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Reviewed, UniProtKB/Swiss-Prot Q9UBU2 (DKK2_HUMAN)

Last modified January 19, 2010. Version 78. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Dickkopf-related protein 2
      Short name=Dickkopf-2
      Short name=Dkk-2
      Short name=hDkk-2
Gene names
Name: DKK2
ORF Names: UNQ682/PRO1316
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length259 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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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's disease By similarity.

Subunit structure

Interacts with LRP5 and LRP6 By similarity.

Subcellular location

Secreted.

Tissue specificity

Expressed in heart, brain, skeletal muscle and lung.

Domain

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

Post-translational modification

May be proteolytically processed by a furin-like protease.

Sequence similarities

Belongs to the dickkopf family.

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Ontologies

Keywords
   Biological processWnt signaling pathway
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DomainSignal
   Molecular functionDevelopmental protein
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Gene Ontology (GO)
   Biological processWnt receptor signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

multicellular organismal development

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of Wnt receptor signaling pathway

Inferred from electronic annotation. Source: InterPro

   Cellular componentextracellular space Ref.1

Traceable author statement. Source: ProtInc

Complete GO annotation...

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3333 Potential
Chain34 – 259226Dickkopf-related protein 2
PRO_0000007220

Regions

Region78 – 12750DKK-type Cys-1
Region183 – 25674DKK-type Cys-2

Amino acid modifications

Glycosylation521N-linked (GlcNAc...) Potential
Disulfide bond183 ↔ 195 By similarity
Disulfide bond189 ↔ 204 By similarity
Disulfide bond194 ↔ 231 By similarity
Disulfide bond214 ↔ 239 By similarity
Disulfide bond233 ↔ 256 By similarity

Natural variations

Natural variant1461R → Q: dbSNP rs17037102. Ref.6
VAR_021966

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Sequences

Sequence LengthMass (Da)Tools
Q9UBU2-1 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: 39DDA3FA8975E87F

FASTA25928,447
        10         20         30         40         50         60 
MAALMRSKDS SCCLLLLAAV LMVESSQIGS SRAKLNSIKS SLGGETPGQA ANRSAGMYQG 

        70         80         90        100        110        120 
LAFGGSKKGK NLGQAYPCSS DKECEVGRYC HSPHQGSSAC MVCRRKKKRC HRDGMCCPST 

       130        140        150        160        170        180 
RCNNGICIPV TESILTPHIP ALDGTRHRDR NHGHYSNHDL GWQNLGRPHT KMSHIKGHEG 

       190        200        210        220        230        240 
DPCLRSSDCI EGFCCARHFW TKICKPVLHQ GEVCTKQRKK GSHGLEIFQR CDCAKGLSCK 

       250 
VWKDATYSSK ARLHVCQKI

« Hide

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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: 10570958] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Fetal lung.
[2]Tanaka S., Sugimachi K., Sugimachi K.
Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"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: 12975309] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]"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: 14702039] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]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 (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLN-146.
Tissue: Brain and Testis.
[7]Tate G., Suzuki T., Mitsuya T.
Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 75-259.
[8]"Function and biological roles of the Dickkopf family of Wnt modulators."
Niehrs C.
Oncogene 25:7469-7481(2006) [PubMed: 17143291] [Abstract]
Cited for: REVIEW OF THE DKK FAMILY.
+Additional computationally mapped references.

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AF177395 mRNA. Translation: AAF02675.1.
AB033208 mRNA. Translation: BAA85465.1.
AY358414 mRNA. Translation: AAQ88780.1.
AK312695 mRNA. Translation: BAG35574.1.
CH471057 Genomic DNA. Translation: EAX06209.1.
BC075077 mRNA. Translation: AAH75077.1.
BC075078 mRNA. Translation: AAH75078.1.
BC126328 mRNA. Translation: AAI26329.1.
BC126330 mRNA. Translation: AAI26331.1.
AB035181 Genomic DNA. Translation: BAA87056.1.
IPIIPI00002779.
RefSeqNP_055236.1.
UniGeneHs.211869

3D structure databases

SMRQ9UBU2. Positions 172-259.
ModBaseSearch...

Protein-protein interaction databases

STRINGQ9UBU2.

Proteomic databases

PRIDEQ9UBU2.

Genome annotation databases

EnsemblENST00000285311; ENSP00000285311; ENSG00000155011; Homo sapiens. [Genome view]
GeneID27123.
KEGGhsa:27123.
UCSCuc003hyi.1. human.

Organism-specific databases

CTD27123.
GeneCardsGC04M108062.
H-InvDBHIX0031344.
HGNCHGNC:2892. DKK2.
HPACAB009727.
MIM605415. gene.
PharmGKBPA27346.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG13961.
HOGENOMHBG445081.
HOVERGENQ9UBU2.
InParanoidQ9UBU2.
OMAMSHIKGH.
OrthoDBEOG9F7R48.
PhylomeDBQ9UBU2.

Enzyme and pathway databases

Pathway_Interaction_DBwnt_canonical_pathway. Canonical Wnt signaling pathway.
ps1pathway. Presenilin action in Notch and Wnt signaling.

Gene expression databases

ArrayExpressQ9UBU2.
BgeeQ9UBU2.
CleanExHS_DKK2.
GenevestigatorQ9UBU2.
GermOnlineENSG00000155011. Homo sapiens.

Family and domain databases

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

Other Resources

NextBio49820.
SOURCESearch...

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Entry information

Entry nameDKK2_HUMAN
AccessionPrimary (citable) accession number: Q9UBU2
Secondary accession number(s): A0AVE9, B2R6S7, Q9UIU3
Entry history
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: May 1, 2000
Last modified: January 19, 2010
This is version 78 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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.

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents