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Protein

Dickkopf-related protein 2

Gene

DKK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 - Molecular functioni

  • co-receptor binding Source: GO_Central
  • receptor antagonist activity Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein
Biological processWnt 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

EuPathDBiHostDB:ENSG00000155011.8
HGNCiHGNC:2892 DKK2
MIMi605415 gene
neXtProtiNX_Q9UBU2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi27123
OpenTargetsiENSG00000155011
PharmGKBiPA27346

Polymorphism and mutation databases

BioMutaiDKK2
DMDMi13124093

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 33Sequence analysisAdd BLAST33
ChainiPRO_000000722034 – 259Dickkopf-related protein 2Add BLAST226

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi52N-linked (GlcNAc...) asparagineSequence analysis1
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

MaxQBiQ9UBU2
PaxDbiQ9UBU2
PeptideAtlasiQ9UBU2
PRIDEiQ9UBU2
ProteomicsDBi84064

PTM databases

iPTMnetiQ9UBU2
PhosphoSitePlusiQ9UBU2

Expressioni

Tissue specificityi

Expressed in heart, brain, skeletal muscle and lung.

Gene expression databases

BgeeiENSG00000155011 Expressed in 148 organ(s), highest expression level in zone of skin
CleanExiHS_DKK2
ExpressionAtlasiQ9UBU2 baseline and differential
GenevisibleiQ9UBU2 HS

Organism-specific databases

HPAiCAB009727
HPA052611

Interactioni

Subunit structurei

Interacts with LRP5 and LRP6.By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi118014, 17 interactors
DIPiDIP-59408N
IntActiQ9UBU2, 2 interactors
STRINGi9606.ENSP00000285311

Structurei

3D structure databases

ProteinModelPortaliQ9UBU2
SMRiQ9UBU2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni78 – 127DKK-type Cys-1Add BLAST50
Regioni183 – 256DKK-type Cys-2Add BLAST74

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
OrthoDBiEOG091G0H13
PhylomeDBiQ9UBU2
TreeFamiTF330916

Family and domain databases

InterProiView protein in InterPro
IPR006796 Dickkopf_N
IPR039863 DKK-like
PANTHERiPTHR12113 PTHR12113, 1 hit
PfamiView protein in Pfam
PF04706 Dickkopf_N, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D6RCC2D6RCC2_HUMAN
Dickkopf-related protein 2
DKK2
213Annotation score:
D6RGF1D6RGF1_HUMAN
Dickkopf-related protein 2
DKK2
159Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_021966146R → Q1 PublicationCorresponds to variant dbSNP:rs17037102Ensembl.1

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

Similar proteinsi

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
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118014, 17 interactors
DIPiDIP-59408N
IntActiQ9UBU2, 2 interactors
STRINGi9606.ENSP00000285311

PTM databases

iPTMnetiQ9UBU2
PhosphoSitePlusiQ9UBU2

Polymorphism and mutation databases

BioMutaiDKK2
DMDMi13124093

Proteomic databases

MaxQBiQ9UBU2
PaxDbiQ9UBU2
PeptideAtlasiQ9UBU2
PRIDEiQ9UBU2
ProteomicsDBi84064

Protocols and materials databases

DNASUi27123
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi27123
DisGeNETi27123
EuPathDBiHostDB:ENSG00000155011.8
GeneCardsiDKK2
HGNCiHGNC:2892 DKK2
HPAiCAB009727
HPA052611
MIMi605415 gene
neXtProtiNX_Q9UBU2
OpenTargetsiENSG00000155011
PharmGKBiPA27346
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1218 Eukaryota
ENOG410XQWV LUCA
GeneTreeiENSGT00390000007000
HOGENOMiHOG000246998
HOVERGENiHBG000441
InParanoidiQ9UBU2
KOiK02165
OrthoDBiEOG091G0H13
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
PROiPR:Q9UBU2
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000155011 Expressed in 148 organ(s), highest expression level in zone of skin
CleanExiHS_DKK2
ExpressionAtlasiQ9UBU2 baseline and differential
GenevisibleiQ9UBU2 HS

Family and domain databases

InterProiView protein in InterPro
IPR006796 Dickkopf_N
IPR039863 DKK-like
PANTHERiPTHR12113 PTHR12113, 1 hit
PfamiView protein in Pfam
PF04706 Dickkopf_N, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiDKK2_HUMAN
AccessioniPrimary (citable) accession number: Q9UBU2
Secondary accession number(s): A0AVE9, B2R6S7, Q9UIU3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: May 1, 2000
Last modified: November 7, 2018
This is version 144 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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