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NFU1 NFU1 iron-sulfur cluster scaffold [ Homo sapiens (human) ]

Gene ID: 27247, updated on 11-Apr-2024

Summary

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Official Symbol
NFU1provided by HGNC
Official Full Name
NFU1 iron-sulfur cluster scaffoldprovided by HGNC
Primary source
HGNC:HGNC:16287
See related
Ensembl:ENSG00000169599 MIM:608100; AllianceGenome:HGNC:16287
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
Nfu; NifU; HIRIP; MMDFS; MMDS1; NIFUC; CGI-33; HIRIP5
Summary
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]
Expression
Ubiquitous expression in fat (RPKM 30.5), kidney (RPKM 17.0) and 25 other tissues See more
Orthologs
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Genomic context

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Location:
2p13.3
Exon count:
11
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (69395750..69439567, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (69408096..69451867, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (69622882..69666699, complement)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124907821 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:69533245-69533984 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11594 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15969 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:69537635-69538137 Neighboring gene glutamine--fructose-6-phosphate transaminase 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15970 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:69614151-69614710 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:69618958-69619458 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15971 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr2:69671824-69672380 Neighboring gene uncharacterized LOC124906020 Neighboring gene AP2 associated kinase 1 Neighboring gene RNA, 7SL, cytoplasmic 604, pseudogene

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Patient-specific variants of NFU1/NFU-1 disrupt cholinergic signaling in a model of multiple mitochondrial dysfunctions syndrome 1. Kropp PA, et al. Dis Model Mech, 2023 Feb 1. PMID 36645076, Free PMC Article
  2. Phenotypic continuum of NFU1-related disorders. Kaiyrzhanov R, et al. Ann Clin Transl Neurol, 2022 Dec. PMID 36256512, Free PMC Article
  3. Assembly of the [4Fe-4S] cluster of NFU1 requires the coordinated donation of two [2Fe-2S] clusters from the scaffold proteins, ISCU2 and ISCA1. Jain A, et al. Hum Mol Genet, 2020 Nov 25. PMID 32776106, Free PMC Article
  4. Multiple mitochondrial dysfunctions syndrome 1: An unusual cause of developmental pulmonary hypertension. Birjiniuk A, et al. Am J Med Genet A, 2020 Apr. PMID 31970900
  5. Analysis of NFU-1 metallocofactor binding-site substitutions-impacts on iron-sulfur cluster coordination and protein structure and function. Wesley NA, et al. FEBS J, 2017 Nov. PMID 28906593

See all (50) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. BOLA3 and NFU1 link mitoribosome iron-sulfur cluster assembly to multiple mitochondrial dysfunctions syndrome.
    Title: BOLA3 and NFU1 link mitoribosome iron-sulfur cluster assembly to multiple mitochondrial dysfunctions syndrome.
  2. Structural Plasticity of NFU1 Upon Interaction with Binding Partners: Insights into the Mitochondrial [4Fe-4S] Cluster Pathway.
    Title: Structural Plasticity of NFU1 Upon Interaction with Binding Partners: Insights into the Mitochondrial [4Fe-4S] Cluster Pathway.
  3. Patient-specific variants of NFU1/NFU-1 disrupt cholinergic signaling in a model of multiple mitochondrial dysfunctions syndrome 1.
    Title: Patient-specific variants of NFU1/NFU-1 disrupt cholinergic signaling in a model of multiple mitochondrial dysfunctions syndrome 1.
  4. Phenotypic continuum of NFU1-related disorders.
    Title: Phenotypic continuum of NFU1-related disorders.
  5. Assembly of the [4Fe-4S] cluster of NFU1 requires the coordinated donation of two [2Fe-2S] clusters from the scaffold proteins, ISCU2 and ISCA1.
    Title: Assembly of the [4Fe-4S] cluster of NFU1 requires the coordinated donation of two [2Fe-2S] clusters from the scaffold proteins, ISCU2 and ISCA1.
  6. ISCA1 Orchestrates ISCA2 and NFU1 in the Maturation of Human Mitochondrial [4Fe-4S] Proteins.
    Title: ISCA1 Orchestrates ISCA2 and NFU1 in the Maturation of Human Mitochondrial [4Fe-4S] Proteins.
  7. A pathway for assembling [4Fe-4S](2+) clusters in mitochondrial iron-sulfur protein biogenesis.
    Title: A pathway for assembling [4Fe-4S](2+) clusters in mitochondrial iron-sulfur protein biogenesis.
  8. Multiple mitochondrial dysfunctions syndrome 1: An unusual cause of developmental pulmonary hypertension.
    Title: Multiple mitochondrial dysfunctions syndrome 1: An unusual cause of developmental pulmonary hypertension.
  9. data support a hypothesis in which Nfu can serve as an alternative carrier protein for chaperone-mediated cluster release and delivery in Fe-S cluster biogenesis and trafficking
    Title: Regulation of human Nfu activity in Fe-S cluster delivery-characterization of the interaction between Nfu and the HSPA9/Hsc20 chaperone complex.
  10. NFU1 gene mutations may cause severe mitochondrial respiratory chain defects, mitochondrial encephalomyopathies and death, early in life (Review)
    Title: NFU1 gene mutation and mitochondrial disorders.
Submit: New GeneRIF Correction See all GeneRIFs (26)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Multiple mitochondrial dysfunctions syndrome 1
MedGen: C3276432 OMIM: 605711 GeneReviews: Not available
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Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Pol gag-pol HIV-1 Pol is identified to have a physical interaction with iron-sulfur cluster scaffold homolog (NFU1) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed
retropepsin gag-pol HIV-1 PR is identified to have a physical interaction with NFU1 iron-sulfur cluster scaffold homolog (NFU1) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC142252, MGC142254

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables 4 iron, 4 sulfur cluster binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables 4 iron, 4 sulfur cluster binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables iron ion binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in iron-sulfur cluster assembly IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein maturation by [4Fe-4S] cluster transfer IBA
Inferred from Biological aspect of Ancestor
more info
  
Component Evidence Code Pubs
located_in cytosol IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in mitochondrion IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
NFU1 iron-sulfur cluster scaffold homolog, mitochondrial
Names
HIRA-interacting protein 5
NifU-like C-terminal domain containing
iron-sulfur cluster scaffold protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_031931.1 RefSeqGene

    Range
    5194..46503
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001002755.4 → NP_001002755.1  NFU1 iron-sulfur cluster scaffold homolog, mitochondrial isoform 2

    See identical proteins and their annotated locations for NP_001002755.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR and uses an upstream, in-frame start codon, compared to variant 1. The encoded isoform (2) has a longer N-terminus, compared to isoform 1.
    Source sequence(s)
    AI129426, BC113692
    Consensus CDS
    CCDS33217.1
    UniProtKB/Swiss-Prot
    B4DUL9, Q53QE5, Q6VNZ8, Q7Z5B1, Q7Z5B2, Q9UMS0, Q9Y322
    Related
    ENSP00000387219.3, ENST00000410022.7
    Conserved Domains (2) summary
    smart00932
    Location:61 → 148
    Nfu_N; Scaffold protein Nfu/NifU N terminal
    pfam01106
    Location:173 → 239
    NifU; NifU-like domain

  2. NM_001002756.2 → NP_001002756.1  NFU1 iron-sulfur cluster scaffold homolog, mitochondrial isoform 3

    See identical proteins and their annotated locations for NP_001002756.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an internal exon and initiates translation at a downstream, in-frame start codon, compared to variant 1. The encoded isoform (3) has a shorter N-terminus, compared to isoform 1.
    Source sequence(s)
    AI129426, BG385940, BM846341, BU507991, DB496651
    Consensus CDS
    CCDS42694.1
    UniProtKB/TrEMBL
    F8W9P7
    Related
    ENSP00000377842.1, ENST00000394305.5
    Conserved Domains (1) summary
    pfam01106
    Location:32 → 98
    NifU; NifU-like domain

  3. NM_001374284.1 → NP_001361213.1  NFU1 iron-sulfur cluster scaffold homolog, mitochondrial isoform 1

    Status: REVIEWED

    Source sequence(s)
    AC114772
    Consensus CDS
    CCDS46315.1
    Conserved Domains (2) summary
    pfam01106
    Location:149 → 215
    NifU; NifU-like domain
    pfam08712
    Location:37 → 124
    Nfu_N; Scaffold protein Nfu/NifU N terminal

  4. NM_015700.4 → NP_056515.2  NFU1 iron-sulfur cluster scaffold homolog, mitochondrial isoform 1

    See identical proteins and their annotated locations for NP_056515.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes isoform 1.
    Source sequence(s)
    AC114772, AI129426, AY286307
    Consensus CDS
    CCDS46315.1
    UniProtKB/Swiss-Prot
    Q9UMS0
    Related
    ENSP00000306965.3, ENST00000303698.7
    Conserved Domains (2) summary
    pfam01106
    Location:149 → 215
    NifU; NifU-like domain
    pfam08712
    Location:37 → 124
    Nfu_N; Scaffold protein Nfu/NifU N terminal

RNA

  1. NR_045631.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) uses an alternate splice site and lacks an internal exon in the 5' region, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AC114772, AI129426, BU178674, DB496651

  2. NR_045632.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) uses an alternate splice site in the 5' region and lacks two internal exons, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AC114772, AI129426, AK308567

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

    Range
    69395750..69439567 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047443939.1 → XP_047299895.1  NFU1 iron-sulfur cluster scaffold homolog, mitochondrial isoform X1

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060926.1 Alternate T2T-CHM13v2.0

    Range
    69408096..69451867 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_001002757.1: Suppressed sequence

    Description
    NM_001002757.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9UMS0.2 GenPept UniProtKB/Swiss-Prot:Q9UMS0

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