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Q9UBP4

- DKK3_HUMAN

UniProt

Q9UBP4 - DKK3_HUMAN

Protein

Dickkopf-related protein 3

Gene

DKK3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 124 (01 Oct 2014)
      Sequence version 2 (02 Nov 2010)
      Previous versions | rss
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    Functioni

    Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6. DKKs play an important role in vertebrate development, where they locally inhibit Wnt regulated processes such as antero-posterior axial patterning, limb development, somitogenesis and eye formation. In the adult, Dkks are implicated in bone formation and bone disease, cancer and Alzheimer disease By similarity.By similarity

    GO - Biological processi

    1. adrenal gland development Source: UniProtKB
    2. anatomical structure morphogenesis Source: ProtInc
    3. negative regulation of aldosterone biosynthetic process Source: UniProtKB
    4. negative regulation of canonical Wnt signaling pathway Source: BHF-UCL
    5. negative regulation of cortisol biosynthetic process Source: UniProtKB
    6. negative regulation of transcription, DNA-templated Source: UniProtKB
    7. Wnt signaling pathway Source: UniProtKB-KW

    Keywords - Molecular functioni

    Developmental protein

    Keywords - Biological processi

    Wnt signaling pathway

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Dickkopf-related protein 3
    Short name:
    Dickkopf-3
    Short name:
    Dkk-3
    Short name:
    hDkk-3
    Gene namesi
    Name:DKK3
    Synonyms:REIC
    ORF Names:UNQ258/PRO295
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:2893. DKK3.

    Subcellular locationi

    GO - Cellular componenti

    1. extracellular space Source: ProtInc

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA27347.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 21212 PublicationsAdd
    BLAST
    Chaini22 – 350329Dickkopf-related protein 3PRO_0000007222Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi26 – 261O-linked (GalNAc...)1 Publication
    Glycosylationi28 – 281O-linked (GalNAc...)1 Publication
    Glycosylationi96 – 961N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi106 – 1061N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi121 – 1211N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi204 – 2041N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi208 ↔ 220By similarity
    Disulfide bondi214 ↔ 231By similarity
    Disulfide bondi219 ↔ 265By similarity
    Disulfide bondi241 ↔ 273By similarity

    Post-translational modificationi

    N- and O-glycosylated.3 Publications

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    MaxQBiQ9UBP4.
    PaxDbiQ9UBP4.
    PRIDEiQ9UBP4.

    PTM databases

    PhosphoSiteiQ9UBP4.

    Expressioni

    Tissue specificityi

    Highest expression in heart, brain, and spinal cord.2 Publications

    Gene expression databases

    ArrayExpressiQ9UBP4.
    BgeeiQ9UBP4.
    CleanExiHS_DKK3.
    GenevestigatoriQ9UBP4.

    Organism-specific databases

    HPAiCAB024949.
    HPA011868.

    Interactioni

    Subunit structurei

    Interacts with LRP5 and LRP6.By similarity

    Protein-protein interaction databases

    BioGridi118013. 1 interaction.
    IntActiQ9UBP4. 2 interactions.
    STRINGi9606.ENSP00000314910.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9UBP4.
    SMRiQ9UBP4. Positions 205-279.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni29 – 4618O-glycosylated at one siteAdd
    BLAST
    Regioni147 – 19549DKK-type Cys-1Add
    BLAST
    Regioni208 – 28477DKK-type Cys-2Add
    BLAST

    Coiled coil

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Coiled coili40 – 8445Sequence AnalysisAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi338 – 3436Poly-Ala

    Domaini

    The C-terminal cysteine-rich domain mediates interaction with LRP5 and LRP6.By similarity

    Sequence similaritiesi

    Belongs to the dickkopf family.Curated

    Keywords - Domaini

    Coiled coil, Signal

    Phylogenomic databases

    eggNOGiNOG302601.
    HOGENOMiHOG000234342.
    HOVERGENiHBG004476.
    InParanoidiQ9UBP4.
    OrthoDBiEOG7JX34Z.
    PhylomeDBiQ9UBP4.
    TreeFamiTF337340.

    Family and domain databases

    InterProiIPR006796. Dickkopf_N.
    [Graphical view]
    PfamiPF04706. Dickkopf_N. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q9UBP4-1 [UniParc]FASTAAdd to Basket

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    MQRLGATLLC LLLAAAVPTA PAPAPTATSA PVKPGPALSY PQEEATLNEM    50
    FREVEELMED TQHKLRSAVE EMEAEEAAAK ASSEVNLANL PPSYHNETNT 100
    DTKVGNNTIH VHREIHKITN NQTGQMVFSE TVITSVGDEE GRRSHECIID 150
    EDCGPSMYCQ FASFQYTCQP CRGQRMLCTR DSECCGDQLC VWGHCTKMAT 200
    RGSNGTICDN QRDCQPGLCC AFQRGLLFPV CTPLPVEGEL CHDPASRLLD 250
    LITWELEPDG ALDRCPCASG LLCQPHSHSL VYVCKPTFVG SRDQDGEILL 300
    PREVPDEYEV GSFMEEVRQE LEDLERSLTE EMALREPAAA AAALLGGEEI 350
    Length:350
    Mass (Da):38,390
    Last modified:November 2, 2010 - v2
    Checksum:i734504122B40AFEE
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti49 – 491E → D.
    Corresponds to variant rs11544816 [ dbSNP | Ensembl ].
    VAR_057516
    Natural varianti335 – 3351R → G.8 Publications
    Corresponds to variant rs3206824 [ dbSNP | Ensembl ].
    VAR_030787

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF177396 mRNA. Translation: AAF02676.1.
    AB034203 mRNA. Translation: BAA90548.1.
    AB057591 mRNA. Translation: BAB84360.1.
    AB057804 Genomic DNA. Translation: BAB84361.1.
    AB033421 mRNA. Translation: BAA85488.1.
    AB035182 Genomic DNA. Translation: BAA87044.2.
    AY358378 mRNA. Translation: AAQ88744.1.
    AK289897 mRNA. Translation: BAF82586.1.
    AC124276 Genomic DNA. No translation available.
    CH471064 Genomic DNA. Translation: EAW68534.1.
    CH471064 Genomic DNA. Translation: EAW68535.1.
    CH471064 Genomic DNA. Translation: EAW68537.1.
    BC007660 mRNA. Translation: AAH07660.1.
    CCDSiCCDS7808.1.
    PIRiJC7188.
    RefSeqiNP_001018067.1. NM_001018057.1.
    NP_037385.2. NM_013253.4.
    NP_056965.3. NM_015881.5.
    XP_006718241.1. XM_006718178.1.
    UniGeneiHs.292156.
    Hs.731954.

    Genome annotation databases

    EnsembliENST00000326932; ENSP00000314910; ENSG00000050165.
    ENST00000396505; ENSP00000379762; ENSG00000050165.
    GeneIDi27122.
    KEGGihsa:27122.
    UCSCiuc001mju.3. human.

    Polymorphism databases

    DMDMi311033372.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF177396 mRNA. Translation: AAF02676.1 .
    AB034203 mRNA. Translation: BAA90548.1 .
    AB057591 mRNA. Translation: BAB84360.1 .
    AB057804 Genomic DNA. Translation: BAB84361.1 .
    AB033421 mRNA. Translation: BAA85488.1 .
    AB035182 Genomic DNA. Translation: BAA87044.2 .
    AY358378 mRNA. Translation: AAQ88744.1 .
    AK289897 mRNA. Translation: BAF82586.1 .
    AC124276 Genomic DNA. No translation available.
    CH471064 Genomic DNA. Translation: EAW68534.1 .
    CH471064 Genomic DNA. Translation: EAW68535.1 .
    CH471064 Genomic DNA. Translation: EAW68537.1 .
    BC007660 mRNA. Translation: AAH07660.1 .
    CCDSi CCDS7808.1.
    PIRi JC7188.
    RefSeqi NP_001018067.1. NM_001018057.1.
    NP_037385.2. NM_013253.4.
    NP_056965.3. NM_015881.5.
    XP_006718241.1. XM_006718178.1.
    UniGenei Hs.292156.
    Hs.731954.

    3D structure databases

    ProteinModelPortali Q9UBP4.
    SMRi Q9UBP4. Positions 205-279.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 118013. 1 interaction.
    IntActi Q9UBP4. 2 interactions.
    STRINGi 9606.ENSP00000314910.

    PTM databases

    PhosphoSitei Q9UBP4.

    Polymorphism databases

    DMDMi 311033372.

    Proteomic databases

    MaxQBi Q9UBP4.
    PaxDbi Q9UBP4.
    PRIDEi Q9UBP4.

    Protocols and materials databases

    DNASUi 27122.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000326932 ; ENSP00000314910 ; ENSG00000050165 .
    ENST00000396505 ; ENSP00000379762 ; ENSG00000050165 .
    GeneIDi 27122.
    KEGGi hsa:27122.
    UCSCi uc001mju.3. human.

    Organism-specific databases

    CTDi 27122.
    GeneCardsi GC11M011984.
    H-InvDB HIX0009450.
    HGNCi HGNC:2893. DKK3.
    HPAi CAB024949.
    HPA011868.
    MIMi 605416. gene.
    neXtProti NX_Q9UBP4.
    PharmGKBi PA27347.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG302601.
    HOGENOMi HOG000234342.
    HOVERGENi HBG004476.
    InParanoidi Q9UBP4.
    OrthoDBi EOG7JX34Z.
    PhylomeDBi Q9UBP4.
    TreeFami TF337340.

    Miscellaneous databases

    ChiTaRSi DKK3. human.
    GeneWikii DKK3.
    GenomeRNAii 27122.
    NextBioi 49812.
    PROi Q9UBP4.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9UBP4.
    Bgeei Q9UBP4.
    CleanExi HS_DKK3.
    Genevestigatori Q9UBP4.

    Family and domain databases

    InterProi IPR006796. Dickkopf_N.
    [Graphical view ]
    Pfami PF04706. Dickkopf_N. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, POSSIBLE FUNCTION, GLYCOSYLATION, VARIANT GLY-335.
      Tissue: Fetal brain.
    2. "A REIC gene shows down-regulation in human immortalized cells and human tumor-derived cell lines."
      Tsuji T., Miyazaki M., Sakaguchi M., Inoue Y., Namba M.
      Biochem. Biophys. Res. Commun. 268:20-24(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLY-335.
    3. "Reduced expression of the REIC/Dkk-3 gene by promoter-hypermethylation in human tumor cells."
      Kobayashi K., Ouchida M., Tsuji T., Hanafusa H., Miyazaki M., Namba M., Shimizu N., Shimizu K.
      Gene 282:151-158(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANT GLY-335.
    4. "Human homologue of Dickkopf-3."
      Tanaka S., Sugimachi K., Sugimachi K.
      Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, VARIANT GLY-335.
    5. "Human Dickkopf-3, genomic sequence."
      Tate G., Mitsuya T.
      Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLY-335.
    7. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLY-335.
      Tissue: Corpus callosum.
    8. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    9. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT GLY-335.
    10. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLY-335.
      Tissue: Kidney.
    11. "Signal peptide prediction based on analysis of experimentally verified cleavage sites."
      Zhang Z., Henzel W.J.
      Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 22-36.
    12. "Function and biological roles of the Dickkopf family of Wnt modulators."
      Niehrs C.
      Oncogene 25:7469-7481(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW OF THE DKK FAMILY.
    13. "Enrichment of glycopeptides for glycan structure and attachment site identification."
      Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., Brinkmalm G., Larson G.
      Nat. Methods 6:809-811(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS], SIGNAL SEQUENCE CLEAVAGE SITE, STRUCTURE OF CARBOHYDRATES.
      Tissue: Cerebrospinal fluid.
    14. "LC-MS/MS characterization of O-glycosylation sites and glycan structures of human cerebrospinal fluid glycoproteins."
      Halim A., Ruetschi U., Larson G., Nilsson J.
      J. Proteome Res. 12:573-584(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION AT THR-26 AND THR-28, IDENTIFICATION BY MASS SPECTROMETRY.

    Entry informationi

    Entry nameiDKK3_HUMAN
    AccessioniPrimary (citable) accession number: Q9UBP4
    Secondary accession number(s): A8K1I2, D3DQW1, Q9ULB7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 21, 2001
    Last sequence update: November 2, 2010
    Last modified: October 1, 2014
    This is version 124 of the entry and version 2 of the sequence. [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, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 11
      Human chromosome 11: entries, gene names and cross-references to MIM
    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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3