P29475 (NOS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Nitric oxide synthase, brain
EC=1.14.13.39

Alternative name(s):
Constitutive NOS
NC-NOS
NOS type I
Neuronal NOS
Short name=N-NOS
Short name=nNOS
Peptidyl-cysteine S-nitrosylase NOS1
bNOS

Gene names

Name:

NOS1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1434 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR.
Catalytic activity	2 L-arginine + 3 NADPH + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O.
Cofactor	Heme group. Binds 1 FAD. Binds 1 FMN. Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme.
Enzyme regulation	Stimulated by calcium/calmodulin. Inhibited by n-Nos-inhibiting protein (PIN) which may prevent the dimerization of the protein. Inhibited by NOSIP.
Subunit structure	Homodimer. Interacts with DLG4; the interaction possibly being prevented by the association between NOS1 and CAPON. Forms a ternary complex with CAPON and RASD1. Forms a ternary complex with CAPON and SYN1. Interacts with ZDHHC23. Interacts with NOSIP; which may impair its synaptic location By similarity. Interacts with HTR4. Interacts with VAC14 By similarity. Interacts with SLC6A4 By similarity.
Subcellular location	Cell membrane › sarcolemma; Peripheral membrane protein. Cell projection › dendritic spine By similarity. Note: In skeletal muscle, it is localized beneath the sarcolemma of fast-twitch muscle fiber by associating with the dystrophin glycoprotein complex. In neurons, enriched in dendritic spines By similarity.
Tissue specificity	Isoform 1 is ubiquitously expressed: detected in skeletal muscle and brain, also in testis, lung and kidney, and at low levels in heart, adrenal gland and retina. Not detected in the platelets. Isoform 3 is expressed only in testis. Isoform 4 is detected in testis, skeletal muscle, lung, and kidney, at low levels in the brain, but not in the heart and adrenal gland.
Domain	The PDZ domain in the N-terminal part of the neuronal isoform participates in protein-protein interaction, and is responsible for targeting nNos to synaptic membranes in muscles. Mediates interaction with VAC14 By similarity.
Post-translational modification	Ubiquitinated; mediated by STUB1/CHIP in the presence of Hsp70 and Hsp40 (in vitro) By similarity.
Sequence similarities	Belongs to the NOS family. Contains 1 FAD-binding FR-type domain. Contains 1 flavodoxin-like domain. Contains 1 PDZ (DHR) domain.

Ontologies

Keywords
Cellular component	Cell membrane Cell projection Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Calmodulin-binding FAD FMN Heme Iron Metal-binding NADP
Molecular function	Oxidoreductase
PTM	Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	arginine catabolic process Inferred by curator PubMed 7545544. Source: BHF-UCL blood coagulation Traceable author statement. Source: Reactome interaction with host Traceable author statement. Source: Reactome multicellular organismal response to stress Inferred from mutant phenotype PubMed 18391107. Source: BHF-UCL myoblast fusion Traceable author statement PubMed 7545544. Source: BHF-UCL negative regulation of blood pressure Inferred from Biological aspect of Ancestor. Source: RefGenome negative regulation of calcium ion transport into cytosol Traceable author statement PubMed 17568574. Source: BHF-UCL neurotransmitter biosynthetic process Traceable author statement PubMed 7545544. Source: BHF-UCL nitric oxide biosynthetic process Inferred from sequence or structural similarity PubMed 7545544. Source: BHF-UCL nitric oxide mediated signal transduction Inferred from Biological aspect of Ancestor. Source: RefGenome phagosome maturation Traceable author statement. Source: Reactome positive regulation of guanylate cyclase activity Inferred from Biological aspect of Ancestor. Source: RefGenome positive regulation of vasodilation Inferred from direct assay PubMed 18048451. Source: BHF-UCL regulation of cardiac muscle contraction Traceable author statement PubMed 9892689. Source: BHF-UCL response to heat Inferred from direct assay PubMed 18048451. Source: BHF-UCL response to hypoxia Inferred from expression pattern PubMed 16276418. Source: BHF-UCL
Cellular_component	cytoskeleton Inferred from sequence or structural similarity PubMed 7545544. Source: BHF-UCL cytosol Traceable author statement. Source: Reactome dendritic spine Inferred from electronic annotation. Source: UniProtKB-SubCell perinuclear region of cytoplasm Inferred from sequence or structural similarity PubMed 17027776. Source: BHF-UCL photoreceptor inner segment Inferred from sequence or structural similarity PubMed 17027776. Source: BHF-UCL sarcolemma Inferred from direct assay PubMed 7545544. Source: BHF-UCL sarcoplasmic reticulum Inferred from direct assay PubMed 9892689. Source: BHF-UCL
Molecular_function	FMN binding Inferred from sequence or structural similarity. Source: BHF-UCL NADP binding Inferred from sequence or structural similarity. Source: BHF-UCL NADPH-hemoprotein reductase activity Inferred from Biological aspect of Ancestor. Source: RefGenome arginine binding Traceable author statement PubMed 17029414. Source: BHF-UCL cadmium ion binding Inferred from sequence or structural similarity. Source: BHF-UCL flavin adenine dinucleotide binding Inferred from sequence or structural similarity. Source: BHF-UCL heme binding Inferred from sequence or structural similarity. Source: BHF-UCL iron ion binding Inferred from electronic annotation. Source: InterPro nitric-oxide synthase activity Inferred from sequence or structural similarity PubMed 7545544. Source: BHF-UCL tetrahydrobiopterin binding Non-traceable author statement PubMed 7488039. Source: BHF-UCL
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Note: Isoform 3 is produced by different alternative splicing events implicating either the untranslated exons TEX1 (TN-NOS) or TEX1B (TN-NOSB) leading to a N-terminus truncated protein which possesses enzymatic activity comparable to that of isoform 1. The C-terminal truncated isoform 4 is produced by insertion of the TEX2 exon between exons 3 and 4 of isoform 1, leading to a frameshift and a premature stop codon.

Isoform 1 (identifier: P29475-1)

Also known as: N-NOS-1;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P29475-2)

Also known as: N-NOS-2;

The sequence of this isoform differs from the canonical sequence as follows:
     509-613: Missing.

Isoform 3 (identifier: P29475-3)

Also known as: TN-NOS; TN-NOSB;

The sequence of this isoform differs from the canonical sequence as follows:
     1-336: Missing.

Isoform 4 (identifier: P29475-4)

Also known as: TEX2-insertion;

The sequence of this isoform differs from the canonical sequence as follows:
     285-407: PPTSGKQSPT...TYQLKDTELI → MRKLRITEGF...PKPTWKGWKR
     408-1434: Missing.

Isoform 5 (identifier: P29475-5)

Also known as: nNOSmu;

The sequence of this isoform differs from the canonical sequence as follows:
     844-844: K → KYPEPLRFFPRKGPPLPNGDTEVHGLAAARDSQHR

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1434	1434	Nitric oxide synthase, brain		PRO_0000170921
Regions
	Domain	17 – 99	83	PDZ
	Domain	760 – 940	181	Flavodoxin-like
	Domain	995 – 1242	248	FAD-binding FR-type
	Nucleotide binding	886 – 917	32	FMN By similarity
	Nucleotide binding	1032 – 1043	12	FAD By similarity
	Nucleotide binding	1175 – 1185	11	FAD By similarity
	Nucleotide binding	1250 – 1268	19	NADP By similarity
	Nucleotide binding	1348 – 1363	16	NADP By similarity
	Region	1 – 205	205	Interaction with NOSIP By similarity
	Region	163 – 245	83	PIN (nNOS-inhibiting protein) binding
	Region	730 – 750	21	Calmodulin-binding Potential
	Region	755 – 774	20	Tetrahydrobiopterin-binding By similarity
Sites
	Metal binding	420	1	Iron (heme axial ligand) By similarity
Natural variations
	Alternative sequence	1 – 336	336	Missing in isoform 3.		VSP_003571
	Alternative sequence	285 – 407	123	PPTSG…DTELI → MRKLRITEGFGVQRGSHNHP PPQENSPPQRMAAPPSVHAS SRSRTGRLRWFSLTPSTLRA HWKRDALSTSAWAPSCILLS MQGGLKTSAQKDSSSLSPKS LLINTIHQLKDLAPKPTWKG WKR in isoform 4.		VSP_003572
	Alternative sequence	408 – 1434	1027	Missing in isoform 4.		VSP_003573
	Alternative sequence	509 – 613	105	Missing in isoform 2.		VSP_003574
	Alternative sequence	844	1	K → KYPEPLRFFPRKGPPLPNGD TEVHGLAAARDSQHR in isoform 5.		VSP_044916
	Natural variant	228	1	P → S. Ref.6 Corresponds to variant rs9658279 [ dbSNP | Ensembl ].		VAR_018948
	Natural variant	394	1	D → A. Ref.6 Corresponds to variant rs9658356 [ dbSNP | Ensembl ].		VAR_018949
	Natural variant	725	1	N → D. Ref.6 Corresponds to variant rs9658403 [ dbSNP | Ensembl ].		VAR_018950
