Q9Y697 (NFS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cysteine desulfurase, mitochondrial
EC=2.8.1.7

Gene names

Name:	NFS1
Synonyms:	NIFS
ORF Names:	HUSSY-08

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	457 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.9
Catalytic activity	L-cysteine + acceptor = L-alanine + S-sulfanyl-acceptor.
Cofactor	Pyridoxal phosphate By similarity.
Subunit structure	Binds ISCU/NIFUN. Forms a complex with LYRM4.
Subcellular location	Mitochondrion. Cytoplasm. Nucleus Ref.10.
Tissue specificity	Predominantly expressed in heart and skeletal muscle. Also found in brain, liver and pancreas.
Sequence similarities	Belongs to the class-V pyridoxal-phosphate-dependent aminotransferase family. NifS/IscS subfamily.
Biophysicochemical properties	Kinetic parameters: Kinetic parameter was determined for the protein lacking the 55 N-terminus amino-acids and in a complex with LYRM4. KM=434.75 µM for L-cysteine Ref.9

Ontologies

Keywords
Biological process	Molybdenum cofactor biosynthesis
Cellular component	Cytoplasm Mitochondrion Nucleus
Coding sequence diversity	Alternative initiation
Domain	Transit peptide
Ligand	Pyridoxal phosphate
Molecular function	Transferase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	Mo-molybdopterin cofactor biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW cysteine metabolic process Inferred from electronic annotation. Source: InterPro iron incorporation into metallo-sulfur cluster Inferred from direct assay. Source: HGNC protein complex assembly Traceable author statement. Source: ProtInc water-soluble vitamin metabolic process Traceable author statement. Source: Reactome
Cellular component	cytosol Inferred from direct assay. Source: HGNC mitochondrial matrix Inferred from direct assay. Source: HGNC nucleus Inferred from direct assay. Source: HGNC
Molecular function	cysteine desulfurase activity Inferred from direct assay. Source: HGNC protein homodimerization activity Inferred from direct assay. Source: HGNC pyridoxal phosphate binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative initiation. [Align] [Select]

Isoform Mitochondrial (identifier: Q9Y697-1)

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.

Isoform Cytoplasmic (identifier: Q9Y697-2)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – ?		Mitochondrion Potential
	Chain	? – 457		Cysteine desulfurase, mitochondrial		PRO_0000001292
Sites
	Active site	381	1	By similarity
Amino acid modifications
	Modified residue	258	1	N6-(pyridoxal phosphate)lysine By similarity
Natural variations
	Alternative sequence	1 – 60	60	Missing in isoform Cytoplasmic.		VSP_018646
Experimental info
	Sequence conflict	5	1	A → V in AAD09187. Ref.1
	Sequence conflict	47	1	A → T in AAD09187. Ref.1
	Sequence conflict	412	1	R → A in AAD09187. Ref.1
	Sequence conflict	431	1	K → N in AAD09187. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform Mitochondrial [UniParc]. Last modified April 12, 2005. Version 3. Checksum: FDE76177DB6E751B	FASTA	457	50,196
	10 20 30 40 50 60 MLLRAAWRRA AVAVTAAPGP KPAAPTRGLR LRVGDRAPQS AVPADTAAAP EVGPVLRPLY 70 80 90 100 110 120 MDVQATTPLD PRVLDAMLPY LINYYGNPHS RTHAYGWESE AAMERARQQV ASLIGADPRE 130 140 150 160 170 180 IIFTSGATES NNIAIKGVAR FYRSRKKHLI TTQTEHKCVL DSCRSLEAEG FQVTYLPVQK 190 200 210 220 230 240 SGIIDLKELE AAIQPDTSLV SVMTVNNEIG VKQPIAEIGR ICSSRKVYFH TDAAQAVGKI 250 260 270 280 290 300 PLDVNDMKID LMSISGHKIY GPKGVGAIYI RRRPRVRVEA LQSGGGQERG MRSGTVPTPL 310 320 330 340 350 360 VVGLGAACEV AQQEMEYDHK RISKLSERLI QNIMKSLPDV VMNGDPKHHY PGCINLSFAY 370 380 390 400 410 420 VEGESLLMAL KDVALSSGSA CTSASLEPSY VLRAIGTDED LAHSSIRFGI GRFTTEEEVD 430 440 450 YTVEKCIQHV KRLREMSPLW EMVQDGIDLK SIKWTQH
	Isoform Cytoplasmic [UniParc]. Checksum: 61DF3AD65D5CDD3C	FASTA	397	44,017
	10 20 30 40 50 60 MDVQATTPLD PRVLDAMLPY LINYYGNPHS RTHAYGWESE AAMERARQQV ASLIGADPRE 70 80 90 100 110 120 IIFTSGATES NNIAIKGVAR FYRSRKKHLI TTQTEHKCVL DSCRSLEAEG FQVTYLPVQK 130 140 150 160 170 180 SGIIDLKELE AAIQPDTSLV SVMTVNNEIG VKQPIAEIGR ICSSRKVYFH TDAAQAVGKI 190 200 210 220 230 240 PLDVNDMKID LMSISGHKIY GPKGVGAIYI RRRPRVRVEA LQSGGGQERG MRSGTVPTPL 250 260 270 280 290 300 VVGLGAACEV AQQEMEYDHK RISKLSERLI QNIMKSLPDV VMNGDPKHHY PGCINLSFAY 310 320 330 340 350 360 VEGESLLMAL KDVALSSGSA CTSASLEPSY VLRAIGTDED LAHSSIRFGI GRFTTEEEVD 370 380 390 YTVEKCIQHV KRLREMSPLW EMVQDGIDLK SIKWTQH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Targeting of a human iron-sulfur cluster assembly enzyme, nifs, to different subcellular compartments is regulated through alternative AUG utilization." Land T., Rouault T.A. Mol. Cell 2:807-815(1998) [PubMed: 9885568] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	Land T., Rouault T.A. Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO 380-402.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." 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 T.-O., 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. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM MITOCHONDRIAL).
[4]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed: 11780052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pancreas.
[7]	"Characterization of 16 novel human genes showing high similarity to yeast sequences." Stanchi F., Bertocco E., Toppo S., Dioguardi R., Simionati B., Cannata N., Zimbello R., Lanfranchi G., Valle G. Yeast 18:69-80(2001) [PubMed: 11124703] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 140-457.
[8]	"Distinct iron-sulfur cluster assembly complexes exist in the cytosol and mitochondria of human cells." Tong W.-H., Rouault T. EMBO J. 19:5692-5700(2000) [PubMed: 11060020] [Abstract] Cited for: INTERACTION WITH ISCU.
[9]	"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., Stoecklein W., Nimtz M., Leimkuehler S. J. Biol. Chem. 283:25178-25185(2008) [PubMed: 18650437] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, INTERACTION WITH LYRM4.
[10]	"Human ISD11 is essential for both iron-sulfur cluster assembly and maintenance of normal cellular iron homeostasis." Shi Y., Ghosh M.C., Tong W.H., Rouault T.A. Hum. Mol. Genet. 18:3014-3025(2009) [PubMed: 19454487] [Abstract] Cited for: INTERACTION WITH LYRM4, SUBCELLULAR LOCATION.
[11]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF097025 mRNA. Translation: AAD09187.2. AL109827, AL357374 Genomic DNA. Translation: CAB87612.2. AK001470 mRNA. Translation: BAG50917.1. AL109827, AL357374 Genomic DNA. Translation: CAI20116.1. CH471077 Genomic DNA. Translation: EAW76170.1. CH471077 Genomic DNA. Translation: EAW76172.1. BC065560 mRNA. Translation: AAH65560.1. AJ010952 mRNA. Translation: CAA09424.1.
IPI	IPI00295240. IPI00643101.
RefSeq	NP_001185918.1. NM_001198989.1. NP_066923.3. NM_021100.4.
UniGene	Hs.194692.
3D structure databases
ProteinModelPortal	Q9Y697.
SMR	Q9Y697. Positions 57-446.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y697. 4 interactions.
MINT	MINT-3087935.
STRING	Q9Y697.
PTM databases
PhosphoSite	Q9Y697.
Polymorphism databases
DMDM	62512153.
Proteomic databases
PRIDE	Q9Y697.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000374092; ENSP00000363205; ENSG00000244005.
GeneID	9054.
KEGG	hsa:9054.
NMPDR	fig|9606.3.peg.20173.
UCSC	uc002xdt.1. human. uc002xdw.1. human.
Organism-specific databases
CTD	9054.
GeneCards	GC20M034220.
HGNC	HGNC:15910. NFS1.
HPA	CAB034314.
MIM	603485. gene.
neXtProt	NX_Q9Y697.
PharmGKB	PA31607.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00530000063513.
HOVERGEN	HBG003708.
InParanoid	Q9Y697.
OMA	CIHHVKR.
PhylomeDB	Q9Y697.
Enzyme and pathway databases
BioCyc	MetaCyc:HS01304-MONOMER.
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	Q9Y697.
Bgee	Q9Y697.
CleanEx	HS_NFS1.
Genevestigator	Q9Y697.
GermOnline	ENSG00000078872. Homo sapiens.
Family and domain databases
InterPro	IPR000192. Aminotrans_V/Cys_dSase. IPR020578. Aminotrans_V_PyrdxlP_BS. IPR010240. Cys_deSase. IPR016454. Cysteine_dSase_NifS. IPR015424. PyrdxlP-dep_Trfase_major_dom. IPR015421. PyrdxlP-dep_Trfase_major_sub1. IPR015422. PyrdxlP-dep_Trfase_major_sub2. [Graphical view]
Gene3D	G3DSA:3.40.640.10. PyrdxlP-dep_Trfase_major_sub1. 1 hit. G3DSA:3.90.1150.10. PyrdxlP-dep_Trfase_major_sub2. 1 hit.
KO	K04487.
Pfam	PF00266. Aminotran_5. 1 hit. [Graphical view]
PIRSF	PIRSF005572. NifS. 1 hit.
SUPFAM	SSF53383. PyrdxlP-dep_Trfase_major. 1 hit.
TIGRFAMs	TIGR02006. IscS. 1 hit.
PROSITE	PS00595. AA_TRANSFER_CLASS_5. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00160. L-Alanine. DB00151. L-Cysteine. DB00114. Pyridoxal Phosphate.
NextBio	33923.
SOURCE	Search...

Entry information

Entry name

NFS1_HUMAN

Accession

Primary (citable) accession number: Q9Y697
Secondary accession number(s): B3KMA5 , E1P5R8, Q6P0L8, Q9NTZ5, Q9Y481

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	April 12, 2005
Last modified:	January 25, 2012
This is version 115 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.