NFU1/YKL040C Summary Help

Standard Name NFU1 1
Systematic Name YKL040C
Alias NUB1
Feature Type ORF, Verified
Description Protein involved in iron metabolism in mitochondria; similar to NifU, which is a protein required for the maturation of the Fe/S clusters of nitrogenase in nitrogen-fixing bacteria (1, 2 and see Summary Paragraph)
Name Description NifU-like protein 1
Chromosomal Location
ChrXI:361828 to 361058 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gene Ontology Annotations All NFU1 GO evidence and references
  View Computational GO annotations for NFU1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 3 genes
Classical genetics
Large-scale survey
79 total interaction(s) for 59 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 1
  • Affinity Capture-RNA: 3
  • Two-hybrid: 2

Genetic Interactions
  • Dosage Growth Defect: 1
  • Negative Genetic: 65
  • Positive Genetic: 4
  • Synthetic Growth Defect: 2
  • Synthetic Lethality: 1

Expression Summary
Length (a.a.) 256
Molecular Weight (Da) 29,174
Isoelectric Point (pI) 4.76
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrXI:361828 to 361058 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..771 361828..361058 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000001523

The NFU1 gene encodes a mitochondrial matrix protein that is thought to be involved in iron-sulfur cluster assembly (1). Expression of Nfu1p is regulated by specific degradation of its mRNA in a process involving Tis11p, which binds to and mediates degradation of mRNAs encoding proteins involved in iron metabolism (3). The nfu1 single mutant does not exhibit large differences from wild type. Activity of aconitase (Aco1p), which is an iron-sulfur cluster-containing enzyme, is reduced in the nfu1 null mutant (1, 4), and mitochondrial iron accumulation is decreased (1). In vitro assembly of iron-sulfur clusters is 40% reduced in mitochondrial lysates from the nfu1 null mutant (2).

NFU1 exhibits genetic interactions with several genes involved in mitochondrial iron metabolism. It was first isolated via a synthetic lethal genetic interaction with SSQ1, which encodes a mitochondrial hsp70-type molecular chaperone that has also been implicated in iron-sulfur cluster assembly (1). The ISU1 gene encodes another mitochondrial protein involved in iron-sulfur cluster assembly; an isu1 single null mutant has no obvious phenotype, but the nfu1 isu1 double mutant exhibits temperature-sensitive fermentative growth and a decreased respiratory growth rate (1). Null nfu1 mutations also exhibit a synthetic slow growth phenotype when combined with null mutations in YFH1, which encodes the mitochondrial iron-storage protein frataxin (5).

Nfu1p is one of three S. cerevisiae proteins with similarity to the bacterial NifU protein, which has been well characterized in nitrogen-fixing bacteria and is thought to act as a scaffold for iron-sulfur cluster assembly (6). Nfu1p has similarity to the C terminus of NifU, while Isu1p and Isu2p have similarity to the NifU N terminus (1). NFU1 is conserved from bacteria to mammals, and the temperature sensitivity and respiratory defect of the isu1 nfu1 double mutant is functionally complemented by its Arabidopsis orthologs (7, 8). The putative mammalian ortholog of NFU1 is HIRIP5 (OMIM). HIRIP5 itself is not implicated in disease, but it interacts physically with the HIRA protein (OMIM), which has been linked to DiGeorge syndrome and velocardiofacial syndrome (9).

Last updated: 2008-06-04 Contact SGD

References cited on this page View Complete Literature Guide for NFU1
1) Schilke B, et al.  (1999) Evidence for a conserved system for iron metabolism in the mitochondria of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 96(18):10206-11
2) Muhlenhoff U, et al.  (2002) Characterization of iron-sulfur protein assembly in isolated mitochondria. A requirement for ATP, NADH, and reduced iron. J Biol Chem 277(33):29810-6
3) Puig S, et al.  (2005) Coordinated remodeling of cellular metabolism during iron deficiency through targeted mRNA degradation. Cell 120(1):99-110
4) Garland SA, et al.  (1999) Saccharomyces cerevisiae ISU1 and ISU2: members of a well-conserved gene family for iron-sulfur cluster assembly. J Mol Biol 294(4):897-907
5) Aloria K, et al.  (2004) Iron-induced oligomerization of yeast frataxin homologue Yfh1 is dispensable in vivo. EMBO Rep 5(11):1096-101
6) Johnson DC, et al.  (2005) Structure, function, and formation of biological iron-sulfur clusters. Annu Rev Biochem 74:247-81
7) Leon S, et al.  (2005) Mitochondrial localization of Arabidopsis thaliana Isu Fe-S scaffold proteins. FEBS Lett 579(9):1930-1934
8) Leon S, et al.  (2003) Iron-sulphur cluster assembly in plants: distinct NFU proteins in mitochondria and plastids from Arabidopsis thaliana. Biochem J 371(Pt 3):823-30
9) Lorain S, et al.  (2001) Identification of human and mouse HIRA-interacting protein-5 (HIRIP5), two mammalian representatives in a family of phylogenetically conserved proteins with a role in the biogenesis of Fe/S proteins. Biochim Biophys Acta 1517(3):376-83