NFS1 NFS1 cysteine desulfurase [Homo sapiens (human)] - Gene

Summary

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: mouse all
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Genomic context

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_000020.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

REN58688 (e-PCR)
- UniSTS:383488

REN58689 (e-PCR)
- UniSTS:383489

REN58690 (e-PCR)
- UniSTS:383490

REN58691 (e-PCR)
- UniSTS:383491

REN58692 (e-PCR)
- UniSTS:383492

REN58693 (e-PCR)
- UniSTS:383493

REN58694 (e-PCR)
- UniSTS:383494

REN58695 (e-PCR)
- UniSTS:383495

REN58696 (e-PCR)
- UniSTS:383496

REN58697 (e-PCR)
- UniSTS:383497

D11S2921 (e-PCR)
- UniSTS:152074

REN58698 (e-PCR)
- UniSTS:383498

SHGC-32196 (e-PCR)
- UniSTS:70667

REN58699 (e-PCR)
- UniSTS:383499

ECD07471 (e-PCR)
- UniSTS:288524

REN58700 (e-PCR)
- UniSTS:383500

L17688 (e-PCR)
- UniSTS:74509

ECD07472 (e-PCR)
- UniSTS:288525

REN58701 (e-PCR)
- UniSTS:383501

REN58702 (e-PCR)
- UniSTS:383502

REN58703 (e-PCR)
- UniSTS:383503

ECD10561 (e-PCR)
- UniSTS:291600

REN58704 (e-PCR)
- UniSTS:383504

REN58705 (e-PCR)
- UniSTS:383505

REN58706 (e-PCR)
- UniSTS:383506

REN58707 (e-PCR)
- UniSTS:383507

REN58708 (e-PCR)
- UniSTS:383508

REN58709 (e-PCR)
- UniSTS:383509

REN58710 (e-PCR)
- UniSTS:383510

REN58711 (e-PCR)
- UniSTS:383511

REN58712 (e-PCR)
- UniSTS:383512

REN58713 (e-PCR)
- UniSTS:383513

REN58714 (e-PCR)
- UniSTS:383514

REN58715 (e-PCR)
- UniSTS:383515

REN58716 (e-PCR)
- UniSTS:383516

REN58717 (e-PCR)
- UniSTS:383517

REN58718 (e-PCR)
- UniSTS:383518

REN58719 (e-PCR)
- UniSTS:383519

REN58720 (e-PCR)
- UniSTS:383520

REN58721 (e-PCR)
- UniSTS:383521

REN58722 (e-PCR)
- UniSTS:383522

REN58723 (e-PCR)
- UniSTS:383523

REN58724 (e-PCR)
- UniSTS:383524

REN58725 (e-PCR)
- UniSTS:383525

REN58726 (e-PCR)
- UniSTS:383526

REN58727 (e-PCR)
- UniSTS:383527

REN58730 (e-PCR)
- UniSTS:383530

REN58731 (e-PCR)
- UniSTS:383531

REN58732 (e-PCR)
- UniSTS:383532

REN58733 (e-PCR)
- UniSTS:383533

REN58734 (e-PCR)
- UniSTS:383534

REN58735 (e-PCR)
- UniSTS:383535

REN58736 (e-PCR)
- UniSTS:383536

REN58737 (e-PCR)
- UniSTS:383537

D8S2278 (e-PCR)
- UniSTS:473906

ECD05448 (e-PCR)
- UniSTS:286514

REN58738 (e-PCR)
- UniSTS:383538

D8S2279 (e-PCR)
- UniSTS:473907

REN58739 (e-PCR)
- UniSTS:383539

REN58740 (e-PCR)
- UniSTS:383540

REN58741 (e-PCR)
- UniSTS:383541

REN58742 (e-PCR)
- UniSTS:383542

ECD00802 (e-PCR)
- UniSTS:281911

REN58743 (e-PCR)
- UniSTS:383543

REN58744 (e-PCR)
- UniSTS:383544

REN58745 (e-PCR)
- UniSTS:383545

REN58746 (e-PCR)
- UniSTS:383546

REN58747 (e-PCR)
- UniSTS:383547

REN58748 (e-PCR)
- UniSTS:383548

REN58749 (e-PCR)
- UniSTS:383549

REN58750 (e-PCR)
- UniSTS:383550

REN58751 (e-PCR)
- UniSTS:383551

REN58752 (e-PCR)
- UniSTS:383552

REN58753 (e-PCR)
- UniSTS:383553

ECD03398 (e-PCR)
- UniSTS:284482

ECD11126 (e-PCR)
- UniSTS:292162

REN58754 (e-PCR)
- UniSTS:383554

REN58755 (e-PCR)
- UniSTS:383555

REN58756 (e-PCR)
- UniSTS:383556

REN58757 (e-PCR)
- UniSTS:383557

REN58758 (e-PCR)
- UniSTS:383558

REN58759 (e-PCR)
- UniSTS:383559

REN58760 (e-PCR)
- UniSTS:383560

REN58761 (e-PCR)
- UniSTS:383561

REN58762 (e-PCR)
- UniSTS:383562

REN58763 (e-PCR)
- UniSTS:383563

REN58764 (e-PCR)
- UniSTS:383564

REN58765 (e-PCR)
- UniSTS:383565

REN58766 (e-PCR)
- UniSTS:383566

REN58767 (e-PCR)
- UniSTS:383567

REN58768 (e-PCR)
- UniSTS:383568

REN58769 (e-PCR)
- UniSTS:383569

ECD23994 (e-PCR)
- UniSTS:304978

REN58770 (e-PCR)
- UniSTS:383570

REN58771 (e-PCR)
- UniSTS:383571

REN58772 (e-PCR)
- UniSTS:383572

L18426 (e-PCR)
- UniSTS:34648

ECD11665 (e-PCR)
- UniSTS:292701

ECD10648 (e-PCR)
- UniSTS:291687

ECD17095 (e-PCR)
- UniSTS:298108

NFS1__6240.2 (e-PCR)
- UniSTS:468093

ECD10162 (e-PCR)
- UniSTS:291202

D10Bir17 (e-PCR), detects polymorphism
- UniSTS:141482

RH41786 (e-PCR)
- UniSTS:14767

ECD21003 (e-PCR)
- UniSTS:302000

ECD22591 (e-PCR)
- UniSTS:303577

ECD23105 (e-PCR)
- UniSTS:304089

ECD22592 (e-PCR)
- UniSTS:303578

ECD10264 (e-PCR)
- UniSTS:291304

REN58665 (e-PCR)
- UniSTS:383465

REN58666 (e-PCR)
- UniSTS:383466

REN58667 (e-PCR)
- UniSTS:383467

REN58668 (e-PCR)
- UniSTS:383468

ECD07439 (e-PCR)
- UniSTS:288493

REN58669 (e-PCR)
- UniSTS:383469

REN58670 (e-PCR)
- UniSTS:383470

REN58671 (e-PCR)
- UniSTS:383471

REN58672 (e-PCR)
- UniSTS:383472

ECD17212 (e-PCR)
- UniSTS:298225

REN58673 (e-PCR)
- UniSTS:383473

REN58674 (e-PCR)
- UniSTS:383474

REN58675 (e-PCR)
- UniSTS:383475

REN58676 (e-PCR)
- UniSTS:383476

REN58677 (e-PCR)
- UniSTS:383477

REN58678 (e-PCR)
- UniSTS:383478

REN58679 (e-PCR)
- UniSTS:383479

REN58680 (e-PCR)
- UniSTS:383480

REN58681 (e-PCR)
- UniSTS:383481

REN58682 (e-PCR)
- UniSTS:383482

STS-D45601 (e-PCR)
- UniSTS:28155

REN58683 (e-PCR)
- UniSTS:383483

REN58684 (e-PCR)
- UniSTS:383484

ECD12340 (e-PCR)
- UniSTS:293373

REN58685 (e-PCR)
- UniSTS:383485

REN58686 (e-PCR)
- UniSTS:383486

REN58687 (e-PCR)
- UniSTS:383487

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

EC 2.8.1.7

NP_066923.3

EC 2.8.1.7

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

NG_033237.1 RefSeqGene

Range

5014..36314

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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 ...
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

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

NC_000020.11 Reference GRCh38.p14 Primary Assembly

Range

35668052..35699352 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

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

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.