LOCUS       NM_001171613            5829 bp    mRNA    linear   PRI 12-NOV-2024
DEFINITION  Homo sapiens prolyl endopeptidase like (PREPL), transcript variant
            6, mRNA.
ACCESSION   NM_001171613
VERSION     NM_001171613.2
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 5829)
  AUTHORS   Monnens,Y., Theodoropoulou,A., Rosier,K., Bhalla,K., Mahy,A.,
            Vanhoutte,R., Meulemans,S., Cavani,E., Antanasijevic,A.,
            Lemmens,I., Lee,J.A., Spellicy,C.J., Schroer,R.J., Maselli,R.A.,
            Laverty,C.G., Agostinis,P., Pagliarini,D.J., Verhelst,S.,
            Marcaida,M.J., Rochtus,A., Dal Peraro,M. and Creemers,J.W.
  TITLE     Missense variants in CMS22 patients reveal that PREPL has both
            enzymatic and nonenzymatic functions
  JOURNAL   JCI Insight 9 (17), e179276 (2024)
   PUBMED   39078710
  REMARK    GeneRIF: Missense variants in CMS22 patients reveal that PREPL has
            both enzymatic and nonenzymatic functions.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 5829)
  AUTHORS   Duarte,M.L., Wang,M., Gomes,I., Liu,C., Sharma,A., Fakira,A.K.,
            Gupta,A., Mack,S.M., Zhang,B. and Devi,L.A.
  TITLE     Multiomics Analyses Identify Proline Endopeptidase-Like Protein As
            a Key Regulator of Protein Trafficking, a Pathway Underlying
            Alzheimer's Disease Pathogenesis
  JOURNAL   Mol Pharmacol 104 (1), 1-16 (2023)
   PUBMED   37147110
  REMARK    GeneRIF: Multiomics Analyses Identify Proline Endopeptidase-Like
            Protein As a Key Regulator of Protein Trafficking, a Pathway
            Underlying Alzheimer's Disease Pathogenesis.
REFERENCE   3  (bases 1 to 5829)
  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   4  (bases 1 to 5829)
  AUTHORS   Shchagina,O., Bessonova,L., Bychkov,I., Beskorovainaya,T. and
            Poliakov,A.
  TITLE     A Family Case of Congenital Myasthenic Syndrome-22 Induced by
            Different Combinations of Molecular Causes in Siblings
  JOURNAL   Genes (Basel) 11 (7), 821 (2020)
   PUBMED   32707643
  REMARK    GeneRIF: A Family Case of Congenital Myasthenic Syndrome-22 Induced
            by Different Combinations of Molecular Causes in Siblings.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 5829)
  AUTHORS   Silva,S., Miyake,N., Tapia,C. and Matsumoto,N.
  TITLE     The second point mutation in PREPL: a case report and literature
            review
  JOURNAL   J Hum Genet 63 (5), 677-681 (2018)
   PUBMED   29483676
  REMARK    GeneRIF: we report the first homozygous PREPL point mutation in a
            girl with typical PREPL deficiency. This syndrome should be
            considered in the differential diagnosis of hypotonic neonates
            exhibiting myasthenic symptoms, hyperphagia, and various degrees of
            ID.
            Review article
REFERENCE   6  (bases 1 to 5829)
  AUTHORS   Parvari,R., Gonen,Y., Alshafee,I., Buriakovsky,S., Regev,K. and
            Hershkovitz,E.
  TITLE     The 2p21 deletion syndrome: characterization of the transcription
            content
  JOURNAL   Genomics 86 (2), 195-211 (2005)
   PUBMED   15913950
REFERENCE   7  (bases 1 to 5829)
  AUTHORS   Kim,D.K., Kanai,Y., Choi,H.W., Tangtrongsup,S., Chairoungdua,A.,
            Babu,E., Tachampa,K., Anzai,N., Iribe,Y. and Endou,H.
  TITLE     Characterization of the system L amino acid transporter in T24
            human bladder carcinoma cells
  JOURNAL   Biochim Biophys Acta 1565 (1), 112-121 (2002)
   PUBMED   12225859
  REMARK    GeneRIF: description of L-leucine transport into bladder carcinoma
            cells
REFERENCE   8  (bases 1 to 5829)
  AUTHORS   Parvari,R., Brodyansky,I., Elpeleg,O., Moses,S., Landau,D. and
            Hershkovitz,E.
