NFS1_HUMAN
ID NFS1_HUMAN Reviewed; 457 AA.
AC Q9Y697; B3KMA5; B4DXK9; E1P5R8; F5GYK5; Q6P0L8; Q9NTZ5; Q9Y481;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 12-APR-2005, sequence version 3.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=Cysteine desulfurase, mitochondrial {ECO:0000305};
DE EC=2.8.1.7 {ECO:0000269|PubMed:18650437};
DE Flags: Precursor;
GN Name=NFS1 {ECO:0000303|PubMed:18650437, ECO:0000312|HGNC:HGNC:15910};
GN Synonyms=NIFS {ECO:0000303|PubMed:9885568}; ORFNames=HUSSY-08;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CYTOPLASMIC), ALTERNATIVE INITIATION,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=9885568; DOI=10.1016/s1097-2765(00)80295-6;
RA Land T., Rouault T.A.;
RT "Targeting of a human iron-sulfur cluster assembly enzyme, nifs, to
RT different subcellular compartments is regulated through alternative AUG
RT utilization.";
RL Mol. Cell 2:807-815(1998).
RN [2]
RP SEQUENCE REVISION TO 380-402.
RA Land T., Rouault T.A.;
RL Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS CYTOPLASMIC AND 3).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CYTOPLASMIC).
RC TISSUE=Pancreas;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 140-457 (ISOFORM CYTOPLASMIC).
RX PubMed=11124703;
RX DOI=10.1002/1097-0061(200101)18:1<69::aid-yea647>3.0.co;2-h;
RA Stanchi F., Bertocco E., Toppo S., Dioguardi R., Simionati B., Cannata N.,
RA Zimbello R., Lanfranchi G., Valle G.;
RT "Characterization of 16 novel human genes showing high similarity to yeast
RT sequences.";
RL Yeast 18:69-80(2001).
RN [8]
RP INTERACTION WITH ISCU.
RX PubMed=11060020; DOI=10.1093/emboj/19.21.5692;
RA Tong W.-H., Rouault T.;
RT "Distinct iron-sulfur cluster assembly complexes exist in the cytosol and
RT mitochondria of human cells.";
RL EMBO J. 19:5692-5700(2000).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP INTERACTION WITH LYRM4.
RX PubMed=18650437; DOI=10.1074/jbc.m804064200;
RA Marelja Z., Stoecklein W., Nimtz M., Leimkuehler S.;
RT "A novel role for human Nfs1 in the cytoplasm: Nfs1 acts as a sulfur donor
RT for MOCS3, a protein involved in molybdenum cofactor biosynthesis.";
RL J. Biol. Chem. 283:25178-25185(2008).
RN [10]
RP INTERACTION WITH LYRM4, AND SUBCELLULAR LOCATION.
RX PubMed=19454487; DOI=10.1093/hmg/ddp239;
RA Shi Y., Ghosh M.C., Tong W.H., Rouault T.A.;
RT "Human ISD11 is essential for both iron-sulfur cluster assembly and
RT maintenance of normal cellular iron homeostasis.";
RL Hum. Mol. Genet. 18:3014-3025(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [13]
RP INTERACTION WITH HSPA9, AND SUBCELLULAR LOCATION.
RX PubMed=26702583; DOI=10.1016/j.mito.2015.12.005;
RA Shan Y., Cortopassi G.;
RT "Mitochondrial Hspa9/Mortalin regulates erythroid differentiation via iron-
RT sulfur cluster assembly.";
RL Mitochondrion 26:94-103(2016).
RN [14]
RP VARIANT COXPD52 GLN-72, INVOLVEMENT IN COXPD52, AND CHARACTERIZATION OF
RP VARIANT COXPD52 GLN-72.
RX PubMed=24498631; DOI=10.1002/mgg3.46;
RA Farhan S.M., Wang J., Robinson J.F., Lahiry P., Siu V.M., Prasad C.,
RA Kronick J.B., Ramsay D.A., Rupar C.A., Hegele R.A.;
RT "Exome sequencing identifies NFS1 deficiency in a novel Fe-S cluster
RT disease, infantile mitochondrial complex II/III deficiency.";
RL Mol. Genet. Genomic Med. 2:73-80(2014).
RN [15]
RP VARIANT COXPD52 GLN-72, AND INVOLVEMENT IN COXPD52.
RX PubMed=33457206; DOI=10.1016/j.ymgmr.2020.100699;
RG Regeneron Genetics Center;
RA Hershkovitz T., Kurolap A., Tal G., Paperna T., Mory A., Staples J.,
RA Brigatti K.W., Gonzaga-Jauregui C., Dumin E., Saada A., Mandel H.,
RA Baris Feldman H.;
RT "A recurring NFS1 pathogenic variant causes a mitochondrial disorder with
RT variable intra-familial patient outcomes.";
RL Mol. Genet. Metab. Rep. 26:100699-100699(2021).
CC -!- FUNCTION: Catalyzes the removal of elemental sulfur from cysteine to
CC produce alanine (PubMed:18650437). It supplies the inorganic sulfur for
CC iron-sulfur (Fe-S) clusters. May be involved in the biosynthesis of
CC molybdenum cofactor (PubMed:18650437). {ECO:0000269|PubMed:18650437}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[sulfur carrier]-H + L-cysteine = [sulfur carrier]-SH + L-
CC alanine; Xref=Rhea:RHEA:43892, Rhea:RHEA-COMP:14737, Rhea:RHEA-
CC COMP:14739, ChEBI:CHEBI:29917, ChEBI:CHEBI:35235, ChEBI:CHEBI:57972,
CC ChEBI:CHEBI:64428; EC=2.8.1.7;
CC Evidence={ECO:0000269|PubMed:18650437};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000250|UniProtKB:O29689};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=434.75 uM for L-cysteine {ECO:0000269|PubMed:18650437};
CC Note=Kinetic parameter was determined for the protein lacking the 55
CC N-terminal amino acids and in a complex with LYRM4.
CC {ECO:0000269|PubMed:18650437};
CC -!- SUBUNIT: Binds ISCU/NIFUN (PubMed:11060020). Forms a complex with LYRM4
CC (PubMed:18650437, PubMed:19454487). Interacts with HSPA9
CC (PubMed:26702583). {ECO:0000269|PubMed:11060020,
CC ECO:0000269|PubMed:18650437, ECO:0000269|PubMed:19454487,
CC ECO:0000269|PubMed:26702583}.
CC -!- INTERACTION:
CC Q9Y697; Q9NZJ6: COQ3; NbExp=3; IntAct=EBI-1751791, EBI-10897372;
CC Q9Y697; Q9HD34: LYRM4; NbExp=8; IntAct=EBI-1751791, EBI-3920810;
CC -!- SUBCELLULAR LOCATION: [Isoform Mitochondrial]: Mitochondrion
CC {ECO:0000269|PubMed:19454487, ECO:0000269|PubMed:26702583,
CC ECO:0000269|PubMed:9885568}.
CC -!- SUBCELLULAR LOCATION: [Isoform Cytoplasmic]: Cytoplasm
CC {ECO:0000269|PubMed:9885568}. Nucleus {ECO:0000269|PubMed:19454487,
CC ECO:0000269|PubMed:9885568}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=3;
CC Comment=Individual cells may vary AUG utilization in accordance with
CC changes in metabolic status, the cytosolic pH being a strong
CC determinant of this modulation.;
CC Name=Mitochondrial;
CC IsoId=Q9Y697-1; Sequence=Displayed;
CC Name=Cytoplasmic;
CC IsoId=Q9Y697-2; Sequence=VSP_018646;
CC Name=3;
CC IsoId=Q9Y697-3; Sequence=VSP_045860;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in heart and skeletal
CC muscle. Also found in brain, liver and pancreas.
