LOCUS       NM_006660               4695 bp    mRNA    linear   PRI 16-FEB-2025
DEFINITION  Homo sapiens caseinolytic mitochondrial matrix peptidase chaperone
            subunit X (CLPX), transcript variant 1, mRNA; nuclear gene for
            mitochondrial product.
ACCESSION   NM_006660
VERSION     NM_006660.5
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 4695)
  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   2  (bases 1 to 4695)
  AUTHORS   Nomura,K., Kitagawa,Y., Aihara,M., Ohki,Y., Furuyama,K. and
            Hirokawa,T.
  TITLE     Heme-dependent recognition of 5-aminolevulinate synthase by the
            human mitochondrial molecular chaperone ClpX
  JOURNAL   FEBS Lett 595 (24), 3019-3029 (2021)
   PUBMED   34704252
  REMARK    GeneRIF: Heme-dependent recognition of 5-aminolevulinate synthase
            by the human mitochondrial molecular chaperone ClpX.
REFERENCE   3  (bases 1 to 4695)
  AUTHORS   Key,J., Torres-Odio,S., Bach,N.C., Gispert,S., Koepf,G.,
            Reichlmeir,M., West,A.P., Prokisch,H., Freisinger,P., Newman,W.G.,
            Shalev,S., Sieber,S.A., Wittig,I. and Auburger,G.
  TITLE     Inactivity of Peptidase ClpP Causes Primary Accumulation of
            Mitochondrial Disaggregase ClpX with Its Interacting Nucleoid
            Proteins, and of mtDNA
  JOURNAL   Cells 10 (12), 3354 (2021)
   PUBMED   34943861
  REMARK    GeneRIF: Inactivity of Peptidase ClpP Causes Primary Accumulation
            of Mitochondrial Disaggregase ClpX with Its Interacting Nucleoid
            Proteins, and of mtDNA.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 4695)
  AUTHORS   Serpeloni,F., Natt,D., Assis,S.G., Wieling,E. and Elbert,T.
  TITLE     Experiencing community and domestic violence is associated with
            epigenetic changes in DNA methylation of BDNF and CLPX in
            adolescents
  JOURNAL   Psychophysiology 57 (1), e13382 (2020)
   PUBMED   31059136
  REMARK    GeneRIF: Experiencing community and domestic violence is associated
            with epigenetic changes in DNA methylation of BDNF and CLPX in
            adolescents.
REFERENCE   5  (bases 1 to 4695)
  AUTHORS   Yien,Y.Y., Ducamp,S., van der Vorm,L.N., Kardon,J.R., Manceau,H.,
            Kannengiesser,C., Bergonia,H.A., Kafina,M.D., Karim,Z., Gouya,L.,
            Baker,T.A., Puy,H., Phillips,J.D., Nicolas,G. and Paw,B.H.
  TITLE     Mutation in human CLPX elevates levels of delta-aminolevulinate
            synthase and protoporphyrin IX to promote erythropoietic
            protoporphyria
  JOURNAL   Proc Natl Acad Sci U S A 114 (38), E8045-E8052 (2017)
   PUBMED   28874591
  REMARK    GeneRIF: The mutation in CLPX inactivates its ATPase activity,
            resulting in coassembly of mutant and WT protomers to form an
            enzyme with reduced activity. The presence of low-activity CLPX
            increases the posttranslational stability of ALAS, causing
            increased ALAS protein and ALA levels, leading to abnormal
            accumulation of PPIX.
REFERENCE   6  (bases 1 to 4695)
  AUTHORS   Kang,S.G., Maurizi,M.R., Thompson,M., Mueser,T. and Ahvazi,B.
  TITLE     Crystallography and mutagenesis point to an essential role for the
            N-terminus of human mitochondrial ClpP
  JOURNAL   J Struct Biol 148 (3), 338-352 (2004)
   PUBMED   15522782
REFERENCE   7  (bases 1 to 4695)
  AUTHORS   Kang,S.G., Ortega,J., Singh,S.K., Wang,N., Huang,N.N., Steven,A.C.
            and Maurizi,M.R.
  TITLE     Functional proteolytic complexes of the human mitochondrial
            ATP-dependent protease, hClpXP
  JOURNAL   J Biol Chem 277 (23), 21095-21102 (2002)
   PUBMED   11923310
REFERENCE   8  (bases 1 to 4695)
  AUTHORS   Corydon,T.J., Wilsbech,M., Jespersgaard,C., Andresen,B.S.,
            Borglum,A.D., Pedersen,S., Bolund,L., Gregersen,N. and Bross,P.
  TITLE     Human and mouse mitochondrial orthologs of bacterial ClpX
  JOURNAL   Mamm Genome 11 (10), 899-905 (2000)
   PUBMED   11003706
REFERENCE   9  (bases 1 to 4695)
  AUTHORS   de Sagarra,M.R., Mayo,I., Marco,S., Rodriguez-Vilarino,S.,
            Oliva,J., Carrascosa,J.L. and Casta n,J.G.
  TITLE     Mitochondrial localization and oligomeric structure of HClpP, the
            human homologue of E. coli ClpP
  JOURNAL   J Mol Biol 292 (4), 819-825 (1999)
   PUBMED   10525407
REFERENCE   10 (bases 1 to 4695)
  AUTHORS   Santagata,S., Bhattacharyya,D., Wang,F.H., Singha,N., Hodtsev,A.
            and Spanopoulou,E.
  TITLE     Molecular cloning and characterization of a mouse homolog of
            bacterial ClpX, a novel mammalian class II member of the Hsp100/Clp
            chaperone family
  JOURNAL   J Biol Chem 274 (23), 16311-16319 (1999)
   PUBMED   10347188
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BG717994.1, AJ006267.3,
            AC013553.14 and CA945006.1.
            
            On Nov 23, 2018 this sequence version replaced NM_006660.4.
            
            Summary: The protein encoded by this gene is part of a protease
            found in mitochondria. This protease is ATP-dependent and targets
            specific proteins for degradation. The protease consists of two
            heptameric rings of the CLPP catalytic subunit sandwiched between
            two hexameric rings of the chaperone subunit encoded by this gene.
            Targeted proteins are unwound by this protein and then passed on to
            the CLPP subunit for degradation. Two transcript variants, one
            protein-coding and the other non-protein coding, have been found
            for this gene. [provided by RefSeq, Nov 2015].
            
            Transcript Variant: This variant (1) represents the longer,
            protein-coding transcript.
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            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 :: SRR1803617.227545.1,
                                           SRR1803617.117099.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000300107.7/
                                                  ENSP00000300107.3
            RefSeq Select criteria             :: based on conservation,
                                                  expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-117               BG717994.1         84-200
            118-2468            AJ006267.3         1-2351
            2469-4033           AC013553.14        158016-159580       c
            4034-4695           CA945006.1         16-677              c
FEATURES             Location/Qualifiers
     source          1..4695
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="15"
                     /map="15q22.31"
     gene            1..4695
                     /gene="CLPX"
                     /gene_synonym="EPP2"
                     /note="caseinolytic mitochondrial matrix peptidase
                     chaperone subunit X"
                     /db_xref="GeneID:10845"
                     /db_xref="HGNC:HGNC:2088"
                     /db_xref="MIM:615611"
     exon            1..268
                     /gene="CLPX"
                     /gene_synonym="EPP2"
                     /inference="alignment:Splign:2.1.0"
     CDS             190..2091
                     /gene="CLPX"
                     /gene_synonym="EPP2"
                     /EC_number="3.6.4.10"
                     /note="energy-dependent regulator of proteolysis;
                     ATP-dependent Clp protease ATP-binding subunit clpX-like,
                     mitochondrial; ClpX caseinolytic protease X homolog; ClpX
                     caseinolytic peptidase X homolog; ATP-dependent clpX-like
                     chaperone, mitochondrial"
                     /codon_start=1
                     /product="ATP-dependent clpX-like chaperone, mitochondrial
                     precursor"
                     /protein_id="NP_006651.2"
                     /db_xref="CCDS:CCDS10202.1"
                     /db_xref="GeneID:10845"
                     /db_xref="HGNC:HGNC:2088"
                     /db_xref="MIM:615611"
                     /translation="MPSCGACTCGAAAVRLITSSLASAQRGISGGRIHMSVLGRLGTF
                     ETQILQRAPLRSFTETPAYFASKDGISKDGSGDGNKKSASEGSSKKSGSGNSGKGGNQ
                     LRCPKCGDLCTHVETFVSSTRFVKCEKCHHFFVVLSEADSKKSIIKEPESAAEAVKLA
                     FQQKPPPPPKKIYNYLDKYVVGQSFAKKVLSVAVYNHYKRIYNNIPANLRQQAEVEKQ
                     TSLTPRELEIRRREDEYRFTKLLQIAGISPHGNALGASMQQQVNQQIPQEKRGGEVLD
                     SSHDDIKLEKSNILLLGPTGSGKTLLAQTLAKCLDVPFAICDCTTLTQAGYVGEDIES
                     VIAKLLQDANYNVEKAQQGIVFLDEVDKIGSVPGIHQLRDVGGEGVQQGLLKLLEGTI
                     VNVPEKNSRKLRGETVQVDTTNILFVASGAFNGLDRIISRRKNEKYLGFGTPSNLGKG
                     RRAAAAADLANRSGESNTHQDIEEKDRLLRHVEARDLIEFGMIPEFVGRLPVVVPLHS
                     LDEKTLVQILTEPRNAVIPQYQALFSMDKCELNVTEDALKAIARLALERKTGARGLRS
                     IMEKLLLEPMFEVPNSDIVCVEVDKEVVEGKKEPGYIRAPTKESSEEEYDSGVEEEGW
                     PRQADAANS"
     exon            269..429
                     /gene="CLPX"
                     /gene_synonym="EPP2"
                     /inference="alignment:Splign:2.1.0"
     exon            430..547
                     /gene="CLPX"
                     /gene_synonym="EPP2"
                     /inference="alignment:Splign:2.1.0"
     exon            548..702
                     /gene="CLPX"
                     /gene_synonym="EPP2"
                     /inference="alignment:Splign:2.1.0"
     exon            703..862
                     /gene="CLPX"
                     /gene_synonym="EPP2"
                     /inference="alignment:Splign:2.1.0"
     exon            863..904
                     /gene="CLPX"
                     /gene_synonym="EPP2"
                     /inference="alignment:Splign:2.1.0"
     exon            905..1081
                     /gene="CLPX"
                     /gene_synonym="EPP2"
                     /inference="alignment:Splign:2.1.0"
     exon            1082..1246
                     /gene="CLPX"
                     /gene_synonym="EPP2"
                     /inference="alignment:Splign:2.1.0"
     exon            1247..1335
                     /gene="CLPX"
                     /gene_synonym="EPP2"
                     /inference="alignment:Splign:2.1.0"
     exon            1336..1500
                     /gene="CLPX"
                     /gene_synonym="EPP2"
                     /inference="alignment:Splign:2.1.0"
     exon            1501..1800
                     /gene="CLPX"
                     /gene_synonym="EPP2"
                     /inference="alignment:Splign:2.1.0"
     exon            1801..1893
                     /gene="CLPX"
                     /gene_synonym="EPP2"
                     /inference="alignment:Splign:2.1.0"
     exon            1894..2000
                     /gene="CLPX"
                     /gene_synonym="EPP2"
                     /inference="alignment:Splign:2.1.0"
     exon            2001..4695
                     /gene="CLPX"
                     /gene_synonym="EPP2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2442..2447
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CLPX"
                     /gene_synonym="EPP2"
                     /note="hexamer: AATAAA"
     polyA_site      2462
                     /gene="CLPX"
                     /gene_synonym="EPP2"
                     /note="major polyA site"
     regulatory      4042..4047
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CLPX"
                     /gene_synonym="EPP2"
                     /note="hexamer: ATTAAA"
     polyA_site      4066
                     /gene="CLPX"
                     /gene_synonym="EPP2"
     regulatory      4676..4681
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CLPX"
                     /gene_synonym="EPP2"
                     /note="hexamer: AACAAA"
     polyA_site      4695
                     /gene="CLPX"
                     /gene_synonym="EPP2"
                     /note="major polyA site"
ORIGIN      
        1 actctggtga atagacggct gtggggcaga gaagcgtgaa ggcctggctg ccgggcaggt
       61 gaactctcca cggggtctag ggcccgcgaa agggttcgga accgagtcag cgcgccttgc
      121 gggcaggatt cacgccgctg tgacccggag gtcctcaggg ggcgaagccc cggcctaggc
      181 ctcgcggaga tgcccagctg cggtgcttgt acttgcggcg cggcggccgt ccggctcatc
      241 acctcctcac tcgcctccgc gcagagaggt atttctggtg gtcgcattca tatgtcagtt
      301 ttaggaaggc ttgggacatt tgaaactcag attctgcaaa gagctcctct tagatccttt
      361 acagaaacac cagcatactt tgcctcaaaa gatgggataa gtaaagatgg ttctggagat
      421 ggaaataaga aatcagcaag tgagggaagt agtaagaaat caggctctgg gaattctggg
      481 aaaggtggaa accagctgcg ctgtcctaaa tgtggcgact tgtgcacaca tgtagagacc
      541 tttgtatcat ccacccgttt tgtcaagtgt gaaaagtgtc atcatttttt tgttgtgcta
      601 tctgaagcag actcaaagaa aagcataatt aaagaacctg aatcagcagc agaagctgta
      661 aaattggcat tccaacagaa accaccacct ccccctaaga agatttataa ctacctcgac
      721 aagtatgttg ttggccagtc atttgctaag aaggtgcttt cagttgctgt gtacaatcat
      781 tataagagaa tatataataa tatcccagct aatctgagac agcaagcaga ggttgagaag
      841 cagacatcat taacaccaag agagttagaa ataagaagac gggaggatga gtacagattt
      901 acaaaattgc ttcagattgc tggaattagc ccacatggta atgctttagg agcatcaatg
      961 cagcaacagg taaatcaaca aatacctcag gaaaaacgag gaggtgaagt attggattct
     1021 tctcatgatg acataaaact tgaaaaaagt aatattttgc tgcttggacc aactgggtca
     1081 ggtaaaactc tgctggcaca aaccctagct aaatgccttg atgtcccttt tgctatctgt
     1141 gactgtacaa ctttgactca ggctggatat gtaggcgaag atattgaatc tgtgattgca
     1201 aaactactcc aagatgccaa ttataatgtg gaaaaagcac aacaaggaat tgtctttctg
     1261 gatgaagtag ataagattgg cagtgtgcca ggcattcatc aattacggga tgtaggtgga
     1321 gaaggcgttc agcaaggctt attaaaacta ctagaaggca caatagtcaa tgttccagaa
     1381 aagaattccc gaaagctccg tggagaaaca gttcaagttg atacaacaaa catcctgttt
     1441 gtggcatctg gtgctttcaa tggtttagac agaatcatca gcaggaggaa aaatgaaaag
     1501 tatcttggat ttggaacacc atctaatctg ggaaaaggca gaagggctgc agctgctgca
     1561 gaccttgcta atcgaagtgg ggaatcgaat actcaccaag acattgaaga aaaagatcgg
     1621 ttattgcgtc atgtggaagc cagagatctg attgagtttg gcatgattcc tgagtttgtg
     1681 ggacggttgc ctgtggtggt tccattgcat agcctagatg agaaaacact tgtacaaata
     1741 ttaactgagc cacgaaatgc tgttattcct cagtaccagg ccttattcag catggataag
     1801 tgtgaactga atgttactga ggatgctttg aaagctatag ccagattggc actagaacga
     1861 aaaacaggtg cacgaggcct tcggtccata atggaaaagc tgttactaga accaatgttt
     1921 gaagtcccta attctgatat cgtatgtgtg gaggttgaca aagaagtagt agaaggaaaa
     1981 aaggaaccag gatacatccg ggctccaaca aaagaatcct ctgaagagga gtatgactct
     2041 ggagttgaag aagaaggatg gccccgccaa gcagatgctg caaacagcta aactgtcata
     2101 ttgctgtctt gtatatacag cttttccttc ttttgtttag gatcataatt gtctctacag
     2161 tctgatatta aaggcattgg atctatcttg gatatcatac atggtcagag aagcctttag
     2221 gagaagaatc agatcatgta tataattgta acatcacatt gattttacgg aagatgttat
     2281 atggacttta atgacacaat gtttagagat aaaatgtaca ttattttggt tcagtttttt
     2341 aaaaaaaata tgctttaaca aaattcttag gaattctttt aagcaatgca ggtattgcga
     2401 taactgtaga ttttacaata atgttactct acaaatggga aaataaattc tttaaaattg
     2461 aatattgaga taccattctt tagtgttacc ttttttaccc acatgtgttt ctgaaaatat
     2521 tggaatttta ttcatcttaa aaattggacc aggtaggccg ggcgtggtgg ctcacgcctg
     2581 taatcccagc actttgggag gccaaggcgg gtggatcacg aggtcaggag ttcaagacca
     2641 gcctggccaa gatggtgaaa ccccatctct actaaaaata tgaaaaatta gctgggtgcc
     2701 gtggcaggtg cctgtaatcc cagctactcg ggaggctgag gcaggagaat cgcttgaact
     2761 cggagggcag agtttacagt gagctgaggt tgtgccactg cactccagcc tgggcgacaa
     2821 agtgagactc cgtctcaggg cgaaaacaaa aaattggacc aggtagtttt caagtagtta
     2881 aacatttcat tgaaaaatac cctgaagaac tatattttga taattggttt agctgtattc
     2941 ctagtcttat ctgctaatgc atgacactaa cttcccaatt ggttctgtaa aaaaggccat
     3001 tttcttacca agttgtctga tttatttacc atcttttttt tttttttttt tttaattgag
     3061 cggagtctca cgctgtccca agctgaagtg cagtggtgcg atcttggctc actgcaacct
     3121 ccgcctccca ggttcaagca attttcctgc ctcagccttc caagtagctg ggattatagg
     3181 cacgcaccac cacacctggc taatttttgt atttttagta gagacagggt ttcaccctgt
     3241 tggccaggct agtctgtaac tcctgacctt gtgatctgct ggcctcagcc tcccaaagtg
     3301 ctgggattgc aggcgtaagc caccacaccc ggccttattt accatcttta atccatttta
     3361 gtactatggg tgagtacatg gaattgaagt ctggcttaaa tcttcagaaa gttatatatc
     3421 tattttattt tatttttttg agacagagtc tcgctgtgtc acccaggctg gagtacagtg
     3481 ccacaatctt ggctcactgc aacctctgag tcccaggttc aagcgatact catgcctcag
     3541 cctcctgagt agctgggact acaggcgtgc accaccacac ctggctaatt ttttgtattt
     3601 ttagtagaga cggggtttcg ccatgttgcc caggctggtc tctcctgagc tcaggcaatc
     3661 ggccaccttg gcctctgaaa gtgctagaat tacgggcatg agccaccgca tccagccaga
     3721 aagatacata tctaattcta gaaatagcat gcagtatcag tcatagtaac agccatgtgc
     3781 tgacctaaat aaaatttctt gatattgtgt atttaacctg aagtattgag ctagtttttt
     3841 tgttttgttt tttggtgctg aacattttgg tctaattctt tggcttctta gaacatttta
     3901 aaaaatctat gttttgctat cagccaaagt aaatgtgttc acactaacat ataagttact
     3961 aaccttcatt atacagcaaa gctaaaaagt ggtgggatat ttggggtctt aatgaaaatt
     4021 gtatcattta attccataaa tattaaaata tttgggtacc ttttaagctt tttttctttc
     4081 cttctataat ggtggtacaa gttctatatt cattcagttt aatctcattt gaaattgttt
     4141 aaatcagagt acatgtaaat atttgtgggt tttttttttt ggtttataga ctcgagcttt
     4201 ccttttacac agtttttttt agggaaaaac taaagctatt aggaaattct aaatcttgtt
     4261 gatgaagagt tgggctttct ttgatataat taataaaagg gatgtatggt atttatggct
     4321 gggtaggacc agaaatgcac tttgtattac agagtgttaa ggctggttgc tatagtatgg
     4381 aacagaaaca cctctccttg gtctccctag taatggttca agttcttccc aggaagtctt
     4441 acatattata actttgttca ttatctttcc cttatagcat cattttcctt tttgtagagt
     4501 ggaaatcaga ctagctgcta aacatattaa ggttaatcct ccagaaatgt actggggagg
     4561 cattttagtc acaacaactt acatttggct ttggaagttg ttaacaaagc atagtcgatg
     4621 tttttaaatc aaacataatt tgtatcttgg aacttacatt ttgacatttg aataaaacaa
     4681 aaagactaaa tgaaa
//
