Q99KU1 · DHDDS_MOUSE

  • Protein
    Dehydrodolichyl diphosphate synthase complex subunit Dhdds
  • Gene
    Dhdds
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    4/5

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

Cofactor

Mg2+ (UniProtKB | Rhea| CHEBI:18420 )

Note: Binds 1 magnesium ion per subunit.

Pathway

Protein modification; protein glycosylation.
Lipid metabolism.

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site34(2E,6E)-farnesyl diphosphate (UniProtKB | ChEBI)
Binding site34Mg2+ (UniProtKB | ChEBI)
Binding site35(2E,6E)-farnesyl diphosphate (UniProtKB | ChEBI)
Binding site37(2E,6E)-farnesyl diphosphate (UniProtKB | ChEBI)
Binding site38(2E,6E)-farnesyl diphosphate (UniProtKB | ChEBI)
Binding site38isopentenyl diphosphate (UniProtKB | ChEBI)
Binding site85(2E,6E)-farnesyl diphosphate (UniProtKB | ChEBI)
Binding site85isopentenyl diphosphate (UniProtKB | ChEBI)
Binding site205isopentenyl diphosphate (UniProtKB | ChEBI)
Binding site211isopentenyl diphosphate (UniProtKB | ChEBI)
Binding site213isopentenyl diphosphate (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentdehydrodolichyl diphosphate synthase complex
Cellular Componentendoplasmic reticulum membrane
Molecular Functiondehydrodolichyl diphosphate synthase activity
Molecular Functionmetal ion binding
Molecular Functionpolyprenyltransferase activity
Biological Processdolichyl diphosphate biosynthetic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Dehydrodolichyl diphosphate synthase complex subunit Dhdds
  • EC number
  • Alternative names
    • Cis-isoprenyltransferase
      (CIT
      ; Cis-IPTase
      )

Gene names

    • Name
      Dhdds

Organism names

  • Taxonomic identifier
  • Strains
    • C57BL/6J
    • NOD
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q99KU1
  • Secondary accessions
    • A3KGL4
    • Q3UF13
    • Q8BZ16
    • Q8BZK8

Proteomes

Organism-specific databases

Subcellular Location

Endoplasmic reticulum membrane
; Peripheral membrane protein
Note: colocalizes with calnexin.

Keywords

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).

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis42Impaired formation of dolichol species, leading to defects in inner retina and synaptic transmission in knockin mice. Knockin mice do notshow retinal degeneration.

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.

Go to variant viewer

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00001237501-333Dehydrodolichyl diphosphate synthase complex subunit Dhdds

Proteomic databases

PTM databases

Expression

Gene expression databases

Interaction

Subunit

The active dehydrodolichyl diphosphate synthase complex is a heterotetramer composed of a dimer of heterodimer of DHDDS and NUS1. Interacts with NPC2.

Protein-protein interaction databases

Miscellaneous

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

Align isoforms (2)
  • Sequence status
    Complete

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.

  • Length
    333
  • Mass (Da)
    38,509
  • Last updated
    2001-06-01 v1
  • Checksum
    53992F5E92D3F2C9
MSWIKEGELSLWERFCANIIKAGPVPKHIAFIMDGNRRYAKKCQVERQEGHTQGFNKLAETLRWCLNLGILEVTVYAFSIENFKRSKSEVDGLLDLARQKFSCLMEEQEKLQKHGVCIRVLGDLHLLPLDLQEKIAHAIQATKNYNKCFLNVCFAYTSRHEIANAVREMAWGVEQGLLEPSDVSESLLDKCLYSNHSPHPDILIRTSGEVRLSDFLLWQTSHSCLVFQPVLWPEYTFWNLCEAILQFQRNHGALQKARDMYAEERKRRQLERDQAAVTEQLLREGLQASGDAQLRRTRLHKLSTKREERVQGFLKALELKRANWLALWGTASA

Q99KU1-2

  • Name
    2
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Computationally mapped potential isoform sequences

There are 4 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A3KGL0A3KGL0_MOUSEDhdds299
A3KGL2A3KGL2_MOUSEDhdds294
A3KGL3A3KGL3_MOUSEDhdds258
A3KGK9A3KGK9_MOUSEDhdds168

Features

Showing features for sequence conflict, alternative sequence.

TypeIDPosition(s)Description
Sequence conflict30in Ref. 1; BAC29643
Alternative sequenceVSP_010032255in isoform 2

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

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