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    NFS1 NFS1 cysteine desulfurase [ Homo sapiens (human) ]

    Gene ID: 9054, updated on 27-Nov-2024

    GeneRIFs: Gene References Into Functions

    GeneRIFPubMed TitleDate
    Phosphorylated NFS1 weakens oxaliplatin-based chemosensitivity of colorectal cancer by preventing PANoptosis.

    Phosphorylated NFS1 weakens oxaliplatin-based chemosensitivity of colorectal cancer by preventing PANoptosis.
    Lin JF, Hu PS, Wang YY, Tan YT, Yu K, Liao K, Wu QN, Li T, Meng Q, Lin JZ, Liu ZX, Pu HY, Ju HQ, Xu RH, Qiu MZ., Free PMC Article

    04/16/2022
    By different methods, this study identified a MOCS3-independent novel localization of NFS1 at the centrosome.

    Analysis of the Cellular Roles of MOCS3 Identifies a MOCS3-Independent Localization of NFS1 at the Tips of the Centrosome.
    Neukranz Y, Kotter A, Beilschmidt L, Marelja Z, Helm M, Gräf R, Leimkühler S.

    01/18/2020
    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.

    Architectural Features of Human Mitochondrial Cysteine Desulfurase Complexes from Crosslinking Mass Spectrometry and Small-Angle X-Ray Scattering.
    Cai K, Frederick RO, Dashti H, Markley JL., Free PMC Article

    08/10/2019
    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.

    Structure of the human frataxin-bound iron-sulfur cluster assembly complex provides insight into its activation mechanism.
    Fox NG, Yu X, Feng X, Bailey HJ, Martelli A, Nabhan JF, Strain-Damerell C, Bulawa C, Yue WW, Han S., Free PMC Article

    06/8/2019
    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

    Zinc(II) binding on human wild-type ISCU and Met140 variants modulates NFS1 desulfurase activity.
    Fox NG, Martelli A, Nabhan JF, Janz J, Borkowska O, Bulawa C, Yue WW., Free PMC Article

    12/1/2018
    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

    Structure of human Fe-S assembly subcomplex reveals unexpected cysteine desulfurase architecture and acyl-ACP-ISD11 interactions.
    Cory SA, Van Vranken JG, Brignole EJ, Patra S, Winge DR, Drennan CL, Rutter J, Barondeau DP., Free PMC Article

    06/9/2018
    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

    NFS1 undergoes positive selection in lung tumours and protects cells from ferroptosis.
    Alvarez SW, Sviderskiy VO, Terzi EM, Papagiannakopoulos T, Moreira AL, Adams S, Sabatini DM, Birsoy K, Possemato R., Free PMC Article

    04/14/2018
    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.

    Functional Complementation Studies Reveal Different Interaction Partners of Escherichia coli IscS and Human NFS1.
    Bühning M, Friemel M, Leimkühler S.

    09/2/2017
    The NFS1/ISD11 complex further interacts with scaffold protein ISCU and regulator protein frataxin, thereby forming a quaternary complex for Fe-S cluster formation.

    The N-Terminus of Iron-Sulfur Cluster Assembly Factor ISD11 Is Crucial for Subcellular Targeting and Interaction with l-Cysteine Desulfurase NFS1.
    Friemel M, Marelja Z, Li K, Leimkühler S.

    06/3/2017
    FDX1 and FDX2 both bind NFS1 and donate electrons for iron-sulfur cluster biosynthesis.

    Human Mitochondrial Ferredoxin 1 (FDX1) and Ferredoxin 2 (FDX2) Both Bind Cysteine Desulfurase and Donate Electrons for Iron-Sulfur Cluster Biosynthesis.
    Cai K, Tonelli M, Frederick RO, Markley JL., Free PMC Article

    05/20/2017
    Molecular dynamics flexible fitting of protein structures docked into the EM map of the model revealed a [FXN(42-210)]24.[NFS1]24.[ISD11]24.[ISCU]24 complex, consistent with the measured 1:1:1:1 stoichiometry of its four components.

    Architecture of the Human Mitochondrial Iron-Sulfur Cluster Assembly Machinery.
    Gakh O, Ranatunga W, Smith DY 4th, Ahlgren EC, Al-Karadaghi S, Thompson JR, Isaya G., Free PMC Article

    05/20/2017
    Our findings highlight that the ISD11 R68A/R68L mutation display reduced affinity to form a stable subcomplex with NFS1, and thereby fails to prevent NFS1 aggregation resulting in impairment of the Fe-S cluster biogenesis

    Mapping Key Residues of ISD11 Critical for NFS1-ISD11 Subcomplex Stability: IMPLICATIONS IN THE DEVELOPMENT OF MITOCHONDRIAL DISORDER, COXPD19.
    Saha PP, Srivastava S, Kumar S K P, Sinha D, D'Silva P., Free PMC Article

    02/27/2016
    The data presented here show that the Isu1 suppressor mimics the frataxin effects on Nfs1, explaining the bypassing activity.

    Frataxin directly stimulates mitochondrial cysteine desulfurase by exposing substrate-binding sites, and a mutant Fe-S cluster scaffold protein with frataxin-bypassing ability acts similarly.
    Pandey A, Gordon DM, Pain J, Stemmler TL, Dancis A, Pain D., Free PMC Article

    02/22/2014
    NFS1 binds preferentially to the D-state of ISCU while mtHSP70 binds preferentially to the D-state of ISCU and HSC20 binds preferentially to the S-state of ISCU.

    Human mitochondrial chaperone (mtHSP70) and cysteine desulfurase (NFS1) bind preferentially to the disordered conformation, whereas co-chaperone (HSC20) binds to the structured conformation of the iron-sulfur cluster scaffold protein (ISCU).
    Cai K, Frederick RO, Kim JH, Reinen NM, Tonelli M, Markley JL., Free PMC Article

    12/7/2013
    the interaction of NFS1 and MOCS3 in the cytosol of human cells, is reported.

    The L-cysteine desulfurase NFS1 is localized in the cytosol where it provides the sulfur for molybdenum cofactor biosynthesis in humans.
    Marelja Z, Mullick Chowdhury M, Dosche C, Hille C, Baumann O, Löhmannsröben HG, Leimkühler S., Free PMC Article

    10/26/2013
    Nfs1, the cysteine desulfurase responsible for providing sulfur for cluster formation, is required for the increased Isu stability occurring after disruption of cluster formation on or transfer from Isu

    Cysteine desulfurase Nfs1 and Pim1 protease control levels of Isu, the Fe-S cluster biogenesis scaffold.
    Song JY, Marszalek J, Craig EA., Free PMC Article

    09/22/2012
    Observational study of gene-disease association. (HuGE Navigator)

    Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
    Hendrickson SL, Lautenberger JA, Chinn LW, Malasky M, Sezgin E, Kingsley LA, Goedert JJ, Kirk GD, Gomperts ED, Buchbinder SP, Troyer JL, O'Brien SJ., Free PMC Article

    12/5/2010
    Icp55 protease and its substrate Nfs1 appear to be dual distributed between the nucleus and mitochondria

    Dual targeting of Nfs1 and discovery of its novel processing enzyme, Icp55.
    Naamati A, Regev-Rudzki N, Galperin S, Lill R, Pines O., Free PMC Article

    01/21/2010
    Nfs1 acts as a sulfur donor for MOCS3, a protein involved in molybdenum cofactor biosynthesis

    A novel role for human Nfs1 in the cytoplasm: Nfs1 acts as a sulfur donor for MOCS3, a protein involved in molybdenum cofactor biosynthesis.
    Marelja Z, Stöcklein W, Nimtz M, Leimkühler S.

    01/21/2010
    the cytosolic form of ISCS is a functional cysteine desulfurase that can collaborate with cytosolic ISCU to promote de novo iron-sulfur cluster formation

    Roles of the mammalian cytosolic cysteine desulfurase, ISCS, and scaffold protein, ISCU, in iron-sulfur cluster assembly.
    Li K, Tong WH, Hughes RM, Rouault TA.

    01/21/2010
    Results show that human Nfs1 is required inside mitochondria for efficient maturation of cellular iron/sulfur proteins.

    Role of human mitochondrial Nfs1 in cytosolic iron-sulfur protein biogenesis and iron regulation.
    Biederbick A, Stehling O, Rösser R, Niggemeyer B, Nakai Y, Elsässer HP, Lill R., Free PMC Article

    01/21/2010
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