P17405 (ASM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sphingomyelin phosphodiesterase
EC=3.1.4.12

Alternative name(s):
Acid sphingomyelinase
Short name=aSMase

Gene names

Name:	SMPD1
Synonyms:	ASM

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	629 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.10 Ref.11 Ref.13 Ref.15 Ref.17 Ref.18 Ref.20 Ref.22 Ref.23 Ref.26 Ref.29 Ref.30 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.12 Ref.14 Ref.15 Ref.16 Ref.19 Ref.21 Ref.22 Ref.24 Ref.25 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31
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 component	Lysosome
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Neurodegeneration Niemann-Pick disease
Domain	Signal
Molecular function	Glycosidase Hydrolase
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cell 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: Compara positive regulation of protein dephosphorylation Inferred from mutant phenotype PubMed 19279008. Source: BHF-UCL response to cocaine Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara signal transduction Traceable author statement PubMed 7670466. Source: ProtInc 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_component	extracellular space Inferred from electronic annotation. Source: Compara lamellar body Inferred from electronic annotation. Source: Compara lysosomal lumen Traceable author statement. Source: Reactome
Molecular_function	hydrolase activity, acting on glycosyl bonds Inferred from electronic annotation. Source: UniProtKB-KW sphingomyelin phosphodiesterase activity Traceable author statement Ref.10. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 3 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%).

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 46	46
	Chain	47 – 629	583	Sphingomyelin phosphodiesterase		PRO_0000002323
Regions
	Domain	85 – 169	85	Saposin B-type
Amino acid modifications
	Glycosylation	86	1	N-linked (GlcNAc...) Ref.7
	Glycosylation	175	1	N-linked (GlcNAc...) Ref.7
	Glycosylation	335	1	N-linked (GlcNAc...) Ref.7
	Glycosylation	395	1	N-linked (GlcNAc...) Ref.7
	Glycosylation	520	1	N-linked (GlcNAc...) Ref.7
	Disulfide bond	89 ↔ 165		By similarity
	Disulfide bond	92 ↔ 157		By similarity
	Disulfide bond	120 ↔ 131		Ref.8
	Disulfide bond	221 ↔ 226		Ref.8
	Disulfide bond	227 ↔ 250		Ref.8
	Disulfide bond	385 ↔ 431		Ref.8
	Disulfide bond	584 ↔ 588		Ref.8
	Disulfide bond	594 ↔ 607		Ref.8
Natural variations
	Alternative sequence	363 – 418	56	Missing in isoform 3.		VSP_000333
	Alternative sequence	363 – 374	12	IGGFY…SPYPG → YLSSVETQEGKR in isoform 2.		VSP_000331
	Alternative sequence	375 – 418	44	Missing in isoform 2.		VSP_000332
	Natural variant	36	1	V → A. Ref.3 Corresponds to variant rs1050228 [ dbSNP | Ensembl ].		VAR_038191
	Natural variant	49	1	D → V in NPDB. Ref.21		VAR_060870
	Natural variant	92	1	C → W in NPDB. Ref.21		VAR_060871
	Natural variant	103	1	L → P in NPDA and NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains very low enzyme activity. Ref.23 Ref.24 Ref.25		VAR_060872
	Natural variant	130	1	V → A in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains 13% residual enzyme activity. Ref.25		VAR_060873
	Natural variant	137	1	L → P in NPDB. Ref.21		VAR_060874
	Natural variant	157	1	C → R in NPDB; seems to be less active. Ref.4 Ref.21		VAR_011387
	Natural variant	166	1	G → R in NPDB; also in patients with an intermediate form. Ref.26 Ref.27		VAR_060875
	Natural variant	176	1	I → N in NPDB. Ref.27		VAR_060876
	Natural variant	184	1	P → L in NPDA/NPDB; intermediate form. Ref.26		VAR_060877
	Natural variant	196	1	A → P in NPDB. Ref.21		VAR_060878
	Natural variant	200	1	R → C in NPDB. Ref.21		VAR_060879
	Natural variant	209	1	W → R in NPDA; results in less than 0.5% of wild-type activity. Ref.30		VAR_068435
	Natural variant	225	1	L → M in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. Ref.21		VAR_060880
	Natural variant	225	1	L → P in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. Ref.24 Ref.25		VAR_060881
	Natural variant	228	1	R → C in NPDB. Ref.21 Ref.29		VAR_060882
	Natural variant	228	1	R → H in NPDA/NPDB; intermediate form. Ref.26		VAR_060883
	Natural variant	232	1	G → D in NPDB. Ref.21		VAR_060884
	Natural variant	241	1	A → V in NPDA/NPDB; intermediate form. Ref.26		VAR_060885
	Natural variant	242	1	G → R in NPDB. Ref.15		VAR_005058
	Natural variant	244	1	W → C in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. Ref.24 Ref.25		VAR_060886
	Natural variant	245	1	G → S in NPDA and NPDB. Ref.21 Ref.23 Ref.29		VAR_060887
	Natural variant	246	1	E → K in NPDA. Ref.23		VAR_060888
	Natural variant	246	1	E → Q in NPDB; 30% residual activity. Ref.19		VAR_005059
	Natural variant	248	1	S → R in NPDA and NPDB; also found in patients with an intermediate form. Ref.21 Ref.22 Ref.26		VAR_015287
	Natural variant	251	1	D → E in NPDA/NPDB; intermediate form. Ref.26		VAR_060889
	Natural variant	251	1	D → H in NPDA; results in loss of activity. Ref.30		VAR_068436
	Natural variant	278	1	D → A in NPDA/NPDB; intermediate form. Ref.26		VAR_060890
	Natural variant	281	1	A → T in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. Ref.24 Ref.25		VAR_060891
	Natural variant	289	1	R → H in NPDB; also in patients with an intermediate form. Ref.21 Ref.26		VAR_060892
	Natural variant	292	1	Q → K in NPDA/NPDB; intermediate form. Ref.20 Ref.24 Ref.26		VAR_060893
	Natural variant	294	1	R → Q in NPDA. Ref.23		VAR_060894
	Natural variant	302	1	L → P in NPDA; in 23% of NPDA Ashkenazi Jewish patients. Ref.13		VAR_005060
	Natural variant	312	1	V → M in NPDB; results in 20% of wild-type activity. Ref.30		VAR_068437
	Natural variant	313	1	Y → H in NPDA. Ref.23		VAR_060895
	Natural variant	316	1	V → E. Corresponds to variant rs12575136 [ dbSNP | Ensembl ].		VAR_054642
	Natural variant	319	1	H → Y in NPDA. Ref.22		VAR_015288
	Natural variant	322	1	T → I. Ref.1 Ref.6 Corresponds to variant rs1050233 [ dbSNP | Ensembl ].		VAR_054643
	Natural variant	323	1	P → A in NPDB. Ref.21		VAR_060896
	Natural variant	330	1	P → R in NPDB. Ref.21 Ref.28		VAR_060897
	Natural variant	341	1	L → P in NPDA/NPDB; intermediate form. Ref.20 Ref.26		VAR_060898
	Natural variant	357	1	A → D in NPDB. Ref.21		VAR_060899
	Natural variant	367	1	Y → C in NPDA. Ref.29		VAR_060900
	Natural variant	371	1	P → S in NPDB. Ref.22		VAR_015289
	Natural variant	376	1	R → H in NPDB; also found in a patient with an intermediate form. Ref.21 Ref.26 Ref.29		VAR_060901
	Natural variant	376	1	R → L in NPDB. Ref.21		VAR_060902
	Natural variant	379	1	S → P in NPDB. Ref.21		VAR_060903
	Natural variant	382	1	M → I in NPDA and NPDB. Ref.15 Ref.24		VAR_005061
	Natural variant	383	1	N → S in NPDB. Ref.15		VAR_005062
	Natural variant	389	1	N → T in NPDA. Ref.17		VAR_005063
	Natural variant	390	1	Missing in NPDA. Ref.29		VAR_060904
	Natural variant	391	1	W → G in NPDB; low sphingomyelin degradation rates. Ref.16		VAR_005064
	Natural variant	413	1	A → V in NPDB. Ref.21		VAR_060905
	Natural variant	421	1	H → R in NPDA. Ref.29		VAR_060906
	Natural variant	421	1	H → Y in NPDB. Ref.21		VAR_015290
	Natural variant	425	1	H → 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.30		VAR_068438
	Natural variant	431	1	C → R in NPDB. Ref.21		VAR_060907
	Natural variant	432	1	L → P in NPDB. Ref.21		VAR_060908
	Natural variant	435	1	W → C in NPDB. Ref.21		VAR_060909
	Natural variant	436	1	S → R in NPDB. Ref.14		VAR_005065
	Natural variant	446	1	Y → C in NPDA. Ref.18		VAR_011388
	Natural variant	450	1	L → P in NPDA. Ref.23		VAR_060910
	Natural variant	451	1	A → D in NPDB. Ref.28		VAR_068439
	Natural variant	452	1	A → V in NPDB. Ref.21		VAR_060911
	Natural variant	456	1	G → D in NPDB. Ref.21		VAR_060912
	Natural variant	463	1	F → S in NPDA. Ref.22		VAR_015291
	Natural variant	467	1	Y → S in NPDA. Ref.29		VAR_060913
	Natural variant	474	1	R → W in NPDB; also in a patient with an intermediate form. Ref.21 Ref.26 Ref.29		VAR_060914
	Natural variant	475	1	P → L in NPDA and NPDB. Ref.21 Ref.22 Ref.23		VAR_015292
	Natural variant	480	1	F → L in NPDB. Ref.21		VAR_060915
	Natural variant	482	1	A → E in NPDA. Ref.29		VAR_060916
	Natural variant	485	1	A → V in NPDB. Ref.21		VAR_060917
	Natural variant	486	1	T → A in NPDB. Ref.29		VAR_060918
	Natural variant	488	1	Y → N in NPDB. Ref.21		VAR_060919
	Natural variant	494	1	G → S in NPDB. Ref.21		VAR_060920
	Natural variant	496	1	R → C in NPDB. Ref.21		VAR_060921
	Natural variant	496	1	R → H in NPDA. Ref.23		VAR_060922
	Natural variant	496	1	R → L in NPDA; in 32% of NPDA Ashkenazi Jewish patients. Ref.11 Ref.23		VAR_005066
	Natural variant	505	1	S → G. Ref.27		VAR_060923
	Natural variant	506	1	G → R. Ref.1 Ref.2 Ref.6 Ref.26 Corresponds to variant rs1050239 [ dbSNP | Ensembl ].		VAR_054644
	Natural variant	514	1	H → Q in NPDB. Ref.21		VAR_060924
	Natural variant	515	1	E → V in NPDB. Ref.21		VAR_060925
	Natural variant	517	1	Y → C in NPDA. Ref.23		VAR_060926
	Natural variant	520	1	N → S in NPDB. Ref.31		VAR_068440
	Natural variant	523	1	Q → H in NPDB; results in 64% of wild-type activity. Ref.30		VAR_068441
	Natural variant	533	1	W → R in NPDB; also in patients with an intermediate form. Ref.21 Ref.26		VAR_060927
	Natural variant	537	1	Y → H in NPDA. Ref.22		VAR_015293
	Natural variant	549	1	L → P in NPDB. Ref.21		VAR_060928
	Natural variant	563	1	D → Y in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains 6.8% residual enzyme activity. Ref.25		VAR_060929
	Natural variant	576	1	K → N in NPDB. Ref.21		VAR_060930
	Natural variant	577	1	G → S in NPDA; also in patients with an intermediate form. Ref.10 Ref.26		VAR_005067
	Natural variant	592	1	Missing in NPDA. Ref.29		VAR_060931
	Natural variant	600	1	R → H in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains about 10% residual enzyme activity. Ref.21 Ref.25		VAR_060932
	Natural variant	600	1	R → P in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains very low enzyme activity. Ref.21 Ref.25		VAR_060933
	Natural variant	608	1	Missing in NPDB; prevalent among NPDB patients from the North African Maghreb region. Ref.12 Ref.22 Ref.29		VAR_005068
Experimental info
	Sequence conflict	35 – 36	2	Missing in CAA42584. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (ASM-1) [UniParc]. Last modified March 3, 2009. Version 4. Checksum: C9888CB8359C42AC	FASTA	629	69,752
	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
	Isoform 2 (ASM-2) [UniParc]. Checksum: A5FC9FE28C0D3E42	FASTA	585	64,889
	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 LRYLSSVETQ EGKRKVHIIG HIPPGHCLKS WSWNYYRIVA RYENTLAAQF FGHTHVDEFE 430 440 450 460 470 480 VFYDEETLSR PLAVAFLAPS ATTYIGLNPG YRVYQIDGNY SGSSHVVLDH ETYILNLTQA 490 500 510 520 530 540 NIPGAIPHWQ LLYRARETYG LPNTLPTAWH NLVYRMRGDM QLFQTFWFLY HKGHPPSEPC 550 560 570 580 GTPCRLATLC AQLSARADSP ALCRHLMPDG SLPEAQSLWP RPLFC
	Isoform 3 (ASM-3) [UniParc]. Checksum: 093B405E0C0AE061	FASTA	573	63,511
	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 LRKVHIIGHI PPGHCLKSWS WNYYRIVARY ENTLAAQFFG HTHVDEFEVF YDEETLSRPL 430 440 450 460 470 480 AVAFLAPSAT TYIGLNPGYR VYQIDGNYSG SSHVVLDHET YILNLTQANI PGAIPHWQLL 490 500 510 520 530 540 YRARETYGLP NTLPTAWHNL VYRMRGDMQL FQTFWFLYHK GHPPSEPCGT PCRLATLCAQ 550 560 570 LSARADSPAL CRHLMPDGSL PEAQSLWPRP LFC

