LOCUS       NM_017951               3749 bp    mRNA    linear   PRI 07-APR-2024
DEFINITION  Homo sapiens sphingomyelin phosphodiesterase 4 (SMPD4), transcript
            variant 2, mRNA.
ACCESSION   NM_017951 NR_033230
VERSION     NM_017951.5
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 3749)
  AUTHORS   Aoki,S., Watanabe,K., Kato,M., Konishi,Y., Kubota,K., Kobayashi,E.,
            Nakashima,M. and Saitsu,H.
  TITLE     Two novel cases of biallelic SMPD4 variants with brain structural
            abnormalities
  JOURNAL   Neurogenetics 25 (1), 3-11 (2024)
   PUBMED   37882972
  REMARK    GeneRIF: Two novel cases of biallelic SMPD4 variants with brain
            structural abnormalities.
            Review article
REFERENCE   2  (bases 1 to 3749)
  AUTHORS   Piet,A.C.A., Post,M., Dekkers,D., Demmers,J.A.A. and Fornerod,M.
  TITLE     Proximity Ligation Mapping of Microcephaly Associated SMPD4 Shows
            Association with Components of the Nuclear Pore Membrane
  JOURNAL   Cells 11 (4), 674 (2022)
   PUBMED   35203325
  REMARK    GeneRIF: Proximity Ligation Mapping of Microcephaly Associated
            SMPD4 Shows Association with Components of the Nuclear Pore
            Membrane.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 3749)
  AUTHORS   Magini,P., Smits,D.J., Vandervore,L., Schot,R., Columbaro,M.,
            Kasteleijn,E., van der Ent,M., Palombo,F., Lequin,M.H., Dremmen,M.,
            de Wit,M.C.Y., Severino,M., Divizia,M.T., Striano,P.,
            Ordonez-Herrera,N., Alhashem,A., Al Fares,A., Al Ghamdi,M.,
            Rolfs,A., Bauer,P., Demmers,J., Verheijen,F.W., Wilke,M., van
            Slegtenhorst,M., van der Spek,P.J., Seri,M., Jansen,A.C.,
            Stottmann,R.W., Hufnagel,R.B., Hopkin,R.J., Aljeaid,D.,
            Wiszniewski,W., Gawlinski,P., Laure-Kamionowska,M., Alkuraya,F.S.,
            Akleh,H., Stanley,V., Musaev,D., Gleeson,J.G., Zaki,M.S.,
            Brunetti-Pierri,N., Cappuccio,G., Davidov,B., Basel-Salmon,L.,
            Bazak,L., Shahar,N.R., Bertoli-Avella,A., Mirzaa,G.M., Dobyns,W.B.,
            Pippucci,T., Fornerod,M. and Mancini,G.M.S.
  TITLE     Loss of SMPD4 Causes a Developmental Disorder Characterized by
            Microcephaly and Congenital Arthrogryposis
  JOURNAL   Am J Hum Genet 105 (4), 689-705 (2019)
   PUBMED   31495489
  REMARK    GeneRIF: data show that SMPD4 links homeostasis of membrane
            sphingolipids to cell fate by regulating the cross-talk between the
            endoplasmic reticulum and the outer nuclear envelope, while its
            loss reveals a pathogenic mechanism in microcephaly
REFERENCE   4  (bases 1 to 3749)
  AUTHORS   Moylan,J.S., Smith,J.D., Wolf Horrell,E.M., McLean,J.B.,
            Deevska,G.M., Bonnell,M.R., Nikolova-Karakashian,M.N. and Reid,M.B.
  TITLE     Neutral sphingomyelinase-3 mediates TNF-stimulated oxidant activity
            in skeletal muscle
  JOURNAL   Redox Biol 2, 910-920 (2014)
   PUBMED   25180167
  REMARK    Publication Status: Online-Only
REFERENCE   5  (bases 1 to 3749)
  AUTHORS   Ito,H., Murakami,M., Furuhata,A., Gao,S., Yoshida,K., Sobue,S.,
            Hagiwara,K., Takagi,A., Kojima,T., Suzuki,M., Banno,Y., Tanaka,K.,
            Tamiya-Koizumi,K., Kyogashima,M., Nozawa,Y. and Murate,T.
