LOCUS       NM_013247               1785 bp    mRNA    linear   PRI 07-DEC-2024
DEFINITION  Homo sapiens HtrA serine peptidase 2 (HTRA2), transcript variant 1,
            mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_013247
VERSION     NM_013247.5
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 1785)
  AUTHORS   Aspholm,E.E., Lidman,J. and Burmann,B.M.
  TITLE     Structural basis of substrate recognition and allosteric activation
            of the proapoptotic mitochondrial HtrA2 protease
  JOURNAL   Nat Commun 15 (1), 4592 (2024)
   PUBMED   38816423
  REMARK    GeneRIF: Structural basis of substrate recognition and allosteric
            activation of the proapoptotic mitochondrial HtrA2 protease.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 1785)
  AUTHORS   Bi,P.Y., Killackey,S.A., Schweizer,L., Arnoult,D., Philpott,D.J.
            and Girardin,S.E.
  TITLE     Cytosolic retention of HtrA2 during mitochondrial protein import
            stress triggers the DELE1-HRI pathway
  JOURNAL   Commun Biol 7 (1), 391 (2024)
   PUBMED   38555279
  REMARK    GeneRIF: Cytosolic retention of HtrA2 during mitochondrial protein
            import stress triggers the DELE1-HRI pathway.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 1785)
  AUTHORS   Liu,Q., Yan,X., Yuan,Y., Li,R., Zhao,Y., Fu,J., Wang,J. and Su,J.
  TITLE     HTRA2/OMI-Mediated Mitochondrial Quality Control Alters Macrophage
            Polarization Affecting Systemic Chronic Inflammation
  JOURNAL   Int J Mol Sci 25 (3), 1577 (2024)
   PUBMED   38338855
  REMARK    GeneRIF: HTRA2/OMI-Mediated Mitochondrial Quality Control Alters
            Macrophage Polarization Affecting Systemic Chronic Inflammation.
            Review article
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 1785)
  AUTHORS   Jeong,G.H., Nam,M.K., Hur,W., Heo,S., Lee,S., Choi,E., Park,J.H.,
            Park,Y., Kim,W.U., Rhim,H. and Yoo,S.A.
  TITLE     Role of high-temperature requirement serine protease A 2 in
            rheumatoid inflammation
  JOURNAL   Arthritis Res Ther 25 (1), 96 (2023)
   PUBMED   37287073
  REMARK    GeneRIF: Role of high-temperature requirement serine protease A 2
            in rheumatoid inflammation.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 1785)
  AUTHORS   Suzuki,Y., Takahashi-Niki,K., Akagi,T., Hashikawa,T. and
            Takahashi,R.
  TITLE     Mitochondrial protease Omi/HtrA2 enhances caspase activation
            through multiple pathways
  JOURNAL   Cell Death Differ 11 (2), 208-216 (2004)
   PUBMED   14605674
  REMARK    GeneRIF: protease activity of Omi/HtrA2 promotes caspase activation
            through multiple pathways
REFERENCE   6  (bases 1 to 1785)
  AUTHORS   Faccio,L., Fusco,C., Viel,A. and Zervos,A.S.
  TITLE     Tissue-specific splicing of Omi stress-regulated endoprotease leads
            to an inactive protease with a modified PDZ motif
  JOURNAL   Genomics 68 (3), 343-347 (2000)
   PUBMED   10995577
REFERENCE   7  (bases 1 to 1785)
  AUTHORS   Gray,C.W., Ward,R.V., Karran,E., Turconi,S., Rowles,A.,
            Viglienghi,D., Southan,C., Barton,A., Fantom,K.G., West,A.,
            Savopoulos,J., Hassan,N.J., Clinkenbeard,H., Hanning,C.,
            Amegadzie,B., Davis,J.B., Dingwall,C., Livi,G.P. and Creasy,C.L.
  TITLE     Characterization of human HtrA2, a novel serine protease involved
            in the mammalian cellular stress response
  JOURNAL   Eur J Biochem 267 (18), 5699-5710 (2000)
   PUBMED   10971580
REFERENCE   8  (bases 1 to 1785)
  AUTHORS   Savopoulos,J.W., Carter,P.S., Turconi,S., Pettman,G.R.,
            Karran,E.H., Gray,C.W., Ward,R.V., Jenkins,O. and Creasy,C.L.
  TITLE     Expression, purification, and functional analysis of the human
            serine protease HtrA2
  JOURNAL   Protein Expr Purif 19 (2), 227-234 (2000)
   PUBMED   10873535
REFERENCE   9  (bases 1 to 1785)
  AUTHORS   Faccio,L., Fusco,C., Chen,A., Martinotti,S., Bonventre,J.V. and
            Zervos,A.S.
  TITLE     Characterization of a novel human serine protease that has
            extensive homology to bacterial heat shock endoprotease HtrA and is
            regulated by kidney ischemia
  JOURNAL   J Biol Chem 275 (4), 2581-2588 (2000)
   PUBMED   10644717
REFERENCE   10 (bases 1 to 1785)
  AUTHORS   Cook Shukla,L., Schulze,J., Farlow,J., Pankratz,N.D., Wojcieszek,J.
            and Foroud,T.
  TITLE     Parkinson Disease Overview
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301402
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AF141305.1 and BF939362.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Dec 23, 2019 this sequence version replaced NM_013247.4.
            
            Summary: This gene encodes a serine protease. The protein has been
            localized in the endoplasmic reticulum and interacts with an
            alternatively spliced form of mitogen-activated protein kinase 14.
            The protein has also been localized to the mitochondria with
            release to the cytosol following apoptotic stimulus. The protein is
            thought to induce apoptosis by binding the apoptosis inhibitory
            protein baculoviral IAP repeat-containing 4. Nuclear localization
            of this protein has also been observed. Alternate splicing of this
            gene results in multiple transcript variants encoding different
            isoforms. [provided by RefSeq, Mar 2016].
            
            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 :: BC000096.2, AF141305.1 [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. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000258080.8/
                                                  ENSP00000258080.3
            RefSeq Select criteria             :: based on manual assertion,
                                                  conservation, expression,
                                                  longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-1645              AF141305.1         529-2173
            1646-1785           BF939362.1         54-193
FEATURES             Location/Qualifiers
     source          1..1785
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="2"
                     /map="2p13.1"
     gene            1..1785
                     /gene="HTRA2"
                     /gene_synonym="MGCA8; OMI; PARK13; PRSS25"
                     /note="HtrA serine peptidase 2"
                     /db_xref="GeneID:27429"
                     /db_xref="HGNC:HGNC:14348"
                     /db_xref="MIM:606441"
     exon            1..580
                     /gene="HTRA2"
                     /gene_synonym="MGCA8; OMI; PARK13; PRSS25"
                     /inference="alignment:Splign:2.1.0"
     CDS             75..1451
                     /gene="HTRA2"
                     /gene_synonym="MGCA8; OMI; PARK13; PRSS25"
                     /EC_number="3.4.21.108"
                     /note="isoform 1 preproprotein is encoded by transcript
                     variant 1; protease, serine, 25; HtrA-like serine
                     protease; high temperature requirement protein A2; Omi
                     stress-regulated endoprotease; serine protease HTRA2,
                     mitochondrial; serine protease 25; serine proteinase OMI;
                     epididymis secretory sperm binding protein"
                     /codon_start=1
                     /product="serine protease HTRA2, mitochondrial isoform 1
                     preproprotein"
                     /protein_id="NP_037379.1"
                     /db_xref="CCDS:CCDS1951.1"
                     /db_xref="GeneID:27429"
                     /db_xref="HGNC:HGNC:14348"
                     /db_xref="MIM:606441"
                     /translation="MAAPRAGRGAGWSLRAWRALGGIRWGRRPRLTPDLRALLTSGTS
                     DPRARVTYGTPSLWARLSVGVTEPRACLTSGTPGPRAQLTAVTPDTRTREASENSGTR
                     SRAWLAVALGAGGAVLLLLWGGGRGPPAVLAAVPSPPPASPRSQYNFIADVVEKTAPA
                     VVYIEILDRHPFLGREVPISNGSGFVVAADGLIVTNAHVVADRRRVRVRLLSGDTYEA
                     VVTAVDPVADIATLRIQTKEPLPTLPLGRSADVRQGEFVVAMGSPFALQNTITSGIVS
                     SAQRPARDLGLPQTNVEYIQTDAAIDFGNSGGPLVNLDGEVIGVNTMKVTAGISFAIP
                     SDRLREFLHRGEKKNSSSGISGSQRRYIGVMMLTLSPSILAELQLREPSFPDVQHGVL
                     IHKVILGSPAHRAGLRPGDVILAIGEQMVQNAEDVYEAVRTQSQLAVQIRRGRETLTL
                     YVTPEVTE"
     exon            581..785
                     /gene="HTRA2"
                     /gene_synonym="MGCA8; OMI; PARK13; PRSS25"
                     /inference="alignment:Splign:2.1.0"
     exon            786..980
                     /gene="HTRA2"
                     /gene_synonym="MGCA8; OMI; PARK13; PRSS25"
                     /inference="alignment:Splign:2.1.0"
     exon            981..1013
                     /gene="HTRA2"
                     /gene_synonym="MGCA8; OMI; PARK13; PRSS25"
                     /inference="alignment:Splign:2.1.0"
     exon            1014..1119
                     /gene="HTRA2"
                     /gene_synonym="MGCA8; OMI; PARK13; PRSS25"
                     /inference="alignment:Splign:2.1.0"
     exon            1120..1189
                     /gene="HTRA2"
                     /gene_synonym="MGCA8; OMI; PARK13; PRSS25"
                     /inference="alignment:Splign:2.1.0"
     exon            1190..1285
                     /gene="HTRA2"
                     /gene_synonym="MGCA8; OMI; PARK13; PRSS25"
                     /inference="alignment:Splign:2.1.0"
     exon            1286..1785
                     /gene="HTRA2"
                     /gene_synonym="MGCA8; OMI; PARK13; PRSS25"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1622..1627
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HTRA2"
                     /gene_synonym="MGCA8; OMI; PARK13; PRSS25"
                     /note="hexamer: AATAAA"
     regulatory      1628..1633
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HTRA2"
                     /gene_synonym="MGCA8; OMI; PARK13; PRSS25"
                     /note="hexamer: ATTATA"
     polyA_site      1643
                     /gene="HTRA2"
                     /gene_synonym="MGCA8; OMI; PARK13; PRSS25"
                     /note="major polyA site"
     polyA_site      1658
                     /gene="HTRA2"
                     /gene_synonym="MGCA8; OMI; PARK13; PRSS25"
     regulatory      1762..1767
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HTRA2"
                     /gene_synonym="MGCA8; OMI; PARK13; PRSS25"
                     /note="hexamer: ATTAAA"
     polyA_site      1785
                     /gene="HTRA2"
                     /gene_synonym="MGCA8; OMI; PARK13; PRSS25"
ORIGIN      
        1 ctactgtccg cctgctcgcg tcctgggtgc cgcctctgag tagggcgggc gaggaggcag
       61 ccaaggcgga gctgatggct gcgccgaggg cggggcgggg tgcaggctgg agccttcggg
      121 catggcgggc tttggggggc attcgctggg ggaggagacc ccgtttgacc cctgacctcc
      181 gggccctgct gacgtcagga acttctgacc cccgggcccg agtgacttat gggaccccca
      241 gtctctgggc ccggttgtct gttggggtca ctgaaccccg agcatgcctg acgtctggga
      301 ccccgggtcc ccgggcacaa ctgactgcgg tgaccccaga taccaggacc cgggaggcct
      361 cagagaactc tggaacccgt tcgcgcgcgt ggctggcggt ggcgctgggc gctggggggg
      421 cagtgctgtt gttgttgtgg ggcgggggtc ggggtcctcc ggccgtcctc gccgccgtcc
      481 ctagcccgcc gcccgcttct ccccggagtc agtacaactt catcgcagat gtggtggaga
      541 agacagcacc tgccgtggtc tatatcgaga tcctggaccg gcaccctttc ttgggccgcg
      601 aggtccctat ctcgaacggc tcaggattcg tggtggctgc cgatgggctc attgtcacca
      661 acgcccatgt ggtggctgat cggcgcagag tccgtgtgag actgctaagc ggcgacacgt
      721 atgaggccgt ggtcacagct gtggatcccg tggcagacat cgcaacgctg aggattcaga
      781 ctaaggagcc tctccccacg ctgcctctgg gacgctcagc tgatgtccgg caaggggagt
      841 ttgttgttgc catgggaagt ccctttgcac tgcagaacac gatcacatcc ggcattgtta
      901 gctctgctca gcgtccagcc agagacctgg gactccccca aaccaatgtg gaatacattc
      961 aaactgatgc agctattgat tttggaaact ctggaggtcc cctggttaac ctggatgggg
     1021 aggtgattgg agtgaacacc atgaaggtca cagctggaat ctcctttgcc atcccttctg
     1081 atcgtcttcg agagtttctg catcgtgggg aaaagaagaa ttcctcctcc ggaatcagtg
     1141 ggtcccagcg gcgctacatt ggggtgatga tgctgaccct gagtcccagc atccttgctg
     1201 aactacagct tcgagaacca agctttcccg atgttcagca tggtgtactc atccataaag
     1261 tcatcctggg ctcccctgca caccgggctg gtctgcggcc tggtgatgtg attttggcca
     1321 ttggggagca gatggtacaa aatgctgaag atgtttatga agctgttcga acccaatccc
     1381 agttggcagt gcagatccgg cggggacgag aaacactgac cttatatgtg acccctgagg
     1441 tcacagaatg aatagatcac caagagtatg aggctcctgc tctgatttcc tccttgcctt
     1501 tctggctgag gttctgaggg caccgagaca gagggttaaa tgaaccagtg ggggcaggtc
     1561 cctccaacca ccagcactga ctcctgggct ctgaagaatc acagaaacac tttttatata
     1621 aaataaaatt atacctagca acatattata gtaaaaaatg aggtgggagg gctggatctt
     1681 ttcccccacc aaaaggctag aggtaaagct gtatccccct aaacttaggg gagatactgg
     1741 agctgaccat cctgacctcc tattaaagaa aatgagctgc tgcca
//
