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Q9UBP4

- DKK3_HUMAN

UniProt

Q9UBP4 - DKK3_HUMAN

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Protein
Dickkopf-related protein 3
Gene
DKK3, REIC, UNQ258/PRO295
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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.1 Publication

GO - Biological processi

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

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
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA27347.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 21211 Publication
Add
BLAST
Chaini22 – 350329Dickkopf-related protein 3
PRO_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...) Reviewed prediction
Glycosylationi106 – 1061N-linked (GlcNAc...) Reviewed prediction
Glycosylationi121 – 1211N-linked (GlcNAc...) Reviewed prediction
Glycosylationi204 – 2041N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi208 ↔ 220 By similarity
Disulfide bondi214 ↔ 231 By similarity
Disulfide bondi219 ↔ 265 By similarity
Disulfide bondi241 ↔ 273 By similarity

Post-translational modificationi

N- and O-glycosylated.2 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.

Family & Domainsi

Region

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

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili40 – 8445 Reviewed prediction
Add
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.

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

« Hide

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

« Hide 'large scale' publications
  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: July 9, 2014
This is version 123 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

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