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P17405 (ASM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 166. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sphingomyelin phosphodiesterase

EC=3.1.4.12
Alternative name(s):
Acid sphingomyelinase
Short name=aSMase
Gene names
Name:SMPD1
Synonyms:ASM
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length629 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 activity

Sphingomyelin + H2O = N-acylsphingosine + phosphocholine.

Subunit structure

Monomer.

Subcellular location

Lysosome.

Polymorphism

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

Involvement in disease

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Ref.12 Ref.14 Ref.16 Ref.18 Ref.19 Ref.21 Ref.23 Ref.24 Ref.27 Ref.30 Ref.31

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13 Ref.15 Ref.16 Ref.17 Ref.20 Ref.22 Ref.23 Ref.25 Ref.26 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32

Miscellaneous

There are two types of sphingomyelinases: ASM (acid), and NSM (neutral).

Sequence similarities

Belongs to the acid sphingomyelinase family.

Contains 1 saposin B-type domain.

Ontologies

Keywords
   Cellular componentLysosome
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
Neurodegeneration
Niemann-Pick disease
   DomainSignal
   Molecular functionGlycosidase
Hydrolase
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcell death

Inferred from electronic annotation. Source: UniProtKB-KW

ceramide biosynthetic process

Inferred from mutant phenotype PubMed 19279011. Source: BHF-UCL

glycosphingolipid metabolic process

Traceable author statement. Source: Reactome

negative regulation of MAP kinase activity

Inferred from mutant phenotype PubMed 19279008. Source: BHF-UCL

nervous system development

Traceable author statement PubMed 7670466. Source: ProtInc

positive regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein dephosphorylation

Inferred from mutant phenotype PubMed 19279008. Source: BHF-UCL

response to cocaine

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

signal transduction

Traceable author statement PubMed 7670466. Source: ProtInc

small molecule metabolic process

Traceable author statement. Source: Reactome

sphingolipid metabolic process

Traceable author statement. Source: Reactome

sphingomyelin catabolic process

Inferred from electronic annotation. Source: InterPro

sphingomyelin metabolic process

Traceable author statement PubMed 7670466. Source: ProtInc

termination of signal transduction

Inferred from mutant phenotype PubMed 19279008. Source: BHF-UCL

   Cellular_componentextracellular space

Inferred from electronic annotation. Source: Ensembl

lamellar body

Inferred from electronic annotation. Source: Ensembl

lysosomal lumen

Traceable author statement. Source: Reactome

   Molecular_functionhydrolase activity, acting on glycosyl bonds

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction PubMed 21157428. Source: IntAct

sphingomyelin phosphodiesterase activity

Traceable author statement Ref.11. Source: ProtInc

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CASP7P552106EBI-7095800,EBI-523958

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P17405-1)

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.
Note: Most abundant (90%).
Isoform 2 (identifier: P17405-2)

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%).
Isoform 3 (identifier: P17405-3)

Also known as: ASM-3;

The sequence of this isoform differs from the canonical sequence as follows:
     363-418: Missing.
Note: Low abundance (<1%).
Isoform 4 (identifier: P17405-4)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 4646
Chain47 – 629583Sphingomyelin phosphodiesterase
PRO_0000002323

Regions

Domain85 – 16985Saposin B-type

Amino acid modifications

Glycosylation861N-linked (GlcNAc...) Ref.8
Glycosylation1751N-linked (GlcNAc...) Ref.8
Glycosylation3351N-linked (GlcNAc...) Ref.8
Glycosylation3951N-linked (GlcNAc...) Ref.8
Glycosylation5201N-linked (GlcNAc...) Ref.8
Disulfide bond89 ↔ 165 By similarity
Disulfide bond92 ↔ 157 By similarity
Disulfide bond120 ↔ 131 Ref.9
Disulfide bond221 ↔ 226 Ref.9
Disulfide bond227 ↔ 250 Ref.9
Disulfide bond385 ↔ 431 Ref.9
Disulfide bond584 ↔ 588 Ref.9
Disulfide bond594 ↔ 607 Ref.9

Natural variations

Alternative sequence1041Missing in isoform 4.
VSP_046964
Alternative sequence363 – 41856Missing in isoform 3.
VSP_000333
Alternative sequence363 – 37412IGGFY…SPYPG → YLSSVETQEGKR in isoform 2.
VSP_000331
Alternative sequence375 – 41844Missing in isoform 2.
VSP_000332
Natural variant361V → A. Ref.3
Corresponds to variant rs1050228 [ dbSNP | Ensembl ].
VAR_038191
Natural variant491D → V in NPDB. Ref.22
VAR_060870
Natural variant921C → W in NPDB. Ref.22
VAR_060871
Natural variant1031L → P in NPDA and NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains very low enzyme activity. Ref.24 Ref.25 Ref.26
VAR_060872
Natural variant1301V → A in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains 13% residual enzyme activity. Ref.26
VAR_060873
Natural variant1371L → P in NPDB. Ref.22
VAR_060874
Natural variant1571C → R in NPDB; seems to be less active. Ref.4 Ref.22
VAR_011387
Natural variant1661G → R in NPDB; also in patients with an intermediate form. Ref.27 Ref.28
VAR_060875
Natural variant1761I → N in NPDB. Ref.28
VAR_060876
Natural variant1841P → L in NPDA/NPDB; intermediate form. Ref.27
VAR_060877
Natural variant1961A → P in NPDB. Ref.22
VAR_060878
Natural variant2001R → C in NPDB. Ref.22
VAR_060879
Natural variant2091W → R in NPDA; results in less than 0.5% of wild-type activity. Ref.31
VAR_068435
Natural variant2251L → M in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. Ref.22
VAR_060880
Natural variant2251L → P in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. Ref.25 Ref.26
VAR_060881
Natural variant2281R → C in NPDB. Ref.22 Ref.30
VAR_060882
Natural variant2281R → H in NPDA/NPDB; intermediate form. Ref.27
VAR_060883
Natural variant2321G → D in NPDB. Ref.22
VAR_060884
Natural variant2411A → V in NPDA/NPDB; intermediate form. Ref.27
VAR_060885
Natural variant2421G → R in NPDB. Ref.16
VAR_005058
Natural variant2441W → C in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. Ref.25 Ref.26
VAR_060886
Natural variant2451G → S in NPDA and NPDB. Ref.22 Ref.24 Ref.30
VAR_060887
Natural variant2461E → K in NPDA. Ref.24
VAR_060888
Natural variant2461E → Q in NPDB; 30% residual activity. Ref.20
VAR_005059
Natural variant2481S → R in NPDA and NPDB; also found in patients with an intermediate form. Ref.22 Ref.23 Ref.27
VAR_015287
Natural variant2511D → E in NPDA/NPDB; intermediate form. Ref.27
VAR_060889
Natural variant2511D → H in NPDA; results in loss of activity. Ref.31
VAR_068436
Natural variant2781D → A in NPDA/NPDB; intermediate form. Ref.27
VAR_060890
Natural variant2811A → T in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. Ref.25 Ref.26
VAR_060891
Natural variant2891R → H in NPDB; also in patients with an intermediate form. Ref.22 Ref.27
VAR_060892
Natural variant2921Q → K in NPDA/NPDB; intermediate form. Ref.21 Ref.25 Ref.27
VAR_060893
Natural variant2941R → Q in NPDA. Ref.24
VAR_060894
Natural variant3021L → P in NPDA; in 23% of NPDA Ashkenazi Jewish patients. Ref.14
VAR_005060
Natural variant3121V → M in NPDB; results in 20% of wild-type activity. Ref.31
VAR_068437
Natural variant3131Y → H in NPDA. Ref.24
VAR_060895
Natural variant3161V → E.
Corresponds to variant rs12575136 [ dbSNP | Ensembl ].
VAR_054642
Natural variant3191H → Y in NPDA. Ref.23
VAR_015288
Natural variant3221T → I. Ref.1 Ref.7
Corresponds to variant rs1050233 [ dbSNP | Ensembl ].
VAR_054643
Natural variant3231P → A in NPDB. Ref.22
VAR_060896
Natural variant3301P → R in NPDB. Ref.22 Ref.29
VAR_060897
Natural variant3411L → P in NPDA/NPDB; intermediate form. Ref.21 Ref.27
VAR_060898
Natural variant3571A → D in NPDB. Ref.22
VAR_060899
Natural variant3671Y → C in NPDA. Ref.30
VAR_060900
Natural variant3711P → S in NPDB. Ref.23
VAR_015289
Natural variant3761R → H in NPDB; also found in a patient with an intermediate form. Ref.22 Ref.27 Ref.30
VAR_060901
Natural variant3761R → L in NPDB. Ref.22
VAR_060902
Natural variant3791S → P in NPDB. Ref.22
VAR_060903
Natural variant3821M → I in NPDA and NPDB. Ref.16 Ref.25
VAR_005061
Natural variant3831N → S in NPDB. Ref.16
VAR_005062
Natural variant3891N → T in NPDA. Ref.18
VAR_005063
Natural variant3901Missing in NPDA. Ref.30
VAR_060904
Natural variant3911W → G in NPDB; low sphingomyelin degradation rates. Ref.17
VAR_005064
Natural variant4131A → V in NPDB. Ref.22
VAR_060905
Natural variant4211H → R in NPDA. Ref.30
VAR_060906
Natural variant4211H → Y in NPDB. Ref.22
VAR_015290
Natural variant4251H → 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. Ref.31
VAR_068438
Natural variant4311C → R in NPDB. Ref.22
VAR_060907
Natural variant4321L → P in NPDB. Ref.22
VAR_060908
Natural variant4351W → C in NPDB. Ref.22
VAR_060909
Natural variant4361S → R in NPDB. Ref.15
VAR_005065
Natural variant4461Y → C in NPDA. Ref.19
VAR_011388
Natural variant4501L → P in NPDA. Ref.24
VAR_060910
Natural variant4511A → D in NPDB. Ref.29
VAR_068439
Natural variant4521A → V in NPDB. Ref.22
VAR_060911
Natural variant4561G → D in NPDB. Ref.22
VAR_060912
Natural variant4631F → S in NPDA. Ref.23
VAR_015291
Natural variant4671Y → S in NPDA. Ref.30
VAR_060913
Natural variant4741R → W in NPDB; also in a patient with an intermediate form. Ref.22 Ref.27 Ref.30
VAR_060914
Natural variant4751P → L in NPDA and NPDB. Ref.22 Ref.23 Ref.24
VAR_015292
Natural variant4801F → L in NPDB. Ref.22
VAR_060915
Natural variant4821A → E in NPDA. Ref.30
VAR_060916
Natural variant4851A → V in NPDB. Ref.22
VAR_060917
Natural variant4861T → A in NPDB. Ref.30
VAR_060918
Natural variant4881Y → N in NPDB. Ref.22
VAR_060919
Natural variant4941G → S in NPDB. Ref.22
VAR_060920
Natural variant4961R → C in NPDB. Ref.22
VAR_060921
Natural variant4961R → H in NPDA. Ref.24
VAR_060922
Natural variant4961R → L in NPDA; in 32% of NPDA Ashkenazi Jewish patients. Ref.12 Ref.24
VAR_005066
Natural variant5051S → G. Ref.28
VAR_060923
Natural variant5061G → R. Ref.1 Ref.2 Ref.5 Ref.7 Ref.27
Corresponds to variant rs1050239 [ dbSNP | Ensembl ].
VAR_054644
Natural variant5141H → Q in NPDB. Ref.22
VAR_060924
Natural variant5151E → V in NPDB. Ref.22
VAR_060925
Natural variant5171Y → C in NPDA. Ref.24
VAR_060926
Natural variant5201N → S in NPDB. Ref.32
VAR_068440
Natural variant5231Q → H in NPDB; results in 64% of wild-type activity. Ref.31
VAR_068441
Natural variant5331W → R in NPDB; also in patients with an intermediate form. Ref.22 Ref.27
VAR_060927
Natural variant5371Y → H in NPDA. Ref.23
VAR_015293
Natural variant5491L → P in NPDB. Ref.22
VAR_060928
Natural variant5631D → Y in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains 6.8% residual enzyme activity. Ref.26
VAR_060929
Natural variant5761K → N in NPDB. Ref.22
VAR_060930
Natural variant5771G → S in NPDA; also in patients with an intermediate form. Ref.11 Ref.27
VAR_005067
Natural variant5921Missing in NPDA. Ref.30
VAR_060931
Natural variant6001R → H in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains about 10% residual enzyme activity. Ref.22 Ref.26
VAR_060932
Natural variant6001R → P in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains very low enzyme activity. Ref.22 Ref.26
VAR_060933
Natural variant6081Missing in NPDB; prevalent among NPDB patients from the North African Maghreb region. Ref.13 Ref.23 Ref.30
VAR_005068

Experimental info

Sequence conflict35 – 362Missing in CAA42584. Ref.4
Sequence conflict2681G → D in BAF85077. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (ASM-1) [UniParc].

Last modified March 3, 2009. Version 4.
Checksum: C9888CB8359C42AC

FASTA62969,752
        10         20         30         40         50         60 
MPRYGASLRQ SCPRSGREQG QDGTAGAPGL LWMGLVLALA LALALALSDS RVLWAPAEAH 

        70         80         90        100        110        120 
PLSPQGHPAR LHRIVPRLRD VFGWGNLTCP ICKGLFTAIN LGLKKEPNVA RVGSVAIKLC 

       130        140        150        160        170        180 
NLLKIAPPAV CQSIVHLFED DMVEVWRRSV LSPSEACGLL LGSTCGHWDI FSSWNISLPT 

       190        200        210        220        230        240 
VPKPPPKPPS PPAPGAPVSR ILFLTDLHWD HDYLEGTDPD CADPLCCRRG SGLPPASRPG 

       250        260        270        280        290        300 
AGYWGEYSKC DLPLRTLESL LSGLGPAGPF DMVYWTGDIP AHDVWHQTRQ DQLRALTTVT 

       310        320        330        340        350        360 
ALVRKFLGPV PVYPAVGNHE STPVNSFPPP FIEGNHSSRW LYEAMAKAWE PWLPAEALRT 

       370        380        390        400        410        420 
LRIGGFYALS PYPGLRLISL NMNFCSRENF WLLINSTDPA GQLQWLVGEL QAAEDRGDKV 

       430        440        450        460        470        480 
HIIGHIPPGH CLKSWSWNYY RIVARYENTL AAQFFGHTHV DEFEVFYDEE TLSRPLAVAF 

       490        500        510        520        530        540 
LAPSATTYIG LNPGYRVYQI DGNYSGSSHV VLDHETYILN LTQANIPGAI PHWQLLYRAR 

       550        560        570        580        590        600 
ETYGLPNTLP TAWHNLVYRM RGDMQLFQTF WFLYHKGHPP SEPCGTPCRL ATLCAQLSAR 

       610        620 
ADSPALCRHL MPDGSLPEAQ SLWPRPLFC 

« Hide

Isoform 2 (ASM-2) [UniParc].

Checksum: A5FC9FE28C0D3E42
Show »

FASTA58564,889
Isoform 3 (ASM-3) [UniParc].

Checksum: 093B405E0C0AE061
Show »

FASTA57363,511
Isoform 4 [UniParc].

Checksum: 3504FAA2AC7A10B2
Show »

FASTA62869,624

References

« Hide 'large scale' references
[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. expand/collapse author list , 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., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), VARIANT ARG-506.
Tissue: Testis.
[6]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"Isolation of cDNA clones encoding human acid sphingomyelinase: occurrence of alternatively processed transcripts."
Quintern L.E., Schuchman E.H., Levran O., Suchi M., Ferlinz K., Reinke H., Sandhoff K., Desnick R.J.
EMBO J. 8:2469-2473(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 128-629, PARTIAL PROTEIN SEQUENCE, ALTERNATIVE SPLICING, VARIANTS ILE-322 AND ARG-506.
Tissue: Fibroblast.
[8]"Functional characterization of the N-glycosylation sites of human acid sphingomyelinase by site-directed mutagenesis."
Ferlinz K., Hurwitz R., Moczall H., Lansmann S., Schuchman E.H., Sandhoff K.
Eur. J. Biochem. 243:511-517(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-86; ASN-175; ASN-335; ASN-395 AND ASN-520.
[9]"Human acid sphingomyelinase."
Lansmann S., Schuette C.G., Bartelsen O., Hoernschemeyer J., Linke T., Weisgerber J., Sandhoff K.
Eur. J. Biochem. 270:1076-1088(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: DISULFIDE BONDS.
[10]"Sphingomyelin phosphodiesterase-1 (SMPD1) coding variants do not contribute to low levels of high-density lipoprotein cholesterol."
Dastani Z., Ruel I.L., Engert J.C., Genest J. Jr., Marcil M.
BMC Med. Genet. 8:79-79(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: POLYMORPHISM.
[11]"Molecular basis of acid sphingomyelinase deficiency in a patient with Niemann-Pick disease type A."
Ferlinz K., Hurwitz R., Sandhoff K.
Biochem. Biophys. Res. Commun. 179:1187-1191(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDA SER-577.
[12]"Niemann-Pick disease: a frequent missense mutation in the acid sphingomyelinase gene of Ashkenazi Jewish type A and B patients."
Levran O., Desnick R.J., Schuchman E.H.
Proc. Natl. Acad. Sci. U.S.A. 88:3748-3752(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDA LEU-496.
[13]"Niemann-Pick type B disease. Identification of a single codon deletion in the acid sphingomyelinase gene and genotype/phenotype correlations in type A and B patients."
Levran O., Desnick R.J., Schuchman E.H.
J. Clin. Invest. 88:806-810(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDB ARG-608 DEL.
[14]"Identification and expression of a common missense mutation (L302P) in the acid sphingomyelinase gene of Ashkenazi Jewish type A Niemann-Pick disease patients."
Levran O., Desnick R.J., Schuchman E.H.
Blood 80:2081-2087(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDA PRO-302.
[15]"Identification of a missense mutation (S436R) in the acid sphingomyelinase gene from a Japanese patient with type B Niemann-Pick disease."
Takahashi T., Desnick R.J., Takada G., Schuchman E.H.
Hum. Mutat. 1:70-71(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDB ARG-436.
[16]"Identification and expression of five mutations in the human acid sphingomyelinase gene causing types A and B Niemann-Pick disease. Molecular evidence for genetic heterogeneity in the neuronopathic and non-neuronopathic forms."
Takahashi T., Suchi M., Desnick R.J., Takada G., Schuchman E.H.
J. Biol. Chem. 267:12552-12558(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDA ILE-382, VARIANTS NPDB ARG-242 AND SER-383.
[17]"A family with visceral course of Niemann-Pick disease, macular halo syndrome and low sphingomyelin degradation rate."
Sperl W., Bart G., Vanier M.T., Christomanou H., Baldissera I., Steichensdorf E., Paschke E.
J. Inherit. Metab. Dis. 17:93-103(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDB GLY-391.
[18]"Two new mutations in the acid sphingomyelinase gene causing type A Niemann-pick disease: N389T and R441X."
Schuchman E.H.
Hum. Mutat. 6:352-354(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDA THR-389.
[19]"Identification and expression of a missense mutation (Y446C) in the acid sphingomyelinase gene from a Japanese patient with type A Niemann-Pick disease."
Takahashi T., Suchi M., Sato W., Ten S.B., Sakuragawa N., Desnick R.J., Schuchman E.H., Takada G.
Tohoku J. Exp. Med. 177:117-123(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDA CYS-446.
[20]"Identification of three novel mutations in the acid sphingomyelinase gene of Japanese patients with Niemann-Pick disease type A and B."
Ida H., Rennert O.M., Maekawa K., Eto Y.
Hum. Mutat. 7:65-67(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDB GLN-246.
[21]"Two novel mutations in patients with atypical phenotypes of acid sphingomyelinase deficiency."
Pavluu H., Elleder M.
J. Inherit. Metab. Dis. 20:615-616(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDA/NPDB LYS-292 AND PRO-341.
[22]"The demographics and distribution of type B Niemann-Pick disease: novel mutations lead to new genotype/phenotype correlations."
Simonaro C.M., Desnick R.J., McGovern M.M., Wasserstein M.P., Schuchman E.H.
Am. J. Hum. Genet. 71:1413-1419(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDB VAL-49; TRP-92; PRO-137; ARG-157; PRO-196; CYS-200; MET-225; CYS-228; ASP-232; SER-245; ARG-248; HIS-289; ALA-323; ARG-330; ASP-357; HIS-376; LEU-376; PRO-379; VAL-413; TYR-421; ARG-431; PRO-432; CYS-435; VAL-452; ASP-456; TRP-474; LEU-475; LEU-480; VAL-485; ASN-488; SER-494; CYS-496; GLN-514; VAL-515; ARG-533; PRO-549; ASN-576; HIS-600 AND PRO-600.
[23]"Seven novel Acid sphingomyelinase gene mutations in Niemann-Pick type A and B patients."
Sikora J., Pavluu-Pereira H., Elleder M., Roelofs H., Wevers R.A.
Ann. Hum. Genet. 67:63-70(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDA ARG-248; TYR-319; SER-463; LEU-475 AND HIS-537, VARIANTS NPDB SER-371 AND ARG-608 DEL.
[24]"Screening of 25 Italian patients with Niemann-Pick A reveals fourteen new mutations, one common and thirteen private, in SMPD1."
Ricci V., Stroppiano M., Corsolini F., Di Rocco M., Parenti G., Regis S., Grossi S., Biancheri R., Mazzotti R., Filocamo M.
Hum. Mutat. 24:105-105(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDA PRO-103; SER-245; LYS-246; GLN-294; HIS-313; PRO-450; LEU-475; LEU-496; HIS-496 AND CYS-517.
[25]"Acid sphingomyelinase: identification of nine novel mutations among Italian Niemann Pick type B patients and characterization of in vivo functional in-frame start codon."
Pittis M.G., Ricci V., Guerci V.I., Marcais C., Ciana G., Dardis A., Gerin F., Stroppiano M., Vanier M.T., Filocamo M., Bembi B.
Hum. Mutat. 24:186-187(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDB PRO-103; PRO-225; CYS-244; THR-281; LYS-292 AND ILE-382.
[26]"Functional in vitro characterization of 14 SMPD1 mutations identified in Italian patients affected by Niemann Pick type B disease."
Dardis A., Zampieri S., Filocamo M., Burlina A., Bembi B., Pittis M.G.
Hum. Mutat. 26:164-164(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDB ALA-130 AND TYR-563, CHARACTERIZATION OF VARIANTS NPDB PRO-103; ALA-130; PRO-225; CYS-244; THR-281; TYR-563; HIS-600 AND PRO-600.
[27]"Acid sphingomyelinase deficiency. Phenotype variability with prevalence of intermediate phenotype in a series of twenty-five Czech and Slovak patients. A multi-approach study."
Pavluu-Pereira H., Asfaw B., Poupctova H., Ledvinova J., Sikora J., Vanier M.T., Sandhoff K., Zeman J., Novotna Z., Chudoba D., Elleder M.
J. Inherit. Metab. Dis. 28:203-227(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDA/NPDB ARG-166; LEU-184; HIS-228; VAL-241; ARG-248; GLU-251; ALA-278; HIS-289; LYS-292; PRO-341; HIS-376; TRP-474; ARG-533 AND SER-577, VARIANT ARG-506.
[28]"Clinical findings in Niemann-Pick disease type B."
Muessig K., Harzer K., Mayrhofer H., Kraegeloh-Mann I., Haering H.-U., Machicao F.
Intern. Med. J. 36:135-136(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDB ARG-166 AND ASN-176, VARIANT GLY-505.
[29]"A novel missense mutation of the SMPD1 gene in a Taiwanese patient with type B Niemann-Pick disease."
Lan M.Y., Lin S.J., Chen Y.F., Peng C.H., Liu Y.F.
Ann. Hematol. 88:695-697(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDB ARG-330 AND ASP-451.
[30]"Identification and characterization of SMPD1 mutations causing Niemann-Pick types A and B in Spanish patients."
Rodriguez-Pascau L., Gort L., Schuchman E.H., Vilageliu L., Grinberg D., Chabas A.
Hum. Mutat. 30:1117-1122(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDA SER-245; CYS-367; PHE-390 DEL; ARG-421; SER-467; GLU-482 AND THR-592 DEL, VARIANTS NPDB CYS-228; HIS-376; TRP-474; ALA-486 AND ARG-608 DEL.
[31]"Identification and characterization of eight novel SMPD1 mutations causing types A and B Niemann-Pick disease."
Desnick J.P., Kim J., He X., Wasserstein M.P., Simonaro C.M., Schuchman E.H.
Mol. Med. 16:316-321(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDA ARG-209 AND HIS-251, VARIANTS NPDB MET-312; ARG-425 AND HIS-523, CHARACTERIZATION OF VARIANTS NPDA ARG-209 AND HIS-251, CHARACTERIZATION OF VARIANTS NPDB MET-312; ARG-425 AND HIS-523.
[32]"A novel SMPD1 mutation in two Chinese sibling patients with type B Niemann-Pick disease."
Hua R., Wu H., Cui Z., Chen J.X., Wang Z.
Chin. Med. J. 125:1511-1512(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDB SER-520.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRS06958.
A39825. S27009.
RefSeqNP_000534.3. NM_000543.4.
NP_001007594.2. NM_001007593.2.
UniGeneHs.498173.

