ASM3B_MOUSE
ID ASM3B_MOUSE Reviewed; 456 AA.
AC P58242;
DT 29-AUG-2001, integrated into UniProtKB/Swiss-Prot.
DT 29-AUG-2001, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Acid sphingomyelinase-like phosphodiesterase 3b;
DE Short=ASM-like phosphodiesterase 3b;
DE EC=3.1.4.- {ECO:0000269|PubMed:26095358, ECO:0000269|PubMed:27687724};
DE Flags: Precursor;
GN Name=Smpdl3b; Synonyms=Asml3b;
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 [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 [2]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-34 AND ASN-223.
RC TISSUE=Myoblast;
RX PubMed=19656770; DOI=10.1074/mcp.m900195-mcp200;
RA Gundry R.L., Raginski K., Tarasova Y., Tchernyshyov I., Bausch-Fluck D.,
RA Elliott S.T., Boheler K.R., Van Eyk J.E., Wollscheid B.;
RT "The mouse C2C12 myoblast cell surface N-linked glycoproteome:
RT identification, glycosite occupancy, and membrane orientation.";
RL Mol. Cell. Proteomics 8:2555-2569(2009).
RN [3]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-34; ASN-164 AND ASN-223.
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, GLYCOSYLATION,
RP INTERACTION WITH TLR4; TLR7; TLR8 AND TLR9, TISSUE SPECIFICITY, MUTAGENESIS
RP OF HIS-135, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26095358; DOI=10.1016/j.celrep.2015.05.006;
RA Heinz L.X., Baumann C.L., Koeberlin M.S., Snijder B., Gawish R., Shui G.,
RA Sharif O., Aspalter I.M., Mueller A.C., Kandasamy R.K., Breitwieser F.P.,
RA Pichlmair A., Bruckner M., Rebsamen M., Blueml S., Karonitsch T.,
RA Fauster A., Colinge J., Bennett K.L., Knapp S., Wenk M.R.,
RA Superti-Furga G.;
RT "The lipid-modifying enzyme SMPDL3B negatively regulates innate immunity.";
RL Cell Rep. 11:1919-1928(2015).
RN [6] {ECO:0007744|PDB:5KAR, ECO:0007744|PDB:5KAS}
RP X-RAY CRYSTALLOGRAPHY (1.14 ANGSTROMS) OF 19-435 IN COMPLEX WITH ZINC AND
RP PHOSPHOCHOLINE, COFACTOR, GLYCOSYLATION AT ASN-34; ASN-72 AND ASN-223,
RP DISULFIDE BONDS, FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-135;
RP 140-LYS-ASN-141; 198-TYR--ASN-200 AND 307-LYS--ASP-315.
RX PubMed=27687724; DOI=10.1074/jbc.m116.755801;
RA Gorelik A., Heinz L.X., Illes K., Superti-Furga G., Nagar B.;
RT "Crystal Structure of the Acid Sphingomyelinase-like Phosphodiesterase
RT SMPDL3B Provides Insights into Determinants of Substrate Specificity.";
RL J. Biol. Chem. 291:24054-24064(2016).
CC -!- FUNCTION: Lipid-modulating phosphodiesterase. Active on the surface of
CC macrophages and dendritic cells and strongly influences macrophage
CC lipid composition and membrane fluidity (PubMed:26095358). Acts as a
CC negative regulator of Toll-like receptor signaling (PubMed:26095358,
CC PubMed:27687724). Has in vitro phosphodiesterase activity, but the
CC physiological substrate is unknown (PubMed:26095358, PubMed:27687724).
CC Lacks activity with phosphocholine-containing lipids, but can cleave
CC CDP-choline, and can release phosphate from ATP and ADP (in vitro)
CC (PubMed:27687724). {ECO:0000269|PubMed:26095358,
CC ECO:0000269|PubMed:27687724}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:27687724};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000269|PubMed:27687724};
CC -!- SUBUNIT: Interacts with TLR4, TLR7, TLR8 and TLR9.
CC {ECO:0000269|PubMed:26095358}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}. Cell membrane; Lipid-
CC anchor, GPI-anchor {ECO:0000269|PubMed:26095358}.
CC -!- TISSUE SPECIFICITY: Macrophages and dendritic cells.
CC {ECO:0000269|PubMed:26095358}.
CC -!- INDUCTION: Strongly up-regulated by TLR stimuli and interferon gamma.
CC {ECO:0000269|PubMed:26095358}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:26095358}.
CC -!- DISRUPTION PHENOTYPE: Mice display higher inflammatory responses in
CC models of TLR-dependent peritonitis. Macrophages show enhanced
CC responsiveness to TLR stimulation and a significant change in membrane
CC fluidity and the global cellular lipid composition.
CC {ECO:0000269|PubMed:26095358}.
CC -!- SIMILARITY: Belongs to the acid sphingomyelinase family. {ECO:0000305}.
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DR EMBL; BC009087; AAH09087.1; -; mRNA.
DR CCDS; CCDS18733.1; -.
DR RefSeq; NP_598649.1; NM_133888.2.
DR PDB; 5KAR; X-ray; 1.14 A; A=19-435.
DR PDB; 5KAS; X-ray; 1.62 A; A=19-435.
DR PDBsum; 5KAR; -.
DR PDBsum; 5KAS; -.
DR AlphaFoldDB; P58242; -.
DR SMR; P58242; -.
DR IntAct; P58242; 2.
DR STRING; 10090.ENSMUSP00000030709; -.
DR GlyConnect; 2104; 1 N-Linked glycan (1 site).
DR GlyGen; P58242; 5 sites, 1 N-linked glycan (1 site).
DR iPTMnet; P58242; -.
DR PhosphoSitePlus; P58242; -.
DR SwissPalm; P58242; -.
DR PaxDb; P58242; -.
DR PeptideAtlas; P58242; -.
DR PRIDE; P58242; -.
DR ProteomicsDB; 277258; -.
DR Antibodypedia; 30880; 96 antibodies from 20 providers.
DR DNASU; 100340; -.
DR Ensembl; ENSMUST00000030709; ENSMUSP00000030709; ENSMUSG00000028885.
DR GeneID; 100340; -.
DR KEGG; mmu:100340; -.
DR UCSC; uc008vbs.1; mouse.
DR CTD; 27293; -.
DR MGI; MGI:1916022; Smpdl3b.
DR VEuPathDB; HostDB:ENSMUSG00000028885; -.
DR eggNOG; KOG3770; Eukaryota.
DR GeneTree; ENSGT00950000183182; -.
DR HOGENOM; CLU_014743_0_2_1; -.
DR InParanoid; P58242; -.
DR OMA; DSPWHLI; -.
DR OrthoDB; 1116351at2759; -.
DR PhylomeDB; P58242; -.
DR TreeFam; TF313674; -.
DR BRENDA; 3.1.4.12; 3474.
DR BioGRID-ORCS; 100340; 2 hits in 74 CRISPR screens.
DR PRO; PR:P58242; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; P58242; protein.
DR Bgee; ENSMUSG00000028885; Expressed in small intestine Peyer's patch and 134 other tissues.
DR ExpressionAtlas; P58242; baseline and differential.
DR Genevisible; P58242; MM.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0016798; F:hydrolase activity, acting on glycosyl bonds; IEA:UniProtKB-KW.
DR GO; GO:0008081; F:phosphoric diester hydrolase activity; IDA:UniProtKB.
DR GO; GO:0004767; F:sphingomyelin phosphodiesterase activity; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0046466; P:membrane lipid catabolic process; IMP:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IMP:UniProtKB.
DR GO; GO:0045824; P:negative regulation of innate immune response; TAS:UniProtKB.
DR GO; GO:0034122; P:negative regulation of toll-like receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0006685; P:sphingomyelin catabolic process; IEA:InterPro.
DR CDD; cd00842; MPP_ASMase; 1.
DR Gene3D; 3.60.21.10; -; 1.
DR InterPro; IPR017064; ASM-like_Pdiesterase_prd.
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 Pfam; PF19272; ASMase_C; 1.
DR Pfam; PF00149; Metallophos; 1.
DR PIRSF; PIRSF036767; ASM-like_PDE; 1.
DR SUPFAM; SSF56300; SSF56300; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Disulfide bond; Glycoprotein; Glycosidase;
KW GPI-anchor; Hydrolase; Immunity; Inflammatory response; Innate immunity;
KW Lipid degradation; Lipid metabolism; Lipoprotein; Membrane; Metal-binding;
KW Reference proteome; Secreted; Signal; Zinc.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..456
FT /note="Acid sphingomyelinase-like phosphodiesterase 3b"
FT /id="PRO_0000002332"
FT BINDING 28
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:27687724,
FT ECO:0007744|PDB:5KAR, ECO:0007744|PDB:5KAS"
FT BINDING 30
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:27687724,
FT ECO:0007744|PDB:5KAR, ECO:0007744|PDB:5KAS"
FT BINDING 93
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:27687724,
FT ECO:0007744|PDB:5KAR, ECO:0007744|PDB:5KAS"
FT BINDING 93
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:27687724,
FT ECO:0007744|PDB:5KAR, ECO:0007744|PDB:5KAS"
FT BINDING 134
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:27687724,
FT ECO:0007744|PDB:5KAR, ECO:0007744|PDB:5KAS"
FT BINDING 236
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:27687724,
FT ECO:0007744|PDB:5KAR, ECO:0007744|PDB:5KAS"
FT BINDING 277
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:27687724,
FT ECO:0007744|PDB:5KAR, ECO:0007744|PDB:5KAS"
FT BINDING 279
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:27687724,
FT ECO:0007744|PDB:5KAR, ECO:0007744|PDB:5KAS"
FT CARBOHYD 34
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973,
FT ECO:0000269|PubMed:19656770, ECO:0000269|PubMed:27687724,
FT ECO:0007744|PDB:5KAR, ECO:0007744|PDB:5KAS"
FT CARBOHYD 72
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:27687724,
FT ECO:0007744|PDB:5KAR, ECO:0007744|PDB:5KAS"
FT CARBOHYD 100
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 164
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 223
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973,
FT ECO:0000269|PubMed:19656770, ECO:0000269|PubMed:27687724,
FT ECO:0007744|PDB:5KAR, ECO:0007744|PDB:5KAS"
FT DISULFID 45..64
FT /evidence="ECO:0000269|PubMed:27687724,
FT ECO:0007744|PDB:5KAR, ECO:0007744|PDB:5KAS"
FT DISULFID 405..409
FT /evidence="ECO:0000269|PubMed:27687724,
FT ECO:0007744|PDB:5KAR, ECO:0007744|PDB:5KAS"
FT DISULFID 415..428
FT /evidence="ECO:0000269|PubMed:27687724,
FT ECO:0007744|PDB:5KAR, ECO:0007744|PDB:5KAS"
FT MUTAGEN 135
FT /note="H->A: Reduced phosphodiesterase activity. Decreases
FT inhibition of innate immune responses."
FT /evidence="ECO:0000269|PubMed:26095358,
FT ECO:0000269|PubMed:27687724"
FT MUTAGEN 140..141
FT /note="KN->MA: Reduced phosphodiesterase activity.
FT Decreases inhibition of innate immune responses."
FT /evidence="ECO:0000269|PubMed:27687724"
FT MUTAGEN 198..200
FT /note="YSN->FSA: No effect on enzyme activity and innate
FT immune responses."
FT /evidence="ECO:0000269|PubMed:27687724"
FT MUTAGEN 307..315
FT /note="KTTLPGVVD->SG: Increased phosphodiesterase activity
FT (in vitro)."
FT /evidence="ECO:0000269|PubMed:27687724"
FT STRAND 21..26
FT /evidence="ECO:0007829|PDB:5KAR"
FT HELIX 41..43
FT /evidence="ECO:0007829|PDB:5KAS"
FT HELIX 46..48
FT /evidence="ECO:0007829|PDB:5KAR"
FT HELIX 68..81
FT /evidence="ECO:0007829|PDB:5KAR"
FT STRAND 86..90
FT /evidence="ECO:0007829|PDB:5KAR"
FT HELIX 100..102
FT /evidence="ECO:0007829|PDB:5KAR"
FT HELIX 105..122
FT /evidence="ECO:0007829|PDB:5KAR"
FT STRAND 128..130
FT /evidence="ECO:0007829|PDB:5KAR"
FT STRAND 136..139
FT /evidence="ECO:0007829|PDB:5KAR"
FT HELIX 149..158
FT /evidence="ECO:0007829|PDB:5KAR"
FT HELIX 159..161
FT /evidence="ECO:0007829|PDB:5KAR"
FT HELIX 164..173
FT /evidence="ECO:0007829|PDB:5KAR"
FT STRAND 176..179
FT /evidence="ECO:0007829|PDB:5KAR"
FT STRAND 184..191
FT /evidence="ECO:0007829|PDB:5KAR"
FT HELIX 194..197
FT /evidence="ECO:0007829|PDB:5KAR"
FT HELIX 202..204
FT /evidence="ECO:0007829|PDB:5KAR"
FT HELIX 210..212
FT /evidence="ECO:0007829|PDB:5KAR"
FT HELIX 213..227
FT /evidence="ECO:0007829|PDB:5KAR"
FT STRAND 230..234
FT /evidence="ECO:0007829|PDB:5KAR"
FT STRAND 239..241
FT /evidence="ECO:0007829|PDB:5KAR"
FT STRAND 245..247
FT /evidence="ECO:0007829|PDB:5KAR"
FT STRAND 249..251
FT /evidence="ECO:0007829|PDB:5KAR"
FT HELIX 253..266
FT /evidence="ECO:0007829|PDB:5KAR"
FT HELIX 267..269
FT /evidence="ECO:0007829|PDB:5KAR"
FT STRAND 270..275
FT /evidence="ECO:0007829|PDB:5KAR"
FT STRAND 282..287
FT /evidence="ECO:0007829|PDB:5KAR"
FT STRAND 293..299
FT /evidence="ECO:0007829|PDB:5KAR"
FT STRAND 321..327
FT /evidence="ECO:0007829|PDB:5KAR"
FT TURN 329..331
FT /evidence="ECO:0007829|PDB:5KAR"
FT STRAND 334..341
FT /evidence="ECO:0007829|PDB:5KAR"
FT HELIX 344..347
FT /evidence="ECO:0007829|PDB:5KAR"
FT STRAND 350..352
FT /evidence="ECO:0007829|PDB:5KAR"
FT STRAND 356..360
FT /evidence="ECO:0007829|PDB:5KAR"
FT HELIX 361..365
FT /evidence="ECO:0007829|PDB:5KAR"
FT STRAND 368..371
FT /evidence="ECO:0007829|PDB:5KAR"
FT HELIX 372..384
FT /evidence="ECO:0007829|PDB:5KAR"
FT HELIX 386..396
FT /evidence="ECO:0007829|PDB:5KAR"
FT TURN 397..399
FT /evidence="ECO:0007829|PDB:5KAR"
FT HELIX 407..418
FT /evidence="ECO:0007829|PDB:5KAR"
FT HELIX 422..429
FT /evidence="ECO:0007829|PDB:5KAR"
SQ SEQUENCE 456 AA; 51600 MW; 11BD6AF4806FD990 CRC64;
MTLLGWLIFL APWGVAGAQL GRFWHISDLH LDPNYTVSKD PLQVCPSAGS QPVLNAGPWG
DYLCDSPWAL INSSLYAMKE IEPKPDFILW TGDDTPHVPN ESLGEAAVLA IVERLTNLIK
EVFPDTKVYA ALGNHDFHPK NQFPAQSNRI YNQVAELWRP WLSNESYALF KRGAFYSEKL
PGPSRAGRVV VLNTNLYYSN NEQTAGMADP GEQFRWLGDV LSNASRDGEM VYVIGHVPPG
FFEKTQNKAW FRESFNEEYL KVIQKHHRVI AGQFFGHHHT DSFRMFYDNT GAPINVMFLT
PGVTPWKTTL PGVVDGANNP GIRIFEYDRA TLNLKDLVTY FLNLRQANVQ ETPRWEQEYR
LTEAYQVPDA SVSSMHTALT RIASEPHILQ RYYVYNSVSY NHLTCEDSCR IEHVCAIQHV
AFNTYATCLH GLGAKLVPGF LLILTLLPSL HVLEVL
