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Protein

Dehydrodolichyl diphosphate synthase complex subunit NUS1

Gene

NUS1

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

Functioni

With DHDDS, 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:21572394, PubMed:25066056, PubMed:28842490). Regulates the glycosylation and stability of nascent NPC2, thereby promoting trafficking of LDL-derived cholesterol. Acts as a specific receptor for the N-terminus of Nogo-B, a neural and cardiovascular regulator (PubMed:16835300).4 Publications

Miscellaneous

NUS1 seems to exist in two topological orientations, a minor glycosylated species with its C-terminus oriented towards the lumen regulating NPC2 stability, and a major fraction oriented with its C-terminus directed towards the cytosol where it regulates cis-IPTase activity.1 Publication

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 substrates.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.2 Publications
    View all proteins of this organism that are known to be involved in Lipid metabolism.

    GO - Molecular functioni

    • dehydrodolichyl diphosphate synthase activity Source: UniProtKB

    GO - Biological processi

    Keywordsi

    Molecular functionDevelopmental protein, Receptor, Transferase
    Biological processAngiogenesis, Differentiation, Lipid metabolism
    LigandMagnesium

    Enzyme and pathway databases

    ReactomeiR-HSA-446199 Synthesis of Dolichyl-phosphate
    UniPathwayi
    UPA00378

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Dehydrodolichyl diphosphate synthase complex subunit NUS1Curated (EC:2.5.1.872 Publications)
    Alternative name(s):
    Cis-prenyltransferase subunit NgBR1 Publication
    Nogo-B receptor1 Publication
    Short name:
    NgBR2 Publications
    Nuclear undecaprenyl pyrophosphate synthase 1 homologCurated
    Gene namesi
    Name:NUS11 PublicationImported
    Synonyms:C6orf68, NGBR
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 6

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000153989.7
    HGNCiHGNC:21042 NUS1
    MIMi610463 gene
    neXtProtiNX_Q96E22

    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

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Transmembranei1 – 23Helical; Name=11 PublicationAdd BLAST23
    Transmembranei35 – 56Helical; Name=21 PublicationAdd BLAST22
    Transmembranei117 – 135Helical; Name=31 PublicationAdd BLAST19

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Congenital disorder of glycosylation 1AA (CDG1AA)1 Publication
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA form of congenital disorder of glycosylation, a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG1AA inheritance is autosomal recessive.
    See also OMIM:617082
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_071210290R → H in CDG1AA; loss of function in protein glycosylation; 5-fold reduction in catalytic activity and reduced affinity for FPP and IPP.. 2 PublicationsCorresponds to variant dbSNP:rs886037858EnsemblClinVar.1
    Mental retardation, autosomal dominant 55, with seizures (MRD55)1 Publication
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD55 patients suffer from seizures appearing during the first years of life.
    See also OMIM:617831

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi100H → A: 3.5-fold reduction in catalytic activity and no marked change in affinity for FPP and IPP. 1 Publication1
    Mutagenesisi292G → A: Almost complete loss of catalytic activity. 1 Publication1
    Mutagenesisi293K → KA: Almost complete loss of catalytic activity. 1 Publication1
    Mutagenesisi293Missing : Almost complete loss of catalytic activity. 1 Publication1

    Keywords - Diseasei

    Congenital disorder of glycosylation, Disease mutation, Mental retardation

    Organism-specific databases

    DisGeNETi116150
    MalaCardsiNUS1
    MIMi617082 phenotype
    617831 phenotype
    OpenTargetsiENSG00000153989
    Orphaneti442835 Undetermined early-onset epileptic encephalopathy
    PharmGKBiPA162398248

    Polymorphism and mutation databases

    BioMutaiNUS1
    DMDMi74762651

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00002731671 – 293Dehydrodolichyl diphosphate synthase complex subunit NUS1Add BLAST293

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Glycosylationi144N-linked (GlcNAc...) asparagine1 Publication1
    Glycosylationi271N-linked (GlcNAc...) asparagine1 Publication1

    Keywords - PTMi

    Glycoprotein

    Proteomic databases

    EPDiQ96E22
    MaxQBiQ96E22
    PaxDbiQ96E22
    PeptideAtlasiQ96E22
    PRIDEiQ96E22
    ProteomicsDBi76366

    PTM databases

    iPTMnetiQ96E22
    PhosphoSitePlusiQ96E22

    Expressioni

    Gene expression databases

    BgeeiENSG00000153989 Expressed in 200 organ(s), highest expression level in endometrium
    CleanExiHS_NUS1
    GenevisibleiQ96E22 HS

    Organism-specific databases

    HPAiHPA027504

    Interactioni

    Subunit structurei

    Forms an active dehydrodolichyl diphosphate synthase complex with DHDDS (PubMed:28842490, PubMed:19723497, PubMed:25066056). Interacts with NPC2 (PubMed:21572394).4 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    C10orf95Q9H7T33EBI-6949352,EBI-6949335

    Protein-protein interaction databases

    BioGridi125481, 26 interactors
    CORUMiQ96E22
    DIPiDIP-61225N
    IntActiQ96E22, 5 interactors
    MINTiQ96E22
    STRINGi9606.ENSP00000357480

    Structurei

    3D structure databases

    ProteinModelPortaliQ96E22
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Motif

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Motifi290 – 292RXG motif; crucial for prenyltransferase activity1 Publication3

    Sequence similaritiesi

    Belongs to the UPP synthase family.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG2818 Eukaryota
    COG0020 LUCA
    GeneTreeiENSGT00390000003223
    HOGENOMiHOG000007321
    HOVERGENiHBG082024
    InParanoidiQ96E22
    KOiK19177
    OMAiYVSVYDH
    OrthoDBiEOG091G0YHE
    PhylomeDBiQ96E22
    TreeFamiTF332448

    Family and domain databases

    Gene3Di3.40.1180.10, 1 hit
    InterProiView protein in InterPro
    IPR038887 Nus1/NgBR
    IPR001441 UPP_synth-like
    IPR036424 UPP_synth-like_sf
    PANTHERiPTHR21528 PTHR21528, 1 hit
    PfamiView protein in Pfam
    PF01255 Prenyltransf, 1 hit
    SUPFAMiSSF64005 SSF64005, 1 hit

    Sequencei

    Sequence statusi: Complete.

    Q96E22-1 [UniParc]FASTAAdd to basket
    « Hide
            10         20         30         40         50
    MTGLYELVWR VLHALLCLHR TLTSWLRVRF GTWNWIWRRC CRAASAAVLA
    60 70 80 90 100
    PLGFTLRKPP AVGRNRRHHR HPRGGSCLAA AHHRMRWRAD GRSLEKLPVH
    110 120 130 140 150
    MGLVITEVEQ EPSFSDIASL VVWCMAVGIS YISVYDHQGI FKRNNSRLMD
    160 170 180 190 200
    EILKQQQELL GLDCSKYSPE FANSNDKDDQ VLNCHLAVKV LSPEDGKADI
    210 220 230 240 250
    VRAAQDFCQL VAQKQKRPTD LDVDTLASLL SSNGCPDPDL VLKFGPVDST
    260 270 280 290
    LGFLPWHIRL TEIVSLPSHL NISYEDFFSA LRQYAACEQR LGK
    Length:293
    Mass (Da):33,224
    Last modified:December 1, 2001 - v1
    Checksum:iE6A0C9D9B39D4BCA
    GO

    Sequence cautioni

    The sequence AAB72234 differs from that shown. Reason: Frameshift at several positions.Curated

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_030092175N → Y. Corresponds to variant dbSNP:rs28362518Ensembl.1
    Natural variantiVAR_030093179D → E. Corresponds to variant dbSNP:rs28362519Ensembl.1
    Natural variantiVAR_030094210Missing . Corresponds to variant dbSNP:rs1052237Ensembl.1
    Natural variantiVAR_030095216K → R1 PublicationCorresponds to variant dbSNP:rs1052239Ensembl.1
    Natural variantiVAR_030096219T → K1 PublicationCorresponds to variant dbSNP:rs1132147Ensembl.1
    Natural variantiVAR_071210290R → H in CDG1AA; loss of function in protein glycosylation; 5-fold reduction in catalytic activity and reduced affinity for FPP and IPP.. 2 PublicationsCorresponds to variant dbSNP:rs886037858EnsemblClinVar.1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    Z98172 Genomic DNA No translation available.
    AL590303 Genomic DNA No translation available.
    CH471051 Genomic DNA Translation: EAW48201.1
    BC013026 mRNA Translation: AAH13026.1
    BC063794 mRNA Translation: AAH63794.1
    BC066910 mRNA Translation: AAH66910.1
    BC110325 mRNA Translation: AAI10326.1
    BC150654 mRNA Translation: AAI50655.1
    BC150655 mRNA Translation: AAI50656.1
    U82319 mRNA Translation: AAB72234.1 Frameshift.
    CCDSiCCDS5118.1
    RefSeqiNP_612468.1, NM_138459.3
    UniGeneiHs.289008
    Hs.525826

    Genome annotation databases

    EnsembliENST00000368494; ENSP00000357480; ENSG00000153989
    GeneIDi116150
    KEGGihsa:116150
    UCSCiuc003pxw.4 human

    Keywords - Coding sequence diversityi

    Polymorphism

    Similar proteinsi

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    Z98172 Genomic DNA No translation available.
    AL590303 Genomic DNA No translation available.
    CH471051 Genomic DNA Translation: EAW48201.1
    BC013026 mRNA Translation: AAH13026.1
    BC063794 mRNA Translation: AAH63794.1
    BC066910 mRNA Translation: AAH66910.1
    BC110325 mRNA Translation: AAI10326.1
    BC150654 mRNA Translation: AAI50655.1
    BC150655 mRNA Translation: AAI50656.1
    U82319 mRNA Translation: AAB72234.1 Frameshift.
    CCDSiCCDS5118.1
    RefSeqiNP_612468.1, NM_138459.3
    UniGeneiHs.289008
    Hs.525826

    3D structure databases

    ProteinModelPortaliQ96E22
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi125481, 26 interactors
    CORUMiQ96E22
    DIPiDIP-61225N
    IntActiQ96E22, 5 interactors
    MINTiQ96E22
    STRINGi9606.ENSP00000357480

    PTM databases

    iPTMnetiQ96E22
    PhosphoSitePlusiQ96E22

    Polymorphism and mutation databases

    BioMutaiNUS1
    DMDMi74762651

    Proteomic databases

    EPDiQ96E22
    MaxQBiQ96E22
    PaxDbiQ96E22
    PeptideAtlasiQ96E22
    PRIDEiQ96E22
    ProteomicsDBi76366

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000368494; ENSP00000357480; ENSG00000153989
    GeneIDi116150
    KEGGihsa:116150
    UCSCiuc003pxw.4 human

    Organism-specific databases

    CTDi116150
    DisGeNETi116150
    EuPathDBiHostDB:ENSG00000153989.7
    GeneCardsiNUS1
    H-InvDBiHIX0022536
    HGNCiHGNC:21042 NUS1
    HPAiHPA027504
    MalaCardsiNUS1
    MIMi610463 gene
    617082 phenotype
    617831 phenotype
    neXtProtiNX_Q96E22
    OpenTargetsiENSG00000153989
    Orphaneti442835 Undetermined early-onset epileptic encephalopathy
    PharmGKBiPA162398248
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG2818 Eukaryota
    COG0020 LUCA
    GeneTreeiENSGT00390000003223
    HOGENOMiHOG000007321
    HOVERGENiHBG082024
    InParanoidiQ96E22
    KOiK19177
    OMAiYVSVYDH
    OrthoDBiEOG091G0YHE
    PhylomeDBiQ96E22
    TreeFamiTF332448

    Enzyme and pathway databases

    UniPathwayi
    UPA00378

    ReactomeiR-HSA-446199 Synthesis of Dolichyl-phosphate

    Miscellaneous databases

    GenomeRNAii116150
    PROiPR:Q96E22
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000153989 Expressed in 200 organ(s), highest expression level in endometrium
    CleanExiHS_NUS1
    GenevisibleiQ96E22 HS

    Family and domain databases

    Gene3Di3.40.1180.10, 1 hit
    InterProiView protein in InterPro
    IPR038887 Nus1/NgBR
    IPR001441 UPP_synth-like
    IPR036424 UPP_synth-like_sf
    PANTHERiPTHR21528 PTHR21528, 1 hit
    PfamiView protein in Pfam
    PF01255 Prenyltransf, 1 hit
    SUPFAMiSSF64005 SSF64005, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiNGBR_HUMAN
    AccessioniPrimary (citable) accession number: Q96E22
    Secondary accession number(s): B2RWQ4, O00251
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 23, 2007
    Last sequence update: December 1, 2001
    Last modified: November 7, 2018
    This is version 140 of the entry and version 1 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 entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. Human chromosome 6
      Human chromosome 6: entries, gene names and cross-references to MIM
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    Main funding by: National Institutes of Health

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