ID A0A2Y9T1B5_PHYMC Unreviewed; 1200 AA.
AC A0A2Y9T1B5;
DT 12-SEP-2018, integrated into UniProtKB/TrEMBL.
DT 12-SEP-2018, sequence version 1.
DT 27-MAR-2024, entry version 27.
DE RecName: Full=Nitric oxide synthase {ECO:0000256|PIRNR:PIRNR000333};
DE EC=1.14.13.39 {ECO:0000256|PIRNR:PIRNR000333};
GN Name=NOS3 {ECO:0000313|RefSeq:XP_023984716.1};
OS Physeter macrocephalus (Sperm whale) (Physeter catodon).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Whippomorpha; Cetacea; Odontoceti;
OC Physeteridae; Physeter.
OX NCBI_TaxID=9755 {ECO:0000313|Proteomes:UP000248484, ECO:0000313|RefSeq:XP_023984716.1};
RN [1] {ECO:0000313|RefSeq:XP_023984716.1}
RP IDENTIFICATION.
RC TISSUE=Muscle {ECO:0000313|RefSeq:XP_023984716.1};
RG RefSeq;
RL Submitted (NOV-2023) to UniProtKB.
CC -!- FUNCTION: Produces nitric oxide (NO) which is a messenger molecule with
CC diverse functions. {ECO:0000256|PIRNR:PIRNR000333}.
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 Evidence={ECO:0000256|ARBA:ARBA00035595};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19898;
CC Evidence={ECO:0000256|ARBA:ARBA00035595};
CC -!- COFACTOR:
CC Name=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin;
CC Xref=ChEBI:CHEBI:59560; Evidence={ECO:0000256|ARBA:ARBA00001950};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000256|PIRNR:PIRNR000333};
CC Note=Binds 1 FAD. {ECO:0000256|PIRNR:PIRNR000333};
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000256|PIRNR:PIRNR000333};
CC Note=Binds 1 FMN. {ECO:0000256|PIRNR:PIRNR000333};
CC -!- COFACTOR:
CC Name=heme b; Xref=ChEBI:CHEBI:60344;
CC Evidence={ECO:0000256|ARBA:ARBA00001970,
CC ECO:0000256|PIRNR:PIRNR000333};
CC -!- SIMILARITY: Belongs to the NOS family. {ECO:0000256|ARBA:ARBA00006267,
CC ECO:0000256|PIRNR:PIRNR000333}.
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DR RefSeq; XP_023984716.1; XM_024128948.3.
DR AlphaFoldDB; A0A2Y9T1B5; -.
DR STRING; 9755.ENSPCTP00005019587; -.
DR Ensembl; ENSPCTT00005021579; ENSPCTP00005019587; ENSPCTG00005013206.
DR Proteomes; UP000248484; Chromosome 5.
DR GO; GO:0005901; C:caveola; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0003785; F:actin monomer binding; IEA:Ensembl.
DR GO; GO:0034618; F:arginine binding; IEA:Ensembl.
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:Ensembl.
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:0097110; F:scaffold protein binding; IEA:Ensembl.
DR GO; GO:0034617; F:tetrahydrobiopterin binding; IEA:Ensembl.
DR GO; GO:0001525; P:angiogenesis; IEA:Ensembl.
DR GO; GO:0003180; P:aortic valve morphogenesis; IEA:Ensembl.
DR GO; GO:0006527; P:arginine catabolic process; IEA:Ensembl.
DR GO; GO:0097746; P:blood vessel diameter maintenance; IEA:Ensembl.
DR GO; GO:0001974; P:blood vessel remodeling; IEA:Ensembl.
DR GO; GO:0006816; P:calcium ion transport; IEA:Ensembl.
DR GO; GO:0003203; P:endocardial cushion morphogenesis; IEA:Ensembl.
DR GO; GO:0043542; P:endothelial cell migration; IEA:Ensembl.
DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl.
DR GO; GO:0048873; P:homeostasis of number of cells within a tissue; IEA:Ensembl.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0030324; P:lung development; IEA:Ensembl.
DR GO; GO:0070168; P:negative regulation of biomineral tissue development; IEA:Ensembl.
DR GO; GO:0051926; P:negative regulation of calcium ion transport; IEA:Ensembl.
DR GO; GO:0014740; P:negative regulation of muscle hyperplasia; IEA:Ensembl.
DR GO; GO:0043267; P:negative regulation of potassium ion transport; IEA:Ensembl.
DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0006809; P:nitric oxide biosynthetic process; IEA:Ensembl.
DR GO; GO:0001542; P:ovulation from ovarian follicle; IEA:Ensembl.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IEA:Ensembl.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:0006813; P:potassium ion transport; IEA:Ensembl.
DR GO; GO:0003184; P:pulmonary valve morphogenesis; IEA:Ensembl.
DR GO; GO:0031644; P:regulation of nervous system process; IEA:Ensembl.
DR GO; GO:0002028; P:regulation of sodium ion transport; IEA:Ensembl.
DR GO; GO:0003100; P:regulation of systemic arterial blood pressure by endothelin; IEA:Ensembl.
DR GO; GO:0003057; P:regulation of the force of heart contraction by chemical signal; IEA:Ensembl.
DR GO; GO:0019430; P:removal of superoxide radicals; IEA:Ensembl.
DR GO; GO:0034405; P:response to fluid shear stress; IEA:Ensembl.
DR GO; GO:0014806; P:smooth muscle hyperplasia; IEA:Ensembl.
DR GO; GO:0060412; P:ventricular septum morphogenesis; IEA:Ensembl.
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 3: Inferred from homology;
KW Calmodulin-binding {ECO:0000256|ARBA:ARBA00022860,
KW ECO:0000256|PIRNR:PIRNR000333};
KW FAD {ECO:0000256|ARBA:ARBA00022827, ECO:0000256|PIRNR:PIRNR000333};
KW Flavoprotein {ECO:0000256|ARBA:ARBA00022630};
KW FMN {ECO:0000256|ARBA:ARBA00022643, ECO:0000256|PIRNR:PIRNR000333};
KW Heme {ECO:0000256|ARBA:ARBA00022617, ECO:0000256|PIRNR:PIRNR000333};
KW Iron {ECO:0000256|ARBA:ARBA00023004, ECO:0000256|PIRNR:PIRNR000333};
KW Metal-binding {ECO:0000256|ARBA:ARBA00022723,
KW ECO:0000256|PIRNR:PIRNR000333};
KW NADP {ECO:0000256|ARBA:ARBA00022857, ECO:0000256|PIRNR:PIRNR000333};
KW Oxidoreductase {ECO:0000256|ARBA:ARBA00023002,
KW ECO:0000256|PIRNR:PIRNR000333};
KW Reference proteome {ECO:0000313|Proteomes:UP000248484}.
FT DOMAIN 517..700
FT /note="Flavodoxin-like"
FT /evidence="ECO:0000259|PROSITE:PS50902"
FT DOMAIN 753..999
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000259|PROSITE:PS51384"
FT REGION 1..67
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 814..841
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 35..61
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 181
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:0000256|PIRSR:PIRSR000333-1"
SQ SEQUENCE 1200 AA; 132780 MW; B9CB4E709B127270 CRC64;
MGNLKSVGQE PGPPCGLGLG LGLGLCSKQG PASPAPEPSR APAPAPPPAP DHSPQLTRPP
EGPRFPRVKN WEVGTIAYDT LCAQSQQDGP CTPRRCLGSL VFPRKLQSRP SQGPPPPEQL
LSQARDFINQ YYSSIKRSGS EAHKERLQEV EAEVAATGTY QLRESELVFG AKQAWRNAPR
CVGRIQWGKL QVFDARDCSS AQEMFTYVCN HIKYATNRGN LRSAITVFPQ RAPGRGDFRI
WNSQLVRYAG YRQQDGSVRG DPANVEITEL CIQHGWTPGN GRFDVLPLLL QTPDEAPELF
VLPPELVLEV PLEHPTLEWF SALGLRWYAL PAVSNMLLEI GGLEFPAAPF SGWYMSTEIG
TRNLCDPHRY NILEDVAVCM DLDTRTTSSL WKDKAAVEIN LAVLHSYQLA KVAIVDHHAA
TASFMKHLEN EQRARGGCPA DWAWIVPPIS GSLTPVFHQE MVNYVLSPAF RYQPDPWKGS
AAKGASITRK KTFKEVANAV KISASLMGTV MAKRVKATIL YASETGRAQS YAQQLGRLFR
KAFDPRVLCM DEYDVVSLEH ETLVLVVTST FGNGDPPENG ESFAAALMEM SGPYNSSPRP
EQHKSYKIRF NSVSCSDPLV SSWRRKRKES SNTDSAGALG TLRFCVFGLG SRAYPHFCAF
ARAVDTRLEE LGGERLLQLG QGDELCGQEE AFRGWAQAAF QASCETFCVG EDAKAAAQDI
FSPKRSWKRQ RYRLSAQAEG LQLLPGLIHA HRRKMFQATV LLVENLQSSK STRATILVRL
DTGGQEGLQY QPGDHIGICP PNRPGLVEAL MSRVEDPPPP TESVAVEQLE KGSPGGPPPG
WVRDPRLPPC TLRQALTFFL DITSPPSPQL LRLLSTLAEE PSEQQELETL SQDPRRYEEW
KWFRCPTLLE ALEQFPSVAL PAPLLLTQLP LLQPRYYSVS SAPSAHPGEV HLTVAVLAYR
TQDGLGPLHY GVCSTWLSQL KTGDPVPCFI RGAPSFRLPP DPSLPCILVG PGTGIAPFRG
FWQERLHDIE SKGLQPAPMT LVFGCRCSQL DHLYREEVQD AQQRGVFGRV LTAFSREPDS
PKTYVQDVLR TELAAEVHRV LCLERGHMFV CGDVTMATSV LQTVQRILAT EGDMELDEAG
DVIGVLRDQQ RYHEDIFGLT LRTQEVTSRI RTQSFSLQER HMRGAVPWAF DPPGPDTPGP
//
