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Protein

Cysteine desulfurase, mitochondrial

Gene

NFS1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalyzes the removal of elemental sulfur from cysteine to produce alanine. It supplies the inorganic sulfur for iron-sulfur (Fe-S) clusters. May be involved in the biosynthesis of molybdenum cofactor.1 Publication

Catalytic activityi

L-cysteine + acceptor = L-alanine + S-sulfanyl-acceptor.

Cofactori

pyridoxal 5'-phosphateBy similarity

Kineticsi

Kinetic parameter was determined for the protein lacking the 55 N-terminal amino acids and in a complex with LYRM4.
  1. KM=434.75 µM for L-cysteine1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei207Pyridoxal phosphateBy similarity1
    Binding sitei235Pyridoxal phosphateBy similarity1
    Binding sitei295Pyridoxal phosphateBy similarity1
    Active sitei381Cysteine persulfide intermediateBy similarity1
    Metal bindingi381Iron-sulfur (2Fe-2S); via persulfide group; shared with ISCUBy similarity1

    GO - Molecular functioni

    • cysteine desulfurase activity Source: HGNC
    • iron-sulfur cluster binding Source: UniProtKB-KW
    • metal ion binding Source: UniProtKB-KW
    • protein homodimerization activity Source: HGNC
    • pyridoxal phosphate binding Source: InterPro

    GO - Biological processi

    Keywordsi

    Molecular functionTransferase
    Biological processMolybdenum cofactor biosynthesis
    LigandIron, Iron-sulfur, Metal-binding, Pyridoxal phosphate

    Enzyme and pathway databases

    BioCyciMetaCyc:HS01304-MONOMER
    ReactomeiR-HSA-1362409 Mitochondrial iron-sulfur cluster biogenesis
    R-HSA-947581 Molybdenum cofactor biosynthesis

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cysteine desulfurase, mitochondrial (EC:2.8.1.7)
    Gene namesi
    Name:NFS1
    Synonyms:NIFS
    ORF Names:HUSSY-08
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 20

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000244005.12
    HGNCiHGNC:15910 NFS1
    MIMi603485 gene
    neXtProtiNX_Q9Y697

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cytoplasm, Mitochondrion, Nucleus

    Pathology & Biotechi

    Organism-specific databases

    MalaCardsiNFS1
    OpenTargetsiENSG00000244005
    Orphaneti397593 Severe neonatal lactic acidosis due to NFS1-ISD11 complex deficiency
    PharmGKBiPA31607

    Chemistry databases

    DrugBankiDB00160 L-Alanine
    DB00151 L-Cysteine
    DB00114 Pyridoxal Phosphate

    Polymorphism and mutation databases

    BioMutaiNFS1
    DMDMi62512153

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_0000001292? – 457Cysteine desulfurase, mitochondrial
    Transit peptidei1 – ?MitochondrionSequence analysis

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei258N6-(pyridoxal phosphate)lysineBy similarity1

    Proteomic databases

    EPDiQ9Y697
    PaxDbiQ9Y697
    PeptideAtlasiQ9Y697
    PRIDEiQ9Y697

    PTM databases

    iPTMnetiQ9Y697
    PhosphoSitePlusiQ9Y697
    SwissPalmiQ9Y697

    Expressioni

    Tissue specificityi

    Predominantly expressed in heart and skeletal muscle. Also found in brain, liver and pancreas.

    Gene expression databases

    BgeeiENSG00000244005
    CleanExiHS_NFS1
    ExpressionAtlasiQ9Y697 baseline and differential
    GenevisibleiQ9Y697 HS

    Organism-specific databases

    HPAiCAB034314
    HPA051801
    HPA054755

    Interactioni

    Subunit structurei

    Binds ISCU/NIFUN (PubMed:11060020). Forms a complex with LYRM4 (PubMed:18650437, PubMed:19454487). Interacts with HSPA9 (PubMed:26702583).4 Publications

    GO - Molecular functioni

    • protein homodimerization activity Source: HGNC

    Protein-protein interaction databases

    BioGridi114516, 38 interactors
    IntActiQ9Y697, 14 interactors
    STRINGi9606.ENSP00000363205

