ASM_MOUSE
ID ASM_MOUSE Reviewed; 627 AA.
AC Q04519; Q3UL52;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Sphingomyelin phosphodiesterase;
DE EC=3.1.4.12 {ECO:0000269|PubMed:27435900, ECO:0000269|PubMed:8702487};
DE EC=3.1.4.3 {ECO:0000250|UniProtKB:P17405};
DE AltName: Full=Acid sphingomyelinase;
DE Short=ASMase;
DE Flags: Precursor;
GN Name=Smpd1 {ECO:0000303|PubMed:27435900};
GN Synonyms=Asm {ECO:0000303|PubMed:27435900};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Liver;
RX PubMed=1292508; DOI=10.1515/bchm3.1992.373.2.1233;
RA Newrzella D., Stoffel W.;
RT "Molecular cloning of the acid sphingomyelinase of the mouse and the
RT organization and complete nucleotide sequence of the gene.";
RL Biol. Chem. Hoppe-Seyler 373:1233-1238(1992).
RN [2]
RP SEQUENCE REVISION TO 224-225 AND 384.
RA Hofmann K.;
RL Submitted (APR-1994) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Hippocampus, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=8706124; DOI=10.1016/s0092-8674(00)80091-4;
RA Santana P., Pena L.A., Haimovitz-Friedman A., Martin S., Green D.,
RA McLoughlin M., Cordon-Cardo C., Schuchman E.H., Fuks Z., Kolesnick R.;
RT "Acid sphingomyelinase-deficient human lymphoblasts and mice are defective
RT in radiation-induced apoptosis.";
RL Cell 86:189-199(1996).
RN [6]
RP CATALYTIC ACTIVITY, COFACTOR, AND SUBCELLULAR LOCATION.
RX PubMed=8702487; DOI=10.1074/jbc.271.31.18431;
RA Schissel S.L., Schuchman E.H., Williams K.J., Tabas I.;
RT "Zn2+-stimulated sphingomyelinase is secreted by many cell types and is a
RT product of the acid sphingomyelinase gene.";
RL J. Biol. Chem. 271:18431-18436(1996).
RN [7]
RP FUNCTION, AND COFACTOR.
RX PubMed=9660788; DOI=10.1074/jbc.273.29.18250;
RA Schissel S.L., Keesler G.A., Schuchman E.H., Williams K.J., Tabas I.;
RT "The cellular trafficking and zinc dependence of secretory and lysosomal
RT sphingomyelinase, two products of the acid sphingomyelinase gene.";
RL J. Biol. Chem. 273:18250-18259(1998).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12563314; DOI=10.1038/nm823;
RA Grassme H., Jendrossek V., Riehle A., von Kuerthy G., Berger J.,
RA Schwarz H., Weller M., Kolesnick R., Gulbins E.;
RT "Host defense against Pseudomonas aeruginosa requires ceramide-rich
RT membrane rafts.";
RL Nat. Med. 9:322-330(2003).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.54 ANGSTROMS) OF 84-611 IN COMPLEXES WITH ZINC AND
RP INHIBITOR, SUBUNIT, DISULFIDE BONDS, GLYCOSYLATION AT ASN-84; ASN-173;
RP ASN-333; ASN-393 AND ASN-518, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND
RP MUTAGENESIS OF VAL-128; VAL-143; HIS-280; TRP-283; HIS-317; PRO-321;
RP PHE-388 AND LEU-391.
RX PubMed=27435900; DOI=10.1038/ncomms12196;
RA Gorelik A., Illes K., Heinz L.X., Superti-Furga G., Nagar B.;
RT "Crystal structure of mammalian acid sphingomyelinase.";
RL Nat. Commun. 7:12196-12196(2016).
CC -!- FUNCTION: Converts sphingomyelin to ceramide (PubMed:9660788,
CC PubMed:8706124). Exists as two enzymatic forms that arise from
CC alternative trafficking of a single protein precursor, one that is
CC targeted to the endolysosomal compartment, whereas the other is
CC released extracellularly. However, in response to various forms of
CC stress, lysosomal exocytosis may represent a major source of the
CC secretory form (By similarity). {ECO:0000250|UniProtKB:P17405,
CC ECO:0000269|PubMed:8706124, ECO:0000269|PubMed:9660788}.
CC -!- FUNCTION: In the lysosomes, converts sphingomyelin to ceramide. Plays
CC an important role in the export of cholesterol from the
CC intraendolysosomal membranes. Also has phospholipase C activities
CC toward 1,2-diacylglycerolphosphocholine and 1,2-
CC diacylglycerolphosphoglycerol (PubMed:27435900). Modulates stress-
CC induced apoptosis through the production of ceramide (PubMed:8706124).
CC {ECO:0000269|PubMed:27435900, ECO:0000269|PubMed:8706124}.
CC -!- FUNCTION: When secreted, modulates cell signaling with its ability to
CC reorganize the plasma membrane by converting sphingomyelin to ceramide.
CC Secreted form is increased in response to stress and inflammatory
CC mediators such as IL1B, IFNG or TNF as well as upon infection with
CC bacteria and viruses. Produces the release of ceramide in the outer
CC leaflet of the plasma membrane playing a central role in host defense.
CC Ceramide reorganizes these rafts into larger signaling platforms that
CC are required to internalize P. aeruginosa, induce apoptosis and
CC regulate the cytokine response in infected cells. In wounded cells, the
CC lysosomal form is released extracellularly in the presence of Ca(2+)
CC and promotes endocytosis and plasma membrane repair.
CC {ECO:0000250|UniProtKB:P17405}.
CC -!- FUNCTION: (Microbial infection) Secretion is activated by bacteria such
CC as P. aeruginos, this activation results in the release of ceramide in
CC the outer leaflet of the plasma membrane which facilitates the
CC infection. {ECO:0000269|PubMed:12563314}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a sphingomyelin + H2O = an N-acylsphing-4-enine + H(+) +
CC phosphocholine; Xref=Rhea:RHEA:19253, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17636, ChEBI:CHEBI:52639,
CC ChEBI:CHEBI:295975; EC=3.1.4.12;
CC Evidence={ECO:0000269|PubMed:27435900, ECO:0000269|PubMed:8702487,
CC ECO:0000269|PubMed:8706124, ECO:0000269|PubMed:9660788};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19254;
CC Evidence={ECO:0000269|PubMed:8706124, ECO:0000305|PubMed:27435900};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(octadecanoyl)-sphing-4-enine-1-phosphocholine = H(+)
CC + N-octadecanoylsphing-4-enine + phosphocholine;
CC Xref=Rhea:RHEA:54284, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:72961, ChEBI:CHEBI:83358, ChEBI:CHEBI:295975;
CC Evidence={ECO:0000250|UniProtKB:P17405};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54285;
CC Evidence={ECO:0000250|UniProtKB:P17405};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1,2-diacyl-
CC sn-glycerol + H(+) + phosphocholine; Xref=Rhea:RHEA:10604,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17815,
CC ChEBI:CHEBI:57643, ChEBI:CHEBI:295975; EC=3.1.4.3;
CC Evidence={ECO:0000250|UniProtKB:P17405};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10605;
CC Evidence={ECO:0000250|UniProtKB:P17405};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1,2-
CC dihexadecanoyl-sn-glycerol + H(+) + phosphocholine;
CC Xref=Rhea:RHEA:45304, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:72999, ChEBI:CHEBI:82929, ChEBI:CHEBI:295975;
CC Evidence={ECO:0000250|UniProtKB:P17405};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45305;
CC Evidence={ECO:0000250|UniProtKB:P17405};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:8702487, ECO:0000269|PubMed:9660788};
CC Note=Binds 2 Zn(2+) ions per subunit (PubMed:27435900).;
CC -!- ACTIVITY REGULATION: Hydrolysis of liposomal sphingomyelin is
CC stimulated by incorporation of diacylglycerol (DAG), ceramide and free
CC fatty acids into the liposomal membranes. Phosphatidylcholine
CC hydrolysis is inhibited by incorporation of cholesterol, ceramide, DAG,
CC monoacylglycerol and fatty acids. {ECO:0000250|UniProtKB:P17405}.
CC -!- SUBUNIT: Monomer (PubMed:27435900). Interacts with SORT1; the
CC interaction is required for SMPD1 targeting to lysosomes (By
CC similarity). {ECO:0000250|UniProtKB:P17405,
CC ECO:0000269|PubMed:27435900}.
CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000250|UniProtKB:P17405}. Lipid
CC droplet {ECO:0000250|UniProtKB:P17405}. Secreted
CC {ECO:0000269|PubMed:8702487}. Note=The secreted form is induced in a
CC time- and dose-dependent by IL1B and TNF as well as stress and viral
CC infection. This increase of the secreted form seems to be due to
CC exocytosis of the lysosomal form and is Ca(2+)-dependent. Secretion is
CC dependent of phosphorylation at Ser-506. Secretion is induced by
CC inflammatory mediators such as IL1B, IFNG or TNF as well as infection
CC with bacteria and viruses. {ECO:0000250|UniProtKB:P17405}.
CC -!- PTM: Proteolytically processed. Mature lysosomal form arises from C-
CC terminal proteolytic processing of pro-sphingomyelin phosphodiesterase.
CC {ECO:0000250|UniProtKB:P17405}.
CC -!- PTM: Both lysosomal and secreted forms are glycosylated but they show a
CC differential pattern of glycosylation. {ECO:0000250|UniProtKB:P17405}.
CC -!- PTM: Phosphorylated at Ser-506 by PRKCD upon stress stimuli.
CC Phosphorylation is required for secretion.
CC {ECO:0000250|UniProtKB:P17405}.
CC -!- DISRUPTION PHENOTYPE: Mutants infected with Pseudomonas aeruginosa die
CC within 7 days whereas all wild-type mice survive the infection
CC (PubMed:12563314). Mutants are defective in radiation-induced apoptosis
CC (PubMed:8706124). {ECO:0000269|PubMed:12563314,
CC ECO:0000269|PubMed:8706124}.
CC -!- MISCELLANEOUS: There are two types of sphingomyelinases: ASM (acid),
CC and NSM (neutral).
CC -!- SIMILARITY: Belongs to the acid sphingomyelinase family. {ECO:0000305}.
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DR EMBL; Z14252; CAA78619.1; -; mRNA.
DR EMBL; Z14132; CAA78506.1; -; Genomic_DNA.
DR EMBL; AK088147; BAC40171.1; -; mRNA.
DR EMBL; AK145534; BAE26489.1; -; mRNA.
DR EMBL; AK145702; BAE26598.1; -; mRNA.
DR EMBL; AK164167; BAE37659.1; -; mRNA.
DR EMBL; BC011304; AAH11304.1; -; mRNA.
DR CCDS; CCDS21653.1; -.
DR PIR; A58720; S27393.
DR RefSeq; NP_035551.1; NM_011421.2.
DR PDB; 5FI9; X-ray; 2.54 A; A/B=84-611.
DR PDB; 5FIB; X-ray; 2.80 A; A/B=84-611.
DR PDB; 5FIC; X-ray; 2.80 A; A/B/C/D=84-611.
DR PDB; 5HQN; X-ray; 2.60 A; A/B=165-627.
DR PDBsum; 5FI9; -.
DR PDBsum; 5FIB; -.
DR PDBsum; 5FIC; -.
DR PDBsum; 5HQN; -.
DR AlphaFoldDB; Q04519; -.
DR SMR; Q04519; -.
DR BioGRID; 203345; 3.
DR STRING; 10090.ENSMUSP00000042187; -.
DR ChEMBL; CHEMBL4295802; -.
DR GlyGen; Q04519; 6 sites.
DR iPTMnet; Q04519; -.
DR PhosphoSitePlus; Q04519; -.
DR EPD; Q04519; -.
DR MaxQB; Q04519; -.
DR PaxDb; Q04519; -.
DR PeptideAtlas; Q04519; -.
DR PRIDE; Q04519; -.
DR ProteomicsDB; 281814; -.
DR Antibodypedia; 1065; 300 antibodies from 31 providers.
DR DNASU; 20597; -.
DR Ensembl; ENSMUST00000046983; ENSMUSP00000042187; ENSMUSG00000037049.
DR GeneID; 20597; -.
DR KEGG; mmu:20597; -.
DR UCSC; uc009iyf.2; mouse.
DR CTD; 6609; -.
DR MGI; MGI:98325; Smpd1.
DR VEuPathDB; HostDB:ENSMUSG00000037049; -.
DR eggNOG; KOG3770; Eukaryota.
DR GeneTree; ENSGT00950000183182; -.
DR HOGENOM; CLU_014743_3_1_1; -.
DR InParanoid; Q04519; -.
DR OMA; WPTEACA; -.
DR OrthoDB; 1142100at2759; -.
DR PhylomeDB; Q04519; -.
