Search
Dickkopf-related protein 1; Dickkopf-1; Dkk-1; hDkk-1; SK (DKK1)
Function:
- antagonizes canonical Wnt signaling by inhibiting LRP5 &/or LRP6
- blocks canonical Wnt-mediated activation of beta-catenin signaling & induces the proapoptotic protein Bax, resulting in apoptosis in outer root sheath keratinocytes
- affects the anagen-to-catagen transition in the hair cycle
- in male pattern baldness, high tissue levels of androgen- inducible DKK-1 may produce the same effects
- interaction with Wnt & by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5 &/or LRP6
- DKKs play a role in vertebrate development, where they locally inhibit Wnt regulated processes such as anteroposterior axial patterning, limb development, somitogenesis & eye formation
- in adults, Dkks are implicated in bone formation
- interacts with LRP6
- interacts (via the C-termianl Cys-rich domain) with LRP5 (via beta-propeller regions 3 & 4)
- interaction is enhanced by MESD & or KREMEN
- interaction antagonizes Wnt-mediated signaling
Structure:
- the C-terminal cysteine-rich domain mediates interaction with LRP5 & LRP6 (putative)
- belongs to the dickkopf family
Compartment: secreted
Expression:
- placenta
- induced by androgens [3]
Pathology:
- Dkks are implicated in bone disease, cancer & Alzheimer disease
- may play a role in male-pattern baldness [3]
General
Dickkopf homolog
Properties
SIZE: entity length = 266 aa
MW = 29 kD
COMPARTMENT: extracellular compartment
MOTIF: signal sequence {1-31}
Ser glycosylation site {S61}
DKK-type Cys-1 {85-138}
MOTIF: cysteine residue {C85}
MODIFICATION: cysteine residue {C97}
cysteine residue {C91}
MODIFICATION: cysteine residue {C111}
cysteine residue {C97}
MODIFICATION: cysteine residue {C85}
cysteine residue {C111}
MODIFICATION: cysteine residue {C91}
cysteine residue {C114}
MODIFICATION: cysteine residue {C128}
cysteine residue {C121}
MODIFICATION: cysteine residue {C133}
cysteine residue {C127}
MODIFICATION: cysteine residue {C138}
cysteine residue {C128}
MODIFICATION: cysteine residue {C114}
cysteine residue {C133}
MODIFICATION: cysteine residue {C121}
cysteine residue {C138}
MODIFICATION: cysteine residue {C127}
DKK-type Cys-2 {189-263}
MOTIF: cysteine residue {C189}
MODIFICATION: cysteine residue {C201}
cysteine residue {C195}
MODIFICATION: cysteine residue {C210}
cysteine residue {C200}
MODIFICATION: cysteine residue {C237}
cysteine residue {C201}
MODIFICATION: cysteine residue {C189}
cysteine residue {C210}
MODIFICATION: cysteine residue {C195}
cysteine residue {C220}
MODIFICATION: cysteine residue {C245}
cysteine residue {C237}
MODIFICATION: cysteine residue {C200}
cysteine residue {C239}
MODIFICATION: cysteine residue {C263}
cysteine residue {C245}
MODIFICATION: cysteine residue {C220}
N-glycosylation site {N256}
cysteine residue {C263}
MODIFICATION: cysteine residue {C239}
Database Correlations
OMIM 605189
UniProt O94907
Pfam PF04706
Entrez Gene 22943
Kegg hsa:22943
References
- UniProt :accession O94907
- Atlas of Genetics & Cytogenetics in Oncology & Haematology
http://atlasgeneticsoncology.org/genes/DKK1ID44007ch10q11.html
- Kwack MH et al.
Dickkopf 1 promotes regression of hair follicles.
J Invest Dermatol 2012 Jun; 132:1554
PMID: 22358062