    Structurei

    Secondary structure

    1457
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi64 – 66Combined sources3
    Helixi71 – 81Combined sources11
    Helixi98 – 114Combined sources17
    Helixi118 – 120Combined sources3
    Beta strandi121 – 126Combined sources6
    Helixi127 – 141Combined sources15
    Turni142 – 145Combined sources4
    Beta strandi148 – 152Combined sources5
    Helixi157 – 168Combined sources12
    Beta strandi172 – 176Combined sources5
    Helixi186 – 192Combined sources7
    Beta strandi197 – 201Combined sources5
    Turni207 – 209Combined sources3
    Helixi215 – 225Combined sources11
    Beta strandi228 – 232Combined sources5
    Turni234 – 239Combined sources6
    Turni244 – 248Combined sources5
    Beta strandi250 – 256Combined sources7
    Turni257 – 260Combined sources4
    Beta strandi266 – 270Combined sources5
    Turni272 – 275Combined sources4
    Helixi288 – 290Combined sources3
    Helixi298 – 336Combined sources39
    Beta strandi340 – 342Combined sources3
    Helixi346 – 348Combined sources3
    Beta strandi353 – 357Combined sources5
    Helixi363 – 369Combined sources7
    Helixi380 – 382Combined sources3
    Beta strandi383 – 385Combined sources3
    Helixi390 – 394Combined sources5
    Helixi399 – 403Combined sources5
    Beta strandi405 – 409Combined sources5
    Helixi416 – 427Combined sources12
    Helixi439 – 442Combined sources4
    Turni449 – 451Combined sources3

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    5KZ5electron microscopy14.301/2/3/4/M/N/O/P/Q/R/S/T67-457[»]
    5USRX-ray3.09A/C/E/G56-457[»]
    5WGBX-ray2.75A56-457[»]
    5WKPX-ray3.15A/E56-457[»]
    5WLWX-ray3.32A/E56-457[»]
    ProteinModelPortaliQ9Y697
    SMRiQ9Y697
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni127 – 128Pyridoxal phosphate bindingBy similarity2
    Regioni255 – 257Pyridoxal phosphate bindingBy similarity3

    Sequence similaritiesi

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    eggNOGiKOG1549 Eukaryota
    COG1104 LUCA
    GeneTreeiENSGT00530000063513
    HOGENOMiHOG000017510
    HOVERGENiHBG003708
    InParanoidiQ9Y697
    KOiK04487
    OMAiEPIQSGG
    OrthoDBiEOG091G072R
    PhylomeDBiQ9Y697
    TreeFamiTF105658

    Family and domain databases

    Gene3Di3.40.640.10, 1 hit
    3.90.1150.10, 2 hits
    HAMAPiMF_00331 Cys_desulf_IscS, 1 hit
    InterProiView protein in InterPro
    IPR000192 Aminotrans_V_dom
    IPR020578 Aminotrans_V_PyrdxlP_BS
    IPR010240 Cys_deSase_IscS
    IPR016454 Cysteine_dSase
    IPR015424 PyrdxlP-dep_Trfase
    IPR015422 PyrdxlP-dep_Trfase_dom1
    IPR015421 PyrdxlP-dep_Trfase_major
    PANTHERiPTHR11601:SF34 PTHR11601:SF34, 1 hit
    PfamiView protein in Pfam
    PF00266 Aminotran_5, 1 hit
    PIRSFiPIRSF005572 NifS, 1 hit
    SUPFAMiSSF53383 SSF53383, 1 hit
    TIGRFAMsiTIGR02006 IscS, 1 hit
    PROSITEiView protein in PROSITE
    PS00595 AA_TRANSFER_CLASS_5, 1 hit

    Sequences (3)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 3 isoformsi produced by alternative splicing and alternative initiation. AlignAdd to basket

    Note: Individual cells may vary AUG utilization in accordance with changes in metabolic status, the cytosolic pH being a strong determinant of this modulation.
    Isoform Mitochondrial (identifier: Q9Y697-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MLLRAAWRRA AVAVTAAPGP KPAAPTRGLR LRVGDRAPQS AVPADTAAAP
    60 70 80 90 100
    EVGPVLRPLY MDVQATTPLD PRVLDAMLPY LINYYGNPHS RTHAYGWESE
    110 120 130 140 150
    AAMERARQQV ASLIGADPRE IIFTSGATES NNIAIKGVAR FYRSRKKHLI
    160 170 180 190 200
    TTQTEHKCVL DSCRSLEAEG FQVTYLPVQK SGIIDLKELE AAIQPDTSLV
    210 220 230 240 250
    SVMTVNNEIG VKQPIAEIGR ICSSRKVYFH TDAAQAVGKI PLDVNDMKID
    260 270 280 290 300
    LMSISGHKIY GPKGVGAIYI RRRPRVRVEA LQSGGGQERG MRSGTVPTPL
    310 320 330 340 350
    VVGLGAACEV AQQEMEYDHK RISKLSERLI QNIMKSLPDV VMNGDPKHHY
    360 370 380 390 400
    PGCINLSFAY VEGESLLMAL KDVALSSGSA CTSASLEPSY VLRAIGTDED
    410 420 430 440 450
    LAHSSIRFGI GRFTTEEEVD YTVEKCIQHV KRLREMSPLW EMVQDGIDLK

    SIKWTQH
    Length:457
    Mass (Da):50,196
    Last modified:April 12, 2005 - v3
    Checksum:iFDE76177DB6E751B
    GO
    Isoform Cytoplasmic (identifier: Q9Y697-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-60: Missing.

    Show »
    Length:397
    Mass (Da):44,017
    Checksum:i61DF3AD65D5CDD3C
    GO
    Isoform 3 (identifier: Q9Y697-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         136-186: Missing.

    Show »
    Length:406
    Mass (Da):44,362
    Checksum:i422B10BDBCD0FAB2
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti5A → V in AAD09187 (PubMed:9885568).Curated1
    Sequence conflicti47A → T in AAD09187 (PubMed:9885568).Curated1
    Sequence conflicti197T → A in BAG63421 (PubMed:14702039).Curated1
    Sequence conflicti412R → A in AAD09187 (PubMed:9885568).Curated1
    Sequence conflicti431K → N in AAD09187 (PubMed:9885568).Curated1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0186461 – 60Missing in isoform Cytoplasmic. 4 PublicationsAdd BLAST60
    Alternative sequenceiVSP_045860136 – 186Missing in isoform 3. 1 PublicationAdd BLAST51

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF097025 mRNA Translation: AAD09187.2
    AK001470 mRNA Translation: BAG50917.1
    AK302023 mRNA Translation: BAG63421.1
    AL109827 Genomic DNA No translation available.
    AL357374 Genomic DNA No translation available.
    CH471077 Genomic DNA Translation: EAW76170.1
    CH471077 Genomic DNA Translation: EAW76172.1
    BC065560 mRNA Translation: AAH65560.1
    AJ010952 mRNA Translation: CAA09424.1
    CCDSiCCDS13262.1 [Q9Y697-1]
    CCDS56185.1 [Q9Y697-3]
    RefSeqiNP_001185918.1, NM_001198989.1 [Q9Y697-3]
    NP_066923.3, NM_021100.4 [Q9Y697-1]
    UniGeneiHs.194692

    Genome annotation databases

    EnsembliENST00000374085; ENSP00000363198; ENSG00000244005 [Q9Y697-2]
    ENST00000374092; ENSP00000363205; ENSG00000244005 [Q9Y697-1]
    ENST00000397425; ENSP00000380570; ENSG00000244005 [Q9Y697-2]
    ENST00000541387; ENSP00000440897; ENSG00000244005 [Q9Y697-3]
    GeneIDi9054
    KEGGihsa:9054
    UCSCiuc002xdt.3 human [Q9Y697-1]

    Keywords - Coding sequence diversityi

    Alternative initiation, Alternative splicing

    Similar proteinsi

    Entry informationi

    Entry nameiNFS1_HUMAN
    AccessioniPrimary (citable) accession number: Q9Y697
    Secondary accession number(s): B3KMA5
    , B4DXK9, E1P5R8, F5GYK5, Q6P0L8, Q9NTZ5, Q9Y481
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
    Last sequence update: April 12, 2005
    Last modified: May 23, 2018
    This is version 174 of the entry and version 3 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

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