Reviewed, UniProtKB/Swiss-Prot Q9TUX8 (NOS3_CANFA)

Names and origin

Protein names

Recommended name:
    Nitric oxide synthase, endothelial
    EC=1.14.13.39
Alternative name(s):
    Endothelial NOS
      Short name=eNOS
    EC-NOS
    NOS type III
      Short name=NOSIII
    Constitutive NOS
      Short name=cNOS

Gene names

Name:	NOS3
Synonyms:	NOS

Organism

Canis familiaris (Dog)

Taxonomic identifier

9615 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Carnivora › Caniformia › Canidae › Canis

Protein attributes

Sequence length	1205 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Function	Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets By similarity.
Catalytic activity	L-arginine + n NADPH + n H+ + m O2 = citrulline + nitric oxide + n NADP+.
Cofactor	Heme group By similarity. Binds 1 FAD By similarity. Binds 1 FMN By similarity. Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme By similarity.
Enzyme regulation	Stimulated by calcium/calmodulin. Inhibited by NOSIP and NOSTRIN By similarity.
Subunit structure	Homodimer. Interacts with NOSIP and NOSTRIN By similarity.
Subcellular location	Membrane › caveola By similarity. Cytoplasm › cytoskeleton By similarity. Golgi apparatus By similarity. Cell membrane By similarity. Note: 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 By similarity.
Sequence similarities	Belongs to the NOS family. Contains 1 FAD-binding FR-type domain. Contains 1 flavodoxin-like domain.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Cytoskeleton Golgi apparatus Membrane
Ligand	Calcium Calmodulin-binding FAD FMN Heme Iron Metal-binding NADP Zinc
Molecular function	Oxidoreductase
PTM	Lipoprotein Myristate Palmitate Phosphoprotein
Gene Ontology (GO)
Biological process	oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell caveola Inferred from electronic annotation. Source: UniProtKB-SubCell cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	FAD binding Inferred from electronic annotation. Source: InterPro FMN binding Inferred from electronic annotation. Source: InterPro NADP or NADPH binding Inferred from electronic annotation. Source: InterPro calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW calmodulin binding Inferred from electronic annotation. Source: UniProtKB-KW electron carrier activity Inferred from electronic annotation. Source: InterPro heme binding Inferred from electronic annotation. Source: InterPro nitric-oxide synthase activity Inferred from electronic annotation. Source: EC zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 1205	1204	Nitric oxide synthase, endothelial		PRO_0000289580
Regions
	Domain	522 – 705	184	Flavodoxin-like
	Domain	758 – 1004	247	FAD-binding FR-type
	Nucleotide binding	651 – 682	32	FMN By similarity
	Nucleotide binding	795 – 806	12	FAD By similarity
	Nucleotide binding	937 – 947	11	FAD By similarity
	Nucleotide binding	1012 – 1030	19	NADP By similarity
	Nucleotide binding	1110 – 1125	16	NADP By similarity
	Region	100 – 488	389	Interaction with NOSIP By similarity
	Region	492 – 512	21	Calmodulin-binding Potential
Sites
	Metal binding	96	1	Zinc By similarity
	Metal binding	101	1	Zinc By similarity
	Metal binding	186	1	Iron (heme axial ligand) By similarity
Amino acid modifications
	Modified residue	83	1	Phosphotyrosine By similarity
	Modified residue	497	1	Phosphothreonine By similarity
	Modified residue	635	1	Phosphoserine By similarity
	Modified residue	1177	1	Phosphothreonine By similarity
	Modified residue	1179	1	Phosphoserine By similarity
	Lipidation	2	1	N-myristoyl glycine By similarity
	Lipidation	15	1	S-palmitoyl cysteine By similarity
	Lipidation	26	1	S-palmitoyl cysteine By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q9TUX8-1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: C150CDEB01685BA5	FASTA	1,205	133,046
	10 20 30 40 50 60 MGNLKSVGQE PGPPCGLGLG LGLGLCGKQG PASPTSEPSR APALAPPPSP PPAPDHSSPP 70 80 90 100 110 120 LTRPPDGPKF PRVKNWEVGS ITYDTLSAQS QQDGPCTPRR CLGSLVFPRK LQSRPSQNPA 130 140 150 160 170 180 PPEQLLSQAR DFISQYYSSI KRSGSQAHEQ RLQEVEAEVA ATGTYQLRES ELVFGAKQAW 190 200 210 220 230 240 RNAPRCVGRI QWGKLQVFDA RDCSSAQEMF TYICNHIKYA TNRGNLRSAI TVFPQRASGR 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 LSPAFRYQTD 490 500 510 520 530 540 PWKGSASKGA GVTRKKTFKE VANAVKISAS LMGTVMAKRV KATILYGSET GRAQSYAQQL 550 560 570 580 590 600 GRLFRKAFDP RVLCMDEYDV VSLEHETLVL VVTSTFGNGD PPENGESFAA ALMEMSGSYN 610 620 630 640 650 660 SSPRPEQHKS YKIRFNSVSC SDPLVSSWRR KRKESRNTDS AGALGTLRFC VFGLGSRAYP 670 680 690 700 710 720 HFCAFARAVD TRLEELGGER LLQLGQGDEL CGQEEAFGGW AQAAFQASWE TFCVGEDAKA 730 740 750 760 770 780 AARDIFSPKR TWKRQRYRLS AQAEGLQLLP GLIHVHRRKM VQATVLAVEN LQSSKSTRAT 790 800 810 820 830 840 ILVRLDTGSQ EALQYQPGDH IGICPPNRPG LVEALLSRVE DPPPPGEPVA VEQLEKGSPG 850 860 870 880 890 900 GPPPSWVRDP RLPPCTLRQA LTFFLDITSP PSPQLLRLLS TLAEESSEQQ ELESLSQDPR 910 920 930 940 950 960 RYEEWKWFRC PTLLEVLEQF PSVALPAPLL LTQLPLLQPR YYSVSSAPSA HPGEIHLTVA 970 980 990 1000 1010 1020 VLAYRTQDGL GPLHYGVCST WLSQLKAGDP VPCFIRGAPS FRLPPDPSLP CILVGPGTGI 1030 1040 1050 1060 1070 1080 APFRGFWQGR LHDIYSKGLQ PAPMTLVFGC RCSQLDHLYR DEVQDAQQRG VFGRVLTAFS 1090 1100 1110 1120 1130 1140 REPDSPKTYV QDILRTELAA EVHRVLCLER GHMFVCGDVT MATSVLQTVQ RILATEGDME 1150 1160 1170 1180 1190 1200 LDEAGDVIGV LRDQQRYHED IFGLTLRTQE VTSRIRTQSF SLQERHLRGA VPWALDPPGP DTVGP

References

[1]	"Assembly and characterization of canine heart endothelial nitric oxide synthase cDNA and 5'-flanking sequence by homology (RT-)PCR cloning." Schwemmer M., Bassenge E. Nitric Oxide 3:254-264(1999) [PubMed: 10442857] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Heart.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF143503 mRNA. Translation: AAD52161.1.
RefSeq	NP_001003158.1.
UniGene	Cfa.108
3D structure databases
HSSP	HSSP built from PDB template 1M9M based on UniProtKB P29474.
SMR	Q9TUX8. Positions 67-482.
ModBase	Search...
Genome annotation databases
Ensembl	ENSCAFG00000004687. Canis familiaris. [Contig view]
GeneID	403784.
KEGG	cfa:403784.
Phylogenomic databases
HOVERGEN	Q9TUX8.
Enzyme and pathway databases
BRENDA	1.14.13.39. 463.
Family and domain databases
InterPro	IPR003097. FAD-binding_1. IPR017927. Fd_Rdtase_FAD-bd. IPR001094. Flavdoxin-like. IPR008254. Flavodoxin/NO_synth. IPR001709. Flavoprot_Pyr_Nucl_cyt_Rdtase. IPR012144. Nitric-oxide_synthase. IPR004030. NO_synthase_oxygenase_reg. IPR001433. OxRdtase_FAD/NAD_bd. [Graphical view]
Gene3D	G3DSA:3.90.340.10. NO_synthase_oxygenase_reg. 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. [Graphical view]
PIRSF	PIRSF000333. NOS. 1 hit.
PRINTS	PR00369. FLAVODOXIN. PR00371. FPNCR.
PROSITE	PS51384. FAD_FR. 1 hit. PS50902. FLAVODOXIN_LIKE. 1 hit. PS60001. NOS. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

NOS3_CANFA

Accession

Primary (citable) accession number: Q9TUX8

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 29, 2007
Last sequence update:	May 1, 2000
Last modified:	June 16, 2009
This is version 51 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)