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Protein

Sphingomyelin phosphodiesterase

Gene

SMPD1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Converts sphingomyelin to ceramide (PubMed:1840600, PubMed:18815062). Also has phospholipase C activities toward 1,2-diacylglycerolphosphocholine and 1,2-diacylglycerolphosphoglycerol.Curated2 Publications
Isoform 2 lacks residues that bind the cofactor Zn2+ and has no enzyme activity.Curated1 Publication
Isoform 3 lacks residues that bind the cofactor Zn2+ and has no enzyme activity.Curated1 Publication

Catalytic activityi

Sphingomyelin + H2O = N-acylsphingosine + phosphocholine.6 Publications

Cofactori

Zn2+1 PublicationNote: Zn2+ is particularly important for enzyme activity at neutral pH.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi206Zinc 1By similarity1
Metal bindingi208Zinc 1By similarity1
Metal bindingi278Zinc 1By similarity1
Metal bindingi278Zinc 2By similarity1
Metal bindingi318Zinc 2By similarity1
Metal bindingi425Zinc 2By similarity1
Metal bindingi457Zinc 2By similarity1
Metal bindingi459Zinc 1By similarity1

GO - Molecular functioni

GO - Biological processi

  • ceramide biosynthetic process Source: UniProtKB
  • glycosphingolipid metabolic process Source: Reactome
  • negative regulation of MAP kinase activity Source: BHF-UCL
  • nervous system development Source: ProtInc
  • positive regulation of apoptotic process Source: Ensembl
  • positive regulation of protein dephosphorylation Source: BHF-UCL
  • response to cocaine Source: Ensembl
  • response to drug Source: Ensembl
  • signal transduction Source: ProtInc
  • sphingomyelin catabolic process Source: UniProtKB
  • sphingomyelin metabolic process Source: ProtInc
  • termination of signal transduction Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Glycosidase, Hydrolase

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:HS09373-MONOMER.
ReactomeiR-HSA-1660662. Glycosphingolipid metabolism.
SIGNORiP17405.

Names & Taxonomyi

Protein namesi
Recommended name:
Sphingomyelin phosphodiesterase (EC:3.1.4.126 Publications)
Alternative name(s):
Acid sphingomyelinase
Short name:
aSMase
Gene namesi
Name:SMPD1
Synonyms:ASM
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:11120. SMPD1.

Subcellular locationi

  • Lysosome 1 Publication
  • Secreted 1 Publication

GO - Cellular componenti

  • endosome Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • extracellular space Source: UniProtKB
  • lamellar body Source: Ensembl
  • lysosomal lumen Source: Reactome
  • lysosome Source: UniProtKB
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Lysosome, Secreted

Pathology & Biotechi

Involvement in diseasei

Niemann-Pick disease A (NPDA)15 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:257200
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_060872103L → P in NPDA and NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains very low enzyme activity. 4 Publications1
Natural variantiVAR_060877184P → L in NPDA; reduces enzyme activity; intermediate form with clinical features of both Niemann-Pick disease types A and B. 1 Publication1
Natural variantiVAR_068435209W → R in NPDA; results in less than 0.5% of wild-type activity. 1 Publication1
Natural variantiVAR_075324226C → R in NPDA. 1 Publication1
Natural variantiVAR_060882228R → C in NPDB; some patients have a NPDA/NPDB intermediate phenotype. 4 Publications1
Natural variantiVAR_060883228R → H in NPDA; intermediate form with clinical features of both Niemann-Pick disease types A and B. 1 Publication1
Natural variantiVAR_060885241A → V in NPDA; intermediate form with clinical features of both Niemann-Pick disease types A and B. 1 Publication1
Natural variantiVAR_075325245G → D in NPDA; severe decrease in activity; the mutant is highly unstable. 1 Publication1
Natural variantiVAR_060887245G → S in NPDA and NPDB. 4 Publications1
Natural variantiVAR_060888246E → K in NPDA. 1 Publication1
Natural variantiVAR_015287248S → R in NPDA and NPDB; also found in patients with an intermediate form. 4 Publications1
Natural variantiVAR_060889251D → E in NPDA; strongly reduces enzyme activity; intermediate form with clinical features of both Niemann-Pick disease types A and B. 1 Publication1
Natural variantiVAR_068436251D → H in NPDA; results in loss of activity. 1 Publication1
Natural variantiVAR_060890278D → A in NPDA; strongly reduces enzyme activity; intermediate form with clinical features of both Niemann-Pick disease types A and B. 1 Publication1
Natural variantiVAR_060893292Q → K in NPDA; strongly reduces enzyme activity; intermediate form with clinical features of both Niemann-Pick disease types A and B. 3 Publications1
Natural variantiVAR_005060302L → P in NPDA; in 23% of NPDA Ashkenazi Jewish patients; abolishes enzyme activity. 2 Publications1
Natural variantiVAR_060895313Y → H in NPDA. 1 Publication1
Natural variantiVAR_015288319H → Y in NPDA. 2 Publications1
Natural variantiVAR_060898341L → P in NPDA; strongly reduces enzyme activity; intermediate form with clinical features of both Niemann-Pick disease types A and B. 2 Publications1
Natural variantiVAR_060900367Y → C in NPDA. 1 Publication1
Natural variantiVAR_060901376R → H in NPDB; reduces enzyme activity; some patients have a NPDA/NPDB intermediate phenotype. 4 Publications1
Natural variantiVAR_005061382M → I in NPDA and NPDB. 2 Publications1
Natural variantiVAR_075327385C → R in NPDA. 1 Publication1
Natural variantiVAR_005063389N → T in NPDA. 1 Publication1
Natural variantiVAR_060904390Missing in NPDA. 1 Publication1
Natural variantiVAR_060906421H → R in NPDA. 1 Publication1
Natural variantiVAR_011388446Y → C in NPDA. 1 Publication1
Natural variantiVAR_060910450L → P in NPDA. 1 Publication1
Natural variantiVAR_015291463F → S in NPDA. 1 Publication1
Natural variantiVAR_060913467Y → S in NPDA. 1 Publication1
Natural variantiVAR_060914474R → W in NPDB; some patients have a NPDA/NPDB intermediate phenotype. 4 Publications1
Natural variantiVAR_015292475P → L in NPDA and NPDB. 4 Publications1
Natural variantiVAR_075329480Missing in NPDA; unknown pathological significance. 1 Publication1
Natural variantiVAR_060916482A → E in NPDA. 1 Publication1
Natural variantiVAR_060922496R → H in NPDA. 1 Publication1
Natural variantiVAR_005066496R → L in NPDA; in 32% of NPDA Ashkenazi Jewish patients; nearly abolishes enzyme activity. 3 Publications1
Natural variantiVAR_060926517Y → C in NPDA. 1 Publication1
Natural variantiVAR_015293537Y → H in NPDA. 2 Publications1
Natural variantiVAR_075331570F → L in NPDA; results in decreased activity; decreased stability. 1 Publication1
Natural variantiVAR_005067577G → S in NPDA; impairs enzyme activity; also in patients with an intermediate form. 2 Publications1
Natural variantiVAR_060931592Missing in NPDA. 1 Publication1
Natural variantiVAR_005068608Missing in NPDB; nearly abolishes enzyme activity; some patients have a NPDA/NPDB intermediate phenotype. 6 Publications1
Niemann-Pick disease B (NPDB)19 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:607616
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06087049D → V in NPDB; unknown pathological significance. 1 Publication1
Natural variantiVAR_07532289C → H in NPDB; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_06087192C → W in NPDB. 1 Publication1
Natural variantiVAR_060872103L → P in NPDA and NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains very low enzyme activity. 4 Publications1
Natural variantiVAR_060873130V → A in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains 13% residual enzyme activity. 1 Publication1
Natural variantiVAR_060874137L → P in NPDB. 1 Publication1
Natural variantiVAR_011387157C → R in NPDB. 2 Publications1
Natural variantiVAR_075323161L → P in NPDB. 1 Publication1
Natural variantiVAR_060875166G → R in NPDB; also in patients with an intermediate form. 2 Publications1
Natural variantiVAR_060876176I → N in NPDB. 1 Publication1
Natural variantiVAR_060878196A → P in NPDB. 1 Publication1
Natural variantiVAR_060879200R → C in NPDB. 1 Publication1
Natural variantiVAR_060880225L → M in NPDB. 1 Publication1
Natural variantiVAR_060881225L → P in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. 2 Publications1
Natural variantiVAR_060882228R → C in NPDB; some patients have a NPDA/NPDB intermediate phenotype. 4 Publications1
Natural variantiVAR_060884232G → D in NPDB. 1 Publication1
Natural variantiVAR_005058242G → R in NPDB. 1 Publication1
Natural variantiVAR_060886244W → C in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. 2 Publications1
Natural variantiVAR_060887245G → S in NPDA and NPDB. 4 Publications1
Natural variantiVAR_005059246E → Q in NPDB; 30% residual activity. 1 Publication1
Natural variantiVAR_015287248S → R in NPDA and NPDB; also found in patients with an intermediate form. 4 Publications1
Natural variantiVAR_075326256T → I in NPDB. 1 Publication1
Natural variantiVAR_060891281A → T in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. 2 Publications1
Natural variantiVAR_060892289R → H in NPDB; also in patients with an intermediate form; unknown pathological significance. 2 Publications1
Natural variantiVAR_068437312V → M in NPDB; results in 20% of wild-type activity. 1 Publication1
Natural variantiVAR_060896323P → A in NPDB; results in 1-4% of wild type activity. 3 Publications1
Natural variantiVAR_060897330P → R in NPDB. 2 Publications1
Natural variantiVAR_060899357A → D in NPDB. 1 Publication1
Natural variantiVAR_015289371P → S in NPDB. 2 Publications1
Natural variantiVAR_060901376R → H in NPDB; reduces enzyme activity; some patients have a NPDA/NPDB intermediate phenotype. 4 Publications1
Natural variantiVAR_060902376R → L in NPDB. 1 Publication1
Natural variantiVAR_060903379S → P in NPDB. 1 Publication1
Natural variantiVAR_005061382M → I in NPDA and NPDB. 2 Publications1
Natural variantiVAR_005062383N → S in NPDB. 1 Publication1
Natural variantiVAR_005064391W → G in NPDB; low sphingomyelin degradation rates. 1 Publication1
Natural variantiVAR_060905413A → V in NPDB. 1 Publication1
Natural variantiVAR_015290421H → Y in NPDB; abolishes enzyme activity. 2 Publications1
Natural variantiVAR_068438425H → 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 Publication1
Natural variantiVAR_060907431C → R in NPDB. 1 Publication1
Natural variantiVAR_060908432L → P in NPDB. 1 Publication1
Natural variantiVAR_060909435W → C in NPDB. 1 Publication1
Natural variantiVAR_005065436S → R in NPDB. 1 Publication1
Natural variantiVAR_068439451A → D in NPDB. 1 Publication1
Natural variantiVAR_060911452A → V in NPDB. 1 Publication1
Natural variantiVAR_060912456G → D in NPDB. 1 Publication1
Natural variantiVAR_075328474R → Q in NPDB; unknown pathological significance. 1 Publication1
Natural variantiVAR_060914474R → W in NPDB; some patients have a NPDA/NPDB intermediate phenotype. 4 Publications1
Natural variantiVAR_015292475P → L in NPDA and NPDB. 4 Publications1
Natural variantiVAR_060915480F → L in NPDB. 1 Publication1
Natural variantiVAR_060918486T → A in NPDB. 1 Publication1
Natural variantiVAR_060919488Y → N in NPDB. 1 Publication1
Natural variantiVAR_075330490G → S in NPDB. 1 Publication1
Natural variantiVAR_060920494G → S in NPDB. 1 Publication1
Natural variantiVAR_060921496R → C in NPDB. 1 Publication1
Natural variantiVAR_060924514H → Q in NPDB. 1 Publication1
Natural variantiVAR_060925515E → V in NPDB. 1 Publication1
Natural variantiVAR_068440520N → S in NPDB. 1 Publication1
Natural variantiVAR_068441523Q → H in NPDB; results in 64% of wild-type activity. 1 Publication1
Natural variantiVAR_060927533W → R in NPDB; also in patients with an intermediate form. 2 Publications1
Natural variantiVAR_060928549L → P in NPDB. 2 Publications1
Natural variantiVAR_060929563D → Y in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains 6.8% residual enzyme activity. 1 Publication1
Natural variantiVAR_075332575H → D in NPDB; unknown pathological significance. 1 Publication1
Natural variantiVAR_060930576K → N in NPDB. 1 Publication1
Natural variantiVAR_075333596Q → R in NPDB. 1 Publication1
Natural variantiVAR_075334597L → F in NPDB; unknown pathological significance. 1 Publication1
Natural variantiVAR_060932600R → H in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains about 10% residual enzyme activity. 2 Publications1
Natural variantiVAR_060933600R → P in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains very low enzyme activity. 2 Publications1
Natural variantiVAR_075335608R → C in NPDB; unknown pathological significance. 1 Publication1
Natural variantiVAR_005068608Missing in NPDB; nearly abolishes enzyme activity; some patients have a NPDA/NPDB intermediate phenotype. 6 Publications1

Keywords - Diseasei

Disease mutation, Neurodegeneration, Niemann-Pick disease

Organism-specific databases

DisGeNETi6609.
MalaCardsiSMPD1.
MIMi257200. phenotype.
607616. phenotype.
Orphaneti77292. Niemann-Pick disease type A.
77293. Niemann-Pick disease type B.
PharmGKBiPA35969.

Chemistry databases

ChEMBLiCHEMBL2760.
DrugBankiDB00381. Amlodipine.
DB00477. Chlorpromazine.
DB01151. Desipramine.

Polymorphism and mutation databases

BioMutaiSMPD1.
DMDMi224471897.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 46Add BLAST46
ChainiPRO_000000232347 – 629Sphingomyelin phosphodiesteraseAdd BLAST583

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi86N-linked (GlcNAc...)PROSITE-ProRule annotation1 Publication1
Disulfide bondi89 ↔ 165PROSITE-ProRule annotation
Disulfide bondi92 ↔ 157PROSITE-ProRule annotation
Disulfide bondi120 ↔ 131PROSITE-ProRule annotation1 Publication
Glycosylationi175N-linked (GlcNAc...)PROSITE-ProRule annotation1 Publication1
Disulfide bondi221 ↔ 226PROSITE-ProRule annotation1 Publication
Disulfide bondi227 ↔ 250PROSITE-ProRule annotation1 Publication
Glycosylationi335N-linked (GlcNAc...)PROSITE-ProRule annotation1 Publication1
Disulfide bondi385 ↔ 431PROSITE-ProRule annotation1 Publication
Glycosylationi395N-linked (GlcNAc...)PROSITE-ProRule annotation1 Publication1
Glycosylationi520N-linked (GlcNAc...)PROSITE-ProRule annotation1 Publication1
Disulfide bondi584 ↔ 588PROSITE-ProRule annotation1 Publication
Disulfide bondi594 ↔ 607PROSITE-ProRule annotation1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiP17405.
PaxDbiP17405.
PeptideAtlasiP17405.
PRIDEiP17405.

PTM databases

iPTMnetiP17405.
PhosphoSitePlusiP17405.

Expressioni

Gene expression databases

BgeeiENSG00000166311.
CleanExiHS_SMPD1.
ExpressionAtlasiP17405. baseline and differential.
GenevisibleiP17405. HS.

Organism-specific databases

HPAiHPA001823.

Interactioni

Subunit structurei

Monomer.

Binary interactionsi

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

Protein-protein interaction databases

BioGridi112493. 14 interactors.
IntActiP17405. 7 interactors.
MINTiMINT-3008689.
STRINGi9606.ENSP00000340409.

Chemistry databases

BindingDBiP17405.

Structurei

Secondary structure

1629
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi85 – 87Combined sources3
Helixi88 – 103Combined sources16
Helixi106 – 122Combined sources17
Helixi128 – 148Combined sources21
Turni149 – 151Combined sources3
Helixi153 – 161Combined sources9
Turni163 – 165Combined sources3
Beta strandi198 – 204Combined sources7
Beta strandi222 – 225Combined sources4
Beta strandi247 – 249Combined sources3
Helixi254 – 262Combined sources9
Helixi265 – 267Combined sources3
Beta strandi271 – 275Combined sources5
Helixi289 – 307Combined sources19
Beta strandi312 – 314Combined sources3
Beta strandi320 – 323Combined sources4
Beta strandi334 – 338Combined sources5
Helixi339 – 348Combined sources10
Turni350 – 352Combined sources3
Helixi355 – 364Combined sources10
Beta strandi367 – 372Combined sources6
Beta strandi375 – 379Combined sources5
Helixi382 – 385Combined sources4
Helixi390 – 393Combined sources4
Helixi399 – 401Combined sources3
Helixi402 – 416Combined sources15
Beta strandi419 – 423Combined sources5
Helixi428 – 430Combined sources3
Helixi433 – 445Combined sources13
Turni446 – 449Combined sources4
Beta strandi450 – 455Combined sources6
Beta strandi462 – 467Combined sources6
Turni469 – 471Combined sources3
Beta strandi474 – 481Combined sources8
Turni488 – 490Combined sources3
Beta strandi494 – 501Combined sources8
Beta strandi511 – 518Combined sources8
Helixi521 – 524Combined sources4
Beta strandi534 – 538Combined sources5
Helixi539 – 543Combined sources5
Helixi550 – 561Combined sources12
Helixi564 – 574Combined sources11
Turni575 – 577Combined sources3
Helixi586 – 597Combined sources12
Beta strandi600 – 602Combined sources3
Helixi604 – 607Combined sources4
Turni608 – 610Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5I81X-ray2.25A47-629[»]
5I85X-ray2.50A47-629[»]
5I8RX-ray3.65A/B/C47-629[»]
5JG8X-ray2.80A/B47-629[»]
ProteinModelPortaliP17405.
SMRiP17405.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini85 – 169Saposin B-typePROSITE-ProRule annotationAdd BLAST85

Sequence similaritiesi

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

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3770. Eukaryota.
ENOG410YYPB. LUCA.
HOVERGENiHBG004288.
InParanoidiP17405.
KOiK12350.
OrthoDBiEOG091G03M6.
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_dom.
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. AlignAdd to basket

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

        10         20         30         40         50
MPRYGASLRQ SCPRSGREQG QDGTAGAPGL LWMGLVLALA LALALALSDS
60 70 80 90 100
RVLWAPAEAH PLSPQGHPAR LHRIVPRLRD VFGWGNLTCP ICKGLFTAIN
110 120 130 140 150
LGLKKEPNVA RVGSVAIKLC NLLKIAPPAV CQSIVHLFED DMVEVWRRSV
160 170 180 190 200
LSPSEACGLL LGSTCGHWDI FSSWNISLPT VPKPPPKPPS PPAPGAPVSR
210 220 230 240 250
ILFLTDLHWD HDYLEGTDPD CADPLCCRRG SGLPPASRPG AGYWGEYSKC
260 270 280 290 300
DLPLRTLESL LSGLGPAGPF DMVYWTGDIP AHDVWHQTRQ DQLRALTTVT
310 320 330 340 350
ALVRKFLGPV PVYPAVGNHE STPVNSFPPP FIEGNHSSRW LYEAMAKAWE
360 370 380 390 400
PWLPAEALRT LRIGGFYALS PYPGLRLISL NMNFCSRENF WLLINSTDPA
410 420 430 440 450
GQLQWLVGEL QAAEDRGDKV HIIGHIPPGH CLKSWSWNYY RIVARYENTL
460 470 480 490 500
AAQFFGHTHV DEFEVFYDEE TLSRPLAVAF LAPSATTYIG LNPGYRVYQI
510 520 530 540 550
DGNYSGSSHV VLDHETYILN LTQANIPGAI PHWQLLYRAR ETYGLPNTLP
560 570 580 590 600
TAWHNLVYRM RGDMQLFQTF WFLYHKGHPP SEPCGTPCRL ATLCAQLSAR
610 620
ADSPALCRHL MPDGSLPEAQ SLWPRPLFC
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)DescriptionActionsGraphical viewLength
Sequence conflicti35 – 36Missing in CAA42584 (PubMed:8407868).Curated2
Sequence conflicti268G → D in BAF85077 (PubMed:14702039).Curated1

Polymorphismi

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

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03819136V → A Polymorphism; does not affect enzymatic activity. 2 PublicationsCorresponds to variant rs1050228dbSNPEnsembl.1
Natural variantiVAR_06087049D → V in NPDB; unknown pathological significance. 1 Publication1
Natural variantiVAR_07532289C → H in NPDB; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_06087192C → W in NPDB. 1 Publication1
Natural variantiVAR_060872103L → P in NPDA and NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains very low enzyme activity. 4 Publications1
Natural variantiVAR_060873130V → A in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains 13% residual enzyme activity. 1 Publication1
Natural variantiVAR_060874137L → P in NPDB. 1 Publication1
Natural variantiVAR_011387157C → R in NPDB. 2 Publications1
Natural variantiVAR_075323161L → P in NPDB. 1 Publication1
Natural variantiVAR_060875166G → R in NPDB; also in patients with an intermediate form. 2 Publications1
Natural variantiVAR_060876176I → N in NPDB. 1 Publication1
Natural variantiVAR_060877184P → L in NPDA; reduces enzyme activity; intermediate form with clinical features of both Niemann-Pick disease types A and B. 1 Publication1
Natural variantiVAR_060878196A → P in NPDB. 1 Publication1
Natural variantiVAR_060879200R → C in NPDB. 1 Publication1
Natural variantiVAR_068435209W → R in NPDA; results in less than 0.5% of wild-type activity. 1 Publication1
Natural variantiVAR_060880225L → M in NPDB. 1 Publication1
Natural variantiVAR_060881225L → P in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. 2 Publications1
Natural variantiVAR_075324226C → R in NPDA. 1 Publication1
Natural variantiVAR_060882228R → C in NPDB; some patients have a NPDA/NPDB intermediate phenotype. 4 Publications1
Natural variantiVAR_060883228R → H in NPDA; intermediate form with clinical features of both Niemann-Pick disease types A and B. 1 Publication1
Natural variantiVAR_060884232G → D in NPDB. 1 Publication1
Natural variantiVAR_060885241A → V in NPDA; intermediate form with clinical features of both Niemann-Pick disease types A and B. 1 Publication1
Natural variantiVAR_005058242G → R in NPDB. 1 Publication1
Natural variantiVAR_060886244W → C in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. 2 Publications1
Natural variantiVAR_075325245G → D in NPDA; severe decrease in activity; the mutant is highly unstable. 1 Publication1
Natural variantiVAR_060887245G → S in NPDA and NPDB. 4 Publications1
Natural variantiVAR_060888246E → K in NPDA. 1 Publication1
Natural variantiVAR_005059246E → Q in NPDB; 30% residual activity. 1 Publication1
Natural variantiVAR_015287248S → R in NPDA and NPDB; also found in patients with an intermediate form. 4 Publications1
Natural variantiVAR_060889251D → E in NPDA; strongly reduces enzyme activity; intermediate form with clinical features of both Niemann-Pick disease types A and B. 1 Publication1
Natural variantiVAR_068436251D → H in NPDA; results in loss of activity. 1 Publication1
Natural variantiVAR_075326256T → I in NPDB. 1 Publication1
Natural variantiVAR_060890278D → A in NPDA; strongly reduces enzyme activity; intermediate form with clinical features of both Niemann-Pick disease types A and B. 1 Publication1
Natural variantiVAR_060891281A → T in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. 2 Publications1
Natural variantiVAR_060892289R → H in NPDB; also in patients with an intermediate form; unknown pathological significance. 2 Publications1
Natural variantiVAR_060893292Q → K in NPDA; strongly reduces enzyme activity; intermediate form with clinical features of both Niemann-Pick disease types A and B. 3 Publications1
Natural variantiVAR_060894294R → Q.1 PublicationCorresponds to variant rs35824453dbSNPEnsembl.1
Natural variantiVAR_005060302L → P in NPDA; in 23% of NPDA Ashkenazi Jewish patients; abolishes enzyme activity. 2 Publications1
Natural variantiVAR_068437312V → M in NPDB; results in 20% of wild-type activity. 1 Publication1
Natural variantiVAR_060895313Y → H in NPDA. 1 Publication1
Natural variantiVAR_054642316V → E.Corresponds to variant rs12575136dbSNPEnsembl.1
Natural variantiVAR_015288319H → Y in NPDA. 2 Publications1
Natural variantiVAR_054643322T → I.3 PublicationsCorresponds to variant rs1050233dbSNPEnsembl.1
Natural variantiVAR_060896323P → A in NPDB; results in 1-4% of wild type activity. 3 Publications1
Natural variantiVAR_060897330P → R in NPDB. 2 Publications