  TITLE     A recessive contiguous gene deletion of chromosome 2p16 associated
            with cystinuria and a mitochondrial disease
  JOURNAL   Am J Hum Genet 69 (4), 869-875 (2001)
   PUBMED   11524703
REFERENCE   9  (bases 1 to 5829)
  AUTHORS   Robertson,N.G., Khetarpal,U., Gutierrez-Espeleta,G.A., Bieber,F.R.
            and Morton,C.C.
  TITLE     Isolation of novel and known genes from a human fetal cochlear cDNA
            library using subtractive hybridization and differential screening
  JOURNAL   Genomics 23 (1), 42-50 (1994)
   PUBMED   7829101
REFERENCE   10 (bases 1 to 5829)
  AUTHORS   Abicht,A., Muller,J.S. and Lochmuller,H.
  TITLE     Congenital Myasthenic Syndromes Overview
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301347
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DA246860.1, DQ023505.1,
            BC151236.1, AC013717.8 and CA951923.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 30, 2019 this sequence version replaced NM_001171613.1.
            
            Summary: The protein encoded by this gene belongs to the prolyl
            oligopeptidase subfamily of serine peptidases. Mutations in this
            gene have been associated with hypotonia-cystinuria syndrome, also
            known as the 2p21 deletion syndrome. Several alternatively spliced
            transcript variants encoding either the same or different isoforms
            have been described for this gene.[provided by RefSeq, Jan 2010].
            
            Transcript Variant: This variant (6) contains an alternate exon at
            the 5' end compared to variant 1, resulting in translation
            initiation from an in-frame downstream AUG and a shorter isoform
            (4) compared to isoform 1. Variants 6 and 7 encode the same
            isoform.
            
            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 :: AB007896.1, SRR14038195.600325.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000409411.6/ ENSP00000387095.2
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-115               DA246860.1         68-182
            116-2254            DQ023505.1         1179-3317
            2255-2628           BC151236.1         2797-3170
            2629-2629           AC013717.8         127749-127749       c
            2630-4670           BC151236.1         3171-5211
            4671-5821           AC013717.8         124557-125707       c
            5822-5829           CA951923.1         12-19               c
FEATURES             Location/Qualifiers
     source          1..5829
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="2"
                     /map="2p21"
     gene            1..5829
                     /gene="PREPL"
                     /gene_synonym="CMS22"
                     /note="prolyl endopeptidase like"
                     /db_xref="GeneID:9581"
                     /db_xref="HGNC:HGNC:30228"
                     /db_xref="MIM:609557"
     exon            1..115
                     /gene="PREPL"
                     /gene_synonym="CMS22"
                     /inference="alignment:Splign:2.1.0"
     exon            116..238
                     /gene="PREPL"
                     /gene_synonym="CMS22"
                     /inference="alignment:Splign:2.1.0"
     CDS             164..2080
                     /gene="PREPL"
                     /gene_synonym="CMS22"
                     /EC_number="3.4.21.-"
                     /note="isoform 4 is encoded by transcript variant 6;
                     putative prolyl oligopeptidase"
                     /codon_start=1
                     /product="prolyl endopeptidase-like isoform 4"
                     /protein_id="NP_001165084.1"
                     /db_xref="CCDS:CCDS54353.1"
                     /db_xref="GeneID:9581"
                     /db_xref="HGNC:HGNC:30228"
                     /db_xref="MIM:609557"
                     /translation="MDAFEKVRTKLETQPQEEYEIINVEVKHGGFVYYQEGCCLVRSK
                     DEEADNDNYEVLFNLEELKLDQPFIDCIRVAPDEKYVAAKIRTEDSEASTCVIIKLSD
                     QPVMEASFPNVSSFEWVKDEEDEDVLFYTFQRNLRCHDVYRATFGDNKRNERFYTEKD
                     PSYFVFLYLTKDSRFLTINIMNKTTSEVWLIDGLSPWDPPVLIQKRIHGVLYYVEHRD
                     DELYILTNVGEPTEFKLMRTAADTPAIMNWDLFFTMKRNTKVIDLDMFKDHCVLFLKH
                     SNLLYVNVIGLADDSVRSLKLPPWACGFIMDTNSDPKNCPFQLCSPIRPPKYYTYKFA
                     EGKLFEETGHEDPITKTSRVLRLEAKSKDGKLVPMTVFHKTDSEDLQKKPLLVHVYGA
                     YGMDLKMNFRPERRVLVDDGWILAYCHVRGGGELGLQWHADGRLTKKLNGLADLEACI
                     KTLHGQGFSQPSLTTLTAFSAGGVLAGALCNSNPELVRAVTLEAPFLDVLNTMMDTTL
                     PLTLEELEEWGNPSSDEKHKNYIKRYCPYQNIKPQHYPSIHITAYENDERVPLKGIVS
                     YTEKLKEAIAEHAKDTGEGYQTPNIILDIQPGGNHVIEDSHKKITAQIKFLYEELGLD
                     STSVFEDLKKYLKF"
     exon            239..305
                     /gene="PREPL"
                     /gene_synonym="CMS22"
                     /inference="alignment:Splign:2.1.0"
     exon            306..512
                     /gene="PREPL"
                     /gene_synonym="CMS22"
                     /inference="alignment:Splign:2.1.0"
     exon            513..648
                     /gene="PREPL"
                     /gene_synonym="CMS22"
                     /inference="alignment:Splign:2.1.0"
     exon            649..865
                     /gene="PREPL"
                     /gene_synonym="CMS22"
                     /inference="alignment:Splign:2.1.0"
     exon            866..1051
                     /gene="PREPL"
                     /gene_synonym="CMS22"
                     /inference="alignment:Splign:2.1.0"
     exon            1052..1249
                     /gene="PREPL"
                     /gene_synonym="CMS22"
                     /inference="alignment:Splign:2.1.0"
     exon            1250..1425
                     /gene="PREPL"
                     /gene_synonym="CMS22"
                     /inference="alignment:Splign:2.1.0"
     exon            1426..1642
                     /gene="PREPL"
                     /gene_synonym="CMS22"
                     /inference="alignment:Splign:2.1.0"
     exon            1643..1792
                     /gene="PREPL"
                     /gene_synonym="CMS22"
                     /inference="alignment:Splign:2.1.0"
     exon            1793..1916
                     /gene="PREPL"
                     /gene_synonym="CMS22"
                     /inference="alignment:Splign:2.1.0"
     exon            1917..1990
                     /gene="PREPL"
                     /gene_synonym="CMS22"
                     /inference="alignment:Splign:2.1.0"
     exon            1991..5829
                     /gene="PREPL"
                     /gene_synonym="CMS22"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4653..4658
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PREPL"
                     /gene_synonym="CMS22"
                     /note="hexamer: ATTAAA"
     polyA_site      4673
                     /gene="PREPL"
                     /gene_synonym="CMS22"
                     /note="major polyA site"
     regulatory      5806..5811
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PREPL"
                     /gene_synonym="CMS22"
                     /note="hexamer: ATTAAA"
     polyA_site      5829
                     /gene="PREPL"
                     /gene_synonym="CMS22"
ORIGIN      
        1 gcagacttcg gctggacttg cctgcggtga cacctgctcc cctctgagag cttcaggttc
       61 tccggcctgc cttcactggt ttgtgtccag agccggactg attctctcaa tttgcgatct
      121 tcagcctgtt aaacaagaaa acgaaaaacc ccttccagaa aacatggatg catttgaaaa
      181 agtgagaaca aaattagaaa cacagccaca agaagaatat gaaatcatca atgtggaagt
      241 taaacatggt ggttttgttt attaccaaga aggttgttgc ttggttcgtt ccaaagatga
      301 agaagcagac aatgataatt atgaagtttt attcaatttg gaggaactta agttagacca
      361 gcccttcatt gattgtatca gagttgctcc agatgaaaaa tatgtggctg ccaagataag
      421 aactgaagat tctgaagcat ctacctgtgt aattataaag ctcagcgatc agcccgtaat
      481 ggaagcttct ttcccgaatg tgtccagttt tgaatgggta aaggacgagg aagatgaaga
      541 tgttttattc tacaccttcc agaggaacct tcgctgtcat gacgtatatc gagccacttt
      601 tggtgataac aaacgtaatg aacgctttta cacagaaaaa gacccaagct actttgtttt
      661 cctttatctt acaaaagaca gtcgtttcct caccataaat attatgaaca agactacttc
      721 tgaagtgtgg ttgatagatg gcctgagccc ttgggaccca ccagtactta tccagaagcg
      781 aatacatggg gtcctttact atgttgaaca cagagatgat gaattataca ttctcactaa
      841 tgttggagaa cctacagaat ttaagctaat gagaacagcg gctgataccc ctgcaattat
      901 gaattgggat ttatttttta caatgaagag aaatacaaaa gtgatagact tggacatgtt
      961 taaggatcac tgtgttctat ttctgaagca cagcaatctc ctttatgtta atgtgattgg
     1021 tctggctgat gattcagttc ggtctctaaa gctccctcct tgggcctgtg gattcataat
     1081 ggatacaaat tctgacccaa agaactgccc ctttcaactt tgctctccaa tacgtccccc
     1141 aaaatattac acatacaagt ttgcagaagg caaactgttt gaggaaactg ggcatgaaga
     1201 cccaatcaca aagactagtc gcgttttacg tctagaagcc aaaagcaagg atggaaaatt
     1261 agtgccaatg actgttttcc acaaaactga ctctgaggac ttgcagaaga aacctctctt
     1321 ggtacatgta tatggagctt atggaatgga tttgaaaatg aatttcaggc ctgagaggcg
     1381 ggtcctggtg gatgatggat ggatattagc atactgccat gttcgaggtg gtggtgagtt
     1441 aggcctccag tggcacgctg atggccgcct aactaaaaaa ctcaatggcc ttgctgattt
     1501 agaggcttgc attaagacgc ttcatggcca aggcttttct cagccaagtc taacaaccct
     1561 gactgctttc agtgctggag gggtgcttgc aggagcattg tgtaattcta atccagagct
     1621 ggtgagagcg gtgactttgg aggcaccttt cttggatgtt ctcaacacca tgatggacac
     1681 tacacttcct ctgacattag aagaattaga agaatggggg aatccttcat ctgatgaaaa
     1741 acacaagaac tacataaaac gttactgtcc ctatcaaaat attaaacctc agcattatcc
     1801 ttcaattcac ataacggcat atgaaaacga tgaacgggta cctctgaaag gaattgtaag
     1861 ttatactgag aaactcaagg aagccatcgc ggagcatgct aaggacacag gtgaaggcta
     1921 tcagacccct aatattattc tagatattca gcctggaggc aatcatgtaa ttgaggattc
     1981 tcacaaaaag attacagccc aaattaaatt cctgtacgag gaacttggac ttgacagcac
     2041 cagtgttttc gaggatctta agaaatacct gaaattctga aacactgcat tcaactggga
     2101 attggaaaca cactgaaata tttcatagtc ttacttccaa ttgagttagc aaaaaaaaaa
     2161 ttaataactt gagactttta agttattaat tttttaaaat gtgcttctcc atctaaattt
     2221 tgcttagtct acatctcact tgcttatact attctctcca ttgatgcaca tgcccattaa
     2281 cctaggaaag taattttcaa atcatgctcc ttagaaggat gtggagtaga gggaagggaa
     2341 ggattggtga tagcagagct ccaggcctcc cttccagtca gaacagttga gcagtttaca
     2401 aattagtgtc ctgcctcttt gctagcaaat gcttttagac actgtggcag tgagtcatcc
     2461 tctaatttct atgactgcat tttaagggaa aagataaaat tcttcccctt aaaattcgtt
     2521 aaagtttttg aataatctgg ggtcctaatg tgttctggtc atccctgatt gatgctatct
     2581 gaataaagtt ataagctcct ataagccata atttactttt aaacatttta tttttttcaa
     2641 aacatttgag aacctttctt aaagcagtta cattcaagct acagaaatat cgaagaatta
     2701 atgattgttc accaagcagc atgctgtaca tgaagctatt acaaatgctt acaatcccac
     2761 tgaaatgcca gtgtcttcat ctcttcataa aggtgcctaa cacgaggtat acagtatgtt
     2821 cagtacactg gaatagcatg ctcgattgga aacaaagcat ctatctctga aagctgtttg
     2881 gcgatgaagg agattcttcg tgttgtgttc aaagatgagt ccctctccct tgtccagaaa
     2941 aatgccactt gtatcaactt tactgccttt gtcggcagaa ttggtactta accttattct
     3001 cattttagcg ggaaggcccg aaatcatatt atgtagattt aacagtgttg attctccaaa
     3061 attcagaacc acgataaaga ttctgtcgat gccatccagc tctcttgtgt acacaacata
     3121 gtggctgtca ttcctcaaat ggcaaaacca gcccctgttg aggagtagct cattggcatg
     3181 aagtagactt aaatcttgat ataacttcaa agccgatctg ggctgagtct tttggaccta
     3241 tttttttaaa aaagtattta cgtaagtgtt tgattctaag aattgtttgt aagtattttt
     3301 aatatattgt aaggagttat ttacccaaaa cacttgctcc aattttgccc cttataattg
     3361 ccaaattgta agcatcaata agtaggtaag aacaatttat ataaaaactg atagaaatga
     3421 caaattcggg gtttcggctt gtctgggagt caataagtac gcacagtgct ctgctacatt
     3481 gtagagtttc tgtagagatc aaatttgact ccactttagg agtcccaaag caaatgtcca
     3541 tgtctaagat gaatatttaa cttgcatagt cattctgtgc tatattgtaa ctgccagatg
     3601 gccagaaaga aggcaacagt ggactcagac ttctgaggaa tttgggtttg ttcccctttg
     3661 tagactaatg tgtaggttgc tgttgtgcga agatcgtgta actttagcag acatgtattt
     3721 cttgcacagc taatagaaga caaagttgaa aaaaaggatg caaaataaaa agctgcctaa
     3781 ggtgaaagtt agaaattgta gacttttttt taccataata gtatgtgttc attaaagatg
     3841 atttgggttt attttacagc tatataaaac ataatttgat gatgtacttc taacctttca
     3901 agcattttct gttattgact atataatata gcctccataa atgtttttaa tgacaatatt
     3961 ctgttgaacg gttgtaccat actcagccat gccctttcat tttgacgata gtgtttctaa
     4021 tattttgtat ttttattccc ctccccccat ttttgtatta cttaagatag attatcagaa
     4081 agacagttac tttgtcaaag agtatgggca cttgatacat aatgccaaat tattcttcat
     4141 aagagctgtt gccaaatcag tgataatgtt catttaattg tattcttgcc agccatgttt
     4201 actggggtga tagttgttat tgtggttgtt attgttcttt aggggtaggt tcccaatatg
     4261 tggtctttaa ataattatct aatggtgttt aaaaagatgt ttattctgtt tgtcaggtac
     4321 aaagatattt atgatacatg tatgacttgt ctaagttatt aacattttct ctagccttag
     4381 gtaatgcatg aaagcacatg tttcagtgcc actcacataa gaagtgcccg gtaagtgtta
     4441 gctattattg tctacttgag ttactacttt ctaaaagtat gttgaagtct ttttctgtaa
     4501 ttgcagattt gttgattttg catttgagta ttttctatat tttgaagctg ttagatgcgt
     4561 agtcatgatt tttggtggaa tgttttatca atttttgaaa attgcctttg tctcatataa
     4621 tgcttttcat attgaactat attttgtctg ctattaaata cttccaagcc tgatttttgt
     4681 aattttattt tttattcaat tacaagaata catactataa aaaggttttc ttcaacacct
     4741 ttccatagct tcacagttcc cctcagagac aggcactata tgttcttttg tttttaatgt
     4801 atcatatgtt tgcataggca cagaatgtat catttcatat gtttatatat ttttctttac
     4861 acagttggtg atatgttacc attctatact ttattgaata cctgtttgaa atggtctcat
     4921 atcaatgtat atagaactgt catttttaaa agctgcatac tgggcccata gttgatagaa
     4981 ctggttttct gttgataaaa tatttaaatc atttcttgtg tcttctatta aaaacaaatt
     5041 ttgcaggcca ggcaaggtgg ctcaggcccg taatcctagc actttgggag gcaaggcaga
     5101 cagatcacca gaggtcagga gttcaagacc agcctggcca acatggtgaa acaccatctc
     5161 tactaaaaaa tacagaaatt acccgggcat aatgacgtgc acctgtaatc ccagctactt
     5221 gggaggctgc agcaggagaa tcacttgaac ccaggaagca gaggctgcag tgtgccgaga
     5281 tcacgccact gcactcgagc atgggtgacg gagcaagact gtctcaaaaa aaaaaaaaaa
     5341 cagtgttgag atcctttaag tattattgtg cacatgtgca aatatttcta agtattagga
     5401 atggaattat taggtcaaaa gataacttca ttttttgtgt ttatagctat agctgggttg
     5461 caagctttct attatttgct tgctatatct tcattttaat tctttgtgtt ttatgttagt
     5521 gtttcttatg tctgtttttg ttatctgagt ggttttatct tttaataggc taatttaacc
     5581 cattcatatt tgtaattatt gtattattta gacataattc ggaagcccta ttttatttgt
     5641 agttatacta ttgtttaggg tttttttcta ttaagctttt tgttggattg actgtataat
     5701 ttttttcttc tagtattctt tgaaaatttg aaaattgtta tattttatgt ctagtgttct
     5761 ttgaaaataa ttctttgaaa attattttta tgtcctaatt ttaccattaa aattatgacc
     5821 acttgaaaa
//
