ID NOS_ANOST Reviewed; 1247 AA. AC O61608; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1999, sequence version 2. DT 22-FEB-2023, entry version 129. DE RecName: Full=Nitric oxide synthase; DE Short=NOS; DE EC=1.14.13.39; OS Anopheles stephensi (Indo-Pakistan malaria mosquito). OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota; OC Neoptera; Endopterygota; Diptera; Nematocera; Culicoidea; Culicidae; OC Anophelinae; Anopheles. OX NCBI_TaxID=30069; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND INDUCTION. RX PubMed=9576947; DOI=10.1073/pnas.95.10.5700; RA Luckhart S., Vodovotz Y., Cui L., Rosenberg R.; RT "The mosquito Anopheles stephensi limits malaria parasite development with RT inducible synthesis of nitric oxide."; RL Proc. Natl. Acad. Sci. U.S.A. 95:5700-5705(1998). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=10333518; DOI=10.1016/s0378-1119(99)00121-3; RA Luckhart S., Rosenberg R.; RT "Gene structure and polymorphism of an invertebrate nitric oxide synthase RT gene."; RL Gene 232:25-34(1999). CC -!- FUNCTION: Produces nitric oxide (NO) which is a messenger molecule with CC diverse functions throughout the body. Nitric oxide limits plasmodium CC development in the midgut. {ECO:0000269|PubMed:9576947}. 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. {ECO:0000250}. CC -!- INDUCTION: Detected in the midgut and carcass soon after invasion of CC the midgut by plasmodium. Early induction is also primed by bacterial CC growth in the blood meal. {ECO:0000269|PubMed:9576947}. CC -!- SIMILARITY: Belongs to the NOS family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF130134; AAC68577.1; -; Genomic_DNA. DR EMBL; AF130124; AAC68577.1; JOINED; Genomic_DNA. DR EMBL; AF130125; AAC68577.1; JOINED; Genomic_DNA. DR EMBL; AF130126; AAC68577.1; JOINED; Genomic_DNA. DR EMBL; AF130127; AAC68577.1; JOINED; Genomic_DNA. DR EMBL; AF130128; AAC68577.1; JOINED; Genomic_DNA. DR EMBL; AF130129; AAC68577.1; JOINED; Genomic_DNA. DR EMBL; AF130130; AAC68577.1; JOINED; Genomic_DNA. DR EMBL; AF130131; AAC68577.1; JOINED; Genomic_DNA. DR EMBL; AF130132; AAC68577.1; JOINED; Genomic_DNA. DR EMBL; AF130133; AAC68577.1; JOINED; Genomic_DNA. DR PIR; T31331; T31331. DR AlphaFoldDB; O61608; -. DR SMR; O61608; -. DR STRING; 30069.O61608; -. DR EnsemblMetazoa; ASTE008595-RA; ASTE008595-PA; ASTE008595. DR VEuPathDB; VectorBase:ASTE008593; -. DR VEuPathDB; VectorBase:ASTE008595; -. DR VEuPathDB; VectorBase:ASTEI03015; -. DR VEuPathDB; VectorBase:ASTEI03016; -. DR VEuPathDB; VectorBase:ASTEI20_044834; -. DR Proteomes; UP000076408; Unassembled WGS sequence. 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 CDD; cd00795; NOS_oxygenase_euk; 1. 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; 1. 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 Calmodulin-binding; FAD; Flavoprotein; FMN; Heme; Iron; Metal-binding; KW NADP; Oxidoreductase; Reference proteome. FT CHAIN 1..1247 FT /note="Nitric oxide synthase" FT /id="PRO_0000170950" FT DOMAIN 567..766 FT /note="Flavodoxin-like" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00088" FT DOMAIN 795..1065 FT /note="FAD-binding FR-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716" FT REGION 13..33 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 537..557 FT /note="Calmodulin-binding" FT /evidence="ECO:0000255" FT BINDING 146 FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin" FT /ligand_id="ChEBI:CHEBI:59560" FT /evidence="ECO:0000250|UniProtKB:P29474" FT BINDING 224 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 287 FT /ligand="L-arginine" FT /ligand_id="ChEBI:CHEBI:32682" FT /evidence="ECO:0000250|UniProtKB:P29474" FT BINDING 396 FT /ligand="L-arginine" FT /ligand_id="ChEBI:CHEBI:32682" FT /evidence="ECO:0000250|UniProtKB:P29474" FT BINDING 397 FT /ligand="L-arginine" FT /ligand_id="ChEBI:CHEBI:32682" FT /evidence="ECO:0000250|UniProtKB:P29474" FT BINDING 401 FT /ligand="L-arginine" FT /ligand_id="ChEBI:CHEBI:32682" FT /evidence="ECO:0000250|UniProtKB:P29474" FT BINDING 406 FT /ligand="L-arginine" FT /ligand_id="ChEBI:CHEBI:32682" FT /evidence="ECO:0000250|UniProtKB:P29474" FT BINDING 487 FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin" FT /ligand_id="ChEBI:CHEBI:59560" FT /evidence="ECO:0000250|UniProtKB:P29474" FT BINDING 500 FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin" FT /ligand_id="ChEBI:CHEBI:59560" FT /evidence="ECO:0000250|UniProtKB:P29474" FT BINDING 515 FT /ligand="heme b" FT /ligand_id="ChEBI:CHEBI:60344" FT /evidence="ECO:0000250|UniProtKB:P29474" FT BINDING 712..743 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00088" FT BINDING 855..866 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250" FT BINDING 998..1008 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250" FT BINDING 1073..1091 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250" FT BINDING 1170..1185 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250" SQ SEQUENCE 1247 AA; 141651 MW; 5F435E5EAC3D3778 CRC64; MADTTTVVVE RREVAEGRES SKANHIGEER RGYDVSRKRC SISVHGGGTE GGGGNMRTNY RELSPASLRI HRKSSHDIRN TLLGPDGEVL HLHDPSGKGG DGMGKMPAVV KPIKLKSIVT KAESYDTMHG KASDVMSCSR EVCMGSVMTP HVIGTETRKP EIVQQHAKDF LDQYYSSIRR LKSPAHDSRW QQVQKEVEAT GSYHLTETEL IYGAKLAWRN SSRCIGRIQW SKLQVFDCRY VTTTSGMFEA ICNHIKYATN KGNLRSAITI FPQRTDGKHD YRIWNNQIIS YAGYKNADGK IIGDPANVEF TDFCVKLGWK SKRTEWDILP LVVSANGHDP DYFDYPPELI LEVPLSHPQF KWFAELNLRW YAVPMVSSML FDCGGIQFTA TAFSGWYMST EIGCRNLCDA NRRNLLEPIA IKMGLDTRNP TSLWKDKALV EINIAVLHSY QSRNITIVDH HTASESFMKH FENETKLRNG CPADWIWIVP PMSASVTPVF HQEMAVYYLR PSFEYQESAM KTHIWKKGRD SAKNKKPRRK FNFKQIARAV KFTSKLFGRA LSRRIKATVL YATETGRSEQ YARQLVELLG HAFNAQIYCM SDYDISSIEH EALLLVVAST FGNGDPPENG ELFAQDLYAM KLHESGHHQA HSELTIAASS KSFIKANSRS DLGKFGPMGG RKIDRLDSLR GSTTDTLSEE TFGPLSNVRF AVFALGSSAY PNFCAFGKYI DNILGELGGE RLMKMATGDE ICGQEQAFRK WAPEVFKIAC ETFCLDPEET LSDAAFALQS ELSENTVRYA PVAEYESLDR ALSKFHNKKS MECSVKRNPI NLHCEMNGTE RSTILVEIMA EGIDYEPGDH VGIFPANRKE IVDGIIERLT GVNDPDEMLQ LQVLKEKQTQ NGVYKSWEPH ERLPVCTLRT LLTRFLDITT PPTRQLLTYL ASCCGDKADE ERLLMLANES SVYEDWRYWK LPHLLEVLEE FPSCRPPAAV FVAQLNALQP RFYSISSSPR KYSNEIHLTV AIVTYRAEDG EGAEHYGVCS NYLANLQSDD KIYLFVRSAP SFHMSKDRTK PVILIGPGTG IAPFRSFWQE WDHIKTEMVD CKIPKVWLFF GCRTKNVDLY RDEKEEMVQH GVLDRVFLAL SREENIPKTY VQDLALKEAE SISELIMQEK GHIYVCGDVT MAEHVYQTLR KILATREKRT ETEMEKYMLT LRDENRYHED IFGITLRTAE IHNKSRATAR IRMASQP //