  TITLE     Transcriptional regulation of neutral sphingomyelinase 2 gene
            expression of a human breast cancer cell line, MCF-7, induced by
            the anti-cancer drug, daunorubicin
  JOURNAL   Biochim Biophys Acta 1789 (11-12), 681-690 (2009)
   PUBMED   19698806
  REMARK    GeneRIF: Data show DA remarkably increased the NSMase2 message and
            protein, whereas little change in NSMase1 and NSMase3 mRNAs.
REFERENCE   6  (bases 1 to 3749)
  AUTHORS   Corcoran,C.A., He,Q., Ponnusamy,S., Ogretmen,B., Huang,Y. and
            Sheikh,M.S.
  TITLE     Neutral sphingomyelinase-3 is a DNA damage and nongenotoxic
            stress-regulated gene that is deregulated in human malignancies
  JOURNAL   Mol Cancer Res 6 (5), 795-807 (2008)
   PUBMED   18505924
  REMARK    GeneRIF: nSMase3 is an important molecule that is linked to
            tumorigenesis and cellular stress response
REFERENCE   7  (bases 1 to 3749)
  AUTHORS   Krut,O., Wiegmann,K., Kashkar,H., Yazdanpanah,B. and Kronke,M.
  TITLE     Novel tumor necrosis factor-responsive mammalian neutral
            sphingomyelinase-3 is a C-tail-anchored protein
  JOURNAL   J Biol Chem 281 (19), 13784-13793 (2006)
   PUBMED   16517606
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC018804.9.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Aug 19, 2020 this sequence version replaced NM_017951.4.
            
            Summary: The protein encoded by this gene is a sphingomyelinase
            that catalyzes the hydrolysis of membrane sphingomyelin to form
            phosphorylcholine and ceramide. This gene is activated by DNA
            damage, cellular stress, and tumor necrosis factor, but it is
            downregulated by wild-type p53. The encoded protein localizes to
            the endoplasmic reticulum and Golgi network. [provided by RefSeq,
            Mar 2017].
            
            Transcript Variant: This variant (2) encodes the longest isoform
            (2).
            
            ##Evidence-Data-START##
            Transcript exon combination :: AB037839.1, SRR11853567.17378.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            CDS uses downstream in-frame AUG :: upstream AUG and CDS extension
                                                is not conserved
            MANE Ensembl match               :: ENST00000680298.1/
                                                ENSP00000506463.1
            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
            1-73                AC018804.9         56826-56898
            74-157              AC018804.9         61791-61874
            158-244             AC018804.9         63428-63514
            245-387             AC018804.9         64772-64914
            388-463             AC018804.9         65074-65149
            464-572             AC018804.9         65533-65641
            573-625             AC018804.9         65751-65803
            626-777             AC018804.9         65928-66079
            778-910             AC018804.9         70838-70970
            911-982             AC018804.9         73983-74054
            983-1069            AC018804.9         77156-77242
            1070-1215           AC018804.9         81032-81177
            1216-1306           AC018804.9         81753-81843
            1307-1407           AC018804.9         82293-82393
            1408-1571           AC018804.9         83169-83332
            1572-1777           AC018804.9         83946-84151
            1778-2011           AC018804.9         84493-84726
            2012-2143           AC018804.9         84978-85109
            2144-2272           AC018804.9         85257-85385
            2273-3749           AC018804.9         85544-87020
FEATURES             Location/Qualifiers
     source          1..3749
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="2"
                     /map="2q21.1"
     gene            1..3749
                     /gene="SMPD4"
                     /gene_synonym="NEDMABA; NEDMEBA; NET13; NSMASE-3; NSMASE3;
                     SKNY"
                     /note="sphingomyelin phosphodiesterase 4"
                     /db_xref="GeneID:55627"
                     /db_xref="HGNC:HGNC:32949"
                     /db_xref="MIM:610457"
     exon            1..73
                     /gene="SMPD4"
                     /gene_synonym="NEDMABA; NEDMEBA; NET13; NSMASE-3; NSMASE3;
                     SKNY"
                     /inference="alignment:Splign:2.1.0"
     exon            74..157
                     /gene="SMPD4"
                     /gene_synonym="NEDMABA; NEDMEBA; NET13; NSMASE-3; NSMASE3;
                     SKNY"
                     /inference="alignment:Splign:2.1.0"
     CDS             119..2602
                     /gene="SMPD4"
                     /gene_synonym="NEDMABA; NEDMEBA; NET13; NSMASE-3; NSMASE3;
                     SKNY"
                     /EC_number="3.1.4.12"
                     /note="isoform 2 is encoded by transcript variant 2;
                     neutral sphingomyelinase 3; neutral sphingomyelinase III;
                     sphingomyelin phosphodiesterase 4, neutral membrane
                     (neutral sphingomyelinase-3)"
                     /codon_start=1
                     /product="sphingomyelin phosphodiesterase 4 isoform 2"
                     /protein_id="NP_060421.3"
                     /db_xref="CCDS:CCDS42751.2"
                     /db_xref="GeneID:55627"
                     /db_xref="HGNC:HGNC:32949"
                     /db_xref="MIM:610457"
                     /translation="MAFPHLQQPSFLLASLKADSINKPFAQQCQDLVKVIEDFPAKEL
                     HTIFPWLVESIFGSLDGVLVGWNLRCLQGRVNPVEYSIVMEFLDPGGPMMKLVYKLQA
                     EDYKFDFPVSYLPGPVKASIQECILPDSPLYHNKVQFTPTGGLGLNLALNPFEYYIFF
                     FALSLITQKPLPVSLHVRTSDCAYFILVDRYLSWFLPTEGSVPPPLSSSPGGTSPSPP
                     PRTPAIPFASYGLHHTSLLKRHISHQTSVNADPASHEIWRSETLLQVFVEMWLHHYSL
                     EMYQKMQSPHAKLEVLHYRLSVSSALYSPAQPSLQALHAYQESFTPTEEHVLVVRLLL
                     KHLHAFANSLKPEQASPSAHSHATSPLEEFKRAAVPRFVQQKLYLFLQHCFGHWPLDA
                     SFRAVLEMWLSYLQPWRYAPDKQAPGSDSQPRCVSEKWAPFVQENLLMYTKLFVGFLN
                     RALRTDLVSPKHALMVFRVAKVFAQPNLAEMIQKGEQLFLEPELVIPHRQHRLFTAPT
                     FTGSFLSPWPPAVTDASFKVKSHVYSLEGQDCKYTPMFGPEARTLVLRLAQLITQAKH
                     TAKSISDQCAESPAGHSFLSWLGFSSMDTNGSYTANDLDEMGQDSVRKTDEYLEKALE
                     YLRQIFRLSEAQLRQFTLALGTTQDENGKKQLPDCIVGEDGLILTPLGRYQIINGLRR
                     FEIEYQGDPELQPIRSYEIASLVRTLFRLSSAINHRFAGQMAALCSRDDFLGSFCRYH
                     LTEPGLASRHLLSPVGRRQVAGHTRGPRLSLRFLGSYRTLVSLLLAFFVASLFCVGPL
                     PCTLLLTLGYVLYASAMTLLTERGKLHQP"
     exon            158..244
                     /gene="SMPD4"
                     /gene_synonym="NEDMABA; NEDMEBA; NET13; NSMASE-3; NSMASE3;
                     SKNY"
                     /inference="alignment:Splign:2.1.0"
     exon            245..387
                     /gene="SMPD4"
                     /gene_synonym="NEDMABA; NEDMEBA; NET13; NSMASE-3; NSMASE3;
                     SKNY"
                     /inference="alignment:Splign:2.1.0"
     exon            388..463
                     /gene="SMPD4"
                     /gene_synonym="NEDMABA; NEDMEBA; NET13; NSMASE-3; NSMASE3;
                     SKNY"
                     /inference="alignment:Splign:2.1.0"
     exon            464..572
                     /gene="SMPD4"
                     /gene_synonym="NEDMABA; NEDMEBA; NET13; NSMASE-3; NSMASE3;
                     SKNY"
                     /inference="alignment:Splign:2.1.0"
     exon            573..625
                     /gene="SMPD4"
                     /gene_synonym="NEDMABA; NEDMEBA; NET13; NSMASE-3; NSMASE3;
                     SKNY"
                     /inference="alignment:Splign:2.1.0"
     exon            626..777
                     /gene="SMPD4"
                     /gene_synonym="NEDMABA; NEDMEBA; NET13; NSMASE-3; NSMASE3;
                     SKNY"
                     /inference="alignment:Splign:2.1.0"
     exon            778..910
                     /gene="SMPD4"
                     /gene_synonym="NEDMABA; NEDMEBA; NET13; NSMASE-3; NSMASE3;
                     SKNY"
                     /inference="alignment:Splign:2.1.0"
     exon            911..982
                     /gene="SMPD4"
                     /gene_synonym="NEDMABA; NEDMEBA; NET13; NSMASE-3; NSMASE3;
                     SKNY"
                     /inference="alignment:Splign:2.1.0"
     exon            983..1069
                     /gene="SMPD4"
                     /gene_synonym="NEDMABA; NEDMEBA; NET13; NSMASE-3; NSMASE3;
                     SKNY"
                     /inference="alignment:Splign:2.1.0"
     exon            1070..1215
                     /gene="SMPD4"
                     /gene_synonym="NEDMABA; NEDMEBA; NET13; NSMASE-3; NSMASE3;
                     SKNY"
                     /inference="alignment:Splign:2.1.0"
     exon            1216..1306
                     /gene="SMPD4"
                     /gene_synonym="NEDMABA; NEDMEBA; NET13; NSMASE-3; NSMASE3;
                     SKNY"
                     /inference="alignment:Splign:2.1.0"
     exon            1307..1407
                     /gene="SMPD4"
                     /gene_synonym="NEDMABA; NEDMEBA; NET13; NSMASE-3; NSMASE3;
                     SKNY"
                     /inference="alignment:Splign:2.1.0"
     exon            1408..1571
                     /gene="SMPD4"
                     /gene_synonym="NEDMABA; NEDMEBA; NET13; NSMASE-3; NSMASE3;
                     SKNY"
