P29473

EV
Gene name
NOS3
Protein name
Nitric oxide synthase, endothelial
Names
Constitutive NOS, cNOS, EC-NOS, Endothelial NOS, eNOS, NOS type III, NOSIII
Species
Bos taurus (Bovine)
KEGG Pathway
EC number
Protein Class
NITRIC OXIDE SYNTHASE OXYGENASE (PTHR43410)

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)

595-639 (Autoinhibitory loop) EV

Target domain

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

Relief mechanism

Partner binding

Assay

Deletion assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

129 structures for P29473

Entry ID Method Resolution Chain Position Source
1D0C X-ray 165 A A/B 39-482 PDB
1D0O X-ray 195 A A/B 39-482 PDB
1D1V X-ray 193 A A/B 39-482 PDB
1D1W X-ray 200 A A/B 39-482 PDB
1D1X X-ray 200 A A/B 39-482 PDB
1D1Y X-ray 220 A A/B 39-482 PDB
1DM6 X-ray 195 A A/B 39-482 PDB
1DM7 X-ray 210 A A/B 39-482 PDB
1DM8 X-ray 225 A A/B 39-482 PDB
1DMI X-ray 200 A A/B 39-482 PDB
1DMJ X-ray 235 A A/B 39-482 PDB
1DMK X-ray 190 A A/B 39-482 PDB
1ED4 X-ray 186 A A/B 39-482 PDB
1ED5 X-ray 180 A A/B 39-482 PDB
1ED6 X-ray 205 A A/B 39-482 PDB
1FOI X-ray 193 A A/B 39-482 PDB
1FOJ X-ray 210 A A/B 39-482 PDB
1FOL X-ray 220 A A/B 39-482 PDB
1FOO X-ray 200 A A/B 39-482 PDB
1FOP X-ray 230 A A/B 39-482 PDB
1I83 X-ray 200 A A/B 39-482 PDB
1NSE X-ray 190 A A/B 39-482 PDB
1P6L X-ray 235 A A/B 67-483 PDB
1P6M X-ray 227 A A/B 67-483 PDB
1P6N X-ray 250 A A/B 67-483 PDB
1Q2O X-ray 174 A A/B 67-482 PDB
1RS8 X-ray 230 A A/B 67-482 PDB
1RS9 X-ray 222 A A/B 67-482 PDB
1ZZS X-ray 185 A A/B 67-482 PDB
1ZZT X-ray 214 A A/B 67-482 PDB
2G6O X-ray 190 A A/B 67-482 PDB
2HX2 X-ray 195 A A/B 67-482 PDB
2NSE X-ray 234 A A/B 39-482 PDB
3DQS X-ray 203 A A/B 67-482 PDB
3DQT X-ray 254 A A/B 67-482 PDB
3E7S X-ray 250 A A/B 57-487 PDB
3JWW X-ray 220 A A/B 39-482 PDB
3JWX X-ray 200 A A/B 39-482 PDB
3JWY X-ray 224 A A/B 39-482 PDB
3JWZ X-ray 240 A A/B 39-482 PDB
3N5P X-ray 239 A A/B 39-482 PDB
3N5Q X-ray 290 A A/B 39-482 PDB
3N5R X-ray 257 A A/B 39-482 PDB
3N5S X-ray 218 A A/B 39-482 PDB
3N5T X-ray 252 A A/B 39-482 PDB
3NLD X-ray 228 A A/B 39-482 PDB
3NLE X-ray 195 A A/B 39-482 PDB
3NLF X-ray 232 A A/B 39-482 PDB
3NLG X-ray 238 A A/B 39-482 PDB
3NLH X-ray 210 A A/B 39-482 PDB
3NLI X-ray 198 A A/B 39-482 PDB
3NLT X-ray 274 A A/B 39-482 PDB
3NLU X-ray 265 A A/B 39-482 PDB
3NSE X-ray 210 A A/B 39-482 PDB
3PNH X-ray 193 A A/B 67-482 PDB