References

	« Hide 'large scale' referencesShow '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]	"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. , 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].
[6]	"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.
[7]	"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.
[8]	"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.
[9]	"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.
[10]	"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.
[11]	"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.
[12]	"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.
[13]	"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.
[14]	"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.
[15]	"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.
[16]	"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.
[17]	"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.
[18]	"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.
[19]	"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.
[20]	"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.
[21]	"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.
[22]	"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.
[23]	"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.
[24]	"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.
[25]	"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.
[26]	"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.
[27]	"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.
[28]	"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.
[29]	"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.
[30]	"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.
[31]	"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

GeneReviews

Mendelian genes sphingomyelin phosphodiesterase 1, acid lysosomal (SMPD1)

Leiden Open Variation Database (LOVD)

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. AC068733 Genomic DNA. No translation available. X52678 mRNA. Translation: CAA36901.1. X52679 mRNA. Translation: CAA36902.1.
IPI	IPI00218785. IPI00296461. IPI00971183.
PIR	S06958. A39825. S27009.
RefSeq	NP_000534.3. NM_000543.4. NP_001007594.2. NM_001007593.2.
UniGene	Hs.498173.
3D structure databases
ProteinModelPortal	P17405.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000340409.
PTM databases
PhosphoSite	P17405.
Polymorphism databases
DMDM	224471897.
Proteomic databases
PaxDb	P17405.
PRIDE	P17405.
Protocols and materials databases
DNASU	6609.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000342245; ENSP00000340409; ENSG00000166311.
GeneID	6609.
KEGG	hsa:6609.
Organism-specific databases
CTD	6609.
GeneCards	GC11P006411.
HGNC	HGNC:11120. SMPD1.
HPA	HPA001823.
MIM	257200. phenotype. 607608. gene. 607616. phenotype.
neXtProt	NX_P17405.
Orphanet	77292. Niemann-Pick disease type A. 77293. Niemann-Pick disease type B.
PharmGKB	PA35969.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG303902.
HOVERGEN	HBG004288.
InParanoid	P17405.
KO	K12350.
OrthoDB	EOG45DWNZ.
Enzyme and pathway databases
Pathway_Interaction_DB	ceramidepathway. Ceramide signaling pathway. il2_pi3kpathway. IL2 signaling events mediated by PI3K. tnfpathway. TNF receptor signaling pathway. trail_pathway. TRAIL signaling pathway.
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	P17405.
Bgee	P17405.
CleanEx	HS_SMPD1.
Genevestigator	P17405.
GermOnline	ENSG00000166311. Homo sapiens.
Family and domain databases
Gene3D	1.10.225.10. 1 hit.
InterPro	IPR004843. Metallo_PEstase_dom. IPR011001. Saposin-like. IPR008139. SaposinB. IPR011160. Sphingomy_PDE. [Graphical view]
Pfam	PF00149. Metallophos. 1 hit. [Graphical view]
PIRSF	PIRSF000948. Sphingomy_PDE. 1 hit.
SMART	SM00741. SapB. 1 hit. [Graphical view]
SUPFAM	SSF47862. Saposin_like. 1 hit.
PROSITE	PS50015. SAP_B. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P17405.
ChEMBL	CHEMBL2760.
ChiTaRS	SMPD1. human.
DrugBank	DB01151. Desipramine.
GenomeRNAi	6609.
NextBio	25729.
SOURCE	Search...

Entry information

Entry name

ASM_HUMAN

Accession

Primary (citable) accession number: P17405
Secondary accession number(s): P17406 , Q13811, Q16837, Q16841

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	March 3, 2009
Last modified:	May 1, 2013
This is version 152 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.