NFU1

Protein identityUniProt · HPA

UniProt accession

Q9UMS0

Gene

NFU1

Ensembl

ENSG00000169599

Chromosome

2

Canonical length

254 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Cytosol

Quaternary structure

Homohexamer

OverviewNCBI Gene

This gene encodes a protein that is localized to mitochondria and plays a critical role in iron-sulfur cluster biogenesis. The encoded protein assembles and transfers 4Fe-4S clusters to target apoproteins including succinate dehydrogenase and lipoic acid synthase. Mutations in this gene are a cause of multiple mitochondrial dysfunctions syndrome-1, and pseudogenes of this gene are located on the short arms of chromosomes 1 and 3. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

Canonical amino-acid sequenceUniProt

254 residues, UniProt reviewed canonical sequence.

>Q9UMS0|NFU1
     1  MAATARRGWG AAAVAAGLRR RFCHMLKNPY TIKKQPLHQF VQRPLFPLPA AFYHPVRYMF
    61  IQTQDTPNPN SLKFIPGKPV LETRTMDFPT PAAAFRSPLA RQLFRIEGVK SVFFGPDFIT
   121  VTKENEELDW NLLKPDIYAT IMDFFASGLP LVTEETPSGE AGSEEDDEVV AMIKELLDTR
   181  IRPTVQEDGG DVIYKGFEDG IVQLKLQGSC TSCPSSIITL KNGIQNMLQF YIPEVEGVEQ
   241  VMDDESDEKE ANSP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NFU1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.41

Highest tissue expression

132 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NFU1.

Disease | AllUniProt

Conditions NFU1 is implicated in, by any mechanism.

• Multiple mitochondrial dysfunctions syndrome 1 (MMDS1) MIM:605711
• Spastic paraplegia 93, autosomal recessive (SPG93) MIM:620938

Disease | GeneticClinVar

18 pathogenic / likely-pathogenic of 213 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Multiple mitochondrial dysfunctions syndrome 1
• Spastic paraplegia 93, autosomal recessive
• NFU1-related disorder
• Familial cancer of breast
• Uterine corpus endometrial carcinoma

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.23

gnomAD pLI

0

gnomAD missense Z

0.37

DepMap mean gene effect

-0.34

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• iron-sulfur cluster assembly
• protein maturation

Molecular functions

• 2 iron, 2 sulfur cluster binding
• 4 iron, 4 sulfur cluster binding
• iron ion binding

Cellular components

• cytosol
• mitochondrial matrix
• mitochondrion
• nucleoplasm
• nucleus

Protein domainsUniProt · Pfam · InterPro

• Fe-S cluster assembly domain superfamily
• NIF system FeS cluster assembly, NifU, C-terminal
• Scaffold protein Nfu/NifU, N-terminal
• Scaffold protein Nfu/NifU, N-terminal domain superfamily
• NifU-like domain
• Scaffold protein Nfu/NifU N terminal

KeywordsUniProt

• Cytoplasm
• Hereditary spastic paraplegia
• Iron
• Iron-sulfur
• Metal-binding
• Mitochondrion
• Neurodegeneration
• Primary mitochondrial disease
• Transit peptide

InteractionsUniProt · HPA

Protein binding partners of NFU1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• BOLA3
• HIRA
• HSPA9