UniProtKB - Q86SQ9 (DHDDS_HUMAN)
Dehydrodolichyl diphosphate synthase complex subunit DHDDS
DHDDS
Functioni
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) (PubMed:25066056, PubMed:28842490, PubMed:32817466).
Synthesizes long-chain polyprenols, mostly of C95 and C100 chain length (PubMed:32817466).
Regulates the glycosylation and stability of nascent NPC2, thereby promoting trafficking of LDL-derived cholesterol (PubMed:21572394).
4 PublicationsCatalytic activityi
- (2E,6E)-farnesyl diphosphate + n isopentenyl diphosphate = di-trans,poly-cis-polyprenyl diphosphate + n diphosphate3 PublicationsEC:2.5.1.873 Publications
Cofactori
Activity regulationi
Kineticsi
- KM=11.1 µM for isopentenyl diphosphate1 Publication
- KM=0.68 µM for (2E,6E)-farnesyl diphosphate1 Publication
pH dependencei
: protein glycosylation Pathwayi
This protein is involved in the pathway protein glycosylation, which is part of Protein modification.1 PublicationView all proteins of this organism that are known to be involved in the pathway protein glycosylation and in Protein modification.
Pathwayi: Lipid metabolism
This protein is involved in Lipid metabolism.1 PublicationView all proteins of this organism that are known to be involved in Lipid metabolism.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 34 | Magnesium1 Publication | 1 | |
Binding sitei | 38 | Isopentenyl diphosphate1 Publication | 1 | |
Binding sitei | 85 | Isopentenyl diphosphate1 Publication | 1 | |
Binding sitei | 205 | Isopentenyl diphosphate1 Publication | 1 | |
Binding sitei | 211 | Isopentenyl diphosphate1 Publication | 1 | |
Binding sitei | 213 | Isopentenyl diphosphate1 Publication | 1 |
GO - Molecular functioni
- dehydrodolichyl diphosphate synthase activity Source: UniProtKB
- metal ion binding Source: UniProtKB-KW
GO - Biological processi
- dolichyl diphosphate biosynthetic process Source: UniProtKB
- polyprenol biosynthetic process Source: GO_Central
Keywordsi
Molecular function | Transferase |
Biological process | Lipid metabolism |
Ligand | Magnesium, Metal-binding |
Enzyme and pathway databases
BRENDAi | 2.5.1.87, 2681 |
PathwayCommonsi | Q86SQ9 |
Reactomei | R-HSA-446199, Synthesis of Dolichyl-phosphate R-HSA-4755609, Defective DHDDS causes retinitis pigmentosa 59 |
SignaLinki | Q86SQ9 |
UniPathwayi | UPA00378 |
Names & Taxonomyi
Protein namesi | Recommended name: Dehydrodolichyl diphosphate synthase complex subunit DHDDSCurated (EC:2.5.1.872 Publications)Alternative name(s): Cis-isoprenyltransferase1 Publication Short name: CIT1 Publication Short name: Cis-IPTase1 Publication Cis-prenyltransferase subunit hCIT1 Publication Epididymis tissue protein Li 189m |
Gene namesi | |
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
HGNCi | HGNC:20603, DHDDS |
MIMi | 608172, gene |
neXtProti | NX_Q86SQ9 |
VEuPathDBi | HostDB:ENSG00000117682 |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum membrane 1 Publication; Peripheral membrane protein 1 Publication
Note: colocalizes with calnexin.
Endoplasmic reticulum
- endoplasmic reticulum Source: GO_Central
- endoplasmic reticulum membrane Source: Reactome
Other locations
- dehydrodolichyl diphosphate synthase complex Source: UniProtKB
Keywords - Cellular componenti
Endoplasmic reticulum, MembranePathology & Biotechi
Involvement in diseasei
Retinitis pigmentosa 59 (RP59)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_065356 | 42 | K → E in RP59; 5-fold reduction in catalytic activity and reduced affinity for FPP but not for IPP.. 2 PublicationsCorresponds to variant dbSNP:rs147394623EnsemblClinVar. | 1 |
Developmental delay and seizures with or without movement abnormalities (DEDSM)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_080708 | 37 | R → H in DEDSM; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1553121073EnsemblClinVar. | 1 | |
Natural variantiVAR_080709 | 211 | R → Q in DEDSM; also found in a patient with progressive myoclonus epilepsy and developmental delay; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs1553122926EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 12 | W → A: Markedly decreases phosphatidylinositol-mediated activation of cis-prenyltransferase activity resulting in products with longer chain length; when associated with A-15 and A-19. 1 Publication | 1 | |
Mutagenesisi | 15 | F → A: Markedly decreases phosphatidylinositol-mediated activation of cis-prenyltransferase activity resulting in products with longer chain length; when associated with A-12 and A-19. 1 Publication | 1 | |
Mutagenesisi | 19 | I → A: Markedly decreases phosphatidylinositol-mediated activation of cis-prenyltransferase activity resulting in products with longer chain length; when associated with A-12 and A-15. 1 Publication | 1 | |
Mutagenesisi | 106 – 109 | Missing : Affects chain elongation resulting in shorter products. 1 Publication | 4 | |
Mutagenesisi | 306 | R → A: Delays cell growth; when associated with A-313 and A-317. 1 Publication | 1 | |
Mutagenesisi | 313 | F → A: Delays cell growth; when associated with A-306 and A-317. 1 Publication | 1 | |
Mutagenesisi | 317 | L → A: Delays cell growth; when associated with A-306 and A-313. 1 Publication | 1 |
Keywords - Diseasei
Disease variant, Epilepsy, Mental retardation, Retinitis pigmentosaOrganism-specific databases
DisGeNETi | 79947 |
GeneReviewsi | DHDDS |
MalaCardsi | DHDDS |
MIMi | 613861, phenotype 617836, phenotype |
OpenTargetsi | ENSG00000117682 |
Orphaneti | 442835, Non-specific early-onset epileptic encephalopathy 791, Retinitis pigmentosa |
PharmGKBi | PA134867119 |
Miscellaneous databases
Pharosi | Q86SQ9, Tbio |
Genetic variation databases
BioMutai | DHDDS |
DMDMi | 116241329 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000123749 | 1 – 333 | Dehydrodolichyl diphosphate synthase complex subunit DHDDSAdd BLAST | 333 |
Proteomic databases
jPOSTi | Q86SQ9 |
MassIVEi | Q86SQ9 |
MaxQBi | Q86SQ9 |
PaxDbi | Q86SQ9 |
PeptideAtlasi | Q86SQ9 |
PRIDEi | Q86SQ9 |
ProteomicsDBi | 6588 69620 [Q86SQ9-1] 69621 [Q86SQ9-2] 69622 [Q86SQ9-3] |
PTM databases
iPTMneti | Q86SQ9 |
PhosphoSitePlusi | Q86SQ9 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000117682, Expressed in right hemisphere of cerebellum and 213 other tissues |
ExpressionAtlasi | Q86SQ9, baseline and differential |
Genevisiblei | Q86SQ9, HS |
Organism-specific databases
HPAi | ENSG00000117682, Low tissue specificity |
Interactioni
Subunit structurei
Binary interactionsi
Q86SQ9
With | #Exp. | IntAct |
---|---|---|
NUS1 [Q96E22] | 3 | EBI-26942900,EBI-6949352 |
Protein-protein interaction databases
BioGRIDi | 123018, 10 interactors |
ComplexPortali | CPX-6701, Dehydrodolichyl diphosphate synthase complex |
CORUMi | Q86SQ9 |
IntActi | Q86SQ9, 2 interactors |
STRINGi | 9606.ENSP00000353104 |
Miscellaneous databases
RNActi | Q86SQ9, protein |
Structurei
Secondary structure
3D structure databases
SASBDBi | Q86SQ9 |
SMRi | Q86SQ9 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG1602, Eukaryota |
GeneTreei | ENSGT00390000007879 |
InParanoidi | Q86SQ9 |
OMAi | PRTEGHK |
OrthoDBi | 1362420at2759 |
PhylomeDBi | Q86SQ9 |
TreeFami | TF323753 |
Family and domain databases
CDDi | cd00475, Cis_IPPS, 1 hit |
Gene3Di | 3.40.1180.10, 1 hit |
HAMAPi | MF_01139, ISPT, 1 hit |
InterProi | View protein in InterPro IPR001441, UPP_synth-like IPR018520, UPP_synth-like_CS IPR036424, UPP_synth-like_sf |
PANTHERi | PTHR10291, PTHR10291, 1 hit |
Pfami | View protein in Pfam PF01255, Prenyltransf, 1 hit |
SUPFAMi | SSF64005, SSF64005, 1 hit |
TIGRFAMsi | TIGR00055, uppS, 1 hit |
PROSITEi | View protein in PROSITE PS01066, UPP_SYNTHASE, 1 hit |
s (4+)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 4 described isoforms and 13 potential isoforms that are computationally mapped.Show allAlign All
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
MSWIKEGELS LWERFCANII KAGPMPKHIA FIMDGNRRYA KKCQVERQEG
60 70 80 90 100
HSQGFNKLAE TLRWCLNLGI LEVTVYAFSI ENFKRSKSEV DGLMDLARQK
110 120 130 140 150
FSRLMEEKEK LQKHGVCIRV LGDLHLLPLD LQELIAQAVQ ATKNYNKCFL
160 170 180 190 200
NVCFAYTSRH EISNAVREMA WGVEQGLLDP SDISESLLDK CLYTNRSPHP
210 220 230 240 250
DILIRTSGEV RLSDFLLWQT SHSCLVFQPV LWPEYTFWNL FEAILQFQMN
260 270 280 290 300
HSVLQKARDM YAEERKRQQL ERDQATVTEQ LLREGLQASG DAQLRRTRLH
310 320 330
KLSARREERV QGFLQALELK RADWLARLGT ASA
Computationally mapped potential isoform sequencesi
There are 13 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketQ5T0A2 | Q5T0A2_HUMAN | Alkyl transferase | DHDDS | 173 | Annotation score: | ||
E9PI09 | E9PI09_HUMAN | Alkyl transferase | DHDDS | 198 | Annotation score: | ||
E9PRS7 | E9PRS7_HUMAN | Alkyl transferase | DHDDS | 122 | Annotation score: | ||
Q5T0A1 | Q5T0A1_HUMAN | Alkyl transferase | DHDDS | 209 | Annotation score: | ||
E9PI64 | E9PI64_HUMAN | Alkyl transferase | DHDDS | 130 | Annotation score: | ||
E9PR24 | E9PR24_HUMAN | Alkyl transferase | DHDDS | 165 | Annotation score: | ||
Q5T0A3 | Q5T0A3_HUMAN | Alkyl transferase | DHDDS | 216 | Annotation score: | ||
H0Y4T1 | H0Y4T1_HUMAN | Alkyl transferase | DHDDS | 162 | Annotation score: | ||
E9PSH7 | E9PSH7_HUMAN | Ditrans,polycis-polyprenyl diphosph... | DHDDS | 85 | Annotation score: | ||
Q5T0A6 | Q5T0A6_HUMAN | Ditrans,polycis-polyprenyl diphosph... | DHDDS | 169 | Annotation score: | ||
There are more potential isoformsShow all |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 151 | N → Y in BAB14439 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 277 | V → E in AAH34152 (PubMed:15489334).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_080708 | 37 | R → H in DEDSM; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1553121073EnsemblClinVar. | 1 | |
Natural variantiVAR_065356 | 42 | K → E in RP59; 5-fold reduction in catalytic activity and reduced affinity for FPP but not for IPP.. 2 PublicationsCorresponds to variant dbSNP:rs147394623EnsemblClinVar. | 1 | |
Natural variantiVAR_085034 | 95 | D → N Found in a patient with progressive myoclonus epilepsy; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_085035 | 205 | R → Q Found in a patient with progressive myoclonus epilepsy; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1557447255EnsemblClinVar. | 1 | |
Natural variantiVAR_080709 | 211 | R → Q in DEDSM; also found in a patient with progressive myoclonus epilepsy and developmental delay; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs1553122926EnsemblClinVar. | 1 | |
Natural variantiVAR_028088 | 253 | V → M3 PublicationsCorresponds to variant dbSNP:rs3816539EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_010030 | 109 – 147 | Missing in isoform 3. 1 PublicationAdd BLAST | 39 | |
Alternative sequenceiVSP_045007 | 147 – 181 | KCFLN…LLDPS → N in isoform 4. 1 PublicationAdd BLAST | 35 | |
Alternative sequenceiVSP_010031 | 255 | Q → QQ in isoform 2. 1 Publication | 1 |
Sequence databases
Genome annotation databases
Ensembli | ENST00000236342; ENSP00000236342; ENSG00000117682 ENST00000360009; ENSP00000353104; ENSG00000117682 [Q86SQ9-2] ENST00000525682; ENSP00000434984; ENSG00000117682 [Q86SQ9-4] ENST00000526219; ENSP00000434219; ENSG00000117682 [Q86SQ9-3] |
GeneIDi | 79947 |
KEGGi | hsa:79947 |
MANE-Selecti | ENST00000236342.12; ENSP00000236342.7; NM_205861.3; NP_995583.1 |
UCSCi | uc001bmk.4, human [Q86SQ9-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
6W2L | X-ray | 2.31 | A | 2-330 | [»] | |
6Z1N | X-ray | 2.30 | A | 1-333 | [»] | |
SASBDBi | Q86SQ9 | |||||
SMRi | Q86SQ9 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 123018, 10 interactors |
ComplexPortali | CPX-6701, Dehydrodolichyl diphosphate synthase complex |
CORUMi | Q86SQ9 |
IntActi | Q86SQ9, 2 interactors |
STRINGi | 9606.ENSP00000353104 |
PTM databases
iPTMneti | Q86SQ9 |
PhosphoSitePlusi | Q86SQ9 |
Genetic variation databases
BioMutai | DHDDS |
DMDMi | 116241329 |
Proteomic databases
jPOSTi | Q86SQ9 |
MassIVEi | Q86SQ9 |
MaxQBi | Q86SQ9 |
PaxDbi | Q86SQ9 |
PeptideAtlasi | Q86SQ9 |
PRIDEi | Q86SQ9 |
ProteomicsDBi | 6588 69620 [Q86SQ9-1] 69621 [Q86SQ9-2] 69622 [Q86SQ9-3] |
Protocols and materials databases
Antibodypediai | 16091, 111 antibodies from 22 providers |
DNASUi | 79947 |
Genome annotation databases
Ensembli | ENST00000236342; ENSP00000236342; ENSG00000117682 ENST00000360009; ENSP00000353104; ENSG00000117682 [Q86SQ9-2] ENST00000525682; ENSP00000434984; ENSG00000117682 [Q86SQ9-4] ENST00000526219; ENSP00000434219; ENSG00000117682 [Q86SQ9-3] |
GeneIDi | 79947 |
KEGGi | hsa:79947 |
MANE-Selecti | ENST00000236342.12; ENSP00000236342.7; NM_205861.3; NP_995583.1 |
UCSCi | uc001bmk.4, human [Q86SQ9-1] |
Organism-specific databases
CTDi | 79947 |
DisGeNETi | 79947 |
GeneCardsi | DHDDS |
GeneReviewsi | DHDDS |
HGNCi | HGNC:20603, DHDDS |
HPAi | ENSG00000117682, Low tissue specificity |
MalaCardsi | DHDDS |
MIMi | 608172, gene 613861, phenotype 617836, phenotype |
neXtProti | NX_Q86SQ9 |
OpenTargetsi | ENSG00000117682 |
Orphaneti | 442835, Non-specific early-onset epileptic encephalopathy 791, Retinitis pigmentosa |
PharmGKBi | PA134867119 |
VEuPathDBi | HostDB:ENSG00000117682 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1602, Eukaryota |
GeneTreei | ENSGT00390000007879 |
InParanoidi | Q86SQ9 |
OMAi | PRTEGHK |
OrthoDBi | 1362420at2759 |
PhylomeDBi | Q86SQ9 |
TreeFami | TF323753 |
Enzyme and pathway databases
UniPathwayi | UPA00378 |
BRENDAi | 2.5.1.87, 2681 |
PathwayCommonsi | Q86SQ9 |
Reactomei | R-HSA-446199, Synthesis of Dolichyl-phosphate R-HSA-4755609, Defective DHDDS causes retinitis pigmentosa 59 |
SignaLinki | Q86SQ9 |
Miscellaneous databases
BioGRID-ORCSi | 79947, 802 hits in 1044 CRISPR screens |
ChiTaRSi | DHDDS, human |
GeneWikii | Dehydrodolichyl_diphosphate_synthase DHDDS |
GenomeRNAii | 79947 |
Pharosi | Q86SQ9, Tbio |
PROi | PR:Q86SQ9 |
RNActi | Q86SQ9, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000117682, Expressed in right hemisphere of cerebellum and 213 other tissues |
ExpressionAtlasi | Q86SQ9, baseline and differential |
Genevisiblei | Q86SQ9, HS |
Family and domain databases
CDDi | cd00475, Cis_IPPS, 1 hit |
Gene3Di | 3.40.1180.10, 1 hit |
HAMAPi | MF_01139, ISPT, 1 hit |
InterProi | View protein in InterPro IPR001441, UPP_synth-like IPR018520, UPP_synth-like_CS IPR036424, UPP_synth-like_sf |
PANTHERi | PTHR10291, PTHR10291, 1 hit |
Pfami | View protein in Pfam PF01255, Prenyltransf, 1 hit |
SUPFAMi | SSF64005, SSF64005, 1 hit |
TIGRFAMsi | TIGR00055, uppS, 1 hit |
PROSITEi | View protein in PROSITE PS01066, UPP_SYNTHASE, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | DHDDS_HUMAN | |
Accessioni | Q86SQ9Primary (citable) accession number: Q86SQ9 Secondary accession number(s): B7Z4B9 Q9H905 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 13, 2004 |
Last sequence update: | October 17, 2006 | |
Last modified: | February 23, 2022 | |
This is version 163 of the entry and version 3 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
3D-structure, Reference proteomeDocuments
- Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families