ID NOS3_BOVIN STANDARD; PRT; 1204 AA. AC P29473; DT 01-APR-1993 (Rel. 25, Created) DT 01-JUL-1993 (Rel. 26, Last sequence update) DT 30-MAY-2000 (Rel. 39, Last annotation update) DE NITRIC-OXIDE SYNTHASE, ENDOTHELIAL (EC 1.14.13.39) (EC-NOS) (NOS, TYPE DE III) (NOSIII) (ENDOTHELIAL NOS) (ENOS) (CONSTITUTIVE NOS) (CNOS). GN NOS3. OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Cetartiodactyla; Ruminantia; Pecora; Bovoidea; OC Bovidae; Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP SEQUENCE FROM N.A. RX MEDLINE=92335295; PubMed=1378626; RA Lamas S., Marsden P.A., Li G.K., Tempst P., Michel T.; RT "Endothelial nitric oxide synthase: molecular cloning and RT characterization of a distinct constitutive enzyme isoform."; RL Proc. Natl. Acad. Sci. U.S.A. 89:6348-6352(1992). RN [2] RP SEQUENCE FROM N.A. RX MEDLINE=93055452; PubMed=1385480; RA Nishida K., Harrison D.G., Navas J.P., Fisher A.A., Dockery S.P., RA Uematsu M., Nerem R.M., Alexander R.W., Murphy T.J.; RT "Molecular cloning and characterization of the constitutive bovine RT aortic endothelial cell nitric oxide synthase."; RL J. Clin. Invest. 90:2092-2096(1992). RN [3] RP SEQUENCE FROM N.A. RC TISSUE=AORTIC ENDOTHELIUM; RX MEDLINE=92348367; PubMed=1379225; RA Sessa W.C., Harrison J.K., Barber C.M., Zeng D., Durieux M.E., RA D'Angelo D.D., Lynch K.R., Peach M.J.; RT "Molecular cloning and expression of a cDNA encoding endothelial cell RT nitric oxide synthase."; RL J. Biol. Chem. 267:15274-15276(1992). RN [4] RP MYRISTOYLATION. RX MEDLINE=93231982; PubMed=7682550; RA Busconi L., Michel T.; RT "Endothelial nitric oxide synthase. N-terminal myristoylation RT determines subcellular localization."; RL J. Biol. Chem. 268:8410-8413(1993). RN [5] RP PALMITOYLATION. RX MEDLINE=96102197; PubMed=8524847; RA Robinson L.J., Michel T.; RT "Mutagenesis of palmitoylation sites in endothelial nitric oxide RT synthase identifies a novel motif for dual acylation and subcellular RT targeting."; RL Proc. Natl. Acad. Sci. U.S.A. 92:11776-11780(1995). RN [6] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 66-481. RX MEDLINE=99091052; PubMed=9875848; RA Raman C.S., Li H., Martasek P., Kral V., Masters B.S., Poulos T.L.; RT "Crystal structure of constitutive endothelial nitric oxide synthase: RT a paradigm for pterin function involving a novel metal center."; RL Cell 95:939-950(1998). CC -!- FUNCTION: PRODUCES NITRIC OXIDE (NO) WHICH IS IMPLICATED IN CC VASCULAR SMOOTH MUSCLE RELAXATION THROUGH A CGMP-MEDIATED SIGNAL CC TRANSDUCTION PATHWAY. NO MEDIATES VASCULAR ENDOTHELIAL GROWTH CC FACTOR (VEGF)-INDUCED ANGIOGENESIS IN CORONARY VESSELS AND CC PROMOTES BLOOD CLOTTING THROUGH THE ACTIVATION OF PLATELETS. CC -!- CATALYTIC ACTIVITY: L-ARGININE + N NADPH + M O(2) = CITRULLINE + CC NITRIC OXIDE + N NADP(+). CC -!- COFACTOR: HEME. BINDS ONE MOLE EACH OF FAD AND FMN. ALSO REQUIRES CC TETRAHYDROBIOPTERIN (BH4) WHICH MAY STABILIZE THE DIMERIC FORM OF CC THE ENZYME. CC -!- ENZYME REGULATION: STIMULATED BY CALCIUM/CALMODULIN. CC -!- SUBUNIT: HOMODIMER. CC -!