Reviewed, UniProtKB/Swiss-Prot Q9QYZ8 (DKK2_MOUSE)

Names and origin

Protein names

Recommended name:
    Dickkopf-related protein 2
      Short name=Dickkopf-2
      Short name=Dkk-2
      Short name=mDkk-2

Gene names

Name:

Dkk2

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	259 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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's disease. Ref.3
Subunit structure	Interacts with LRP5 and LRP6. Ref.3
Subcellular location	Secreted.
Domain	The C-terminal cysteine-rich domain mediates interaction with LRP5 and LRP6.
Post-translational modification	May be proteolytically processed by a furin-like protease.
Sequence similarities	Belongs to the dickkopf family.

Ontologies

Keywords
Biological process	Wnt signaling pathway
Cellular component	Secreted
Domain	Signal
Molecular function	Developmental protein
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	Wnt 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 component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 33

33

Potential

Chain

34 – 259

226

Dickkopf-related protein 2

PRO_0000007221

Regions

Region

78 – 127

50

DKK-type Cys-1

Region

183 – 256

74

DKK-type Cys-2

Amino acid modifications

Glycosylation

52

1

N-linked (GlcNAc...) Potential

Disulfide bond

183 ↔ 195

Ref.3

Disulfide bond

189 ↔ 204

Ref.3

Disulfide bond

194 ↔ 231

Ref.3

Disulfide bond

214 ↔ 239

Ref.3

Disulfide bond

233 ↔ 256

Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

259

Helix Strand Turn

Details...

Beta strand

194 – 197

4

Beta strand

199 – 201

3

Beta strand

203 – 205

3

Beta strand

238 – 241

4

Helix

247 – 249

3

Beta strand

254 – 257

4

Sequences

	Sequence		Length	Mass (Da)
	Q9QYZ8-1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: EAAB76F2D2C9780D	FASTA	259	28,416
	10 20 30 40 50 60 MAALMRVKDS SRCLLLLAAV LMVESSQLGS SRAKPNSIKS SLGGETPAQS ANRSAGMNQG 70 80 90 100 110 120 LAFGGSKKGK SLGQAYPCSS DKECEVGRYC HSPHQGSSAC MLCRRKKKRC HRDGMCCPGT 130 140 150 160 170 180 RCNNGICIPV TESILTPHIP ALDGTRHRDR NHGHYSNHDL GWQNLGRPHS KMPHIKGHEG 190 200 210 220 230 240 DPCLRSSDCI DGFCCARHFW TKICKPVLHQ GEVCTKQRKK GSHGLEIFQR CDCAKGLSCK 250 VWKDATYSSK ARLHVCQKI

References

[1]	"Dickkopf genes are co-ordinately expressed in mesodermal lineages." Monaghan P.A., Kioschis P., Wu W., Zuniga A., Bock D., Poustka A., Delius H., Niehrs C. Mech. Dev. 87:45-56(1999) [PubMed: 10495270] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"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.
[3]	"Structural insight into the mechanisms of Wnt signaling antagonism by Dkk." Chen L., Wang K., Shao Y., Huang J., Li X., Shan J., Wu D., Zheng J.J. J. Biol. Chem. 283:23364-23370(2008) [PubMed: 18524778] [Abstract] Cited for: STRUCTURE BY NMR OF 172-259, SUBUNIT, FUNCTION, INTERACTION WITH LRP5 AND LRP6, DISULFIDE BONDS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AJ243963 mRNA. Translation: CAB60110.1.

IPI

IPI00136960.

UniGene

Mm.103593

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2JTK	NMR	-	A	172-259	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

Q9QYZ8.

Proteomic databases

PRIDE

Q9QYZ8.

Genome annotation databases

Ensembl

ENSMUST00000029665; ENSMUSP00000029665; ENSMUSG00000028031; Mus musculus. [Genome view]

Organism-specific databases

MGI

MGI:1890663. Dkk2.

Phylogenomic databases

HOGENOM

HBG445081.

HOVERGEN

Q9QYZ8.

InParanoid

Q9QYZ8.

Gene expression databases

ArrayExpress

Q9QYZ8.

Bgee

Q9QYZ8.

CleanEx

MM_DKK2.

Genevestigator

Q9QYZ8.

GermOnline

ENSMUSG00000028031. Mus musculus.

Family and domain databases

InterPro

IPR006796. Dickkopf_N.
[Graphical view]

Pfam

PF04706. Dickkopf_N. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

SOURCE

Search...

Entry information

Entry name

DKK2_MOUSE

Accession

Primary (citable) accession number: Q9QYZ8

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	May 1, 2000
Last modified:	January 19, 2010
This is version 60 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)