ASM3A_MOUSE
ID ASM3A_MOUSE Reviewed; 445 AA.
AC P70158; Q3U8C2;
DT 29-AUG-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Acid sphingomyelinase-like phosphodiesterase 3a;
DE Short=ASM-like phosphodiesterase 3a;
DE EC=3.1.4.- {ECO:0000269|PubMed:26792860};
DE Flags: Precursor;
GN Name=Smpdl3a; Synonyms=Asml3a;
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].
RA Hofmann K.;
RT "Acid sphingomyelinase is a member of a multi-gene family and shares motifs
RT with a large family of metallo-phosphoesterases.";
RL Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Bone marrow;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC and Spleen;
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 [6]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=25288789; DOI=10.1074/jbc.m114.612341;
RA Traini M., Quinn C.M., Sandoval C., Johansson E., Schroder K., Kockx M.,
RA Meikle P.J., Jessup W., Kritharides L.;
RT "Sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A) is a novel
RT nucleotide phosphodiesterase regulated by cholesterol in human
RT macrophages.";
RL J. Biol. Chem. 289:32895-32913(2014).
RN [7]
RP SUBCELLULAR LOCATION, AND GLYCOSYLATION.
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 [8]
RP X-RAY CRYSTALLOGRAPHY (1.39 ANGSTROMS) OF 23-445 IN COMPLEXES WITH ZINC
RP IONS; ATP ANALOG AND PHOSPHOCHOLINE, CATALYTIC ACTIVITY, FUNCTION,
RP COFACTOR, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS
RP OF HIS-111 AND HIS-149, SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-66;
RP ASN-128; ASN-235; ASN-353 AND ASN-364, AND DISULFIDE BONDS.
RX PubMed=26792860; DOI=10.1074/jbc.m115.711085;
RA Gorelik A., Illes K., Superti-Furga G., Nagar B.;
RT "Structural basis for nucleotide hydrolysis by the acid sphingomyelinase-
RT like phosphodiesterase SMPDL3A.";
RL J. Biol. Chem. 291:6376-6385(2016).
CC -!- FUNCTION: Has in vitro nucleotide phosphodiesterase activity with
CC nucleoside triphosphates, such as ATP (PubMed:26792860). Has in vitro
CC activity with p-nitrophenyl-TMP. Has lower activity with nucleoside
CC diphosphates, and no activity with nucleoside monophosphates. Has in
CC vitro activity with CDP-choline, giving rise to CMP and phosphocholine.
CC Has in vitro activity with CDP-ethanolamine. Does not have
CC sphingomyelin phosphodiesterase activity (By similarity).
CC {ECO:0000250|UniProtKB:Q92484, ECO:0000269|PubMed:26792860}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:26792860};
CC Note=Binds 2 Zn(2+) per subunit. {ECO:0000269|PubMed:26792860};
CC -!- ACTIVITY REGULATION: Requires micromolar levels of Zn(2+) for activity.
CC Inhibited by millimolar levels of Zn(2+).
CC {ECO:0000269|PubMed:26792860}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=107 uM for ATP at pH 5 {ECO:0000269|PubMed:26792860};
CC KM=330 uM for ATP at pH 7.5 {ECO:0000269|PubMed:26792860};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:25288789,
CC ECO:0000269|PubMed:26095358, ECO:0000269|PubMed:26792860}.
CC -!- TISSUE SPECIFICITY: Detected in blood serum (at protein level).
CC {ECO:0000269|PubMed:25288789}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:26095358}.
CC -!- SIMILARITY: Belongs to the acid sphingomyelinase family. {ECO:0000305}.
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DR EMBL; Y08135; CAA69329.1; -; mRNA.
DR EMBL; AK151683; BAE30607.1; -; mRNA.
DR EMBL; AK152282; BAE31096.1; -; mRNA.
DR EMBL; CH466540; EDL05124.1; -; Genomic_DNA.
DR EMBL; BC139288; AAI39289.1; -; mRNA.
DR EMBL; BC139289; AAI39290.1; -; mRNA.
DR CCDS; CCDS23857.1; -.
DR RefSeq; NP_065586.3; NM_020561.2.
DR PDB; 5FC1; X-ray; 1.39 A; A=23-445.
DR PDB; 5FC5; X-ray; 1.68 A; A=23-445.
DR PDB; 5FC6; X-ray; 1.66 A; A=23-445.
