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Q9UBP4 (DKK3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Dickkopf-related protein 3

Short name=Dickkopf-3
Short name=Dkk-3
Short name=hDkk-3
Gene names
Name:DKK3
Synonyms:REIC
ORF Names:UNQ258/PRO295
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length350 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1

Subunit structure

Interacts with LRP5 and LRP6 By similarity.

Subcellular location

Secreted.

Tissue specificity

Highest expression in heart, brain, and spinal cord. Ref.1 Ref.4

Domain

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

Post-translational modification

N- and O-glycosylated. Ref.1 Ref.14

Sequence similarities

Belongs to the dickkopf family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Ref.11
Chain22 – 350329Dickkopf-related protein 3
PRO_0000007222

Regions

Region29 – 4618O-glycosylated at one site
Region147 – 19549DKK-type Cys-1
Region208 – 28477DKK-type Cys-2
Coiled coil40 – 8445 Potential
Compositional bias338 – 3436Poly-Ala

Amino acid modifications

Glycosylation261O-linked (GalNAc...) Ref.14
Glycosylation281O-linked (GalNAc...) Ref.14
Glycosylation961N-linked (GlcNAc...) Potential
Glycosylation1061N-linked (GlcNAc...) Potential
Glycosylation1211N-linked (GlcNAc...) Potential
Glycosylation2041N-linked (GlcNAc...) Potential
Disulfide bond208 ↔ 220 By similarity
Disulfide bond214 ↔ 231 By similarity
Disulfide bond219 ↔ 265 By similarity
Disulfide bond241 ↔ 273 By similarity

Natural variations

Natural variant491E → D.
Corresponds to variant rs11544816 [ dbSNP | Ensembl ].
VAR_057516
Natural variant3351R → G. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6 Ref.7 Ref.9 Ref.10
Corresponds to variant rs3206824 [ dbSNP | Ensembl ].
VAR_030787

Sequences

Sequence LengthMass (Da)Tools
Q9UBP4 [UniParc].

Last modified November 2, 2010. Version 2.
Checksum: 734504122B40AFEE

FASTA35038,390
        10         20         30         40         50         60 
MQRLGATLLC LLLAAAVPTA PAPAPTATSA PVKPGPALSY PQEEATLNEM FREVEELMED 

        70         80         90        100        110        120 
TQHKLRSAVE EMEAEEAAAK ASSEVNLANL PPSYHNETNT DTKVGNNTIH VHREIHKITN 

       130        140        150        160        170        180 
NQTGQMVFSE TVITSVGDEE GRRSHECIID EDCGPSMYCQ FASFQYTCQP CRGQRMLCTR 

       190        200        210        220        230        240 
DSECCGDQLC VWGHCTKMAT RGSNGTICDN QRDCQPGLCC AFQRGLLFPV CTPLPVEGEL 

       250        260        270        280        290        300 
CHDPASRLLD LITWELEPDG ALDRCPCASG LLCQPHSHSL VYVCKPTFVG SRDQDGEILL 

       310        320        330        340        350 
PREVPDEYEV GSFMEEVRQE LEDLERSLTE EMALREPAAA AAALLGGEEI 

« Hide

References

« Hide 'large scale' references
[1]"Functional and structural diversity of the human Dickkopf gene family."
Krupnik V.E., Sharp J.D., Jiang C., Robison K., Chickering T.W., Amaravadi L., Brown D.E., Guyot D., Mays G., Leiby K., Chang B., Duong T., Goodearl A.D.J., Gearing D.P., Sokol S.Y., McCarthy S.A.
Gene 238:301-313(1999) [PubMed] [Europe PMC] [Abstract]
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]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRJC7188.
RefSeqNP_001018067.1. NM_001018057.1.
NP_037385.2. NM_013253.4.
NP_056965.3. NM_015881.5.
UniGeneHs.292156.
Hs.731954.

3D structure databases

ProteinModelPortalQ9UBP4.
SMRQ9UBP4. Positions 205-279.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid118013. 1 interaction.
IntActQ9UBP4. 2 interactions.
STRING9606.ENSP00000314910.

PTM databases

PhosphoSiteQ9UBP4.

Polymorphism databases

DMDM311033372.

Proteomic databases

PaxDbQ9UBP4.
PRIDEQ9UBP4.

Protocols and materials databases

DNASU27122.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000326932; ENSP00000314910; ENSG00000050165.
ENST00000396505; ENSP00000379762; ENSG00000050165.
GeneID27122.
KEGGhsa:27122.
UCSCuc001mju.3. human.

Organism-specific databases

CTD27122.
GeneCardsGC11M011984.
H-InvDBHIX0009450.
HGNCHGNC:2893. DKK3.
HPACAB024949.
HPA011868.
MIM605416. gene.
neXtProtNX_Q9UBP4.
PharmGKBPA27347.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG302601.
HOGENOMHOG000234342.
HOVERGENHBG004476.
InParanoidQ9UBP4.
OrthoDBEOG7JX34Z.
PhylomeDBQ9UBP4.
TreeFamTF337340.

Gene expression databases

ArrayExpressQ9UBP4.
BgeeQ9UBP4.
CleanExHS_DKK3.
GenevestigatorQ9UBP4.

Family and domain databases

InterProIPR006796. Dickkopf_N.
[Graphical view]
PfamPF04706. Dickkopf_N. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSDKK3. human.
GeneWikiDKK3.
GenomeRNAi27122.
NextBio49812.
PROQ9UBP4.
SOURCESearch...

Entry information

Entry nameDKK3_HUMAN
AccessionPrimary (citable) accession number: Q9UBP4
Secondary accession number(s): A8K1I2, D3DQW1, Q9ULB7
Entry history
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: November 2, 2010
Last modified: April 16, 2014
This is version 121 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM