ID F1LSH9_RAT Unreviewed; 1146 AA.
AC F1LSH9;
DT 03-MAY-2011, integrated into UniProtKB/TrEMBL.
DT 25-MAY-2022, sequence version 3.
DT 27-MAR-2024, entry version 94.
DE RecName: Full=Nitric oxide synthase {ECO:0000256|PIRNR:PIRNR000333};
DE EC=1.14.13.39 {ECO:0000256|PIRNR:PIRNR000333};
GN Name=Nos2 {ECO:0000313|Ensembl:ENSRNOP00000016133.5,
GN ECO:0000313|RGD:3185};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116 {ECO:0000313|Ensembl:ENSRNOP00000016133.5, ECO:0000313|Proteomes:UP000002494};
RN [1] {ECO:0000313|Ensembl:ENSRNOP00000016133.5, ECO:0000313|Proteomes:UP000002494}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway {ECO:0000313|Ensembl:ENSRNOP00000016133.5,
RC ECO:0000313|Proteomes:UP000002494};
RX PubMed=15057822; DOI=10.1038/nature02426;
RG Rat Genome Sequencing Project Consortium;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2] {ECO:0007829|PubMed:16641100}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
RN [3] {ECO:0000313|Ensembl:ENSRNOP00000016133.5}
RP IDENTIFICATION.
RC STRAIN=Brown Norway {ECO:0000313|Ensembl:ENSRNOP00000016133.5};
RG Ensembl;
RL Submitted (NOV-2023) to UniProtKB.
CC -!- FUNCTION: Produces nitric oxide (NO) which is a messenger molecule with
CC diverse functions. {ECO:0000256|PIRNR:PIRNR000333}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + 2 L-arginine + 3 NADPH + 4 O2 = 4 H2O + 2 L-citrulline
CC + 3 NADP(+) + 2 nitric oxide; Xref=Rhea:RHEA:19897,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16480, ChEBI:CHEBI:32682, ChEBI:CHEBI:57743,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.14.13.39;
CC Evidence={ECO:0000256|ARBA:ARBA00035595};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19898;
CC Evidence={ECO:0000256|ARBA:ARBA00035595};
CC -!- COFACTOR:
CC Name=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin;
CC Xref=ChEBI:CHEBI:59560; Evidence={ECO:0000256|ARBA:ARBA00001950};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000256|PIRNR:PIRNR000333};
CC Note=Binds 1 FAD. {ECO:0000256|PIRNR:PIRNR000333};
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000256|PIRNR:PIRNR000333};
CC Note=Binds 1 FMN. {ECO:0000256|PIRNR:PIRNR000333};
CC -!- COFACTOR:
CC Name=heme b; Xref=ChEBI:CHEBI:60344;
CC Evidence={ECO:0000256|ARBA:ARBA00001970,
CC ECO:0000256|PIRNR:PIRNR000333};
CC -!- SIMILARITY: Belongs to the NOS family. {ECO:0000256|ARBA:ARBA00006267,
CC ECO:0000256|PIRNR:PIRNR000333}.
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DR RefSeq; XP_006247011.1; XM_006246949.3.
DR AlphaFoldDB; F1LSH9; -.
DR PaxDb; 10116-ENSRNOP00000016133; -.
DR Ensembl; ENSRNOT00000016133.7; ENSRNOP00000016133.5; ENSRNOG00000057443.2.
DR RGD; 3185; Nos2.
DR VEuPathDB; HostDB:ENSRNOG00000057443; -.
DR eggNOG; KOG1158; Eukaryota.
DR GeneTree; ENSGT00940000159752; -.
DR HOGENOM; CLU_001570_16_0_1; -.
DR TreeFam; TF324410; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000057443; Expressed in ovary and 11 other cell types or tissues.
DR ExpressionAtlas; F1LSH9; baseline and differential.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0010181; F:FMN binding; IEA:InterPro.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR GO; GO:0004517; F:nitric-oxide synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0070887; P:cellular response to chemical stimulus; IEA:UniProt.
DR GO; GO:0006809; P:nitric oxide biosynthetic process; IEA:InterPro.
DR CDD; cd00795; NOS_oxygenase_euk; 1.
DR Gene3D; 3.40.50.360; -; 2.
DR Gene3D; 6.10.250.410; -; 1.
DR Gene3D; 3.90.440.10; Nitric Oxide Synthase;Heme Domain;Chain A domain 2; 1.
DR Gene3D; 3.40.50.80; Nucleotide-binding domain of ferredoxin-NADP reductase (FNR) module; 1.
DR Gene3D; 2.40.30.10; Translation factors; 1.
DR InterPro; IPR003097; CysJ-like_FAD-binding.
DR InterPro; IPR017927; FAD-bd_FR_type.
DR InterPro; IPR001094; Flavdoxin-like.
DR InterPro; IPR008254; Flavodoxin/NO_synth.
DR InterPro; IPR001709; Flavoprot_Pyr_Nucl_cyt_Rdtase.
DR InterPro; IPR029039; Flavoprotein-like_sf.
DR InterPro; IPR039261; FNR_nucleotide-bd.
DR InterPro; IPR023173; NADPH_Cyt_P450_Rdtase_alpha.
DR InterPro; IPR044943; NOS_dom_1.
DR InterPro; IPR044940; NOS_dom_2.
DR InterPro; IPR044944; NOS_dom_3.
DR InterPro; IPR012144; NOS_euk.
DR InterPro; IPR004030; NOS_N.
DR InterPro; IPR036119; NOS_N_sf.
DR InterPro; IPR001433; OxRdtase_FAD/NAD-bd.
DR InterPro; IPR017938; Riboflavin_synthase-like_b-brl.
