NINAB_DROME
ID NINAB_DROME Reviewed; 620 AA.
AC Q9VFS2;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Carotenoid isomerooxygenase;
DE EC=1.13.11.65;
DE AltName: Full=Beta-carotene 15,15'-monooxygenase and retinoid isomerase;
DE AltName: Full=Beta-carotene dioxygenase and retinoid isomerase;
DE AltName: Full=Neither inactivation nor afterpotential mutant B;
GN Name=ninaB; Synonyms=beta-diox; ORFNames=CG9347;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY.
RX PubMed=10766819; DOI=10.1074/jbc.275.16.11915;
RA von Lintig J., Vogt K.;
RT "Filling the gap in vitamin A research. Molecular identification of an
RT enzyme cleaving beta-carotene to retinal.";
RL J. Biol. Chem. 275:11915-11920(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo, and Head;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [5]
RP FUNCTION, AND MUTAGENESIS OF GLU-280; MET-471 AND GLU-477.
RX PubMed=11158606; DOI=10.1073/pnas.98.3.1130;
RA von Lintig J., Dreher A., Kiefer C., Wernet M.F., Vogt K.;
RT "Analysis of the blind Drosophila mutant ninaB identifies the gene encoding
RT the key enzyme for vitamin A formation invivo.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:1130-1135(2001).
RN [6]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=14982930; DOI=10.1074/jbc.m400323200;
RA Gu G., Yang J., Mitchell K.A., O'Tousa J.E.;
RT "Drosophila ninaB and ninaD act outside of retina to produce rhodopsin
RT chromophore.";
RL J. Biol. Chem. 279:18608-18613(2004).
RN [7]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=17452532; DOI=10.1083/jcb.200610081;
RA Wang T., Jiao Y., Montell C.;
RT "Dissection of the pathway required for generation of vitamin A and for
RT Drosophila phototransduction.";
RL J. Cell Biol. 177:305-316(2007).
RN [8]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=17344064; DOI=10.1016/j.mcn.2007.02.001;
RA Yang J., O'Tousa J.E.;
RT "Cellular sites of Drosophila NinaB and NinaD activity in vitamin A
RT metabolism.";
RL Mol. Cell. Neurosci. 35:49-56(2007).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY.
RX PubMed=19889630; DOI=10.1074/jbc.m109.056101;
RA Voolstra O., Oberhauser V., Sumser E., Meyer N.E., Maguire M.E., Huber A.,
RA von Lintig J.;
RT "NinaB is essential for Drosophila vision but induces retinal degeneration
RT in opsin-deficient photoreceptors.";
RL J. Biol. Chem. 285:2130-2139(2010).
CC -!- FUNCTION: Catalyzes the oxidative cleavage at the 15,15'-double bond of
CC carotenoids and the simultaneous all-trans to 11-cis isomerization of
CC one cleavage product. Carotenoids like 11-cis retinal can promote
CC visual pigment biogenesis in the dark. Essential for the biosynthesis
CC of the 3-hydroxyretinal chromophore of rhodopsin from zeaxanthin and
CC for proper photoreceptor development. Also essential for larval light
CC perception. {ECO:0000269|PubMed:11158606, ECO:0000269|PubMed:14982930,
CC ECO:0000269|PubMed:17344064, ECO:0000269|PubMed:17452532,
CC ECO:0000269|PubMed:19889630}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-zeaxanthin + O2 = (3R)-11-cis-3-hydroxyretinal +
CC (3R)-all-trans-3-hydroxyretinal; Xref=Rhea:RHEA:33931,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:27547, ChEBI:CHEBI:52228,
CC ChEBI:CHEBI:66898; EC=1.13.11.65;
CC Evidence={ECO:0000269|PubMed:10766819, ECO:0000269|PubMed:19889630};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000250};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000250};
CC -!- PATHWAY: Cofactor metabolism; retinol metabolism.
CC -!- TISSUE SPECIFICITY: Expression follows organogenesis of the larval
CC Bolwig's organ (BO), which mediates larval photophobic behavior. In the
CC adult, expression is restricted exclusively to the brain. Expressed in
CC both neuronal cells and glia cells. Not active within photoreceptors.
CC Active within neuronal cells within the central nervous system.
CC {ECO:0000269|PubMed:10766819, ECO:0000269|PubMed:14982930,
CC ECO:0000269|PubMed:17344064, ECO:0000269|PubMed:17452532,
CC ECO:0000269|PubMed:19889630}.
CC -!- SIMILARITY: Belongs to the carotenoid oxygenase family. {ECO:0000305}.
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DR EMBL; AJ276682; CAB93141.1; -; mRNA.
DR EMBL; AE014297; AAF54978.1; -; Genomic_DNA.
DR EMBL; AY121617; AAM51944.1; -; mRNA.
DR RefSeq; NP_650307.2; NM_142050.3.
DR AlphaFoldDB; Q9VFS2; -.
DR SMR; Q9VFS2; -.
DR IntAct; Q9VFS2; 1.
DR STRING; 7227.FBpp0082288; -.
DR PaxDb; Q9VFS2; -.
