UniProtKB - Q92485 (ASM3B_HUMAN)
Protein
Acid sphingomyelinase-like phosphodiesterase 3b
Gene
SMPDL3B
Organism
Homo sapiens (Human)
Status
Functioni
Lipid-modulating phosphodiesterase (PubMed:26095358). Active on the surface of macrophages and dendritic cells and strongly influences macrophage lipid composition and membrane fluidity. Acts as a negative regulator of Toll-like receptor signaling (By similarity). Has in vitro phosphodiesterase activity, but the physiological substrate is unknown (PubMed:26095358). Lacks activity with phosphocholine-containing lipids, but can cleave CDP-choline, and can release phosphate from ATP and ADP (in vitro) (By similarity).By similarity1 Publication
Cofactori
Zn2+By similarityNote: Binds 2 Zn2+ ions per subunit.By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 28 | Zinc 1By similarity | 1 | |
Metal bindingi | 30 | Zinc 1By similarity | 1 | |
Metal bindingi | 93 | Zinc 1By similarity | 1 | |
Metal bindingi | 93 | Zinc 2By similarity | 1 | |
Metal bindingi | 134 | Zinc 2By similarity | 1 | |
Metal bindingi | 236 | Zinc 2By similarity | 1 | |
Metal bindingi | 277 | Zinc 2By similarity | 1 | |
Metal bindingi | 279 | Zinc 1By similarity | 1 |
GO - Molecular functioni
- hydrolase activity, acting on glycosyl bonds Source: UniProtKB-KW
- phosphoric diester hydrolase activity Source: UniProtKB
- sphingomyelin phosphodiesterase activity Source: InterPro
- zinc ion binding Source: UniProtKB
GO - Biological processi
- inflammatory response Source: UniProtKB-KW
- innate immune response Source: UniProtKB-KW
- membrane lipid catabolic process Source: UniProtKB
- negative regulation of inflammatory response Source: UniProtKB
- negative regulation of toll-like receptor signaling pathway Source: UniProtKB
- sphingomyelin catabolic process Source: InterPro
Keywordsi
Molecular function | Glycosidase, Hydrolase |
Biological process | Immunity, Inflammatory response, Innate immunity, Lipid degradation, Lipid metabolism |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | Q92485 |
Names & Taxonomyi
Protein namesi | Recommended name: Acid sphingomyelinase-like phosphodiesterase 3b (EC:3.1.4.-1 Publication)Short name: ASM-like phosphodiesterase 3b |
Gene namesi | Name:SMPDL3B Synonyms:ASML3B, ASMLPD |
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
EuPathDBi | HostDB:ENSG00000130768.14 |
HGNCi | HGNC:21416, SMPDL3B |
MIMi | 617737, gene |
neXtProti | NX_Q92485 |
Subcellular locationi
Extracellular region or secreted
- Secreted By similarity
Plasma membrane
- Cell membrane By similarity; GPI-anchor By similarity
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
- extracellular space Source: UniProtKB
Plasma Membrane
- plasma membrane Source: UniProtKB
Other locations
- anchored component of membrane Source: UniProtKB-KW
Keywords - Cellular componenti
Cell membrane, Membrane, SecretedPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 135 | H → A: Reduced phosphodiesterase activity. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 27293 |
OpenTargetsi | ENSG00000130768 |
PharmGKBi | PA134889099 |
Miscellaneous databases
Pharosi | Q92485, Tbio |
Polymorphism and mutation databases
BioMutai | SMPDL3B |
DMDMi | 62906890 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 18 | Sequence analysisAdd BLAST | 18 | |
ChainiPRO_0000002331 | 19 – 455 | Acid sphingomyelinase-like phosphodiesterase 3bAdd BLAST | 437 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 45 ↔ 64 | By similarity | ||
Glycosylationi | 72 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 164 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 343 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 405 ↔ 409 | By similarity | ||
Disulfide bondi | 415 ↔ 428 | By similarity |
Post-translational modificationi
N-glycosylated.1 Publication
Keywords - PTMi
Disulfide bond, Glycoprotein, GPI-anchor, LipoproteinProteomic databases
EPDi | Q92485 |
jPOSTi | Q92485 |
MassIVEi | Q92485 |
MaxQBi | Q92485 |
PaxDbi | Q92485 |
PeptideAtlasi | Q92485 |
PRIDEi | Q92485 |
ProteomicsDBi | 75266 [Q92485-1] 75267 [Q92485-2] |
PTM databases
GlyGeni | Q92485, 3 sites |
iPTMneti | Q92485 |
PhosphoSitePlusi | Q92485 |
Expressioni
Gene expression databases
Bgeei | ENSG00000130768, Expressed in pancreas and 120 other tissues |
ExpressionAtlasi | Q92485, baseline and differential |
Genevisiblei | Q92485, HS |
Organism-specific databases
HPAi | ENSG00000130768, Tissue enhanced (intestine, pancreas, salivary gland, thyroid gland) |
Interactioni
Subunit structurei
Interacts with TLR4, TLR7, TLR8 and TLR9.