DR TreeFam; TF313674; -.
DR BRENDA; 3.1.4.12; 3474.
DR Reactome; R-MMU-1660662; Glycosphingolipid metabolism.
DR BioGRID-ORCS; 20597; 10 hits in 75 CRISPR screens.
DR ChiTaRS; Smpd1; mouse.
DR PRO; PR:Q04519; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q04519; protein.
DR Bgee; ENSMUSG00000037049; Expressed in choroid plexus of fourth ventricle and 262 other tissues.
DR Genevisible; Q04519; MM.
DR GO; GO:0036019; C:endolysosome; ISS:UniProtKB.
DR GO; GO:0005768; C:endosome; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0042599; C:lamellar body; ISO:MGI.
DR GO; GO:0005811; C:lipid droplet; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0061750; F:acid sphingomyelin phosphodiesterase activity; IDA:UniProtKB.
DR GO; GO:0016798; F:hydrolase activity, acting on glycosyl bonds; IEA:UniProtKB-KW.
DR GO; GO:0034480; F:phosphatidylcholine phospholipase C activity; IEA:RHEA.
DR GO; GO:0008081; F:phosphoric diester hydrolase activity; IBA:GO_Central.
DR GO; GO:0004767; F:sphingomyelin phosphodiesterase activity; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0071277; P:cellular response to calcium ion; ISS:UniProtKB.
DR GO; GO:0034644; P:cellular response to UV; ISS:UniProtKB.
DR GO; GO:0046513; P:ceramide biosynthetic process; IMP:UniProtKB.
DR GO; GO:0006672; P:ceramide metabolic process; IMP:MGI.
DR GO; GO:0008203; P:cholesterol metabolic process; IMP:MGI.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; ISO:MGI.
DR GO; GO:0001778; P:plasma membrane repair; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0045807; P:positive regulation of endocytosis; ISS:UniProtKB.
DR GO; GO:0035307; P:positive regulation of protein dephosphorylation; ISO:MGI.
DR GO; GO:0042220; P:response to cocaine; ISO:MGI.
DR GO; GO:0070555; P:response to interleukin-1; ISS:UniProtKB.
DR GO; GO:0010212; P:response to ionizing radiation; IMP:UniProtKB.
DR GO; GO:0034612; P:response to tumor necrosis factor; ISS:UniProtKB.
DR GO; GO:0034340; P:response to type I interferon; ISS:UniProtKB.
DR GO; GO:0009615; P:response to virus; ISS:UniProtKB.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0006685; P:sphingomyelin catabolic process; IMP:MGI.
DR GO; GO:0023021; P:termination of signal transduction; ISO:MGI.
DR GO; GO:0046718; P:viral entry into host cell; ISS:UniProtKB.
DR GO; GO:0042060; P:wound healing; ISS:UniProtKB.
DR CDD; cd00842; MPP_ASMase; 1.
DR Gene3D; 3.60.21.10; -; 1.
DR InterPro; IPR045473; ASM_C.
DR InterPro; IPR041805; ASMase/PPN1_MPP.
DR InterPro; IPR004843; Calcineurin-like_PHP_ApaH.
DR InterPro; IPR029052; Metallo-depent_PP-like.
DR InterPro; IPR011001; Saposin-like.
DR InterPro; IPR008139; SaposinB_dom.
DR InterPro; IPR011160; Sphingomy_PDE.
DR Pfam; PF19272; ASMase_C; 1.
DR Pfam; PF00149; Metallophos; 1.
DR PIRSF; PIRSF000948; Sphingomy_PDE; 1.
DR SMART; SM00741; SapB; 1.
DR SUPFAM; SSF47862; SSF47862; 1.
DR SUPFAM; SSF56300; SSF56300; 1.
DR PROSITE; PS50015; SAP_B; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; Glycoprotein; Glycosidase; Hydrolase;
KW Lipid droplet; Lipid metabolism; Lysosome; Metal-binding; Phosphoprotein;
KW Reference proteome; Secreted; Signal; Zinc.
