Q8IV08 · PLD3_HUMAN
- Protein5'-3' exonuclease PLD3
- GenePLD3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids490 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
5'->3' DNA exonuclease which digests single-stranded DNA (ssDNA) (PubMed:30312375).
Regulates inflammatory cytokine responses via the degradation of nucleic acids, by reducing the concentration of ssDNA able to stimulate TLR9, a nucleotide-sensing receptor in collaboration with PLD4 (By similarity).
May be important in myotube formation (PubMed:22428023).
Plays a role in lysosomal homeostasis (PubMed:28128235).
Involved in the regulation of endosomal protein sorting (PubMed:29368044).
Regulates inflammatory cytokine responses via the degradation of nucleic acids, by reducing the concentration of ssDNA able to stimulate TLR9, a nucleotide-sensing receptor in collaboration with PLD4 (By similarity).
May be important in myotube formation (PubMed:22428023).
Plays a role in lysosomal homeostasis (PubMed:28128235).
Involved in the regulation of endosomal protein sorting (PubMed:29368044).
Catalytic activity
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 201 | |||||
Sequence: H | ||||||
Active site | 203 | |||||
Sequence: K | ||||||
Active site | 208 | |||||
Sequence: D |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | early endosome membrane | |
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | extracellular exosome | |
Cellular Component | Golgi membrane | |
Cellular Component | late endosome membrane | |
Cellular Component | lysosomal lumen | |
Cellular Component | lysosomal membrane | |
Molecular Function | phospholipase D activity | |
Molecular Function | single-stranded DNA 5'-3' DNA exonuclease activity | |
Biological Process | immune system process | |
Biological Process | inflammatory response | |
Biological Process | myotube differentiation | |
Biological Process | regulation of cytokine production involved in inflammatory response |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended name5'-3' exonuclease PLD3
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ8IV08
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Single-pass type II membrane protein
Early endosome membrane ; Single-pass type II membrane protein
Late endosome membrane ; Single-pass type II membrane protein
Golgi apparatus membrane ; Single-pass type II membrane protein
Endosome membrane ; Single-pass type II membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-38 | Cytoplasmic | ||||
Sequence: MKPKLMYQELKVPAEEPANELPMNEIEAWKAAEKKARW | ||||||
Transmembrane | 39-59 | Helical; Signal-anchor for type II membrane protein | ||||
Sequence: VLLVLILAVVGFGALMTQLFL | ||||||
Topological domain | 60-490 | Lumenal | ||||
Sequence: WEYGDLHLFGPNQRPAPCYDPCEAVLVESIPEGLDFPNASTGNPSTSQAWLGLLAGAHSSLDIASFYWTLTNNDTHTQEPSAQQGEEVLRQLQTLAPKGVNVRIAVSKPSGPQPQADLQALLQSGAQVRMVDMQKLTHGVLHTKFWVVDQTHFYLGSANMDWRSLTQVKELGVVMYNCSCLARDLTKIFEAYWFLGQAGSSIPSTWPRFYDTRYNQETPMEICLNGTPALAYLASAPPPLCPSGRTPDLKALLNVVDNARSFIYVAVMNYLPTLEFSHPHRFWPAIDDGLRRATYERGVKVRLLISCWGHSEPSMRAFLLSLAALRDNHTHSDIQVKLFVVPADEAQARIPYARVNHNKYMVTERATYIGTSNWSGNYFTETAGTSLLVTQNGRGGLRSQLEAIFLRDWDSPYSHDLDTSADSVGNACRLL |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Spinocerebellar ataxia 46 (SCA46)
- Note
- DescriptionA form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA46 is a slowly progressive, autosomal dominant form with onset in adulthood.
