PROD_DROME
ID PROD_DROME Reviewed; 681 AA.
AC Q04499; O61349; Q8IQ45; Q8IQ46; Q8T0C7; Q9VRH7; Q9VRH8; Q9VRH9; Q9VRI2;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2005, sequence version 2.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Proline dehydrogenase 1, mitochondrial;
DE EC=1.5.5.2 {ECO:0000305|PubMed:8096642};
DE AltName: Full=Proline oxidase {ECO:0000303|PubMed:8096642};
DE AltName: Full=Protein sluggish-A;
DE Flags: Precursor;
GN Name=slgA; Synonyms=slg; ORFNames=CG1417;
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] (ISOFORM A), FUNCTION, CATALYTIC ACTIVITY,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND
RP DISRUPTION PHENOTYPE.
RC STRAIN=Canton-S;
RX PubMed=8096642; DOI=10.1073/pnas.90.7.2979;
RA Hayward D.C., Delaney S.J., Campbell H.D., Ghysen A., Benzer S.,
RA Kasprzak A.B., Cotsell J.N., Young I.G., Miklos G.L.G.;
RT "The sluggish-A gene of Drosophila melanogaster is expressed in the nervous
RT system and encodes proline oxidase, a mitochondrial enzyme involved in
RT glutamate biosynthesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:2979-2983(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM A).
RC STRAIN=Canton-S;
RX PubMed=9520435; DOI=10.1073/pnas.95.7.3731;
RA Maleszka R., de Couet H.G., Miklos G.L.G.;
RT "Data transferability from model organisms to human beings: insights from
RT the functional genomics of the flightless region of Drosophila.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:3731-3736(1998).
RN [3]
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 [4]
RP GENOME REANNOTATION, AND ALTERNATIVE SPLICING.
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC STRAIN=Berkeley; TISSUE=Embryo;
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).
CC -!- FUNCTION: Converts proline to delta-1-pyrroline-5-carboxylate
CC (PubMed:8096642). Involved in the conversion of proline to glutamate,
CC which functions as transmitter at neuromuscular junctions
CC (PubMed:8096642). Glutamate deficiency could possibly account for
CC reduced motor activity (PubMed:8096642). {ECO:0000269|PubMed:8096642,
CC ECO:0000303|PubMed:8096642}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a quinone + L-proline = (S)-1-pyrroline-5-carboxylate + a
CC quinol + H(+); Xref=Rhea:RHEA:23784, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17388, ChEBI:CHEBI:24646, ChEBI:CHEBI:60039,
CC ChEBI:CHEBI:132124; EC=1.5.5.2;
CC Evidence={ECO:0000305|PubMed:8096642};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23785;
CC Evidence={ECO:0000305|PubMed:8096642};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC -!- PATHWAY: Amino-acid degradation; L-proline degradation into L-
CC glutamate; L-glutamate from L-proline: step 1/2.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000269|PubMed:8096642}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=D;
CC IsoId=Q04499-1; Sequence=Displayed;
CC Name=A; Synonyms=F;
CC IsoId=Q04499-2; Sequence=VSP_015401, VSP_015402;
CC Name=B;
CC IsoId=Q04499-3; Sequence=VSP_015402;
CC Name=C;
CC IsoId=Q04499-4; Sequence=VSP_015400;
CC Name=E;
CC IsoId=Q04499-5; Sequence=VSP_015401;
CC -!- TISSUE SPECIFICITY: Most abundant in developing nervous system.
CC {ECO:0000269|PubMed:8096642}.
CC -!- DEVELOPMENTAL STAGE: Expressed in developing embryo as well as in
CC adult. {ECO:0000269|PubMed:8096642}.
CC -!- DISRUPTION PHENOTYPE: Flies exhibit reduced proline oxidase activity
CC which produces sluggish behavior. {ECO:0000269|PubMed:8096642}.
CC -!- SIMILARITY: Belongs to the proline oxidase family. {ECO:0000305}.
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DR EMBL; L07330; AAA02748.1; -; mRNA.
DR EMBL; AF017777; AAC28410.1; -; Genomic_DNA.
DR EMBL; AE014298; AAF50814.2; -; Genomic_DNA.
DR EMBL; AE014298; AAF50819.2; -; Genomic_DNA.
