UniProtKB - Q92484 (ASM3A_HUMAN)
Protein
Acid sphingomyelinase-like phosphodiesterase 3a
Gene
SMPDL3A
Organism
Homo sapiens (Human)
Status
Functioni
Has in vitro nucleotide phosphodiesterase activity with nucleoside triphosphates, such as ATP (PubMed:25288789, PubMed:26783088). Has in vitro activity with p-nitrophenyl-TMP (PubMed:25288789). Has lower activity with nucleoside diphosphates, and no activity with nucleoside monophosphates (PubMed:25288789, PubMed:26783088). Has in vitro activity with CDP-choline, giving rise to CMP and phosphocholine. Has in vitro activity with CDP-ethanolamine (PubMed:26783088). Does not have sphingomyelin phosphodiesterase activity (PubMed:25288789, PubMed:26783088).2 Publications
Cofactori
Zn2+1 PublicationNote: Binds 2 Zn2+ per subunit.1 Publication
Activity regulationi
Requires micromolar levels of Zn2+ for activity (PubMed:26783088). Inhibited by millimolar levels of Zn2+ (PubMed:25288789, PubMed:26783088).2 Publications
Kineticsi
- KM=326 µM for ATP1 Publication
- KM=306 µM for ADP1 Publication
- KM=348 µM for ADP-ribose1 Publication
- KM=390 µM for CDP-ethanolamine1 Publication
- KM=262 µM for CDP-choline1 Publication
pH dependencei
Optimum pH is 4-6.1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 45 | Zinc 11 Publication | 1 | |
Metal bindingi | 47 | Zinc 11 Publication | 1 | |
Metal bindingi | 110 | Zinc 11 Publication | 1 | |
Metal bindingi | 110 | Zinc 21 Publication | 1 | |
Binding sitei | 114 | Substrate1 Publication | 1 | |
Metal bindingi | 151 | Zinc 21 Publication | 1 | |
Binding sitei | 151 | Substrate1 Publication | 1 | |
Binding sitei | 152 | Substrate1 Publication | 1 | |
Metal bindingi | 252 | Zinc 21 Publication | 1 | |
Metal bindingi | 293 | Zinc 21 Publication | 1 | |
Metal bindingi | 295 | Zinc 11 Publication | 1 |
GO - Molecular functioni
- phosphoric diester hydrolase activity Source: UniProtKB
- zinc ion binding Source: UniProtKB
GO - Biological processi
- nucleoside triphosphate catabolic process Source: UniProtKB
Keywordsi
Molecular function | Hydrolase |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | Q92484 |
SABIO-RKi | Q92484 |
Names & Taxonomyi
Protein namesi | Recommended name: Acid sphingomyelinase-like phosphodiesterase 3a (EC:3.1.4.-2 Publications)Short name: ASM-like phosphodiesterase 3a |
Gene namesi | Name:SMPDL3A Synonyms:ASML3A |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:17389, SMPDL3A |
MIMi | 610728, gene |
neXtProti | NX_Q92484 |
VEuPathDBi | HostDB:ENSG00000172594.12 |
Subcellular locationi
Extracellular region or secreted
- Secreted 1 Publication
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
- extracellular space Source: UniProtKB
Keywords - Cellular componenti
SecretedPathology & Biotechi
Organism-specific databases
DisGeNETi | 10924 |
OpenTargetsi | ENSG00000172594 |
PharmGKBi | PA134932128 |
Miscellaneous databases
Pharosi | Q92484, Tbio |
Genetic variation databases
BioMutai | SMPDL3A |
DMDMi | 39932730 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 22 | Sequence analysisAdd BLAST | 22 | |
ChainiPRO_0000002328 | 23 – 453 | Acid sphingomyelinase-like phosphodiesterase 3aAdd BLAST | 431 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 62 ↔ 81 | Combined sources | ||
Glycosylationi | 69 | N-linked (GlcNAc...) asparagineSequence analysis1 Publication | 1 | |
Glycosylationi | 131 | N-linked (GlcNAc...) asparagineSequence analysis1 Publication | 1 | |
Glycosylationi | 222 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 238 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 263 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 356 | N-linked (GlcNAc...) asparagine2 Publications | 1 | |
Disulfide bondi | 420 ↔ 424 | Sequence analysis | ||
Disulfide bondi | 430 ↔ 443 | Combined sources | ||
Glycosylationi | 437 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Post-translational modificationi
N-glycosylated.1 Publication
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
EPDi | Q92484 |
jPOSTi | Q92484 |
MassIVEi | Q92484 |
MaxQBi | Q92484 |
PaxDbi | Q92484 |
PeptideAtlasi | Q92484 |
PRIDEi | Q92484 |
ProteomicsDBi | 6826 75265 [Q92484-1] |
PTM databases
GlyConnecti | 987, 3 N-Linked glycans (2 sites) |
GlyGeni | Q92484, 7 sites, 1 N-linked glycan (1 site) |
iPTMneti | Q92484 |
PhosphoSitePlusi | Q92484 |
Expressioni
Tissue specificityi
Detected in blood serum. Detected in macrophages (at protein level).1 Publication
Inductioni
Up-regulated in macrophages in response to cholesterol accumulation. Up-regulated by cAMP.1 Publication
Gene expression databases
Bgeei | ENSG00000172594, Expressed in colonic mucosa and 234 other tissues |
Genevisiblei | Q92484, HS |
Organism-specific databases
HPAi | ENSG00000172594, Low tissue specificity |
Interactioni
Subunit structurei
Monomer.
