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NFS1 NFS1 cysteine desulfurase [ Homo sapiens (human) ]

Gene ID: 9054, updated on 5-Mar-2024

Summary

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Official Symbol
NFS1provided by HGNC
Official Full Name
NFS1 cysteine desulfuraseprovided by HGNC
Primary source
HGNC:HGNC:15910
See related
Ensembl:ENSG00000244005 MIM:603485; AllianceGenome:HGNC:15910
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
IscS; NIFS; COXPD52; HUSSY-08
Summary
Iron-sulfur clusters are required for the function of many cellular enzymes. The proteins encoded by this gene supply inorganic sulfur to these clusters by removing the sulfur from cysteine, creating alanine in the process. This gene uses alternate in-frame translation initiation sites to generate mitochondrial forms and cytoplasmic/nuclear forms. Selection of the alternative initiation sites is determined by the cytosolic pH. The encoded proteins belong to the class-V family of pyridoxal phosphate-dependent aminotransferases. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2010]
Expression
Ubiquitous expression in kidney (RPKM 16.1), testis (RPKM 12.1) and 25 other tissues See more
Orthologs
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Genomic context

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Location:
20q11.22
Exon count:
14
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 20 NC_000020.11 (35668052..35699352, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 20 NC_060944.1 (37389027..37420327, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 20 NC_000020.10 (34255974..34287274, complement)

Chromosome 20 - NC_000020.11Genomic Context describing neighboring genes Neighboring gene copine 1 Neighboring gene RNA, U6 small nuclear 759, pseudogene Neighboring gene RNA binding motif protein 12 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17790 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:34251645-34252150 Neighboring gene Sharpr-MPRA regulatory region 3991 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:34252655-34253159 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:34286841-34287500 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:34287501-34288160 Neighboring gene reactive oxygen species modulator 1 Neighboring gene RNA binding motif protein 39 Neighboring gene small nucleolar RNA U13

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Phosphorylated NFS1 weakens oxaliplatin-based chemosensitivity of colorectal cancer by preventing PANoptosis. Lin JF, et al. Signal Transduct Target Ther, 2022 Feb 28. PMID 35221331, Free PMC Article
  2. Targeting of a human iron-sulfur cluster assembly enzyme, nifs, to different subcellular compartments is regulated through alternative AUG utilization. Land T, et al. Mol Cell, 1998 Dec. PMID 9885568
  3. Analysis of the Cellular Roles of MOCS3 Identifies a MOCS3-Independent Localization of NFS1 at the Tips of the Centrosome. Neukranz Y, et al. Biochemistry, 2019 Apr 2. PMID 30817134
  4. Zinc(II) binding on human wild-type ISCU and Met140 variants modulates NFS1 desulfurase activity. Fox NG, et al. Biochimie, 2018 Sep. PMID 30031876, Free PMC Article
  5. NFS1 undergoes positive selection in lung tumours and protects cells from ferroptosis. Alvarez SW, et al. Nature, 2017 Nov 30. PMID 29168506, Free PMC Article

See all (79) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Phosphorylated NFS1 weakens oxaliplatin-based chemosensitivity of colorectal cancer by preventing PANoptosis.
    Title: Phosphorylated NFS1 weakens oxaliplatin-based chemosensitivity of colorectal cancer by preventing PANoptosis.
  2. By different methods, this study identified a MOCS3-independent novel localization of NFS1 at the centrosome.
    Title: Analysis of the Cellular Roles of MOCS3 Identifies a MOCS3-Independent Localization of NFS1 at the Tips of the Centrosome.
  3. The molecular structure of the human mitochondrial cysteine desulfurase complex consisting of two copies each of NFS1, ISD11, and acyl carrier protein has been described.
    Title: Architectural Features of Human Mitochondrial Cysteine Desulfurase Complexes from Crosslinking Mass Spectrometry and Small-Angle X-Ray Scattering.
  4. Study reports 3.2 A resolution cryo-electron microscopy structure of the FXN-bound active human iron-sulfur clusters biosynthesis complex. FXN binds at the interface of two NFS1 and one ISCU subunits, modifying the local environment of a bound zinc ion that would otherwise inhibit NFS1 activity in complexes without FXN.
    Title: Structure of the human frataxin-bound iron-sulfur cluster assembly complex provides insight into its activation mechanism.
  5. FXN binds the NFS1-ISD11-ACP-ISCU complex (SDAU), to activate the desulfurase activity and Fe-S cluster biosynthesis. In the absence of FXN, the NFS1-ISD11-ACP (SDA) complex was reportedly inhibited by binding of recombinant ISCU
    Title: Zinc(II) binding on human wild-type ISCU and Met140 variants modulates NFS1 desulfurase activity.
  6. analysis of the NFS1-ISD11-ACP (SDA) complex forms the core of the iron-sulfur (Fe-S) assembly complex and associates with assembly proteins ISCU2, frataxin (FXN), and ferredoxin to synthesize Fe-S clusters
    Title: Structure of human Fe-S assembly subcomplex reveals unexpected cysteine desulfurase architecture and acyl-ACP-ISD11 interactions.
  7. NFS1 maintains the iron sulfur clusters in proteins that are essential for protecting them from oxidative damage; inactivating NFS1 or iron sulfur clusters can trigger ferroptosis, a non-apoptotic form of cell death, in cancer cells
    Title: NFS1 undergoes positive selection in lung tumours and protects cells from ferroptosis.
  8. human NFS1 was almost fully able to complement the role of IscS in Moco biosynthesis when its specific interaction partner protein MOCS3 from humans was also present.
    Title: Functional Complementation Studies Reveal Different Interaction Partners of Escherichia coli IscS and Human NFS1.
  9. The NFS1/ISD11 complex further interacts with scaffold protein ISCU and regulator protein frataxin, thereby forming a quaternary complex for Fe-S cluster formation.
    Title: The N-Terminus of Iron-Sulfur Cluster Assembly Factor ISD11 Is Crucial for Subcellular Targeting and Interaction with l-Cysteine Desulfurase NFS1.
  10. FDX1 and FDX2 both bind NFS1 and donate electrons for iron-sulfur cluster biosynthesis.
    Title: Human Mitochondrial Ferredoxin 1 (FDX1) and Ferredoxin 2 (FDX2) Both Bind Cysteine Desulfurase and Donate Electrons for Iron-Sulfur Cluster Biosynthesis.
Submit: New GeneRIF Correction See all GeneRIFs (21)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Combined oxidative phosphorylation deficiency 52
MedGen: C5543592 OMIM: 619386 GeneReviews: Not available
not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Potential readthrough

Included gene: CPNE1

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables cysteine desulfurase activity EXP
Inferred from Experiment
more info
 PubMed 
enables cysteine desulfurase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables cysteine desulfurase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables iron-sulfur cluster binding IEA
Inferred from Electronic Annotation
more info
  
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein homodimerization activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables pyridoxal phosphate binding IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in Mo-molybdopterin cofactor biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
involved_in [2Fe-2S] cluster assembly IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in [4Fe-4S] cluster assembly IEA
Inferred from Electronic Annotation
more info
  
involved_in iron incorporation into metallo-sulfur cluster IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in iron-sulfur cluster assembly IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in iron-sulfur cluster assembly NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in iron-sulfur cluster assembly TAS
Traceable Author Statement
more info
  
Component Evidence Code Pubs
located_in centrosome IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in cytosol IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
  
part_of iron-sulfur cluster assembly complex NAS
Non-traceable Author Statement
more info
 PubMed 
part_of mitochondrial iron-sulfur cluster assembly complex IDA
Inferred from Direct Assay
more info
 PubMed 
located_in mitochondrial matrix IDA
Inferred from Direct Assay
more info
 PubMed 
located_in mitochondrial matrix TAS
Traceable Author Statement
more info
  
is_active_in mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in mitochondrion IDA
Inferred from Direct Assay
more info
 PubMed 
located_in mitochondrion NAS
Non-traceable Author Statement
more info
 PubMed 
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
cysteine desulfurase
Names
NFS1 nitrogen fixation 1 homolog
cysteine desulfurase, mitochondrial
nitrogen fixation 1 (S. cerevisiae, homolog)
nitrogen-fixing bacteria S-like protein
NP_001185918.1
NP_066923.3

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_033237.1 RefSeqGene

    Range
    5014..36314
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001198989.2 → NP_001185918.1  cysteine desulfurase isoform b precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an in-frame exon in the 5' coding region, compared to variant 1. This results in a shorter protein (isoform b), compared to isoform a.
    Source sequence(s)
    AK001470, AK223239, AK302023, AL109827, R16676
    Consensus CDS
    CCDS56185.1
    UniProtKB/TrEMBL
    Q53FP3
    Related
    ENSP00000440897.1, ENST00000541387.5
    Conserved Domains (2) summary
    pfam00266
    Location:60 → 370
    Aminotran_5; Aminotransferase class-V
    cl18945
    Location:58 → 406
    AAT_I; Aspartate aminotransferase (AAT) superfamily (fold type I) of pyridoxal phosphate (PLP)-dependent enzymes. PLP combines with an alpha-amino acid to form a compound called a Schiff base or aldimine intermediate, which depending on the reaction, is the ...

  2. NM_021100.5 → NP_066923.3  cysteine desulfurase isoform a precursor

    See identical proteins and their annotated locations for NP_066923.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longer isoform (a).
    Source sequence(s)
    AK001265, AK001470, AK223239, AL109827, DA082829, R16676
    Consensus CDS
    CCDS13262.1
    UniProtKB/Swiss-Prot
    B3KMA5, B4DXK9, E1P5R8, F5GYK5, Q6P0L8, Q9NTZ5, Q9Y481, Q9Y697
    UniProtKB/TrEMBL
    Q53FP3
    Related
    ENSP00000363205.3, ENST00000374092.9
    Conserved Domains (2) summary
    PRK14012
    Location:58 → 457
    PRK14012; cysteine desulfurase; Provisional
    pfam00266
    Location:60 → 421
    Aminotran_5; Aminotransferase class-V

RNA

  1. NR_037570.3 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) contains an alternate internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AK001470, AK297969, AL109827, R16676

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000020.11 Reference GRCh38.p14 Primary Assembly

    Range
    35668052..35699352 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060944.1 Alternate T2T-CHM13v2.0

    Range
    37389027..37420327 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_181679.1: Suppressed sequence

    Description
    NM_181679.1: This RefSeq was permanently suppressed because its 3'' coding region exon was mostly repetitive sequence and the C-terminus of its predicted protein has no support.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9Y697.3 GenPept UniProtKB/Swiss-Prot:Q9Y697

Gene LinkOut

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