FT SIGNAL 1..44
FT /evidence="ECO:0000255"
FT CHAIN 45..627
FT /note="Sphingomyelin phosphodiesterase"
FT /id="PRO_0000002324"
FT DOMAIN 83..167
FT /note="Saposin B-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT BINDING 204
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:27435900,
FT ECO:0007744|PDB:5FI9, ECO:0007744|PDB:5FIB,
FT ECO:0007744|PDB:5FIC, ECO:0007744|PDB:5HQN"
FT BINDING 206
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:27435900,
FT ECO:0007744|PDB:5FI9, ECO:0007744|PDB:5FIB,
FT ECO:0007744|PDB:5FIC, ECO:0007744|PDB:5HQN"
FT BINDING 276
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:27435900,
FT ECO:0007744|PDB:5FI9, ECO:0007744|PDB:5FIB,
FT ECO:0007744|PDB:5FIC, ECO:0007744|PDB:5HQN"
FT BINDING 276
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:27435900,
FT ECO:0007744|PDB:5FI9, ECO:0007744|PDB:5FIB,
FT ECO:0007744|PDB:5FIC, ECO:0007744|PDB:5HQN"
FT BINDING 316
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:27435900,
FT ECO:0007744|PDB:5FI9, ECO:0007744|PDB:5FIB,
FT ECO:0007744|PDB:5FIC, ECO:0007744|PDB:5HQN"
FT BINDING 423
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:27435900,
FT ECO:0007744|PDB:5FI9, ECO:0007744|PDB:5FIB,
FT ECO:0007744|PDB:5FIC, ECO:0007744|PDB:5HQN"
FT BINDING 455
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:27435900,
FT ECO:0007744|PDB:5FI9, ECO:0007744|PDB:5FIB,
FT ECO:0007744|PDB:5FIC, ECO:0007744|PDB:5HQN"
FT BINDING 457
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0007744|PDB:5FI9, ECO:0007744|PDB:5FIB,
FT ECO:0007744|PDB:5FIC, ECO:0007744|PDB:5HQN"
FT MOD_RES 506
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P17405"
FT CARBOHYD 84
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT ECO:0000269|PubMed:27435900, ECO:0007744|PDB:5FI9,
FT ECO:0007744|PDB:5FIB"
FT CARBOHYD 173
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT ECO:0000269|PubMed:27435900, ECO:0007744|PDB:5FI9,
FT ECO:0007744|PDB:5FIB, ECO:0007744|PDB:5HQN"
FT CARBOHYD 333
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT ECO:0000269|PubMed:27435900, ECO:0007744|PDB:5FI9,
FT ECO:0007744|PDB:5FIB, ECO:0007744|PDB:5HQN"
FT CARBOHYD 393
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT ECO:0000269|PubMed:27435900, ECO:0007744|PDB:5FI9,
FT ECO:0007744|PDB:5FIB, ECO:0007744|PDB:5FIC,
FT ECO:0007744|PDB:5HQN"
FT CARBOHYD 518
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT ECO:0000269|PubMed:27435900, ECO:0007744|PDB:5FI9,
FT ECO:0007744|PDB:5FIB, ECO:0007744|PDB:5FIC,
FT ECO:0007744|PDB:5HQN"
FT CARBOHYD 611
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT DISULFID 87..163
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT ECO:0000269|PubMed:27435900, ECO:0007744|PDB:5FI9,
FT ECO:0007744|PDB:5FIB, ECO:0007744|PDB:5FIC,
FT ECO:0007744|PDB:5HQN"
FT DISULFID 90..155
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT ECO:0000269|PubMed:27435900, ECO:0007744|PDB:5FI9,
FT ECO:0007744|PDB:5FIB, ECO:0007744|PDB:5FIC,
FT ECO:0007744|PDB:5HQN"
FT DISULFID 118..129
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT ECO:0000269|PubMed:27435900, ECO:0007744|PDB:5FI9,
FT ECO:0007744|PDB:5FIB, ECO:0007744|PDB:5FIC,
FT ECO:0007744|PDB:5HQN"
FT DISULFID 219..224
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT ECO:0000269|PubMed:27435900, ECO:0007744|PDB:5FI9,
FT ECO:0007744|PDB:5FIB, ECO:0007744|PDB:5FIC,
FT ECO:0007744|PDB:5HQN"
FT DISULFID 225..248
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT ECO:0000269|PubMed:27435900, ECO:0007744|PDB:5FI9,
FT ECO:0007744|PDB:5FIB, ECO:0007744|PDB:5FIC,
FT ECO:0007744|PDB:5HQN"
FT DISULFID 383..429
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT ECO:0000269|PubMed:27435900, ECO:0007744|PDB:5FI9,
FT ECO:0007744|PDB:5FIB, ECO:0007744|PDB:5FIC,
FT ECO:0007744|PDB:5HQN"
FT DISULFID 582..586
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT ECO:0000269|PubMed:27435900, ECO:0007744|PDB:5FI9,
FT ECO:0007744|PDB:5FIB, ECO:0007744|PDB:5FIC,
FT ECO:0007744|PDB:5HQN"
FT DISULFID 592..605
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT ECO:0000269|PubMed:27435900, ECO:0007744|PDB:5FI9,
FT ECO:0007744|PDB:5FIB, ECO:0007744|PDB:5FIC,
FT ECO:0007744|PDB:5HQN"
FT MUTAGEN 128
FT /note="V->E: Retains 20% of wild-type activity with
FT sphingomyelin as substrate; retains 70% of wild-type
FT activity with bis(p-nitrophenyl) phosphate as substrate."
FT /evidence="ECO:0000269|PubMed:27435900"
FT MUTAGEN 143
FT /note="V->R: Retains 10% of wild-type activity with
FT sphingomyelin as substrate; retains 70% of wild-type
FT activity with bis(p-nitrophenyl) phosphate as substrate."
FT /evidence="ECO:0000269|PubMed:27435900"
FT MUTAGEN 280
FT /note="H->A: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:27435900"
FT MUTAGEN 283
FT /note="W->N: Retains 10% of wild-type activity."
FT /evidence="ECO:0000269|PubMed:27435900"
FT MUTAGEN 317
FT /note="H->A: No activity with sphingomyelin as substrate;
FT retains 70% of wild-type activity with bis(p-nitrophenyl)
FT phosphate as substrate."
FT /evidence="ECO:0000269|PubMed:27435900"
FT MUTAGEN 321
FT /note="P->E: Retains 10% of wild-type activity."
FT /evidence="ECO:0000269|PubMed:27435900"
FT MUTAGEN 388
FT /note="F->R: Retains 10% of wild-type activity."
FT /evidence="ECO:0000269|PubMed:27435900"
FT MUTAGEN 391
FT /note="L->R: Retains 20% of wild-type activity with
FT sphingomyelin as substrate; retains 50% of wild-type
FT activity with bis(p-nitrophenyl) phosphate as substrate."
FT /evidence="ECO:0000269|PubMed:27435900"
FT CONFLICT 48
FT /note="S -> T (in Ref. 4; AAH11304)"
FT /evidence="ECO:0000305"
FT CONFLICT 450
FT /note="G -> S (in Ref. 4; AAH11304)"
FT /evidence="ECO:0000305"
FT HELIX 87..101
FT /evidence="ECO:0007829|PDB:5FI9"
FT HELIX 107..121
FT /evidence="ECO:0007829|PDB:5FI9"
FT HELIX 126..136
FT /evidence="ECO:0007829|PDB:5FI9"
FT HELIX 140..145
FT /evidence="ECO:0007829|PDB:5FI9"
FT TURN 147..149
FT /evidence="ECO:0007829|PDB:5FIC"
FT HELIX 151..159
FT /evidence="ECO:0007829|PDB:5FI9"
FT TURN 161..163
FT /evidence="ECO:0007829|PDB:5FIB"
FT TURN 166..168
FT /evidence="ECO:0007829|PDB:5FI9"
FT STRAND 196..202
FT /evidence="ECO:0007829|PDB:5FI9"
FT STRAND 220..223
FT /evidence="ECO:0007829|PDB:5FI9"
FT STRAND 225..227
FT /evidence="ECO:0007829|PDB:5HQN"
FT HELIX 235..237
FT /evidence="ECO:0007829|PDB:5HQN"
FT STRAND 245..247
FT /evidence="ECO:0007829|PDB:5FI9"
FT HELIX 252..260
FT /evidence="ECO:0007829|PDB:5FI9"
FT HELIX 261..265
FT /evidence="ECO:0007829|PDB:5FI9"
FT STRAND 269..273
FT /evidence="ECO:0007829|PDB:5FI9"
FT HELIX 282..284
FT /evidence="ECO:0007829|PDB:5FI9"
FT HELIX 287..305
FT /evidence="ECO:0007829|PDB:5FI9"
FT STRAND 310..312
FT /evidence="ECO:0007829|PDB:5FI9"
FT STRAND 316..321
FT /evidence="ECO:0007829|PDB:5FI9"