3D structure databases

ProteinModelPortalP17405.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112493. 5 interactions.
IntActP17405. 7 interactions.
MINTMINT-3008689.
STRING9606.ENSP00000340409.

Chemistry

BindingDBP17405.
ChEMBLCHEMBL2760.
DrugBankDB01151. Desipramine.

PTM databases

PhosphoSiteP17405.

Polymorphism databases

DMDM224471897.

Proteomic databases

MaxQBP17405.
PaxDbP17405.
PRIDEP17405.

Protocols and materials databases

DNASU6609.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000342245; ENSP00000340409; ENSG00000166311.
ENST00000527275; ENSP00000435350; ENSG00000166311.
GeneID6609.
KEGGhsa:6609.

Organism-specific databases

CTD6609.
GeneCardsGC11P006411.
GeneReviewsSMPD1.
HGNCHGNC:11120. SMPD1.
HPAHPA001823.
MIM257200. phenotype.
607608. gene.
607616. phenotype.
neXtProtNX_P17405.
Orphanet77292. Niemann-Pick disease type A.
77293. Niemann-Pick disease type B.
PharmGKBPA35969.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG303902.
HOVERGENHBG004288.
InParanoidP17405.
KOK12350.
OrthoDBEOG79PJP3.
PhylomeDBP17405.
TreeFamTF313674.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressP17405.
BgeeP17405.
CleanExHS_SMPD1.
GenevestigatorP17405.

Family and domain databases

Gene3D1.10.225.10. 1 hit.
3.60.21.10. 1 hit.
InterProIPR004843. Calcineurin-like_PHP_apaH.
IPR029052. Metallo-depent_PP-like.
IPR011001. Saposin-like.
IPR008139. SaposinB.
IPR011160. Sphingomy_PDE.
[Graphical view]
PfamPF00149. Metallophos. 1 hit.
[Graphical view]
PIRSFPIRSF000948. Sphingomy_PDE. 1 hit.
SMARTSM00741. SapB. 1 hit.
[Graphical view]
SUPFAMSSF47862. SSF47862. 1 hit.
SSF56300. SSF56300. 1 hit.
PROSITEPS50015. SAP_B. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSMPD1. human.
GeneWikiSphingomyelin_phosphodiesterase_1.
GenomeRNAi6609.
NextBio25729.
PROP17405.
SOURCESearch...

Entry information

Entry nameASM_HUMAN
AccessionPrimary (citable) accession number: P17405
Secondary accession number(s): A8K8M3 expand/collapse secondary AC list , E9PKS3, P17406, Q13811, Q16837, Q16841
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: March 3, 2009
Last modified: July 9, 2014
This is version 166 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM