Q99KU1 · DHDDS_MOUSE
- ProteinDehydrodolichyl diphosphate synthase complex subunit Dhdds
- GeneDhdds
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids333 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score4/5
Function
function
With NUS1, forms the dehydrodolichyl diphosphate synthase (DDS) complex, an essential component of the dolichol monophosphate (Dol-P) biosynthetic machinery. Both subunits contribute to enzymatic activity, i.e. condensation of multiple copies of isopentenyl pyrophosphate (IPP) to farnesyl pyrophosphate (FPP) to produce dehydrodolichyl diphosphate (Dedol-PP), a precursor of dolichol phosphate which is utilized as a sugar carrier in protein glycosylation in the endoplasmic reticulum (ER). Synthesizes long-chain polyprenols, mostly of C95 and C100 chain length. Regulates the glycosylation and stability of nascent NPC2, thereby promoting trafficking of LDL-derived cholesterol.
Catalytic activity
- n isopentenyl diphosphate + (2E,6E)-farnesyl diphosphate = a di-trans,poly-cis-polyprenyl diphosphate + n diphosphate
n CHEBI:128769 + CHEBI:175763 = a di-trans,poly-cis-polyprenyl diphosphate RHEA-COMP:19494 + n CHEBI:33019
Cofactor
Note: Binds 1 magnesium ion per subunit.
Pathway
Protein modification; protein glycosylation.
Lipid metabolism.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 34 | (2E,6E)-farnesyl diphosphate (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 34 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 35 | (2E,6E)-farnesyl diphosphate (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 37 | (2E,6E)-farnesyl diphosphate (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 38 | (2E,6E)-farnesyl diphosphate (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 38 | isopentenyl diphosphate (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 85 | (2E,6E)-farnesyl diphosphate (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 85 | isopentenyl diphosphate (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 205 | isopentenyl diphosphate (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 211 | isopentenyl diphosphate (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 213 | isopentenyl diphosphate (UniProtKB | ChEBI) | ||||
Sequence: S |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | dehydrodolichyl diphosphate synthase complex | |
Cellular Component | endoplasmic reticulum membrane | |
Molecular Function | dehydrodolichyl diphosphate synthase activity | |
Molecular Function | metal ion binding | |
Molecular Function | polyprenyltransferase activity | |
Biological Process | dolichyl diphosphate biosynthetic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDehydrodolichyl diphosphate synthase complex subunit Dhdds
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ99KU1
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Peripheral membrane protein
Note: colocalizes with calnexin.
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Embryonic lethality (PubMed:32245241).
Conditional deletion in retinal pigment epithelium causes deficits in the retinal pigment epithelium and the photoreceptors, leading to retinal degeneration (PubMed:32245241).
Conditional deletion in rod photoreceptor cells causes retinal degeneration (PubMed:32526701).
Conditional deletion in retinal pigment epithelium causes deficits in the retinal pigment epithelium and the photoreceptors, leading to retinal degeneration (PubMed:32245241).
Conditional deletion in rod photoreceptor cells causes retinal degeneration (PubMed:32526701).
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 42 | Impaired formation of dolichol species, leading to defects in inner retina and synaptic transmission in knockin mice. Knockin mice do notshow retinal degeneration. | ||||
Sequence: K → E |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 16 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000123750 | 1-333 | Dehydrodolichyl diphosphate synthase complex subunit Dhdds | |||
Sequence: MSWIKEGELSLWERFCANIIKAGPVPKHIAFIMDGNRRYAKKCQVERQEGHTQGFNKLAETLRWCLNLGILEVTVYAFSIENFKRSKSEVDGLLDLARQKFSCLMEEQEKLQKHGVCIRVLGDLHLLPLDLQEKIAHAIQATKNYNKCFLNVCFAYTSRHEIANAVREMAWGVEQGLLEPSDVSESLLDKCLYSNHSPHPDILIRTSGEVRLSDFLLWQTSHSCLVFQPVLWPEYTFWNLCEAILQFQRNHGALQKARDMYAEERKRRQLERDQAAVTEQLLREGLQASGDAQLRRTRLHKLSTKREERVQGFLKALELKRANWLALWGTASA |
Proteomic databases
PTM databases
Expression
Gene expression databases
Structure
Family & Domains
Domain
The catalytic site at NUS1-DHDDS interface accomodates both the allylic and the homoallylic IPP substrates to the S1 and S2 pockets respectively. The beta-phosphate groups of IPP substrates form hydrogen bonds with the RXG motif of NUS1 and four conserved residues of DHDDS (Arg-85, Arg-205, Arg-211 and Ser-213), while the allylic isopentenyl group is pointed toward the hydrophobic tunnel of the S1 pocket where the product elongation occurs.
Sequence similarities
Belongs to the UPP synthase family.
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q99KU1-1
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
- Length333
- Mass (Da)38,509
- Last updated2001-06-01 v1
- Checksum53992F5E92D3F2C9
Q99KU1-2
- Name2
- Differences from canonical
- 255-255: Q → QQ
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Features
Showing features for sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 30 | in Ref. 1; BAC29643 | ||||
Sequence: A → L | ||||||
Alternative sequence | VSP_010032 | 255 | in isoform 2 | |||
Sequence: Q → QQ |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK034277 EMBL· GenBank· DDBJ | BAC28657.1 EMBL· GenBank· DDBJ | mRNA | ||
AK036929 EMBL· GenBank· DDBJ | BAC29643.1 EMBL· GenBank· DDBJ | mRNA | ||
AK049991 EMBL· GenBank· DDBJ | BAC34020.1 EMBL· GenBank· DDBJ | mRNA | ||
AK135087 EMBL· GenBank· DDBJ | BAE22416.1 EMBL· GenBank· DDBJ | mRNA | ||
AK149138 EMBL· GenBank· DDBJ | BAE28748.1 EMBL· GenBank· DDBJ | mRNA | ||
AK171207 EMBL· GenBank· DDBJ | BAE42313.1 EMBL· GenBank· DDBJ | mRNA | ||
AL670680 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL837508 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC004011 EMBL· GenBank· DDBJ | AAH04011.1 EMBL· GenBank· DDBJ | mRNA |