Descriptions

Nitric oxide synthase produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. The primary sequences of the three mammalian nitric oxide synthase (NOS) isoforms differ by the insertion of a 52-55-amino acid loop into the reductase domains of the endothelial (eNOS) and neuronal (nNOS), but not inducible (iNOS). The loop mediates the autoinhibition in eNOS and nNOS. Deletion of the autoinhibitory loop increases the catalytic activity of eNOS.

Autoinhibitory domains (AIDs)

Target domain

122-483 (NO synthase domain);732-1164 (FAD/NAD-binding domain)

Relief mechanism

Partner binding

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for Q28969

Entry ID Method Resolution Chain Position Source
AF-Q28969-F1 Predicted AlphaFoldDB

No variants for Q28969

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q28969

No associated diseases with Q28969

17 regional properties for Q28969

Type Name Position InterPro Accession
domain Flavodoxin-like 523 - 536 IPR001094-1
domain Flavodoxin-like 570 - 581 IPR001094-2
domain Flavodoxin-like 646 - 656 IPR001094-3
domain Flavodoxin-like 670 - 689 IPR001094-4
domain Oxidoreductase FAD/NAD(P)-binding 1013 - 1125 IPR001433
domain Flavoprotein pyridine nucleotide cytochrome reductase 795 - 805 IPR001709-1
domain Flavoprotein pyridine nucleotide cytochrome reductase 940 - 947 IPR001709-2
domain Flavoprotein pyridine nucleotide cytochrome reductase 976 - 985 IPR001709-3
domain Flavoprotein pyridine nucleotide cytochrome reductase 1012 - 1031 IPR001709-4
domain Flavoprotein pyridine nucleotide cytochrome reductase 1042 - 1051 IPR001709-5
domain Flavoprotein pyridine nucleotide cytochrome reductase 1055 - 1066 IPR001709-6
domain Flavoprotein pyridine nucleotide cytochrome reductase 1087 - 1103 IPR001709-7
domain Flavoprotein pyridine nucleotide cytochrome reductase 1112 - 1120 IPR001709-8
domain Sulfite reductase [NADPH] flavoprotein alpha-component-like, FAD-binding 754 - 981 IPR003097
domain Nitric oxide synthase, N-terminal 122 - 483 IPR004030
domain Flavodoxin/nitric oxide synthase 522 - 705 IPR008254
domain FAD-binding domain, ferredoxin reductase-type 758 - 1004 IPR017927

Functions

Description
EC Number 1.14.13.39 With NADH or NADPH as one donor, and incorporation of one atom of oxygen
Subcellular Localization
  • Membrane, caveola
  • Cytoplasm, cytoskeleton
  • Golgi apparatus
  • Cell membrane
  • Specifically associates with actin cytoskeleton in the G2 phase of the cell cycle, which is favored by interaction with NOSIP and results in a reduced enzymatic activity
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

6 GO annotations of cellular component

Name Definition
caveola A membrane raft that forms small pit, depression, or invagination that communicates with the outside of a cell and extends inward, indenting the cytoplasm and the cell membrane. Examples include flask-shaped invaginations of the plasma membrane in adipocytes associated with caveolin proteins, and minute pits or incuppings of the cell membrane formed during pinocytosis. Caveolae may be pinched off to form free vesicles within the cytoplasm.
cytoskeleton A cellular structure that forms the internal framework of eukaryotic and prokaryotic cells. The cytoskeleton includes intermediate filaments, microfilaments, microtubules, the microtrabecular lattice, and other structures characterized by a polymeric filamentous nature and long-range order within the cell. The various elements of the cytoskeleton not only serve in the maintenance of cellular shape but also have roles in other cellular functions, including cellular movement, cell division, endocytosis, and movement of organelles.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
Golgi apparatus A membrane-bound cytoplasmic organelle of the endomembrane system that further processes the core oligosaccharides (e.g. N-glycans) added to proteins in the endoplasmic reticulum and packages them into membrane-bound vesicles. The Golgi apparatus operates at the intersection of the secretory, lysosomal, and endocytic pathways.
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.

7 GO annotations of molecular function

Name Definition
calmodulin binding Binding to calmodulin, a calcium-binding protein with many roles, both in the calcium-bound and calcium-free states.
flavin adenine dinucleotide binding Binding to FAD, flavin-adenine dinucleotide, the coenzyme or the prosthetic group of various flavoprotein oxidoreductase enzymes, in either the oxidized form, FAD, or the reduced form, FADH2.
FMN binding Binding to flavin mono nucleotide. Flavin mono nucleotide (FMN) is the coenzyme or the prosthetic group of various flavoprotein oxidoreductase enzymes.
heme binding Binding to a heme, a compound composed of iron complexed in a porphyrin (tetrapyrrole) ring.
metal ion binding Binding to a metal ion.
NADP binding Binding to nicotinamide-adenine dinucleotide phosphate, a coenzyme involved in many redox and biosynthetic reactions; binding may be to either the oxidized form, NADP+, or the reduced form, NADPH.
nitric-oxide synthase activity Catalysis of the reaction

7 GO annotations of biological process

Name Definition
arginine catabolic process The chemical reactions and pathways resulting in the breakdown of arginine, 2-amino-5-(carbamimidamido)pentanoic acid.
negative regulation of blood pressure Any process in which the force of blood traveling through the circulatory system is decreased.
nitric oxide biosynthetic process The chemical reactions and pathways resulting in the formation of nitric oxide, nitrogen monoxide (NO), a colorless gas only slightly soluble in water.
nitric oxide mediated signal transduction Any intracellular signal transduction in which the signal is passed on within the cell via nitric oxide (NO). Includes synthesis of nitric oxide, receptors/sensors for nitric oxide (such as soluble guanylyl cyclase/sGC) and downstream effectors that further transmit the signal within the cell. Nitric oxide transmits its downstream effects through either cyclic GMP (cGMP)-dependent or independent mechanisms.
response to hormone Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a hormone stimulus.
response to lipopolysaccharide Any process that results in a change in state or activity of an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lipopolysaccharide stimulus; lipopolysaccharide is a major component of the cell wall of gram-negative bacteria.
vasodilation An increase in the internal diameter of blood vessels, especially arterioles or capillaries, due to relaxation of smooth muscle cells that line the vessels, and usually resulting in a decrease in blood pressure.

11 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
P29473 NOS3 Nitric oxide synthase, endothelial Bos taurus (Bovine) EV
Q9TUX8 NOS3 Nitric oxide synthase 3 Canis lupus familiaris (Dog) (Canis familiaris) SS
Q9UBK8 MTRR Methionine synthase reductase Homo sapiens (Human) PR
P29475 NOS1 Nitric oxide synthase, brain Homo sapiens (Human) SS
P29474 NOS3 Nitric oxide synthase, endothelial Homo sapiens (Human) SS
Q8C1A3 Mtrr Methionine synthase reductase Mus musculus (Mouse) PR
P70313 Nos3 Nitric oxide synthase 3 Mus musculus (Mouse) SS
Q498R1 Mtrr Methionine synthase reductase Rattus norvegicus (Rat) PR
P29476 Nos1 Nitric oxide synthase, brain Rattus norvegicus (Rat) SS
Q62600 Nos3 Nitric oxide synthase 3 Rattus norvegicus (Rat) SS
Q9FKW6 LFNR1 Ferredoxin--NADP reductase, leaf isozyme 1, chloroplastic Arabidopsis thaliana (Mouse-ear cress) PR
10 20 30 40 50 60
MGNLKSVGQE PGPPCGLGLG LGLGLCGKQG PATPAPEPSR APAPATPHAP EHSPAPNSPT
70 80 90 100 110 120
LTRPPEGPKF PRVKNWEVGS ITYDTLCAQS QQDGPCTPRR CLGSLVLPRK LQSRPSPGPP
130 140 150 160 170 180
PAEQLLSQAR DFINQYYSSI KRSGSQAHEE RLQEVEAEVA TTGTYHLGES ELVFGAKQAW
190 200 210 220 230 240
RNAPRCVGRI QWGKLQVFDA RDCSSAQEMF TYICNHIKYA TNRGNLRSAI TVFPQRTPGR
250 260 270 280 290 300
GDFRIWNSQL VRYAGYRQQD GSVRGDPANV EITELCIQHG WTPGNGRFDV LPLLLQAPDE
310 320 330 340 350 360
PPELFALPPE LVLEVPLEHP TLEWFAALGL RWYALPAVSN MLLEIGGLEF PAAPFSGWYM
370 380 390 400 410 420
STEIGTRNLC DPHRYNILED VAVCMDLDTR TTSSLWKDKA AVEINLAVLH SYQLAKVTIV
430 440 450 460 470 480
DHHAATASFM KHLENEQKAR GGCPADWAWI VPPISGSLTP VFHQEMVNYV LSPAFRYQPD
490 500 510 520 530 540
PWKGSAAKGT GIARKKTFKE VANAVKISAS LMATVMPKRV KASILYASET VRAQSYAQQL
550 560 570 580 590 600
GRLFRKAFDP RVLCMDEYDV VSLEHETLVL VVTSTFGNGD PPENGESFAA ALMEMSGPYN
610 620 630 640 650 660
GSPRPEQHRS YKIRFNSVSC SDPLVSSWRR KRKESSNTDS AGALGTLRFC VFGLGSRAYP
670 680 690 700 710 720
HFCAFARAVD TRLEELGGER LLQLGQGDEL CGQEEAFRGW AQAAFQASCE TFCVGEDAKA
730 740 750 760 770 780
AARDIFSPKR SWKRQRYRLS AQVEGLQLLP GLVHVHRRKM FQATVLSVEN LQSSKSTRAT
790 800 810 820 830 840
ILVRLDTEGQ EGLQYQPGDH IGICPPNRTG LVEALLSRVE DPTPPTESVG VEQLEKGSPG
850 860 870 880 890 900
GPPPSWVRDP RLPPYTLRQA LTFFLDITSP PSPRLLRVLS TLAEEPSEQQ ELETLSQDPR
910 920 930 940 950 960
RYEEWKWFRC PTLLEVLEQF PSVALPTPLL LTQLALLQPR YYSVSSAPST YPGEIHPTVA
970 980 990 1000 1010 1020
VLAYRTQDGL GPLHYGVCST WLGQLKPGDP VPCFIRAAPS FRLPPDPSLP CILVGPGTGI
1030 1040 1050 1060 1070 1080
APFRGFWQER LHDIESKGLQ PAPMTLVFGC RCSQLDHLYR DEVQDAQQRG VFGRVLTAFS
1090 1100 1110 1120 1130 1140
REPDSPKTYV QDILRTELAA EVHRVLCLER GHMFVCGDVT MATSVLQTVQ RILATEGNME
1150 1160 1170 1180 1190 1200
LDEAGDVIGV LRDQQRYHED IFGLTLRTQE VTSRIRTQSF SLQERHLRGA VPWTFDPPGP
DTPGP