DR PDB; 5FC7; X-ray; 1.46 A; A=23-445.
DR PDB; 5FCA; X-ray; 1.92 A; A/B=23-445.
DR PDB; 5FCB; X-ray; 1.55 A; A=23-445.
DR PDBsum; 5FC1; -.
DR PDBsum; 5FC5; -.
DR PDBsum; 5FC6; -.
DR PDBsum; 5FC7; -.
DR PDBsum; 5FCA; -.
DR PDBsum; 5FCB; -.
DR AlphaFoldDB; P70158; -.
DR SMR; P70158; -.
DR BioGRID; 208256; 2.
DR STRING; 10090.ENSMUSP00000020022; -.
DR GlyConnect; 2103; 1 N-Linked glycan (1 site).
DR GlyGen; P70158; 6 sites, 1 N-linked glycan (1 site).
DR iPTMnet; P70158; -.
DR PhosphoSitePlus; P70158; -.
DR EPD; P70158; -.
DR jPOST; P70158; -.
DR MaxQB; P70158; -.
DR PaxDb; P70158; -.
DR PeptideAtlas; P70158; -.
DR PRIDE; P70158; -.
DR ProteomicsDB; 281813; -.
DR Antibodypedia; 32649; 135 antibodies from 22 providers.
DR DNASU; 57319; -.
DR Ensembl; ENSMUST00000020022; ENSMUSP00000020022; ENSMUSG00000019872.
DR GeneID; 57319; -.
DR KEGG; mmu:57319; -.
DR UCSC; uc007fcu.1; mouse.
DR CTD; 10924; -.
DR MGI; MGI:1931437; Smpdl3a.
DR VEuPathDB; HostDB:ENSMUSG00000019872; -.
DR eggNOG; KOG3770; Eukaryota.
DR GeneTree; ENSGT00950000183182; -.
DR HOGENOM; CLU_014743_0_0_1; -.
DR InParanoid; P70158; -.
DR OMA; VICDKTC; -.
DR OrthoDB; 1142100at2759; -.
DR PhylomeDB; P70158; -.
DR TreeFam; TF313674; -.
DR BRENDA; 3.1.4.1; 3474.
DR SABIO-RK; P70158; -.
DR BioGRID-ORCS; 57319; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Smpdl3a; mouse.
DR PRO; PR:P70158; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; P70158; protein.
DR Bgee; ENSMUSG00000019872; Expressed in parotid gland and 256 other tissues.
DR ExpressionAtlas; P70158; baseline and differential.
DR Genevisible; P70158; MM.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0008081; F:phosphoric diester hydrolase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0009143; P:nucleoside triphosphate catabolic process; ISS:UniProtKB.
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; Disulfide bond; Glycoprotein; Hydrolase; Metal-binding;
KW Reference proteome; Secreted; Signal; Zinc.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..445
FT /note="Acid sphingomyelinase-like phosphodiesterase 3a"
FT /id="PRO_0000002329"
FT BINDING 42
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:26792860"
FT BINDING 44
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:26792860"
FT BINDING 107
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:26792860"
FT BINDING 107
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:26792860"
FT BINDING 111
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:26792860"
FT BINDING 148
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:26792860"
FT BINDING 148
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:26792860"
FT BINDING 149
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:26792860"
FT BINDING 249
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:26792860"
FT BINDING 257
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:26792860"
FT BINDING 290
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:26792860"
FT BINDING 292
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:26792860"
FT CARBOHYD 66
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:26792860"
FT CARBOHYD 128
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:26792860"
FT CARBOHYD 219
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 235
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:26792860"
FT CARBOHYD 353
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:26792860"
FT CARBOHYD 364
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:26792860"
FT DISULFID 59..78
FT /evidence="ECO:0000269|PubMed:26792860"
FT DISULFID 417..421
FT /evidence="ECO:0000255"
FT DISULFID 427..440
FT /evidence="ECO:0000269|PubMed:26792860"
FT MUTAGEN 111
FT /note="H->A,Q: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:26792860"
FT MUTAGEN 149
FT /note="H->A: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:26792860"
FT MUTAGEN 149
FT /note="H->Q: Nearly abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:26792860"
FT STRAND 35..40
FT /evidence="ECO:0007829|PDB:5FC1"
FT HELIX 55..57
FT /evidence="ECO:0007829|PDB:5FC1"
FT HELIX 60..62
FT /evidence="ECO:0007829|PDB:5FC1"
FT HELIX 82..94
FT /evidence="ECO:0007829|PDB:5FC1"
FT STRAND 100..104
FT /evidence="ECO:0007829|PDB:5FC1"
FT HELIX 114..116
FT /evidence="ECO:0007829|PDB:5FC1"
FT HELIX 119..136
FT /evidence="ECO:0007829|PDB:5FC1"
FT STRAND 141..144
FT /evidence="ECO:0007829|PDB:5FC1"
FT STRAND 150..153
FT /evidence="ECO:0007829|PDB:5FC1"
FT HELIX 163..172
FT /evidence="ECO:0007829|PDB:5FC1"
FT TURN 173..175
FT /evidence="ECO:0007829|PDB:5FC1"
FT HELIX 178..187
FT /evidence="ECO:0007829|PDB:5FC1"
FT STRAND 190..193
FT /evidence="ECO:0007829|PDB:5FC1"
FT STRAND 200..204
FT /evidence="ECO:0007829|PDB:5FC1"
FT HELIX 207..210
FT /evidence="ECO:0007829|PDB:5FC1"
FT HELIX 215..217
FT /evidence="ECO:0007829|PDB:5FC1"
FT HELIX 223..225
FT /evidence="ECO:0007829|PDB:5FC1"
FT HELIX 226..239
FT /evidence="ECO:0007829|PDB:5FC1"
FT STRAND 243..250
FT /evidence="ECO:0007829|PDB:5FC1"
FT STRAND 252..254
FT /evidence="ECO:0007829|PDB:5FC1"
FT STRAND 258..260
FT /evidence="ECO:0007829|PDB:5FC1"
FT STRAND 262..264
FT /evidence="ECO:0007829|PDB:5FC1"
FT HELIX 266..278
FT /evidence="ECO:0007829|PDB:5FC1"
FT TURN 279..282
FT /evidence="ECO:0007829|PDB:5FC1"
FT STRAND 283..288
FT /evidence="ECO:0007829|PDB:5FC1"
FT STRAND 295..300
FT /evidence="ECO:0007829|PDB:5FC1"
FT STRAND 306..312
FT /evidence="ECO:0007829|PDB:5FC1"
FT STRAND 331..337
FT /evidence="ECO:0007829|PDB:5FC1"
FT TURN 339..341
FT /evidence="ECO:0007829|PDB:5FC1"
FT STRAND 344..351
FT /evidence="ECO:0007829|PDB:5FC1"
FT HELIX 354..360
FT /evidence="ECO:0007829|PDB:5FC1"
FT STRAND 366..370
FT /evidence="ECO:0007829|PDB:5FC1"
FT HELIX 371..375
FT /evidence="ECO:0007829|PDB:5FC1"
FT HELIX 382..392
FT /evidence="ECO:0007829|PDB:5FC1"
FT HELIX 398..407
FT /evidence="ECO:0007829|PDB:5FC1"
FT TURN 408..410
FT /evidence="ECO:0007829|PDB:5FC1"
FT HELIX 419..430
FT /evidence="ECO:0007829|PDB:5FC1"
FT HELIX 434..444
FT /evidence="ECO:0007829|PDB:5FC1"
SQ SEQUENCE 445 AA; 49858 MW; 20D986E3463CB720 CRC64;
MALLGNFLCC LLVAWLCGPG LGVPLAPADR APAVGQFWHV TDLHLDPTYH ITDDRTKVCA
SSKGANASNP GPFGDVLCDS PYQLILSAFD FIKNSGQEAS FMIWTGDSPP HVPVPELSTG
TVIKVITNMT MTVQNLFPNL QVFPALGNHD YWPQDQLPIV TSKVYSAVAD LWKPWLGEEA
ISTLKKGGFY SQKVASNPGL RIISLNTNLY YGPNIMTLNK TDPANQFEWL ENTLNSSLWN
KEKVYIIAHV PVGYLPYATD TPAIRQYYNE KLLDIFRRYS SVIAGQFYGH THRDSLMVLS
DKNGNPLNSV FVAPAVTPVK GVLQKETNNP GVRLFQYKPG DYTLLDMVQY YLNLTEANLK
GESNWTLEYV LTQAYSVADL QPKSLYALVQ QFATKDSKQF LKYYHYYFVS YDSSATCDQH
CKTLQVCAIM NLDSMSYDDC LKQHL
