LOCUS       NM_018622               1501 bp    mRNA    linear   PRI 21-SEP-2024
DEFINITION  Homo sapiens presenilin associated rhomboid like (PARL), transcript
            variant 1, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_018622
VERSION     NM_018622.7
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 1501)
  AUTHORS   Siebert,V., Silber,M., Heuten,E., Muhle-Goll,C. and Lemberg,M.K.
  TITLE     Cleavage of mitochondrial homeostasis regulator PGAM5 by the
            intramembrane protease PARL is governed by transmembrane helix
            dynamics and oligomeric state
  JOURNAL   J Biol Chem 298 (9), 102321 (2022)
   PUBMED   35921890
  REMARK    GeneRIF: Cleavage of mitochondrial homeostasis regulator PGAM5 by
            the intramembrane protease PARL is governed by transmembrane helix
            dynamics and oligomeric state.
REFERENCE   2  (bases 1 to 1501)
  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   3  (bases 1 to 1501)
  AUTHORS   Lysyk,L., Brassard,R., Touret,N. and Lemieux,M.J.
  TITLE     PARL Protease: A Glimpse at Intramembrane Proteolysis in the Inner
            Mitochondrial Membrane
  JOURNAL   J Mol Biol 432 (18), 5052-5062 (2020)
   PUBMED   32320686
  REMARK    GeneRIF: PARL Protease: A Glimpse at Intramembrane Proteolysis in
            the Inner Mitochondrial Membrane.
            Review article
REFERENCE   4  (bases 1 to 1501)
  AUTHORS   Kawamoto,Y., Ayaki,T., Urushitani,M., Ito,H. and Takahashi,R.
  TITLE     Accumulation of HAX-1 and PARL in brainstem- and cortical-type Lewy
            bodies in Parkinson's disease and dementia with Lewy bodies
  JOURNAL   J Neurol Sci 415, 116928 (2020)
   PUBMED   32470650
  REMARK    GeneRIF: Accumulation of HAX-1 and PARL in brainstem- and
            cortical-type Lewy bodies in Parkinson's disease and dementia with
            Lewy bodies.
REFERENCE   5  (bases 1 to 1501)
  AUTHORS   Zhang,J., Zhao,Z.J., Fu,X., Niu,H., Hu,C., Dong,Y., Cui,M.Z.,
            Zhang,F., Zeng,L. and Xu,X.
  TITLE     Proapoptotic Mitochondrial Carrier Homolog Protein PSAP Mediates
            Death Receptor 6 Induced Apoptosis
  JOURNAL   J Alzheimers Dis 74 (4), 1097-1106 (2020)
   PUBMED   32144986
  REMARK    GeneRIF: Proapoptotic Mitochondrial Carrier Homolog Protein PSAP
            Mediates Death Receptor 6 Induced Apoptosis.
REFERENCE   6  (bases 1 to 1501)
  AUTHORS   Chan,E.Y. and McQuibban,G.A.
  TITLE     The mitochondrial rhomboid protease: its rise from obscurity to the
            pinnacle of disease-relevant genes
  JOURNAL   Biochim Biophys Acta 1828 (12), 2916-2925 (2013)
   PUBMED   24099009
  REMARK    Review article
REFERENCE   7  (bases 1 to 1501)
  AUTHORS   Walder,K., Kerr-Bayles,L., Civitarese,A., Jowett,J., Curran,J.,
            Elliott,K., Trevaskis,J., Bishara,N., Zimmet,P., Mandarino,L.,
            Ravussin,E., Blangero,J., Kissebah,A. and Collier,G.R.
  TITLE     The mitochondrial rhomboid protease PSARL is a new candidate gene
            for type 2 diabetes
  JOURNAL   Diabetologia 48 (3), 459-468 (2005)
   PUBMED   15729572
  REMARK    GeneRIF: Variation in PSARL sequence and/or expression may be an
            important new risk factor for type 2 diabetes and other components
            of the metabolic syndrome.
REFERENCE   8  (bases 1 to 1501)
  AUTHORS   Sik,A., Passer,B.J., Koonin,E.V. and Pellegrini,L.
  TITLE     Self-regulated cleavage of the mitochondrial intramembrane-cleaving
            protease PARL yields Pbeta, a nuclear-targeted peptide
  JOURNAL   J Biol Chem 279 (15), 15323-15329 (2004)
   PUBMED   14732705
  REMARK    GeneRIF: PARL might mediate a developmentally regulated
            mitochondria-to-nuclei signaling through regulated proteolysis of
            its N terminus and release of the Pbeta peptide
REFERENCE   9  (bases 1 to 1501)
  AUTHORS   McQuibban,G.A., Saurya,S. and Freeman,M.
  TITLE     Mitochondrial membrane remodelling regulated by a conserved
            rhomboid protease
  JOURNAL   Nature 423 (6939), 537-541 (2003)
   PUBMED   12774122
REFERENCE   10 (bases 1 to 1501)
  AUTHORS   Pellegrini,L., Passer,B.J., Canelles,M., Lefterov,I., Ganjei,J.K.,
            Fowlkes,B.J., Koonin,E.V. and D'Adamio,L.
  TITLE     PAMP and PARL, two novel putative metalloproteases interacting with
            the COOH-terminus of Presenilin-1 and -2
  JOURNAL   J Alzheimers Dis 3 (2), 181-190 (2001)
   PUBMED   12214059
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from CB122278.1, BC014058.2,
            CA417847.1 and AC131160.6.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Jun 2, 2019 this sequence version replaced NM_018622.6.
            
            Summary: This gene encodes a member of the rhomboid family of
            intramembrane serine proteases that is localized to the inner
            mitochondrial membrane. The encoded protein regulates mitochondrial
            remodeling and apoptosis through regulated substrate proteolysis.
            Proteolytic processing of the encoded protein results in the
            release of a small peptide, P-beta, which may transit to the
            nucleus. Mutations in this gene may be associated with Parkinson's
            disease. [provided by RefSeq, May 2016].
            
            Transcript Variant: This variant (1) encodes the longest isoform
            (1), which is localized to the mitochondria.
            
            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 :: AK024765.1, BC014058.2 [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                 :: ENST00000317096.9/
                                                  ENSP00000325421.5
            RefSeq Select criteria             :: based on conservation,
                                                  expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-14                CB122278.1         26-39
            15-1382             BC014058.2         1-1368
            1383-1387           CA417847.1         12-16               c
            1388-1501           AC131160.6         33222-33335
FEATURES             Location/Qualifiers
     source          1..1501
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="3"
                     /map="3q27.1"
     gene            1..1501
                     /gene="PARL"
                     /gene_synonym="PRO2207; PSARL; PSARL1; PSENIP2; RHBDS1"
                     /note="presenilin associated rhomboid like"
                     /db_xref="GeneID:55486"
                     /db_xref="HGNC:HGNC:18253"
                     /db_xref="MIM:607858"
     exon            1..159
                     /gene="PARL"
                     /gene_synonym="PRO2207; PSARL; PSARL1; PSENIP2; RHBDS1"
                     /inference="alignment:Splign:2.1.0"
     CDS             35..1174
                     /gene="PARL"
                     /gene_synonym="PRO2207; PSARL; PSARL1; PSENIP2; RHBDS1"
                     /EC_number="3.4.21.105"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1; mitochondrial intramembrane-cleaving protease
                     PARL; presenilins-associated rhomboid-like protein,
                     mitochondrial; rhomboid 7 homolog 1; presenilin-associated
                     rhomboid-like protein, mitochondrial"
                     /codon_start=1
                     /product="presenilin-associated rhomboid-like protein,
                     mitochondrial isoform 1 precursor"
                     /protein_id="NP_061092.3"
                     /db_xref="CCDS:CCDS3248.1"
                     /db_xref="GeneID:55486"
                     /db_xref="HGNC:HGNC:18253"
                     /db_xref="MIM:607858"
                     /translation="MAWRGWAQRGWGCGQAWGASVGGRSCEELTAVLTPPQLLGRRFN
                     FFIQQKCGFRKAPRKVEPRRSDPGTSGEAYKRSALIPPVEETVFYPSPYPIRSLIKPL
                     FFTVGFTGCAFGSAAIWQYESLKSRVQSYFDGIKADWLDSIRPQKEGDFRKEINKWWN
                     NLSDGQRTVTGIIAANVLVFCLWRVPSLQRTMIRYFTSNPASKVLCSPMLLSTFSHFS
                     LFHMAANMYVLWSFSSSIVNILGQEQFMAVYLSAGVISNFVSYVGKVATGRYGPSLGA
                     SGAIMTVLAAVCTKIPEGRLAIIFLPMFTFTAGNALKAIIAMDTAGMILGWKFFDHAA
                     HLGGALFGIWYVTYGHELIWKNREPLVKIWHEIRTNGPKKGGGSK"
     exon            160..355
                     /gene="PARL"
                     /gene_synonym="PRO2207; PSARL; PSARL1; PSENIP2; RHBDS1"
                     /inference="alignment:Splign:2.1.0"
     exon            356..496
                     /gene="PARL"
                     /gene_synonym="PRO2207; PSARL; PSARL1; PSENIP2; RHBDS1"
                     /inference="alignment:Splign:2.1.0"
     exon            497..545
                     /gene="PARL"
                     /gene_synonym="PRO2207; PSARL; PSARL1; PSENIP2; RHBDS1"
                     /inference="alignment:Splign:2.1.0"
     exon            546..641
                     /gene="PARL"
                     /gene_synonym="PRO2207; PSARL; PSARL1; PSENIP2; RHBDS1"
                     /inference="alignment:Splign:2.1.0"
     exon            642..791
                     /gene="PARL"
                     /gene_synonym="PRO2207; PSARL; PSARL1; PSENIP2; RHBDS1"
                     /inference="alignment:Splign:2.1.0"
     exon            792..862
                     /gene="PARL"
                     /gene_synonym="PRO2207; PSARL; PSARL1; PSENIP2; RHBDS1"
                     /inference="alignment:Splign:2.1.0"
     exon            863..964
                     /gene="PARL"
                     /gene_synonym="PRO2207; PSARL; PSARL1; PSENIP2; RHBDS1"
                     /inference="alignment:Splign:2.1.0"
     exon            965..1062
                     /gene="PARL"
                     /gene_synonym="PRO2207; PSARL; PSARL1; PSENIP2; RHBDS1"
                     /inference="alignment:Splign:2.1.0"
     exon            1063..1501
                     /gene="PARL"
                     /gene_synonym="PRO2207; PSARL; PSARL1; PSENIP2; RHBDS1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1357..1362
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PARL"
                     /gene_synonym="PRO2207; PSARL; PSARL1; PSENIP2; RHBDS1"
                     /note="hexamer: AATAAA"
     polyA_site      1382
                     /gene="PARL"
                     /gene_synonym="PRO2207; PSARL; PSARL1; PSENIP2; RHBDS1"
                     /note="major polyA site"
ORIGIN      
        1 aaggtcgggc catggtgggg cagaggttgg gaagatggcg tggcgaggct gggcgcagag
       61 aggctggggc tgcggccagg cgtggggtgc gtcggtgggc ggccgcagct gcgaggagct
      121 cactgcggtc ctaaccccgc cgcagctcct cggacgcagg tttaacttct ttattcaaca
      181 aaaatgcgga ttcagaaaag cacccaggaa ggttgaacct cgaagatcag acccagggac
      241 aagtggtgaa gcatacaaga gaagtgcttt gattcctcct gtggaagaaa cagtctttta
      301 tccttctccc tatcctataa ggagtctcat aaaaccttta ttttttactg ttgggtttac
      361 aggctgtgca tttggatcag ctgctatttg gcaatatgaa tcactgaaat ccagggtcca
      421 gagttatttt gatggtataa aagctgattg gttggatagc ataagaccac aaaaagaagg
      481 agacttcaga aaggagatta acaagtggtg gaataaccta agtgatggcc agcggactgt
      541 gacaggtatt atagctgcaa atgtccttgt attctgttta tggagagtac cttctctgca
      601 gcggacaatg atcagatatt tcacatcgaa tccagcctca aaggtccttt gttctccaat
      661 gttgctgtca acattcagtc atttctcctt atttcacatg gcagcaaata tgtatgtttt
      721 gtggagcttc tcttccagca tagtgaacat tctgggtcaa gagcagttca tggcagtgta
      781 cctatctgca ggtgttattt ccaattttgt cagttacgtg ggtaaagttg ccacaggaag
      841 atatggacca tcacttggtg catctggtgc catcatgaca gtcctcgcag ctgtctgcac
      901 taagatccca gaagggaggc ttgccattat tttccttccg atgttcacgt tcacagcagg
      961 gaatgccctg aaagccatta tcgccatgga tacagcagga atgatcctgg gatggaaatt
     1021 ttttgatcat gcggcacatc ttgggggagc tctttttgga atatggtatg ttacttacgg
     1081 tcatgaactg atttggaaga acagggagcc gctagtgaaa atctggcatg aaataaggac
     1141 taatggcccc aaaaaaggag gtggctctaa gtaaaactgg gattggacag tagtggtgca
     1201 tctggtcctt gccgcctgag agccccagga gacatcggct agagtgacca tggctatgct
     1261 cccgtctgga agatgccagc atctggcctc ccactgtttt cagctgtgtc ccccagtccg
     1321 tgtcttttta gaatgtgaat gatgataaag ttgtgaaata aaggtttcta tctagtttgt
     1381 aagcagatgt gtgtgttctc tctttaaggg gccgacacgg ctctggcatt ttgctttggt
     1441 tgttgcattg acaggacctg gggagagtgc accctgaaag gcctgatcag aacatgaagg
     1501 c
//