DR DNASU; 41678; -.
DR EnsemblMetazoa; FBtr0082820; FBpp0082288; FBgn0002937.
DR GeneID; 41678; -.
DR KEGG; dme:Dmel_CG9347; -.
DR UCSC; CG9347-RA; d. melanogaster.
DR CTD; 41678; -.
DR FlyBase; FBgn0002937; ninaB.
DR VEuPathDB; VectorBase:FBgn0002937; -.
DR eggNOG; KOG1285; Eukaryota.
DR GeneTree; ENSGT00950000182913; -.
DR HOGENOM; CLU_016472_1_1_1; -.
DR InParanoid; Q9VFS2; -.
DR OMA; RDFFAVK; -.
DR OrthoDB; 895046at2759; -.
DR PhylomeDB; Q9VFS2; -.
DR BioCyc; MetaCyc:MON-17370; -.
DR BRENDA; 1.13.11.63; 1994.
DR BRENDA; 1.13.11.65; 1994.
DR Reactome; R-DME-2453902; The canonical retinoid cycle in rods (twilight vision).
DR Reactome; R-DME-975634; Retinoid metabolism and transport.
DR UniPathway; UPA00912; -.
DR BioGRID-ORCS; 41678; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 41678; -.
DR PRO; PR:Q9VFS2; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0002937; Expressed in head capsule and 11 other tissues.
DR ExpressionAtlas; Q9VFS2; baseline and differential.
DR Genevisible; Q9VFS2; DM.
DR GO; GO:0003834; F:beta-carotene 15,15'-dioxygenase activity; IDA:FlyBase.
DR GO; GO:0010436; F:carotenoid dioxygenase activity; IDA:FlyBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0004744; F:retinal isomerase activity; IDA:FlyBase.
DR GO; GO:0016121; P:carotene catabolic process; IBA:GO_Central.
DR GO; GO:0016119; P:carotene metabolic process; IDA:FlyBase.
DR GO; GO:0007602; P:phototransduction; TAS:FlyBase.
DR GO; GO:0007604; P:phototransduction, UV; IMP:FlyBase.
DR GO; GO:0007603; P:phototransduction, visible light; IMP:FlyBase.
DR GO; GO:0042574; P:retinal metabolic process; IDA:FlyBase.
DR GO; GO:0042572; P:retinol metabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0016063; P:rhodopsin biosynthetic process; IDA:FlyBase.
DR GO; GO:0035238; P:vitamin A biosynthetic process; IDA:FlyBase.
DR GO; GO:0009110; P:vitamin biosynthetic process; IMP:FlyBase.
DR InterPro; IPR004294; Carotenoid_Oase.
DR PANTHER; PTHR10543; PTHR10543; 1.
DR Pfam; PF03055; RPE65; 1.
PE 1: Evidence at protein level;
KW Iron; Metal-binding; Monooxygenase; Oxidoreductase; Reference proteome.
FT CHAIN 1..620
FT /note="Carotenoid isomerooxygenase"
FT /id="PRO_0000424157"
FT REGION 440..459
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 211
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 267
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 337
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 612
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT MUTAGEN 280
FT /note="E->K: In ninaB(P315); abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:11158606"
FT MUTAGEN 471
FT /note="M->L: In ninaB(P315); no effect."
FT /evidence="ECO:0000269|PubMed:11158606"
FT MUTAGEN 477
FT /note="E->A: In ninaB(P315); no effect."
FT /evidence="ECO:0000269|PubMed:11158606"
SQ SEQUENCE 620 AA; 69932 MW; 91EC22EB102C31C3 CRC64;
MAAGVFKSFM RDFFAVKYDE QRNDPQAERL DGNGRLYPNC SSDVWLRSCE REIVDPIEGH
HSGHIPKWIC GSLLRNGPGS WKVGDMTFGH LFDCSALLHR FAIRNGRVTY QNRFVDTETL
RKNRSAQRIV VTEFGTAAVP DPCHSIFDRF AAIFRPDSGT DNSMISIYPF GDQYYTFTET
PFMHRINPCT LATEARICTT DFVGVVNHTS HPHVLPSGTV YNLGTTMTRS GPAYTILSFP
HGEQMFEDAH VVATLPCRWK LHPGYMHTFG LTDHYFVIVE QPLSVSLTEY IKAQLGGQNL
SACLKWFEDR PTLFHLIDRV SGKLVQTYES EAFFYLHIIN CFERDGHVVV DICSYRNPEM
INCMYLEAIA NMQTNPNYAT LFRGRPLRFV LPLGTIPPAS IAKRGLVKSF SLAGLSAPQV
SRTMKHSVSQ YADITYMPTN GKQATAGEES PKRDAKRGRY EEENLVNLVT MEGSQAEAFQ
GTNGIQLRPE MLCDWGCETP RIYYERYMGK NYRYFYAISS DVDAVNPGTL IKVDVWNKSC
LTWCEENVYP SEPIFVPSPD PKSEDDGVIL ASMVLGGLND RYVGLIVLCA KTMTELGRCD
FHTNGPVPKC LHGWFAPNAI
