ID NFS1_PONAB Reviewed; 457 AA.
AC Q5RDE7;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 08-NOV-2023, entry version 93.
DE RecName: Full=Cysteine desulfurase {ECO:0000250|UniProtKB:Q9Y697};
DE EC=2.8.1.7 {ECO:0000250|UniProtKB:Q9Y697};
DE Flags: Precursor;
GN Name=NFS1 {ECO:0000250|UniProtKB:Q9Y697};
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: [Isoform Mitochondrial]: Cysteine desulfurase, of the core
CC iron-sulfur cluster (ISC) assembly complex, that catalyzes the
CC desulfuration of L-cysteine to L-alanine, as component of the cysteine
CC desulfurase complex leading to the formation of a cysteine persulfide
CC intermediate at the active site cysteine residue and participates in
CC the [2Fe-2S] clusters assembly on the scaffolding protein ISCU. The
CC persulfide is then transferred on the flexible Cys loop from the
CC catalytic site of NFS1 to the surface of NFS1 (By similarity). After
CC the NFS1-linked persulfide sulfur is transferred to one of the
CC conserved Cys residues of the scaffold, a reaction assisted by FXN (By
CC similarity). The core iron-sulfur cluster (ISC) assembly complex is
CC involved in the de novo synthesis of a [2Fe-2S] cluster, the first step
CC of the mitochondrial iron-sulfur protein biogenesis. This process is
CC initiated by the cysteine desulfurase complex (NFS1:LYRM4:NDUFAB1) that
CC produces persulfide which is delivered on the scaffold protein ISCU in
CC a FXN-dependent manner. Then this complex is stabilized by FDX2 which
CC provides reducing equivalents to accomplish the [2Fe-2S] cluster
CC assembly. Finally, the [2Fe-2S] cluster is transferred from ISCU to
CC chaperone proteins, including HSCB, HSPA9 and GLRX5 (By similarity).
CC {ECO:0000250|UniProtKB:Q9H1K1, ECO:0000250|UniProtKB:Q9Y697,
CC ECO:0000250|UniProtKB:Q9Z1J3}.
CC -!- FUNCTION: [Isoform Cytoplasmic]: May catalyze the desulfuration of L-
CC cysteine to L-alanine as component of the cysteine desulfurase complex
CC (NFS1:LYRM4), leading to the formation of a cysteine persulfide
CC intermediate. Acts as a sulfur donor for MOCS3 by transferring the
CC sulfur of the cysteine persulfide intermediate on MOCS3.
CC {ECO:0000250|UniProtKB:Q9Y697}.
CC -!- CATALYTIC ACTIVITY: [Isoform Cytoplasmic]:
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 -!- CATALYTIC ACTIVITY: [Isoform Mitochondrial]:
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 -!- CATALYTIC ACTIVITY: [Isoform Cytoplasmic]:
CC Reaction=[sulfur-carrier protein]-L-cysteine + L-cysteine = [sulfur-
CC carrier protein]-S-sulfanyl-L-cysteine + L-alanine;
CC Xref=Rhea:RHEA:17457, Rhea:RHEA-COMP:10742, Rhea:RHEA-COMP:10744,
CC ChEBI:CHEBI:29950, ChEBI:CHEBI:35235, ChEBI:CHEBI:57972,
CC ChEBI:CHEBI:61963; Evidence={ECO:0000250|UniProtKB:Q9Y697};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000250|UniProtKB:Q9Y697};
CC -!- ACTIVITY REGULATION: Active only in complex with LYRM4.
CC {ECO:0000250|UniProtKB:Q9Y697}.
CC -!- SUBUNIT: [Isoform Mitochondrial]: Homodimer. Component of the
CC mitochondrial core iron-sulfur cluster (ISC) complex composed of NFS1,
CC LYRM4, NDUFAB1, ISCU, FXN, and FDX2; this complex is an heterohexamer
CC containing two copies of each monomer. Component of cyteine desulfurase
CC complex composed of NFS1, LYRM4 and NDUFAB1; this complex contributes
CC to the activation of cysteine desulfurase activity and NFS1
CC stabilization. Interacts (homodimer form) with ISCU (D-state); each
CC monomer interacts with the C-terminal regions of each NFS1 monomer.
CC Interacts with HSPA9. Interacts (via homodimer form) with FDX2.
CC Interacts (via homodimer form) with FXN. Interacts with LYRM4 (By
CC similarity). Component of a complex composed of FXN, NFS1, LYRM4 and
CC ISCU (By similarity). {ECO:0000250|UniProtKB:Q9Y697,
CC ECO:0000250|UniProtKB:Q9Z1J3}.
CC -!- SUBUNIT: [Isoform Cytoplasmic]: Monomer. Homodimer. Oligomer. Interacts
CC with ISCU. Component of the cysteine desulfurase complex composed of
CC NFS1 and LYRM4; this complex contributes to the activation of cysteine
CC desulfurase activity. Interacts with MOCS3.
CC {ECO:0000250|UniProtKB:Q9Y697}.
CC -!- SUBCELLULAR LOCATION: [Isoform Mitochondrial]: Mitochondrion
CC {ECO:0000250|UniProtKB:Q9Y697}.
CC -!- SUBCELLULAR LOCATION: [Isoform Cytoplasmic]: Cytoplasm
CC {ECO:0000250|UniProtKB:Q9Y697}. Nucleus {ECO:0000250|UniProtKB:Q9Y697}.
CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000250|UniProtKB:Q9Y697}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=Mitochondrial;
CC IsoId=Q5RDE7-1; Sequence=Displayed;
CC Name=Cytoplasmic;
CC IsoId=Q5RDE7-2; Sequence=VSP_021590;
CC -!- PTM: N-gluconoylated. {ECO:0000250|UniProtKB:Q9Z1J3}.
CC -!- PTM: Cysteine persulfide intermediate is reduced by thiol-containing
CC molecules like glutathione and L-cysteine. Persulfide reduction is a
CC rate-limiting step of cysteine desulfurase catalytic cycle.
CC {ECO:0000250|UniProtKB:Q9Z1J3}.
CC -!- SIMILARITY: Belongs to the class-V pyridoxal-phosphate-dependent
CC aminotransferase family. NifS/IscS subfamily. {ECO:0000305}.
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DR EMBL; CR857965; CAH90210.1; -; mRNA.
DR RefSeq; NP_001127252.1; NM_001133780.1. [Q5RDE7-1]
DR AlphaFoldDB; Q5RDE7; -.
DR SMR; Q5RDE7; -.
DR STRING; 9601.ENSPPYP00000012238; -.
DR GeneID; 100174307; -.
DR KEGG; pon:100174307; -.
DR CTD; 9054; -.
DR eggNOG; KOG1549; Eukaryota.
DR InParanoid; Q5RDE7; -.
DR OrthoDB; 212394at2759; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0099128; C:mitochondrial iron-sulfur cluster assembly complex; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0031071; F:cysteine desulfurase activity; ISS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0044571; P:[2Fe-2S] cluster assembly; ISS:UniProtKB.
DR GO; GO:0044572; P:[4Fe-4S] cluster assembly; ISS:UniProtKB.
DR GO; GO:0006777; P:Mo-molybdopterin cofactor biosynthetic process; IEA:UniProtKB-KW.
DR Gene3D; 3.90.1150.10; Aspartate Aminotransferase, domain 1; 1.
DR Gene3D; 3.40.640.10; Type I PLP-dependent aspartate aminotransferase-like (Major domain); 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 NCBIfam; TIGR02006; IscS; 1.
DR PANTHER; PTHR11601:SF34; CYSTEINE DESULFURASE, MITOCHONDRIAL; 1.
DR PANTHER; PTHR11601; CYSTEINE DESULFURYLASE FAMILY MEMBER; 1.
DR Pfam; PF00266; Aminotran_5; 1.
DR PIRSF; PIRSF005572; NifS; 1.
DR SUPFAM; SSF53383; PLP-dependent transferases; 1.
DR PROSITE; PS00595; AA_TRANSFER_CLASS_5; 1.
PE 2: Evidence at transcript level;
KW Alternative initiation; Cytoplasm; Cytoskeleton; Iron; Iron-sulfur;
KW Metal-binding; Mitochondrion; Molybdenum cofactor biosynthesis; Nucleus;
KW Pyridoxal phosphate; Reference proteome; Transferase; Transit peptide;
KW Zinc.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN ?..457
FT /note="Cysteine desulfurase"
FT /id="PRO_0000260249"
FT ACT_SITE 381
FT /note="Cysteine persulfide intermediate"
FT /evidence="ECO:0000250|UniProtKB:Q9Z1J3"
FT BINDING 127
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:Q9Y697"
FT BINDING 128
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:Q9Y697"
FT BINDING 235
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:Q9Y697"
FT BINDING 255
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:Q9Y697"
FT BINDING 257
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:Q9Y697"
FT BINDING 295
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:Q9Y697"
FT BINDING 381
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 BINDING 381
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="ligand shared with ISCU (isoform 2)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y697"
FT MOD_RES 258
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y697"
FT MOD_RES 381
FT /note="Cysteine persulfide"
FT /evidence="ECO:0000250|UniProtKB:Q9Z1J3"
FT VAR_SEQ 1..60
FT /note="Missing (in isoform Cytoplasmic)"
FT /evidence="ECO:0000305"
FT /id="VSP_021590"
SQ SEQUENCE 457 AA; 50135 MW; 45F66BDFAC605E2F CRC64;
MLLRAAWRRA AVAVTAAPGP KPAAPTRGLR LRVGDHAPQS AVPADTAAAP EAGPVLRPLY
MDVQATTPLD PRVLDAMLPY LINYYGNPHS RTHAYGWESE AAMERARQQV ASLIGADPRE
IIFTSGATES NNIAIKGVAR FYRSRKKHLI TTQTEHKCVL DSCRSLEAEG FQVTYLPVQK
SGIIDLKELE AAIQPDTSLV SVMTVNNEIG VKQPIAEIGR ICSSRKVYFH TDAAQAVGKI
PLDVNDMKID LMSISGHKIY GPKGVGAIYI RRRPRVRVEA LQSGGGQERG MRSGTVPTPL
VVGLGAACEV AQQEMEYDHK RISKLSERLI QNIMKSLPDV VMNGDPEHHY PGCINLSFAY
VEGESLLMAL KDVALSSGSA CTSASLEPSY VLRAIGTDED LAHSSIRFGV GRFTTEEEVD
YTVEKCIQHV KRLREMSPLW EMVQDGIDLK SIKWTQH
//
