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"
misc_feature 2..4
/gene="SMPD4"
/gene_synonym="NEDMABA; NEDMEBA; NET13; NSMASE-3; NSMASE3;
SKNY"
/note="upstream_AUG_codon; putative N-terminal extension:
MTTFGAVAEWRLPSLRRATLWIPQWFAKKAIFNSPLEAA"
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
//