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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
    mouse all
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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
    		Compare labs

    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

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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