Cysteine desulfurase

Details

Name
Cysteine desulfurase
Synonyms
  • 2.8.1.7
  • NIFS
Gene Name
NFS1
UniProtKB Entry
Q9Y697Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0000301|Cysteine desulfurase
MLLRAAWRRAAVAVTAAPGPKPAAPTRGLRLRVGDRAPQSAVPADTAAAPEVGPVLRPLY
MDVQATTPLDPRVLDAMLPYLINYYGNPHSRTHAYGWESEAAMERARQQVASLIGADPRE
IIFTSGATESNNIAIKGVARFYRSRKKHLITTQTEHKCVLDSCRSLEAEGFQVTYLPVQK
SGIIDLKELEAAIQPDTSLVSVMTVNNEIGVKQPIAEIGRICSSRKVYFHTDAAQAVGKI
PLDVNDMKIDLMSISGHKIYGPKGVGAIYIRRRPRVRVEALQSGGGQERGMRSGTVPTPL
VVGLGAACEVAQQEMEYDHKRISKLSERLIQNIMKSLPDVVMNGDPKHHYPGCINLSFAY
VEGESLLMALKDVALSSGSACTSASLEPSYVLRAIGTDEDLAHSSIRFGIGRFTTEEEVD
YTVEKCIQHVKRLREMSPLWEMVQDGIDLKSIKWTQH
Number of residues
457
Molecular Weight
50195.21
Theoretical pI
8.45
GO Classification
Functions
cysteine desulfurase activity / iron-sulfur cluster binding / metal ion binding / protein homodimerization activity / pyridoxal phosphate binding
Processes
[2Fe-2S] cluster assembly / iron incorporation into metallo-sulfur cluster / Mo-molybdopterin cofactor biosynthetic process
Components
cytoplasm / cytosol / mitochondrial matrix / mitochondrion / nucleoplasm / nucleus
General Function
Cysteine desulfurase, of the core iron-sulfur cluster (ISC) assembly complex, that catalyzes the desulfuration of L-cysteine to L-alanine, as component of the cysteine desulfurase complex, leading to the formation of a cysteine persulfide intermediate at the active site cysteine residue and participates in the [2Fe-2S] clusters assembly on the scaffolding protein ISCU (PubMed:18650437, PubMed:29097656, PubMed:31101807). The persulfide is then transferred on the flexible Cys loop from the catalytic site of NFS1 to the surface of NFS1 (PubMed:29097656). After the NFS1-linked persulfide sulfur is transferred to one of the conserved Cys residues of the scaffold, a reaction assisted by FXN (By similarity). The core iron-sulfur cluster (ISC) assembly complex is involved in the de novo synthesis of a [2Fe-2S] cluster, the first step of the mitochondrial iron-sulfur protein biogenesis. This process is initiated by the cysteine desulfurase complex (NFS1:LYRM4:NDUFAB1) that produces persulfide which is delivered on the scaffold protein ISCU in a FXN-dependent manner. Then this complex is stabilized by FDX2 which provides reducing equivalents to accomplish the [2Fe-2S] cluster assembly. Finally, the [2Fe-2S] cluster is transferred from ISCU to chaperone proteins, including HSCB, HSPA9 and GLRX5 (By similarity)
Specific Function
Cysteine desulfurase activity
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Mitochondrion
Gene sequence
>lcl|BSEQ0009970|Cysteine desulfurase, mitochondrial (NFS1)
ATGCTGCTCCGAGCCGCTTGGAGGCGGGCGGCAGTGGCGGTGACAGCGGCTCCAGGGCCG
AAGCCCGCGGCGCCCACTCGGGGGCTGCGCCTGCGCGTTGGAGACCGTGCTCCTCAGTCT
GCGGTTCCCGCAGATACAGCCGCTGCCCCGGAGGTGGGGCCAGTGCTGCGACCTCTCTAT
ATGGATGTGCAAGCTACAACTCCTCTGGACCCCCGGGTGCTTGATGCCATGCTCCCTTAC
CTAATCAACTACTATGGGAACCCACACTCCCGGACACATGCTTATGGCTGGGAGAGTGAG
GCAGCCATGGAACGTGCTCGTCAGCAAGTAGCATCTCTGATTGGAGCTGATCCTCGTGAG
ATCATTTTTACTAGTGGTGCTACTGAATCCAACAACATAGCAATTAAGGAACTAGAGGCT
GCTATCCAGCCAGATACTAGCCTGGTGTCAGTCATGACTGTGAACAATGAGATTGGAGTG
AAGCAGCCTATTGCAGAAATAGGGCGGATTTGCAGTTCCAGAAAGGTATATTTCCATACT
GATGCAGCCCAGGCTGTTGGAAAAATCCCACTTGATGTCAATGACATGAAAATTGATCTC
ATGAGCATTAGTGGTCACAAAATCTACGGTCCCAAAGGGGTTGGTGCCATCTACATCCGT
CGCCGGCCCCGTGTGCGTGTGGAGGCCCTGCAGAGTGGAGGGGGGCAGGAGCGGGGTATG
CGGTCTGGGACAGTGCCCACACCCTTAGTGGTGGGGCTGGGGGCTGCGTGTGAGGTGGCA
CAGCAAGAGATGGAGTATGACCACAAGCGAATCTCAAAGTTGTCAGAGCGGCTGATACAG
AATATAATGAAGAGCCTTCCAGATGTGGTGATGAATGGGGACCCTAAGCACCATTATCCC
GGCTGTATCAACCTCTCCTTTGCATATGTGGAAGGGGAAAGTCTGCTGATGGCACTGAAG
GACGTTGCCTTATCCTCAGGGAGTGCCTGCACCTCTGCATCCCTGGAGCCCTCTTATGTG
CTTAGAGCAATTGGCACTGATGAGGATTTAGCGCACTCTTCTATCAGGTTTGGAATTGGC
CGCTTCACTACAGAGGAGGAAGTGGACTACACAGTGGAGAAATGCATTCAGCATGTGAAG
CGTCTTCGAGAAATGAGCCCTCTCTGGGAGATGGTTCAGGATGGCATTGACCTCAAGAGC
ATCAAGTGGACCCAACACTAG
Chromosome Location
20
Locus
20q11.22
External Identifiers
ResourceLink
UniProtKB IDQ9Y697
UniProtKB Entry NameNFS1_HUMAN
GenBank Protein ID24042327
GenBank Gene IDAF097025
GeneCard IDNFS1
GenAtlas IDNFS1
HGNC IDHGNC:15910
PDB ID(s)5KZ5, 5USR, 5WGB, 5WKP, 5WLW, 6NZU, 6UXE, 6W1D, 6WI2, 6WIH, 7RTK
KEGG IDhsa:9054
NCBI Gene ID9054
General References
  1. Land T, Rouault TA: Targeting of a human iron-sulfur cluster assembly enzyme, nifs, to different subcellular compartments is regulated through alternative AUG utilization. Mol Cell. 1998 Dec;2(6):807-15. [Article]
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Associated Data

Bio-Entities
Bio-EntityType
Cysteine desulfurase (Humans)protein
primary
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Pyridoxal phosphateapproved, investigational, nutraceuticalunknowntargetcofactorDetails
AlaninenutraceuticalunknowntargetDetails
Cysteineapproved, nutraceuticalunknowntargetDetails