NFS1_DROME
ID NFS1_DROME Reviewed; 462 AA.
AC Q9VKD3; Q9VKD4;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Cysteine desulfurase, mitochondrial {ECO:0000305};
DE EC=2.8.1.7 {ECO:0000269|PubMed:29491838};
DE Flags: Precursor;
GN Name=Nfs1 {ECO:0000303|PubMed:29491838, ECO:0000312|FlyBase:FBgn0032393};
GN ORFNames=CG12264 {ECO:0000312|FlyBase:FBgn0032393};
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 [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 [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=20534482; DOI=10.1073/pnas.1006503107;
RA Rogers R.L., Bedford T., Lyons A.M., Hartl D.L.;
RT "Adaptive impact of the chimeric gene Quetzalcoatl in Drosophila
RT melanogaster.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:10943-10948(2010).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, INTERACTION WITH BCN92; FH AND ISCU, AND
RP MUTAGENESIS OF 1-MET--ASN-53.
RX PubMed=29491838; DOI=10.3389/fphys.2018.00050;
RA Marelja Z., Leimkuehler S., Missirlis F.;
RT "Iron Sulfur and Molybdenum Cofactor Enzymes Regulate the Drosophila Life
RT Cycle by Controlling Cell Metabolism.";
RL Front. Physiol. 9:50-50(2018).
CC -!- FUNCTION: Catalyzes the removal of elemental sulfur from cysteine to
CC produce alanine. It supplies the inorganic sulfur for iron-sulfur (Fe-
CC S) clusters. {ECO:0000269|PubMed:29491838}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[sulfur carrier]-H + L-cysteine = [sulfur carrier]-SH + L-
CC alanine; Xref=Rhea:RHEA:43892, Rhea:RHEA-COMP:14737, Rhea:RHEA-
CC COMP:14739, ChEBI:CHEBI:29917, ChEBI:CHEBI:35235, ChEBI:CHEBI:57972,
CC ChEBI:CHEBI:64428; EC=2.8.1.7;
CC Evidence={ECO:0000269|PubMed:29491838};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000269|PubMed:29491838};
CC -!- ACTIVITY REGULATION: L-cysteine binding is slower in the presence of
CC bcn92 and IscU (PubMed:29491838). Activation requires bcn92, IscU and
CC fh (PubMed:29491838). {ECO:0000269|PubMed:29491838}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.290 mM for L-cysteine {ECO:0000269|PubMed:29491838};
CC -!- SUBUNIT: Interacts with bcn92 and IscU (PubMed:29491838). Might form a
CC complex with bcn92, IscU and fh (Probable).
CC {ECO:0000269|PubMed:29491838, ECO:0000305|PubMed:29491838}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q9Y697}.
CC Nucleus {ECO:0000250|UniProtKB:Q9Y697}.
CC -!- TISSUE SPECIFICITY: Ubiquitous expression at high levels in any life
CC stage. {ECO:0000269|PubMed:20534482}.
CC -!- SIMILARITY: Belongs to the class-V pyridoxal-phosphate-dependent
CC aminotransferase family. NifS/IscS subfamily. {ECO:0000305}.
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DR EMBL; AE014134; AAF53143.1; -; Genomic_DNA.
DR EMBL; AY113363; AAM29368.1; -; mRNA.
DR RefSeq; NP_609533.1; NM_135689.2.
DR AlphaFoldDB; Q9VKD3; -.
DR SMR; Q9VKD3; -.
DR BioGRID; 60665; 57.
DR STRING; 7227.FBpp0079874; -.
DR PaxDb; Q9VKD3; -.
DR PRIDE; Q9VKD3; -.
DR DNASU; 34613; -.
DR EnsemblMetazoa; FBtr0080290; FBpp0079874; FBgn0032393.
DR GeneID; 34613; -.
DR KEGG; dme:Dmel_CG12264; -.
DR UCSC; CG12264-RA; d. melanogaster.
DR CTD; 9054; -.
DR FlyBase; FBgn0032393; Nfs1.
DR VEuPathDB; VectorBase:FBgn0032393; -.
DR eggNOG; KOG1549; Eukaryota.
DR GeneTree; ENSGT00940000155740; -.
DR HOGENOM; CLU_003433_0_2_1; -.
DR InParanoid; Q9VKD3; -.
DR OMA; KGLYWAR; -.
DR OrthoDB; 664730at2759; -.
DR PhylomeDB; Q9VKD3; -.
DR Reactome; R-DME-1362409; Mitochondrial iron-sulfur cluster biogenesis.
DR Reactome; R-DME-947581; Molybdenum cofactor biosynthesis.
DR BioGRID-ORCS; 34613; 2 hits in 3 CRISPR screens.
DR GenomeRNAi; 34613; -.
DR PRO; PR:Q9VKD3; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0032393; Expressed in embryonic/larval hemocyte (Drosophila) and 25 other tissues.
DR Genevisible; Q9VKD3; DM.
DR GO; GO:0005829; C:cytosol; IDA:FlyBase.
DR GO; GO:1990221; C:L-cysteine desulfurase complex; IPI:FlyBase.
DR GO; GO:0005739; C:mitochondrion; ISS:FlyBase.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0031071; F:cysteine desulfurase activity; IDA:FlyBase.
DR GO; GO:0051536; F:iron-sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0044571; P:[2Fe-2S] cluster assembly; IEA:InterPro.
DR GO; GO:0016226; P:iron-sulfur cluster assembly; IDA:FlyBase.
DR GO; GO:0070903; P:mitochondrial tRNA thio-modification; ISS:FlyBase.
DR Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 1.
DR HAMAP; MF_00331; Cys_desulf_IscS; 1.
DR InterPro; IPR000192; Aminotrans_V_dom.
DR InterPro; IPR020578; Aminotrans_V_PyrdxlP_BS.
DR InterPro; IPR010240; Cys_deSase_IscS.
DR InterPro; IPR016454; Cysteine_dSase.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
DR PANTHER; PTHR11601:SF34; PTHR11601:SF34; 1.
DR Pfam; PF00266; Aminotran_5; 1.
DR PIRSF; PIRSF005572; NifS; 1.
DR SUPFAM; SSF53383; SSF53383; 1.
DR TIGRFAMs; TIGR02006; IscS; 1.
DR PROSITE; PS00595; AA_TRANSFER_CLASS_5; 1.
PE 1: Evidence at protein level;
KW Iron; Iron-sulfur; Metal-binding; Mitochondrion; Nucleus;
KW Pyridoxal phosphate; Reference proteome; Transferase; Transit peptide.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN ?..462
FT /note="Cysteine desulfurase, mitochondrial"
FT /id="PRO_0000001298"
FT ACT_SITE 386
FT /note="Cysteine persulfide intermediate"
FT /evidence="ECO:0000250|UniProtKB:P0A6B7"
FT BINDING 132..133
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P0A6B9"
FT BINDING 212
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:O29689"
FT BINDING 240
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P0A6B9"
FT BINDING 260..262
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P0A6B9"
FT BINDING 300
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P0A6B9"
FT BINDING 386
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /note="via persulfide group"
FT /evidence="ECO:0000250|UniProtKB:O29689"
FT MOD_RES 263
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:P0A6B9"
FT MUTAGEN 1..53
FT /note="Missing: Retains interaction with bcn92 and IscU."
FT /evidence="ECO:0000269|PubMed:29491838"
SQ SEQUENCE 462 AA; 51074 MW; FC4107341FE2AA74 CRC64;
MQKVLGRIQA QVLRSRATNA LANVVRHEAT SSRTAAKPAA TSKEFRERQV RFNIKNEQTE
GRPLYLDAQA TTPMDPRVLD AMLPYLTNFY GNPHSRTHAY GWETESAVEK AREQVATLIG
ADPKEIIFTS GATESNNIAV KGVARFYGTK KRHVITTQTE HKCVLDSCRA LENEGFKVTY
LPVLANGLID LQQLEETITS ETSLVSIMTV NNEIGVRQPV DEIGKLCRSR RVFFHTDAAQ
AVGKVPLDVN AMNIDLMSIS GHKIYGPKGV GALYVRRRPR VRLEPIQSGG GQERGLRSGT
VPAPLAVGLG AAAELSLREM DYDKKWVDFL SNRLLDRISS ALPHVIRNGD AKATYNGCLN
LSFAYVEGES LLMALKDVAL SSGSACTSAS LEPSYVLRAI GTDEDLAHSS IRFGIGRFTT
VEEVDYTADK CIKHVERLRE MSPLWEMVQE GIDLKTIQWS QH
