF215694, AF215695, AF215696, AF215697, AF215698, AF215699 Genomic DNA. Translation: AAF25682.1.
AE014134 Genomic DNA. Translation: AAF53014.1.
AE014134 Genomic DNA. Translation: AAZ66450.1.
AE014134 Genomic DNA. Translation: AAZ66451.1.
AE014134 Genomic DNA. Translation: AAZ66452.2. Sequence problems.
AE014134 Genomic DNA. Translation: AAZ66453.1.
AE014134 Genomic DNA. Translation: AAZ66454.1.
AE014134 Genomic DNA. Translation: AAZ66455.1.
AE014134 Genomic DNA. Translation: AAZ66456.1.
AE014134 Genomic DNA. Translation: AAZ66457.1.
BT010016 mRNA. Translation: AAQ22485.1.
PIRiT13254.
RefSeqiNP_001027240.1. NM_001032069.2. [Q27571-4]
NP_001027243.2. NM_001032072.2.
NP_523541.2. NM_078817.4. [Q27571-1]
UniGeneiDm.2707.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2I86model-@217-629[»]
ProteinModelPortaliQ27571.
SMRiQ27571.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi60568. 1 interactor.
IntActiQ27571. 2 interactors.
MINTiMINT-964951.
STRINGi7227.FBpp0099922.

Proteomic databases

PaxDbiQ27571.
PRIDEiQ27571.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaiFBtr0080188; FBpp0079777; FBgn0011676. [Q27571-1]
GeneIDi34495.
KEGGidme:Dmel_CG6713.

Organism-specific databases

CTDi34495.
FlyBaseiFBgn0011676. Nos.

Phylogenomic databases

eggNOGiKOG1158. Eukaryota.
COG0369. LUCA.
COG4362. LUCA.
GeneTreeiENSGT00840000129757.
InParanoidiQ27571.
KOiK13240.
OMAiQFTEICI.
OrthoDBiEOG091G10Z0.
PhylomeDBiQ27571.

Enzyme and pathway databases

ReactomeiR-DME-1222556. ROS, RNS production in response to bacteria.
R-DME-1474151. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
R-DME-203615. eNOS activation.
R-DME-203641. NOSTRIN mediated eNOS trafficking.
R-DME-203754. NOSIP mediated eNOS trafficking.
R-DME-392154. Nitric oxide stimulates guanylate cyclase.
R-DME-5218920. VEGFR2 mediated vascular permeability.
R-DME-5578775. Ion homeostasis.

Miscellaneous databases

GenomeRNAii34495.
PROiQ27571.

Gene expression databases

BgeeiFBgn0011676.
GenevisibleiQ27571. DM.

Family and domain databases

Gene3Di1.20.990.10. 1 hit.
3.40.50.360. 2 hits.
3.90.340.10. 1 hit.
InterProiIPR003097. FAD-binding_1.
IPR017927. Fd_Rdtase_FAD-bd.
IPR001094. Flavdoxin-like.
IPR008254. Flavodoxin/NO_synth.
IPR001709. Flavoprot_Pyr_Nucl_cyt_Rdtase.
IPR029039. Flavoprotein-like_dom.
IPR023173. NADPH_Cyt_P450_Rdtase_dom3.
IPR012144. NOS_euk.
IPR004030. NOS_N.
IPR001433. OxRdtase_FAD/NAD-bd.
IPR017938. Riboflavin_synthase-like_b-brl.
[Graphical view]
PfamiPF00667. FAD_binding_1. 1 hit.
PF00258. Flavodoxin_1. 1 hit.
PF00175. NAD_binding_1. 1 hit.
PF02898. NO_synthase. 1 hit.
[Graphical view]
PIRSFiPIRSF000333. NOS. 1 hit.
PRINTSiPR00369. FLAVODOXIN.
PR00371. FPNCR.
SUPFAMiSSF52218. SSF52218. 1 hit.
SSF56512. SSF56512. 1 hit.
SSF63380. SSF63380. 1 hit.
PROSITEiPS51384. FAD_FR. 1 hit.
PS50902. FLAVODOXIN_LIKE. 1 hit.
PS60001. NOS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNOS_DROME
AccessioniPrimary (citable) accession number: Q27571
Secondary accession number(s): A4V0K9
, A4V0L0, Q4ABG3, Q4ABG4, Q4ABG5, Q4ABG6, Q4ABG7, Q7YU33, Q9U096, Q9VKP8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: June 10, 2008
Last modified: November 2, 2016
This is version 158 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programDrosophila annotation project

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Drosophila
    Drosophila: entries, gene names and cross-references to FlyBase
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.