DR EMBL; AE014298; AAF50820.2; -; Genomic_DNA.
DR EMBL; AE014298; AAF50821.1; -; Genomic_DNA.
DR EMBL; AE014298; AAF50822.3; -; Genomic_DNA.
DR EMBL; AY069407; AAL39552.1; -; mRNA.
DR PIR; A47302; A47302.
DR RefSeq; NP_001245791.1; NM_001258862.2. [Q04499-3]
DR RefSeq; NP_001245792.1; NM_001258863.2. [Q04499-2]
DR RefSeq; NP_001245793.1; NM_001258864.2. [Q04499-2]
DR RefSeq; NP_001245794.1; NM_001258865.2. [Q04499-2]
DR RefSeq; NP_001245795.1; NM_001258866.2. [Q04499-3]
DR RefSeq; NP_001245796.1; NM_001258867.2. [Q04499-5]
DR RefSeq; NP_523433.2; NM_078709.4. [Q04499-5]
DR RefSeq; NP_728422.1; NM_167751.3. [Q04499-2]
DR RefSeq; NP_728423.1; NM_167752.3. [Q04499-1]
DR RefSeq; NP_728424.1; NM_167753.3. [Q04499-3]
DR RefSeq; NP_728425.1; NM_167754.2. [Q04499-4]
DR RefSeq; NP_996526.1; NM_206803.3. [Q04499-2]
DR RefSeq; NP_996527.1; NM_206804.3. [Q04499-2]
DR RefSeq; NP_996528.1; NM_206805.3. [Q04499-2]
DR AlphaFoldDB; Q04499; -.
DR BioGRID; 59392; 20.
DR IntAct; Q04499; 5.
DR STRING; 7227.FBpp0076903; -.
DR PaxDb; Q04499; -.
DR DNASU; 33117; -.
DR EnsemblMetazoa; FBtr0077203; FBpp0076902; FBgn0003423. [Q04499-2]
DR EnsemblMetazoa; FBtr0077204; FBpp0076903; FBgn0003423. [Q04499-1]
DR EnsemblMetazoa; FBtr0077205; FBpp0076904; FBgn0003423. [Q04499-5]
DR EnsemblMetazoa; FBtr0077206; FBpp0076905; FBgn0003423. [Q04499-3]
DR EnsemblMetazoa; FBtr0077207; FBpp0076906; FBgn0003423. [Q04499-4]
DR EnsemblMetazoa; FBtr0077208; FBpp0089304; FBgn0003423. [Q04499-2]
DR EnsemblMetazoa; FBtr0077209; FBpp0089305; FBgn0003423. [Q04499-2]
DR EnsemblMetazoa; FBtr0077210; FBpp0089306; FBgn0003423. [Q04499-2]
DR EnsemblMetazoa; FBtr0307524; FBpp0300179; FBgn0003423. [Q04499-3]
DR EnsemblMetazoa; FBtr0307525; FBpp0300180; FBgn0003423. [Q04499-2]
DR EnsemblMetazoa; FBtr0307526; FBpp0300181; FBgn0003423. [Q04499-2]
DR EnsemblMetazoa; FBtr0307527; FBpp0300182; FBgn0003423. [Q04499-2]
DR EnsemblMetazoa; FBtr0307528; FBpp0300183; FBgn0003423. [Q04499-3]
DR EnsemblMetazoa; FBtr0307529; FBpp0300184; FBgn0003423. [Q04499-5]
DR GeneID; 33117; -.
DR KEGG; dme:Dmel_CG1417; -.
DR CTD; 33117; -.
DR FlyBase; FBgn0003423; slgA.
DR VEuPathDB; VectorBase:FBgn0003423; -.
DR eggNOG; KOG0186; Eukaryota.
DR GeneTree; ENSGT00390000006265; -.
DR InParanoid; Q04499; -.
DR OMA; YLNEASC; -.
DR PhylomeDB; Q04499; -.
DR Reactome; R-DME-389661; Glyoxylate metabolism and glycine degradation.
DR Reactome; R-DME-70688; Proline catabolism.
DR UniPathway; UPA00261; UER00373.
DR BioGRID-ORCS; 33117; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 33117; -.
DR PRO; PR:Q04499; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0003423; Expressed in second segment of antenna (Drosophila) and 33 other tissues.
DR ExpressionAtlas; Q04499; baseline and differential.
