Q6ZPR5 (NSMA3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sphingomyelin phosphodiesterase 4
EC=3.1.4.12

Alternative name(s):
Neutral sphingomyelinase 3
Short name=nSMase-3
Short name=nSMase3
Neutral sphingomyelinase III

Gene names

Name:	Smpd4
Synonyms:	Kiaa1418

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	823 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Catalyzes the hydrolysis of membrane sphingomyelin to form phosphorylcholine and ceramide By similarity.
Catalytic activity	Sphingomyelin + H2O = N-acylsphingosine + choline phosphate.
Cofactor	Magnesium By similarity.
Enzyme regulation	Activated by phosphatidylserine and tumor necrosis factor (TNF). Inhibited by scyphostatin By similarity.
Subcellular location	Endoplasmic reticulum membrane; Single-pass membrane protein. Golgi apparatus membrane; Single-pass membrane protein By similarity.
Sequence caution	The sequence BAC98164.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Golgi apparatus Membrane
Coding sequence diversity	Alternative splicing
Domain	Transmembrane Transmembrane helix
Ligand	Magnesium Metal-binding
Molecular function	Hydrolase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	sphingomyelin catabolic process Inferred from sequence or structural similarity. Source: HGNC
Cellular component	Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW trans-Golgi network Inferred from sequence or structural similarity. Source: HGNC
Molecular function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW sphingomyelin phosphodiesterase D activity Inferred from sequence or structural similarity. Source: HGNC sphingomyelin phosphodiesterase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q6ZPR5-1)

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.

Isoform 2 (identifier: Q6ZPR5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     288-316: Missing.

Isoform 3 (identifier: Q6ZPR5-3)

The sequence of this isoform differs from the canonical sequence as follows:
     288-316: Missing.
     429-429: Missing.

Note: No experimental confirmation available.

Isoform 4 (identifier: Q6ZPR5-4)

The sequence of this isoform differs from the canonical sequence as follows:
     288-316: Missing.
     429-429: W → CLAPWSPYQHRGLR

Note: No experimental confirmation available.

Isoform 5 (identifier: Q6ZPR5-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-157: Missing.
     288-316: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 823	823	Sphingomyelin phosphodiesterase 4		PRO_0000273164
Regions
	Transmembrane	776 – 796	21	Helical; Potential
Amino acid modifications
	Modified residue	130	1	Phosphoserine By similarity
	Modified residue	349	1	Phosphoserine By similarity
	Modified residue	460	1	N6-acetyllysine By similarity
	Modified residue	665	1	Phosphothreonine By similarity
	Modified residue	749	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	1 – 157	157	Missing in isoform 5.		VSP_022484
	Alternative sequence	288 – 316	29	Missing in isoform 2, isoform 3, isoform 4 and isoform 5.		VSP_022485
	Alternative sequence	429	1	Missing in isoform 3.		VSP_022486
	Alternative sequence	429	1	W → CLAPWSPYQHRGLR in isoform 4.		VSP_022487
Experimental info
	Sequence conflict	7	1	Q → P in AAH26767. Ref.3
	Sequence conflict	15	1	S → T in BAC27221. Ref.2
	Sequence conflict	141	1	P → T in BAC27512. Ref.2
	Sequence conflict	195	1	F → V in AAH26767. Ref.3
	Sequence conflict	368	1	V → E in BAB31737. Ref.2
	Sequence conflict	732	1	F → Y in BAC27221. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 3C082D335608BA70	FASTA	823	93,276
	10 20 30 40 50 60 MAFPHLQQPS FLLASLKADS INKPFAQRCQ DLVKVIEDFP AKELHAVFPW LVESIFGSLD 70 80 90 100 110 120 GVLVGWNLRC LQGRVNPVEY STAMEFLDPS GPMMKLVYKL QAEDYNFDFP VSCLPGPVKA 130 140 150 160 170 180 SIQENVLPDS PLYHNKVQFP PTGGLGLNLA LNPFEYYMFY FALSLISQKP MSMTLHVRTS 190 200 210 220 230 240 DCAYFTLVDR YLSWFLPTEG SVPPPLCSSP GGSSPSPAPR TPAMPFASYG LHTSLLKRHI 250 260 270 280 290 300 SHQTSVNADP ASHEIWRSET LLQVFVEMWL HHYSLEMYQK MQSPHAKLEV LHYRLTVSSA 310 320 330 340 350 360 LHSPAQPSLQ ALHAYQESFT PTEEHVLVVR LLLKHLHAFA NSLKPDQASP SAHSHATSPL 370 380 390 400 410 420 EEFKRAAVPR FVQQKLYVFL QHCFGHWPLD ATFRAVLEMW LSYLQPWRYA PEKQAQGSDP 430 440 450 460 470 480 QPRCVSEKWA PFIQENLLMY TKLFVSFLNR ALRTDLVSPK NALMVFRVAK VFAQPNLAEM 490 500 510 520 530 540 IQKGEQLFLE PELIIPHRQH RLFTVTTSFL SPWPPVVTDA SFKVKSHVYS LEGQDCKYTP 550 560 570 580 590 600 MFGPEIRTLV LRLAQLITQA KQTAKSISDQ YVESPTGRSF LSWLTFGLTD TNSCYPANDL 610 620 630 640 650 660 DEIGQDSIRK TDEYLEKALE YLRQIFRLSE AQLAQLTLAL GSARDENGKQ QLPDCIVGEE 670 680 690 700 710 720 GLILTPLGRY QIINGLRRFE IEYQGDLELQ PIRSYEITSL VRALFRLSSA INRRFAGQMA 730 740 750 760 770 780 ALCSRNDFLG SFCRYHLTEP ALSNRHLLSP VGRRQVTNPA RGPRLSLRFL GSYRTLLLLL 790 800 810 820 MAFFVASLFC IGPLSCSLLL VLGYVLYAIA MTLLTERGKL HQL
	Isoform 2 [UniParc]. Checksum: 326A83F65CEF2603	FASTA	794	90,063
	10 20 30 40 50 60 MAFPHLQQPS FLLASLKADS INKPFAQRCQ DLVKVIEDFP AKELHAVFPW LVESIFGSLD 70 80 90 100 110 120 GVLVGWNLRC LQGRVNPVEY STAMEFLDPS GPMMKLVYKL QAEDYNFDFP VSCLPGPVKA 130 140 150 160 170 180 SIQENVLPDS PLYHNKVQFP PTGGLGLNLA LNPFEYYMFY FALSLISQKP MSMTLHVRTS 190 200 210 220 230 240 DCAYFTLVDR YLSWFLPTEG SVPPPLCSSP GGSSPSPAPR TPAMPFASYG LHTSLLKRHI 250 260 270 280 290 300 SHQTSVNADP ASHEIWRSET LLQVFVEMWL HHYSLEMYQK MQSPHAKESF TPTEEHVLVV 310 320 330 340 350 360 RLLLKHLHAF ANSLKPDQAS PSAHSHATSP LEEFKRAAVP RFVQQKLYVF LQHCFGHWPL 370 380 390 400 410 420 DATFRAVLEM WLSYLQPWRY APEKQAQGSD PQPRCVSEKW APFIQENLLM YTKLFVSFLN 430 440 450 460 470 480 RALRTDLVSP KNALMVFRVA KVFAQPNLAE MIQKGEQLFL EPELIIPHRQ HRLFTVTTSF 490 500 510 520 530 540 LSPWPPVVTD ASFKVKSHVY SLEGQDCKYT PMFGPEIRTL VLRLAQLITQ AKQTAKSISD 550 560 570 580 590 600 QYVESPTGRS FLSWLTFGLT DTNSCYPAND LDEIGQDSIR KTDEYLEKAL EYLRQIFRLS 610 620 630 640 650 660 EAQLAQLTLA LGSARDENGK QQLPDCIVGE EGLILTPLGR YQIINGLRRF EIEYQGDLEL 670 680 690 700 710 720 QPIRSYEITS LVRALFRLSS AINRRFAGQM AALCSRNDFL GSFCRYHLTE PALSNRHLLS 730 740 750 760 770 780 PVGRRQVTNP ARGPRLSLRF LGSYRTLLLL LMAFFVASLF CIGPLSCSLL LVLGYVLYAI 790 AMTLLTERGK LHQL
	Isoform 3 [UniParc]. Checksum: 78B7FB3C9954C1B1	FASTA	793	89,877
	10 20 30 40 50 60 MAFPHLQQPS FLLASLKADS INKPFAQRCQ DLVKVIEDFP AKELHAVFPW LVESIFGSLD 70 80 90 100 110 120 GVLVGWNLRC LQGRVNPVEY STAMEFLDPS GPMMKLVYKL QAEDYNFDFP VSCLPGPVKA 130 140 150 160 170 180 SIQENVLPDS PLYHNKVQFP PTGGLGLNLA LNPFEYYMFY FALSLISQKP MSMTLHVRTS 190 200 210 220 230 240 DCAYFTLVDR YLSWFLPTEG SVPPPLCSSP GGSSPSPAPR TPAMPFASYG LHTSLLKRHI 250 260 270 280 290 300 SHQTSVNADP ASHEIWRSET LLQVFVEMWL HHYSLEMYQK MQSPHAKESF TPTEEHVLVV 310 320 330 340 350 360 RLLLKHLHAF ANSLKPDQAS PSAHSHATSP LEEFKRAAVP RFVQQKLYVF LQHCFGHWPL 370 380 390 400 410 420 DATFRAVLEM WLSYLQPWRY APEKQAQGSD PQPRCVSEKA PFIQENLLMY TKLFVSFLNR 430 440 450 460 470 480 ALRTDLVSPK NALMVFRVAK VFAQPNLAEM IQKGEQLFLE PELIIPHRQH RLFTVTTSFL 490 500 510 520 530 540 SPWPPVVTDA SFKVKSHVYS LEGQDCKYTP MFGPEIRTLV LRLAQLITQA KQTAKSISDQ 550 560 570 580 590 600 YVESPTGRSF LSWLTFGLTD TNSCYPANDL DEIGQDSIRK TDEYLEKALE YLRQIFRLSE 610 620 630 640 650 660 AQLAQLTLAL GSARDENGKQ QLPDCIVGEE GLILTPLGRY QIINGLRRFE IEYQGDLELQ 670 680 690 700 710 720 PIRSYEITSL VRALFRLSSA INRRFAGQMA ALCSRNDFLG SFCRYHLTEP ALSNRHLLSP 730 740 750 760 770 780 VGRRQVTNPA RGPRLSLRFL GSYRTLLLLL MAFFVASLFC IGPLSCSLLL VLGYVLYAIA 790 MTLLTERGKL HQL
	Isoform 4 [UniParc]. Checksum: 2DF7496773312AFD	FASTA	807	91,543
	10 20 30 40 50 60 MAFPHLQQPS FLLASLKADS INKPFAQRCQ DLVKVIEDFP AKELHAVFPW LVESIFGSLD 70 80 90 100 110 120 GVLVGWNLRC LQGRVNPVEY STAMEFLDPS GPMMKLVYKL QAEDYNFDFP VSCLPGPVKA 130 140 150 160 170 180 SIQENVLPDS PLYHNKVQFP PTGGLGLNLA LNPFEYYMFY FALSLISQKP MSMTLHVRTS 190 200 210 220 230 240 DCAYFTLVDR YLSWFLPTEG SVPPPLCSSP GGSSPSPAPR TPAMPFASYG LHTSLLKRHI 250 260 270 280 290 300 SHQTSVNADP ASHEIWRSET LLQVFVEMWL HHYSLEMYQK MQSPHAKESF TPTEEHVLVV 310 320 330 340 350 360 RLLLKHLHAF ANSLKPDQAS PSAHSHATSP LEEFKRAAVP RFVQQKLYVF LQHCFGHWPL 370 380 390 400 410 420 DATFRAVLEM WLSYLQPWRY APEKQAQGSD PQPRCVSEKC LAPWSPYQHR GLRAPFIQEN 430 440 450 460 470 480 LLMYTKLFVS FLNRALRTDL VSPKNALMVF RVAKVFAQPN LAEMIQKGEQ LFLEPELIIP 490 500 510 520 530 540 HRQHRLFTVT TSFLSPWPPV VTDASFKVKS HVYSLEGQDC KYTPMFGPEI RTLVLRLAQL 550 560 570 580 590 600 ITQAKQTAKS ISDQYVESPT GRSFLSWLTF GLTDTNSCYP ANDLDEIGQD SIRKTDEYLE 610 620 630 640 650 660 KALEYLRQIF RLSEAQLAQL TLALGSARDE NGKQQLPDCI VGEEGLILTP LGRYQIINGL 670 680 690 700 710 720 RRFEIEYQGD LELQPIRSYE ITSLVRALFR LSSAINRRFA GQMAALCSRN DFLGSFCRYH 730 740 750 760 770 780 LTEPALSNRH LLSPVGRRQV TNPARGPRLS LRFLGSYRTL LLLLMAFFVA SLFCIGPLSC 790 800 SLLLVLGYVL YAIAMTLLTE RGKLHQL
	Isoform 5 [UniParc]. Checksum: 188248B501580BB4	FASTA	637	72,493
	10 20 30 40 50 60 MFYFALSLIS QKPMSMTLHV RTSDCAYFTL VDRYLSWFLP TEGSVPPPLC SSPGGSSPSP 70 80 90 100 110 120 APRTPAMPFA SYGLHTSLLK RHISHQTSVN ADPASHEIWR SETLLQVFVE MWLHHYSLEM 130 140 150 160 170 180 YQKMQSPHAK ESFTPTEEHV LVVRLLLKHL HAFANSLKPD QASPSAHSHA TSPLEEFKRA 190 200 210 220 230 240 AVPRFVQQKL YVFLQHCFGH WPLDATFRAV LEMWLSYLQP WRYAPEKQAQ GSDPQPRCVS 250 260 270 280 290 300 EKWAPFIQEN LLMYTKLFVS FLNRALRTDL VSPKNALMVF RVAKVFAQPN LAEMIQKGEQ 310 320 330 340 350 360 LFLEPELIIP HRQHRLFTVT TSFLSPWPPV VTDASFKVKS HVYSLEGQDC KYTPMFGPEI 370 380 390 400 410 420 RTLVLRLAQL ITQAKQTAKS ISDQYVESPT GRSFLSWLTF GLTDTNSCYP ANDLDEIGQD 430 440 450 460 470 480 SIRKTDEYLE KALEYLRQIF RLSEAQLAQL TLALGSARDE NGKQQLPDCI VGEEGLILTP 490 500 510 520 530 540 LGRYQIINGL RRFEIEYQGD LELQPIRSYE ITSLVRALFR LSSAINRRFA GQMAALCSRN 550 560 570 580 590 600 DFLGSFCRYH LTEPALSNRH LLSPVGRRQV TNPARGPRLS LRFLGSYRTL LLLLMAFFVA 610 620 630 SLFCIGPLSC SLLLVLGYVL YAIAMTLLTE RGKLHQL