By similarityBinary interactionsi
Hide detailsIsoform 2 [Q92485-2]
With | #Exp. | IntAct |
---|---|---|
INSR - isoform Long [P06213-1] | 2 | EBI-21501656,EBI-15558981 |
INSR - isoform Short [P06213-2] | 2 | EBI-21501656,EBI-9984921 |
Protein-protein interaction databases
BioGRIDi | 118117, 14 interactors |
IntActi | Q92485, 7 interactors |
MINTi | Q92485 |
STRINGi | 9606.ENSP00000363001 |
Miscellaneous databases
RNActi | Q92485, protein |
Family & Domainsi
Sequence similaritiesi
Belongs to the acid sphingomyelinase family.Curated
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | KOG3770, Eukaryota |
GeneTreei | ENSGT00950000183182 |
HOGENOMi | CLU_014743_0_2_1 |
InParanoidi | Q92485 |
OMAi | DHVCAIR |
OrthoDBi | 1116351at2759 |
PhylomeDBi | Q92485 |
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 basketThis entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q92485-1) [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
MRLLAWLIFL ANWGGARAEP GKFWHIADLH LDPDYKVSKD PFQVCPSAGS
60 70 80 90 100
QPVPDAGPWG DYLCDSPWAL INSSIYAMKE IEPEPDFILW TGDDTPHVPD
110 120 130 140 150
EKLGEAAVLE IVERLTKLIR EVFPDTKVYA ALGNHDFHPK NQFPAGSNNI
160 170 180 190 200
YNQIAELWKP WLSNESIALF KKGAFYCEKL PGPSGAGRIV VLNTNLYYTS
210 220 230 240 250
NALTADMADP GQQFQWLEDV LTDASKAGDM VYIVGHVPPG FFEKTQNKAW
260 270 280 290 300
FREGFNEKYL KVVRKHHRVI AGQFFGHHHT DSFRMLYDDA GVPISAMFIT
310 320 330 340 350
PGVTPWKTTL PGVVNGANNP AIRVFEYDRA TLSLKDMVTY FMNLSQANAQ
360 370 380 390 400
GTPRWELEYQ LTEAYGVPDA SAHSMHTVLD RIAGDQSTLQ RYYVYNSVSY
410 420 430 440 450
SAGVCDEACS MQHVCAMRQV DIDAYTTCLY ASGTTPVPQL PLLLMALLGL
CTLVL
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketF8VWW8 | F8VWW8_HUMAN | Acid sphingomyelinase-like phosphod... | SMPDL3B | 407 | Annotation score: | ||
Q5T0Y8 | Q5T0Y8_HUMAN | Acid sphingomyelinase-like phosphod... | SMPDL3B | 269 | Annotation score: | ||
F8VXS3 | F8VXS3_HUMAN | Acid sphingomyelinase-like phosphod... | SMPDL3B | 102 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 375 – 376 | MH → ID in CAA69328 (Ref. 1) Curated | 2 | |
Sequence conflicti | 453 – 455 | LVL → TRAVTCQAHHSSW in CAA69328 (Ref. 1) Curated | 3 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_048340 | 381 | R → H. Corresponds to variant dbSNP:rs34560878EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_013478 | 336 – 373 | DMVTY…DASAH → VRSPAEARGGGWEGLKCITT FPHSQLIHLPLTTEPQEG in isoform 2. 1 PublicationAdd BLAST | 38 | |
Alternative sequenceiVSP_013479 | 374 – 455 | Missing in isoform 2. 1 PublicationAdd BLAST | 82 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Y08134 mRNA Translation: CAA69328.1 AK316500 mRNA Translation: BAH14871.1 AL512288 Genomic DNA No translation available. CH471059 Genomic DNA Translation: EAX07721.1 BC014444 mRNA Translation: AAH14444.1 |
CCDSi | CCDS30655.1 [Q92485-1] CCDS30656.1 [Q92485-2] |
RefSeqi | NP_001009568.1, NM_001009568.2 [Q92485-2] NP_055289.2, NM_014474.3 [Q92485-1] |
Genome annotation databases