1 PublicationProtein-protein interaction databases
BioGRIDi | 116128, 1 interactor |
IntActi | Q92484, 2 interactors |
STRINGi | 9606.ENSP00000357425 |
Miscellaneous databases
RNActi | Q92484, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q92484 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Sequence similaritiesi
Belongs to the acid sphingomyelinase family.Curated
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | KOG3770, Eukaryota |
GeneTreei | ENSGT00950000183182 |
HOGENOMi | CLU_014743_0_0_1 |
InParanoidi | Q92484 |
OMAi | VICDKTC |
OrthoDBi | 1142100at2759 |
PhylomeDBi | Q92484 |
TreeFami | TF313674 |
Family and domain databases
CDDi | cd00842, MPP_ASMase, 1 hit |
Gene3Di | 3.60.21.10, 1 hit |
InterProi | View protein in InterPro IPR017064, ASM-like_Pdiesterase_prd IPR041805, ASMase/PPN1_MPP IPR004843, Calcineurin-like_PHP_ApaH IPR029052, Metallo-depent_PP-like |
Pfami | View protein in Pfam PF00149, Metallophos, 1 hit |
PIRSFi | PIRSF036767, ASM-like_PDE, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketIsoform 1 (identifier: Q92484-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MALVRALVCC LLTAWHCRSG LGLPVAPAGG RNPPPAIGQF WHVTDLHLDP
60 70 80 90 100
TYHITDDHTK VCASSKGANA SNPGPFGDVL CDSPYQLILS AFDFIKNSGQ
110 120 130 140 150
EASFMIWTGD SPPHVPVPEL STDTVINVIT NMTTTIQSLF PNLQVFPALG
160 170 180 190 200
NHDYWPQDQL PVVTSKVYNA VANLWKPWLD EEAISTLRKG GFYSQKVTTN
210 220 230 240 250
PNLRIISLNT NLYYGPNIMT LNKTDPANQF EWLESTLNNS QQNKEKVYII
260 270 280 290 300
AHVPVGYLPS SQNITAMREY YNEKLIDIFQ KYSDVIAGQF YGHTHRDSIM
310 320 330 340 350
VLSDKKGSPV NSLFVAPAVT PVKSVLEKQT NNPGIRLFQY DPRDYKLLDM
360 370 380 390 400
LQYYLNLTEA NLKGESIWKL EYILTQTYDI EDLQPESLYG LAKQFTILDS
410 420 430 440 450
KQFIKYYNYF FVSYDSSVTC DKTCKAFQIC AIMNLDNISY ADCLKQLYIK
HNY
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 452 | N → K in CAA69330 (Ref. 5) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_048338 | 16 | H → Y. Corresponds to variant dbSNP:rs12523814Ensembl. | 1 | |
Natural variantiVAR_048339 | 161 | P → S. Corresponds to variant dbSNP:rs28385609Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_054640 | 1 – 131 | Missing in isoform 2. 1 PublicationAdd BLAST | 131 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK301365 mRNA Translation: BAH13465.1 AL732431 Genomic DNA No translation available. CH471051 Genomic DNA Translation: EAW48164.1 BC018999 mRNA Translation: AAH18999.1 Y08136 mRNA Translation: CAA69330.1 |
CCDSi | CCDS5128.1 [Q92484-1] CCDS69190.1 [Q92484-2] |
RefSeqi | NP_001273067.1, NM_001286138.1 [Q92484-2] NP_006705.1, NM_006714.4 [Q92484-1] |
Genome annotation databases
Ensembli | ENST00000368440; ENSP00000357425; ENSG00000172594 [Q92484-1] ENST00000539041; ENSP00000442152; ENSG00000172594 [Q92484-2] |
GeneIDi | 10924 |
KEGGi | hsa:10924 |
UCSCi | uc003pzg.5, human [Q92484-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK301365 mRNA Translation: BAH13465.1 AL732431 Genomic DNA No translation available. CH471051 Genomic DNA Translation: EAW48164.1 BC018999 mRNA Translation: AAH18999.1 Y08136 mRNA Translation: CAA69330.1 |
CCDSi | CCDS5128.1 [Q92484-1] CCDS69190.1 [Q92484-2] |
RefSeqi | NP_001273067.1, NM_001286138.1 [Q92484-2] NP_006705.1, NM_006714.4 [Q92484-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5EBB | X-ray | 2.60 | A/B/C | 34-443 | [»] | |
5EBE | X-ray | 3.00 | A | 33-450 | [»] | |
B/C | 33-447 | [»] | ||||
SMRi | Q92484 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 116128, 1 interactor |
IntActi | Q92484, 2 interactors |
STRINGi | 9606.ENSP00000357425 |
PTM databases
GlyConnecti | 987, 3 N-Linked glycans (2 sites) |
GlyGeni | Q92484, 7 sites, 1 N-linked glycan (1 site) |
iPTMneti | Q92484 |
PhosphoSitePlusi | Q92484 |
Genetic variation databases
BioMutai | SMPDL3A |
DMDMi | 39932730 |
Proteomic databases
EPDi | Q92484 |
jPOSTi | Q92484 |
MassIVEi | Q92484 |
MaxQBi | Q92484 |
PaxDbi | Q92484 |
PeptideAtlasi | Q92484 |
PRIDEi | Q92484 |
ProteomicsDBi | 6826 75265 [Q92484-1] |
Protocols and materials databases
Antibodypediai | 32649, 131 antibodies |
DNASUi | 10924 |
Genome annotation databases
Ensembli | ENST00000368440; ENSP00000357425; ENSG00000172594 [Q92484-1] ENST00000539041; ENSP00000442152; ENSG00000172594 [Q92484-2] |
GeneIDi | 10924 |
KEGGi | hsa:10924 |
UCSCi | uc003pzg.5, human [Q92484-1] |
Organism-specific databases
CTDi | 10924 |
DisGeNETi | 10924 |
GeneCardsi | SMPDL3A |
HGNCi | HGNC:17389, SMPDL3A |
HPAi | ENSG00000172594, Low tissue specificity |
MIMi | 610728, gene |
neXtProti | NX_Q92484 |
OpenTargetsi | ENSG00000172594 |
PharmGKBi | PA134932128 |
VEuPathDBi | HostDB:ENSG00000172594.12 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3770, Eukaryota |
GeneTreei | ENSGT00950000183182 |
HOGENOMi | CLU_014743_0_0_1 |
InParanoidi | Q92484 |
OMAi | VICDKTC |
OrthoDBi | 1142100at2759 |
PhylomeDBi | Q92484 |
TreeFami | TF313674 |
Enzyme and pathway databases
PathwayCommonsi | Q92484 |
SABIO-RKi | Q92484 |
Miscellaneous databases
BioGRID-ORCSi | 10924, 3 hits in 873 CRISPR screens |
ChiTaRSi | SMPDL3A, human |
GenomeRNAii | 10924 |
Pharosi | Q92484, Tbio |
PROi | PR:Q92484 |
RNActi | Q92484, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000172594, Expressed in colonic mucosa and 234 other tissues |
Genevisiblei | Q92484, HS |
Family and domain databases
CDDi | cd00842, MPP_ASMase, 1 hit |
Gene3Di | 3.60.21.10, 1 hit |
InterProi | View protein in InterPro IPR017064, ASM-like_Pdiesterase_prd IPR041805, ASMase/PPN1_MPP IPR004843, Calcineurin-like_PHP_ApaH IPR029052, Metallo-depent_PP-like |
Pfami | View protein in Pfam PF00149, Metallophos, 1 hit |
PIRSFi | PIRSF036767, ASM-like_PDE, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | ASM3A_HUMAN | |
Accessioni | Q92484Primary (citable) accession number: Q92484 Secondary accession number(s): B7Z729, Q8WV13 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 29, 2001 |
Last sequence update: | December 15, 2003 | |
Last modified: | February 10, 2021 | |
This is version 148 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 6
Human chromosome 6: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants