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P17405

- ASM_HUMAN

UniProt

P17405 - ASM_HUMAN

Protein

Sphingomyelin phosphodiesterase

Gene

SMPD1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 168 (01 Oct 2014)
      Sequence version 4 (03 Mar 2009)
      Previous versions | rss
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    Functioni

    Converts sphingomyelin to ceramide. Also has phospholipase C activities toward 1,2-diacylglycerolphosphocholine and 1,2-diacylglycerolphosphoglycerol. Isoform 2 and isoform 3 have lost catalytic activity.

    Catalytic activityi

    Sphingomyelin + H2O = N-acylsphingosine + phosphocholine.

    GO - Molecular functioni

    1. hydrolase activity, acting on glycosyl bonds Source: UniProtKB-KW
    2. protein binding Source: IntAct
    3. sphingomyelin phosphodiesterase activity Source: ProtInc

    GO - Biological processi

    1. cell death Source: UniProtKB-KW
    2. ceramide biosynthetic process Source: BHF-UCL
    3. glycosphingolipid metabolic process Source: Reactome
    4. negative regulation of MAP kinase activity Source: BHF-UCL
    5. nervous system development Source: ProtInc
    6. positive regulation of apoptotic process Source: Ensembl
    7. positive regulation of protein dephosphorylation Source: BHF-UCL
    8. response to cocaine Source: Ensembl
    9. response to drug Source: Ensembl
    10. signal transduction Source: ProtInc
    11. small molecule metabolic process Source: Reactome
    12. sphingolipid metabolic process Source: Reactome
    13. sphingomyelin catabolic process Source: InterPro
    14. sphingomyelin metabolic process Source: ProtInc
    15. termination of signal transduction Source: BHF-UCL

    Keywords - Molecular functioni

    Glycosidase, Hydrolase

    Enzyme and pathway databases

    ReactomeiREACT_116105. Glycosphingolipid metabolism.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Sphingomyelin phosphodiesterase (EC:3.1.4.12)
    Alternative name(s):
    Acid sphingomyelinase
    Short name:
    aSMase
    Gene namesi
    Name:SMPD1
    Synonyms:ASM
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:11120. SMPD1.

    Subcellular locationi

    GO - Cellular componenti

    1. extracellular space Source: Ensembl
    2. extracellular vesicular exosome Source: UniProt
    3. lamellar body Source: Ensembl
    4. lysosomal lumen Source: Reactome

    Keywords - Cellular componenti

    Lysosome

    Pathology & Biotechi

    Involvement in diseasei

    Niemann-Pick disease A (NPDA) [MIM:257200]: An early-onset lysosomal storage disorder caused by failure to hydrolyze sphingomyelin to ceramide. It results in the accumulation of sphingomyelin and other metabolically related lipids in reticuloendothelial and other cell types throughout the body, leading to cell death. Niemann-Pick disease type A is a primarily neurodegenerative disorder characterized by onset within the first year of life, mental retardation, digestive disorders, failure to thrive, major hepatosplenomegaly, and severe neurologic symptoms. The severe neurological disorders and pulmonary infections lead to an early death, often around the age of four. Clinical features are variable. A phenotypic continuum exists between type A (basic neurovisceral) and type B (purely visceral) forms of Niemann-Pick disease, and the intermediate types encompass a cluster of variants combining clinical features of both types A and B.12 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti103 – 1031L → P in NPDA and NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains very low enzyme activity. 2 Publications
    VAR_060872
    Natural varianti184 – 1841P → L in NPDA/NPDB; intermediate form. 1 Publication
    VAR_060877
    Natural varianti209 – 2091W → R in NPDA; results in less than 0.5% of wild-type activity. 1 Publication
    VAR_068435
    Natural varianti228 – 2281R → H in NPDA/NPDB; intermediate form. 1 Publication
    VAR_060883
    Natural varianti241 – 2411A → V in NPDA/NPDB; intermediate form. 1 Publication
    VAR_060885
    Natural varianti245 – 2451G → S in NPDA and NPDB. 3 Publications
    VAR_060887
    Natural varianti246 – 2461E → K in NPDA. 1 Publication
    VAR_060888
    Natural varianti248 – 2481S → R in NPDA and NPDB; also found in patients with an intermediate form. 3 Publications
    VAR_015287
    Natural varianti251 – 2511D → E in NPDA/NPDB; intermediate form. 1 Publication
    VAR_060889
    Natural varianti251 – 2511D → H in NPDA; results in loss of activity. 1 Publication
    VAR_068436
    Natural varianti278 – 2781D → A in NPDA/NPDB; intermediate form. 1 Publication
    VAR_060890
    Natural varianti292 – 2921Q → K in NPDA/NPDB; intermediate form. 3 Publications
    VAR_060893
    Natural varianti294 – 2941R → Q in NPDA. 1 Publication
    VAR_060894
    Natural varianti302 – 3021L → P in NPDA; in 23% of NPDA Ashkenazi Jewish patients. 1 Publication
    VAR_005060
    Natural varianti313 – 3131Y → H in NPDA. 1 Publication
    VAR_060895
    Natural varianti319 – 3191H → Y in NPDA. 1 Publication
    VAR_015288
    Natural varianti341 – 3411L → P in NPDA/NPDB; intermediate form. 2 Publications
    VAR_060898
    Natural varianti367 – 3671Y → C in NPDA. 1 Publication
    VAR_060900
    Natural varianti382 – 3821M → I in NPDA and NPDB. 2 Publications
    VAR_005061
    Natural varianti389 – 3891N → T in NPDA. 1 Publication
    VAR_005063
    Natural varianti390 – 3901Missing in NPDA. 1 Publication
    VAR_060904
    Natural varianti421 – 4211H → R in NPDA. 1 Publication
    VAR_060906
    Natural varianti446 – 4461Y → C in NPDA. 1 Publication
    VAR_011388
    Natural varianti450 – 4501L → P in NPDA. 1 Publication
    VAR_060910
    Natural varianti463 – 4631F → S in NPDA. 1 Publication
    VAR_015291
    Natural varianti467 – 4671Y → S in NPDA. 1 Publication
    VAR_060913
    Natural varianti475 – 4751P → L in NPDA and NPDB. 3 Publications
    VAR_015292
    Natural varianti482 – 4821A → E in NPDA. 1 Publication
    VAR_060916
    Natural varianti496 – 4961R → H in NPDA. 1 Publication
    VAR_060922
    Natural varianti496 – 4961R → L in NPDA; in 32% of NPDA Ashkenazi Jewish patients. 2 Publications
    VAR_005066
    Natural varianti517 – 5171Y → C in NPDA. 1 Publication
    VAR_060926
    Natural varianti537 – 5371Y → H in NPDA. 1 Publication
    VAR_015293
    Natural varianti577 – 5771G → S in NPDA; also in patients with an intermediate form. 2 Publications
    VAR_005067
    Natural varianti592 – 5921Missing in NPDA. 1 Publication
    VAR_060931
    Niemann-Pick disease B (NPDB) [MIM:607616]: A late-onset lysosomal storage disorder caused by failure to hydrolyze sphingomyelin to ceramide. It results in the accumulation of sphingomyelin and other metabolically related lipids in reticuloendothelial and other cell types throughout the body, leading to cell death. Clinical signs involve only visceral organs. The most constant sign is hepatosplenomegaly which can be associated with pulmonary symptoms. Patients remain free of neurologic manifestations. However, a phenotypic continuum exists between type A (basic neurovisceral) and type B (purely visceral) forms of Niemann-Pick disease, and the intermediate types encompass a cluster of variants combining clinical features of both types A and B. In Niemann-Pick disease type B, onset of the first symptoms occurs in early childhood and patients can survive into adulthood.14 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti49 – 491D → V in NPDB. 1 Publication
    VAR_060870
    Natural varianti92 – 921C → W in NPDB. 1 Publication
    VAR_060871
    Natural varianti103 – 1031L → P in NPDA and NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains very low enzyme activity. 2 Publications
    VAR_060872
    Natural varianti130 – 1301V → A in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains 13% residual enzyme activity. 1 Publication
    VAR_060873
    Natural varianti137 – 1371L → P in NPDB. 1 Publication
    VAR_060874
    Natural varianti157 – 1571C → R in NPDB; seems to be less active. 2 Publications
    VAR_011387
    Natural varianti166 – 1661G → R in NPDB; also in patients with an intermediate form. 2 Publications
    VAR_060875
    Natural varianti176 – 1761I → N in NPDB. 1 Publication
    VAR_060876
    Natural varianti184 – 1841P → L in NPDA/NPDB; intermediate form. 1 Publication
    VAR_060877
    Natural varianti196 – 1961A → P in NPDB. 1 Publication
    VAR_060878
    Natural varianti200 – 2001R → C in NPDB. 1 Publication
    VAR_060879
    Natural varianti225 – 2251L → M in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. 1 Publication
    VAR_060880
    Natural varianti225 – 2251L → P in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. 1 Publication
    VAR_060881
    Natural varianti228 – 2281R → C in NPDB. 2 Publications
    VAR_060882
    Natural varianti228 – 2281R → H in NPDA/NPDB; intermediate form. 1 Publication
    VAR_060883
    Natural varianti232 – 2321G → D in NPDB. 1 Publication
    VAR_060884
    Natural varianti241 – 2411A → V in NPDA/NPDB; intermediate form. 1 Publication
    VAR_060885
    Natural varianti242 – 2421G → R in NPDB. 1 Publication
    VAR_005058
    Natural varianti244 – 2441W → C in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. 1 Publication
    VAR_060886
    Natural varianti245 – 2451G → S in NPDA and NPDB. 3 Publications
    VAR_060887
    Natural varianti246 – 2461E → Q in NPDB; 30% residual activity. 1 Publication
    VAR_005059
    Natural varianti248 – 2481S → R in NPDA and NPDB; also found in patients with an intermediate form. 3 Publications
    VAR_015287
    Natural varianti251 – 2511D → E in NPDA/NPDB; intermediate form. 1 Publication
    VAR_060889
    Natural varianti278 – 2781D → A in NPDA/NPDB; intermediate form. 1 Publication
    VAR_060890
    Natural varianti281 – 2811A → T in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. 1 Publication
    VAR_060891
    Natural varianti289 – 2891R → H in NPDB; also in patients with an intermediate form. 2 Publications
    VAR_060892
    Natural varianti292 – 2921Q → K in NPDA/NPDB; intermediate form. 3 Publications
    VAR_060893
    Natural varianti312 – 3121V → M in NPDB; results in 20% of wild-type activity. 1 Publication
    VAR_068437
    Natural varianti323 – 3231P → A in NPDB. 1 Publication
    VAR_060896
    Natural varianti330 – 3301P → R in NPDB. 2 Publications
    VAR_060897
    Natural varianti341 – 3411L → P in NPDA/NPDB; intermediate form. 2 Publications
    VAR_060898
    Natural varianti357 – 3571A → D in NPDB. 1 Publication
    VAR_060899
    Natural varianti371 – 3711P → S in NPDB. 1 Publication
    VAR_015289
    Natural varianti376 – 3761R → H in NPDB; also found in a patient with an intermediate form. 3 Publications
    VAR_060901
    Natural varianti376 – 3761R → L in NPDB. 1 Publication
    VAR_060902
    Natural varianti379 – 3791S → P in NPDB. 1 Publication
    VAR_060903
    Natural varianti382 – 3821M → I in NPDA and NPDB. 2 Publications
    VAR_005061
    Natural varianti383 – 3831N → S in NPDB. 1 Publication
    VAR_005062
    Natural varianti391 – 3911W → G in NPDB; low sphingomyelin degradation rates. 1 Publication
    VAR_005064
    Natural varianti413 – 4131A → V in NPDB. 1 Publication
    VAR_060905
    Natural varianti421 – 4211H → Y in NPDB. 1 Publication
    VAR_015290
    Natural varianti425 – 4251H → R in NPDB; results in loss of activity; the patient also carries mutation H-228 that has sufficient activity to account for the Niemann-Pick disease type B phenotype. 1 Publication
    VAR_068438
    Natural varianti431 – 4311C → R in NPDB. 1 Publication
    VAR_060907
    Natural varianti432 – 4321L → P in NPDB. 1 Publication
    VAR_060908
    Natural varianti435 – 4351W → C in NPDB. 1 Publication
    VAR_060909
    Natural varianti436 – 4361S → R in NPDB. 1 Publication
    VAR_005065
    Natural varianti451 – 4511A → D in NPDB. 1 Publication
    VAR_068439
    Natural varianti452 – 4521A → V in NPDB. 1 Publication
    VAR_060911
    Natural varianti456 – 4561G → D in NPDB. 1 Publication
    VAR_060912
    Natural varianti474 – 4741R → W in NPDB; also in a patient with an intermediate form. 3 Publications
    VAR_060914
    Natural varianti475 – 4751P → L in NPDA and NPDB. 3 Publications
    VAR_015292
    Natural varianti480 – 4801F → L in NPDB. 1 Publication
    VAR_060915
    Natural varianti485 – 4851A → V in NPDB. 1 Publication
    VAR_060917
    Natural varianti486 – 4861T → A in NPDB. 1 Publication
    VAR_060918
    Natural varianti488 – 4881Y → N in NPDB. 1 Publication
    VAR_060919
    Natural varianti494 – 4941G → S in NPDB. 1 Publication
    VAR_060920
    Natural varianti496 – 4961R → C in NPDB. 1 Publication
    VAR_060921
    Natural varianti514 – 5141H → Q in NPDB. 1 Publication
    VAR_060924
    Natural varianti515 – 5151E → V in NPDB. 1 Publication
    VAR_060925
    Natural varianti520 – 5201N → S in NPDB. 1 Publication
    VAR_068440
    Natural varianti523 – 5231Q → H in NPDB; results in 64% of wild-type activity. 1 Publication
    VAR_068441
    Natural varianti533 – 5331W → R in NPDB; also in patients with an intermediate form. 2 Publications
    VAR_060927
    Natural varianti549 – 5491L → P in NPDB. 1 Publication
    VAR_060928
    Natural varianti563 – 5631D → Y in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains 6.8% residual enzyme activity. 1 Publication
    VAR_060929
    Natural varianti576 – 5761K → N in NPDB. 1 Publication
    VAR_060930
    Natural varianti600 – 6001R → H in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains about 10% residual enzyme activity. 1 Publication
    VAR_060932
    Natural varianti600 – 6001R → P in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains very low enzyme activity. 1 Publication
    VAR_060933
    Natural varianti608 – 6081Missing in NPDB; prevalent among NPDB patients from the North African Maghreb region. 3 Publications
    VAR_005068

    Keywords - Diseasei

    Disease mutation, Neurodegeneration, Niemann-Pick disease

    Organism-specific databases

    MIMi257200. phenotype.
    607616. phenotype.
    Orphaneti77292. Niemann-Pick disease type A.
    77293. Niemann-Pick disease type B.
    PharmGKBiPA35969.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 4646Add
    BLAST
    Chaini47 – 629583Sphingomyelin phosphodiesterasePRO_0000002323Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi86 – 861N-linked (GlcNAc...)1 PublicationPROSITE-ProRule annotation
    Disulfide bondi89 ↔ 165PROSITE-ProRule annotation
    Disulfide bondi92 ↔ 157PROSITE-ProRule annotation
    Disulfide bondi120 ↔ 1311 PublicationPROSITE-ProRule annotation
    Glycosylationi175 – 1751N-linked (GlcNAc...)1 PublicationPROSITE-ProRule annotation
    Disulfide bondi221 ↔ 2261 PublicationPROSITE-ProRule annotation
    Disulfide bondi227 ↔ 2501 PublicationPROSITE-ProRule annotation
    Glycosylationi335 – 3351N-linked (GlcNAc...)1 PublicationPROSITE-ProRule annotation
    Disulfide bondi385 ↔ 4311 PublicationPROSITE-ProRule annotation
    Glycosylationi395 – 3951N-linked (GlcNAc...)1 PublicationPROSITE-ProRule annotation
    Glycosylationi520 – 5201N-linked (GlcNAc...)1 PublicationPROSITE-ProRule annotation
    Disulfide bondi584 ↔ 5881 PublicationPROSITE-ProRule annotation
    Disulfide bondi594 ↔ 6071 PublicationPROSITE-ProRule annotation

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    MaxQBiP17405.
    PaxDbiP17405.
    PRIDEiP17405.

    PTM databases

    PhosphoSiteiP17405.

    Expressioni

    Gene expression databases

    ArrayExpressiP17405.
    BgeeiP17405.
    CleanExiHS_SMPD1.
    GenevestigatoriP17405.

    Organism-specific databases

    HPAiHPA001823.

    Interactioni

    Subunit structurei

    Monomer.

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CASP7P552106EBI-7095800,EBI-523958

    Protein-protein interaction databases

    BioGridi112493. 5 interactions.
    IntActiP17405. 7 interactions.
    MINTiMINT-3008689.
    STRINGi9606.ENSP00000340409.

    Structurei

    3D structure databases

    ProteinModelPortaliP17405.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini85 – 16985Saposin B-typePROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the acid sphingomyelinase family.Curated
    Contains 1 saposin B-type domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG303902.
    HOVERGENiHBG004288.
    InParanoidiP17405.
    KOiK12350.
    OrthoDBiEOG79PJP3.
    PhylomeDBiP17405.
    TreeFamiTF313674.

    Family and domain databases

    Gene3Di1.10.225.10. 1 hit.
    3.60.21.10. 1 hit.
    InterProiIPR004843. Calcineurin-like_PHP_apaH.
    IPR029052. Metallo-depent_PP-like.
    IPR011001. Saposin-like.
    IPR008139. SaposinB.
    IPR011160. Sphingomy_PDE.
    [Graphical view]
    PfamiPF00149. Metallophos. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000948. Sphingomy_PDE. 1 hit.
    SMARTiSM00741. SapB. 1 hit.
    [Graphical view]
    SUPFAMiSSF47862. SSF47862. 1 hit.
    SSF56300. SSF56300. 1 hit.
    PROSITEiPS50015. SAP_B. 1 hit.
    [Graphical view]

    Sequences (4)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 4 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P17405-1) [UniParc]FASTAAdd to Basket

    Also known as: ASM-1

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MPRYGASLRQ SCPRSGREQG QDGTAGAPGL LWMGLVLALA LALALALSDS    50
    RVLWAPAEAH PLSPQGHPAR LHRIVPRLRD VFGWGNLTCP ICKGLFTAIN 100
    LGLKKEPNVA RVGSVAIKLC NLLKIAPPAV CQSIVHLFED DMVEVWRRSV 150
    LSPSEACGLL LGSTCGHWDI FSSWNISLPT VPKPPPKPPS PPAPGAPVSR 200
    ILFLTDLHWD HDYLEGTDPD CADPLCCRRG SGLPPASRPG AGYWGEYSKC 250
    DLPLRTLESL LSGLGPAGPF DMVYWTGDIP AHDVWHQTRQ DQLRALTTVT 300
    ALVRKFLGPV PVYPAVGNHE STPVNSFPPP FIEGNHSSRW LYEAMAKAWE 350
    PWLPAEALRT LRIGGFYALS PYPGLRLISL NMNFCSRENF WLLINSTDPA 400
    GQLQWLVGEL QAAEDRGDKV HIIGHIPPGH CLKSWSWNYY RIVARYENTL 450
    AAQFFGHTHV DEFEVFYDEE TLSRPLAVAF LAPSATTYIG LNPGYRVYQI 500
    DGNYSGSSHV VLDHETYILN LTQANIPGAI PHWQLLYRAR ETYGLPNTLP 550
    TAWHNLVYRM RGDMQLFQTF WFLYHKGHPP SEPCGTPCRL ATLCAQLSAR 600
    ADSPALCRHL MPDGSLPEAQ SLWPRPLFC 629

    Note: Most abundant (90%).

    Length:629
    Mass (Da):69,752
    Last modified:March 3, 2009 - v4
    Checksum:iC9888CB8359C42AC
    GO
    Isoform 2 (identifier: P17405-2) [UniParc]FASTAAdd to Basket

    Also known as: ASM-2

    The sequence of this isoform differs from the canonical sequence as follows:
         363-374: IGGFYALSPYPG → YLSSVETQEGKR
         375-418: Missing.

    Note: Intermediate abundance (10%).

    Show »
    Length:585
    Mass (Da):64,889
    Checksum:iA5FC9FE28C0D3E42
    GO
    Isoform 3 (identifier: P17405-3) [UniParc]FASTAAdd to Basket

    Also known as: ASM-3

    The sequence of this isoform differs from the canonical sequence as follows:
         363-418: Missing.

    Note: Low abundance (<1%).

    Show »
    Length:573
    Mass (Da):63,511
    Checksum:i093B405E0C0AE061
    GO
    Isoform 4 (identifier: P17405-4) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         104-104: Missing.

    Show »
    Length:628
    Mass (Da):69,624
    Checksum:i3504FAA2AC7A10B2
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti35 – 362Missing in CAA42584. (PubMed:8407868)Curated
    Sequence conflicti268 – 2681G → D in BAF85077. (PubMed:14702039)Curated

    Polymorphismi

    A common polymorphism arises from a variable number of hexanucleotide repeat sequence within the signal peptide region.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti36 – 361V → A.1 Publication
    Corresponds to variant rs1050228 [ dbSNP | Ensembl ].
    VAR_038191
    Natural varianti49 – 491D → V in NPDB. 1 Publication
    VAR_060870
    Natural varianti92 – 921C → W in NPDB. 1 Publication
    VAR_060871
    Natural varianti103 – 1031L → P in NPDA and NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains very low enzyme activity. 2 Publications
    VAR_060872
    Natural varianti130 – 1301V → A in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains 13% residual enzyme activity. 1 Publication
    VAR_060873
    Natural varianti137 – 1371L → P in NPDB. 1 Publication
    VAR_060874
    Natural varianti157 – 1571C → R in NPDB; seems to be less active. 2 Publications
    VAR_011387
    Natural varianti166 – 1661G → R in NPDB; also in patients with an intermediate form. 2 Publications
    VAR_060875
    Natural varianti176 – 1761I → N in NPDB. 1 Publication
    VAR_060876
    Natural varianti184 – 1841P → L in NPDA/NPDB; intermediate form. 1 Publication
    VAR_060877
    Natural varianti196 – 1961A → P in NPDB. 1 Publication
    VAR_060878
    Natural varianti200 – 2001R → C in NPDB. 1 Publication
    VAR_060879
    Natural varianti209 – 2091W → R in NPDA; results in less than 0.5% of wild-type activity. 1 Publication
    VAR_068435
    Natural varianti225 – 2251L → M in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. 1 Publication
    VAR_060880
    Natural varianti225 – 2251L → P in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. 1 Publication
    VAR_060881
    Natural varianti228 – 2281R → C in NPDB. 2 Publications
    VAR_060882
    Natural varianti228 – 2281R → H in NPDA/NPDB; intermediate form. 1 Publication
    VAR_060883
    Natural varianti232 – 2321G → D in NPDB. 1 Publication
    VAR_060884
    Natural varianti241 – 2411A → V in NPDA/NPDB; intermediate form. 1 Publication
    VAR_060885
    Natural varianti242 – 2421G → R in NPDB. 1 Publication
    VAR_005058
    Natural varianti244 – 2441W → C in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. 1 Publication
    VAR_060886
    Natural varianti245 – 2451G → S in NPDA and NPDB. 3 Publications
    VAR_060887
    Natural varianti246 – 2461E → K in NPDA. 1 Publication
    VAR_060888
    Natural varianti246 – 2461E → Q in NPDB; 30% residual activity. 1 Publication
    VAR_005059
    Natural varianti248 – 2481S → R in NPDA and NPDB; also found in patients with an intermediate form. 3 Publications
    VAR_015287
    Natural varianti251 – 2511D → E in NPDA/NPDB; intermediate form. 1 Publication
    VAR_060889
    Natural varianti251 – 2511D → H in NPDA; results in loss of activity. 1 Publication
    VAR_068436
    Natural varianti278 – 2781D → A in NPDA/NPDB; intermediate form. 1 Publication
    VAR_060890
    Natural varianti281 – 2811A → T in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. 1 Publication
    VAR_060891
    Natural varianti289 – 2891R → H in NPDB; also in patients with an intermediate form. 2 Publications
    VAR_060892
    Natural varianti292 – 2921Q → K in NPDA/NPDB; intermediate form. 3 Publications
    VAR_060893
    Natural varianti294 – 2941R → Q in NPDA. 1 Publication
    VAR_060894
    Natural varianti302 – 3021L → P in NPDA; in 23% of NPDA Ashkenazi Jewish patients. 1 Publication
    VAR_005060
    Natural varianti312 – 3121V → M in NPDB; results in 20% of wild-type activity. 1 Publication
    VAR_068437
    Natural varianti313 – 3131Y → H in NPDA. 1 Publication
    VAR_060895
    Natural varianti316 – 3161V → E.
    Corresponds to variant rs12575136 [ dbSNP | Ensembl ].
    VAR_054642
    Natural varianti319 – 3191H → Y in NPDA. 1 Publication
    VAR_015288
    Natural varianti322 – 3221T → I.2 Publications
    Corresponds to variant rs1050233 [ dbSNP | Ensembl ].
    VAR_054643
    Natural varianti323 – 3231P → A in NPDB. 1 Publication
    VAR_060896
    Natural varianti330 – 3301P → R in NPDB. 2 Publications
    VAR_060897
    Natural varianti341 – 3411L → P in NPDA/NPDB; intermediate form. 2 Publications
    VAR_060898
    Natural varianti357 – 3571A → D in NPDB. 1 Publication
    VAR_060899
    Natural varianti367 – 3671Y → C in NPDA. 1 Publication
    VAR_060900
    Natural varianti371 – 3711P → S in NPDB. 1 Publication
    VAR_015289
    Natural varianti376 – 3761R → H in NPDB; also found in a patient with an intermediate form. 3 Publications
    VAR_060901
    Natural varianti376 – 3761R → L in NPDB. 1 Publication
    VAR_060902
    Natural varianti379 – 3791S → P in NPDB. 1 Publication
    VAR_060903
    Natural varianti382 – 3821M → I in NPDA and NPDB. 2 Publications
    VAR_005061
    Natural varianti383 – 3831N → S in NPDB. 1 Publication
    VAR_005062
    Natural varianti389 – 3891N → T in NPDA. 1 Publication
    VAR_005063
    Natural varianti390 – 3901Missing in NPDA. 1 Publication
    VAR_060904
    Natural varianti391 – 3911W → G in NPDB; low sphingomyelin degradation rates. 1 Publication
    VAR_005064
    Natural varianti413 – 4131A → V in NPDB. 1 Publication
    VAR_060905
    Natural varianti421 – 4211H → R in NPDA. 1 Publication
    VAR_060906
    Natural varianti421 – 4211H → Y in NPDB. 1 Publication
    VAR_015290
    Natural varianti425 – 4251H → R in NPDB; results in loss of activity; the patient also carries mutation H-228 that has sufficient activity to account for the Niemann-Pick disease type B phenotype. 1 Publication
    VAR_068438
    Natural varianti431 – 4311C → R in NPDB. 1 Publication
    VAR_060907
    Natural varianti432 – 4321L → P in NPDB. 1 Publication
    VAR_060908
    Natural varianti435 – 4351W → C in NPDB. 1 Publication
    VAR_060909
    Natural varianti436 – 4361S → R in NPDB. 1 Publication
    VAR_005065
    Natural varianti446 – 4461Y → C in NPDA. 1 Publication
    VAR_011388
    Natural varianti450 – 4501L → P in NPDA. 1 Publication
    VAR_060910
    Natural varianti451 – 4511A → D in NPDB. 1 Publication
    VAR_068439
    Natural varianti452 – 4521A → V in NPDB. 1 Publication
    VAR_060911
    Natural varianti456 – 4561G → D in NPDB. 1 Publication
    VAR_060912
    Natural varianti463 – 4631F → S in NPDA. 1 Publication
    VAR_015291
    Natural varianti467 – 4671Y → S in NPDA. 1 Publication
    VAR_060913
    Natural varianti474 – 4741R → W in NPDB; also in a patient with an intermediate form. 3 Publications
    VAR_060914
    Natural varianti475 – 4751P → L in NPDA and NPDB. 3 Publications
    VAR_015292
    Natural varianti480 – 4801F → L in NPDB. 1 Publication
    VAR_060915
    Natural varianti482 – 4821A → E in NPDA. 1 Publication
    VAR_060916
    Natural varianti485 – 4851A → V in NPDB. 1 Publication
    VAR_060917
    Natural varianti486 – 4861T → A in NPDB. 1 Publication
    VAR_060918
    Natural varianti488 – 4881Y → N in NPDB. 1 Publication
    VAR_060919
    Natural varianti494 – 4941G → S in NPDB. 1 Publication
    VAR_060920
    Natural varianti496 – 4961R → C in NPDB. 1 Publication
    VAR_060921
    Natural varianti496 – 4961R → H in NPDA. 1 Publication
    VAR_060922
    Natural varianti496 – 4961R → L in NPDA; in 32% of NPDA Ashkenazi Jewish patients. 2 Publications
    VAR_005066
    Natural varianti505 – 5051S → G.1 Publication
    VAR_060923
    Natural varianti506 – 5061G → R.5 Publications
    Corresponds to variant rs1050239 [ dbSNP | Ensembl ].
    VAR_054644
    Natural varianti514 – 5141H → Q in NPDB. 1 Publication
    VAR_060924
    Natural varianti515 – 5151E → V in NPDB. 1 Publication
    VAR_060925
    Natural varianti517 – 5171Y → C in NPDA. 1 Publication
    VAR_060926
    Natural varianti520 – 5201N → S in NPDB. 1 Publication
    VAR_068440
    Natural varianti523 – 5231Q → H in NPDB; results in 64% of wild-type activity. 1 Publication
    VAR_068441
    Natural varianti533 – 5331W → R in NPDB; also in patients with an intermediate form. 2 Publications
    VAR_060927
    Natural varianti537 – 5371Y → H in NPDA. 1 Publication
    VAR_015293
    Natural varianti549 – 5491L → P in NPDB. 1 Publication
    VAR_060928
    Natural varianti563 – 5631D → Y in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains 6.8% residual enzyme activity. 1 Publication
    VAR_060929
    Natural varianti576 – 5761K → N in NPDB. 1 Publication
    VAR_060930
    Natural varianti577 – 5771G → S in NPDA; also in patients with an intermediate form. 2 Publications
    VAR_005067
    Natural varianti592 – 5921Missing in NPDA. 1 Publication
    VAR_060931
    Natural varianti600 – 6001R → H in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains about 10% residual enzyme activity. 1 Publication
    VAR_060932
    Natural varianti600 – 6001R → P in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains very low enzyme activity. 1 Publication
    VAR_060933
    Natural varianti608 – 6081Missing in NPDB; prevalent among NPDB patients from the North African Maghreb region. 3 Publications
    VAR_005068

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei104 – 1041Missing in isoform 4. 1 PublicationVSP_046964
    Alternative sequencei363 – 41856Missing in isoform 3. CuratedVSP_000333Add
    BLAST
    Alternative sequencei363 – 37412IGGFY…SPYPG → YLSSVETQEGKR in isoform 2. CuratedVSP_000331Add
    BLAST
    Alternative sequencei375 – 41844Missing in isoform 2. CuratedVSP_000332Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M59916 mRNA. Translation: AAA58377.1.
    M59917 Genomic DNA. Translation: AAA58378.1.
    X63600 Genomic DNA. Translation: CAA45145.1.
    M81780 Genomic DNA. Translation: AAA75008.1.
    M81780 Genomic DNA. Translation: AAA75009.1.
    X59960 mRNA. Translation: CAA42584.1.
    AK292388 mRNA. Translation: BAF85077.1.
    AC068733 Genomic DNA. No translation available.
    X52678 mRNA. Translation: CAA36901.1.
    X52679 mRNA. Translation: CAA36902.1.
    PIRiS06958.
    S27009. A39825.
    RefSeqiNP_000534.3. NM_000543.4.
    NP_001007594.2. NM_001007593.2.
    UniGeneiHs.498173.

    Genome annotation databases

    EnsembliENST00000342245; ENSP00000340409; ENSG00000166311.
    ENST00000527275; ENSP00000435350; ENSG00000166311.
    GeneIDi6609.
    KEGGihsa:6609.

    Polymorphism databases

    DMDMi224471897.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Web resourcesi

    Mendelian genes sphingomyelin phosphodiesterase 1, acid lysosomal (SMPD1)

    Leiden Open Variation Database (LOVD)

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M59916 mRNA. Translation: AAA58377.1 .
    M59917 Genomic DNA. Translation: AAA58378.1 .
    X63600 Genomic DNA. Translation: CAA45145.1 .
    M81780 Genomic DNA. Translation: AAA75008.1 .
    M81780 Genomic DNA. Translation: AAA75009.1 .
    X59960 mRNA. Translation: CAA42584.1 .
    AK292388 mRNA. Translation: BAF85077.1 .
    AC068733 Genomic DNA. No translation available.
    X52678 mRNA. Translation: CAA36901.1 .
    X52679 mRNA. Translation: CAA36902.1 .
    PIRi S06958.
    S27009. A39825.
    RefSeqi NP_000534.3. NM_000543.4.
    NP_001007594.2. NM_001007593.2.
    UniGenei Hs.498173.

    3D structure databases

    ProteinModelPortali P17405.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 112493. 5 interactions.
    IntActi P17405. 7 interactions.
    MINTi MINT-3008689.
    STRINGi 9606.ENSP00000340409.

    Chemistry

    BindingDBi P17405.
    ChEMBLi CHEMBL2760.
    DrugBanki DB00381. Amlodipine.
    DB00477. Chlorpromazine.
    DB01151. Desipramine.

    PTM databases

    PhosphoSitei P17405.

    Polymorphism databases

    DMDMi 224471897.

    Proteomic databases

    MaxQBi P17405.
    PaxDbi P17405.
    PRIDEi P17405.

    Protocols and materials databases

    DNASUi 6609.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000342245 ; ENSP00000340409 ; ENSG00000166311 .
    ENST00000527275 ; ENSP00000435350 ; ENSG00000166311 .
    GeneIDi 6609.
    KEGGi hsa:6609.

    Organism-specific databases

    CTDi 6609.
    GeneCardsi GC11P006411.
    GeneReviewsi SMPD1.
    HGNCi HGNC:11120. SMPD1.
    HPAi HPA001823.
    MIMi 257200. phenotype.
    607608. gene.
    607616. phenotype.
    neXtProti NX_P17405.
    Orphaneti 77292. Niemann-Pick disease type A.
    77293. Niemann-Pick disease type B.
    PharmGKBi PA35969.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG303902.
    HOVERGENi HBG004288.
    InParanoidi P17405.
    KOi K12350.
    OrthoDBi EOG79PJP3.
    PhylomeDBi P17405.
    TreeFami TF313674.

    Enzyme and pathway databases

    Reactomei REACT_116105. Glycosphingolipid metabolism.

    Miscellaneous databases

    ChiTaRSi SMPD1. human.
    GeneWikii Sphingomyelin_phosphodiesterase_1.
    GenomeRNAii 6609.
    NextBioi 25729.
    PROi P17405.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P17405.
    Bgeei P17405.
    CleanExi HS_SMPD1.
    Genevestigatori P17405.

    Family and domain databases

    Gene3Di 1.10.225.10. 1 hit.
    3.60.21.10. 1 hit.
    InterProi IPR004843. Calcineurin-like_PHP_apaH.
    IPR029052. Metallo-depent_PP-like.
    IPR011001. Saposin-like.
    IPR008139. SaposinB.
    IPR011160. Sphingomy_PDE.
    [Graphical view ]
    Pfami PF00149. Metallophos. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF000948. Sphingomy_PDE. 1 hit.
    SMARTi SM00741. SapB. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47862. SSF47862. 1 hit.
    SSF56300. SSF56300. 1 hit.
    PROSITEi PS50015. SAP_B. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Human acid sphingomyelinase. Isolation, nucleotide sequence and expression of the full-length and alternatively spliced cDNAs."
      Schuchman E.H., Suchi M., Takahashi T., Sandhoff K., Desnick R.J.
      J. Biol. Chem. 266:8531-8539(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING, VARIANTS ILE-322 AND ARG-506.
    2. "Molecular cloning of the acid sphingomyelinase of the mouse and the organization and complete nucleotide sequence of the gene."
      Newrzella D., Stoffel W.
      Biol. Chem. Hoppe-Seyler 373:1233-1238(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ARG-506.
    3. "Structural organization and complete nucleotide sequence of the gene encoding human acid sphingomyelinase (SMPD1)."
      Schuchman E.H., Levran O., Pereira L.V., Desnick R.J.
      Genomics 12:197-205(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ALA-36.
    4. "Cloning of a human acid sphingomyelinase cDNA with a new mutation that renders the enzyme inactive."
      Ida H., Rennert O.M., Eto Y., Chan W.Y.
      J. Biochem. 114:15-20(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ARG-157.
    5. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N.,