                     /inference="alignment:Splign:2.1.0"
     exon            1572..1777
                     /gene="SMPD4"
                     /gene_synonym="NEDMABA; NEDMEBA; NET13; NSMASE-3; NSMASE3;
                     SKNY"
                     /inference="alignment:Splign:2.1.0"
     exon            1778..2011
                     /gene="SMPD4"
                     /gene_synonym="NEDMABA; NEDMEBA; NET13; NSMASE-3; NSMASE3;
                     SKNY"
                     /inference="alignment:Splign:2.1.0"
     exon            2012..2143
                     /gene="SMPD4"
                     /gene_synonym="NEDMABA; NEDMEBA; NET13; NSMASE-3; NSMASE3;
                     SKNY"
                     /inference="alignment:Splign:2.1.0"
     exon            2144..2272
                     /gene="SMPD4"
                     /gene_synonym="NEDMABA; NEDMEBA; NET13; NSMASE-3; NSMASE3;
                     SKNY"
                     /inference="alignment:Splign:2.1.0"
     exon            2273..3749
                     /gene="SMPD4"
                     /gene_synonym="NEDMABA; NEDMEBA; NET13; NSMASE-3; NSMASE3;
                     SKNY"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3727..3732
                     /regulatory_class="polyA_signal_sequence"
                     /gene="SMPD4"
                     /gene_synonym="NEDMABA; NEDMEBA; NET13; NSMASE-3; NSMASE3;
                     SKNY"
                     /note="hexamer: AATAAA"
     polyA_site      3749
                     /gene="SMPD4"
                     /gene_synonym="NEDMABA; NEDMEBA; NET13; NSMASE-3; NSMASE3;
                     SKNY"
                     /note="major polyA site"
ORIGIN      
        1 gatgacgact ttcggcgccg tggcggaatg gcggcttcca tctctgaggc gagcgacgct
       61 atggatccca cagtggtttg ctaagaaggc cattttcaac tctccactgg aggctgctat
      121 ggcgttccct cacctgcagc agcccagctt tctactggct agcctgaaag ctgactctat
      181 aaataagccc tttgcacagc agtgccaaga cttggttaaa gtcattgagg actttccagc
      241 aaaggagctg cacaccatct tcccatggct ggtagaaagc atttttggca gcctagatgg
      301 tgtcctcgtt ggctggaacc tccgctgctt acaggggcgc gtgaatcctg tggagtacag
      361 catcgtgatg gaatttctcg accctggtgg cccaatgatg aagttggttt ataagcttca
      421 agctgaagac tataagttcg actttcctgt ctcctacttg cctggtcctg tgaaggcgtc
      481 catccaggag tgcatcctcc ctgacagtcc tctgtaccac aacaaggtcc agttcacccc
      541 tactgggggc cttggtctga acttggccct gaatccgttc gagtattaca tattcttctt
      601 tgccttgagc ctcatcactc agaagccact tcctgtgtcc ctccacgtcc gtacttcaga
      661 ctgtgcctat ttcatcctgg tggacaggta cctgtcatgg ttcctgccca ccgaaggcag
      721 tgtgccccca ccactctcct ccagcccagg ggggaccagc ccctcaccac ctcccaggac
      781 accagccata ccctttgctt cctatggcct ccaccacact agcctcctaa agcgacacat
      841 ctctcatcag acgtctgtga atgcagaccc cgcctcccac gagatctgga ggtcagaaac
      901 tctgctccag gtttttgttg aaatgtggct tcatcactat tccttggaga tgtatcaaaa
      961 aatgcagtcc cctcatgcca agctggaggt tctgcactac cgactcagtg tctccagcgc
     1021 cctctacagc cccgcccaac ccagcctcca ggccctccac gcctaccaag agtcgttcac
     1081 gcctactgag gagcatgtgt tggtggtgcg cctgctgctg aagcacctgc acgcctttgc
     1141 caacagcctg aagccagagc aggcctcacc ctccgcccac tcccacgcca ccagccccct
     1201 ggaggagttc aaacgggctg ctgtcccgag gttcgtccag cagaaactct acctcttctt
     1261 gcagcattgc tttggccact ggcccctgga cgcatcgttc agagctgtcc tggagatgtg
     1321 gctgagctac ctgcagccgt ggcggtacgc gcctgacaag caggctccgg gcagcgactc
     1381 ccagccccgg tgtgtgtcgg agaaatgggc accctttgtc caggagaacc tgctgatgta
     1441 caccaagttg tttgtgggct ttctgaaccg cgcgctccgc acagacctgg tcagccccaa
     1501 gcacgcgctc atggtgttcc gagtggccaa agtctttgcc cagcccaacc tggctgagat
     1561 gattcagaaa ggtgagcagc tattcctgga gccagagctg gtcatccccc accgccagca
     1621 ccgactcttc acggccccca cattcactgg gagcttcctg tcaccctggc caccagcggt
     1681 cactgatgcc tccttcaagg tgaagagcca cgtctacagc ctggagggcc aggactgcaa
     1741 gtacaccccg atgtttgggc ccgaggcccg caccctggtc ctgcgcctcg ctcagctcat
     1801 cacacaggcc aaacacacag ccaagtccat ctccgaccag tgtgcggaga gcccggctgg
     1861 ccactccttc ctctcatggc tgggctttag ctccatggac accaatggct cctacacagc
     1921 caacgacctg gacgagatgg ggcaagacag tgtccggaag acagatgaat acctggagaa
     1981 ggccctggag tacctgcgcc agatattccg gctcagcgaa gcgcagctca ggcagttcac
     2041 actcgccttg ggcaccaccc aggatgagaa tggaaaaaag caactccccg actgcatcgt
     2101 gggtgaggac ggactcatcc ttacgcccct ggggcggtac cagatcatca atgggctgcg
     2161 aaggtttgaa attgagtacc agggggaccc ggagctgcag cccatccgga gctatgagat
     2221 cgccagcttg gtccgcacac tctttaggct gtcgtctgcc atcaaccaca gatttgcagg
     2281 acagatggcg gctctgtgtt cccgggatga cttcctcggc agcttctgtc gctaccacct
     2341 cacagaacct gggctggcca gcaggcacct gctgagccct gtggggcgga ggcaggtggc
     2401 cggccacacc cgcggcccca ggctcagcct gcgcttcctg ggcagttacc ggacgctggt
     2461 ctcgctgctg ctggccttct tcgtggcctc tctgttctgc gtcgggcccc tcccatgcac
     2521 gctgctgctc accctgggct atgtcctcta cgcctctgcc atgacactgc tgaccgagcg
     2581 ggggaagctg caccagccct gaaggtgtca gctgccttca gagcaggctg gagggatttg
     2641 ccacacagcc ccacccttgg gctgagagga cctgggaagc ccctccagga gggaacacgg
     2701 tcatcctcgg gcttctggag cggggttcct gcagccgcag aggcatctgg aggaaacgca
     2761 accaagaaag gaaggcaggt gggccccagc aaaggagtag ctgccagggc tcaacagcta
     2821 cgctctgtga cagcgcagag ctcagcggcg gcctttccct ccctccgcca aggactcacg
     2881 gccaagccag ctctcggggc cttttttcca ctgcccattt ggctactctg ctgcaccaag
     2941 cttgggagcc agcctgccaa cagccacctg ggcctggcct ccccactggc tggccttgag
     3001 gttggcagag tgggttgtgg cgcttcctct ctctgtgtgg gaccaggaca gtggcttaag
     3061 tctccactcc aggaaagaat caaagtttct agagttgtga gaaaaccaga gagtggctgt
     3121 cctgattctt cactgtgagg ggcgttcttc atgttctccc agctgttcca agactgggcc
     3181 gtagaattcc atgtttcagg agcctaagac cctcccagag cccaggggct tcaccgcaga
     3241 ccccaagcca ttgagcacat cacccaaagc agtggccaac atcgcggacc cctgtgcctt
     3301 gtcacagatg ggtgctggtc ctcaggcgtt ggggacactg ctgggtcgat ggggtcggat
     3361 tctgccagtt tctgctctgc agccaaagat ggtcagaagc attgtcactt cagtaacatc
     3421 aagtgctcaa agacatggca accgttcagt ggtacttaag tattcaaaat atacaactac
     3481 agattctctg acagaaacca gcacggggtc ttcaccttca ttcaccccac aggcgacatg
     3541 cgagggagaa cagcatctca gtggtgattt ccaaaccaag cctttgtttt cggtgtgggg
     3601 ttttgggggt ttgctttaat gtttttgaaa ttgtaaatgt tgggctttgt attttgatgt
     3661 aaactgagca taatggcatt ttagggcctg tgaccaaaaa tgaagcttgt aacgaccatg
     3721 gatctgaata aacatgtcct tgcttctga
//
