Cysteine desulfurase
Details
- Name
- Cysteine desulfurase
- Synonyms
- 2.8.1.7
- NIFS
- Gene Name
- NFS1
- UniProtKB Entry
- Q9Y697Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- Amino acid sequence
>lcl|BSEQ0000301|Cysteine desulfurase MLLRAAWRRAAVAVTAAPGPKPAAPTRGLRLRVGDRAPQSAVPADTAAAPEVGPVLRPLY MDVQATTPLDPRVLDAMLPYLINYYGNPHSRTHAYGWESEAAMERARQQVASLIGADPRE IIFTSGATESNNIAIKGVARFYRSRKKHLITTQTEHKCVLDSCRSLEAEGFQVTYLPVQK SGIIDLKELEAAIQPDTSLVSVMTVNNEIGVKQPIAEIGRICSSRKVYFHTDAAQAVGKI PLDVNDMKIDLMSISGHKIYGPKGVGAIYIRRRPRVRVEALQSGGGQERGMRSGTVPTPL VVGLGAACEVAQQEMEYDHKRISKLSERLIQNIMKSLPDVVMNGDPKHHYPGCINLSFAY VEGESLLMALKDVALSSGSACTSASLEPSYVLRAIGTDEDLAHSSIRFGIGRFTTEEEVD YTVEKCIQHVKRLREMSPLWEMVQDGIDLKSIKWTQH
- Number of residues
- 457
- Molecular Weight
- 50195.21
- Theoretical pI
- 8.45
- GO Classification
- Functionscysteine desulfurase activity / iron-sulfur cluster binding / metal ion binding / protein homodimerization activity / pyridoxal phosphate bindingProcesses[2Fe-2S] cluster assembly / iron incorporation into metallo-sulfur cluster / Mo-molybdopterin cofactor biosynthetic processComponentscytoplasm / cytosol / mitochondrial matrix / mitochondrion / nucleoplasm / nucleus
- General Function
- Cysteine desulfurase, of the core iron-sulfur cluster (ISC) assembly complex, that catalyzes the desulfuration of L-cysteine to L-alanine, as component of the cysteine desulfurase complex, leading to the formation of a cysteine persulfide intermediate at the active site cysteine residue and participates in the [2Fe-2S] clusters assembly on the scaffolding protein ISCU (PubMed:18650437, PubMed:29097656, PubMed:31101807). The persulfide is then transferred on the flexible Cys loop from the catalytic site of NFS1 to the surface of NFS1 (PubMed:29097656). After the NFS1-linked persulfide sulfur is transferred to one of the conserved Cys residues of the scaffold, a reaction assisted by FXN (By similarity). The core iron-sulfur cluster (ISC) assembly complex is involved in the de novo synthesis of a [2Fe-2S] cluster, the first step of the mitochondrial iron-sulfur protein biogenesis. This process is initiated by the cysteine desulfurase complex (NFS1:LYRM4:NDUFAB1) that produces persulfide which is delivered on the scaffold protein ISCU in a FXN-dependent manner. Then this complex is stabilized by FDX2 which provides reducing equivalents to accomplish the [2Fe-2S] cluster assembly. Finally, the [2Fe-2S] cluster is transferred from ISCU to chaperone proteins, including HSCB, HSPA9 and GLRX5 (By similarity)
- Specific Function
- Cysteine desulfurase activity
- Pfam Domain Function
- Aminotran_5 (PF00266)
- Signal Regions
- Not Available
- Transmembrane Regions
- Not Available
- Cellular Location
- Mitochondrion
- Gene sequence
>lcl|BSEQ0009970|Cysteine desulfurase, mitochondrial (NFS1) ATGCTGCTCCGAGCCGCTTGGAGGCGGGCGGCAGTGGCGGTGACAGCGGCTCCAGGGCCG AAGCCCGCGGCGCCCACTCGGGGGCTGCGCCTGCGCGTTGGAGACCGTGCTCCTCAGTCT GCGGTTCCCGCAGATACAGCCGCTGCCCCGGAGGTGGGGCCAGTGCTGCGACCTCTCTAT ATGGATGTGCAAGCTACAACTCCTCTGGACCCCCGGGTGCTTGATGCCATGCTCCCTTAC CTAATCAACTACTATGGGAACCCACACTCCCGGACACATGCTTATGGCTGGGAGAGTGAG GCAGCCATGGAACGTGCTCGTCAGCAAGTAGCATCTCTGATTGGAGCTGATCCTCGTGAG ATCATTTTTACTAGTGGTGCTACTGAATCCAACAACATAGCAATTAAGGAACTAGAGGCT GCTATCCAGCCAGATACTAGCCTGGTGTCAGTCATGACTGTGAACAATGAGATTGGAGTG AAGCAGCCTATTGCAGAAATAGGGCGGATTTGCAGTTCCAGAAAGGTATATTTCCATACT GATGCAGCCCAGGCTGTTGGAAAAATCCCACTTGATGTCAATGACATGAAAATTGATCTC ATGAGCATTAGTGGTCACAAAATCTACGGTCCCAAAGGGGTTGGTGCCATCTACATCCGT CGCCGGCCCCGTGTGCGTGTGGAGGCCCTGCAGAGTGGAGGGGGGCAGGAGCGGGGTATG CGGTCTGGGACAGTGCCCACACCCTTAGTGGTGGGGCTGGGGGCTGCGTGTGAGGTGGCA CAGCAAGAGATGGAGTATGACCACAAGCGAATCTCAAAGTTGTCAGAGCGGCTGATACAG AATATAATGAAGAGCCTTCCAGATGTGGTGATGAATGGGGACCCTAAGCACCATTATCCC GGCTGTATCAACCTCTCCTTTGCATATGTGGAAGGGGAAAGTCTGCTGATGGCACTGAAG GACGTTGCCTTATCCTCAGGGAGTGCCTGCACCTCTGCATCCCTGGAGCCCTCTTATGTG CTTAGAGCAATTGGCACTGATGAGGATTTAGCGCACTCTTCTATCAGGTTTGGAATTGGC CGCTTCACTACAGAGGAGGAAGTGGACTACACAGTGGAGAAATGCATTCAGCATGTGAAG CGTCTTCGAGAAATGAGCCCTCTCTGGGAGATGGTTCAGGATGGCATTGACCTCAAGAGC ATCAAGTGGACCCAACACTAG
- Chromosome Location
- 20
- Locus
- 20q11.22
- External Identifiers
Resource Link UniProtKB ID Q9Y697 UniProtKB Entry Name NFS1_HUMAN GenBank Protein ID 24042327 GenBank Gene ID AF097025 GeneCard ID NFS1 GenAtlas ID NFS1 HGNC ID HGNC:15910 PDB ID(s) 5KZ5, 5USR, 5WGB, 5WKP, 5WLW, 6NZU, 6UXE, 6W1D, 6WI2, 6WIH, 7RTK KEGG ID hsa:9054 NCBI Gene ID 9054 - General References
- Land T, Rouault TA: Targeting of a human iron-sulfur cluster assembly enzyme, nifs, to different subcellular compartments is regulated through alternative AUG utilization. Mol Cell. 1998 Dec;2(6):807-15. [Article]
- Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
- Deloukas P, Matthews LH, Ashurst J, Burton J, Gilbert JG, Jones M, Stavrides G, Almeida JP, Babbage AK, Bagguley CL, Bailey J, Barlow KF, Bates KN, Beard LM, Beare DM, Beasley OP, Bird CP, Blakey SE, Bridgeman AM, Brown AJ, Buck D, Burrill W, Butler AP, Carder C, Carter NP, Chapman JC, Clamp M, Clark G, Clark LN, Clark SY, Clee CM, Clegg S, Cobley VE, Collier RE, Connor R, Corby NR, Coulson A, Coville GJ, Deadman R, Dhami P, Dunn M, Ellington AG, Frankland JA, Fraser A, French L, Garner P, Grafham DV, Griffiths C, Griffiths MN, Gwilliam R, Hall RE, Hammond S, Harley JL, Heath PD, Ho S, Holden JL, Howden PJ, Huckle E, Hunt AR, Hunt SE, Jekosch K, Johnson CM, Johnson D, Kay MP, Kimberley AM, King A, Knights A, Laird GK, Lawlor S, Lehvaslaiho MH, Leversha M, Lloyd C, Lloyd DM, Lovell JD, Marsh VL, Martin SL, McConnachie LJ, McLay K, McMurray AA, Milne S, Mistry D, Moore MJ, Mullikin JC, Nickerson T, Oliver K, Parker A, Patel R, Pearce TA, Peck AI, Phillimore BJ, Prathalingam SR, Plumb RW, Ramsay H, Rice CM, Ross MT, Scott CE, Sehra HK, Shownkeen R, Sims S, Skuce CD, Smith ML, Soderlund C, Steward CA, Sulston JE, Swann M, Sycamore N, Taylor R, Tee L, Thomas DW, Thorpe A, Tracey A, Tromans AC, Vaudin M, Wall M, Wallis JM, Whitehead SL, Whittaker P, Willey DL, Williams L, Williams SA, Wilming L, Wray PW, Hubbard T, Durbin RM, Bentley DR, Beck S, Rogers J: The DNA sequence and comparative analysis of human chromosome 20. Nature. 2001 Dec 20-27;414(6866):865-71. [Article]
- Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
- Stanchi F, Bertocco E, Toppo S, Dioguardi R, Simionati B, Cannata N, Zimbello R, Lanfranchi G, Valle G: Characterization of 16 novel human genes showing high similarity to yeast sequences. Yeast. 2001 Jan 15;18(1):69-80. [Article]
- Tong WH, Rouault T: Distinct iron-sulfur cluster assembly complexes exist in the cytosol and mitochondria of human cells. EMBO J. 2000 Nov 1;19(21):5692-700. [Article]
- Marelja Z, Stocklein W, Nimtz M, Leimkuhler S: A novel role for human Nfs1 in the cytoplasm: Nfs1 acts as a sulfur donor for MOCS3, a protein involved in molybdenum cofactor biosynthesis. J Biol Chem. 2008 Sep 12;283(37):25178-85. doi: 10.1074/jbc.M804064200. Epub 2008 Jul 23. [Article]
- Shi Y, Ghosh MC, Tong WH, Rouault TA: Human ISD11 is essential for both iron-sulfur cluster assembly and maintenance of normal cellular iron homeostasis. Hum Mol Genet. 2009 Aug 15;18(16):3014-25. doi: 10.1093/hmg/ddp239. Epub 2009 May 18. [Article]
- Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
- Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [Article]
Associated Data
- Bio-Entities
Bio-Entity Type Cysteine desulfurase (Humans) protein primary- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details Pyridoxal phosphate approved, investigational, nutraceutical unknown target cofactor Details Alanine nutraceutical unknown target Details Cysteine approved, nutraceutical unknown target Details