ASM2_CAEEL
ID ASM2_CAEEL Reviewed; 618 AA.
AC Q23498;
DT 19-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 3.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Sphingomyelin phosphodiesterase 2;
DE EC=3.1.4.12 {ECO:0000269|PubMed:9603947};
DE AltName: Full=Acid sphingomyelinase 2;
DE Short=ASM-2 {ECO:0000303|PubMed:9603947};
DE Flags: Precursor;
GN Name=asm-2; ORFNames=ZK455.4;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, PATHWAY,
RP COFACTOR, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=9603947; DOI=10.1074/jbc.273.23.14374;
RA Lin X., Hengartner M.O., Kolesnick R.;
RT "Caenorhabditis elegans contains two distinct acid sphingomyelinases.";
RL J. Biol. Chem. 273:14374-14379(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-525, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=Bristol N2;
RX PubMed=17761667; DOI=10.1074/mcp.m600392-mcp200;
RA Kaji H., Kamiie J., Kawakami H., Kido K., Yamauchi Y., Shinkawa T.,
RA Taoka M., Takahashi N., Isobe T.;
RT "Proteomics reveals N-linked glycoprotein diversity in Caenorhabditis
RT elegans and suggests an atypical translocation mechanism for integral
RT membrane proteins.";
RL Mol. Cell. Proteomics 6:2100-2109(2007).
CC -!- FUNCTION: Sphingomyelin phosphodiesterase (sphingomyelinase) that
CC converts sphingomyelin (N-acyl-sphingoid-1-phosphocholine) to ceramide
CC (N-acyl-sphingoid base) and phosphocholine at acidic pH. Displays its
CC enzymatic activity when secreted. May play distinct roles in signaling.
CC {ECO:0000269|PubMed:9603947}.
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:9603947};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19254;
CC Evidence={ECO:0000269|PubMed:9603947};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-acyl-15-methylhexadecasphing-4-enine-1-phosphocholine
CC = H(+) + N-acyl-15-methylhexadecasphing-4-enine + phosphocholine;
CC Xref=Rhea:RHEA:34739, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:70775, ChEBI:CHEBI:70846, ChEBI:CHEBI:295975;
CC Evidence={ECO:0000305|PubMed:9603947};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34740;
CC Evidence={ECO:0000305|PubMed:9603947};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:9603947};
CC Note=Binds 2 Zn(2+) per subunit. {ECO:0000250|UniProtKB:Q92484};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=288 uM for sphingomyelin (N-acyl-sphing-4-enine-1-phosphocholine)
CC (at pH 5.0) {ECO:0000269|PubMed:9603947};
CC Vmax=4.8 umol/h/mg enzyme (at pH 5.0) {ECO:0000269|PubMed:9603947};
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000269|PubMed:9603947}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:9603947}. Note=Only
CC the secreted form is enzymatically active.
CC {ECO:0000269|PubMed:9603947}.
CC -!- DEVELOPMENTAL STAGE: Preferentially expressed in postembryonic
CC development. {ECO:0000269|PubMed:9603947}.
CC -!- MISCELLANEOUS: Requires Zn(2+) to be fully active.
CC {ECO:0000269|PubMed:9603947}.
CC -!- MISCELLANEOUS: There are two types of sphingomyelinases: asm (acid),
CC and nsm (neutral). Only acid sphingomyelinases have been found in
CC worms. {ECO:0000269|PubMed:9603947}.
CC -!- SIMILARITY: Belongs to the acid sphingomyelinase family. {ECO:0000305}.
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DR EMBL; Z66567; CAA91493.2; -; Genomic_DNA.
DR PIR; T27869; T27869.
DR RefSeq; NP_509894.2; NM_077493.4.
DR AlphaFoldDB; Q23498; -.
DR SMR; Q23498; -.
DR STRING; 6239.ZK455.4; -.
DR SwissLipids; SLP:000000010; -.
DR iPTMnet; Q23498; -.
DR PaxDb; Q23498; -.
DR PeptideAtlas; Q23498; -.
DR EnsemblMetazoa; ZK455.4.1; ZK455.4.1; WBGene00000212.
DR GeneID; 181323; -.
DR KEGG; cel:CELE_ZK455.4; -.
