ID   NFS1_RAT                Reviewed;         451 AA.
AC   Q99P39;
DT   23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2001, sequence version 1.
DT   03-AUG-2022, entry version 130.
DE   RecName: Full=Cysteine desulfurase, mitochondrial {ECO:0000305};
DE            EC=2.8.1.7 {ECO:0000250|UniProtKB:P0A6B9};
DE   Flags: Precursor;
GN   Name=Nfs1; Synonyms=Nifs;
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;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Liver;
RA   Hsu S.-C., Liew Y.-F., Shaw N.-S.;
RT   "cDNA cloning of cysteine desulfurase (NifS) protein in rat liver.";
RL   Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases.
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. May be involved in the biosynthesis of molybdenum
CC       cofactor. {ECO:0000250|UniProtKB:Q9Y697}.
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:0000250|UniProtKB:Q9Y697};
CC   -!- COFACTOR:
CC       Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC         Evidence={ECO:0000250|UniProtKB:P0A6B9};
CC   -!- SUBUNIT: Binds ISCU/NIFUN. Forms a complex with LYRM4. Interacts with
CC       HSPA9. {ECO:0000250|UniProtKB:Q9Y697}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q9Y697}.
CC       Cytoplasm {ECO:0000250|UniProtKB:Q9Y697}. Nucleus
CC       {ECO:0000250|UniProtKB:Q9Y697}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative initiation; Named isoforms=2;
CC       Name=Mitochondrial;
CC         IsoId=Q99P39-1; Sequence=Displayed;
CC       Name=Cytoplasmic;
CC         IsoId=Q99P39-2; Sequence=VSP_018648;
CC   -!- SIMILARITY: Belongs to the class-V pyridoxal-phosphate-dependent
CC       aminotransferase family. NifS/IscS subfamily. {ECO:0000305}.
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DR   EMBL; AF336041; AAK12337.1; -; mRNA.
DR   AlphaFoldDB; Q99P39; -.
DR   SMR; Q99P39; -.
DR   IntAct; Q99P39; 2.
DR   STRING; 10116.ENSRNOP00000026820; -.
DR   iPTMnet; Q99P39; -.
DR   PhosphoSitePlus; Q99P39; -.
DR   jPOST; Q99P39; -.
DR   PaxDb; Q99P39; -.
DR   PeptideAtlas; Q99P39; -.
DR   PRIDE; Q99P39; -.
DR   UCSC; RGD:620912; rat. [Q99P39-1]
DR   RGD; 620912; Nfs1.
DR   eggNOG; KOG1549; Eukaryota.
DR   InParanoid; Q99P39; -.
DR   BRENDA; 2.8.1.7; 5301.
DR   Reactome; R-RNO-1362409; Mitochondrial iron-sulfur cluster biogenesis.
DR   Reactome; R-RNO-947581; Molybdenum cofactor biosynthesis.
DR   PRO; PR:Q99P39; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0005759; C:mitochondrial matrix; ISO:RGD.
DR   GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; ISO:RGD.
DR   GO; GO:0031071; F:cysteine desulfurase activity; ISO:RGD.
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:0042803; F:protein homodimerization activity; ISO:RGD.
DR   GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR   GO; GO:0044571; P:[2Fe-2S] cluster assembly; IEA:InterPro.
DR   GO; GO:0018283; P:iron incorporation into metallo-sulfur cluster; ISO:RGD.
DR   GO; GO:0016226; P:iron-sulfur cluster assembly; IBA:GO_Central.
DR   GO; GO:0006777; P:Mo-molybdopterin cofactor biosynthetic process; IEA:UniProtKB-KW.
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   2: Evidence at transcript level;
KW   Alternative initiation; Cytoplasm; Iron; Iron-sulfur; Metal-binding;
KW   Mitochondrion; Molybdenum cofactor biosynthesis; Nucleus;
KW   Pyridoxal phosphate; Reference proteome; Transferase; Transit peptide.
FT   TRANSIT         1..?
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           ?..451
FT                   /note="Cysteine desulfurase, mitochondrial"
FT                   /id="PRO_0000001296"
FT   ACT_SITE        375
FT                   /note="Cysteine persulfide intermediate"
FT                   /evidence="ECO:0000250|UniProtKB:P0A6B7"
FT   BINDING         121..122
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /evidence="ECO:0000250|UniProtKB:P0A6B9"
FT   BINDING         201
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /evidence="ECO:0000250|UniProtKB:O29689"
FT   BINDING         229
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /evidence="ECO:0000250|UniProtKB:P0A6B9"
FT   BINDING         249..251
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /evidence="ECO:0000250|UniProtKB:P0A6B9"
FT   BINDING         289
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /evidence="ECO:0000250|UniProtKB:P0A6B9"
FT   BINDING         375
FT                   /ligand="[2Fe-2S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:190135"
FT                   /ligand_note="ligand shared with ISCU"
FT                   /note="via persulfide group"
FT                   /evidence="ECO:0000250|UniProtKB:O29689"
FT   MOD_RES         252
FT                   /note="N6-(pyridoxal phosphate)lysine"
FT                   /evidence="ECO:0000250|UniProtKB:P0A6B9"
FT   VAR_SEQ         1..54
FT                   /note="Missing (in isoform Cytoplasmic)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_018648"
SQ   SEQUENCE   451 AA;  50013 MW;  8E9083D6222F3087 CRC64;
     MLLRVAWRRA SLAATSVALR RSSVPTRGLR LRVVDHAPHS AVPSEAEAVL RPLYMDVRAT
     TPLDPRVLDA MLPYLVNYYG NPHSRTHAYG WESEAAMERA RQQVASLIGA DPREIIFTSG
     ATESNNIAIK GVARFYRSRK KHLVTTQTEH KCVLDSCRSL EAEGFRVTYL PVQKSGIIDL
     KELEAAIQPD TSLVSVMTVN NEIGVKQPIA EIGQICSSRK LYFHTDAAQA VGKIPLDVND
     MKIDLMSISG HKLYGPKGVG AIYIRRRPRV RVEALQSGGG QERGMRSGTV PTPLVVGLGA
     ACELAQQEME YDHKRISKLA ERLIQKIMKN LPDVVMNGDP KQHYPGCINL SFAYVEGESL
     LMALKDVALS SGSACTSASL EPSYVLRAIG TDEDLAHSSI RFGIGRFTTE EEVDYTVQKC
     IHHVKRLREM SPLWEMVQDG IDLKSIKWTQ H