LOCUS       NM_194279               2581 bp    mRNA    linear   PRI 04-OCT-2024
DEFINITION  Homo sapiens iron-sulfur cluster assembly 2 (ISCA2), transcript
            variant 1, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_194279 XM_058670
VERSION     NM_194279.4
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 2581)
  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 2581)
  AUTHORS   Green,Y.S., Ferreira Dos Santos,M.C., Fuja,D.G., Reichert,E.C.,
            Campos,A.R., Cowman,S.J., Acuna Pilarte,K., Kohan,J., Tripp,S.R.,
            Leibold,E.A., Sirohi,D., Agarwal,N., Liu,X. and Koh,M.Y.
  TITLE     ISCA2 inhibition decreases HIF and induces ferroptosis in clear
            cell renal carcinoma
  JOURNAL   Oncogene 41 (42), 4709-4723 (2022)
   PUBMED   36097192
  REMARK    GeneRIF: ISCA2 inhibition decreases HIF and induces ferroptosis in
            clear cell renal carcinoma.
REFERENCE   3  (bases 1 to 2581)
  AUTHORS   Wang,J., Jiang,M., Yue,G., Zhu,L., Wang,X., Liang,M., Wu,X., Li,B.,
            Pang,Y., Tan,G. and Li,J.
  TITLE     ISCA2 deficiency leads to heme synthesis defects and impaired
            erythroid differentiation in K562 cells by indirect ROS-mediated
            IRP1 activation
  JOURNAL   Biochim Biophys Acta Mol Cell Res 1869 (10), 119307 (2022)
   PUBMED   35714932
  REMARK    GeneRIF: ISCA2 deficiency leads to heme synthesis defects and
            impaired erythroid differentiation in K562 cells by indirect
            ROS-mediated IRP1 activation.
REFERENCE   4  (bases 1 to 2581)
  AUTHORS   Morgenstern,M., Peikert,C.D., Lubbert,P., Suppanz,I., Klemm,C.,
            Alka,O., Steiert,C., Naumenko,N., Schendzielorz,A., Melchionda,L.,
            Muhlhauser,W.W.D., Knapp,B., Busch,J.D., Stiller,S.B.,
            Dannenmaier,S., Lindau,C., Licheva,M., Eickhorst,C., Galbusera,R.,
            Zerbes,R.M., Ryan,M.T., Kraft,C., Kozjak-Pavlovic,V., Drepper,F.,
            Dennerlein,S., Oeljeklaus,S., Pfanner,N., Wiedemann,N. and
            Warscheid,B.
  TITLE     Quantitative high-confidence human mitochondrial proteome and its
            dynamics in cellular context
  JOURNAL   Cell Metab 33 (12), 2464-2483 (2021)
   PUBMED   34800366
REFERENCE   5  (bases 1 to 2581)
  AUTHORS   Huttlin,E.L., Bruckner,R.J., Navarrete-Perea,J., Cannon,J.R.,
            Baltier,K., Gebreab,F., Gygi,M.P., Thornock,A., Zarraga,G., Tam,S.,
            Szpyt,J., Gassaway,B.M., Panov,A., Parzen,H., Fu,S., Golbazi,A.,
            Maenpaa,E., Stricker,K., Guha Thakurta,S., Zhang,T., Rad,R.,
            Pan,J., Nusinow,D.P., Paulo,J.A., Schweppe,D.K., Vaites,L.P.,
            Harper,J.W. and Gygi,S.P.
  TITLE     Dual proteome-scale networks reveal cell-specific remodeling of the
            human interactome
  JOURNAL   Cell 184 (11), 3022-3040 (2021)
   PUBMED   33961781
REFERENCE   6  (bases 1 to 2581)
  AUTHORS   Sheftel,A.D., Wilbrecht,C., Stehling,O., Niggemeyer,B.,
            Elsasser,H.P., Muhlenhoff,U. and Lill,R.
  TITLE     The human mitochondrial ISCA1, ISCA2, and IBA57 proteins are
            required for [4Fe-4S] protein maturation
  JOURNAL   Mol Biol Cell 23 (7), 1157-1166 (2012)
   PUBMED   22323289
  REMARK    GeneRIF: ISCA1, ISCA2, and IBA57 were depleted by RNA interference.
            Depleted cells contained massively swollen and enlarged
            mitochondria that were virtually devoid of cristae membranes,
            demonstrating the importance of these proteins for mitochondrial
            biogenesis.
REFERENCE   7  (bases 1 to 2581)
  AUTHORS   Bailey,S.D., Xie,C., Do,R., Montpetit,A., Diaz,R., Mohan,V.,
            Keavney,B., Yusuf,S., Gerstein,H.C., Engert,J.C. and Anand,S.
  CONSRTM   DREAM investigators
  TITLE     Variation at the NFATC2 locus increases the risk of
            thiazolidinedione-induced edema in the Diabetes REduction
            Assessment with ramipril and rosiglitazone Medication (DREAM) study
  JOURNAL   Diabetes Care 33 (10), 2250-2253 (2010)
   PUBMED   20628086
  REMARK    GeneRIF: Observational study of gene-disease association,
            gene-environment interaction, and pharmacogenomic / toxicogenomic.
            (HuGE Navigator)
REFERENCE   8  (bases 1 to 2581)
  AUTHORS   Hendrickson,S.L., Lautenberger,J.A., Chinn,L.W., Malasky,M.,
            Sezgin,E., Kingsley,L.A., Goedert,J.J., Kirk,G.D., Gomperts,E.D.,
            Buchbinder,S.P., Troyer,J.L. and O'Brien,S.J.
  TITLE     Genetic variants in nuclear-encoded mitochondrial genes influence
            AIDS progression
  JOURNAL   PLoS One 5 (9), e12862 (2010)
   PUBMED   20877624
  REMARK    GeneRIF: Observational study of gene-disease association. (HuGE
            Navigator)
            Publication Status: Online-Only
REFERENCE   9  (bases 1 to 2581)
  AUTHORS   Talmud,P.J., Drenos,F., Shah,S., Shah,T., Palmen,J., Verzilli,C.,
            Gaunt,T.R., Pallas,J., Lovering,R., Li,K., Casas,J.P., Sofat,R.,
            Kumari,M., Rodriguez,S., Johnson,T., Newhouse,S.J., Dominiczak,A.,
            Samani,N.J., Caulfield,M., Sever,P., Stanton,A., Shields,D.C.,
            Padmanabhan,S., Melander,O., Hastie,C., Delles,C., Ebrahim,S.,
            Marmot,M.G., Smith,G.D., Lawlor,D.A., Munroe,P.B., Day,I.N.,
            Kivimaki,M., Whittaker,J., Humphries,S.E. and Hingorani,A.D.
  CONSRTM   ASCOT investigators; NORDIL investigators; BRIGHT Consortium
  TITLE     Gene-centric association signals for lipids and apolipoproteins
            identified via the HumanCVD BeadChip
  JOURNAL   Am J Hum Genet 85 (5), 628-642 (2009)
   PUBMED   19913121
  REMARK    GeneRIF: Observational study of gene-disease association. (HuGE
            Navigator)
REFERENCE   10 (bases 1 to 2581)
  AUTHORS   Al-Hassnan,Z.N. and Kaya,N.
  TITLE     ISCA2-Related Mitochondrial Disorder
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   29470032
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BX248252.1 and AC005479.2.
            This sequence is a reference standard in the RefSeqGene project.
            
            On May 17, 2019 this sequence version replaced NM_194279.3.
            
            Summary: The protein encoded by this gene is an A-type iron-sulfur
            cluster (ISC) protein found in mitochondria. The encoded protein
            appears to be involved in the maturation of mitochondrial
            iron-sulfur proteins. Two transcript variants encoding different
            isoforms have been found for this gene. [provided by RefSeq, Dec
            2012].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the longer isoform (1).
            
            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 :: SRR1803613.130689.1,
                                           SRR1803614.117327.1 [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. :: PMID: 22323289; reported by
                                                  MitoCarta
            MANE Ensembl match                 :: ENST00000556816.6/
                                                  ENSP00000452007.1
            RefSeq Select criteria             :: based on conservation,
                                                  expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-1043              BX248252.1         4-1046
            1044-2581           AC005479.2         37821-39358         c
FEATURES             Location/Qualifiers
     source          1..2581
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="14"
                     /map="14q24.3"
     gene            1..2581
                     /gene="ISCA2"
                     /gene_synonym="c14_5557; HBLD1; ISA2; MMDS4"
                     /note="iron-sulfur cluster assembly 2"
                     /db_xref="GeneID:122961"
                     /db_xref="HGNC:HGNC:19857"
                     /db_xref="MIM:615317"
     exon            1..81
                     /gene="ISCA2"
                     /gene_synonym="c14_5557; HBLD1; ISA2; MMDS4"
                     /inference="alignment:Splign:2.1.0"
     CDS             11..475
                     /gene="ISCA2"
                     /gene_synonym="c14_5557; HBLD1; ISA2; MMDS4"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1; iron-sulfur cluster assembly 2 homolog,
                     mitochondrial; HESB-like domain-containing protein 1"
                     /codon_start=1
                     /product="iron-sulfur cluster assembly 2 homolog,
                     mitochondrial isoform 1 precursor"
                     /protein_id="NP_919255.2"
                     /db_xref="CCDS:CCDS32122.1"
                     /db_xref="GeneID:122961"
                     /db_xref="HGNC:HGNC:19857"
                     /db_xref="MIM:615317"
                     /translation="MAAAWGSSLTAATQRAVTPWPRGRLLTASLGPQARREASSSSPE
                     AGEGQIRLTDSCVQRLLEITEGSEFLRLQVEGGGCSGFQYKFSLDTVINPDDRVFEQG
                     GARVVVDSDSLAFVKGAQVDFSQELIRSSFQVLNNPQAQQGCSCGSSFSIKL"
     exon            82..184
                     /gene="ISCA2"
                     /gene_synonym="c14_5557; HBLD1; ISA2; MMDS4"
                     /inference="alignment:Splign:2.1.0"
     exon            185..300
                     /gene="ISCA2"
                     /gene_synonym="c14_5557; HBLD1; ISA2; MMDS4"
                     /inference="alignment:Splign:2.1.0"
     exon            301..2581
                     /gene="ISCA2"
                     /gene_synonym="c14_5557; HBLD1; ISA2; MMDS4"
                     /inference="alignment:Splign:2.1.0"
     regulatory      819..824
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ISCA2"
                     /gene_synonym="c14_5557; HBLD1; ISA2; MMDS4"
                     /note="hexamer: TATAAA"
     polyA_site      841
                     /gene="ISCA2"
                     /gene_synonym="c14_5557; HBLD1; ISA2; MMDS4"
                     /note="major polyA site"
     regulatory      917..922
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ISCA2"
                     /gene_synonym="c14_5557; HBLD1; ISA2; MMDS4"
                     /note="hexamer: AATGAA"
     polyA_site      942
                     /gene="ISCA2"
                     /gene_synonym="c14_5557; HBLD1; ISA2; MMDS4"
     regulatory      1728..1733
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ISCA2"
                     /gene_synonym="c14_5557; HBLD1; ISA2; MMDS4"
                     /note="hexamer: AGTAAA"
     polyA_site      1754
                     /gene="ISCA2"
                     /gene_synonym="c14_5557; HBLD1; ISA2; MMDS4"
     regulatory      2099..2104
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ISCA2"
                     /gene_synonym="c14_5557; HBLD1; ISA2; MMDS4"
                     /note="hexamer: AATATA"
     polyA_site      2117
                     /gene="ISCA2"
                     /gene_synonym="c14_5557; HBLD1; ISA2; MMDS4"
ORIGIN      
        1 gtggaggaag atggctgccg cctgggggtc gtccctaacg gccgcgacgc agagagcggt
       61 cactccctgg ccgaggggca ggctcctcac ggcctccctg ggaccccagg cgcgtcggga
      121 ggcgtcgtcc tccagccccg aggccggcga agggcagatc cgcctcacag acagttgcgt
      181 ccagaggctt ttggaaatca ccgaagggtc agaattcctc aggctgcaag tggagggagg
      241 tggatgctcc ggattccaat acaaattttc actggataca gttatcaacc ccgacgacag
      301 ggtatttgaa cagggtgggg caagagtggt ggttgactct gatagcttgg ccttcgtgaa
      361 aggggcccag gtggacttca gccaagaact gatccgaagc tcatttcaag tgttgaacaa
      421 tcctcaagca cagcaaggct gctcctgtgg gtcatctttc tctatcaaac tttgatgtga
      481 tgactggtga ctctgggatt gtcaccagtt gtaccaattt gaagaacctg gaattagtag
      541 aattctagaa gtttacttct aatcatgtcc ctctcaattt tatttcccgc agtccaggag
      601 tgttatgttt tgccactatt attttcagaa tgtgaagatt ttactcttgg cttaattttt
      661 ccctccactc agtgctaagg ctgagcctcc agatgctgtt acctcagatt taatcactgg
      721 ttgaaactcc gtataatctg tagagcctcc atggctctaa aatttggaat taacttctct
      781 tgccttaaga gctgcttgta catatgtgga tagctatgta taaaagcttc attttaaaga
      841 aggttcttat tgtgttgtgg atcagggtca cagattgggt agcttggaca ccagttatta
      901 gaggatgaga aaagtaaatg aaatgttctc tttttcactt caccctgcca gaatgtgcca
      961 cttgacttat ctttattgtc tatgcaaccc atttgccact tcctgtttga taggacagat
     1021 acattttact ctcatgctcg tggatctgct atgagtcata aaaccaagag cccgttaccc
     1081 agaaaacttg gaccaaaccc tcactgatag tgaattattt caaaaatagc ctccctactc
     1141 atacagacat tttaagattc tgtgacaatt taatgactga atctttttag gatatgttgc
     1201 tttacctgcc ttctgttgta aaatggctct ggtctcatgc acagcaggaa gtgatccctt
     1261 tattgttata ggtaatagat tcttgggaac ctttttttag attgggttac cagatgaaat
     1321 gtaggatgcc cagttaaatt tgaatttcag gtaaataatt ttttagtatg catatgtctc
     1381 aaatattgca tatactaaaa attactattt gaaattcaaa tttaactcat atttttattt
     1441 gctgaccttg gcaactctgc tttagggtca ccaaacagct tttaaaatca caaattctag
     1501 tgaattaaag tacttgtgta ggtgtggcac ttaaataggc ttcggagctt gaaataatcc
     1561 tgttagagta ctgtggagct gtgtggacag acagtgaaag aaatctacca ccatcaccac
     1621 accgaatgat ttattaatac tgatgttgga gaaactacaa ccaagttgat tctggaagag
     1681 ttactggtta aatccatctt ttgcttggga gcctagaagt ttgttacagt aaagacttgc
     1741 atttctgcac tggattggaa ttaaggtcat ttagtaagaa tttactattt aaaaaaatgg
     1801 aaatagagtt tagaaaatat ctgagacaga aacttagata catttccaac atggcaaaac
     1861 ctaggactta gagaaaacaa acctatcatg cggttagagg agagaagggg acactcagaa
     1921 acctgagcac atttcttaga gctggtggaa ggaggcagaa agcagcatac catgggagca
     1981 tctgtgtgca cacatgacca agacagtgcc gccagtacct gcgcctgata gggtttcagt
     2041 tcagactacc tgtcctttca tcctccttaa aaagattttg ctacatttta aacattagaa
     2101 tatattcttt aagaatattt ttgtgggtta tttattgatt ttgtggtttt aaaactcttg
     2161 agcacgagca gaacagcttt tgttgctaaa tcaatcaaat tacagtggtg cactagacag
     2221 aaacagtccc ttagaatgca gcttatatgt gagtatctac tgttaatggg agaattggaa
     2281 ttttatgttt agaaaaaggc agatttgggg ctgggcacgg tggctcacgc ctgtgatccc
     2341 agcactttgg gaggccaaag caggcagatc acctgaggtc aggagtttga gaccagcctg
     2401 ggcaacatgg tgaaacccca tctctactaa aaatacaaaa attaactgcg tggtggacac
     2461 ctgtaatccc agctactcgg gagactgagg caagagaatc acttgaaccc aggaggtgga
     2521 gattgcagtg agccaagatt gcaccactgg actccagcct gggtggcaga gtgagactct
     2581 g
//