DR UCSC; ZK455.4; c. elegans.
DR CTD; 181323; -.
DR WormBase; ZK455.4; CE31674; WBGene00000212; asm-2.
DR eggNOG; KOG3770; Eukaryota.
DR GeneTree; ENSGT00950000183182; -.
DR HOGENOM; CLU_014743_3_0_1; -.
DR InParanoid; Q23498; -.
DR OMA; WPTEACA; -.
DR OrthoDB; 1142100at2759; -.
DR PhylomeDB; Q23498; -.
DR Reactome; R-CEL-1660662; Glycosphingolipid metabolism.
DR UniPathway; UPA00222; -.
DR PRO; PR:Q23498; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00000212; Expressed in larva and 2 other tissues.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005764; C:lysosome; IBA:GO_Central.
DR GO; GO:0061750; F:acid sphingomyelin phosphodiesterase activity; IBA:GO_Central.
DR GO; GO:0016798; F:hydrolase activity, acting on glycosyl bonds; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008081; F:phosphoric diester hydrolase activity; IBA:GO_Central.
DR GO; GO:0004767; F:sphingomyelin phosphodiesterase activity; IDA:UniProtKB.
DR GO; GO:0046513; P:ceramide biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006685; P:sphingomyelin catabolic process; IDA: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; IPR007856; SapB_1.
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 Pfam; PF05184; SapB_1; 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 Disulfide bond; Glycoprotein; Glycosidase; Hydrolase; Lipid metabolism;
KW Metal-binding; Reference proteome; Secreted; Signal;
KW Sphingolipid metabolism; Zinc.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..618
FT /note="Sphingomyelin phosphodiesterase 2"
FT /id="PRO_0000002326"
FT DOMAIN 68..151
FT /note="Saposin B-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT BINDING 189
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P17405"
FT BINDING 191
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P17405"
FT BINDING 278
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P17405"
FT BINDING 278
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P17405"
FT BINDING 318
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P17405"
FT BINDING 427
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P17405"
FT BINDING 461
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P17405"
FT BINDING 463
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P17405"
FT CARBOHYD 89
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT CARBOHYD 159
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT CARBOHYD 298
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT CARBOHYD 525
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT ECO:0000269|PubMed:17761667"
FT CARBOHYD 568
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT DISULFID 72..147
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT DISULFID 75..140
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT DISULFID 103..114
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT DISULFID 204..216
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT DISULFID 217..249
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT DISULFID 387..435
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT DISULFID 588..594
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT DISULFID 600..613
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
SQ SEQUENCE 618 AA; 71925 MW; CF24C82DC09BA115 CRC64;
MQQPLIILGI GIVLALVSNV ESGVLRKPVD EHEYEKWTNA RGNEAAVPPP KYKMLRYAKK
AINEPENRKM SCLFCTFAVD GVQALIAQNS TDNEIAAFLV NLCDLFDVEQ PHVCKNIIYA
FKDEVVFVLE RSVFTPEEIC GAFIANCGHS DKPLTHMWNI TIPGGKPPIK PWPKIPDNKP
TFKVLHLSDI HIDHQYVVGT EAYCQLDSAL GTYAMCCRDY SQDSQGAPTN LKDKPIYVPA
GPWGMPYLCD LPYQTFESAM KHISKTFKDL DYIIITGDFE AHDSWDYTED LTRENMNNMT
NVFLEYFPGV PVYVSIGNHE GVPQDAMAPH TMPEYDTRGP QWLYKIMSEM WSHWIPQEAL
DTVQYRASYA VYPKPGLKLI SLNTIYCSEF NFYLYVNEVD PDATLEWLIE ELQDSENKGE
LVHIISHIPP GDNYCLKGWS WNFFEIVKRY ENTIAQMFYG HTHYDQFMVY YDMDDPNRRP
FHFNWISPSL TTYDWLNPAY RIYEIDGGYE GATYTVKDAK TYFANVTEAN MKNKEPEWVL
SYDTREHYQM ADFSPQSWSD LSDKLWTNTT LFRDYVRLYY RNHYNNECYT DYKCRYTFVC
DIKKGRSYDE SFCDHLTK
