Reviewed, UniProtKB/Swiss-Prot O54908 (DKK1_MOUSE)

Names and origin

Protein names

Recommended name:
    Dickkopf-related protein 1
      Short name=Dickkopf-1
      Short name=Dkk-1
      Short name=mDkk-1

Gene names

Name:

Dkk1

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	272 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. 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.
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
Gene Ontology (GO)
Biological process	Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW cardioblast anterior-lateral migration Inferred from expression pattern. Source: UniProtKB cell morphogenesis involved in differentiation Inferred from mutant phenotype. Source: MGI embryonic limb morphogenesis Inferred from genetic interaction. Source: MGI endoderm development Inferred from mutant phenotype. Source: MGI forebrain development Inferred from genetic interaction. Source: MGI head morphogenesis Inferred from genetic interaction. Source: MGI negative regulation of canonical Wnt receptor signaling pathway involved in heart induction Inferred from direct assay. Source: UniProtKB
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 – 31	31	Potential
	Chain	32 – 272	241	Dickkopf-related protein 1		PRO_0000007219
Regions
	Region	86 – 141	56	DKK-type Cys-1
	Region	195 – 269	75	DKK-type Cys-2
Amino acid modifications
	Glycosylation	262	1	N-linked (GlcNAc...) Potential
	Disulfide bond	195 ↔ 207		By similarity
	Disulfide bond	201 ↔ 216		By similarity
	Disulfide bond	206 ↔ 243		By similarity
	Disulfide bond	226 ↔ 251		By similarity
	Disulfide bond	245 ↔ 269		By similarity
Experimental info
	Mutagenesis	210	1	H → E: 50% reduced binding to LRP6. Ref.3
	Mutagenesis	217	1	K → E: 50% reduced binding to LRP6. Ref.3
	Mutagenesis	242	1	R → E: 50% reduced binding to LRP6. Ref.3
	Mutagenesis	267	1	H → E: 43% reduced binding to LRP6. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	O54908-1 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: AB9FA35DFA57D3EE	FASTA	272	29,269
	10 20 30 40 50 60 MMVVCAPAAV RFLAVFTMMA LCSLPLLGAS ATLNSVLINS NAIKNLPPPL GGAGGQPGSA 70 80 90 100 110 120 VSVAPGVLYE GGNKYQTLDN YQPYPCAEDE ECGSDEYCSS PSRGAAGVGG VQICLACRKR 130 140 150 160 170 180 RKRCMTHAMC CPGNYCKNGI CMPSDHSHFP RGEIEESIIE NLGNDHNAAA GDGYPRRTTL 190 200 210 220 230 240 TSKIYHTKGQ EGSVCLRSSD CAAGLCCARH FWSKICKPVL KEGQVCTKHK RKGSHGLEIF 250 260 270 QRCYCGEGLA CRIQKDHHQA SNSSRLHTCQ RH

References

[1]	"Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction." Glinka A., Wu W., Delius H., Monaghan A.P., Blumenstock C., Niehrs C. Nature 391:357-362(1998) [PubMed: 9450748] [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: FUNCTION, SUBUNIT, INTERACTION WITH LRP5 AND LRP6, MUTAGENESIS OF HIS-210; LYS-217; ARG-242 AND HIS-267.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF030433 mRNA. Translation: AAC02426.1.
IPI	IPI00330317.
UniGene	Mm.214717
3D structure databases
SMR	O54908. Positions 186-271.
ModBase	Search...
Protein-protein interaction databases
STRING	O54908.
Proteomic databases
PRIDE	O54908.
Genome annotation databases
Ensembl	ENSMUST00000025803; ENSMUSP00000025803; ENSMUSG00000024868; Mus musculus. [Genome view]
Organism-specific databases
MGI	MGI:1329040. Dkk1.
Phylogenomic databases
eggNOG	roNOG09714.
HOGENOM	HBG445081.
HOVERGEN	O54908.
InParanoid	O54908.
Gene expression databases
ArrayExpress	O54908.
Bgee	O54908.
CleanEx	MM_DKK1.
Genevestigator	O54908.
GermOnline	ENSMUSG00000024868. 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

DKK1_MOUSE

Accession

Primary (citable) accession number: O54908

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	June 1, 1998
Last modified:	January 19, 2010
This is version 62 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)