NOS_ANOST
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 03-AUG-2022, entry version 127.
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}.
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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:LOC118512972; -.
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 Gene3D; 1.20.990.10; -; 1.
DR Gene3D; 3.40.50.360; -; 1.
DR Gene3D; 3.40.50.80; -; 1.
DR Gene3D; 3.90.1230.10; -; 1.
DR Gene3D; 3.90.340.10; -; 1.
DR Gene3D; 3.90.440.10; -; 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 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; SSF52218; SSF52218; 1.
DR SUPFAM; SSF52343; SSF52343; 1.
DR SUPFAM; SSF56512; SSF56512; 1.
DR SUPFAM; SSF63380; SSF63380; 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