FT HELIX 337..346
FT /evidence="ECO:0007829|PDB:5FI9"
FT TURN 347..350
FT /evidence="ECO:0007829|PDB:5FI9"
FT HELIX 353..362
FT /evidence="ECO:0007829|PDB:5FI9"
FT STRAND 365..370
FT /evidence="ECO:0007829|PDB:5FI9"
FT STRAND 373..377
FT /evidence="ECO:0007829|PDB:5FI9"
FT HELIX 380..383
FT /evidence="ECO:0007829|PDB:5FI9"
FT HELIX 388..391
FT /evidence="ECO:0007829|PDB:5FI9"
FT HELIX 397..399
FT /evidence="ECO:0007829|PDB:5FI9"
FT HELIX 400..414
FT /evidence="ECO:0007829|PDB:5FI9"
FT STRAND 417..421
FT /evidence="ECO:0007829|PDB:5FI9"
FT HELIX 426..428
FT /evidence="ECO:0007829|PDB:5FI9"
FT HELIX 431..443
FT /evidence="ECO:0007829|PDB:5FI9"
FT TURN 444..447
FT /evidence="ECO:0007829|PDB:5FI9"
FT STRAND 448..453
FT /evidence="ECO:0007829|PDB:5FI9"
FT STRAND 460..465
FT /evidence="ECO:0007829|PDB:5FI9"
FT TURN 467..469
FT /evidence="ECO:0007829|PDB:5FI9"
FT STRAND 472..479
FT /evidence="ECO:0007829|PDB:5FI9"
FT TURN 486..488
FT /evidence="ECO:0007829|PDB:5FI9"
FT STRAND 492..499
FT /evidence="ECO:0007829|PDB:5FI9"
FT STRAND 509..517
FT /evidence="ECO:0007829|PDB:5FI9"
FT HELIX 519..522
FT /evidence="ECO:0007829|PDB:5FI9"
FT STRAND 531..536
FT /evidence="ECO:0007829|PDB:5FI9"
FT HELIX 537..541
FT /evidence="ECO:0007829|PDB:5FI9"
FT HELIX 548..560
FT /evidence="ECO:0007829|PDB:5FI9"
FT HELIX 562..572
FT /evidence="ECO:0007829|PDB:5FI9"
FT TURN 573..575
FT /evidence="ECO:0007829|PDB:5HQN"
FT HELIX 584..594
FT /evidence="ECO:0007829|PDB:5FI9"
FT STRAND 598..600
FT /evidence="ECO:0007829|PDB:5FI9"
FT HELIX 602..605
FT /evidence="ECO:0007829|PDB:5FI9"
FT TURN 606..608
FT /evidence="ECO:0007829|PDB:5FIB"
SQ SEQUENCE 627 AA; 69927 MW; 0FFC7EA74EE71E91 CRC64;
MPHHRASSGQ DHLRAGWEQR LERSLPAPRV GLLWMGLGLA LVLALFDSTV LWVPARAYPL
PSEGHSVKFS AIAPPLQSAF GWQNLTCPAC KVLFTALNHG LKKEPNVARV GSVAIKICKM
LNIAPLDVCQ SAVHLFEDDV VEVWTRSVLS PSEACGLLLG SSCGHWDIFS TWNISLPSVP
KPPPKPPSPP APGAPVSRVL FLTDLHWDHE YLEGTDPYCA DPLCCRRGSG WPPNSQKGAG
FWGEYSKCDL PLRTLESLLK GLGPAGPFEM VYWTGDIPAH DVWQQSRQDQ LRALTTITDL
VRKFLGPVPV YPAVGNHEST PVNGFPPPFI KGNQSSQWLY EAMAKAWEPW LPADALHTLR
IGGFYALTPR PGLRLISLNM NFCSRENFWL LINSTDPAGQ LQWLVEELQA AENRGDKVHI
IGHIPPGHCL KSWSWNYYKI IARYENTLAG QFFGHTHVDE FEIFYDEETL SRPLAVAFLA
PSATTFINLN PGYRVYQIDG NYPGSSHVVL DHETYILNLT QANAAGGTPS WKRLYRARET
YGLPDAMPAS WHNLVYRMRD DEQLFQTFWF LYHKGHPPSE PCGTPCRLAT LCAQLSARAD
SPALCRHLMP NGSLPDANRL WSRPLLC