3RQO X-ray 208 A A/B 40-482 PDB
3RQP X-ray 235 A A/B 40-482 PDB
4C3A X-ray 220 A A/B 40-482 PDB
4CAR X-ray 205 A A/B 40-482 PDB
4CFT X-ray 179 A A/B 40-482 PDB
4CTY X-ray 230 A A/B 40-482 PDB
4CTZ X-ray 201 A A/B 40-482 PDB
4CU0 X-ray 208 A A/B 40-482 PDB
4CU1 X-ray 189 A A/B 40-482 PDB
4CUL X-ray 223 A A/B 40-482 PDB
4CUM X-ray 233 A A/B 40-482 PDB
4CUN X-ray 248 A A/B 40-482 PDB
4CVG X-ray 231 A A/B 40-482 PDB
4CWV X-ray 234 A A/B 40-482 PDB
4CWW X-ray 216 A A/B 40-482 PDB
4CWX X-ray 215 A A/B 40-482 PDB
4CWY X-ray 215 A A/B 40-482 PDB
4CWZ X-ray 208 A A/B 40-482 PDB
4CX0 X-ray 220 A A/B 40-482 PDB
4CX1 X-ray 213 A A/B 40-482 PDB
4CX2 X-ray 204 A A/B 40-482 PDB
4D33 X-ray 209 A A/B 40-482 PDB
4D34 X-ray 225 A A/B 40-482 PDB
4D35 X-ray 218 A A/B 40-482 PDB
4D36 X-ray 205 A A/B 40-482 PDB
4D37 X-ray 210 A A/B 40-482 PDB
4D38 X-ray 230 A A/B 40-482 PDB
4D39 X-ray 200 A A/B 40-482 PDB
4D3A X-ray 225 A A/B 40-482 PDB
4IMX X-ray 225 A A/B 40-482 PDB
4JSK X-ray 228 A A/B 40-482 PDB
4JSL X-ray 204 A A/B 40-482 PDB
4JSM X-ray 225 A A/B 40-482 PDB
4K5H X-ray 225 A A/B 40-482 PDB
4K5I X-ray 208 A A/B 40-482 PDB
4K5J X-ray 236 A A/B 40-482 PDB
4K5K X-ray 200 A A/B 40-482 PDB
4KCP X-ray 207 A A/B 40-482 PDB
4KCQ X-ray 203 A A/B 40-482 PDB
4KCR X-ray 209 A A/B 40-482 PDB
4KCS X-ray 205 A A/B 40-482 PDB
4LUW X-ray 225 A A/B 41-482 PDB
4NSE X-ray 195 A A/B 39-482 PDB
4UH7 X-ray 223 A A/B 40-482 PDB
4UH8 X-ray 230 A A/B 40-482 PDB
4UH9 X-ray 214 A A/B 40-482 PDB
4UHA X-ray 220 A A/B 40-482 PDB
4UPQ X-ray 203 A A/B 40-482 PDB
4UPR X-ray 193 A A/B 40-482 PDB
4UPS X-ray 195 A A/B 40-482 PDB
4UPT X-ray 220 A A/B 40-482 PDB
5ADJ X-ray 222 A A/B 40-482 PDB
5ADK X-ray 180 A A/B 40-482 PDB
5ADL X-ray 221 A A/B 40-482 PDB
5ADM X-ray 220 A A/B 40-482 PDB
5ADN X-ray 200 A A/B 40-482 PDB
5FJ2 X-ray 205 A A/B 40-482 PDB
5FJ3 X-ray 220 A A/B 40-482 PDB
5FVY X-ray 210 A A/B 40-482 PDB
5FVZ X-ray 205 A A/B 40-482 PDB
5NSE X-ray 190 A A/B 39-482 PDB
5UOD X-ray 201 A A/B 40-482 PDB
5VV6 X-ray 200 A A/B 40-482 PDB
5VV7 X-ray 220 A A/B 40-482 PDB
5VV8 X-ray 215 A A/B 40-482 PDB
5VV9 X-ray 250 A A/B 40-482 PDB
5VVA X-ray 255 A A/B 40-482 PDB
5VVG X-ray 230 A A/B 40-482 PDB
5VVN X-ray 240 A A/B 40-482 PDB
6NSE X-ray 235 A A/B 39-482 PDB
7NSE X-ray 235 A A/B 39-482 PDB
8NSE X-ray 225 A A/B 39-482 PDB
9NSE X-ray 224 A A/B 39-482 PDB
AF-P29473-F1 Predicted AlphaFoldDB

No variants for P29473

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for P29473

No associated diseases with P29473

17 regional properties for P29473

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
Subcellular Localization
  • Cell membrane
  • Membrane, caveola
  • Cytoplasm, cytoskeleton
  • Golgi apparatus
  • 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 PTHR43410 NITRIC OXIDE SYNTHASE OXYGENASE
PANTHER Subfamily PTHR43410:SF1 NITRIC OXIDE SYNTHASE OXYGENASE
PANTHER Protein Class protein modifying enzyme
PANTHER Pathway Category No pathway information available

3 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.
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.

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: L-arginine + n NADPH + n H+ + m O2 = citrulline + nitric oxide + n NADP+.

8 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.
blood coagulation The sequential process in which the multiple coagulation factors of the blood interact, ultimately resulting in the formation of an insoluble fibrin clot; it may be divided into three stages: stage 1, the formation of intrinsic and extrinsic prothrombin converting principle; stage 2, the formation of thrombin; stage 3, the formation of stable fibrin polymers.
cellular response to laminar fluid shear stress Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a laminar fluid shear stress stimulus. Laminar fluid flow is the force acting on an object in a system where the fluid is moving across a solid surface in parallel layers.
mitochondrion organization A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of a mitochondrion; includes mitochondrial morphogenesis and distribution, and replication of the mitochondrial genome as well as synthesis of new mitochondrial components.
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors Any process that stops, prevents or reduces the frequency, rate or extent of extrinsic apoptotic signaling pathway via death domain receptors.
negative regulation of leukocyte cell-cell adhesion Any process that stops, prevents or reduces the frequency, rate or extent of leukocyte cell-cell adhesion.
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.
positive regulation of guanylate cyclase activity Any process that activates or increases the frequency, rate or extent of guanylate cyclase activity.

12 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q1JPJ0 NDOR1 NADPH-dependent diflavin oxidoreductase 1 Bos taurus (Bovine) PR
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
Q28969 NOS3 Nitric oxide synthase 3 Sus scrofa (Pig) 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 PASPAPEPSR APAPATPHAP DHSPAPNSPT
70 80 90 100 110 120
LTRPPEGPKF PRVKNWELGS ITYDTLCAQS QQDGPCTPRC CLGSLVLPRK LQTRPSPGPP
130 140 150 160 170 180
PAEQLLSQAR DFINQYYSSI KRSGSQAHEE RLQEVEAEVA STGTYHLRES ELVFGAKQAW
190 200 210 220 230 240
RNAPRCVGRI QWGKLQVFDA RDCSSAQEMF TYICNHIKYA TNRGNLRSAI TVFPQRAPGR
250 260 270 280 290 300
GDFRIWNSQL VRYAGYRQQD GSVRGDPANV EITELCIQHG WTPGNGRFDV LPLLLQAPDE
310 320 330 340 350 360
APELFVLPPE LVLEVPLEHP TLEWFAALGL RWYALPAVSN MLLEIGGLEF SAAPFSGWYM
370 380 390 400 410 420
STEIGTRNLC DPHRYNILED VAVCMDLDTR TTSSLWKDKA AVEINLAVLH SFQLAKVTIV
430 440 450 460 470 480
DHHAATVSFM KHLDNEQKAR GGCPADWAWI VPPISGSLTP VFHQEMVNYI LSPAFRYQPD
490 500 510 520 530 540
PWKGSATKGA GITRKKTFKE VANAVKISAS LMGTLMAKRV KATILYASET GRAQSYAQQL
550 560 570 580 590 600
GRLFRKAFDP RVLCMDEYDV VSLEHEALVL VVTSTFGNGD PPENGESFAA ALMEMSGPYN
610 620 630 640 650 660
SSPRPEQHKS YKIRFNSVSC SDPLVSSWRR KRKESSNTDS AGALGTLRFC VFGLGSRAYP
670 680 690 700 710 720
HFCAFARAVD TRLEELGGER LLQLGQGDEL CGQEEAFRGW AKAAFQASCE TFCVGEEAKA
730 740 750 760 770 780
AAQDIFSPKR SWKRQRYRLS TQAEGLQLLP GLIHVHRRKM FQATVLSVEN LQSSKSTRAT
790 800 810 820 830 840
ILVRLDTAGQ EGLQYQPGDH IGICPPNRPG LVEALLSRVE DPPPPTESVA VEQLEKGSPG
850 860 870 880 890 900
GPPPSWVRDP RLPPCTLRQA LTFFLDITSP PSPRLLRLLS TLAEEPSEQQ ELETLSQDPR
910 920 930 940 950 960
RYEEWKWFRC PTLLEVLEQF PSVALPAPLL LTQLPLLQPR YYSVSSAPNA HPGEVHLTVA
970 980 990 1000 1010 1020
VLAYRTQDGL GPLHYGVCST WLSQLKTGDP VPCFIRGAPS FRLPPDPYVP CILVGPGTGI
1030 1040 1050 1060 1070 1080
APFRGFWQER LHDIESKGLQ PAPMTLVFGC RCSQLDHLYR DEVQDAQERG VFGRVLTAFS
1090 1100 1110 1120 1130 1140
REPDSPKTYV QDILRTELAA EVHRVLCLER GHMFVCGDVT MATSVLQTVQ RILATEGDME
1150 1160 1170 1180 1190 1200
LDEAGDVIGV LRDQQRYHED IFGLTLRTQE VTSRIRTQSF SLQERHLRGA VPWAFDPPGP
DTPGP