Q9UBU2 (DKK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Gene names

Name:	DKK2
ORF Names:	UNQ682/PRO1316

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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 disease By similarity.
Subunit structure	Interacts with LRP5 and LRP6 By similarity.
Subcellular location	Secreted.
Tissue specificity	Expressed in heart, brain, skeletal muscle and lung.
Domain	The C-terminal cysteine-rich domain mediates interaction with LRP5 and LRP6 By similarity.
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
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Developmental protein
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
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 canonical Wnt receptor signaling pathway Inferred from direct assay. Source: BHF-UCL positive regulation of canonical Wnt receptor signaling pathway Inferred from direct assay. Source: BHF-UCL
Cellular component	extracellular space Inferred from direct assay. Source: BHF-UCL
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_0000007220
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		By similarity
	Disulfide bond	189 ↔ 204		By similarity
	Disulfide bond	194 ↔ 231		By similarity
	Disulfide bond	214 ↔ 239		By similarity
	Disulfide bond	233 ↔ 256		By similarity
Natural variations
	Natural variant	146	1	R → Q. Ref.6 Corresponds to variant rs17037102 [ dbSNP | Ensembl ].		VAR_021966

Sequences

	Sequence		Length	Mass (Da)
	Q9UBU2 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 39DDA3FA8975E87F	FASTA	259	28,447
	10 20 30 40 50 60 MAALMRSKDS SCCLLLLAAV LMVESSQIGS SRAKLNSIKS SLGGETPGQA ANRSAGMYQG 70 80 90 100 110 120 LAFGGSKKGK NLGQAYPCSS DKECEVGRYC HSPHQGSSAC MVCRRKKKRC HRDGMCCPST 130 140 150 160 170 180 RCNNGICIPV TESILTPHIP ALDGTRHRDR NHGHYSNHDL GWQNLGRPHT KMSHIKGHEG 190 200 210 220 230 240 DPCLRSSDCI EGFCCARHFW TKICKPVLHQ GEVCTKQRKK GSHGLEIFQR CDCAKGLSCK 250 VWKDATYSSK ARLHVCQKI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Functional and structural diversity of the human Dickkopf gene family." Krupnik V.E., Sharp J.D., Jiang C., Robison K., Chickering T.W., Amaravadi L., Brown D.E., Guyot D., Mays G., Leiby K., Chang B., Duong T., Goodearl A.D.J., Gearing D.P., Sokol S.Y., McCarthy S.A. Gene 238:301-313(1999) [PubMed: 10570958] [Abstract] 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]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] 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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases 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: 15489334] [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: 17143291] [Abstract] Cited for: REVIEW OF THE DKK FAMILY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00002779.
RefSeq	NP_055236.1. NM_014421.2.
UniGene	Hs.211869.
3D structure databases
ProteinModelPortal	Q9UBU2.
SMR	Q9UBU2. Positions 172-259.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9UBU2.
Polymorphism databases
DMDM	13124093.
Proteomic databases
PRIDE	Q9UBU2.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000285311; ENSP00000285311; ENSG00000155011.
GeneID	27123.
KEGG	hsa:27123.
UCSC	uc003hyi.1. human.
Organism-specific databases
CTD	27123.
GeneCards	GC04M107842.
H-InvDB	HIX0031344.
HGNC	HGNC:2892. DKK2.
HPA	CAB009727.
MIM	605415. gene.
neXtProt	NX_Q9UBU2.
PharmGKB	PA27346.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG13961.
GeneTree	ENSGT00390000007000.
HOGENOM	HBG445081.
HOVERGEN	HBG000441.
InParanoid	Q9UBU2.
OMA	AANRSAG.
OrthoDB	EOG4N8R5J.
PhylomeDB	Q9UBU2.
Enzyme and pathway databases
Pathway_Interaction_DB	wnt_canonical_pathway. Canonical Wnt signaling pathway. ps1pathway. Presenilin action in Notch and Wnt signaling.
Gene expression databases
ArrayExpress	Q9UBU2.
Bgee	Q9UBU2.
CleanEx	HS_DKK2.
Genevestigator	Q9UBU2.
GermOnline	ENSG00000155011. Homo sapiens.
Family and domain databases
InterPro	IPR006796. Dickkopf_N. [Graphical view]
KO	K02165.
Pfam	PF04706. Dickkopf_N. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	49820.
SOURCE	Search...

Entry information

Entry name

DKK2_HUMAN

Accession

Primary (citable) accession number: Q9UBU2
Secondary accession number(s): A0AVE9, B2R6S7, Q9UIU3

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	May 1, 2000
Last modified:	January 25, 2012
This is version 93 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.