Q9BRC7 · PLCD4_HUMAN
- Protein1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4
- GenePLCD4
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids762 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Hydrolyzes the phosphatidylinositol 4,5-bisphosphate (PIP2) to generate 2 second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG mediates the activation of protein kinase C (PKC), while IP3 releases Ca2+ from intracellular stores. Required for acrosome reaction in sperm during fertilization, probably by acting as an important enzyme for intracellular Ca2+ mobilization in the zona pellucida-induced acrosome reaction. May play a role in cell growth. Modulates the liver regeneration in cooperation with nuclear PKC. Overexpression up-regulates the Erk signaling pathway and proliferation.
Isoform 2
Acts as a non-receptor guanine nucleotide exchange factor which binds to and activates guanine nucleotide-binding protein (G-protein) alpha subunit GNAI3.
Catalytic activity
- a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + H2O = 1D-myo-inositol 1,4,5-trisphosphate + a 1,2-diacyl-sn-glycerol + H+This reaction proceeds in the forward direction.
- a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + H2O = 1D-myo-inositol 1-phosphate + a 1,2-diacyl-sn-glycerol + H+This reaction proceeds in the forward direction.
Cofactor
Note: Binds 5 Ca2+ ions per subunit. Two of the Ca2+ ions are bound to the C2 domain.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 147 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 149 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 151 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 153 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 158 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 183 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 185 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 187 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 189 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 194 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Active site | 305 | |||||
Sequence: H | ||||||
Binding site | 306 | Ca2+ 3 (UniProtKB | ChEBI); catalytic | ||||
Sequence: N | ||||||
Binding site | 335 | Ca2+ 3 (UniProtKB | ChEBI); catalytic | ||||
Sequence: E | ||||||
Binding site | 337 | Ca2+ 3 (UniProtKB | ChEBI); catalytic | ||||
Sequence: D | ||||||
Active site | 350 | |||||
Sequence: H | ||||||
Binding site | 384 | Ca2+ 3 (UniProtKB | ChEBI); catalytic | ||||
Sequence: E | ||||||
Binding site | 433 | substrate | ||||
Sequence: K | ||||||
Binding site | 435 | substrate | ||||
Sequence: K | ||||||
Binding site | 522 | substrate | ||||
Sequence: S | ||||||
Binding site | 549 | substrate | ||||
Sequence: R | ||||||
Binding site | 650 | Ca2+ 4 (UniProtKB | ChEBI) | ||||
Sequence: I | ||||||
Binding site | 652 | Ca2+ 4 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 676 | Ca2+ 4 (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 705 | Ca2+ 5 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 706 | Ca2+ 5 (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 707 | Ca2+ 5 (UniProtKB | ChEBI) | ||||
Sequence: D |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Cellular Component | endoplasmic reticulum | |
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | nucleus | |
Cellular Component | plasma membrane | |
Molecular Function | calcium ion binding | |
Molecular Function | G-protein alpha-subunit binding | |
Molecular Function | guanyl-nucleotide exchange factor activity | |
Molecular Function | phosphatidylinositol phospholipase C activity | |
Biological Process | acrosome reaction | |
Biological Process | intracellular signal transduction | |
Biological Process | lipid catabolic process | |
Biological Process | small GTPase-mediated signal transduction |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Chemistry
Names & Taxonomy
Protein names
- Recommended name1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4
- EC number
- Short nameshPLCD4
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9BRC7
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Membrane ; Peripheral membrane protein
Note: Localizes primarily to intracellular membranes mostly to the endoplasmic reticulum.
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 224-228 | Abolishes binding to and activation of GNAI3. | ||||
Sequence: LLEFL → ALEAA | ||||||
Mutagenesis | 227 | Marked but incomplete decrease in GNAI3 binding and reduced activation of G-protein signaling. | ||||
Sequence: F → A | ||||||
Mutagenesis | 227-228 | Abolishes binding to GNAI3. | ||||
Sequence: FL → AA |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 898 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000306824 | 1-762 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4 | |||
Sequence: MASLLQDQLTTDQDLLLMQEGMPMRKVRSKSWKKLRYFRLQNDGMTVWHARQARGSAKPSFSISDVETIRNGHDSELLRSLAEELPLEQGFTIVFHGRRSNLDLMANSVEEAQIWMRGLQLLVDLVTSMDHQERLDQWLSDWFQRGDKNQDGKMSFQEVQRLLHLMNVEMDQEYAFSLFQAADTSQSGTLEGEEFVQFYKALTKRAEVQELFESFSADGQKLTLLEFLDFLQEEQKERDCTSELALELIDRYEPSDSGKLRHVLSMDGFLSYLCSKDGDIFNPACLPIYQDMTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDGPSGEPVVYHGHTLTSRILFKDVVATVAQYAFQTSDYPVILSLETHCSWEQQQTMARHLTEILGEQLLSTTLDGVLPTQLPSPEELRRKILVKGKKLTLEEDLEYEEEEAEPELEESELALESQFETEPEPQEQNLQNKDKKKKSKPILCPALSSLVIYLKSVSFRSFTHSKEHYHFYEISSFSETKAKRLIKEAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQELWNAGCQMVAMNMQTAGLEMDICDGHFRQNGGCGYVLKPDFLRDIQSSFHPEKPISPFKAQTLLIQVISGQQLPKVDKTKEGSIVDPLVKVQIFGVRLDTARQETNYVENNGFNPYWGQTLCFRVLVPELAMLRFVVMDYDWKSRNDFIGQYTLPWTCMQQGYRHIHLLSKDGISLRPASIFVYICIQEGLEGDES | ||||||
Modified residue | 457 | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Highly expressed in skeletal muscle and kidney tissues, and at moderate level in intestinal tissue. Expressed in corneal epithelial cells.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with GRIP1 (By similarity).
Isoform 2
Interacts (via GBA motif) with guanine nucleotide-binding protein G(i) alpha subunit GNAI3 (inactive GDP-bound form); high-affinity interaction (PubMed:30194280).
Isoform 1
Interacts (via GBA motif) with guanine nucleotide-binding protein G(i) alpha subunit GNAI3 (inactive GDP-bound form); low-affinity interaction (PubMed:30194280).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9BRC7 | MEOX1 P50221 | 3 | EBI-748799, EBI-2864512 | |
BINARY | Q9BRC7 | MEOX2 Q6FHY5 | 3 | EBI-748799, EBI-16439278 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region, motif, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 16-124 | PH | ||||
Sequence: LLMQEGMPMRKVRSKSWKKLRYFRLQNDGMTVWHARQARGSAKPSFSISDVETIRNGHDSELLRSLAEELPLEQGFTIVFHGRRSNLDLMANSVEEAQIWMRGLQLLVD | ||||||
Region | 26-53 | Substrate binding | ||||
Sequence: KVRSKSWKKLRYFRLQNDGMTVWHARQA | ||||||
Domain | 134-169 | EF-hand 1 | ||||
Sequence: RLDQWLSDWFQRGDKNQDGKMSFQEVQRLLHLMNVE | ||||||
Domain | 170-205 | EF-hand 2 | ||||
Sequence: MDQEYAFSLFQAADTSQSGTLEGEEFVQFYKALTKR | ||||||
Domain | 206-237 | EF-hand 3 | ||||
Sequence: AEVQELFESFSADGQKLTLLEFLDFLQEEQKE | ||||||
Motif | 213-243 | GBA | ||||
Sequence: ESFSADGQKLTLLEFLDFLQEEQKERDCTSE | ||||||
Domain | 290-435 | PI-PLC X-box | ||||
Sequence: QDMTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDGPSGEPVVYHGHTLTSRILFKDVVATVAQYAFQTSDYPVILSLETHCSWEQQQTMARHLTEILGEQLLSTTLDGVLPTQLPSPEELRRKILVKGK | ||||||
Compositional bias | 443-463 | Acidic residues | ||||
Sequence: LEYEEEEAEPELEESELALES | ||||||
Region | 443-483 | Disordered | ||||
Sequence: LEYEEEEAEPELEESELALESQFETEPEPQEQNLQNKDKKK | ||||||
Domain | 493-609 | PI-PLC Y-box | ||||
Sequence: LSSLVIYLKSVSFRSFTHSKEHYHFYEISSFSETKAKRLIKEAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQELWNAGCQMVAMNMQTAGLEMDICDGHFRQNGGCGYVLKPDFLR | ||||||
Domain | 609-736 | C2 | ||||
Sequence: RDIQSSFHPEKPISPFKAQTLLIQVISGQQLPKVDKTKEGSIVDPLVKVQIFGVRLDTARQETNYVENNGFNPYWGQTLCFRVLVPELAMLRFVVMDYDWKSRNDFIGQYTLPWTCMQQGYRHIHLLS | ||||||
Motif | 731-734 | PDZ-binding | ||||
Sequence: HIHL |
Domain
The PDZ-binding motif mediates the interaction with GRIP1.
The C2 domain mediates pre-localization to the membrane prior to Ca2+ import and non-selective Ca2+-mediated targeting to various cellular membranes.
The PH domain is not a critical determinant of the membrane localization.
The GBA (G-alpha binding and activating) motif mediates binding to the alpha subunits of guanine nucleotide-binding proteins (G proteins).
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q9BRC7-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- NoteAcceptor splice site between exons 4 and 5 is non-canonical but conserved through species for that particular gene.
- Length762
- Mass (Da)87,585
- Last updated2001-06-01 v1
- Checksum5444BE5CE2AEA3EF
Q9BRC7-2
- Name2
- SynonymsPLCD4b
- NoteMay be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Computationally mapped potential isoform sequences
There are 5 potential isoforms mapped to this entry
Features
Showing features for sequence conflict, alternative sequence, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 98 | in Ref. 2; BAD96923 | ||||
Sequence: R → H | ||||||
Alternative sequence | VSP_028501 | 259-272 | in isoform 2 | |||
Sequence: KLRHVLSMDGFLSY → ASEEDPGEGEEVNT | ||||||
Alternative sequence | VSP_028502 | 273-762 | in isoform 2 | |||
Sequence: Missing | ||||||
Compositional bias | 443-463 | Acidic residues | ||||
Sequence: LEYEEEEAEPELEESELALES |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AY512961 EMBL· GenBank· DDBJ | AAS82574.1 EMBL· GenBank· DDBJ | mRNA | ||
AK223203 EMBL· GenBank· DDBJ | BAD96923.1 EMBL· GenBank· DDBJ | mRNA | ||
BC006355 EMBL· GenBank· DDBJ | AAH06355.1 EMBL· GenBank· DDBJ | mRNA |