LOCUS       NM_213595                983 bp    mRNA    linear   PRI 12-OCT-2024
DEFINITION  Homo sapiens iron-sulfur cluster assembly enzyme (ISCU), transcript
            variant 2, mRNA.
ACCESSION   NM_213595
VERSION     NM_213595.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 983)
  AUTHORS   Du,J., Huang,Z., Li,Y., Ren,X., Zhou,C., Liu,R., Zhang,P., Lei,G.,
            Lyu,J., Li,J. and Tan,G.
  TITLE     Copper exerts cytotoxicity through inhibition of iron-sulfur
            cluster biogenesis on ISCA1/ISCA2/ISCU assembly proteins
  JOURNAL   Free Radic Biol Med 204, 359-373 (2023)
   PUBMED   37225108
  REMARK    GeneRIF: Copper exerts cytotoxicity through inhibition of
            iron-sulfur cluster biogenesis on ISCA1/ISCA2/ISCU assembly
            proteins.
REFERENCE   2  (bases 1 to 983)
  AUTHORS   Maio,N. and Rouault,T.A.
  TITLE     Iron-sulfur cluster biogenesis in mammalian cells: New insights
            into the molecular mechanisms of cluster delivery
  JOURNAL   Biochim Biophys Acta 1853 (6), 1493-1512 (2015)
   PUBMED   25245479
  REMARK    Review article
REFERENCE   3  (bases 1 to 983)
  AUTHORS   Crooks,D.R., Jeong,S.Y., Tong,W.H., Ghosh,M.C., Olivierre,H.,
            Haller,R.G. and Rouault,T.A.
  TITLE     Tissue specificity of a human mitochondrial disease:
            differentiation-enhanced mis-splicing of the Fe-S scaffold gene
            ISCU renders patient cells more sensitive to oxidative stress in
            ISCU myopathy
  JOURNAL   J Biol Chem 287 (48), 40119-40130 (2012)
   PUBMED   23035118
  REMARK    GeneRIF: ISCU protein deficiency in patients results from
            muscle-specific mis-splicing and oxidative stress.
REFERENCE   4  (bases 1 to 983)
  AUTHORS   Nordin,A., Larsson,E., Thornell,L.E. and Holmberg,M.
  TITLE     Tissue-specific splicing of ISCU results in a skeletal muscle
            phenotype in myopathy with lactic acidosis, while complete loss of
            ISCU results in early embryonic death in mice
  JOURNAL   Hum Genet 129 (4), 371-378 (2011)
   PUBMED   21165651
  REMARK    GeneRIF: Data show that the highest level of incorrectly spliced
            ISCU mRNA was found in skeletal muscle.
REFERENCE   5  (bases 1 to 983)
  AUTHORS   Sanaker,P.S., Toompuu,M., Hogan,V.E., He,L., Tzoulis,C.,
            Chrzanowska-Lightowlers,Z.M., Taylor,R.W. and Bindoff,L.A.
  TITLE     Differences in RNA processing underlie the tissue specific
            phenotype of ISCU myopathy
  JOURNAL   Biochim Biophys Acta 1802 (6), 539-544 (2010)
   PUBMED   20206689
REFERENCE   6  (bases 1 to 983)
  AUTHORS   Olsson,A., Lind,L., Thornell,L.E. and Holmberg,M.
  TITLE     Myopathy with lactic acidosis is linked to chromosome 12q23.3-24.11
            and caused by an intron mutation in the ISCU gene resulting in a
            splicing defect
  JOURNAL   Hum Mol Genet 17 (11), 1666-1672 (2008)
   PUBMED   18296749
  REMARK    GeneRIF: Intron mutation in the ISCU gene, leading to incorrectly
            spliced mRNA, is the cause of myopathy with lactic acidosis in this
            family.
REFERENCE   7  (bases 1 to 983)
  AUTHORS   Mochel,F., Knight,M.A., Tong,W.H., Hernandez,D., Ayyad,K.,
            Taivassalo,T., Andersen,P.M., Singleton,A., Rouault,T.A.,
            Fischbeck,K.H. and Haller,R.G.
  TITLE     Splice mutation in the iron-sulfur cluster scaffold protein ISCU
            causes myopathy with exercise intolerance
  JOURNAL   Am J Hum Genet 82 (3), 652-660 (2008)
   PUBMED   18304497
  REMARK    GeneRIF: Gene ISCU was identified as a candidate within a region of
            shared homozygosity among patients with myopathy with severe
            exercise intolerance and myoglobinuria.
REFERENCE   8  (bases 1 to 983)
  AUTHORS   Tong,W.H. and Rouault,T.
  TITLE     Distinct iron-sulfur cluster assembly complexes exist in the
            cytosol and mitochondria of human cells
  JOURNAL   EMBO J 19 (21), 5692-5700 (2000)
   PUBMED   11060020
REFERENCE   9  (bases 1 to 983)
  AUTHORS   Hwang,D.M., Dempsey,A., Tan,K.T. and Liew,C.C.
  TITLE     A modular domain of NifU, a nitrogen fixation cluster protein, is
            highly conserved in evolution
  JOURNAL   J Mol Evol 43 (5), 536-540 (1996)
   PUBMED   8875867
REFERENCE   10 (bases 1 to 983)
  AUTHORS   Mochel,F. and Haller,R.G.
  TITLE     Myopathy with Deficiency of ISCU - RETIRED CHAPTER, FOR HISTORICAL
            REFERENCE ONLY
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301757
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AK057251.1, BC011906.2 and
            BQ020993.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Feb 27, 2020 this sequence version replaced NM_213595.3.
            
            Summary: This gene encodes a component of the iron-sulfur (Fe-S)
            cluster scaffold. Fe-S clusters are cofactors that play a role in
            the function of a diverse set of enzymes, including those that
            regulate metabolism, iron homeostasis, and oxidative stress
            response. Alternative splicing results in transcript variants
            encoding different protein isoforms that localize either to the
            cytosol or to the mitochondrion. Mutations in this gene have been
            found in patients with hereditary myopathy with lactic acidosis. A
            disease-associated mutation in an intron may activate a cryptic
            splice site, resulting in the production of a splice variant
            encoding a putatively non-functional protein. A pseudogene of this
            gene is present on chromosome 1. [provided by RefSeq, Feb 2016].
            
            Transcript Variant: This variant (2) encodes the longest isoform
            (2). Isoform 2 is localized to the mitochondrion.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: BC011906.2, AK000574.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: inferred from homology
            MANE Ensembl match                 :: ENST00000311893.14/
                                                  ENSP00000310623.9
            RefSeq Select criteria             :: based on manual assertion,
                                                  conservation, expression,
                                                  longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-62                AK057251.1         1134-1195
            63-935              BC011906.2         52-924
            936-983             BQ020993.1         33-80               c
FEATURES             Location/Qualifiers
     source          1..983
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="12"
                     /map="12q23.3"
     gene            1..983
                     /gene="ISCU"
                     /gene_synonym="2310020H20Rik; HML; hnifU; ISU2; NIFU;
                     NIFUN"
                     /note="iron-sulfur cluster assembly enzyme"
                     /db_xref="GeneID:23479"
                     /db_xref="HGNC:HGNC:29882"
                     /db_xref="MIM:611911"
     exon            1..141
                     /gene="ISCU"
                     /gene_synonym="2310020H20Rik; HML; hnifU; ISU2; NIFU;
                     NIFUN"
                     /inference="alignment:Splign:2.1.0"
     CDS             28..531
                     /gene="ISCU"
                     /gene_synonym="2310020H20Rik; HML; hnifU; ISU2; NIFU;
                     NIFUN"
                     /note="isoform 2 precursor is encoded by transcript
                     variant 2; iron-sulfur cluster assembly enzyme ISCU,
                     mitochondrial; nifU-like N-terminal domain-containing
                     protein; IscU iron-sulfur cluster scaffold homolog"
                     /codon_start=1
                     /product="iron-sulfur cluster assembly enzyme ISCU isoform
                     2 precursor"
                     /protein_id="NP_998760.1"
                     /db_xref="CCDS:CCDS44966.1"
                     /db_xref="GeneID:23479"
                     /db_xref="HGNC:HGNC:29882"
                     /db_xref="MIM:611911"
                     /translation="MAAAGAFRLRRAASALLLRSPRLPARELSAPARLYHKKVVDHYE
                     NPRNVGSLDKTSKNVGTGLVGAPACGDVMKLQIQVDEKGKIVDARFKTFGCGSAIASS
                     SLATEWVKGKTVEEALTIKNTDIAKELCLPPVKLHCSMLAEDAIKAALADYKLKQEPK
                     KGEAEKK"
     exon            142..255
                     /gene="ISCU"
                     /gene_synonym="2310020H20Rik; HML; hnifU; ISU2; NIFU;
                     NIFUN"
                     /inference="alignment:Splign:2.1.0"
     exon            256..366
                     /gene="ISCU"
                     /gene_synonym="2310020H20Rik; HML; hnifU; ISU2; NIFU;
                     NIFUN"
                     /inference="alignment:Splign:2.1.0"
     exon            367..445
                     /gene="ISCU"
                     /gene_synonym="2310020H20Rik; HML; hnifU; ISU2; NIFU;
                     NIFUN"
                     /inference="alignment:Splign:2.1.0"
     exon            446..983
                     /gene="ISCU"
                     /gene_synonym="2310020H20Rik; HML; hnifU; ISU2; NIFU;
                     NIFUN"
                     /inference="alignment:Splign:2.1.0"
     regulatory      924..929
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ISCU"
                     /gene_synonym="2310020H20Rik; HML; hnifU; ISU2; NIFU;
                     NIFUN"
                     /note="hexamer: CATAAA"
     polyA_site      962
                     /gene="ISCU"
                     /gene_synonym="2310020H20Rik; HML; hnifU; ISU2; NIFU;
                     NIFUN"
                     /note="major polyA site"
     regulatory      964..969
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ISCU"
                     /gene_synonym="2310020H20Rik; HML; hnifU; ISU2; NIFU;
                     NIFUN"
                     /note="hexamer: AATAAA"
     polyA_site      983
                     /gene="ISCU"
                     /gene_synonym="2310020H20Rik; HML; hnifU; ISU2; NIFU;
                     NIFUN"
                     /note="major polyA site"
ORIGIN      
        1 ggactggcgc aggcgcaagc cggcaagatg gcggcggctg gggctttccg tctgaggcgg
       61 gcggcatcgg ctctgctgct gcggagcccc cgcctgcccg cccgggagct gtcggccccg
      121 gcccgactct atcacaagaa ggttgttgat cattatgaaa atcctagaaa cgtggggtcc
      181 cttgacaaga catctaaaaa tgttggaact ggactggtgg gggctccagc atgtggtgac
      241 gtaatgaaat tacagattca agtggatgaa aaggggaaga ttgtggatgc taggtttaaa
      301 acatttggct gtggttccgc aattgcctcc agctcattag ccactgaatg ggtgaaagga
      361 aagacggtgg aggaagcctt gactatcaaa aacacagata tcgccaagga gctctgcctt
      421 cctcccgtga aactgcactg ctccatgctg gctgaagatg caatcaaggc cgccctggct
      481 gattacaaat tgaaacaaga acccaaaaaa ggagaggcag agaagaaatg agccctccct
      541 cggcgaagcc tccagcaggc cacaccagct gtttcccacc tgctgtgcag tcaccttaga
      601 tgttcagaag ccgcttcctc tccactgaag agctatgaga tacgcacaat acttgctgtt
      661 cacgttatga ctctcatgca agcaaaatac acagtttcat tgttctgaat cctgtggttt
      721 ctttcagccc acttttatcg ccttaaccta gttaatgtat attttgaatt gtgtgtatga
      781 cctcagaact gaaattgata atgaagttgc aagttttgat agcccgtgaa gtgcataagt
      841 atctaatttt acctgaattg atttgggggg aaattaccag tagaatgcct tggtctgaat
      901 atttgataga accaattgtt gtacataaaa cagattgcgc atatatatat atgtataaaa
      961 aataataaaa taatggaaga tga
//
