Q9UBP4 (DKK3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Dickkopf-related protein 3
Short name=Dickkopf-3
Short name=Dkk-3
Short name=hDkk-3

Gene names

Name:	DKK3
Synonyms:	REIC
ORF Names:	UNQ258/PRO295

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	350 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. Ref.1
Subunit structure	Interacts with LRP5 and LRP6 By similarity.
Subcellular location	Secreted.
Tissue specificity	Highest expression in heart, brain, and spinal cord. Ref.1 Ref.4
Domain	The C-terminal cysteine-rich domain mediates interaction with LRP5 and LRP6 By similarity.
Post-translational modification	N- and O-glycosylated. Ref.1 Ref.14
Sequence similarities	Belongs to the dickkopf family.

Ontologies

Keywords
Biological process	Wnt signaling pathway
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Coiled coil Signal
Molecular function	Developmental protein
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW adrenal gland development Inferred from expression pattern PubMed 12844346. Source: UniProtKB anatomical structure morphogenesis Traceable author statement Ref.1. Source: ProtInc negative regulation of aldosterone biosynthetic process Inferred from direct assay PubMed 16981135. Source: UniProtKB negative regulation of canonical Wnt receptor signaling pathway Inferred from direct assay PubMed 12857724. Source: BHF-UCL negative regulation of cortisol biosynthetic process Inferred from direct assay PubMed 16981135. Source: UniProtKB negative regulation of transcription, DNA-dependent Inferred from direct assay PubMed 16981135. Source: UniProtKB
Cellular_component	extracellular space Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Ref.11
	Chain	22 – 350	329	Dickkopf-related protein 3		PRO_0000007222
Regions
	Region	29 – 46	18	O-glycosylated at one site
	Region	147 – 195	49	DKK-type Cys-1
	Region	208 – 284	77	DKK-type Cys-2
	Coiled coil	40 – 84	45	Potential
	Compositional bias	338 – 343	6	Poly-Ala
Amino acid modifications
	Glycosylation	26	1	O-linked (GalNAc...) Ref.14
	Glycosylation	28	1	O-linked (GalNAc...) Ref.14
	Glycosylation	96	1	N-linked (GlcNAc...) Potential
	Glycosylation	106	1	N-linked (GlcNAc...) Potential
	Glycosylation	121	1	N-linked (GlcNAc...) Potential
	Glycosylation	204	1	N-linked (GlcNAc...) Potential
	Disulfide bond	208 ↔ 220		By similarity
	Disulfide bond	214 ↔ 231		By similarity
	Disulfide bond	219 ↔ 265		By similarity
	Disulfide bond	241 ↔ 273		By similarity
Natural variations
	Natural variant	49	1	E → D. Corresponds to variant rs11544816 [ dbSNP | Ensembl ].		VAR_057516
	Natural variant	335	1	R → G. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6 Ref.7 Ref.9 Ref.10 Corresponds to variant rs3206824 [ dbSNP | Ensembl ].		VAR_030787

Sequences

	Sequence		Length	Mass (Da)
	Q9UBP4 [UniParc]. Last modified November 2, 2010. Version 2. Checksum: 734504122B40AFEE	FASTA	350	38,390
	10 20 30 40 50 60 MQRLGATLLC LLLAAAVPTA PAPAPTATSA PVKPGPALSY PQEEATLNEM FREVEELMED 70 80 90 100 110 120 TQHKLRSAVE EMEAEEAAAK ASSEVNLANL PPSYHNETNT DTKVGNNTIH VHREIHKITN 130 140 150 160 170 180 NQTGQMVFSE TVITSVGDEE GRRSHECIID EDCGPSMYCQ FASFQYTCQP CRGQRMLCTR 190 200 210 220 230 240 DSECCGDQLC VWGHCTKMAT RGSNGTICDN QRDCQPGLCC AFQRGLLFPV CTPLPVEGEL 250 260 270 280 290 300 CHDPASRLLD LITWELEPDG ALDRCPCASG LLCQPHSHSL VYVCKPTFVG SRDQDGEILL 310 320 330 340 350 PREVPDEYEV GSFMEEVRQE LEDLERSLTE EMALREPAAA AAALLGGEEI

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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, POSSIBLE FUNCTION, GLYCOSYLATION, VARIANT GLY-335. Tissue: Fetal brain.
[2]	"A REIC gene shows down-regulation in human immortalized cells and human tumor-derived cell lines." Tsuji T., Miyazaki M., Sakaguchi M., Inoue Y., Namba M. Biochem. Biophys. Res. Commun. 268:20-24(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLY-335.
[3]	"Reduced expression of the REIC/Dkk-3 gene by promoter-hypermethylation in human tumor cells." Kobayashi K., Ouchida M., Tsuji T., Hanafusa H., Miyazaki M., Namba M., Shimizu N., Shimizu K. Gene 282:151-158(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANT GLY-335.
[4]	"Human homologue of Dickkopf-3." Tanaka S., Sugimachi K., Sugimachi K. Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, VARIANT GLY-335.
[5]	"Human Dickkopf-3, genomic sequence." Tate G., Mitsuya T. Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLY-335.
[7]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLY-335. Tissue: Corpus callosum.
[8]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT GLY-335.
[10]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLY-335. Tissue: Kidney.
[11]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 22-36.
[12]	"Function and biological roles of the Dickkopf family of Wnt modulators." Niehrs C. Oncogene 25:7469-7481(2006) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW OF THE DKK FAMILY.
[13]	"Enrichment of glycopeptides for glycan structure and attachment site identification." Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., Brinkmalm G., Larson G. Nat. Methods 6:809-811(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS], SIGNAL SEQUENCE CLEAVAGE SITE, STRUCTURE OF CARBOHYDRATES, MASS SPECTROMETRY. Tissue: Cerebrospinal fluid.
[14]	"LC-MS/MS characterization of O-glycosylation sites and glycan structures of human cerebrospinal fluid glycoproteins." Halim A., Ruetschi U., Larson G., Nilsson J. J. Proteome Res. 12:573-584(2013) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT THR-26 AND THR-28, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF177396 mRNA. Translation: AAF02676.1. AB034203 mRNA. Translation: BAA90548.1. AB057591 mRNA. Translation: BAB84360.1. AB057804 Genomic DNA. Translation: BAB84361.1. AB033421 mRNA. Translation: BAA85488.1. AB035182 Genomic DNA. Translation: BAA87044.2. AY358378 mRNA. Translation: AAQ88744.1. AK289897 mRNA. Translation: BAF82586.1. AC124276 Genomic DNA. No translation available. CH471064 Genomic DNA. Translation: EAW68534.1. CH471064 Genomic DNA. Translation: EAW68535.1. CH471064 Genomic DNA. Translation: EAW68537.1. BC007660 mRNA. Translation: AAH07660.1.
IPI	IPI00002714.
PIR	JC7188.
RefSeq	NP_001018067.1. NM_001018057.1. NP_037385.2. NM_013253.4. NP_056965.3. NM_015881.5.
UniGene	Hs.292156. Hs.731954.
3D structure databases
ProteinModelPortal	Q9UBP4.
SMR	Q9UBP4. Positions 205-281.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UBP4. 2 interactions.
STRING	9606.ENSP00000314910.
PTM databases
PhosphoSite	Q9UBP4.
Polymorphism databases
DMDM	311033372.
Proteomic databases
PaxDb	Q9UBP4.
PRIDE	Q9UBP4.
Protocols and materials databases
DNASU	27122.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000326932; ENSP00000314910; ENSG00000050165. ENST00000396505; ENSP00000379762; ENSG00000050165.
GeneID	27122.
KEGG	hsa:27122.
UCSC	uc001mju.3. human.
Organism-specific databases
CTD	27122.
GeneCards	GC11M011984.
H-InvDB	HIX0009450.
HGNC	HGNC:2893. DKK3.
HPA	CAB024949. HPA011868.
MIM	605416. gene.
neXtProt	NX_Q9UBP4.
PharmGKB	PA27347.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG302601.
HOGENOM	HOG000234342.
HOVERGEN	HBG004476.
InParanoid	Q9UBP4.
OrthoDB	EOG4KD6NC.
PhylomeDB	Q9UBP4.
Gene expression databases
ArrayExpress	Q9UBP4.
Bgee	Q9UBP4.
CleanEx	HS_DKK3.
Genevestigator	Q9UBP4.
GermOnline	ENSG00000050165. Homo sapiens.
Family and domain databases
InterPro	IPR006796. Dickkopf_N. [Graphical view]
Pfam	PF04706. Dickkopf_N. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	DKK3. human.
GenomeRNAi	27122.
NextBio	49812.
SOURCE	Search...

Entry information

Entry name

DKK3_HUMAN

Accession

Primary (citable) accession number: Q9UBP4
Secondary accession number(s): A8K1I2, D3DQW1, Q9ULB7

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	November 2, 2010
Last modified:	May 1, 2013
This is version 114 of the entry and version 2 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.