DPS1_HUMAN
ID DPS1_HUMAN Reviewed; 415 AA.
AC Q5T2R2; Q53F75; Q6P473; Q86WQ8; Q9Y2W5;
DT 24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=All trans-polyprenyl-diphosphate synthase PDSS1 {ECO:0000305};
DE AltName: Full=All-trans-decaprenyl-diphosphate synthase subunit 1;
DE EC=2.5.1.91 {ECO:0000269|PubMed:16262699};
DE AltName: Full=Decaprenyl pyrophosphate synthase subunit 1;
DE AltName: Full=Decaprenyl-diphosphate synthase subunit 1 {ECO:0000312|HGNC:HGNC:17759};
DE AltName: Full=Solanesyl-diphosphate synthase subunit 1;
DE AltName: Full=Trans-prenyltransferase 1;
DE Short=TPT 1;
GN Name=PDSS1 {ECO:0000312|HGNC:HGNC:17759};
GN Synonyms=DPS1 {ECO:0000303|PubMed:16262699}, TPRT;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RX PubMed=10972372; DOI=10.1016/s0140-6736(00)02531-9;
RA Roetig A., Appelkvist E.-L., Geromel V., Chretien D., Kadhom N., Edery P.,
RA Lebideau M., Dallner G., Munnich A., Ernster L., Rustin P.;
RT "Quinone-responsive multiple respiratory-chain dysfunction due to
RT widespread coenzyme Q10 deficiency.";
RL Lancet 356:391-395(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, AND
RP SUBUNIT.
RX PubMed=16262699; DOI=10.1111/j.1742-4658.2005.04956.x;
RA Saiki R., Nagata A., Kainou T., Matsuda H., Kawamukai M.;
RT "Characterization of solanesyl and decaprenyl diphosphate synthases in mice
RT and humans.";
RL FEBS J. 272:5606-5622(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Coronary arterial endothelium;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 2-415 (ISOFORM 1).
RC TISSUE=Brain, and Duodenum;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [7]
RP VARIANT COQ10D2 GLU-308.
RX PubMed=17332895; DOI=10.1172/jci29089;
RA Mollet J., Giurgea I., Schlemmer D., Dallner G., Chretien D., Delahodde A.,
RA Bacq D., de Lonlay P., Munnich A., Rotig A.;
RT "Prenyldiphosphate synthase, subunit 1 (PDSS1) and OH-benzoate
RT polyprenyltransferase (COQ2) mutations in ubiquinone deficiency and
RT oxidative phosphorylation disorders.";
RL J. Clin. Invest. 117:765-772(2007).
CC -!- FUNCTION: Heterotetrameric enzyme that catalyzes the condensation of
CC farnesyl diphosphate (FPP), which acts as a primer, and isopentenyl
CC diphosphate (IPP) to produce prenyl diphosphates of varying chain
CC lengths and participates in the determination of the side chain of
CC ubiquinone (PubMed:16262699). Supplies nona and decaprenyl diphosphate,
CC the precursors for the side chain of the isoprenoid quinones
CC ubiquinone-9 (Q9)and ubiquinone-10 (Q10) respectively
CC (PubMed:16262699). The enzyme adds isopentenyl diphosphate molecules
CC sequentially to farnesyl diphosphate with trans stereochemistry
CC (PubMed:16262699). {ECO:0000269|PubMed:16262699}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E)-farnesyl diphosphate + 7 isopentenyl diphosphate =
CC all-trans-decaprenyl diphosphate + 7 diphosphate;
CC Xref=Rhea:RHEA:27802, ChEBI:CHEBI:33019, ChEBI:CHEBI:60721,
CC ChEBI:CHEBI:128769, ChEBI:CHEBI:175763; EC=2.5.1.91;
CC Evidence={ECO:0000269|PubMed:16262699};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27803;
CC Evidence={ECO:0000305|PubMed:16262699};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E)-farnesyl diphosphate + 6 isopentenyl diphosphate =
CC all-trans-nonaprenyl diphosphate + 6 diphosphate;
CC Xref=Rhea:RHEA:55364, ChEBI:CHEBI:33019, ChEBI:CHEBI:58391,
CC ChEBI:CHEBI:128769, ChEBI:CHEBI:175763;
CC Evidence={ECO:0000250|UniProtKB:Q33DR2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55365;
CC Evidence={ECO:0000250|UniProtKB:Q33DR2};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Note=Binds 2 Mg(2+) ions per subunit. {ECO:0000250};
CC -!- PATHWAY: Cofactor biosynthesis; ubiquinone biosynthesis.
CC -!- SUBUNIT: Heterotetramer composed of 2 PDSS1/DPS1 and 2 PDSS2/DLP1
CC subunits. {ECO:0000269|PubMed:16262699}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q5T2R2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5T2R2-2; Sequence=VSP_017101;
CC Name=3;
CC IsoId=Q5T2R2-3; Sequence=VSP_017100;
CC -!- DISEASE: Coenzyme Q10 deficiency, primary, 2 (COQ10D2) [MIM:614651]: An
CC autosomal recessive multisystem disorder characterized by early-onset
CC deafness, optic atrophy, mild intellectual disability, peripheral
CC neuropathy, obesity, livedo reticularis, and cardiac valvulopathy.
CC {ECO:0000269|PubMed:17332895}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the FPP/GGPP synthase family. {ECO:0000305}.
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DR EMBL; AF118395; AAD28559.1; -; mRNA.
DR EMBL; AB210838; BAE48216.1; -; mRNA.
DR EMBL; AK223414; BAD97134.1; -; mRNA.
DR EMBL; AL390961; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC049211; AAH49211.1; -; mRNA.
DR EMBL; BC063635; AAH63635.1; -; mRNA.
DR CCDS; CCDS31168.1; -. [Q5T2R2-1]
DR RefSeq; NP_001308907.1; NM_001321978.1. [Q5T2R2-2]
DR RefSeq; NP_055132.2; NM_014317.4. [Q5T2R2-1]
DR AlphaFoldDB; Q5T2R2; -.
DR SMR; Q5T2R2; -.
DR BioGRID; 117125; 22.
DR IntAct; Q5T2R2; 8.
DR MINT; Q5T2R2; -.
DR STRING; 9606.ENSP00000365388; -.
DR iPTMnet; Q5T2R2; -.
DR PhosphoSitePlus; Q5T2R2; -.
DR BioMuta; PDSS1; -.
DR DMDM; 74744657; -.
DR EPD; Q5T2R2; -.
DR jPOST; Q5T2R2; -.
DR MassIVE; Q5T2R2; -.
DR MaxQB; Q5T2R2; -.
DR PaxDb; Q5T2R2; -.
DR PeptideAtlas; Q5T2R2; -.
DR PRIDE; Q5T2R2; -.
DR ProteomicsDB; 64353; -. [Q5T2R2-1]
DR ProteomicsDB; 64354; -. [Q5T2R2-2]
DR ProteomicsDB; 64355; -. [Q5T2R2-3]
DR Antibodypedia; 25917; 61 antibodies from 17 providers.
DR DNASU; 23590; -.
DR Ensembl; ENST00000376215.10; ENSP00000365388.5; ENSG00000148459.16. [Q5T2R2-1]
DR GeneID; 23590; -.
DR KEGG; hsa:23590; -.
DR MANE-Select; ENST00000376215.10; ENSP00000365388.5; NM_014317.5; NP_055132.2.
DR UCSC; uc001isv.4; human. [Q5T2R2-1]
DR CTD; 23590; -.
DR DisGeNET; 23590; -.
DR GeneCards; PDSS1; -.
DR GeneReviews; PDSS1; -.
DR HGNC; HGNC:17759; PDSS1.
DR HPA; ENSG00000148459; Tissue enhanced (intestine, lymphoid tissue).
DR MalaCards; PDSS1; -.
DR MIM; 607429; gene.
DR MIM; 614651; phenotype.
DR neXtProt; NX_Q5T2R2; -.
DR OpenTargets; ENSG00000148459; -.
DR Orphanet; 254898; Deafness-encephaloneuropathy-obesity-valvulopathy syndrome.
DR PharmGKB; PA134982512; -.
DR VEuPathDB; HostDB:ENSG00000148459; -.
DR eggNOG; KOG0776; Eukaryota.
DR GeneTree; ENSGT00940000153498; -.
DR HOGENOM; CLU_014015_1_2_1; -.
DR InParanoid; Q5T2R2; -.
DR OMA; GKQMRPM; -.
DR OrthoDB; 381154at2759; -.
DR PhylomeDB; Q5T2R2; -.
DR TreeFam; TF313548; -.
DR BioCyc; MetaCyc:HS07530-MON; -.
DR BRENDA; 2.5.1.91; 2681.
DR PathwayCommons; Q5T2R2; -.
DR Reactome; R-HSA-2142789; Ubiquinol biosynthesis.
DR SignaLink; Q5T2R2; -.
DR UniPathway; UPA00232; -.
DR BioGRID-ORCS; 23590; 169 hits in 1076 CRISPR screens.
DR ChiTaRS; PDSS1; human.
DR GeneWiki; PDSS1; -.
DR GenomeRNAi; 23590; -.
DR Pharos; Q5T2R2; Tbio.
DR PRO; PR:Q5T2R2; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q5T2R2; protein.
DR Bgee; ENSG00000148459; Expressed in mucosa of transverse colon and 156 other tissues.
DR ExpressionAtlas; Q5T2R2; baseline and differential.
DR Genevisible; Q5T2R2; HS.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:1990234; C:transferase complex; IDA:BHF-UCL.
DR GO; GO:0097269; F:all-trans-decaprenyl-diphosphate synthase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004659; F:prenyltransferase activity; IBA:GO_Central.
DR GO; GO:0046982; F:protein heterodimerization activity; IEA:Ensembl.
DR GO; GO:0000010; F:trans-hexaprenyltranstransferase activity; IEA:Ensembl.
DR GO; GO:0050347; F:trans-octaprenyltranstransferase activity; IEA:Ensembl.
DR GO; GO:0008299; P:isoprenoid biosynthetic process; IDA:HGNC-UCL.
DR GO; GO:0006744; P:ubiquinone biosynthetic process; IDA:HGNC-UCL.
DR CDD; cd00685; Trans_IPPS_HT; 1.
DR Gene3D; 1.10.600.10; -; 1.
DR InterPro; IPR008949; Isoprenoid_synthase_dom_sf.
DR InterPro; IPR000092; Polyprenyl_synt.
DR InterPro; IPR033749; Polyprenyl_synt_CS.
DR Pfam; PF00348; polyprenyl_synt; 1.
DR SUPFAM; SSF48576; SSF48576; 1.
DR PROSITE; PS00723; POLYPRENYL_SYNTHASE_1; 1.
DR PROSITE; PS00444; POLYPRENYL_SYNTHASE_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disease variant; Isoprene biosynthesis;
KW Lipid metabolism; Magnesium; Metal-binding; Mitochondrion;
KW Primary mitochondrial disease; Reference proteome; Transferase;
KW Ubiquinone biosynthesis.
FT CHAIN 1..415
FT /note="All trans-polyprenyl-diphosphate synthase PDSS1"
FT /id="PRO_0000123975"
FT REGION 16..35
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 134
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 137
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 173
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 180
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 180
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 184
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 184
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 189
FT /ligand="an all-trans-polyprenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:58914"
FT /evidence="ECO:0000250"
FT BINDING 190
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 266
FT /ligand="an all-trans-polyprenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:58914"
FT /evidence="ECO:0000250"
FT BINDING 267
FT /ligand="an all-trans-polyprenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:58914"
FT /evidence="ECO:0000250"
FT BINDING 304
FT /ligand="an all-trans-polyprenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:58914"
FT /evidence="ECO:0000250"
FT BINDING 321
FT /ligand="an all-trans-polyprenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:58914"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..42
FT /note="MASRWWRWRRGCSWKPAARSPGPGSPGRAGPLGPSAAAEVRA -> MPA
FT (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10972372"
FT /id="VSP_017100"
FT VAR_SEQ 279..415
FT /note="SVLGCPDPVVHEIAYQYGKNVGIAFQLIDDVLDFTSCSDQMGKPTSADLKLG
FT LATGPVLFACQQFPEMNAMIMRRFSLPGDVDRARQYVLQSDGVQQTTYLAQQYCHEAIR
FT EISKLRPSPERDALIQLSEIVLTRDK -> FPRNECYDHATVQFAWRCRQSSTVCTTE
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_017101"
FT VARIANT 308
FT /note="D -> E (in COQ10D2; dbSNP:rs119463988)"
FT /evidence="ECO:0000269|PubMed:17332895"
FT /id="VAR_034879"
FT CONFLICT 30
FT /note="G -> V (in Ref. 5; AAH63635)"
FT /evidence="ECO:0000305"
FT CONFLICT 44
FT /note="V -> A (in Ref. 1; AAD28559)"
FT /evidence="ECO:0000305"
FT CONFLICT 47
FT /note="R -> Q (in Ref. 1; AAD28559)"
FT /evidence="ECO:0000305"
FT CONFLICT 58
FT /note="I -> F (in Ref. 1; AAD28559)"
FT /evidence="ECO:0000305"
FT CONFLICT 66
FT /note="S -> P (in Ref. 1; AAD28559)"
FT /evidence="ECO:0000305"
FT CONFLICT 72..73
FT /note="CR -> YS (in Ref. 1; AAD28559)"
FT /evidence="ECO:0000305"
FT CONFLICT 76
FT /note="R -> Q (in Ref. 1; AAD28559)"
FT /evidence="ECO:0000305"
FT CONFLICT 83
FT /note="D -> Y (in Ref. 1; AAD28559)"
FT /evidence="ECO:0000305"
FT CONFLICT 109
FT /note="D -> G (in Ref. 1; AAD28559)"
FT /evidence="ECO:0000305"
FT CONFLICT 114
FT /note="L -> P (in Ref. 1; AAD28559)"
FT /evidence="ECO:0000305"
FT CONFLICT 119
FT /note="S -> T (in Ref. 1; AAD28559)"
FT /evidence="ECO:0000305"
FT CONFLICT 124
FT /note="M -> I (in Ref. 1; AAD28559)"
FT /evidence="ECO:0000305"
FT CONFLICT 131
FT /note="G -> V (in Ref. 1; AAD28559)"
FT /evidence="ECO:0000305"
FT CONFLICT 142
FT /note="A -> V (in Ref. 1; AAD28559)"
FT /evidence="ECO:0000305"
FT CONFLICT 186
FT /note="A -> V (in Ref. 3; BAD97134)"
FT /evidence="ECO:0000305"
FT CONFLICT 298
FT /note="N -> D (in Ref. 3; BAD97134)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 415 AA; 46261 MW; F0B073C75CBD06D2 CRC64;
MASRWWRWRR GCSWKPAARS PGPGSPGRAG PLGPSAAAEV RAQVHRRKGL DLSQIPYINL
VKHLTSACPN VCRISRFHHT TPDSKTHSGE KYTDPFKLGW RDLKGLYEDI RKELLISTSE
LKEMSEYYFD GKGKAFRPII VALMARACNI HHNNSRHVQA SQRAIALIAE MIHTASLVHD
DVIDDASSRR GKHTVNKIWG EKKAVLAGDL ILSAASIALA RIGNTTVISI LTQVIEDLVR
GEFLQLGSKE NENERFAHYL EKTFKKTASL IANSCKAVSV LGCPDPVVHE IAYQYGKNVG
IAFQLIDDVL DFTSCSDQMG KPTSADLKLG LATGPVLFAC QQFPEMNAMI MRRFSLPGDV
DRARQYVLQS DGVQQTTYLA QQYCHEAIRE ISKLRPSPER DALIQLSEIV LTRDK