References

[1]	"Prediction of the coding sequences of mouse homologues of KIAA gene: III. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries." Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Nagase T., Ohara O., Koga H. DNA Res. 10:167-180(2003) [PubMed: 14621295] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Embryonic tail.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3; 4 AND 5). Strain: C57BL/6J. Tissue: Cerebellum, Head, Testis and Thymus.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Strain: FVB/N. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK129354 mRNA. Translation: BAC98164.1. Different initiation. AK019466 mRNA. Translation: BAB31737.1. AK031029 mRNA. Translation: BAC27221.1. AK031685 mRNA. Translation: BAC27512.1. AK035892 mRNA. Translation: BAC29229.1. AK164234 mRNA. Translation: BAE37694.1. AK164456 mRNA. Translation: BAE37796.1. BC026767 mRNA. Translation: AAH26767.1.
IPI	IPI00273052. IPI00420541. IPI00828457. IPI00828579. IPI00828632.
RefSeq	NP_001158081.1. NM_001164609.1. NP_001158082.1. NM_001164610.1. NP_001158083.1. NM_001164611.1. NP_084221.2. NM_029945.3.
UniGene	Mm.34659.
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	Q6ZPR5.
PTM databases
PhosphoSite	Q6ZPR5.
Proteomic databases
PRIDE	Q6ZPR5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000006053; ENSMUSP00000006053; ENSMUSG00000005899. ENSMUST00000090159; ENSMUSP00000087620; ENSMUSG00000005899. ENSMUST00000163476; ENSMUSP00000131867; ENSMUSG00000005899. ENSMUST00000165363; ENSMUSP00000130720; ENSMUSG00000005899.
GeneID	77626.
KEGG	mmu:77626.
UCSC	uc007yll.2. mouse. uc007ylm.2. mouse. uc007yln.2. mouse. uc007ylo.2. mouse. uc007ylp.2. mouse.
Organism-specific databases
CTD	55627.
MGI	MGI:1924876. Smpd4.
Rouge	Search...
Phylogenomic databases
eggNOG	roNOG08396.
GeneTree	ENSGT00390000006044.
HOVERGEN	HBG082060.
InParanoid	Q6ZPR5.
OMA	PHRQHRL.
OrthoDB	EOG4S7JPM.
PhylomeDB	Q6ZPR5.
Gene expression databases
ArrayExpress	Q6ZPR5.
Bgee	Q6ZPR5.
CleanEx	MM_SMPD4.
Genevestigator	Q6ZPR5.
Family and domain databases
InterPro	IPR024129. Sphingomy_SMPD4. [Graphical view]
KO	K12353.
PANTHER	PTHR12988. PTHR12988. 1 hit.
ProtoNet	Search...
Other
NextBio	347250.
SOURCE	Search...

Entry information

Entry name

NSMA3_MOUSE

Accession

Primary (citable) accession number: Q6ZPR5
Secondary accession number(s): Q3TPE0 , Q3TPP1, Q8CBJ5, Q8CD12, Q8CD83, Q8R0J3, Q9CX74

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 23, 2007
Last sequence update:	January 23, 2007
Last modified:	November 16, 2011
This is version 50 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program