DLP1_HUMAN
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 03-AUG-2022, entry version 160.
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 BioMuta; PDSS2; -.
DR DMDM; 73620006; -.
DR EPD; Q86YH6; -.
DR jPOST; Q86YH6; -.
DR MassIVE; Q86YH6; -.
DR MaxQB; Q86YH6; -.
DR PaxDb; Q86YH6; -.
DR PeptideAtlas; Q86YH6; -.
DR PRIDE; Q86YH6; -.
DR ProteomicsDB; 70415; -. [Q86YH6-1]
DR ProteomicsDB; 70416; -. [Q86YH6-2]
DR Antibodypedia; 32171; 324 antibodies from 23 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 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 Orphanet; 255249; Leigh syndrome with nephrotic syndrome.
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; GRNNMQA; -.
DR OrthoDB; 1424831at2759; -.
DR PhylomeDB; Q86YH6; -.
DR TreeFam; TF354277; -.
DR BioCyc; MetaCyc:HS15203-MON; -.
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; 90 hits in 1087 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 176 other tissues.
DR ExpressionAtlas; Q86YH6; baseline and differential.
DR Genevisible; Q86YH6; HS.
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: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: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; -; 1.
DR InterPro; IPR008949; Isoprenoid_synthase_dom_sf.
DR InterPro; IPR000092; Polyprenyl_synt.
DR Pfam; PF00348; polyprenyl_synt; 1.
DR SUPFAM; SSF48576; SSF48576; 1.
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