CC {ECO:0000269|PubMed:9885568}.
CC -!- DISEASE: Combined oxidative phosphorylation deficiency 52 (COXPD52)
CC [MIM:619386]: An autosomal recessive mitochondrial disorder with onset
CC in infancy, characterized by lactic acidemia, hypotonia, respiratory
CC chain complex II and III deficiency, multisystem organ failure and
CC abnormal mitochondria. {ECO:0000269|PubMed:24498631,
CC ECO:0000269|PubMed:33457206}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the class-V pyridoxal-phosphate-dependent
CC aminotransferase family. NifS/IscS subfamily. {ECO:0000305}.
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DR EMBL; AF097025; AAD09187.2; -; mRNA.
DR EMBL; AK001470; BAG50917.1; -; mRNA.
DR EMBL; AK302023; BAG63421.1; -; mRNA.
DR EMBL; AL109827; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL357374; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471077; EAW76170.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76172.1; -; Genomic_DNA.
DR EMBL; BC065560; AAH65560.1; -; mRNA.
DR EMBL; AJ010952; CAA09424.1; -; mRNA.
DR CCDS; CCDS13262.1; -. [Q9Y697-1]
DR CCDS; CCDS56185.1; -. [Q9Y697-3]
DR RefSeq; NP_001185918.1; NM_001198989.1. [Q9Y697-3]
DR RefSeq; NP_066923.3; NM_021100.4. [Q9Y697-1]
DR PDB; 5KZ5; EM; 14.30 A; 1/2/3/4/M/N/O/P/Q/R/S/T=67-457.
DR PDB; 5USR; X-ray; 3.09 A; A/C/E/G=56-457.
DR PDB; 5WGB; X-ray; 2.75 A; A=56-457.
DR PDB; 5WKP; X-ray; 3.15 A; A/E=56-457.
DR PDB; 5WLW; X-ray; 3.32 A; A/E=56-457.
DR PDB; 6NZU; EM; 3.20 A; A/E=55-457.
DR PDB; 6UXE; X-ray; 1.57 A; A=56-457.
DR PDB; 6W1D; X-ray; 1.79 A; A=56-457.
DR PDB; 6WI2; X-ray; 1.95 A; A=56-457.
DR PDB; 6WIH; X-ray; 1.90 A; A=56-457.
DR PDB; 7RTK; X-ray; 2.50 A; A=56-457.
DR PDBsum; 5KZ5; -.
DR PDBsum; 5USR; -.
DR PDBsum; 5WGB; -.
DR PDBsum; 5WKP; -.
DR PDBsum; 5WLW; -.
DR PDBsum; 6NZU; -.
DR PDBsum; 6UXE; -.
DR PDBsum; 6W1D; -.
DR PDBsum; 6WI2; -.
DR PDBsum; 6WIH; -.
DR PDBsum; 7RTK; -.
DR AlphaFoldDB; Q9Y697; -.
DR SASBDB; Q9Y697; -.
DR SMR; Q9Y697; -.
DR BioGRID; 114516; 132.
DR ComplexPortal; CPX-5641; Mitochondrial NIAUFX iron-sulfur cluster assembly complex.
DR IntAct; Q9Y697; 50.
DR MINT; Q9Y697; -.
DR STRING; 9606.ENSP00000363205; -.
DR DrugBank; DB00160; Alanine.
DR DrugBank; DB00151; Cysteine.
DR DrugBank; DB00114; Pyridoxal phosphate.
DR GlyGen; Q9Y697; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9Y697; -.
DR PhosphoSitePlus; Q9Y697; -.
DR SwissPalm; Q9Y697; -.
DR BioMuta; NFS1; -.
DR DMDM; 62512153; -.
DR EPD; Q9Y697; -.
DR jPOST; Q9Y697; -.
DR MassIVE; Q9Y697; -.
DR MaxQB; Q9Y697; -.
DR PaxDb; Q9Y697; -.
DR PeptideAtlas; Q9Y697; -.
DR PRIDE; Q9Y697; -.
DR ProteomicsDB; 24766; -.
DR ProteomicsDB; 86633; -. [Q9Y697-1]
DR ProteomicsDB; 86634; -. [Q9Y697-2]
DR Antibodypedia; 35035; 233 antibodies from 26 providers.
DR DNASU; 9054; -.
DR Ensembl; ENST00000374085.5; ENSP00000363198.1; ENSG00000244005.13. [Q9Y697-2]
DR Ensembl; ENST00000374092.9; ENSP00000363205.3; ENSG00000244005.13. [Q9Y697-1]
DR Ensembl; ENST00000397425.5; ENSP00000380570.1; ENSG00000244005.13. [Q9Y697-2]
DR Ensembl; ENST00000541387.5; ENSP00000440897.1; ENSG00000244005.13. [Q9Y697-3]
DR GeneID; 9054; -.
DR KEGG; hsa:9054; -.
DR MANE-Select; ENST00000374092.9; ENSP00000363205.3; NM_021100.5; NP_066923.3.
DR UCSC; uc002xdt.3; human. [Q9Y697-1]
DR CTD; 9054; -.
DR DisGeNET; 9054; -.
DR GeneCards; NFS1; -.
DR HGNC; HGNC:15910; NFS1.
DR HPA; ENSG00000244005; Low tissue specificity.
DR MalaCards; NFS1; -.
DR MIM; 603485; gene.
DR MIM; 619386; phenotype.
DR neXtProt; NX_Q9Y697; -.
DR OpenTargets; ENSG00000244005; -.
DR Orphanet; 397593; Severe neonatal lactic acidosis due to NFS1-ISD11 complex deficiency.
DR PharmGKB; PA31607; -.
DR VEuPathDB; HostDB:ENSG00000244005; -.
DR eggNOG; KOG1549; Eukaryota.
DR GeneTree; ENSGT00940000155740; -.
DR HOGENOM; CLU_003433_0_2_1; -.
DR InParanoid; Q9Y697; -.
DR OMA; KGLYWAR; -.
DR PhylomeDB; Q9Y697; -.
DR TreeFam; TF105658; -.
DR BioCyc; MetaCyc:HS01304-MON; -.
DR BRENDA; 2.8.1.7; 2681.
DR PathwayCommons; Q9Y697; -.
DR Reactome; R-HSA-1362409; Mitochondrial iron-sulfur cluster biogenesis. [Q9Y697-1]
DR Reactome; R-HSA-947581; Molybdenum cofactor biosynthesis. [Q9Y697-2]
DR SignaLink; Q9Y697; -.
DR SIGNOR; Q9Y697; -.
DR BioGRID-ORCS; 9054; 662 hits in 1058 CRISPR screens.
DR ChiTaRS; NFS1; human.
DR GeneWiki; NFS1; -.
DR GenomeRNAi; 9054; -.
DR Pharos; Q9Y697; Tbio.
DR PRO; PR:Q9Y697; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9Y697; protein.
DR Bgee; ENSG00000244005; Expressed in right adrenal gland cortex and 178 other tissues.
DR ExpressionAtlas; Q9Y697; baseline and differential.
DR Genevisible; Q9Y697; HS.
DR GO; GO:0005829; C:cytosol; IDA:HGNC-UCL.
DR GO; GO:1990229; C:iron-sulfur cluster assembly complex; IC:ComplexPortal.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:HGNC-UCL.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:HGNC-UCL.
DR GO; GO:0031071; F:cysteine desulfurase activity; IDA:HGNC-UCL.
DR GO; GO:0051536; F:iron-sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:HGNC-UCL.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0044571; P:[2Fe-2S] cluster assembly; IEA:InterPro.
DR GO; GO:0018283; P:iron incorporation into metallo-sulfur cluster; IDA:HGNC-UCL.
DR GO; GO:0016226; P:iron-sulfur cluster assembly; IBA:GO_Central.
DR GO; GO:0006777; P:Mo-molybdopterin cofactor biosynthetic process; IEA:UniProtKB-KW.
DR Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 1.
DR HAMAP; MF_00331; Cys_desulf_IscS; 1.
DR InterPro; IPR000192; Aminotrans_V_dom.
DR InterPro; IPR020578; Aminotrans_V_PyrdxlP_BS.
DR InterPro; IPR010240; Cys_deSase_IscS.
DR InterPro; IPR016454; Cysteine_dSase.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
DR PANTHER; PTHR11601:SF34; PTHR11601:SF34; 1.
DR Pfam; PF00266; Aminotran_5; 1.
DR PIRSF; PIRSF005572; NifS; 1.
DR SUPFAM; SSF53383; SSF53383; 1.
DR TIGRFAMs; TIGR02006; IscS; 1.
DR PROSITE; PS00595; AA_TRANSFER_CLASS_5; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative initiation; Alternative splicing; Cytoplasm;
KW Disease variant; Iron; Iron-sulfur; Metal-binding; Mitochondrion;
KW Molybdenum cofactor biosynthesis; Nucleus; Primary mitochondrial disease;
KW Pyridoxal phosphate; Reference proteome; Transferase; Transit peptide.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN ?..457
FT /note="Cysteine desulfurase, mitochondrial"
FT /id="PRO_0000001292"
FT ACT_SITE 381
FT /note="Cysteine persulfide intermediate"
FT /evidence="ECO:0000250|UniProtKB:P0A6B7"
FT BINDING 127..128
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P0A6B9"
FT BINDING 207
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:O29689"
FT BINDING 235
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P0A6B9"
FT BINDING 255..257
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P0A6B9"
FT BINDING 295
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P0A6B9"
FT BINDING 381
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_note="ligand shared with ISCU"
FT /note="via persulfide group"
FT /evidence="ECO:0000250|UniProtKB:O29689"
FT MOD_RES 258
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:P0A6B9"
FT VAR_SEQ 1..60
FT /note="Missing (in isoform Cytoplasmic)"
FT /evidence="ECO:0000303|PubMed:11124703,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9885568"
FT /id="VSP_018646"
FT VAR_SEQ 136..186
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045860"
FT VARIANT 72
FT /note="R -> Q (in COXPD52; decreased protein expression in
FT homozygous patient cells)"
FT /evidence="ECO:0000269|PubMed:24498631,
FT ECO:0000269|PubMed:33457206"
FT /id="VAR_085966"
FT CONFLICT 5
FT /note="A -> V (in Ref. 1; AAD09187)"
FT /evidence="ECO:0000305"
FT CONFLICT 47
FT /note="A -> T (in Ref. 1; AAD09187)"
FT /evidence="ECO:0000305"
FT CONFLICT 197
FT /note="T -> A (in Ref. 3; BAG63421)"
FT /evidence="ECO:0000305"
FT CONFLICT 412
FT /note="R -> A (in Ref. 1; AAD09187)"
FT /evidence="ECO:0000305"
FT CONFLICT 431
FT /note="K -> N (in Ref. 1; AAD09187)"
FT /evidence="ECO:0000305"
FT TURN 63..65
FT /evidence="ECO:0007829|PDB:6UXE"
FT HELIX 71..82
FT /evidence="ECO:0007829|PDB:6UXE"
FT HELIX 94..114
FT /evidence="ECO:0007829|PDB:6UXE"
FT HELIX 118..120
FT /evidence="ECO:0007829|PDB:6UXE"
FT STRAND 121..125
FT /evidence="ECO:0007829|PDB:6UXE"
FT HELIX 127..141
FT /evidence="ECO:0007829|PDB:6UXE"
FT TURN 142..145
FT /evidence="ECO:0007829|PDB:6UXE"
FT STRAND 148..152
FT /evidence="ECO:0007829|PDB:6UXE"
FT HELIX 157..168
FT /evidence="ECO:0007829|PDB:6UXE"
FT STRAND 172..176
FT /evidence="ECO:0007829|PDB:6UXE"
FT HELIX 186..192
FT /evidence="ECO:0007829|PDB:6UXE"
FT STRAND 197..201
FT /evidence="ECO:0007829|PDB:6UXE"
FT TURN 207..209
FT /evidence="ECO:0007829|PDB:6UXE"
FT HELIX 215..224
FT /evidence="ECO:0007829|PDB:6UXE"
FT STRAND 228..232
FT /evidence="ECO:0007829|PDB:6UXE"
FT TURN 234..239
FT /evidence="ECO:0007829|PDB:6UXE"
FT TURN 244..248
FT /evidence="ECO:0007829|PDB:6UXE"
FT STRAND 250..255
FT /evidence="ECO:0007829|PDB:6UXE"
FT HELIX 256..258
FT /evidence="ECO:0007829|PDB:6UXE"
FT STRAND 266..270
FT /evidence="ECO:0007829|PDB:6UXE"
FT TURN 272..275
FT /evidence="ECO:0007829|PDB:6UXE"
FT TURN 287..291
FT /evidence="ECO:0007829|PDB:6UXE"
FT HELIX 298..336
FT /evidence="ECO:0007829|PDB:6UXE"
FT STRAND 337..344
FT /evidence="ECO:0007829|PDB:6UXE"
FT HELIX 346..348
FT /evidence="ECO:0007829|PDB:7RTK"
FT STRAND 353..358
FT /evidence="ECO:0007829|PDB:6UXE"
FT HELIX 363..369
FT /evidence="ECO:0007829|PDB:6UXE"
FT STRAND 376..378
FT /evidence="ECO:0007829|PDB:6UXE"
FT HELIX 380..382
FT /evidence="ECO:0007829|PDB:6WIH"
FT TURN 384..386
FT /evidence="ECO:0007829|PDB:6WIH"
FT HELIX 390..394
FT /evidence="ECO:0007829|PDB:6UXE"
FT HELIX 399..402
FT /evidence="ECO:0007829|PDB:6UXE"
FT STRAND 405..409
FT /evidence="ECO:0007829|PDB:6UXE"
FT HELIX 416..435
FT /evidence="ECO:0007829|PDB:6UXE"
FT HELIX 438..444
FT /evidence="ECO:0007829|PDB:6UXE"
FT HELIX 449..451
FT /evidence="ECO:0007829|PDB:6UXE"
SQ SEQUENCE 457 AA; 50196 MW; FDE76177DB6E751B CRC64;
MLLRAAWRRA AVAVTAAPGP KPAAPTRGLR LRVGDRAPQS AVPADTAAAP EVGPVLRPLY
MDVQATTPLD PRVLDAMLPY LINYYGNPHS RTHAYGWESE AAMERARQQV ASLIGADPRE
IIFTSGATES NNIAIKGVAR FYRSRKKHLI TTQTEHKCVL DSCRSLEAEG FQVTYLPVQK
SGIIDLKELE AAIQPDTSLV SVMTVNNEIG VKQPIAEIGR ICSSRKVYFH TDAAQAVGKI
PLDVNDMKID LMSISGHKIY GPKGVGAIYI RRRPRVRVEA LQSGGGQERG MRSGTVPTPL
VVGLGAACEV AQQEMEYDHK RISKLSERLI QNIMKSLPDV VMNGDPKHHY PGCINLSFAY
VEGESLLMAL KDVALSSGSA CTSASLEPSY VLRAIGTDED LAHSSIRFGI GRFTTEEEVD
YTVEKCIQHV KRLREMSPLW EMVQDGIDLK SIKWTQH
