ID NOS1_HUMAN Reviewed; 1434 AA. AC P29475; E9PH30; O75713; DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 2. DT 27-MAR-2024, entry version 242. DE RecName: Full=Nitric oxide synthase 1 {ECO:0000312|HGNC:HGNC:7872}; DE EC=1.14.13.39 {ECO:0000269|PubMed:35772285}; 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=Nitric oxide synthase, brain {ECO:0000305}; DE Short=bNOS {ECO:0000305}; DE AltName: Full=Peptidyl-cysteine S-nitrosylase NOS1; GN Name=NOS1 {ECO:0000312|HGNC:HGNC:7872}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). RX PubMed=7528745; DOI=10.1016/s0021-9258(20)30099-5; RA Hall A.V., Antoniou H., Wang Y., Cheung A.H., Arbus A.M., Olson S.L., RA Lu W.C., Kau C.-L., Marsden P.A.; RT "Structural organization of the human neuronal nitric oxide synthase gene RT (NOS1)."; RL J. Biol. Chem. 269:33082-33090(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Cerebellum; RX PubMed=7515942; DOI=10.1046/j.1471-4159.1994.63010140.x; RA Fujisawa H., Ogura T., Kurashima Y., Yokoyama T., Yamashita J., Esumi H.; RT "Expression of two types of nitric oxide synthase mRNA in human RT neuroblastoma cell lines."; RL J. Neurochem. 63:140-145(1994). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Brain; RX PubMed=7678401; DOI=10.1016/0014-5793(93)81210-q; RA Nakane M., Schmidt H.H.H.W., Pollock J.S., Foerstermann U., Murad F.; RT "Cloned human brain nitric oxide synthase is highly expressed in skeletal RT muscle."; RL FEBS Lett. 316:175-180(1993). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Retina; RX PubMed=8879752; DOI=10.1007/bf02150230; RA Park C.-S., Gianotti C., Park R., Krishna G.; RT "Neuronal isoform of nitric oxide synthase is expressed at low levels in RT human retina."; RL Cell. Mol. Neurobiol. 16:499-515(1996). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 3 AND 4). RC TISSUE=Testis; RX PubMed=9111048; RA Wang Y., Goligorsky M.S., Lin M., Wilcox J.N., Marsden P.A.; RT "A novel, testis-specific mRNA transcript encoding an NH2-terminal RT truncated nitric-oxide synthase."; RL J. Biol. Chem. 272:11392-11401(1997). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-228; ALA-394; ASP-725; RP ASP-864 AND ARG-1064. RG NIEHS SNPs program; RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 835-901 (ISOFORM 5), AND ALTERNATIVE RP SPLICING. RC TISSUE=Skeletal muscle; RX PubMed=9791007; DOI=10.1006/bbrc.1998.9578; RA Larsson B., Phillips S.C.; RT "Isolation and characterization of a novel, human neuronal nitric oxide RT synthase cDNA."; RL Biochem. Biophys. Res. Commun. 251:898-902(1998). RN [9] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=35772285; DOI=10.1016/j.bmc.2022.116878; RA Vasu D., Li H., Hardy C.D., Poulos T.L., Silverman R.B.; RT "2-Aminopyridines with a shortened amino sidechain as potent, selective, RT and highly permeable human neuronal nitric oxide synthase inhibitors."; RL Bioorg. Med. Chem. 69:116878-116878(2022). RN [10] {ECO:0007744|PDB:4D1N} RP X-RAY CRYSTALLOGRAPHY (2.03 ANGSTROMS) OF 302-721 IN COMPLEX WITH RP 5,6,7,8-TETRAHYDROBIOPTERIN; L-ARGININE AND HEME, AND COFACTOR. RX PubMed=25286850; DOI=10.1107/s1399004714017064; RA Li H., Jamal J., Plaza C., Pineda S.H., Chreifi G., Jing Q., Cinelli M.A., RA Silverman R.B., Poulos T.L.; RT "Structures of human constitutive nitric oxide synthases."; RL Acta Crystallogr. D 70:2667-2674(2014). 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. {ECO:0000269|PubMed:35772285}. 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:0000269|PubMed:35772285}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19898; CC Evidence={ECO:0000305|PubMed:35772285}; CC -!- COFACTOR: CC Name=heme b; Xref=ChEBI:CHEBI:60344; CC Evidence={ECO:0000269|PubMed:25286850}; CC -!- COFACTOR: CC Name=FAD; Xref=ChEBI:CHEBI:57692; CC Evidence={ECO:0000250|UniProtKB:P29476}; CC Note=Binds 1 FAD. {ECO:0000250|UniProtKB:P29476}; CC -!- COFACTOR: CC Name=FMN; Xref=ChEBI:CHEBI:58210; CC Evidence={ECO:0000250|UniProtKB:P29476}; CC Note=Binds 1 FMN. {ECO:0000250|UniProtKB:P29476}; CC -!- COFACTOR: CC Name=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin; CC Xref=ChEBI:CHEBI:59560; Evidence={ECO:0000269|PubMed:25286850}; CC Note=Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the CC enzyme. {ECO:0000269|PubMed:25286850}; CC -!- ACTIVITY REGULATION: Stimulated by calcium/calmodulin. Inhibited by CC DYNLL1 that prevents the dimerization of the protein. Inhibited by CC NOSIP. {ECO:0000250|UniProtKB:P29476}. 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). Interacts with DMD; localizes NOS1 to sarcolemma in CC muscle cells (By similarity). Interacts with DYNLL1; inhibits the CC nitric oxide synthase activity (By similarity). CC {ECO:0000250|UniProtKB:P29476, ECO:0000250|UniProtKB:Q9Z0J4}. CC -!- INTERACTION: CC P29475; Q08AM6: VAC14; NbExp=5; IntAct=EBI-7164065, EBI-2107455; CC -!- SUBCELLULAR LOCATION: Cell membrane, sarcolemma CC {ECO:0000250|UniProtKB:Q9Z0J4}; Peripheral membrane protein CC {ECO:0000255}. Cell projection, dendritic spine CC {ECO:0000250|UniProtKB:P29476}. Note=In skeletal muscle, it is CC localized beneath the sarcolemma of fast-twitch muscle fiber by CC associating with the dystrophin glycoprotein complex (By similarity). CC In neurons, enriched in dendritic spines (By similarity). CC {ECO:0000250|UniProtKB:P29476, ECO:0000250|UniProtKB:Q9Z0J4}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Comment=Isoform 3 is produced by different alternative splicing CC events implicating either the untranslated exons TEX1 (TN-NOS) or CC TEX1B (TN-NOSB) leading to a N-terminally truncated protein which CC possesses enzymatic activity comparable to that of isoform 1. The C- CC terminally truncated isoform 4 is produced by insertion of the TEX2 CC exon between exons 3 and 4 of isoform 1, leading to a frameshift and CC a premature stop codon. {ECO:0000269|PubMed:9791007}; CC Name=1; Synonyms=N-NOS-1; CC IsoId=P29475-1; Sequence=Displayed; CC Name=2; Synonyms=N-NOS-2; CC IsoId=P29475-2; Sequence=VSP_003574; CC Name=3; Synonyms=TN-NOS, TN-NOSB; CC IsoId=P29475-3; Sequence=VSP_003571; CC Name=4; Synonyms=TEX2-insertion; CC IsoId=P29475-4; Sequence=VSP_003572, VSP_003573; CC Name=5; Synonyms=nNOSmu; CC IsoId=P29475-5; Sequence=VSP_044916; CC -!- TISSUE SPECIFICITY: Isoform 1 is ubiquitously expressed: detected in CC skeletal muscle and brain, also in testis, lung and kidney, and at low CC levels in heart, adrenal gland and retina. Not detected in the CC platelets. Isoform 3 is expressed only in testis. Isoform 4 is detected CC in testis, skeletal muscle, lung, and kidney, at low levels in the CC brain, but not in the heart and adrenal gland. CC -!- DOMAIN: The PDZ domain participates in protein-protein interaction, and CC is responsible for targeting nNos to synaptic membranes. Mediates CC interaction with VAC14. {ECO:0000250|UniProtKB:P29476}. CC -!- PTM: Ubiquitinated; mediated by STUB1/CHIP in the presence of Hsp70 and CC Hsp40 (in vitro). {ECO:0000250|UniProtKB:P29476}. CC -!- SIMILARITY: Belongs to the NOS family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/nos1/"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Nitric oxide synthase entry; CC URL="https://en.wikipedia.org/wiki/Nitric_oxide_synthase"; 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; U17327; AAA62405.1; -; mRNA. DR EMBL; U17326; AAB60654.1; ALT_SEQ; Genomic_DNA. DR EMBL; U17299; AAB60654.1; JOINED; Genomic_DNA. DR EMBL; U17300; AAB60654.1; JOINED; Genomic_DNA. DR EMBL; U17301; AAB60654.1; JOINED; Genomic_DNA. DR EMBL; U17302; AAB60654.1; JOINED; Genomic_DNA. DR EMBL; U17303; AAB60654.1; JOINED; Genomic_DNA. DR EMBL; U17304; AAB60654.1; JOINED; Genomic_DNA. DR EMBL; U17305; AAB60654.1; JOINED; Genomic_DNA. DR EMBL; U17307; AAB60654.1; JOINED; Genomic_DNA. DR EMBL; U17308; AAB60654.1; JOINED; Genomic_DNA. DR EMBL; U17309; AAB60654.1; JOINED; Genomic_DNA. DR EMBL; U17310; AAB60654.1; JOINED; Genomic_DNA. DR EMBL; U17311; AAB60654.1; JOINED; Genomic_DNA. DR EMBL; U17312; AAB60654.1; JOINED; Genomic_DNA. DR EMBL; U17313; AAB60654.1; JOINED; Genomic_DNA. DR EMBL; U17314; AAB60654.1; JOINED; Genomic_DNA. DR EMBL; U17315; AAB60654.1; JOINED; Genomic_DNA. DR EMBL; U17316; AAB60654.1; JOINED; Genomic_DNA. DR EMBL; U17317; AAB60654.1; JOINED; Genomic_DNA. DR EMBL; U17318; AAB60654.1; JOINED; Genomic_DNA. DR EMBL; U17319; AAB60654.1; JOINED; Genomic_DNA. DR EMBL; U17320; AAB60654.1; JOINED; Genomic_DNA. DR EMBL; U17321; AAB60654.1; JOINED; Genomic_DNA. DR EMBL; U17322; AAB60654.1; JOINED; Genomic_DNA. DR EMBL; U17323; AAB60654.1; JOINED; Genomic_DNA. DR EMBL; U17324; AAB60654.1; JOINED; Genomic_DNA. DR EMBL; U17325; AAB60654.1; JOINED; Genomic_DNA. DR EMBL; D16408; BAA03895.1; -; mRNA. DR EMBL; L02881; AAA36376.1; -; mRNA. DR EMBL; U31466; AAB49040.1; -; mRNA. DR EMBL; U66362; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AY445095; AAR07069.1; -; Genomic_DNA. DR EMBL; AC026364; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC068799; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC073864; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AJ004918; CAA06218.1; -; mRNA. DR CCDS; CCDS41842.1; -. [P29475-1] DR CCDS; CCDS55890.1; -. [P29475-5] DR PIR; G01946; G01946. DR RefSeq; NP_000611.1; NM_000620.4. [P29475-1] DR RefSeq; NP_001191142.1; NM_001204213.1. [P29475-3] DR RefSeq; NP_001191143.1; NM_001204214.1. [P29475-3] DR RefSeq; NP_001191147.1; NM_001204218.1. [P29475-5] DR RefSeq; XP_011536700.1; XM_011538398.2. DR RefSeq; XP_016874834.1; XM_017019345.1. DR RefSeq; XP_016874835.1; XM_017019346.1. DR RefSeq; XP_016874836.1; XM_017019347.1. DR PDB; 4D1N; X-ray; 2.03 A; A/B/C/D=302-721. DR PDB; 4UCH; X-ray; 2.20 A; A/B=302-723. DR PDB; 4UH5; X-ray; 1.98 A; A/B=302-722. DR PDB; 4UH6; X-ray; 1.98 A; A/B=302-722. DR PDB; 4V3U; X-ray; 2.30 A; A/B/C/D=302-721. DR PDB; 5ADF; X-ray; 1.97 A; A/B=302-722. DR PDB; 5ADG; X-ray; 1.98 A; A/B=302-722. DR PDB; 5ADI; X-ray; 2.20 A; A/B=302-722. DR PDB; 5FVU; X-ray; 2.22 A; A/B=302-722. DR PDB; 5FVV; X-ray; 2.05 A; A/B=302-722. DR PDB; 5FVW; X-ray; 2.20 A; A/B=302-722. DR PDB; 5FVX; X-ray; 2.30 A; A/B=302-722. DR PDB; 5UO1; X-ray; 1.90 A; A/B=302-722. DR PDB; 5UO2; X-ray; 1.95 A; A/B=302-722. DR PDB; 5UO3; X-ray; 2.20 A; A/B=302-722. DR PDB; 5UO4; X-ray; 2.00 A; A/B=302-722. DR PDB; 5UO5; X-ray; 2.00 A; A/B=302-722. DR PDB; 5UO6; X-ray; 1.96 A; A/B=302-722. DR PDB; 5UO7; X-ray; 2.06 A; A/B=302-722. DR PDB; 5VUV; X-ray; 1.98 A; A/B=302-722. DR PDB; 5VUW; X-ray; 2.03 A; A/B=302-722. DR PDB; 5VUX; X-ray; 2.30 A; A/B=302-722. DR PDB; 5VUY; X-ray; 2.15 A; A/B=302-722. DR PDB; 5VUZ; X-ray; 1.97 A; A/B=302-722. DR PDB; 5VV0; X-ray; 1.80 A; A/B=302-722. DR PDB; 5VV1; X-ray; 1.95 A; A/B=302-722. DR PDB; 5VV2; X-ray; 2.00 A; A/B=302-722. DR PDB; 5VV3; X-ray; 2.18 A; A/B=302-722. DR PDB; 5VV4; X-ray; 2.10 A; A/B=302-722. DR PDB; 5VV5; X-ray; 2.15 A; A/B=302-722. DR PDB; 6AUY; X-ray; 1.92 A; A/B=302-722. DR PDB; 6AUZ; X-ray; 2.00 A; A/B=302-722. DR PDB; 6AV0; X-ray; 2.00 A; A/B=302-722. DR PDB; 6AV1; X-ray; 2.45 A; A/B=302-722. DR PDB; 6AV2; X-ray; 2.10 A; A/B=302-722. DR PDB; 6AV3; X-ray; 1.95 A; A/B=302-722. DR PDB; 6AV4; X-ray; 1.87 A; A/B=302-722. DR PDB; 6AV5; X-ray; 1.90 A; A/B=302-722. DR PDB; 6CIC; X-ray; 1.75 A; A/B=302-722. DR PDB; 6CID; X-ray; 1.75 A; A/B=302-722. DR PDB; 6NG1; X-ray; 2.15 A; A/B=302-722. DR PDB; 6NG2; X-ray; 1.93 A; A/B=302-722. DR PDB; 6NG4; X-ray; 1.78 A; A/B=302-722. DR PDB; 6NG5; X-ray; 1.96 A; A/B=302-722. DR PDB; 6NG6; X-ray; 2.04 A; A/B=302-722. DR PDB; 6NG7; X-ray; 2.00 A; A/B=302-722. DR PDB; 6NG8; X-ray; 1.90 A; A/B=302-722. DR PDB; 6NGA; X-ray; 1.98 A; A/B=302-722. DR PDB; 6NGB; X-ray; 1.90 A; A/B=302-722. DR PDB; 6NGC; X-ray; 2.00 A; A/B=302-722. DR PDB; 6NGD; X-ray; 1.80 A; A/B=302-722. DR PDB; 6NGE; X-ray; 2.10 A; A/B=302-722. DR PDB; 6NGF; X-ray; 1.99 A; A/B=302-722. DR PDB; 6NGH; X-ray; 2.00 A; A/B=302-722. DR PDB; 6NGI; X-ray; 1.80 A; A/B=302-722. DR PDB; 6NHB; X-ray; 2.03 A; A/B=302-722. DR PDB; 6NHC; X-ray; 2.16 A; A/B=302-722. DR PDB; 6PNA; X-ray; 1.95 A; A/B=302-722. DR PDB; 6PNB; X-ray; 2.05 A; A/B=302-722. DR PDB; 6PNC; X-ray; 2.15 A; A/B=302-722. DR PDB; 6PND; X-ray; 2.40 A; A/B=302-722. DR PDB; 6PNE; X-ray; 2.10 A; A/B=302-722. DR PDB; 6PNF; X-ray; 2.10 A; A/B=302-722. DR PDB; 6PNG; X-ray; 1.77 A; A/B=302-722. DR PDB; 6PNH; X-ray; 1.85 A; A/B=302-722. DR PDB; 6PO5; X-ray; 1.82 A; A/B=302-722. DR PDB; 6PO7; X-ray; 1.95 A; A/B=302-722. DR PDB; 6PO8; X-ray; 1.90 A; A/B=302-722. DR PDB; 6PO9; X-ray; 1.81 A; A/B=302-722. DR PDB; 6POA; X-ray; 1.81 A; A/B=302-722. DR PDB; 6POB; X-ray; 1.95 A; A/B=302-722. DR PDB; 6POC; X-ray; 2.00 A; A/B=302-722. DR PDB; 6POT; X-ray; 2.30 A; A/B=302-722. DR PDB; 7TS1; X-ray; 2.06 A; A/B/C/D=302-722. DR PDB; 7TS2; X-ray; 1.98 A; A/B/C/D=302-722. DR PDB; 7TS3; X-ray; 2.10 A; A/B/C/D=302-722. DR PDB; 7TS4; X-ray; 1.85 A; A/B/C/D=302-722. DR PDB; 7TS5; X-ray; 1.84 A; A/B/C/D=302-722. DR PDB; 7TS6; X-ray; 1.80 A; A/B/C/D=302-722. DR PDB; 7TS7; X-ray; 1.90 A; A/B/C/D=302-722. DR PDB; 7TS8; X-ray; 2.30 A; A/B/C/D=302-722. DR PDB; 7UAM; X-ray; 1.84 A; A/B/C/D=302-722. DR PDB; 7US7; X-ray; 1.93 A; A/B/C/D=302-722. DR PDB; 7US8; X-ray; 1.82 A; A/B/C/D=302-722. DR PDB; 8BI8; X-ray; 1.59 A; A/B=105-125. DR PDB; 8BI9; X-ray; 1.44 A; A/B/C/D=105-125. DR PDB; 8FGF; X-ray; 1.83 A; A/B=302-722. DR PDB; 8FGG; X-ray; 1.86 A; A/B=302-722. DR PDB; 8FGH; X-ray; 2.17 A; A/B/C/D=302-722. DR PDB; 8FGI; X-ray; 2.15 A; A/B=302-722. DR PDB; 8FGJ; X-ray; 2.15 A; A/B/C/D=302-722. DR PDB; 8FGK; X-ray; 2.25 A; A/B/C/D=302-722. DR PDB; 8FGL; X-ray; 2.10 A; A/B/C/D=302-722. DR PDB; 8FGM; X-ray; 2.10 A; A/B/C/D=302-722. DR PDBsum; 4D1N; -. DR PDBsum; 4UCH; -. DR PDBsum; 4UH5; -. DR PDBsum; 4UH6; -. DR PDBsum; 4V3U; -. DR PDBsum; 5ADF; -. DR PDBsum; 5ADG; -. DR PDBsum; 5ADI; -. DR PDBsum; 5FVU; -. DR PDBsum; 5FVV; -. DR PDBsum; 5FVW; -. DR PDBsum; 5FVX; -. DR PDBsum; 5UO1; -. DR PDBsum; 5UO2; -. DR PDBsum; 5UO3; -. DR PDBsum; 5UO4; -. DR PDBsum; 5UO5; -. DR PDBsum; 5UO6; -. DR PDBsum; 5UO7; -. DR PDBsum; 5VUV; -. DR PDBsum; 5VUW; -. DR PDBsum; 5VUX; -. DR PDBsum; 5VUY; -. DR PDBsum; 5VUZ; -. DR PDBsum; 5VV0; -. DR PDBsum; 5VV1; -. DR PDBsum; 5VV2; -. DR PDBsum; 5VV3; -. DR PDBsum; 5VV4; -. DR PDBsum; 5VV5; -. DR PDBsum; 6AUY; -. DR PDBsum; 6AUZ; -. DR PDBsum; 6AV0; -. DR PDBsum; 6AV1; -. DR PDBsum; 6AV2; -. DR PDBsum; 6AV3; -. DR PDBsum; 6AV4; -. DR PDBsum; 6AV5; -. DR PDBsum; 6CIC; -. DR PDBsum; 6CID; -. DR PDBsum; 6NG1; -. DR PDBsum; 6NG2; -. DR PDBsum; 6NG4; -. DR PDBsum; 6NG5; -. DR PDBsum; 6NG6; -. DR PDBsum; 6NG7; -. DR PDBsum; 6NG8; -. DR PDBsum; 6NGA; -. DR PDBsum; 6NGB; -. DR PDBsum; 6NGC; -. DR PDBsum; 6NGD; -. DR PDBsum; 6NGE; -. DR PDBsum; 6NGF; -. DR PDBsum; 6NGH; -. DR PDBsum; 6NGI; -. DR PDBsum; 6NHB; -. DR PDBsum; 6NHC; -. DR PDBsum; 6PNA; -. DR PDBsum; 6PNB; -. DR PDBsum; 6PNC; -. DR PDBsum; 6PND; -. DR PDBsum; 6PNE; -. DR PDBsum; 6PNF; -. DR PDBsum; 6PNG; -. DR PDBsum; 6PNH; -. DR PDBsum; 6PO5; -. DR PDBsum; 6PO7; -. DR PDBsum; 6PO8; -. DR PDBsum; 6PO9; -. DR PDBsum; 6POA; -. DR PDBsum; 6POB; -. DR PDBsum; 6POC; -. DR PDBsum; 6POT; -. DR PDBsum; 7TS1; -. DR PDBsum; 7TS2; -. DR PDBsum; 7TS3; -. DR PDBsum; 7TS4; -. DR PDBsum; 7TS5; -. DR PDBsum; 7TS6; -. DR PDBsum; 7TS7; -. DR PDBsum; 7TS8; -. DR PDBsum; 7UAM; -. DR PDBsum; 7US7; -. DR PDBsum; 7US8; -. DR PDBsum; 8BI8; -. DR PDBsum; 8BI9; -. DR PDBsum; 8FGF; -. DR PDBsum; 8FGG; -. DR PDBsum; 8FGH; -. DR PDBsum; 8FGI; -. DR PDBsum; 8FGJ; -. DR PDBsum; 8FGK; -. DR PDBsum; 8FGL; -. DR PDBsum; 8FGM; -. DR AlphaFoldDB; P29475; -. DR BMRB; P29475; -. DR SMR; P29475; -. DR BioGRID; 110905; 36. DR CORUM; P29475; -. DR DIP; DIP-40999N; -. DR IntAct; P29475; 6. DR MINT; P29475; -. DR STRING; 9606.ENSP00000477999; -. DR BindingDB; P29475; -. DR ChEMBL; CHEMBL3568; -. DR DrugBank; DB02143; 1-hydroxy-2-isopropylguanidine. DR DrugBank; DB02727; 2-butyl-1-hydroxyguanidine. DR DrugBank; DB01997; 3-Bromo-7-Nitroindazole. DR DrugBank; DB03892; 5-N-Allyl-arginine. DR DrugBank; DB02207; 7-Nitroindazole. DR DrugBank; DB03710; [(1S)-4-(1-Aminobutylideneamino)-1-carboxybutyl]azanium. DR DrugBank; DB00155; Citrulline. DR DrugBank; DB00843; Donepezil. DR DrugBank; DB00997; Doxorubicin. DR DrugBank; DB03147; Flavin adenine dinucleotide. DR DrugBank; DB03247; Flavin mononucleotide. DR DrugBank; DB01942; Formic acid. DR DrugBank; DB01221; Ketamine. DR DrugBank; DB02077; L-N(omega)-nitroarginine-(4R)-amino-L-proline amide. DR DrugBank; DB01821; L-N(omega)-Nitroarginine-2,4-L-diaminobutyric amide. DR DrugBank; DB09241; Methylene blue. DR DrugBank; DB03144; N(5)-[(hydroxyamino)(imino)methyl]-L-ornithine. DR DrugBank; DB03449; N-(4-{2-[(3-chlorobenzyl)amino]ethyl}phenyl)thiophene-2-carboximidamide. DR DrugBank; DB02044; N-[3-(aminomethyl)benzyl]acetamidine. DR DrugBank; DB02644; N-omega-propyl-L-arginine. DR DrugBank; DB08019; N-{(3R,4S)-4-[(6-amino-4-methylpyridin-2-yl)methyl]pyrrolidin-3-yl}-N'-(3-chlorobenzyl)ethane-1,2-diamine. DR DrugBank; DB08018; N-{(3S,4S)-4-[(6-AMINO-4-METHYLPYRIDIN-2-YL)METHYL]PYRROLIDIN-3-YL}-N'-(4-CHLOROBENZYL)ETHANE-1,2-DIAMINE. DR DrugBank; DB02027; N-{(4S)-4-Amino-5-[(2-aminoethyl)amino]pentyl}-N'-nitroguanidine. DR DrugBank; DB03461; Nicotinamide adenine dinucleotide phosphate. DR DrugBank; DB04223; Nitroarginine. DR DrugBank; DB06096; NXN-188. DR DrugBank; DB02991; S-Ethyl-N-[4-(Trifluoromethyl)Phenyl]Isothiourea. DR DrugBank; DB03707; S-Ethyl-N-Phenyl-Isothiourea. DR DrugCentral; P29475; -. DR GuidetoPHARMACOLOGY; 1251; -. DR TCDB; 8.A.24.2.4; the ezrin/radixin/moesin-binding phosphoprotein 50 (ebp50) family. DR GlyGen; P29475; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P29475; -. DR PhosphoSitePlus; P29475; -. DR BioMuta; NOS1; -. DR DMDM; 1709333; -. DR jPOST; P29475; -. DR MassIVE; P29475; -. DR MaxQB; P29475; -. DR PaxDb; 9606-ENSP00000477999; -. DR PeptideAtlas; P29475; -. DR ProteomicsDB; 20446; -. DR ProteomicsDB; 54578; -. [P29475-1] DR ProteomicsDB; 54579; -. [P29475-2] DR ProteomicsDB; 54580; -. [P29475-3] DR ProteomicsDB; 54581; -. [P29475-4] DR Pumba; P29475; -. DR ABCD; P29475; 2 sequenced antibodies. DR Antibodypedia; 3691; 1055 antibodies from 47 providers. DR DNASU; 4842; -. DR Ensembl; ENST00000317775.11; ENSP00000320758.6; ENSG00000089250.20. [P29475-1] DR Ensembl; ENST00000338101.8; ENSP00000337459.4; ENSG00000089250.20. [P29475-5] DR Ensembl; ENST00000618760.4; ENSP00000477999.1; ENSG00000089250.20. [P29475-5] DR GeneID; 4842; -. DR KEGG; hsa:4842; -. DR MANE-Select; ENST00000317775.11; ENSP00000320758.6; NM_000620.5; NP_000611.1. DR UCSC; uc001twm.3; human. [P29475-1] DR AGR; HGNC:7872; -. DR CTD; 4842; -. DR DisGeNET; 4842; -. DR GeneCards; NOS1; -. DR HGNC; HGNC:7872; NOS1. DR HPA; ENSG00000089250; Group enriched (skeletal muscle, tongue). DR MalaCards; NOS1; -. DR MIM; 163731; gene. DR neXtProt; NX_P29475; -. DR OpenTargets; ENSG00000089250; -. DR Orphanet; 930; Idiopathic achalasia. DR PharmGKB; PA252; -. DR VEuPathDB; HostDB:ENSG00000089250; -. DR eggNOG; KOG1158; Eukaryota. DR GeneTree; ENSGT00940000159357; -. DR HOGENOM; CLU_001570_16_0_1; -. DR InParanoid; P29475; -. DR OMA; KCPEPLR; -. DR OrthoDB; 276396at2759; -. DR PhylomeDB; P29475; -. DR TreeFam; TF324410; -. DR BioCyc; MetaCyc:HS01647-MONOMER; -. DR BRENDA; 1.14.13.39; 2681. DR PathwayCommons; P29475; -. DR Reactome; R-HSA-1222556; ROS and RNS production in phagocytes. DR Reactome; R-HSA-392154; Nitric oxide stimulates guanylate cyclase. DR Reactome; R-HSA-5578775; Ion homeostasis. DR SignaLink; P29475; -. DR SIGNOR; P29475; -. DR BioGRID-ORCS; 4842; 17 hits in 1156 CRISPR screens. DR ChiTaRS; NOS1; human. DR GeneWiki; NOS1; -. DR GenomeRNAi; 4842; -. DR Pharos; P29475; Tchem. DR PRO; PR:P29475; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; P29475; Protein. DR Bgee; ENSG00000089250; Expressed in body of tongue and 124 other cell types or tissues. DR ExpressionAtlas; P29475; baseline and differential. DR GO; GO:0071944; C:cell periphery; ISS:ARUK-UCL. DR GO; GO:0005737; C:cytoplasm; ISS:ARUK-UCL. DR GO; GO:0005856; C:cytoskeleton; ISS:BHF-UCL. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0043197; C:dendritic spine; IEA:UniProtKB-SubCell. DR GO; GO:0045121; C:membrane raft; ISS:BHF-UCL. DR GO; GO:0005739; C:mitochondrion; ISS:BHF-UCL. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:BHF-UCL. DR GO; GO:0001917; C:photoreceptor inner segment; ISS:BHF-UCL. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0014069; C:postsynaptic density; IBA:GO_Central. DR GO; GO:0032991; C:protein-containing complex; ISS:BHF-UCL. DR GO; GO:0042383; C:sarcolemma; IDA:BHF-UCL. DR GO; GO:0016529; C:sarcoplasmic reticulum; IDA:BHF-UCL. DR GO; GO:0045202; C:synapse; ISS:BHF-UCL. DR GO; GO:0034618; F:arginine binding; TAS:BHF-UCL. DR GO; GO:0046870; F:cadmium ion binding; ISS:BHF-UCL. DR GO; GO:0048306; F:calcium-dependent protein binding; ISS:ARUK-UCL. DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW. DR GO; GO:0050660; F:flavin adenine dinucleotide binding; ISS:BHF-UCL. DR GO; GO:0010181; F:FMN binding; ISS:BHF-UCL. DR GO; GO:0020037; F:heme binding; ISS:BHF-UCL. DR GO; GO:0050661; F:NADP binding; ISS:BHF-UCL. DR GO; GO:0004517; F:nitric-oxide synthase activity; IDA:UniProtKB. DR GO; GO:0097110; F:scaffold protein binding; ISS:BHF-UCL. DR GO; GO:0017080; F:sodium channel regulator activity; ISS:BHF-UCL. DR GO; GO:0034617; F:tetrahydrobiopterin binding; NAS:BHF-UCL. DR GO; GO:0044325; F:transmembrane transporter binding; ISS:BHF-UCL. DR GO; GO:0006527; P:arginine catabolic process; IBA:GO_Central. DR GO; GO:0045454; P:cell redox homeostasis; TAS:Reactome. DR GO; GO:0071363; P:cellular response to growth factor stimulus; ISS:BHF-UCL. DR GO; GO:0033555; P:multicellular organismal response to stress; IMP:BHF-UCL. DR GO; GO:0006936; P:muscle contraction; IBA:GO_Central. DR GO; GO:0007520; P:myoblast fusion; TAS:BHF-UCL. DR GO; GO:0045776; P:negative regulation of blood pressure; IBA:GO_Central. DR GO; GO:0051926; P:negative regulation of calcium ion transport; ISS:BHF-UCL. DR GO; GO:0010523; P:negative regulation of calcium ion transport into cytosol; TAS:BHF-UCL. DR GO; GO:0051346; P:negative regulation of hydrolase activity; ISS:BHF-UCL. DR GO; GO:0043267; P:negative regulation of potassium ion transport; ISS:BHF-UCL. DR GO; GO:0051612; P:negative regulation of serotonin uptake; ISS:BHF-UCL. DR GO; GO:0006809; P:nitric oxide biosynthetic process; ISS:BHF-UCL. DR GO; GO:0007263; P:nitric oxide mediated signal transduction; IBA:GO_Central. DR GO; GO:0018119; P:peptidyl-cysteine S-nitrosylation; ISS:BHF-UCL. DR GO; GO:0106071; P:positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway; ISS:BHF-UCL. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISS:BHF-UCL. DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IMP:ARUK-UCL. DR GO; GO:1902307; P:positive regulation of sodium ion transmembrane transport; ISS:BHF-UCL. DR GO; GO:0098735; P:positive regulation of the force of heart contraction; ISS:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:BHF-UCL. DR GO; GO:1902514; P:regulation of calcium ion transmembrane transport via high voltage-gated calcium channel; TAS:BHF-UCL. DR GO; GO:0055117; P:regulation of cardiac muscle contraction; TAS:BHF-UCL. DR GO; GO:0060314; P:regulation of ryanodine-sensitive calcium-release channel activity; TAS:BHF-UCL. DR GO; GO:0002028; P:regulation of sodium ion transport; ISS:BHF-UCL. DR GO; GO:0009408; P:response to heat; IDA:BHF-UCL. DR GO; GO:0009725; P:response to hormone; IBA:GO_Central. DR GO; GO:0001666; P:response to hypoxia; IEP:BHF-UCL. DR GO; GO:0032496; P:response to lipopolysaccharide; IBA:GO_Central. DR GO; GO:0098924; P:retrograde trans-synaptic signaling by nitric oxide; IBA:GO_Central. DR GO; GO:0006941; P:striated muscle contraction; ISS:BHF-UCL. DR GO; GO:0042311; P:vasodilation; IDA:BHF-UCL. DR GO; GO:0042178; P:xenobiotic catabolic process; ISS:BHF-UCL. DR CDD; cd06202; Nitric_oxide_synthase; 1. DR CDD; cd00795; NOS_oxygenase_euk; 1. DR CDD; cd00992; PDZ_signaling; 1. DR Gene3D; 2.30.42.10; -; 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; IPR001478; PDZ. DR InterPro; IPR036034; PDZ_sf. 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 Pfam; PF00595; PDZ; 1. DR PIRSF; PIRSF000333; NOS; 1. DR PRINTS; PR00369; FLAVODOXIN. DR PRINTS; PR00371; FPNCR. DR SMART; SM00228; PDZ; 1. 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; SSF50156; PDZ domain-like; 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. DR PROSITE; PS50106; PDZ; 1. DR Genevisible; P29475; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Calmodulin-binding; Cell membrane; KW Cell projection; FAD; Flavoprotein; FMN; Heme; Iron; Membrane; KW Metal-binding; NADP; Oxidoreductase; Phosphoprotein; Reference proteome; KW Synapse; Ubl conjugation. FT CHAIN 1..1434 FT /note="Nitric oxide synthase 1" FT /id="PRO_0000170921" FT DOMAIN 17..99 FT /note="PDZ" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143" FT DOMAIN 760..940 FT /note="Flavodoxin-like" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00088" FT DOMAIN 995..1242 FT /note="FAD-binding FR-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716" FT REGION 1..205 FT /note="Interaction with NOSIP" FT /evidence="ECO:0000250|UniProtKB:P29476" FT REGION 112..192 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 163..245 FT /note="Interaction with DYNLL1/PIN" FT /evidence="ECO:0000250|UniProtKB:P29476" FT REGION 276..302 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 730..750 FT /note="Calmodulin-binding" FT /evidence="ECO:0000250|UniProtKB:P29476" FT COMPBIAS 280..299 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 339 FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin" FT /ligand_id="ChEBI:CHEBI:59560" FT /evidence="ECO:0000269|PubMed:25286850, FT ECO:0007744|PDB:4D1N" FT BINDING 420 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:0000269|PubMed:25286850, FT ECO:0007744|PDB:4D1N" FT BINDING 483 FT /ligand="L-arginine" FT /ligand_id="ChEBI:CHEBI:32682" FT /evidence="ECO:0000269|PubMed:25286850, FT ECO:0007744|PDB:4D1N" FT BINDING 592 FT /ligand="L-arginine" FT /ligand_id="ChEBI:CHEBI:32682" FT /evidence="ECO:0000269|PubMed:25286850, FT ECO:0007744|PDB:4D1N" FT BINDING 593 FT /ligand="L-arginine" FT /ligand_id="ChEBI:CHEBI:32682" FT /evidence="ECO:0000269|PubMed:25286850, FT ECO:0007744|PDB:4D1N" FT BINDING 597 FT /ligand="L-arginine" FT /ligand_id="ChEBI:CHEBI:32682" FT /evidence="ECO:0000269|PubMed:25286850, FT ECO:0007744|PDB:4D1N" FT BINDING 682 FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin" FT /ligand_id="ChEBI:CHEBI:59560" FT /evidence="ECO:0000269|PubMed:25286850, FT ECO:0007744|PDB:4D1N" FT BINDING 683 FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin" FT /ligand_id="ChEBI:CHEBI:59560" FT /evidence="ECO:0000269|PubMed:25286850, FT ECO:0007744|PDB:4D1N" FT BINDING 696 FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin" FT /ligand_id="ChEBI:CHEBI:59560" FT /evidence="ECO:0000269|PubMed:25286850, FT ECO:0007744|PDB:4D1N" FT BINDING 711 FT /ligand="heme b" FT /ligand_id="ChEBI:CHEBI:60344" FT /evidence="ECO:0000269|PubMed:25286850, FT ECO:0007744|PDB:4D1N" FT BINDING 766 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 767 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 768 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 770 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 771 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 812 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 813 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 817 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 891 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 896 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 898 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 924 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 928 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1015 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1037 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1178 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1179 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1180 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1181 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1196 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1198 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1201 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1202 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1215 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1216 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1217 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1256 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1289 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1318 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1319 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1325 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1327 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1329 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1362 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1403 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1405 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT MOD_RES 852 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P29476" FT MOD_RES 862 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9Z0J4" FT MOD_RES 863 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9Z0J4" FT VAR_SEQ 1..336 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_003571" FT VAR_SEQ 285..407 FT /note="PPTSGKQSPTKNGSPSKCPRFLKVKNWETEVVLTDTLHLKSTLETGCTEYIC FT MGSIMHPSQHARRPEDVRTKGQLFPLAKEFIDQYYSSIKRFGSKAHMERLEEVNKEIDT FT TSTYQLKDTELI -> MRKLRITEGFGVQRGSHNHPPPQENSPPQRMAAPPSVHASSRS FT RTGRLRWFSLTPSTLRAHWKRDALSTSAWAPSCILLSMQGGLKTSAQKDSSSLSPKSLL FT INTIHQLKDLAPKPTWKGWKR (in isoform 4)" FT /evidence="ECO:0000305" FT /id="VSP_003572" FT VAR_SEQ 408..1434 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000305" FT /id="VSP_003573" FT VAR_SEQ 509..613 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:7515942, FT ECO:0000303|PubMed:7678401" FT /id="VSP_003574" FT VAR_SEQ 844 FT /note="K -> KYPEPLRFFPRKGPPLPNGDTEVHGLAAARDSQHR (in isoform FT 5)" FT /evidence="ECO:0000303|PubMed:9791007" FT /id="VSP_044916" FT VARIANT 228 FT /note="P -> S (in dbSNP:rs9658279)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_018948" FT VARIANT 394 FT /note="D -> A (in dbSNP:rs9658356)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_018949" FT VARIANT 725 FT /note="N -> D (in dbSNP:rs9658403)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_018950" FT VARIANT 864 FT /note="G -> D (in dbSNP:rs9658445)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_018951" FT VARIANT 1064 FT /note="Q -> R (in dbSNP:rs9658482)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_018952" FT CONFLICT 131 FT /note="K -> E (in Ref. 4; AAB49040)" FT /evidence="ECO:0000305" FT CONFLICT 178..184 FT /note="LAPRPPG -> WPQAPR (in Ref. 3 and 4)" FT /evidence="ECO:0000305" FT CONFLICT 492..493 FT /note="QP -> HR (in Ref. 3; AAA36376)" FT /evidence="ECO:0000305" FT CONFLICT 549 FT /note="V -> L (in Ref. 3; AAA36376)" FT /evidence="ECO:0000305" FT CONFLICT 563 FT /note="G -> A (in Ref. 3; AAA36376)" FT /evidence="ECO:0000305" FT CONFLICT 1407 FT /note="Y -> I (in Ref. 3; AAA36376)" FT /evidence="ECO:0000305" FT STRAND 105..111 FT /evidence="ECO:0007829|PDB:8BI9" FT STRAND 117..123 FT /evidence="ECO:0007829|PDB:8BI9" FT STRAND 306..310 FT /evidence="ECO:0007829|PDB:6CID" FT TURN 311..313 FT /evidence="ECO:0007829|PDB:6CID" FT STRAND 316..319 FT /evidence="ECO:0007829|PDB:6CID" FT HELIX 321..324 FT /evidence="ECO:0007829|PDB:6CID" FT STRAND 333..336 FT /evidence="ECO:0007829|PDB:6NG6" FT HELIX 344..346 FT /evidence="ECO:0007829|PDB:6CID" FT STRAND 351..353 FT /evidence="ECO:0007829|PDB:7TS6" FT HELIX 356..373 FT /evidence="ECO:0007829|PDB:6CID" FT STRAND 377..379 FT /evidence="ECO:0007829|PDB:7TS6" FT HELIX 380..396 FT /evidence="ECO:0007829|PDB:6CID" FT HELIX 403..415 FT /evidence="ECO:0007829|PDB:6CID" FT HELIX 423..425 FT /evidence="ECO:0007829|PDB:6CID" FT STRAND 430..433 FT /evidence="ECO:0007829|PDB:6CID" FT HELIX 440..455 FT /evidence="ECO:0007829|PDB:6CID" FT HELIX 456..458 FT /evidence="ECO:0007829|PDB:6CID" FT STRAND 463..466 FT /evidence="ECO:0007829|PDB:6CID" FT STRAND 471..475 FT /evidence="ECO:0007829|PDB:6CID" FT STRAND 481..485 FT /evidence="ECO:0007829|PDB:6CID" FT STRAND 489..491 FT /evidence="ECO:0007829|PDB:6CID" FT STRAND 493..495 FT /evidence="ECO:0007829|PDB:7TS6" FT STRAND 497..499 FT /evidence="ECO:0007829|PDB:6CID" FT HELIX 501..503 FT /evidence="ECO:0007829|PDB:6CID" FT HELIX 504..512 FT /evidence="ECO:0007829|PDB:6CID" FT STRAND 520..522 FT /evidence="ECO:0007829|PDB:6POA" FT STRAND 527..530 FT /evidence="ECO:0007829|PDB:6CID" FT STRAND 537..539 FT /evidence="ECO:0007829|PDB:6CID" FT HELIX 543..545 FT /evidence="ECO:0007829|PDB:6CID" FT STRAND 548..550 FT /evidence="ECO:0007829|PDB:6CID" FT HELIX 557..562 FT /evidence="ECO:0007829|PDB:6CID" FT STRAND 565..568 FT /evidence="ECO:0007829|PDB:6CID" FT STRAND 576..579 FT /evidence="ECO:0007829|PDB:6CID" FT STRAND 582..585 FT /evidence="ECO:0007829|PDB:6CID" FT HELIX 595..599 FT /evidence="ECO:0007829|PDB:6CID" FT HELIX 601..604 FT /evidence="ECO:0007829|PDB:6CID" FT TURN 606..609 FT /evidence="ECO:0007829|PDB:6CID" FT HELIX 612..618 FT /evidence="ECO:0007829|PDB:6CID" FT HELIX 626..628 FT /evidence="ECO:0007829|PDB:6CID" FT HELIX 630..648 FT /evidence="ECO:0007829|PDB:6CID" FT HELIX 656..674 FT /evidence="ECO:0007829|PDB:6CID" FT HELIX 681..684 FT /evidence="ECO:0007829|PDB:6CID" FT STRAND 687..689 FT /evidence="ECO:0007829|PDB:6CID" FT HELIX 690..692 FT /evidence="ECO:0007829|PDB:6CID" FT HELIX 694..697 FT /evidence="ECO:0007829|PDB:6CID" FT STRAND 702..704 FT /evidence="ECO:0007829|PDB:6AV1" FT STRAND 706..711 FT /evidence="ECO:0007829|PDB:6CID" FT HELIX 715..718 FT /evidence="ECO:0007829|PDB:6CID" SQ SEQUENCE 1434 AA; 160970 MW; 99235793B953BF37 CRC64; MEDHMFGVQQ IQPNVISVRL FKRKVGGLGF LVKERVSKPP VIISDLIRGG AAEQSGLIQA GDIILAVNGR PLVDLSYDSA LEVLRGIASE THVVLILRGP EGFTTHLETT FTGDGTPKTI RVTQPLGPPT KAVDLSHQPP AGKEQPLAVD GASGPGNGPQ HAYDDGQEAG SLPHANGLAP RPPGQDPAKK ATRVSLQGRG ENNELLKEIE PVLSLLTSGS RGVKGGAPAK AEMKDMGIQV DRDLDGKSHK PLPLGVENDR VFNDLWGKGN VPVVLNNPYS EKEQPPTSGK QSPTKNGSPS KCPRFLKVKN WETEVVLTDT LHLKSTLETG CTEYICMGSI MHPSQHARRP EDVRTKGQLF PLAKEFIDQY YSSIKRFGSK AHMERLEEVN KEIDTTSTYQ LKDTELIYGA KHAWRNASRC VGRIQWSKLQ VFDARDCTTA HGMFNYICNH VKYATNKGNL RSAITIFPQR TDGKHDFRVW NSQLIRYAGY KQPDGSTLGD PANVQFTEIC IQQGWKPPRG RFDVLPLLLQ ANGNDPELFQ IPPELVLEVP IRHPKFEWFK DLGLKWYGLP AVSNMLLEIG GLEFSACPFS GWYMGTEIGV RDYCDNSRYN ILEEVAKKMN LDMRKTSSLW KDQALVEINI AVLYSFQSDK VTIVDHHSAT ESFIKHMENE YRCRGGCPAD WVWIVPPMSG SITPVFHQEM LNYRLTPSFE YQPDPWNTHV WKGTNGTPTK RRAIGFKKLA EAVKFSAKLM GQAMAKRVKA TILYATETGK SQAYAKTLCE IFKHAFDAKV MSMEEYDIVH LEHETLVLVV TSTFGNGDPP ENGEKFGCAL MEMRHPNSVQ EERKSYKVRF NSVSSYSDSQ KSSGDGPDLR DNFESAGPLA NVRFSVFGLG SRAYPHFCAF GHAVDTLLEE LGGERILKMR EGDELCGQEE AFRTWAKKVF KAACDVFCVG DDVNIEKANN SLISNDRSWK RNKFRLTFVA EAPELTQGLS NVHKKRVSAA RLLSRQNLQS PKSSRSTIFV RLHTNGSQEL QYQPGDHLGV FPGNHEDLVN ALIERLEDAP PVNQMVKVEL LEERNTALGV ISNWTDELRL PPCTIFQAFK YYLDITTPPT PLQLQQFASL ATSEKEKQRL LVLSKGLQEY EEWKWGKNPT IVEVLEEFPS IQMPATLLLT QLSLLQPRYY SISSSPDMYP DEVHLTVAIV SYRTRDGEGP IHHGVCSSWL NRIQADELVP CFVRGAPSFH LPRNPQVPCI LVGPGTGIAP FRSFWQQRQF DIQHKGMNPC PMVLVFGCRQ SKIDHIYREE TLQAKNKGVF RELYTAYSRE PDKPKKYVQD ILQEQLAESV YRALKEQGGH IYVCGDVTMA ADVLKAIQRI MTQQGKLSAE DAGVFISRMR DDNRYHEDIF GVTLRTYEVT NRLRSESIAF IEESKKDTDE VFSS //