NOS1_RABIT
ID NOS1_RABIT Reviewed; 1435 AA.
AC O19132;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Nitric oxide synthase, brain;
DE EC=1.14.13.39;
DE AltName: Full=Constitutive NOS;
DE AltName: Full=NC-NOS;
DE AltName: Full=NOS type I;
DE AltName: Full=Neuronal NOS;
DE Short=N-NOS;
DE Short=nNOS;
DE AltName: Full=Peptidyl-cysteine S-nitrosylase NOS1;
DE AltName: Full=bNOS;
GN Name=NOS1;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RA Jeong Y., Yim J.;
RT "Molecular cloning of a cDNA encoding a constitutive nitric oxide synthase
RT from rabbit brain.";
RL Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Produces nitric oxide (NO) which is a messenger molecule with
CC diverse functions throughout the body. In the brain and peripheral
CC nervous system, NO displays many properties of a neurotransmitter.
CC Probably has nitrosylase activity and mediates cysteine S-nitrosylation
CC of cytoplasmic target proteins such SRR (By similarity). {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 -!- COFACTOR:
CC Name=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin;
CC Xref=ChEBI:CHEBI:59560; Evidence={ECO:0000250};
CC Note=Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the
CC enzyme. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Stimulated by calcium/calmodulin. Inhibited by n-
CC Nos-inhibiting protein (PIN) which may prevent the dimerization of the
CC protein. Inhibited by NOSIP (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer. Interacts with DLG4; the interaction possibly being
CC prevented by the association between NOS1 and CAPON. Forms a ternary
CC complex with CAPON and RASD1. Forms a ternary complex with CAPON and
CC SYN1. Interacts with ZDHHC23. Interacts with NOSIP; which may impair
CC its synaptic location (By similarity). Interacts with HTR4 (By
CC similarity). Interacts with SLC6A4. Interacts with VAC14 (By
CC similarity). Interacts (via N-terminal domain) with DLG4 (via N-
CC terminal tandem pair of PDZ domains). Interacts with SLC6A4. Forms a
CC complex with ASL, ASS1 and SLC7A1; the complex regulates cell-
CC autonomous L-arginine synthesis and citrulline recycling while
CC channeling extracellular L-arginine to nitric oxide synthesis pathway
CC (By similarity). {ECO:0000250|UniProtKB:P29476,
CC ECO:0000250|UniProtKB:Q9Z0J4}.
CC -!- SUBCELLULAR LOCATION: Cell membrane, sarcolemma {ECO:0000250};
CC Peripheral membrane protein {ECO:0000250}. Cell projection, dendritic
CC spine {ECO:0000250}. Note=In skeletal muscle, it is localized beneath
CC the sarcolemma of fast-twitch muscle fiber by associating with the
CC dystrophin glycoprotein complex. In neurons, enriched in dendritic
CC spines (By similarity). {ECO:0000250}.
CC -!- DOMAIN: The PDZ domain in the N-terminal part of the neuronal isoform
CC participates in protein-protein interaction, and is responsible for
CC targeting nNos to synaptic membranes in muscles. Mediates interaction
CC with VAC14 (By similarity). {ECO:0000250}.
CC -!- PTM: Ubiquitinated; mediated by STUB1/CHIP in the presence of Hsp70 and
CC Hsp40 (in vitro). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the NOS family. {ECO:0000305}.
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DR EMBL; U91584; AAB68663.1; -; mRNA.
DR RefSeq; NP_001075854.1; NM_001082385.1.
DR AlphaFoldDB; O19132; -.
DR BMRB; O19132; -.
DR SMR; O19132; -.
DR STRING; 9986.ENSOCUP00000020745; -.
DR PRIDE; O19132; -.
DR GeneID; 100009243; -.
DR KEGG; ocu:100009243; -.
DR CTD; 4842; -.
DR eggNOG; KOG1158; Eukaryota.
DR InParanoid; O19132; -.
DR OrthoDB; 90349at2759; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0043197; C:dendritic spine; IEA:UniProtKB-SubCell.
DR GO; GO:0042383; C:sarcolemma; IEA:UniProtKB-SubCell.
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; 2.30.42.10; -; 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; IPR001478; PDZ.
DR InterPro; IPR036034; PDZ_sf.
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 Pfam; PF00595; PDZ; 1.
DR PIRSF; PIRSF000333; NOS; 1.
DR PRINTS; PR00369; FLAVODOXIN.
DR PRINTS; PR00371; FPNCR.
DR SMART; SM00228; PDZ; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
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.
DR PROSITE; PS50106; PDZ; 1.
PE 2: Evidence at transcript level;
KW Calmodulin-binding; Cell membrane; Cell projection; FAD; Flavoprotein; FMN;
KW Heme; Iron; Membrane; Metal-binding; NADP; Oxidoreductase; Phosphoprotein;
KW Reference proteome; Synapse; Ubl conjugation.
FT CHAIN 1..1435
FT /note="Nitric oxide synthase, brain"
FT /id="PRO_0000170923"
FT DOMAIN 17..99
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 761..941
FT /note="Flavodoxin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00088"
FT DOMAIN 996..1243
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT REGION 1..206
FT /note="Interaction with NOSIP"
FT /evidence="ECO:0000250"
FT REGION 110..201
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 164..246
FT /note="PIN (nNOS-inhibiting protein) binding"
FT /evidence="ECO:0000250"
FT REGION 277..304
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 731..751
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 161..191
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 282..300
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 340
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000250|UniProtKB:P29475"
FT BINDING 421
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:P29475"
FT BINDING 484
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29475"
FT BINDING 593
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29475"
FT BINDING 594
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29475"
FT BINDING 598
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29475"
FT BINDING 683
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000250|UniProtKB:P29475"
FT BINDING 684
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000250|UniProtKB:P29475"
FT BINDING 697
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000250|UniProtKB:P29475"
FT BINDING 712
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /evidence="ECO:0000250|UniProtKB:P29475"
FT BINDING 887..918
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00088"
FT BINDING 1033..1044
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 1176..1186
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 1251..1269
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 1349..1364
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT MOD_RES 853
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29476"
FT MOD_RES 863
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0J4"
FT MOD_RES 864
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0J4"
SQ SEQUENCE 1435 AA; 160865 MW; 3ED87ECDD83A7A5A CRC64;
MEEHVFGVQQ IQPNVISVRL FKRKVGGLGF LVKERVSKPP VIISDLIRGG AAEQSGLIQA
GDIILAVNGR PLVDLSYDSA LEVLRGVASE THVVLILRGP EGFTTNLETT FTGDGTPKTI
RVTQPLGAPT KAVDLSHQPP SAGKEQPRPV DGAAGPGSWP QPTQGHGQEA GSPSRANGLA
PRTSSQDPAK KSGWAGLQGS GDKNELLKEI EPVLTLLAGG SKAVDGGGPA KAETRDTGVQ
VDRDFDAKSH KPLPLGVEND RVFSDLWGKG SAPVVLNNPY SEKEQPPASG KQSPTKNGSP
SKCPRFLKVK NWETDVVLTD TLHLKSTLET GCTEHICMGS IMFPSQHTRR PEDIRTKEQL
FPLAKEFIDQ YYSSIKRFGS KAHMERLEEV NKEIESTSTY QLKDTELIYG AKHAWRNASR
CVGRIQWSKL QVFDARDCTT AHGMFNYICN HIKYATNKGN LRSAITIFPQ RTDGKHDFRV
WNSQLIRYAG YKQPDGSTLG DPANVQFTEI CIQQGWKPPR SRFDVLPLLL QANGNDPELF
QIPPELVLEV PIRHPKFEWF KDLGLKWYGL PAVSNMLLEI GGLEFSACPF SGWYMGTEIG
VRDYCDNSRY NILEEVAKKM NLDMRKTSSL WKDQALVEIN IAVLYSFQSD KVTIVDHHSA
TESFIKHMEN EYRCRGGCPA DWVWIVPPMS GSITPVFHQE MLNYRLTPCF EYQPDPWNTH
VWKGTNGTPT KRRAIGFKKL AEAVKFSAKL MGQAMAKRVK ATILYATETG KSQAYAKTLC
EIFKHAFDAK VMSMEEYDIV HLEHETLVLV VTSTFGNGDP PENGEKFRCA LMEMRHPNSL
QEERKSYKVR FNSVSSYSDS RKSSGDGPDV RDHFESAGPL ANVRFSVFGL GSRAYPHFCA
FGHAVDTLLE ELGGERILKM REGDELCGQE EAFRTWAKKV FKAACDVFCV GDDVNIEKAN
NSLISNDRSW KRNKFRLTYV AEAPGLTQGL SSVHKKRVSA ARLLSRQNLQ SPKSSRSTIF
VRLHTNGSQE LQYQPGDHLG VFPGNHEDLV NALIERLEDA PPANQMVKVE LLEERNTALG
VISNWKDEPR LPPCTVFQAF KYYLDITTPP TPLQLQQFAS LASNEKEKQR LLVLSKGLQE
YEEWKWGKNP TIVEVLEEFP SIQMPATLLL TQLSLLQPRY YSISSSPDMY PDEVHLTVAI
VSYHTRDGEG PIHHGVCSSW LNRIPADEVV PCFVRGAPSF RLPRNPQVPC ILVGPGTAFA
PFRSFWQQRQ FDIQHKGMSP CPMVLVFGCR QSKIDHIYRE EALQAKNKGV FRELYTAYSR
EPDKPKKYVQ DILQEQLAEQ VYRALKEQGG HIYVCGDVTM AADVLKAVQR IMAQQGKLSA
EDAGVFISRL RDDNRYHEDI FGVTLRTYEV TNRLRSESIA FIEESKKDTD EVFSS