	Natural variant	864	1	G → D. Ref.6 Corresponds to variant rs9658445 [ dbSNP | Ensembl ].		VAR_018951
	Natural variant	1064	1	Q → R. Ref.6 Corresponds to variant rs9658482 [ dbSNP | Ensembl ].		VAR_018952
Experimental info
	Sequence conflict	131	1	K → E in AAB49040. Ref.4
	Sequence conflict	178 – 184	7	LAPRPPG → WPQAPR Ref.3
	Sequence conflict	178 – 184	7	LAPRPPG → WPQAPR Ref.4
	Sequence conflict	492 – 493	2	QP → HR in AAA36376. Ref.3
	Sequence conflict	549	1	V → L in AAA36376. Ref.3
	Sequence conflict	563	1	G → A in AAA36376. Ref.3
	Sequence conflict	1407	1	Y → I in AAA36376. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (N-NOS-1) [UniParc]. Last modified October 1, 1996. Version 2. Checksum: 99235793B953BF37	FASTA	1,434	160,970
	10 20 30 40 50 60 MEDHMFGVQQ IQPNVISVRL FKRKVGGLGF LVKERVSKPP VIISDLIRGG AAEQSGLIQA 70 80 90 100 110 120 GDIILAVNGR PLVDLSYDSA LEVLRGIASE THVVLILRGP EGFTTHLETT FTGDGTPKTI 130 140 150 160 170 180 RVTQPLGPPT KAVDLSHQPP AGKEQPLAVD GASGPGNGPQ HAYDDGQEAG SLPHANGLAP 190 200 210 220 230 240 RPPGQDPAKK ATRVSLQGRG ENNELLKEIE PVLSLLTSGS RGVKGGAPAK AEMKDMGIQV 250 260 270 280 290 300 DRDLDGKSHK PLPLGVENDR VFNDLWGKGN VPVVLNNPYS EKEQPPTSGK QSPTKNGSPS 310 320 330 340 350 360 KCPRFLKVKN WETEVVLTDT LHLKSTLETG CTEYICMGSI MHPSQHARRP EDVRTKGQLF 370 380 390 400 410 420 PLAKEFIDQY YSSIKRFGSK AHMERLEEVN KEIDTTSTYQ LKDTELIYGA KHAWRNASRC 430 440 450 460 470 480 VGRIQWSKLQ VFDARDCTTA HGMFNYICNH VKYATNKGNL RSAITIFPQR TDGKHDFRVW 490 500 510 520 530 540 NSQLIRYAGY KQPDGSTLGD PANVQFTEIC IQQGWKPPRG RFDVLPLLLQ ANGNDPELFQ 550 560 570 580 590 600 IPPELVLEVP IRHPKFEWFK DLGLKWYGLP AVSNMLLEIG GLEFSACPFS GWYMGTEIGV 610 620 630 640 650 660 RDYCDNSRYN ILEEVAKKMN LDMRKTSSLW KDQALVEINI AVLYSFQSDK VTIVDHHSAT 670 680 690 700 710 720 ESFIKHMENE YRCRGGCPAD WVWIVPPMSG SITPVFHQEM LNYRLTPSFE YQPDPWNTHV 730 740 750 760 770 780 WKGTNGTPTK RRAIGFKKLA EAVKFSAKLM GQAMAKRVKA TILYATETGK SQAYAKTLCE 790 800 810 820 830 840 IFKHAFDAKV MSMEEYDIVH LEHETLVLVV TSTFGNGDPP ENGEKFGCAL MEMRHPNSVQ 850 860 870 880 890 900 EERKSYKVRF NSVSSYSDSQ KSSGDGPDLR DNFESAGPLA NVRFSVFGLG SRAYPHFCAF 910 920 930 940 950 960 GHAVDTLLEE LGGERILKMR EGDELCGQEE AFRTWAKKVF KAACDVFCVG DDVNIEKANN 970 980 990 1000 1010 1020 SLISNDRSWK RNKFRLTFVA EAPELTQGLS NVHKKRVSAA RLLSRQNLQS PKSSRSTIFV 1030 1040 1050 1060 1070 1080 RLHTNGSQEL QYQPGDHLGV FPGNHEDLVN ALIERLEDAP PVNQMVKVEL LEERNTALGV 1090 1100 1110 1120 1130 1140 ISNWTDELRL PPCTIFQAFK YYLDITTPPT PLQLQQFASL ATSEKEKQRL LVLSKGLQEY 1150 1160 1170 1180 1190 1200 EEWKWGKNPT IVEVLEEFPS IQMPATLLLT QLSLLQPRYY SISSSPDMYP DEVHLTVAIV 1210 1220 1230 1240 1250 1260 SYRTRDGEGP IHHGVCSSWL NRIQADELVP CFVRGAPSFH LPRNPQVPCI LVGPGTGIAP 1270 1280 1290 1300 1310 1320 FRSFWQQRQF DIQHKGMNPC PMVLVFGCRQ SKIDHIYREE TLQAKNKGVF RELYTAYSRE 1330 1340 1350 1360 1370 1380 PDKPKKYVQD ILQEQLAESV YRALKEQGGH IYVCGDVTMA ADVLKAIQRI MTQQGKLSAE 1390 1400 1410 1420 1430 DAGVFISRMR DDNRYHEDIF GVTLRTYEVT NRLRSESIAF IEESKKDTDE VFSS
	Isoform 2 (N-NOS-2) [UniParc]. Checksum: DF791B80FDB12302	FASTA	1,329	148,919
	10 20 30 40 50 60 MEDHMFGVQQ IQPNVISVRL FKRKVGGLGF LVKERVSKPP VIISDLIRGG AAEQSGLIQA 70 80 90 100 110 120 GDIILAVNGR PLVDLSYDSA LEVLRGIASE THVVLILRGP EGFTTHLETT FTGDGTPKTI 130 140 150 160 170 180 RVTQPLGPPT KAVDLSHQPP AGKEQPLAVD GASGPGNGPQ HAYDDGQEAG SLPHANGLAP 190 200 210 220 230 240 RPPGQDPAKK ATRVSLQGRG ENNELLKEIE PVLSLLTSGS RGVKGGAPAK AEMKDMGIQV 250 260 270 280 290 300 DRDLDGKSHK PLPLGVENDR VFNDLWGKGN VPVVLNNPYS EKEQPPTSGK QSPTKNGSPS 310 320 330 340 350 360 KCPRFLKVKN WETEVVLTDT LHLKSTLETG CTEYICMGSI MHPSQHARRP EDVRTKGQLF 370 380 390 400 410 420 PLAKEFIDQY YSSIKRFGSK AHMERLEEVN KEIDTTSTYQ LKDTELIYGA KHAWRNASRC 430 440 450 460 470 480 VGRIQWSKLQ VFDARDCTTA HGMFNYICNH VKYATNKGNL RSAITIFPQR TDGKHDFRVW 490 500 510 520 530 540 NSQLIRYAGY KQPDGSTLGD PANVQFTEEV AKKMNLDMRK TSSLWKDQAL VEINIAVLYS 550 560 570 580 590 600 FQSDKVTIVD HHSATESFIK HMENEYRCRG GCPADWVWIV PPMSGSITPV FHQEMLNYRL 610 620 630 640 650 660 TPSFEYQPDP WNTHVWKGTN GTPTKRRAIG FKKLAEAVKF SAKLMGQAMA KRVKATILYA 670 680 690 700 710 720 TETGKSQAYA KTLCEIFKHA FDAKVMSMEE YDIVHLEHET LVLVVTSTFG NGDPPENGEK 730 740 750 760 770 780 FGCALMEMRH PNSVQEERKS YKVRFNSVSS YSDSQKSSGD GPDLRDNFES AGPLANVRFS 790 800 810 820 830 840 VFGLGSRAYP HFCAFGHAVD TLLEELGGER ILKMREGDEL CGQEEAFRTW AKKVFKAACD 850 860 870 880 890 900 VFCVGDDVNI EKANNSLISN DRSWKRNKFR LTFVAEAPEL TQGLSNVHKK RVSAARLLSR 910 920 930 940 950 960 QNLQSPKSSR STIFVRLHTN GSQELQYQPG DHLGVFPGNH EDLVNALIER LEDAPPVNQM 970 980 990 1000 1010 1020 VKVELLEERN TALGVISNWT DELRLPPCTI FQAFKYYLDI TTPPTPLQLQ QFASLATSEK 1030 1040 1050 1060 1070 1080 EKQRLLVLSK GLQEYEEWKW GKNPTIVEVL EEFPSIQMPA TLLLTQLSLL QPRYYSISSS 1090 1100 1110 1120 1130 1140 PDMYPDEVHL TVAIVSYRTR DGEGPIHHGV CSSWLNRIQA DELVPCFVRG APSFHLPRNP 1150 1160 1170 1180 1190 1200 QVPCILVGPG TGIAPFRSFW QQRQFDIQHK GMNPCPMVLV FGCRQSKIDH IYREETLQAK 1210 1220 1230 1240 1250 1260 NKGVFRELYT AYSREPDKPK KYVQDILQEQ LAESVYRALK EQGGHIYVCG DVTMAADVLK 1270 1280 1290 1300 1310 1320 AIQRIMTQQG KLSAEDAGVF ISRMRDDNRY HEDIFGVTLR TYEVTNRLRS ESIAFIEESK KDTDEVFSS