DR Genevisible; Q04499; DM.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:FlyBase.
DR GO; GO:0071949; F:FAD binding; ISS:UniProtKB.
DR GO; GO:0004657; F:proline dehydrogenase activity; IMP:FlyBase.
DR GO; GO:0002118; P:aggressive behavior; IMP:FlyBase.
DR GO; GO:0007626; P:locomotory behavior; IMP:FlyBase.
DR GO; GO:0042331; P:phototaxis; IMP:FlyBase.
DR GO; GO:0006562; P:proline catabolic process; IMP:FlyBase.
DR GO; GO:0010133; P:proline catabolic process to glutamate; IBA:GO_Central.
DR InterPro; IPR029041; FAD-linked_oxidoreductase-like.
DR InterPro; IPR002872; Proline_DH_dom.
DR InterPro; IPR015659; Proline_oxidase.
DR PANTHER; PTHR13914; PTHR13914; 1.
DR Pfam; PF01619; Pro_dh; 1.
DR SUPFAM; SSF51730; SSF51730; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; FAD; Flavoprotein; Mitochondrion; Oxidoreductase;
KW Proline metabolism; Reference proteome; Transit peptide.
FT TRANSIT 1..30
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 31..681
FT /note="Proline dehydrogenase 1, mitochondrial"
FT /id="PRO_0000025803"
FT REGION 76..113
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 216..239
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 76..106
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..325
FT /note="Missing (in isoform C)"
FT /evidence="ECO:0000305"
FT /id="VSP_015400"
FT VAR_SEQ 158..192
FT /note="LARNLLGQKLFVLLMKSSFYGHFVAGENRHTIVPA -> WSKNVLGQRLFTL
FT LMKATFYGHFVAGEDQIKIIPT (in isoform A and isoform E)"
FT /evidence="ECO:0000303|PubMed:12537569,
FT ECO:0000303|PubMed:8096642"
FT /id="VSP_015401"
FT VAR_SEQ 285..296
FT /note="Missing (in isoform A and isoform B)"
FT /evidence="ECO:0000303|PubMed:12537569,
FT ECO:0000303|PubMed:8096642"
FT /id="VSP_015402"
FT CONFLICT 42
FT /note="S -> N (in Ref. 1; AAA02748)"
FT /evidence="ECO:0000305"
FT CONFLICT 147
FT /note="K -> N (in Ref. 1; AAA02748)"
FT /evidence="ECO:0000305"
FT CONFLICT 149
FT /note="V -> F (in Ref. 2; AAC28410)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 681 AA; 77153 MW; 2AB69ABB67D83FF8 CRC64;
MALLRSLSAQ RTAISLVYGR NSSKSSNSVA VAACRSFHQR GSGSTSIAGE GAASESTRGV
NGARFLHSGD RPLQASTLVQ PEVVSSETVK RSMKQESSQE KNPSPAGSPQ RDPLDVSFND
PIAAFKSKTT GELIRAYLVY MICSSEKLVE HNMTLMKLAR NLLGQKLFVL LMKSSFYGHF
VAGENRHTIV PALERLRSFG VKPILDYSVE EDITQEEAEK REVESSVSSA GDKKEEGSMP
QYHVDKSFAD RRYKVSSART YFYLNEATCE RNMEIFIKCL EAVSDDDRKA PRAVATGATF
GTGITAIKLT ALGRPQLLLQ LSEVIMRTRK YMEDMVGGQG NVLTHHKTIK DLEKYYATLG
DNKDVKEFLN NVTSDKEGIL HLFPWSGIVD EDSQLSDTFR VPDPQTGQMR RLISQIPPKE
EEMFRNMIRR LNTIVKAAAD LDVRIMVDAE QTYFQPAISR ITLEMMRKYN KDKAIVFNTY
QCYLRETFRE VNTDLEQAKR QNFYFGAKLV RGAYMDQERD RAKSLGYPDP VNPTFEATTD
MYHRTLSECL RRIKLMKDCD DDARKIGIMV ASHNEDTVRF AIQQMKEIGI SPEDKVICFG
QLLGMCDYIT FPLGQAGYSA YKYIPYGPVE EVLPYLSRRA QENKGVLKKI KKEKRLLLSE
IRRRLMRGQL FYKPKGNYVP I
