ID   DLP1_HUMAN              Reviewed;         399 AA.
AC   Q86YH6; Q33DR4; Q4G158; Q5VU38; Q5VU39; Q9NR58;
DT   16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT   16-AUG-2005, sequence version 2.
DT   24-JAN-2024, entry version 168.
DE   RecName: Full=All trans-polyprenyl-diphosphate synthase PDSS2 {ECO:0000305};
DE   AltName: Full=All-trans-decaprenyl-diphosphate synthase subunit 2;
DE            EC=2.5.1.91 {ECO:0000269|PubMed:16262699};
DE   AltName: Full=Candidate tumor suppressor protein;
DE   AltName: Full=Decaprenyl pyrophosphate synthase subunit 2;
DE   AltName: Full=Decaprenyl-diphosphate synthase subunit 2 {ECO:0000312|HGNC:HGNC:23041};
DE   AltName: Full=Solanesyl-diphosphate synthase subunit 2 {ECO:0000250|UniProtKB:Q33DR3};
GN   Name=PDSS2 {ECO:0000312|HGNC:HGNC:23041}; Synonyms=C6orf210, DLP1;
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 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   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Melanoma;
RA   Guan X.-Y.Y., Zhou H., Sham J.S.T., Zhang H.-E., Trent J.M.;
RT   "Characterization of a complex chromosome rearrangement involving 6q in a
RT   melanoma cell line: isolation of a candidate tumor suppressor gene
RT   interrupted by the breakpoint at 6q16.";
RL   Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=14574404; DOI=10.1038/nature02055;
RA   Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA   Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA   Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA   Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA   Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA   Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA   Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA   Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA   Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA   French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA   Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA   Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA   Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA   Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA   Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA   Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA   Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA   Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA   Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA   Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA   Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA   Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA   Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA   Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA   West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA   Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA   Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA   Rogers J., Beck S.;
RT   "The DNA sequence and analysis of human chromosome 6.";
RL   Nature 425:805-811(2003).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Testis;
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   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
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 COQ10D3 LEU-382.
RX   PubMed=17186472; DOI=10.1086/510023;
RA   Lopez L.C., Schuelke M., Quinzii C.M., Kanki T., Rodenburg R.J.T.,
RA   Naini A., Dimauro S., Hirano M.;
RT   "Leigh syndrome with nephropathy and CoQ10 deficiency due to decaprenyl
RT   diphosphate synthase subunit 2 (PDSS2) mutations.";
RL   Am. J. Hum. Genet. 79:1125-1129(2006).
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). May play a role during cerebellar development (By
CC       similarity). May regulate mitochondrial respiratory chain function (By
CC       similarity). {ECO:0000250|UniProtKB:Q33DR3,
CC       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:Q33DR3};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55365;
CC         Evidence={ECO:0000250|UniProtKB:Q33DR3};
CC   -!- PATHWAY: Cofactor biosynthesis; ubiquinone biosynthesis.
CC       {ECO:0000269|PubMed:16262699}.
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=2;
CC       Name=1;
CC         IsoId=Q86YH6-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q86YH6-2; Sequence=VSP_017098, VSP_017099;
CC   -!- DISEASE: Coenzyme Q10 deficiency, primary, 3 (COQ10D3) [MIM:614652]: A
CC       fatal encephalomyopathic form of coenzyme Q10 deficiency with nephrotic
CC       syndrome. Coenzyme Q10 deficiency is an autosomal recessive disorder
CC       with variable manifestations consistent with 5 major phenotypes. The
CC       phenotypes include an encephalomyopathic form with seizures and ataxia;
CC       a multisystem infantile form with encephalopathy, cardiomyopathy and
CC       renal failure; a predominantly cerebellar form with ataxia and
CC       cerebellar atrophy; Leigh syndrome with growth retardation; and an
CC       isolated myopathic form. {ECO:0000269|PubMed:17186472}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- SIMILARITY: Belongs to the FPP/GGPP synthase family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAH29491.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; AB210839; BAE48217.1; -; mRNA.
DR   EMBL; AF254956; AAF97788.1; -; mRNA.
DR   EMBL; AL121957; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL355586; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL590489; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL591516; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC029491; AAH29491.1; ALT_FRAME; mRNA.
DR   EMBL; BC039906; AAH39906.1; -; mRNA.
DR   CCDS; CCDS5059.1; -. [Q86YH6-1]
DR   RefSeq; NP_065114.3; NM_020381.3. [Q86YH6-1]
DR   RefSeq; XP_011534265.1; XM_011535963.2. [Q86YH6-2]
DR   AlphaFoldDB; Q86YH6; -.
DR   SMR; Q86YH6; -.
DR   BioGRID; 121373; 27.
DR   IntAct; Q86YH6; 6.
DR   MINT; Q86YH6; -.
DR   STRING; 9606.ENSP00000358033; -.
DR   GlyGen; Q86YH6; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q86YH6; -.
DR   PhosphoSitePlus; Q86YH6; -.
DR   SwissPalm; Q86YH6; -.
DR   BioMuta; PDSS2; -.
DR   DMDM; 73620006; -.
DR   EPD; Q86YH6; -.
DR   jPOST; Q86YH6; -.
DR   MassIVE; Q86YH6; -.
DR   MaxQB; Q86YH6; -.
DR   PaxDb; 9606-ENSP00000358033; -.
DR   PeptideAtlas; Q86YH6; -.
DR   ProteomicsDB; 70415; -. [Q86YH6-1]
DR   ProteomicsDB; 70416; -. [Q86YH6-2]
DR   Pumba; Q86YH6; -.
DR   Antibodypedia; 32171; 390 antibodies from 24 providers.
DR   DNASU; 57107; -.
DR   Ensembl; ENST00000369031.4; ENSP00000358027.4; ENSG00000164494.12. [Q86YH6-2]
DR   Ensembl; ENST00000369037.9; ENSP00000358033.4; ENSG00000164494.12. [Q86YH6-1]
DR   GeneID; 57107; -.
DR   KEGG; hsa:57107; -.
DR   MANE-Select; ENST00000369037.9; ENSP00000358033.4; NM_020381.4; NP_065114.3.
DR   UCSC; uc003prt.3; human. [Q86YH6-1]
DR   AGR; HGNC:23041; -.
DR   CTD; 57107; -.
DR   DisGeNET; 57107; -.
DR   GeneCards; PDSS2; -.
DR   GeneReviews; PDSS2; -.
DR   HGNC; HGNC:23041; PDSS2.
DR   HPA; ENSG00000164494; Low tissue specificity.
DR   MalaCards; PDSS2; -.
DR   MIM; 610564; gene.
DR   MIM; 614652; phenotype.
DR   neXtProt; NX_Q86YH6; -.
DR   OpenTargets; ENSG00000164494; -.
DR   PharmGKB; PA134957167; -.
DR   VEuPathDB; HostDB:ENSG00000164494; -.
DR   eggNOG; KOG0776; Eukaryota.
DR   GeneTree; ENSGT00940000153498; -.
DR   HOGENOM; CLU_014015_3_1_1; -.
DR   InParanoid; Q86YH6; -.
DR   OMA; HEQVRWT; -.
DR   OrthoDB; 2899987at2759; -.
DR   PhylomeDB; Q86YH6; -.
DR   TreeFam; TF354277; -.
DR   BioCyc; MetaCyc:HS15203-MONOMER; -.
DR   BRENDA; 2.5.1.91; 2681.
DR   PathwayCommons; Q86YH6; -.
DR   Reactome; R-HSA-2142789; Ubiquinol biosynthesis.
DR   SignaLink; Q86YH6; -.
DR   UniPathway; UPA00232; -.
DR   BioGRID-ORCS; 57107; 108 hits in 1167 CRISPR screens.
DR   ChiTaRS; PDSS2; human.
DR   GeneWiki; PDSS2; -.
DR   GenomeRNAi; 57107; -.
DR   Pharos; Q86YH6; Tbio.
DR   PRO; PR:Q86YH6; -.
DR   Proteomes; UP000005640; Chromosome 6.
DR   RNAct; Q86YH6; Protein.
DR   Bgee; ENSG00000164494; Expressed in buccal mucosa cell and 178 other cell types or tissues.
DR   ExpressionAtlas; Q86YH6; baseline and differential.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
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:0052923; F:all-trans-nonaprenyl-diphosphate synthase (geranyl-diphosphate specific) activity; IEA:Ensembl.
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:0021549; P:cerebellum development; ISS:UniProtKB.
DR   GO; GO:0008299; P:isoprenoid biosynthetic process; IDA:HGNC-UCL.
DR   GO; GO:0050878; P:regulation of body fluid levels; IEA:Ensembl.
DR   GO; GO:0006744; P:ubiquinone biosynthetic process; IDA:HGNC-UCL.
DR   Gene3D; 1.10.600.10; Farnesyl Diphosphate Synthase; 1.
DR   InterPro; IPR008949; Isoprenoid_synthase_dom_sf.
DR   InterPro; IPR000092; Polyprenyl_synt.
DR   PANTHER; PTHR12001:SF55; ALL TRANS-POLYPRENYL-DIPHOSPHATE SYNTHASE PDSS2; 1.
DR   PANTHER; PTHR12001; GERANYLGERANYL PYROPHOSPHATE SYNTHASE; 1.
DR   Pfam; PF00348; polyprenyl_synt; 1.
DR   SUPFAM; SSF48576; Terpenoid synthases; 1.
DR   Genevisible; Q86YH6; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Disease variant; Isoprene biosynthesis;
KW   Lipid metabolism; Mitochondrion; Primary mitochondrial disease;
KW   Reference proteome; Transferase; Ubiquinone biosynthesis.
FT   CHAIN           1..399
FT                   /note="All trans-polyprenyl-diphosphate synthase PDSS2"
FT                   /id="PRO_0000123978"
FT   VAR_SEQ         211..240
FT                   /note="VVELLASALMDLVQGVYHENSTSKESYITD -> SFSFNGPIAIYQMGDCES
FT                   AWILSKHPRALS (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_017098"
FT   VAR_SEQ         241..399
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_017099"
FT   VARIANT         3
FT                   /note="F -> L (in dbSNP:rs3734675)"
FT                   /id="VAR_049645"
FT   VARIANT         382
FT                   /note="S -> L (in COQ10D3; dbSNP:rs118203956)"
FT                   /evidence="ECO:0000269|PubMed:17186472"
FT                   /id="VAR_055398"
FT   CONFLICT        335
FT                   /note="G -> R (in Ref. 4; AAH39906)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   399 AA;  44129 MW;  C6519BC97C0ECA02 CRC64;
     MNFRQLLLHL PRYLGASGSP RRLWWSPSLD TISSVGSWRG RSSKSPAHWN QVVSEAEKIV
     GYPTSFMSLR CLLSDELSNI AMQVRKLVGT QHPLLTTARG LVHDSWNSLQ LRGLVVLLIS
     KAAGPSSVNT SCQNYDMVSG IYSCQRSLAE ITELIHIALL VHRGIVNLNE LQSSDGPLKD
     MQFGNKIAIL SGDFLLANAC NGLALLQNTK VVELLASALM DLVQGVYHEN STSKESYITD
     DIGISTWKEQ TFLSHGALLA KSCQAAMELA KHDAEVQNMA FQYGKHMAMS HKINSDVQPF
     IKEKTSDSMT FNLNSAPVVL HQEFLGRDLW IKQIGEAQEK GRLDYAKLRE RIKAGKGVTS
     AIDLCRYHGN KALEALESFP PSEARSALEN IVFAVTRFS
//