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Reviewed, UniProtKB/Swiss-Prot O94907 (DKK1_HUMAN)

Last modified January 19, 2010. Version 83. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Dickkopf-related protein 1
      Short name=Dickkopf-1
      Short name=Dkk-1
      Short name=hDkk-1
Alternative name(s):
    SK
Gene names
Name: DKK1
ORF Names: UNQ492/PRO1008
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length266 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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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.

Subunit structure

Interacts with LRP5 and LRP6 By similarity.

Subcellular location

Secreted.

Tissue specificity

Placenta.

Domain

The C-terminal cysteine-rich domain mediates interaction with LRP5 and LRP6 By similarity.

Sequence similarities

Belongs to the dickkopf family.

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Binary interactions

With

Entry

#Exp.

IntAct

Notes

CORO1AP311461EBI-742864,EBI-1046676
MDFIQ997502EBI-742864,EBI-724076

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3131 Ref.9
Chain32 – 266235Dickkopf-related protein 1
PRO_0000007218

Regions

Region85 – 13854DKK-type Cys-1
Region189 – 26375DKK-type Cys-2

Amino acid modifications

Glycosylation2561N-linked (GlcNAc...) Potential
Disulfide bond189 ↔ 201 By similarity
Disulfide bond195 ↔ 210 By similarity
Disulfide bond200 ↔ 237 By similarity
Disulfide bond220 ↔ 245 By similarity
Disulfide bond239 ↔ 263 By similarity

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Sequences

Sequence LengthMass (Da)Tools
O94907-1 [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: 5E878B2CCE4236BA

FASTA26628,672
        10         20         30         40         50         60 
MMALGAAGAT RVFVAMVAAA LGGHPLLGVS ATLNSVLNSN AIKNLPPPLG GAAGHPGSAV 

        70         80         90        100        110        120 
SAAPGILYPG GNKYQTIDNY QPYPCAEDEE CGTDEYCASP TRGGDAGVQI CLACRKRRKR 

       130        140        150        160        170        180 
CMRHAMCCPG NYCKNGICVS SDQNHFRGEI EETITESFGN DHSTLDGYSR RTTLSSKMYH 

       190        200        210        220        230        240 
TKGQEGSVCL RSSDCASGLC CARHFWSKIC KPVLKEGQVC TKHRRKGSHG LEIFQRCYCG 

       250        260 
EGLSCRIQKD HHQASNSSRL HTCQRH

« Hide

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References

« Hide 'large scale' references
[1]"Isolation and biochemical characterization of the human Dkk-1 homologue, a novel inhibitor of mammalian Wnt signaling."
Fedi P., Bafico A., Nieto Soria A., Burgess W.H., Miki T., Bottaro D.P., Kraus M.H., Aaronson S.A.
J. Biol. Chem. 274:19465-19472(1999) [PubMed: 10383463] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Leiomyosarcoma.
[2]"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 kidney.
[3]Tate G., Suzuki T., Mitsuya T.
Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"The genomic structure, chromosome location, and analysis of the human DKK1 head inducer gene as a candidate for holoprosencephaly."
Roessler E., Du Y., Glinka A., Dutra A., Niehrs C., Muenke M.
Cytogenet. Cell Genet. 89:220-224(2000) [PubMed: 10965128] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"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. expand/collapse author list , 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].
[6]"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. expand/collapse author list , 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].
Tissue: Cerebellum.
[7]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. expand/collapse author list , 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].
[8]"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].
Tissue: Brain.
[9]"Signal peptide prediction based on analysis of experimentally verified cleavage sites."
Zhang Z., Henzel W.J.
Protein Sci. 13:2819-2824(2004) [PubMed: 15340161] [Abstract]
Cited for: PROTEIN SEQUENCE OF 32-46.
[10]"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.

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AF127563 mRNA. Translation: AAD21087.1.
AF177394 mRNA. Translation: AAF02674.1.
AB020315 Genomic DNA. Translation: BAA34651.1.
AF261158, AF261157 Genomic DNA. Translation: AAG15544.1.
AY359005 mRNA. Translation: AAQ89364.1.
AK314902 mRNA. Translation: BAG37416.1.
CH471083 Genomic DNA. Translation: EAW54144.1.
BC001539 mRNA. Translation: AAH01539.1.
IPIIPI00016353.
RefSeqNP_036374.1.
UniGeneHs.40499

3D structure databases

SMRO94907. Positions 178-265.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-46461N.
IntActO94907. 2 interactions.
STRINGO94907.

Proteomic databases

PRIDEO94907.

Genome annotation databases

EnsemblENST00000373970; ENSP00000363081; ENSG00000107984; Homo sapiens. [Genome view]
GeneID22943.
KEGGhsa:22943.
UCSCuc001jjr.1. human.

Organism-specific databases

CTD22943.
GeneCardsGC10P053744.
H-InvDBHIX0008834.
HGNCHGNC:2891. DKK1.
HPACAB009726.
HPA018995.
MIM605189. gene.
PharmGKBPA27345.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG09232.
HOGENOMHBG445081.
HOVERGENO94907.
InParanoidO94907.
OMADNYQPYP.
OrthoDBEOG9F7R48.
PhylomeDBO94907.

Enzyme and pathway databases

Pathway_Interaction_DBwnt_canonical_pathway. Canonical Wnt signaling pathway.
ps1pathway. Presenilin action in Notch and Wnt signaling.

Gene expression databases

ArrayExpressO94907.
BgeeO94907.
CleanExHS_DKK1.
GenevestigatorO94907.
GermOnlineENSG00000107984. Homo sapiens.

Family and domain databases

InterProIPR006796. Dickkopf_N.
[Graphical view]
PfamPF04706. Dickkopf_N. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio43697.
PMAP-CutDBO94907.
SOURCESearch...

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Entry information

Entry nameDKK1_HUMAN
AccessionPrimary (citable) accession number: O94907
Secondary accession number(s): B2RC19
Entry history
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: May 1, 1999
Last modified: January 19, 2010
This is version 83 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
DisclaimerAny 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.

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Relevant documents

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents