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Protein

Dehydrodolichyl diphosphate synthase complex subunit DHDDS

Gene

DHDDS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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). Regulates the glycosylation and stability of nascent NPC2, thereby promoting trafficking of LDL-derived cholesterol (PubMed:21572394).3 Publications

Catalytic activityi

(2E,6E)-farnesyl diphosphate + n isopentenyl diphosphate = n diphosphate + ditrans,polycis-polyprenyl diphosphate (n = 10-55).2 Publications

Cofactori

Mg2+1 Publication

Activity regulationi

Activated by phospholipids including cardiolipin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and phosphatidylserine.1 Publication

Kineticsi

Values were measured with the heterodimer. kcat is 0.58 sec(-1) with (2E,6E)-farnesyl diphosphate and isopentenyl diphosphate as substrate.1 Publication
  1. KM=11.1 µM for isopentenyl diphosphate1 Publication
  2. KM=0.68 µM for (2E,6E)-farnesyl diphosphate1 Publication

    pH dependencei

    Optimum pH is 8-9. Active from pH 5.5 to 9.3.1 Publication

    Pathwayi: protein glycosylation

    This protein is involved in the pathway protein glycosylation, which is part of Protein modification.1 Publication
    View 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 Publication
    View all proteins of this organism that are known to be involved in Lipid metabolism.

    GO - Molecular functioni

    • dehydrodolichyl diphosphate synthase activity Source: UniProtKB
    • polyprenyltransferase activity Source: GO_Central

    GO - Biological processi

    Keywordsi

    Molecular functionTransferase
    Biological processLipid metabolism
    LigandMagnesium

    Enzyme and pathway databases

    BRENDAi2.5.1.87 2681
    ReactomeiR-HSA-446199 Synthesis of Dolichyl-phosphate
    R-HSA-4755609 Defective DHDDS causes retinitis pigmentosa 59
    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
    Name:DHDDS1 PublicationImported
    Synonyms:HDS
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 1

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000117682.16
    HGNCiHGNC:20603 DHDDS
    MIMi608172 gene
    neXtProtiNX_Q86SQ9

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Retinitis pigmentosa 59 (RP59)1 Publication
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.
    See also OMIM:613861
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_06535642K → 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
    The disease may be caused by mutations affecting the gene represented in this entry.
    Disease descriptionAn autosomal dominant neurodevelopmental disorder characterized by global developmental delay, variable intellectual disability, and early-onset seizures with a myoclonic component. Most patients have delayed motor development and show abnormal movements, including ataxia, dystonia, and tremor.
    See also OMIM:617836
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_08070837R → H in DEDSM; unknown pathological significance. 1 Publication1
    Natural variantiVAR_080709211R → Q in DEDSM; unknown pathological significance. 1 Publication1

    Keywords - Diseasei

    Disease mutation, Epilepsy, Mental retardation, Retinitis pigmentosa

    Organism-specific databases

    DisGeNETi79947
    GeneReviewsiDHDDS
    MalaCardsiDHDDS
    MIMi613861 phenotype
    617836 phenotype
    OpenTargetsiENSG00000117682
    Orphaneti791 Retinitis pigmentosa
    442835 Undetermined early-onset epileptic encephalopathy
    PharmGKBiPA134867119

    Polymorphism and mutation databases

    BioMutaiDHDDS
    DMDMi116241329

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001237491 – 333Dehydrodolichyl diphosphate synthase complex subunit DHDDSAdd BLAST333

    Proteomic databases

    EPDiQ86SQ9
    MaxQBiQ86SQ9
    PaxDbiQ86SQ9
    PeptideAtlasiQ86SQ9
    PRIDEiQ86SQ9
    ProteomicsDBi69620
    69621 [Q86SQ9-2]
    69622 [Q86SQ9-3]

    PTM databases

    iPTMnetiQ86SQ9
    PhosphoSitePlusiQ86SQ9

    Expressioni

    Tissue specificityi

    Expressed at high levels in testis and kidney. Expressed in epididymis (at protein level). Slightly expressed in heart, spleen and thymus.1 Publication

    Gene expression databases

    BgeeiENSG00000117682 Expressed in 198 organ(s), highest expression level in right hemisphere of cerebellum
    CleanExiHS_DHDDS
    ExpressionAtlasiQ86SQ9 baseline and differential
    GenevisibleiQ86SQ9 HS

    Organism-specific databases

    HPAiHPA026721
    HPA026727

    Interactioni

    Subunit structurei

    Forms an active dehydrodolichyl diphosphate synthase complex with NUS1 (PubMed:25066056, PubMed:28842490). Interacts with NPC2 (PubMed:21572394).3 Publications

    Protein-protein interaction databases

    BioGridi123018, 6 interactors
    CORUMiQ86SQ9
    STRINGi9606.ENSP00000353104

    Structurei

    3D structure databases

    ProteinModelPortaliQ86SQ9
    SMRiQ86SQ9
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the UPP synthase family.Curated

    Phylogenomic databases

    eggNOGiKOG1602 Eukaryota
    COG0020 LUCA
    GeneTreeiENSGT00390000007879
    HOVERGENiHBG051350
    InParanoidiQ86SQ9
    KOiK11778
    OMAiFDRRDLW
    OrthoDBiEOG091G0K4O
    PhylomeDBiQ86SQ9
    TreeFamiTF323753

    Family and domain databases

    CDDicd00475 Cis_IPPS, 1 hit
    Gene3Di3.40.1180.10, 1 hit
    HAMAPiMF_01139 ISPT, 1 hit
    InterProiView protein in InterPro
    IPR001441 UPP_synth-like
    IPR018520 UPP_synth-like_CS
    IPR036424 UPP_synth-like_sf
    PANTHERiPTHR10291 PTHR10291, 1 hit
    PfamiView protein in Pfam
    PF01255 Prenyltransf, 1 hit
    SUPFAMiSSF64005 SSF64005, 1 hit
    TIGRFAMsiTIGR00055 uppS, 1 hit
    PROSITEiView protein in PROSITE
    PS01066 UPP_SYNTHASE, 1 hit

    Sequences (4+)i

    Sequence statusi: Complete.

    This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

    This entry has 4 described isoforms and 13 potential isoforms that are computationally mapped.Show allAlign All

    Isoform 1 (identifier: Q86SQ9-1) [UniParc]FASTAAdd to basket

    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.

    « Hide
            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
    Length:333
    Mass (Da):38,657
    Last modified:October 17, 2006 - v3
    Checksum:i12EF3A15437A2583
    GO
    Isoform 2 (identifier: Q86SQ9-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         255-255: Q → QQ

    Show »
    Length:334
    Mass (Da):38,786
    Checksum:i8B91F530F1E538E2
    GO
    Isoform 3 (identifier: Q86SQ9-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         109-147: Missing.

    Note: May be due to exon skipping.
    Show »
    Length:294
    Mass (Da):34,264
    Checksum:i1EF92BC4658FFDF9
    GO
    Isoform 4 (identifier: Q86SQ9-4) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         147-181: KCFLNVCFAYTSRHEISNAVREMAWGVEQGLLDPS → N

    Note: No experimental confirmation available.
    Show »
    Length:299
    Mass (Da):34,817
    Checksum:i55AE4DA2A326CA58
    GO

    Computationally mapped potential isoform sequencesi

    There are 13 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    Q5T0A2Q5T0A2_HUMAN
    Alkyl transferase
    DHDDS
    173Annotation score:
    Q5T0A1Q5T0A1_HUMAN
    Alkyl transferase
    DHDDS
    209Annotation score:
    E9PI09E9PI09_HUMAN
    Alkyl transferase
    DHDDS
    198Annotation score:
    E9PR24E9PR24_HUMAN
    Alkyl transferase
    DHDDS
    165Annotation score:
    E9PRS7E9PRS7_HUMAN
    Alkyl transferase
    DHDDS
    122Annotation score:
    E9PI64E9PI64_HUMAN
    Alkyl transferase
    DHDDS
    130Annotation score:
    Q5T0A3Q5T0A3_HUMAN
    Alkyl transferase
    DHDDS
    216Annotation score:
    H0Y4T1H0Y4T1_HUMAN
    Alkyl transferase
    DHDDS
    162Annotation score:
    Q5T0A0Q5T0A0_HUMAN
    Dehydrodolichyl diphosphate synthas...
    DHDDS
    73Annotation score:
    Q5T0A6Q5T0A6_HUMAN
    Dehydrodolichyl diphosphate synthas...
    DHDDS
    169Annotation score:
    There are more potential isoformsShow all

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti151N → Y in BAB14439 (PubMed:14702039).Curated1
    Sequence conflicti277V → E in AAH34152 (PubMed:15489334).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_08070837R → H in DEDSM; unknown pathological significance. 1 Publication1
    Natural variantiVAR_06535642K → 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_080709211R → Q in DEDSM; unknown pathological significance. 1 Publication1
    Natural variantiVAR_028088253V → M3 PublicationsCorresponds to variant dbSNP:rs3816539EnsemblClinVar.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_010030109 – 147Missing in isoform 3. 1 PublicationAdd BLAST39
    Alternative sequenceiVSP_045007147 – 181KCFLN…LLDPS → N in isoform 4. 1 PublicationAdd BLAST35
    Alternative sequenceiVSP_010031255Q → QQ in isoform 2. 1 Publication1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB090852 mRNA Translation: BAC57588.1
    GU727641 mRNA Translation: ADU87642.1
    AK023164 mRNA Translation: BAB14439.1
    AK297134 mRNA Translation: BAH12505.1
    AK316485 mRNA Translation: BAH14856.1
    AL513365 Genomic DNA No translation available.
    CH471059 Genomic DNA Translation: EAX07806.1
    CH471059 Genomic DNA Translation: EAX07808.1
    CH471059 Genomic DNA Translation: EAX07809.1
    CH471059 Genomic DNA Translation: EAX07810.1
    CH471059 Genomic DNA Translation: EAX07811.1
    CH471059 Genomic DNA Translation: EAX07812.1
    BC003643 mRNA Translation: AAH03643.1
    BC004117 mRNA Translation: AAH04117.1
    BC034152 mRNA Translation: AAH34152.1
    CCDSiCCDS281.1 [Q86SQ9-2]
    CCDS282.1 [Q86SQ9-1]
    CCDS57983.1 [Q86SQ9-4]
    CCDS57984.1 [Q86SQ9-3]
    RefSeqiNP_001230493.1, NM_001243564.1 [Q86SQ9-4]
    NP_001230494.1, NM_001243565.1 [Q86SQ9-3]
    NP_079163.2, NM_024887.3 [Q86SQ9-2]
    NP_995583.1, NM_205861.2 [Q86SQ9-1]
    XP_006710975.1, XM_006710912.2
    XP_006710976.1, XM_006710913.2
    XP_006710977.1, XM_006710914.2
    XP_011540485.1, XM_011542183.2
    XP_011540486.1, XM_011542184.2
    XP_011540488.1, XM_011542186.2
    XP_016857868.1, XM_017002379.1
    XP_016857869.1, XM_017002380.1
    UniGeneiHs.369385

    Genome annotation databases

    EnsembliENST00000236342; ENSP00000236342; ENSG00000117682 [Q86SQ9-1]
    ENST00000360009; ENSP00000353104; ENSG00000117682 [Q86SQ9-2]
    ENST00000525682; ENSP00000434984; ENSG00000117682 [Q86SQ9-4]
    ENST00000526219; ENSP00000434219; ENSG00000117682 [Q86SQ9-3]
    GeneIDi79947
    KEGGihsa:79947
    UCSCiuc001bmk.4 human [Q86SQ9-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB090852 mRNA Translation: BAC57588.1
    GU727641 mRNA Translation: ADU87642.1
    AK023164 mRNA Translation: BAB14439.1
    AK297134 mRNA Translation: BAH12505.1
    AK316485 mRNA Translation: BAH14856.1
    AL513365 Genomic DNA No translation available.
    CH471059 Genomic DNA Translation: EAX07806.1
    CH471059 Genomic DNA Translation: EAX07808.1
    CH471059 Genomic DNA Translation: EAX07809.1
    CH471059 Genomic DNA Translation: EAX07810.1
    CH471059 Genomic DNA Translation: EAX07811.1
    CH471059 Genomic DNA Translation: EAX07812.1
    BC003643 mRNA Translation: AAH03643.1
    BC004117 mRNA Translation: AAH04117.1
    BC034152 mRNA Translation: AAH34152.1
    CCDSiCCDS281.1 [Q86SQ9-2]
    CCDS282.1 [Q86SQ9-1]
    CCDS57983.1 [Q86SQ9-4]
    CCDS57984.1 [Q86SQ9-3]
    RefSeqiNP_001230493.1, NM_001243564.1 [Q86SQ9-4]
    NP_001230494.1, NM_001243565.1 [Q86SQ9-3]
    NP_079163.2, NM_024887.3 [Q86SQ9-2]
    NP_995583.1, NM_205861.2 [Q86SQ9-1]
    XP_006710975.1, XM_006710912.2
    XP_006710976.1, XM_006710913.2
    XP_006710977.1, XM_006710914.2
    XP_011540485.1, XM_011542183.2
    XP_011540486.1, XM_011542184.2
    XP_011540488.1, XM_011542186.2
    XP_016857868.1, XM_017002379.1
    XP_016857869.1, XM_017002380.1
    UniGeneiHs.369385

    3D structure databases

    ProteinModelPortaliQ86SQ9
    SMRiQ86SQ9
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi123018, 6 interactors
    CORUMiQ86SQ9
    STRINGi9606.ENSP00000353104

    PTM databases

    iPTMnetiQ86SQ9
    PhosphoSitePlusiQ86SQ9

    Polymorphism and mutation databases

    BioMutaiDHDDS
    DMDMi116241329

    Proteomic databases

    EPDiQ86SQ9
    MaxQBiQ86SQ9
    PaxDbiQ86SQ9
    PeptideAtlasiQ86SQ9
    PRIDEiQ86SQ9
    ProteomicsDBi69620
    69621 [Q86SQ9-2]
    69622 [Q86SQ9-3]

    Protocols and materials databases

    DNASUi79947
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000236342; ENSP00000236342; ENSG00000117682 [Q86SQ9-1]
    ENST00000360009; ENSP00000353104; ENSG00000117682 [Q86SQ9-2]
    ENST00000525682; ENSP00000434984; ENSG00000117682 [Q86SQ9-4]
    ENST00000526219; ENSP00000434219; ENSG00000117682 [Q86SQ9-3]
    GeneIDi79947
    KEGGihsa:79947
    UCSCiuc001bmk.4 human [Q86SQ9-1]

    Organism-specific databases

    CTDi79947
    DisGeNETi79947
    EuPathDBiHostDB:ENSG00000117682.16
    GeneCardsiDHDDS
    GeneReviewsiDHDDS
    HGNCiHGNC:20603 DHDDS
    HPAiHPA026721
    HPA026727
    MalaCardsiDHDDS
    MIMi608172 gene
    613861 phenotype
    617836 phenotype
    neXtProtiNX_Q86SQ9
    OpenTargetsiENSG00000117682
    Orphaneti791 Retinitis pigmentosa
    442835 Undetermined early-onset epileptic encephalopathy
    PharmGKBiPA134867119
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG1602 Eukaryota
    COG0020 LUCA
    GeneTreeiENSGT00390000007879
    HOVERGENiHBG051350
    InParanoidiQ86SQ9
    KOiK11778
    OMAiFDRRDLW
    OrthoDBiEOG091G0K4O
    PhylomeDBiQ86SQ9
    TreeFamiTF323753

    Enzyme and pathway databases

    UniPathwayi
    UPA00378

    BRENDAi2.5.1.87 2681
    ReactomeiR-HSA-446199 Synthesis of Dolichyl-phosphate
    R-HSA-4755609 Defective DHDDS causes retinitis pigmentosa 59

    Miscellaneous databases

    ChiTaRSiDHDDS human
    GeneWikiiDehydrodolichyl_diphosphate_synthase
    DHDDS
    GenomeRNAii79947
    PROiPR:Q86SQ9
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000117682 Expressed in 198 organ(s), highest expression level in right hemisphere of cerebellum
    CleanExiHS_DHDDS
    ExpressionAtlasiQ86SQ9 baseline and differential
    GenevisibleiQ86SQ9 HS

    Family and domain databases

    CDDicd00475 Cis_IPPS, 1 hit
    Gene3Di3.40.1180.10, 1 hit
    HAMAPiMF_01139 ISPT, 1 hit
    InterProiView protein in InterPro
    IPR001441 UPP_synth-like
    IPR018520 UPP_synth-like_CS
    IPR036424 UPP_synth-like_sf
    PANTHERiPTHR10291 PTHR10291, 1 hit
    PfamiView protein in Pfam
    PF01255 Prenyltransf, 1 hit
    SUPFAMiSSF64005 SSF64005, 1 hit
    TIGRFAMsiTIGR00055 uppS, 1 hit
    PROSITEiView protein in PROSITE
    PS01066 UPP_SYNTHASE, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiDHDDS_HUMAN
    AccessioniPrimary (citable) accession number: Q86SQ9
    Secondary accession number(s): B7Z4B9
    , B7ZB20, D3DPK7, D3DPK8, D3DPK9, E9KL43, Q5T0A4, Q8NE90, Q9BTG5, Q9BTK3, Q9H905
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 13, 2004
    Last sequence update: October 17, 2006
    Last modified: November 7, 2018
    This is version 144 of the entry and version 3 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny 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

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families
    2. Human chromosome 1
      Human chromosome 1: entries, gene names and cross-references to MIM
    3. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    UniProt is an ELIXIR core data resource
    Main funding by: National Institutes of Health

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