- SIMILARITY: BELONGS TO THE NOS FAMILY. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; M99057; AAA30667.1; -. DR EMBL; M89952; AAA30494.1; -. DR EMBL; M95674; AAA30669.1; -. DR PDB; 1NSE; 18-MAY-99. DR PDB; 2NSE; 25-MAY-99. DR PDB; 3NSE; 18-MAY-99. DR PDB; 4NSE; 18-MAY-99. DR INTERPRO; IPR001094; -. DR INTERPRO; IPR001433; -. DR INTERPRO; IPR001709; -. DR INTERPRO; IPR003097; -. DR PFAM; PF00667; FAD_binding; 1. DR PFAM; PF00175; oxidored_fad; 1. DR PRINTS; PR00369; FLAVODOXIN. DR PRINTS; PR00371; FPNCR. KW Oxidoreductase; NADP; FAD; FMN; Calmodulin-binding; Myristate; KW Lipoprotein; Palmitate; Phosphorylation; Calcium-binding; Heme; KW Zinc; Metal-binding; Multigene family; 3D-structure. FT INIT_MET 0 0 FT BINDING 185 185 HEME (BY SIMILARITY). FT DOMAIN 491 511 CALMODULIN-BINDING (POTENTIAL). FT NP_BIND 650 681 FMN (PYRIMIDINE PART) (BY SIMILARITY). FT NP_BIND 794 805 FAD (ADP PART) (BY SIMILARITY). FT NP_BIND 936 946 FAD (FLAVIN PART) (BY SIMILARITY). FT NP_BIND 1011 1029 NADP (RIBOSE PART) (BY SIMILARITY). FT NP_BIND 1109 1124 NADP (ADP PART) (BY SIMILARITY). FT LIPID 1 1 MYRISTATE. FT LIPID 14 14 PALMITATE. FT LIPID 25 25 PALMITATE. FT METAL 95 95 ZINC. FT METAL 100 100 ZINC. FT MOD_RES 142 142 PHOSPHORYLATION (BY CAPK). FT CONFLICT 99 99 C -> R (IN REF. 3). FT CONFLICT 164 164 Y -> I (IN REF. 3). FT CONFLICT 317 327 EHPTLEWFAAL -> GAPHTGVVRGP (IN REF. 3). FT CONFLICT 454 454 S -> Y (IN REF. 3). FT CONFLICT 458 458 T -> P (IN REF. 3). FT CONFLICT 740 740 T -> A (IN REF. 3). FT CONFLICT 803 804 CP -> SA (IN REF. 3). FT CONFLICT 856 856 L -> V (IN REF. 3). FT CONFLICT 906 907 WF -> LV (IN REF. 3). FT CONFLICT 1041 1041 A -> H (IN REF. 3). SQ SEQUENCE 1204 AA; 133155 MW; D017210062ABE4B0 CRC64; GNLKSVGQEP GPPCGLGLGL GLGLCGKQGP ASPAPEPSRA PAPATPHAPD HSPAPNSPTL TRPPEGPKFP RVKNWELGSI TYDTLCAQSQ QDGPCTPRCC LGSLVLPRKL QTRPSPGPPP AEQLLSQARD FINQYYSSIK RSGSQAHEER LQEVEAEVAS TGTYHLRESE LVFGAKQAWR NAPRCVGRIQ WGKLQVFDAR DCSSAQEMFT YICNHIKYAT NRGNLRSAIT VFPQRAPGRG DFRIWNSQLV RYAGYRQQDG SVRGDPANVE ITELCIQHGW TPGNGRFDVL PLLLQAPDEA PELFVLPPEL VLEVPLEHPT LEWFAALGLR WYALPAVSNM LLEIGGLEFS AAPFSGWYMS TEIGTRNLCD PHRYNILEDV AVCMDLDTRT TSSLWKDKAA VEINLAVLHS FQLAKVTIVD HHAATVSFMK HLDNEQKARG GCPADWAWIV PPISGSLTPV FHQEMVNYIL SPAFRYQPDP WKGSATKGAG ITRKKTFKEV ANAVKISASL MGTLMAKRVK ATILYASETG RAQSYAQQLG RLFRKAFDPR VLCMDEYDVV SLEHEALVLV VTSTFGNGDP PENGESFAAA LMEMSGPYNS SPRPEQHKSY KIRFNSVSCS DPLVSSWRRK RKESSNTDSA GALGTLRFCV FGLGSRAYPH FCAFARAVDT RLEELGGERL LQLGQGDELC GQEEAFRGWA KAAFQASCET FCVGEEAKAA AQDIFSPKRS WKRQRYRLST QAEGLQLLPG LIHVHRRKMF QATVLSVENL QSSKSTRATI LVRLDTAGQE GLQYQPGDHI GICPPNRPGL VEALLSRVED PPPPTESVAV EQLEKGSPGG PPPSWVRDPR LPPCTLRQAL TFFLDITSPP SPRLLRLLST LAEEPSEQQE LETLSQDPRR YEEWKWFRCP TLLEVLEQFP SVALPAPLLL TQLPLLQPRY YSVSSAPNAH PGEVHLTVAV LAYRTQDGLG PLHYGVCSTW LSQLKTGDPV PCFIRGAPSF RLPPDPYVPC ILVGPGTGIA PFRGFWQERL HDIESKGLQP APMTLVFGCR CSQLDHLYRD EVQDAQERGV FGRVLTAFSR EPDSPKTYVQ DILRTELAAE VHRVLCLERG HMFVCGDVTM ATSVLQTVQR ILATEGDMEL DEAGDVIGVL RDQQRYHEDI FGLTLRTQEV TSRIRTQSFS LQERHLRGAV PWAFDPPGPD TPGP //