Ensembli | ENST00000373888; ENSP00000362995; ENSG00000130768 [Q92485-2] ENST00000373894; ENSP00000363001; ENSG00000130768 [Q92485-1] |
GeneIDi | 27293 |
KEGGi | hsa:27293 |
UCSCi | uc001bpf.4, human [Q92485-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Y08134 mRNA Translation: CAA69328.1 AK316500 mRNA Translation: BAH14871.1 AL512288 Genomic DNA No translation available. CH471059 Genomic DNA Translation: EAX07721.1 BC014444 mRNA Translation: AAH14444.1 |
CCDSi | CCDS30655.1 [Q92485-1] CCDS30656.1 [Q92485-2] |
RefSeqi | NP_001009568.1, NM_001009568.2 [Q92485-2] NP_055289.2, NM_014474.3 [Q92485-1] |
3D structure databases
SMRi | Q92485 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 118117, 14 interactors |
IntActi | Q92485, 7 interactors |
MINTi | Q92485 |
STRINGi | 9606.ENSP00000363001 |
PTM databases
GlyGeni | Q92485, 3 sites |
iPTMneti | Q92485 |
PhosphoSitePlusi | Q92485 |
Polymorphism and mutation databases
BioMutai | SMPDL3B |
DMDMi | 62906890 |
Proteomic databases
EPDi | Q92485 |
jPOSTi | Q92485 |
MassIVEi | Q92485 |
MaxQBi | Q92485 |
PaxDbi | Q92485 |
PeptideAtlasi | Q92485 |
PRIDEi | Q92485 |
ProteomicsDBi | 75266 [Q92485-1] 75267 [Q92485-2] |
Protocols and materials databases
Antibodypediai | 30880, 94 antibodies |
Genome annotation databases
Ensembli | ENST00000373888; ENSP00000362995; ENSG00000130768 [Q92485-2] ENST00000373894; ENSP00000363001; ENSG00000130768 [Q92485-1] |
GeneIDi | 27293 |
KEGGi | hsa:27293 |
UCSCi | uc001bpf.4, human [Q92485-1] |
Organism-specific databases
CTDi | 27293 |
DisGeNETi | 27293 |
EuPathDBi | HostDB:ENSG00000130768.14 |
GeneCardsi | SMPDL3B |
HGNCi | HGNC:21416, SMPDL3B |
HPAi | ENSG00000130768, Tissue enhanced (intestine, pancreas, salivary gland, thyroid gland) |
MIMi | 617737, gene |
neXtProti | NX_Q92485 |
OpenTargetsi | ENSG00000130768 |
PharmGKBi | PA134889099 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3770, Eukaryota |
GeneTreei | ENSGT00950000183182 |
HOGENOMi | CLU_014743_0_2_1 |
InParanoidi | Q92485 |
OMAi | DHVCAIR |
OrthoDBi | 1116351at2759 |
PhylomeDBi | Q92485 |
TreeFami | TF313674 |
Enzyme and pathway databases
PathwayCommonsi | Q92485 |
Miscellaneous databases
BioGRID-ORCSi | 27293, 11 hits in 844 CRISPR screens |
ChiTaRSi | SMPDL3B, human |
GenomeRNAii | 27293 |
Pharosi | Q92485, Tbio |
PROi | PR:Q92485 |
RNActi | Q92485, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000130768, Expressed in pancreas and 120 other tissues |
ExpressionAtlasi | Q92485, baseline and differential |
Genevisiblei | Q92485, 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 | ASM3B_HUMAN | |
Accessioni | Q92485Primary (citable) accession number: Q92485 Secondary accession number(s): B7ZB35, Q5T0Z0, Q96CB7 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 29, 2001 |
Last sequence update: | April 26, 2005 | |
Last modified: | December 2, 2020 | |
This is version 160 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
Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families - Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations