ID   NOS_LYMST               Reviewed;        1153 AA.
AC   O61309;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1998, sequence version 1.
DT   22-FEB-2023, entry version 129.
DE   RecName: Full=Nitric oxide synthase;
DE            EC=1.14.13.39;
DE   AltName: Full=NOS type I;
DE   AltName: Full=Neuronal NOS;
DE            Short=N-NOS;
DE            Short=nNOS;
GN   Name=NOS;
OS   Lymnaea stagnalis (Great pond snail) (Helix stagnalis).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Heterobranchia; Euthyneura; Panpulmonata; Hygrophila; Lymnaeoidea;
OC   Lymnaeidae; Lymnaea.
OX   NCBI_TaxID=6523;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT).
RC   TISSUE=CNS;
RX   PubMed=9552167;
RX   DOI=10.1002/(sici)1097-4695(199804)35:1<65::aid-neu6>3.0.co;2-9;
RA   Korneev S.A., Piper M.R., Picot J., Phillips R., Korneeva E.I., O'Shea M.;
RT   "Molecular characterization of NOS in a mollusc: expression in a giant
RT   modulatory neuron.";
RL   J. Neurobiol. 35:65-76(1998).
CC   -!- FUNCTION: Produces nitric oxide (NO) which is a messenger molecule with
CC       diverse functions throughout the body. {ECO:0000250}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H(+) + 2 L-arginine + 3 NADPH + 4 O2 = 4 H2O + 2 L-citrulline
CC         + 3 NADP(+) + 2 nitric oxide; Xref=Rhea:RHEA:19897,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:16480, ChEBI:CHEBI:32682, ChEBI:CHEBI:57743,
CC         ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.14.13.39;
CC   -!- COFACTOR:
CC       Name=heme b; Xref=ChEBI:CHEBI:60344; Evidence={ECO:0000250};
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC       Note=Binds 1 FAD. {ECO:0000250};
CC   -!- COFACTOR:
CC       Name=FMN; Xref=ChEBI:CHEBI:58210; Evidence={ECO:0000250};
CC       Note=Binds 1 FMN. {ECO:0000250};
CC   -!- ACTIVITY REGULATION: Stimulated by calcium/calmodulin.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=Long;
CC         IsoId=O61309-1; Sequence=Displayed;
CC       Name=Short;
CC         IsoId=O61309-2; Sequence=VSP_003584;
CC   -!- TISSUE SPECIFICITY: Expressed in the central nervous system, in the
CC       serotonergic cerebral giant cells. The isoform Long and isoform Short
CC       are expressed equally in the CNS.
CC   -!- SIMILARITY: Belongs to the NOS family. {ECO:0000305}.
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DR   EMBL; AF012531; AAC17487.1; -; mRNA.
DR   PIR; T31080; T31080.
DR   AlphaFoldDB; O61309; -.
DR   SMR; O61309; -.
DR   BRENDA; 1.14.13.39; 3112.
DR   GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR   GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR   GO; GO:0010181; F:FMN binding; IEA:InterPro.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR   GO; GO:0004517; F:nitric-oxide synthase activity; IEA:UniProtKB-EC.
DR   GO; GO:0006809; P:nitric oxide biosynthetic process; IEA:InterPro.
DR   Gene3D; 3.40.50.360; -; 1.
DR   Gene3D; 3.90.440.10; Nitric Oxide Synthase;Heme Domain;Chain A domain 2; 1.
DR   Gene3D; 3.40.50.80; Nucleotide-binding domain of ferredoxin-NADP reductase (FNR) module; 1.
DR   Gene3D; 2.40.30.10; Translation factors; 1.
DR   InterPro; IPR003097; CysJ-like_FAD-binding.
DR   InterPro; IPR017927; FAD-bd_FR_type.
DR   InterPro; IPR001094; Flavdoxin-like.
DR   InterPro; IPR008254; Flavodoxin/NO_synth.
DR   InterPro; IPR001709; Flavoprot_Pyr_Nucl_cyt_Rdtase.
DR   InterPro; IPR029039; Flavoprotein-like_sf.
DR   InterPro; IPR039261; FNR_nucleotide-bd.
DR   InterPro; IPR023173; NADPH_Cyt_P450_Rdtase_alpha.
DR   InterPro; IPR044943; NOS_dom_1.
DR   InterPro; IPR044940; NOS_dom_2.
DR   InterPro; IPR044944; NOS_dom_3.
DR   InterPro; IPR012144; NOS_euk.
DR   InterPro; IPR004030; NOS_N.
DR   InterPro; IPR036119; NOS_N_sf.
DR   InterPro; IPR001433; OxRdtase_FAD/NAD-bd.
DR   InterPro; IPR017938; Riboflavin_synthase-like_b-brl.
DR   PANTHER; PTHR43410; NITRIC OXIDE SYNTHASE OXYGENASE; 1.
DR   PANTHER; PTHR43410:SF1; NITRIC OXIDE SYNTHASE OXYGENASE; 1.
DR   Pfam; PF00667; FAD_binding_1; 1.
DR   Pfam; PF00258; Flavodoxin_1; 1.
DR   Pfam; PF00175; NAD_binding_1; 1.
DR   Pfam; PF02898; NO_synthase; 1.
DR   PIRSF; PIRSF000333; NOS; 1.
DR   PRINTS; PR00369; FLAVODOXIN.
DR   PRINTS; PR00371; FPNCR.
DR   SUPFAM; SSF52343; Ferredoxin reductase-like, C-terminal NADP-linked domain; 2.
DR   SUPFAM; SSF52218; Flavoproteins; 1.
DR   SUPFAM; SSF56512; Nitric oxide (NO) synthase oxygenase domain; 1.
DR   SUPFAM; SSF63380; Riboflavin synthase domain-like; 1.
DR   PROSITE; PS51384; FAD_FR; 1.
DR   PROSITE; PS50902; FLAVODOXIN_LIKE; 1.
DR   PROSITE; PS60001; NOS; 1.
PE   2: Evidence at transcript level;
KW   Alternative splicing; Calmodulin-binding; FAD; Flavoprotein; FMN; Heme;
KW   Iron; Metal-binding; NADP; Oxidoreductase; Repeat.
FT   CHAIN           1..1153
FT                   /note="Nitric oxide synthase"
FT                   /id="PRO_0000170949"
FT   DOMAIN          427..610
FT                   /note="Flavodoxin-like"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00088"
FT   DOMAIN          660..903
FT                   /note="FAD-binding FR-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT   REPEAT          934..940
FT                   /note="1"
FT   REPEAT          941..947
FT                   /note="2"
FT   REPEAT          948..954
FT                   /note="3"
FT   REPEAT          955..961
FT                   /note="4"
FT   REPEAT          962..968
FT                   /note="5"
FT   REPEAT          969..975
FT                   /note="6"
FT   REPEAT          976..982
FT                   /note="7"
FT   REPEAT          983..989
FT                   /note="8"
FT   REPEAT          990..996
FT                   /note="9"
FT   REPEAT          997..1003
FT                   /note="10"
FT   REPEAT          1004..1010
FT                   /note="11"
FT   REGION          397..417
FT                   /note="Calmodulin-binding"
FT                   /evidence="ECO:0000255"
FT   REGION          934..1010
FT                   /note="11 X 7 AA tandem repeats of E-[NTR]-[ST]-[IM]-[PLQ]-
FT                   [SP]-[CW]"
FT   BINDING         3
FT                   /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT                   /ligand_id="ChEBI:CHEBI:59560"
FT                   /evidence="ECO:0000250|UniProtKB:P29474"
FT   BINDING         82
FT                   /ligand="heme b"
FT                   /ligand_id="ChEBI:CHEBI:60344"
FT                   /ligand_part="Fe"
FT                   /ligand_part_id="ChEBI:CHEBI:18248"
FT                   /note="axial binding residue"
FT                   /evidence="ECO:0000250|UniProtKB:P29474"
FT   BINDING         145
FT                   /ligand="L-arginine"
FT                   /ligand_id="ChEBI:CHEBI:32682"
FT                   /evidence="ECO:0000250|UniProtKB:P29474"
FT   BINDING         254
FT                   /ligand="L-arginine"
FT                   /ligand_id="ChEBI:CHEBI:32682"
FT                   /evidence="ECO:0000250|UniProtKB:P29474"
FT   BINDING         264
FT                   /ligand="L-arginine"
FT                   /ligand_id="ChEBI:CHEBI:32682"
FT                   /evidence="ECO:0000250|UniProtKB:P29474"
FT   BINDING         358
FT                   /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT                   /ligand_id="ChEBI:CHEBI:59560"
FT                   /evidence="ECO:0000250|UniProtKB:P29474"
FT   BINDING         556..587
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00088"
FT   BINDING         697..708
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         836..846
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         911..929
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         1089..1104
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         276..309
FT                   /note="Missing (in isoform Short)"
FT                   /evidence="ECO:0000303|PubMed:9552167"
FT                   /id="VSP_003584"
SQ   SEQUENCE   1153 AA;  129086 MW;  101B77D02B66B109 CRC64;
     MGSLSQQAHG PPDAPRSKEE LLIHAKDFIN QYFTSFQMNK TRAHFHRLGE INDLIEKSGT
     YDLTMAELTF GAKHAWRNAP GCIGRSQWSK LQVFDAREIG TPREMFEALC SHIRYATNEG
     KIRSTITIFP QRKEGRPDFR VWNTQLISYA GYKLGDGKVI GDPANVEFTE MCVEMGWKPK
     HGMFDLLPLV LSAAENSPEY FELPTELVLE VTLKHPEYPW FAEMGLKWYA LPTDSGMLLD
     CGGLEFPSCP FNGWFMGTMI GSRNLCDPHR YNMLEPIGLK MGLNTETASS LWKDRVLIEV
     NVAVLYSFES ANVTIVNHHD ASTDFISHMD KEIKLRGGCP SDWVRMVPPM SGSTLEVFHQ
     EMLLYNLHPA FVRQDVKPWK KHVWKSDQSV PINSCNPKRK LGFKALARAV EFSASLMSKA
     LSSRVKCSIF YATETGRSER FARRLSEIFK PVFHSRVVCM DDYAVETLEH ESLVMVITST
     FGNGEPPENG KQFAQSLLDM KRKYDCDLGF LESCSSISTC IKSSILTEGP LAADVIGDRQ
     SLAMGTGPLC NVRFAVFGLG SKAYPYYAAY GKYIYLMLQE LGAERLVNYC AGDALYGQEQ
     SFRAWSEEVF KASCEAFCLD NRNDAPGPQT KGDCSKVRIV PVENCQEPDL CQVLRNIHGK
     EVMPLILAER IQLQAKDSDQ QTILIKLDAH NATDLKYAPG DHVAIFPANS PEIVDAILVR
     LDTSKGPSPD QVVKTEISTQ LGTNDTWRSH LPICTSRTAF SFLLDVTTPP SQEILQVLAT
     QASSDMDKHK LEQLASNSEA YEKWRLDLSP NILEILDEFP SLKIPPSLLL TQLPLLQPRY
     YSISSSQQKN PNEVHATIAV VRFKTQDGDG PVHEGVCSSW LNRSPIGTVV PCFLRSAPHF
     HLPEDPSLPI IMIGPGSGIA PFRSFWQQRL GEIENTMPSC ENTMLSCETT IPSCENSMPS
     CENTMPSCEN TMPSCENTIP SCENTIPSCE NTMPSCENTI PSWERTMQPC QIILPSQTKK
     HFGEMVLYTG CRTAKHMIYA AELEEMKRLG VLSNYHVALS REAALPKMYV QDIIIKNAAA
     VYEIVMKKGG HFYVSGDVSM AHDVTRALEL VLCQQGGREA SQQVMSLRDE NLFHEDIFGS
     FVRKAGGQRS EDE
//