DR PANTHER; PTHR43410; NITRIC OXIDE SYNTHASE OXYGENASE; 1.
DR PANTHER; PTHR43410:SF1; NITRIC OXIDE SYNTHASE OXYGENASE; 1.
DR Pfam; PF00667; FAD_binding_1; 1.
DR Pfam; PF00258; Flavodoxin_1; 1.
DR Pfam; PF00175; NAD_binding_1; 1.
DR Pfam; PF02898; NO_synthase; 1.
DR PIRSF; PIRSF000333; NOS; 2.
DR PRINTS; PR00369; FLAVODOXIN.
DR PRINTS; PR00371; FPNCR.
DR SUPFAM; SSF52343; Ferredoxin reductase-like, C-terminal NADP-linked domain; 1.
DR SUPFAM; SSF52218; Flavoproteins; 1.
DR SUPFAM; SSF56512; Nitric oxide (NO) synthase oxygenase domain; 1.
DR SUPFAM; SSF63380; Riboflavin synthase domain-like; 1.
DR PROSITE; PS51384; FAD_FR; 1.
DR PROSITE; PS50902; FLAVODOXIN_LIKE; 1.
DR PROSITE; PS60001; NOS; 1.
PE 1: Evidence at protein level;
KW Calmodulin-binding {ECO:0000256|ARBA:ARBA00022860,
KW ECO:0000256|PIRNR:PIRNR000333};
KW FAD {ECO:0000256|ARBA:ARBA00022827, ECO:0000256|PIRNR:PIRNR000333};
KW Flavoprotein {ECO:0000256|ARBA:ARBA00022630};
KW FMN {ECO:0000256|ARBA:ARBA00022643, ECO:0000256|PIRNR:PIRNR000333};
KW Heme {ECO:0000256|ARBA:ARBA00022617, ECO:0000256|PIRNR:PIRNR000333};
KW Iron {ECO:0000256|ARBA:ARBA00023004, ECO:0000256|PIRNR:PIRNR000333};
KW Metal-binding {ECO:0000256|ARBA:ARBA00022723,
KW ECO:0000256|PIRNR:PIRNR000333};
KW NADP {ECO:0000256|ARBA:ARBA00022857, ECO:0000256|PIRNR:PIRNR000333};
KW Oxidoreductase {ECO:0000256|ARBA:ARBA00023002,
KW ECO:0000256|PIRNR:PIRNR000333};
KW Reference proteome {ECO:0000313|Proteomes:UP000002494}.
FT DOMAIN 535..673
FT /note="Flavodoxin-like"
FT /evidence="ECO:0000259|PROSITE:PS50902"
FT DOMAIN 726..966
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000259|PROSITE:PS51384"
FT REGION 29..58
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 196
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000256|PIRSR:PIRSR000333-1"
SQ SEQUENCE 1146 AA; 130302 MW; B5C69B4811FCFFB2 CRC64;
MREGLSSACD AARPRLCRFL RRIFGPKVAS RVGPASPTTQ DDPKSHKHQN GFPQFLTGTA
QNVPESLDKL HVTPSTRPQH VRIKNWGNGE IFHDTLHHKA TSDISCKSKL CMGSIMNSKS
LTRGPRDKPT PVEELLPQAI EFINQYYGSF KEAKIEEHLA RLEAVTKEIE TTGTYQLTLD
ELIFATKMAW RNAPRCIGRI QWSNLQVFDA RSCSTASEMF QHICRHILYA TNSGNIRSAI
TVFPQRSDGK HDFRIWNSQL IRYAGYQMPD GTIRGDPATL EFTQLCIDLG WKPRYGRFDV
LPLVLQAHGQ DPEVFEIPPD LVLEVTMEHP KYEWFQELGL KWYALPAVAN MLLEVGGLEF
PACPFNGWYM GTEIGVRDFC DTQRYNILEE VGRRMGLETH TLASLWKDRA VTEINAAVLH
SFQKQNVTIM DHHTASESFM KHMQNEYRAR GGCPADWIWL VPPVSGSITP VFHQEMLNYV
LSPFYYYQIE PWKTHIWQDE KLRPRRREIR FTVLVKAVFF ASVLMRKVMA SRVRATVLFA
TETGKSEALA RDLAALFSYA FNTKVVCMEQ YKANTLEEEQ LLLVVTSTFG NGDCPSNGQT
LKKSLFMMKE LGHTFRYAVF GLGSSMYPQF CAFAHDIDQK LSHLGASQLA PTGEGDELSG
QEDAFRSWAV QTFRAACETF DVRSKHCIQI PKRYTSNATW EPEQYKLTQS PEPLDLNKAL
SSIHAKNVFT MRLKSLQNLQ SEKSSRTTLL VQLTFEGSRG PSYLPGEHLG IFPGNQTGLV
QGILERVVDC SSPDQTVCLE VLDESGSYWV KDKRLPPCSL RQALTYFLDI TTPPTQLQLH
KLARFATEET HRQRLEALCQ PSEYNDWKFS NNPTFLEVLE EFPSLRVPAA FLLSQLPILK
PRYYSISSSQ DHTPSEVHLT VAVVTYRTRD GQGPLHHGVC STWINNLKPE DPVPCFVRSV
SGFQLPEDPS QPCILIGPGT GIAPFRSFWQ QRLHDSQHRG LKGGRMTLVF GCRHPEEDHL
YQEEMQEMVR KGVLFQVHTG YSRLPGKPKV YVQDILQKEL ADEVFSVLHG EQGHLYVCGD
VRMARDVATT LKKLVAAKLN LSEEQVEDYF FQLKSQKRYH EDIFGAVFSY GAKKGNTLEE
PKGTRL
//