	Isoform 3 (TN-NOS) (TN-NOSB) [UniParc]. Checksum: A1CD5C5012436233	FASTA	1,098	125,113
	10 20 30 40 50 60 MGSIMHPSQH ARRPEDVRTK GQLFPLAKEF IDQYYSSIKR FGSKAHMERL EEVNKEIDTT 70 80 90 100 110 120 STYQLKDTEL IYGAKHAWRN ASRCVGRIQW SKLQVFDARD CTTAHGMFNY ICNHVKYATN 130 140 150 160 170 180 KGNLRSAITI FPQRTDGKHD FRVWNSQLIR YAGYKQPDGS TLGDPANVQF TEICIQQGWK 190 200 210 220 230 240 PPRGRFDVLP LLLQANGNDP ELFQIPPELV LEVPIRHPKF EWFKDLGLKW YGLPAVSNML 250 260 270 280 290 300 LEIGGLEFSA CPFSGWYMGT EIGVRDYCDN SRYNILEEVA KKMNLDMRKT SSLWKDQALV 310 320 330 340 350 360 EINIAVLYSF QSDKVTIVDH HSATESFIKH MENEYRCRGG CPADWVWIVP PMSGSITPVF 370 380 390 400 410 420 HQEMLNYRLT PSFEYQPDPW NTHVWKGTNG TPTKRRAIGF KKLAEAVKFS AKLMGQAMAK 430 440 450 460 470 480 RVKATILYAT ETGKSQAYAK TLCEIFKHAF DAKVMSMEEY DIVHLEHETL VLVVTSTFGN 490 500 510 520 530 540 GDPPENGEKF GCALMEMRHP NSVQEERKSY KVRFNSVSSY SDSQKSSGDG PDLRDNFESA 550 560 570 580 590 600 GPLANVRFSV FGLGSRAYPH FCAFGHAVDT LLEELGGERI LKMREGDELC GQEEAFRTWA 610 620 630 640 650 660 KKVFKAACDV FCVGDDVNIE KANNSLISND RSWKRNKFRL TFVAEAPELT QGLSNVHKKR 670 680 690 700 710 720 VSAARLLSRQ NLQSPKSSRS TIFVRLHTNG SQELQYQPGD HLGVFPGNHE DLVNALIERL 730 740 750 760 770 780 EDAPPVNQMV KVELLEERNT ALGVISNWTD ELRLPPCTIF QAFKYYLDIT TPPTPLQLQQ 790 800 810 820 830 840 FASLATSEKE KQRLLVLSKG LQEYEEWKWG KNPTIVEVLE EFPSIQMPAT LLLTQLSLLQ 850 860 870 880 890 900 PRYYSISSSP DMYPDEVHLT VAIVSYRTRD GEGPIHHGVC SSWLNRIQAD ELVPCFVRGA 910 920 930 940 950 960 PSFHLPRNPQ VPCILVGPGT GIAPFRSFWQ QRQFDIQHKG MNPCPMVLVF GCRQSKIDHI 970 980 990 1000 1010 1020 YREETLQAKN KGVFRELYTA YSREPDKPKK YVQDILQEQL AESVYRALKE QGGHIYVCGD 1030 1040 1050 1060 1070 1080 VTMAADVLKA IQRIMTQQGK LSAEDAGVFI SRMRDDNRYH EDIFGVTLRT YEVTNRLRSE 1090 SIAFIEESKK DTDEVFSS
	Isoform 4 (TEX2-insertion) [UniParc]. Checksum: 7E9420C658EFACD2	FASTA	407	43,838
	10 20 30 40 50 60 MEDHMFGVQQ IQPNVISVRL FKRKVGGLGF LVKERVSKPP VIISDLIRGG AAEQSGLIQA 70 80 90 100 110 120 GDIILAVNGR PLVDLSYDSA LEVLRGIASE THVVLILRGP EGFTTHLETT FTGDGTPKTI 130 140 150 160 170 180 RVTQPLGPPT KAVDLSHQPP AGKEQPLAVD GASGPGNGPQ HAYDDGQEAG SLPHANGLAP 190 200 210 220 230 240 RPPGQDPAKK ATRVSLQGRG ENNELLKEIE PVLSLLTSGS RGVKGGAPAK AEMKDMGIQV 250 260 270 280 290 300 DRDLDGKSHK PLPLGVENDR VFNDLWGKGN VPVVLNNPYS EKEQMRKLRI TEGFGVQRGS 310 320 330 340 350 360 HNHPPPQENS PPQRMAAPPS VHASSRSRTG RLRWFSLTPS TLRAHWKRDA LSTSAWAPSC 370 380 390 400 ILLSMQGGLK TSAQKDSSSL SPKSLLINTI HQLKDLAPKP TWKGWKR
	Isoform 5 (nNOSmu) [UniParc]. Checksum: 95906AC90699A0E2	FASTA	1,468	164,779
	10 20 30 40 50 60 MEDHMFGVQQ IQPNVISVRL FKRKVGGLGF LVKERVSKPP VIISDLIRGG AAEQSGLIQA 70 80 90 100 110 120 GDIILAVNGR PLVDLSYDSA LEVLRGIASE THVVLILRGP EGFTTHLETT FTGDGTPKTI 130 140 150 160 170 180 RVTQPLGPPT KAVDLSHQPP AGKEQPLAVD GASGPGNGPQ HAYDDGQEAG SLPHANGLAP 190 200 210 220 230 240 RPPGQDPAKK ATRVSLQGRG ENNELLKEIE PVLSLLTSGS RGVKGGAPAK AEMKDMGIQV 250 260 270 280 290 300 DRDLDGKSHK PLPLGVENDR VFNDLWGKGN VPVVLNNPYS EKEQPPTSGK QSPTKNGSPS 310 320 330 340 350 360 KCPRFLKVKN WETEVVLTDT LHLKSTLETG CTEYICMGSI MHPSQHARRP EDVRTKGQLF 370 380 390 400 410 420 PLAKEFIDQY YSSIKRFGSK AHMERLEEVN KEIDTTSTYQ LKDTELIYGA KHAWRNASRC 430 440 450 460 470 480 VGRIQWSKLQ VFDARDCTTA HGMFNYICNH VKYATNKGNL RSAITIFPQR TDGKHDFRVW 490 500 510 520 530 540 NSQLIRYAGY KQPDGSTLGD PANVQFTEIC IQQGWKPPRG RFDVLPLLLQ ANGNDPELFQ 550 560 570 580 590 600 IPPELVLEVP IRHPKFEWFK DLGLKWYGLP AVSNMLLEIG GLEFSACPFS GWYMGTEIGV 610 620 630 640 650 660 RDYCDNSRYN ILEEVAKKMN LDMRKTSSLW KDQALVEINI AVLYSFQSDK VTIVDHHSAT 670 680 690 700 710 720 ESFIKHMENE YRCRGGCPAD WVWIVPPMSG SITPVFHQEM LNYRLTPSFE YQPDPWNTHV 730 740 750 760 770 780 WKGTNGTPTK RRAIGFKKLA EAVKFSAKLM GQAMAKRVKA TILYATETGK SQAYAKTLCE 790 800 810 820 830 840 IFKHAFDAKV MSMEEYDIVH LEHETLVLVV TSTFGNGDPP ENGEKFGCAL MEMRHPNSVQ 850 860 870 880 890 900 EERKYPEPLR FFPRKGPPLP NGDTEVHGLA AARDSQHRSY KVRFNSVSSY SDSQKSSGDG 910 920 930 940 950 960 PDLRDNFESA GPLANVRFSV FGLGSRAYPH FCAFGHAVDT LLEELGGERI LKMREGDELC 970 980 990 1000 1010 1020 GQEEAFRTWA KKVFKAACDV FCVGDDVNIE KANNSLISND RSWKRNKFRL TFVAEAPELT 1030 1040 1050 1060 1070 1080 QGLSNVHKKR VSAARLLSRQ NLQSPKSSRS TIFVRLHTNG SQELQYQPGD HLGVFPGNHE 1090 1100 1110 1120 1130 1140 DLVNALIERL EDAPPVNQMV KVELLEERNT ALGVISNWTD ELRLPPCTIF QAFKYYLDIT 1150 1160 1170 1180 1190 1200 TPPTPLQLQQ FASLATSEKE KQRLLVLSKG LQEYEEWKWG KNPTIVEVLE EFPSIQMPAT 1210 1220 1230 1240 1250 1260 LLLTQLSLLQ PRYYSISSSP DMYPDEVHLT VAIVSYRTRD GEGPIHHGVC SSWLNRIQAD 1270 1280 1290 1300 1310 1320 ELVPCFVRGA PSFHLPRNPQ VPCILVGPGT GIAPFRSFWQ QRQFDIQHKG MNPCPMVLVF 1330 1340 1350 1360 1370 1380 GCRQSKIDHI YREETLQAKN KGVFRELYTA YSREPDKPKK YVQDILQEQL AESVYRALKE 1390 1400 1410 1420 1430 1440 QGGHIYVCGD VTMAADVLKA IQRIMTQQGK LSAEDAGVFI SRMRDDNRYH EDIFGVTLRT 1450 1460 YEVTNRLRSE SIAFIEESKK DTDEVFSS