- See alsoMIM:617770
Natural variants in SCA46
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_075920 | 308 | L>P | in SCA46; uncertain significance; reduced lysosomal localization; induces retention in the ER; reduction of proteolityc cleavage; loss of exonuclease activity; dbSNP:rs537053537 |
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 7 | Slightly increased plasma membrane localization, does not affect delivery to lysosomes. | ||||
Sequence: Y → A | ||||||
Natural variant | VAR_075905 | 63 | in dbSNP:rs142070038 | |||
Sequence: G → S | ||||||
Natural variant | VAR_075906 | 76 | in dbSNP:rs138674695 | |||
Sequence: P → A | ||||||
Natural variant | VAR_075907 | 159 | in dbSNP:rs374184677 | |||
Sequence: V → M | ||||||
Natural variant | VAR_075908 | 162 | ||||
Sequence: R → C | ||||||
Natural variant | VAR_075909 | 173 | in dbSNP:rs866850284 | |||
Sequence: P → S | ||||||
Natural variant | VAR_075910 | 175 | in dbSNP:rs780604999 | |||
Sequence: A → G | ||||||
Natural variant | VAR_075911 | 188 | in dbSNP:rs1326374111 | |||
Sequence: R → C | ||||||
Natural variant | VAR_075912 | 222 | in dbSNP:rs765630414 | |||
Sequence: R → H | ||||||
Natural variant | VAR_071186 | 232 | found in patients with Alzheimer disease; uncertain significance; does not reduce either amyloid-beta levels or APP expression; dbSNP:rs145999145 | |||
Sequence: V → M | ||||||
Natural variant | VAR_075913 | 242 | in dbSNP:rs757965784 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_075914 | 249 | in dbSNP:rs746715924 | |||
Sequence: E → G | ||||||
Natural variant | VAR_075915 | 272 | in dbSNP:rs144312764 | |||
Sequence: R → C | ||||||
Natural variant | VAR_075916 | 284 | in dbSNP:rs200274020 | |||
Sequence: N → S | ||||||
Natural variant | VAR_075917 | 293 | in dbSNP:rs368737000 | |||
Sequence: A → V | ||||||
Natural variant | VAR_075918 | 297 | ||||
Sequence: P → L | ||||||
Natural variant | VAR_075919 | 300 | in dbSNP:rs146083475 | |||
Sequence: C → Y | ||||||
Natural variant | VAR_075920 | 308 | in SCA46; uncertain significance; reduced lysosomal localization; induces retention in the ER; reduction of proteolityc cleavage; loss of exonuclease activity; dbSNP:rs537053537 | |||
Sequence: L → P | ||||||
Natural variant | VAR_075921 | 358 | in dbSNP:rs370488565 | |||
Sequence: V → I | ||||||
Mutagenesis | 418 | Impairs myotube formation. | ||||
Sequence: K → R | ||||||
Natural variant | VAR_075922 | 426 | in dbSNP:rs745463234 | |||
Sequence: T → A | ||||||
Natural variant | VAR_075923 | 429 | in dbSNP:rs986006936 | |||
Sequence: G → R |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 619 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000280326 | 1-490 | 5'-3' exonuclease PLD3 | |||
Sequence: MKPKLMYQELKVPAEEPANELPMNEIEAWKAAEKKARWVLLVLILAVVGFGALMTQLFLWEYGDLHLFGPNQRPAPCYDPCEAVLVESIPEGLDFPNASTGNPSTSQAWLGLLAGAHSSLDIASFYWTLTNNDTHTQEPSAQQGEEVLRQLQTLAPKGVNVRIAVSKPSGPQPQADLQALLQSGAQVRMVDMQKLTHGVLHTKFWVVDQTHFYLGSANMDWRSLTQVKELGVVMYNCSCLARDLTKIFEAYWFLGQAGSSIPSTWPRFYDTRYNQETPMEICLNGTPALAYLASAPPPLCPSGRTPDLKALLNVVDNARSFIYVAVMNYLPTLEFSHPHRFWPAIDDGLRRATYERGVKVRLLISCWGHSEPSMRAFLLSLAALRDNHTHSDIQVKLFVVPADEAQARIPYARVNHNKYMVTERATYIGTSNWSGNYFTETAGTSLLVTQNGRGGLRSQLEAIFLRDWDSPYSHDLDTSADSVGNACRLL | ||||||
Glycosylation | 97 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 132 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Post-translational modification
N-glycosylated.
Proteolytically processed to a soluble form that is stable within endosomes and lysosomes. During transport through the secretory pathway becomes proteolysed by cysteine proteases, thereby releasing a stable soluble lysosomal lumenal polypeptide, whereas the transmembrane-bound fragment is rapidly degraded. Its transport route to lysosomes involves ubiquitination and the ESCRT complex.
Ubiquitinated at N-terminus. Ubiquitination mediates sorting into lysosomes.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Widely expressed. In the brain, high levels of expression are detected in the frontal, temporal and occipital cortices and hippocampus. Expressed at low level in corpus callosum.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with APP.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q8IV08 | CNIH3 Q8TBE1 | 3 | EBI-2689908, EBI-12208021 | |
BINARY | Q8IV08 | NFKB1 P19838 | 2 | EBI-2689908, EBI-300010 | |
BINARY | Q8IV08 | OPRM1 P35372-10 | 3 | EBI-2689908, EBI-12807478 | |
BINARY | Q8IV08 | SMCO4 Q9NRQ5 | 3 | EBI-2689908, EBI-8640191 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 196-223 | PLD phosphodiesterase 1 | ||||
Sequence: THGVLHTKFWVVDQTHFYLGSANMDWRS | ||||||
Domain | 411-437 | PLD phosphodiesterase 2 | ||||
Sequence: YARVNHNKYMVTERATYIGTSNWSGNY |
Sequence similarities
Belongs to the phospholipase D family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length490
- Mass (Da)54,705
- Last updated2003-03-01 v1
- Checksum444EC4D02F5610F1
Computationally mapped potential isoform sequences
There are 15 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
M0R1F7 | M0R1F7_HUMAN | PLD3 | 213 | ||
M0R3G9 | M0R3G9_HUMAN | PLD3 | 71 | ||
M0R2W7 | M0R2W7_HUMAN | PLD3 | 111 | ||
M0R2E7 | M0R2E7_HUMAN | PLD3 | 44 | ||
A0A0A0MS28 | A0A0A0MS28_HUMAN | PLD3 | 128 | ||
M0QY94 | M0QY94_HUMAN | PLD3 | 70 | ||
M0QX50 | M0QX50_HUMAN | PLD3 | 81 | ||
M0QX99 | M0QX99_HUMAN | PLD3 | 119 | ||
M0QZK2 | M0QZK2_HUMAN | PLD3 | 28 | ||
M0QYJ4 | M0QYJ4_HUMAN | PLD3 | 121 | ||
A0A8V8TRD4 | A0A8V8TRD4_HUMAN | PLD3 | 507 | ||
A0A8V8TPY8 | A0A8V8TPY8_HUMAN | PLD3 | 468 | ||
A0A8V8TQH4 | A0A8V8TQH4_HUMAN | PLD3 | 346 | ||
A0A8V8TQH6 | A0A8V8TQH6_HUMAN | PLD3 | 464 | ||
E2QRG1 | E2QRG1_HUMAN | PLD3 | 177 |
Sequence caution
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 473 | in Ref. 1; AAB16799 | ||||
Sequence: S → I |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U60644 EMBL· GenBank· DDBJ | AAB16799.1 EMBL· GenBank· DDBJ | mRNA | Frameshift | |
BC000553 EMBL· GenBank· DDBJ | AAH00553.2 EMBL· GenBank· DDBJ | mRNA | ||
BC036327 EMBL· GenBank· DDBJ | AAH36327.1 EMBL· GenBank· DDBJ | mRNA | ||
BC096820 EMBL· GenBank· DDBJ | AAH96820.1 EMBL· GenBank· DDBJ | mRNA |