LOCUS       NM_016139                797 bp    mRNA    linear   PRI 18-OCT-2024
DEFINITION  Homo sapiens coiled-coil-helix-coiled-coil-helix domain containing
            2 (CHCHD2), transcript variant 2, mRNA.
ACCESSION   NM_016139 XM_001125916
VERSION     NM_016139.4
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 797)
  AUTHORS   Ren,Y.L., Jiang,Z., Wang,J.Y., He,Q., Li,S.X., Gu,X.J., Qi,Y.R.,
            Zhang,M., Yang,W.J., Cao,B., Li,J.Y., Wang,Y. and Chen,Y.P.
  TITLE     Loss of CHCHD2 Stability Coordinates with C1QBP/CHCHD2/CHCHD10
            Complex Impairment to Mediate PD-Linked Mitochondrial Dysfunction
  JOURNAL   Mol Neurobiol 61 (10), 7968-7988 (2024)
   PUBMED   38453793
  REMARK    GeneRIF: Loss of CHCHD2 Stability Coordinates with
            C1QBP/CHCHD2/CHCHD10 Complex Impairment to Mediate PD-Linked
            Mitochondrial Dysfunction.
REFERENCE   2  (bases 1 to 797)
  AUTHORS   Lisowski,P., Lickfett,S., Rybak-Wolf,A., Menacho,C., Le,S.,
            Pentimalli,T.M., Notopoulou,S., Dykstra,W., Oehler,D.,
            Lopez-Calcerrada,S., Mlody,B., Otto,M., Wu,H., Richter,Y., Roth,P.,
            Anand,R., Kulka,L.A.M., Meierhofer,D., Glazar,P., Legnini,I.,
            Telugu,N.S., Hahn,T., Neuendorf,N., Miller,D.C., Boddrich,A.,
            Polzin,A., Mayatepek,E., Diecke,S., Olzscha,H., Kirstein,J.,
            Ugalde,C., Petrakis,S., Cambridge,S., Rajewsky,N., Kuhn,R.,
            Wanker,E.E., Priller,J., Metzger,J.J. and Prigione,A.
  TITLE     Mutant huntingtin impairs neurodevelopment in human brain organoids
            through CHCHD2-mediated neurometabolic failure
  JOURNAL   Nat Commun 15 (1), 7027 (2024)
   PUBMED   39174523
  REMARK    GeneRIF: Mutant huntingtin impairs neurodevelopment in human brain
            organoids through CHCHD2-mediated neurometabolic failure.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 797)
  AUTHORS   Leventoux,N., Morimoto,S., Ishikawa,M., Nakamura,S., Ozawa,F.,
            Kobayashi,R., Watanabe,H., Supakul,S., Okamoto,S., Zhou,Z.,
            Kobayashi,H., Kato,C., Hirokawa,Y., Aiba,I., Takahashi,S.,
            Shibata,S., Takao,M., Yoshida,M., Endo,F., Yamanaka,K., Kokubo,Y.
            and Okano,H.
  TITLE     Aberrant CHCHD2-associated mitochondriopathy in Kii ALS/PDC
            astrocytes
  JOURNAL   Acta Neuropathol 147 (1), 84 (2024)
   PUBMED   38750212
  REMARK    GeneRIF: Aberrant CHCHD2-associated mitochondriopathy in Kii
            ALS/PDC astrocytes.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 797)
  AUTHORS   Tio,M., Wen,R., Choo,C.N., Tan,J.B., Chua,A., Xiao,B.,
            Sundaram,J.R., Chan,C.H.S. and Tan,E.K.
  TITLE     Genetic and pharmacologic p32-inhibition rescue CHCHD2-linked
            Parkinson's disease phenotypes in vivo and in cell models
  JOURNAL   J Biomed Sci 31 (1), 24 (2024)
   PUBMED   38395904
  REMARK    GeneRIF: Genetic and pharmacologic p32-inhibition rescue
            CHCHD2-linked Parkinson's disease phenotypes in vivo and in cell
            models.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 797)
  AUTHORS   Liu,Y., Clegg,H.V., Leslie,P.L., Di,J., Tollini,L.A., He,Y.,
            Kim,T.H., Jin,A., Graves,L.M., Zheng,J. and Zhang,Y.
  TITLE     CHCHD2 inhibits apoptosis by interacting with Bcl-x L to regulate
            Bax activation
  JOURNAL   Cell Death Differ 22 (6), 1035-1046 (2015)
   PUBMED   25476776
  REMARK    GeneRIF: findings establish CHCHD2, a previously uncharacterized
            small mitochondrial protein with no known homology to the Bcl-2
            family, as one of the negative regulators of mitochondria-mediated
            apoptosis.
REFERENCE   6  (bases 1 to 797)
  AUTHORS   Aras,S., Bai,M., Lee,I., Springett,R., Huttemann,M. and
            Grossman,L.I.
  TITLE     MNRR1 (formerly CHCHD2) is a bi-organellar regulator of
            mitochondrial metabolism
  JOURNAL   Mitochondrion 20, 43-51 (2015)
   PUBMED   25315652
  REMARK    GeneRIF: MNRR1 (formerly CHCHD2) is imported to the mitochondrial
            intermembrane space by a Mia40-mediated pathway, where it binds to
            cytochrome c oxidase (COX).
REFERENCE   7  (bases 1 to 797)
  AUTHORS   Aras,S., Pak,O., Sommer,N., Finley,R. Jr., Huttemann,M.,
            Weissmann,N. and Grossman,L.I.
  TITLE     Oxygen-dependent expression of cytochrome c oxidase subunit 4-2
            gene expression is mediated by transcription factors RBPJ, CXXC5
            and CHCHD2
  JOURNAL   Nucleic Acids Res 41 (4), 2255-2266 (2013)
   PUBMED   23303788
REFERENCE   8  (bases 1 to 797)
  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 797)
  AUTHORS   Baughman,J.M., Nilsson,R., Gohil,V.M., Arlow,D.H., Gauhar,Z. and
            Mootha,V.K.
  TITLE     A computational screen for regulators of oxidative phosphorylation
            implicates SLIRP in mitochondrial RNA homeostasis
  JOURNAL   PLoS Genet 5 (8), e1000590 (2009)
   PUBMED   19680543
  REMARK    GeneRIF: Silencing CHCHD2 reduces cellular oxygen consumption and
            disrupts the assembly and activity of Cytochrome C Oxidase.
            Erratum:[PLoS Genet. 2010;6(3). doi:
            10.1371/annotation/36fe7624-0904-46d4-a013-4be6195245c4]
REFERENCE   10 (bases 1 to 797)
  AUTHORS   Kaltenbach,L.S., Romero,E., Becklin,R.R., Chettier,R., Bell,R.,
            Phansalkar,A., Strand,A., Torcassi,C., Savage,J., Hurlburt,A.,
            Cha,G.H., Ukani,L., Chepanoske,C.L., Zhen,Y., Sahasrabudhe,S.,
            Olson,J., Kurschner,C., Ellerby,L.M., Peltier,J.M., Botas,J. and
            Hughes,R.E.
  TITLE     Huntingtin interacting proteins are genetic modifiers of
            neurodegeneration
  JOURNAL   PLoS Genet 3 (5), e82 (2007)
   PUBMED   17500595
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DB442753.1 and BC003079.2.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_016139.3.
            
            Summary: The protein encoded by this gene belongs to a class of
            eukaryotic CX(9)C proteins characterized by four cysteine residues
            spaced ten amino acids apart from one another. These residues form
            disulfide linkages that define a CHCH fold. In response to stress,
            the protein translocates from the mitochondrial intermembrane space
            to the nucleus where it binds to a highly conserved 13 nucleotide
            oxygen responsive element in the promoter of cytochrome oxidase
            4I2, a subunit of the terminal enzyme of the electron transport
            chain. In concert with recombination signal sequence-binding
            protein J, binding of this protein activates the oxygen responsive
            element at four percent oxygen. In addition, it has been shown that
            this protein is a negative regulator of mitochondria-mediated
            apoptosis. In response to apoptotic stimuli, mitochondrial levels
            of this protein decrease, allowing BCL2-associated X protein to
            oligomerize and activate the caspase cascade. Pseudogenes of this
            gene are found on multiple chromosomes. Alternative splicing
            results in multiple transcript variants. [provided by RefSeq, Feb
            2016].
            
            Transcript Variant: This variant (2) uses an alternate splice site
            in the 3' coding region, which results in a frameshift compared to
            variant 1. It encodes isoform 2, which has a shorter and distinct
            C-terminus compared to 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 :: BI458479.1, BI457765.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1968540, SAMEA1968832
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: inferred from homology
            MANE Ensembl match                 :: ENST00000395422.4/
                                                  ENSP00000378812.3
            RefSeq Select criteria             :: based on conservation,
                                                  expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-26                DB442753.1         155-180
            27-797              BC003079.2         1-771
FEATURES             Location/Qualifiers
     source          1..797
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="7"
                     /map="7p11.2"
     gene            1..797
                     /gene="CHCHD2"
                     /gene_synonym="C7orf17; MIX17B; MNRR1; NS2TP; PARK22"
                     /note="coiled-coil-helix-coiled-coil-helix domain
                     containing 2"
                     /db_xref="GeneID:51142"
                     /db_xref="HGNC:HGNC:21645"
                     /db_xref="MIM:616244"
     exon            1..113
                     /gene="CHCHD2"
                     /gene_synonym="C7orf17; MIX17B; MNRR1; NS2TP; PARK22"
                     /inference="alignment:Splign:2.1.0"
     CDS             64..519
                     /gene="CHCHD2"
                     /gene_synonym="C7orf17; MIX17B; MNRR1; NS2TP; PARK22"
                     /EC_number="2.3.1.15"
                     /note="isoform 2 precursor is encoded by transcript
                     variant 2; 16.7kD protein;
                     coiled-coil-helix-coiled-coil-helix domain-containing
                     protein 2, mitochondrial; aging-associated gene 10
                     protein; HCV NS2 trans-regulated protein; mitochondria
                     nuclear retrograde regulator 1; MIX17 homolog B;
                     mitochondrial nuclear retrograde regulator 1"
                     /codon_start=1
                     /product="coiled-coil-helix-coiled-coil-helix
                     domain-containing protein 2 isoform 2 precursor"
                     /protein_id="NP_057223.1"
                     /db_xref="CCDS:CCDS5526.1"
                     /db_xref="GeneID:51142"
                     /db_xref="HGNC:HGNC:21645"
                     /db_xref="MIM:616244"
                     /translation="MPRGSRSRTSRMAPPASRAPQMRAAPRPAPVAQPPAAAPPSAVG
                     SSAAAPRQPGLMAQMATTAAGVAVGSAVGHTLGHAITGGFSGGSNAEPARPDITYQEP
                     QGTQPAQQQQPCLYEIKQFLECAQNQGDIKLCEGFNEVLKQCRLANGLA"
     exon            114..363
                     /gene="CHCHD2"
                     /gene_synonym="C7orf17; MIX17B; MNRR1; NS2TP; PARK22"
                     /inference="alignment:Splign:2.1.0"
     exon            364..508
                     /gene="CHCHD2"
                     /gene_synonym="C7orf17; MIX17B; MNRR1; NS2TP; PARK22"
                     /inference="alignment:Splign:2.1.0"
     exon            509..797
                     /gene="CHCHD2"
                     /gene_synonym="C7orf17; MIX17B; MNRR1; NS2TP; PARK22"
                     /inference="alignment:Splign:2.1.0"
     regulatory      777..782
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CHCHD2"
                     /gene_synonym="C7orf17; MIX17B; MNRR1; NS2TP; PARK22"
                     /note="hexamer: AATAAA"
     polyA_site      797
                     /gene="CHCHD2"
                     /gene_synonym="C7orf17; MIX17B; MNRR1; NS2TP; PARK22"
                     /note="major polyA site"
ORIGIN      
        1 agaagtcgct tagctcttcg gtggttgtcc cacgtccgga ggcctagccg tcgcttacct
       61 aggatgccgc gtggaagccg aagccgcacc tcccgcatgg cccctccggc cagccgggcc
      121 cctcagatga gagctgcacc caggccagca ccagtcgctc agccaccagc agcggcaccc
      181 ccatctgcag ttggctcttc tgctgctgcg ccccggcagc caggtctgat ggcccagatg
      241 gcaaccactg cagctggcgt ggctgtgggc tctgctgtgg ggcacacatt gggtcacgcc
      301 attactgggg gcttcagtgg aggaagtaat gctgagcctg cgaggcctga catcacttac
      361 caggagcctc agggaaccca gccagcacag cagcagcagc cttgcctcta tgagatcaaa
      421 cagtttctgg agtgtgccca gaaccagggt gacatcaagc tctgtgaggg tttcaatgag
      481 gtgctgaaac agtgccgact tgcaaacgga ttggcctaat gaagaagttc aacctggaga
      541 gatggaaaat cagctctcat aactaagtta atttagtata aaaatagaat tgatagtgag
      601 ggtataaagt gtaaccatca gttaaacctc tcctgtcatt cctggcttcc ttgcttcaga
      661 attgaaatgg aagtgggggt gtccctactc tgtagaatct gggactgggc aaatgtttgt
      721 gtggcctcct taaactagct gttatgttat gattttattc tttgtgagtt aattagaata
      781 aagtcatttt cttccaa
//