References

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[1]	"Structural organization of the human neuronal nitric oxide synthase gene (NOS1)." Hall A.V., Antoniou H., Wang Y., Cheung A.H., Arbus A.M., Olson S.L., Lu W.C., Kau C.-L., Marsden P.A. J. Biol. Chem. 269:33082-33090(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[2]	"Expression of two types of nitric oxide synthase mRNA in human neuroblastoma cell lines." Fujisawa H., Ogura T., Kurashima Y., Yokoyama T., Yamashita J., Esumi H. J. Neurochem. 63:140-145(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). Tissue: Cerebellum.
[3]	"Cloned human brain nitric oxide synthase is highly expressed in skeletal muscle." Nakane M., Schmidt H.H.H.W., Pollock J.S., Foerstermann U., Murad F. FEBS Lett. 316:175-180(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Brain.
[4]	"Neuronal isoform of nitric oxide synthase is expressed at low levels in human retina." Park C.-S., Gianotti C., Park R., Krishna G. Cell. Mol. Neurobiol. 16:499-515(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Retina.
[5]	"A novel, testis-specific mRNA transcript encoding an NH2-terminal truncated nitric-oxide synthase." Wang Y., Goligorsky M.S., Lin M., Wilcox J.N., Marsden P.A. J. Biol. Chem. 272:11392-11401(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 3 AND 4). Tissue: Testis.
[6]	NIEHS SNPs program Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-228; ALA-394; ASP-725; ASP-864 AND ARG-1064.
[7]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"Isolation and characterization of a novel, human neuronal nitric oxide synthase cDNA." Larsson B., Phillips S.C. Biochem. Biophys. Res. Commun. 251:898-902(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 835-901 (ISOFORM 5), ALTERNATIVE SPLICING. Tissue: Skeletal muscle.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Wikipedia

Nitric oxide synthase entry

Cross-references

Sequence databases
EMBL GenBank DDBJ	U17327 mRNA. Translation: AAA62405.1. U17326 , U17299, U17300, U17301, U17302, U17303, U17304, U17305, U17307, U17308, U17309, U17310, U17311, U17312, U17313, U17314, U17315, U17316, U17317, U17318, U17319, U17320, U17321, U17322, U17323, U17324, U17325 Genomic DNA. Translation: AAB60654.1. Sequence problems. D16408 mRNA. Translation: BAA03895.1. L02881 mRNA. Translation: AAA36376.1. U31466 mRNA. Translation: AAB49040.1. U66362 Genomic DNA. No translation available. AY445095 Genomic DNA. Translation: AAR07069.1. AC026364 Genomic DNA. No translation available. AC068799 Genomic DNA. No translation available. AC073864 Genomic DNA. No translation available. AJ004918 mRNA. Translation: CAA06218.1.
IPI	IPI00216232. IPI00217225. IPI00472618. IPI00746356. IPI00795843.
PIR	G01946.
RefSeq	NP_000611.1. NM_000620.4. NP_001191142.1. NM_001204213.1. NP_001191143.1. NM_001204214.1. NP_001191147.1. NM_001204218.1.
UniGene	Hs.654410. Hs.684465. Hs.684466. Hs.684467. Hs.735734.
3D structure databases
ProteinModelPortal	P29475.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-122019.
STRING	9606.ENSP00000320758.
PTM databases
PhosphoSite	P29475.
Polymorphism databases
DMDM	1709333.
Proteomic databases
PaxDb	P29475.
PRIDE	P29475.
Protocols and materials databases
DNASU	4842.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000317775; ENSP00000320758; ENSG00000089250. ENST00000338101; ENSP00000337459; ENSG00000089250.
GeneID	4842.
KEGG	hsa:4842.
UCSC	uc001twm.2. human. uc001twn.2. human.
Organism-specific databases
CTD	4842.
GeneCards	GC12M117636.
HGNC	HGNC:7872. NOS1.
HPA	CAB002167.
MIM	163731. gene.
neXtProt	NX_P29475.
PharmGKB	PA252.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG4362.
HOGENOM	HOG000220884.
HOVERGEN	HBG000159.
KO	K13240.
OMA	QVPCILI.
OrthoDB	EOG4MKNFC.
Enzyme and pathway databases
BioCyc	MetaCyc:HS01647-MONOMER.
Reactome	REACT_116125. Disease. REACT_604. Hemostasis.
Gene expression databases
ArrayExpress	P29475.
Bgee	P29475.
CleanEx	HS_NOS1.
Genevestigator	P29475.
GermOnline	ENSG00000089250. Homo sapiens.
Family and domain databases
Gene3D	1.20.990.10. 1 hit. 3.90.340.10. 1 hit.
InterPro	IPR003097. FAD-binding_1. IPR017927. Fd_Rdtase_FAD-bd. IPR001094. Flavdoxin. IPR008254. Flavodoxin/NO_synth. IPR001709. Flavoprot_Pyr_Nucl_cyt_Rdtase. IPR023173. NADPH_Cyt_P450_Rdtase_dom3. IPR004030. NO_synthase_oxygenase_dom. IPR026009. NOS. IPR012144. NOS_met. IPR001433. OxRdtase_FAD/NAD-bd. IPR001478. PDZ. IPR017938. Riboflavin_synthase-like_b-brl. [Graphical view]
PANTHER	PTHR19384:SF5. PTHR19384:SF5. 1 hit.
Pfam	PF00667. FAD_binding_1. 1 hit. PF00258. Flavodoxin_1. 1 hit. PF00175. NAD_binding_1. 1 hit. PF02898. NO_synthase. 1 hit. PF00595. PDZ. 1 hit. [Graphical view]
PIRSF	PIRSF000333. NOS. 1 hit.
PRINTS	PR00369. FLAVODOXIN. PR00371. FPNCR.
SMART	SM00228. PDZ. 1 hit. [Graphical view]
SUPFAM	SSF56512. NO_synthase_oxygenase_reg. 1 hit. SSF50156. PDZ. 1 hit. SSF63380. Riboflavin_synthase_like_b-brl. 1 hit.
PROSITE	PS51384. FAD_FR. 1 hit. PS50902. FLAVODOXIN_LIKE. 1 hit. PS60001. NOS. 1 hit. PS50106. PDZ. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P29475.
ChEMBL	CHEMBL3568.
ChiTaRS	NOS1. human.
DrugBank	DB00155. L-Citrulline.
GenomeRNAi	4842.
NextBio	18658.
PMAP-CutDB	P29475.
SOURCE	Search...

Entry information

Entry name

NOS1_HUMAN

Accession

Primary (citable) accession number: P29475
Secondary accession number(s): E9PH30, O75713

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	October 1, 1996
Last modified:	May 29, 2013
This is version 150 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.