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Protein

Dickkopf-related protein 2

Gene

DKK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at transcript 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).By similarity

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Wnt signaling pathway

Enzyme and pathway databases

ReactomeiR-HSA-201681. TCF dependent signaling in response to WNT.
R-HSA-3772470. Negative regulation of TCF-dependent signaling by WNT ligand antagonists.
R-HSA-5339717. Misspliced LRP5 mutants have enhanced beta-catenin-dependent signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Dickkopf-related protein 2
Short name:
Dickkopf-2
Short name:
Dkk-2
Short name:
hDkk-2
Gene namesi
Name:DKK2
ORF Names:UNQ682/PRO1316
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:2892. DKK2.

Subcellular locationi

GO - Cellular componenti

  • extracellular space Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA27346.

Polymorphism and mutation databases

BioMutaiDKK2.
DMDMi13124093.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3333Sequence analysisAdd
BLAST
Chaini34 – 259226Dickkopf-related protein 2PRO_0000007220Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi52 – 521N-linked (GlcNAc...)Sequence analysis
Disulfide bondi183 ↔ 195By similarity
Disulfide bondi189 ↔ 204By similarity
Disulfide bondi194 ↔ 231By similarity
Disulfide bondi214 ↔ 239By similarity
Disulfide bondi233 ↔ 256By similarity

Post-translational modificationi

May be proteolytically processed by a furin-like protease.

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9UBU2.
PRIDEiQ9UBU2.

PTM databases

iPTMnetiQ9UBU2.
PhosphoSiteiQ9UBU2.

Expressioni

Tissue specificityi

Expressed in heart, brain, skeletal muscle and lung.

Gene expression databases

BgeeiQ9UBU2.
CleanExiHS_DKK2.
ExpressionAtlasiQ9UBU2. baseline and differential.
GenevisibleiQ9UBU2. HS.

Organism-specific databases

HPAiCAB009727.

Interactioni

Subunit structurei

Interacts with LRP5 and LRP6.By similarity

Protein-protein interaction databases

BioGridi118014. 1 interaction.
DIPiDIP-59408N.
STRINGi9606.ENSP00000285311.

Structurei

3D structure databases

ProteinModelPortaliQ9UBU2.
SMRiQ9UBU2. Positions 172-259.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni78 – 12750DKK-type Cys-1Add
BLAST
Regioni183 – 25674DKK-type Cys-2Add
BLAST

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

Signal

Phylogenomic databases

eggNOGiKOG1218. Eukaryota.
ENOG410XQWV. LUCA.
GeneTreeiENSGT00390000007000.
HOGENOMiHOG000246998.
HOVERGENiHBG000441.
InParanoidiQ9UBU2.
KOiK02165.
OrthoDBiEOG7K3TMT.
PhylomeDBiQ9UBU2.
TreeFamiTF330916.

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.

Q9UBU2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAALMRSKDS SCCLLLLAAV LMVESSQIGS SRAKLNSIKS SLGGETPGQA
60 70 80 90 100
ANRSAGMYQG LAFGGSKKGK NLGQAYPCSS DKECEVGRYC HSPHQGSSAC
110 120 130 140 150
MVCRRKKKRC HRDGMCCPST RCNNGICIPV TESILTPHIP ALDGTRHRDR
160 170 180 190 200
NHGHYSNHDL GWQNLGRPHT KMSHIKGHEG DPCLRSSDCI EGFCCARHFW
210 220 230 240 250
TKICKPVLHQ GEVCTKQRKK GSHGLEIFQR CDCAKGLSCK VWKDATYSSK

ARLHVCQKI
Length:259
Mass (Da):28,447
Last modified:May 1, 2000 - v1
Checksum:i39DDA3FA8975E87F
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti146 – 1461R → Q.1 Publication
Corresponds to variant rs17037102 [ dbSNP | Ensembl ].
VAR_021966

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS3675.1.
RefSeqiNP_055236.1. NM_014421.2.
UniGeneiHs.211869.

Genome annotation databases

EnsembliENST00000285311; ENSP00000285311; ENSG00000155011.
GeneIDi27123.
KEGGihsa:27123.
UCSCiuc003hyi.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS3675.1.
RefSeqiNP_055236.1. NM_014421.2.
UniGeneiHs.211869.

3D structure databases

ProteinModelPortaliQ9UBU2.
SMRiQ9UBU2. Positions 172-259.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118014. 1 interaction.
DIPiDIP-59408N.
STRINGi9606.ENSP00000285311.

PTM databases

iPTMnetiQ9UBU2.
PhosphoSiteiQ9UBU2.

Polymorphism and mutation databases

BioMutaiDKK2.
DMDMi13124093.

Proteomic databases

PaxDbiQ9UBU2.
PRIDEiQ9UBU2.

Protocols and materials databases

DNASUi27123.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000285311; ENSP00000285311; ENSG00000155011.
GeneIDi27123.
KEGGihsa:27123.
UCSCiuc003hyi.4. human.

Organism-specific databases

CTDi27123.
GeneCardsiDKK2.
HGNCiHGNC:2892. DKK2.
HPAiCAB009727.
MIMi605415. gene.
neXtProtiNX_Q9UBU2.
PharmGKBiPA27346.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1218. Eukaryota.
ENOG410XQWV. LUCA.
GeneTreeiENSGT00390000007000.
HOGENOMiHOG000246998.
HOVERGENiHBG000441.
InParanoidiQ9UBU2.
KOiK02165.
OrthoDBiEOG7K3TMT.
PhylomeDBiQ9UBU2.
TreeFamiTF330916.

Enzyme and pathway databases

ReactomeiR-HSA-201681. TCF dependent signaling in response to WNT.
R-HSA-3772470. Negative regulation of TCF-dependent signaling by WNT ligand antagonists.
R-HSA-5339717. Misspliced LRP5 mutants have enhanced beta-catenin-dependent signaling.

Miscellaneous databases

ChiTaRSiDKK2. human.
GeneWikiiDKK2.
GenomeRNAii27123.
PROiQ9UBU2.
SOURCEiSearch...

Gene expression databases

BgeeiQ9UBU2.
CleanExiHS_DKK2.
ExpressionAtlasiQ9UBU2. baseline and differential.
GenevisibleiQ9UBU2. HS.

Family and domain databases

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

Publicationsi

« Hide 'large scale' publications
  1. 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. 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.
    , 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].
  5. 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] [Europe PMC] [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] [Europe PMC] [Abstract]
    Cited for: REVIEW OF THE DKK FAMILY.

Entry informationi

Entry nameiDKK2_HUMAN
AccessioniPrimary (citable) accession number: Q9UBU2
Secondary accession number(s): A0AVE9, B2R6S7, Q9UIU3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: May 1, 2000
Last modified: June 8, 2016
This is version 129 of the entry and version 1 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, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.