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Protein

Dickkopf-related protein 3

Gene

DKK3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity

GO - Biological processi

  • adrenal gland development Source: UniProtKB
  • anatomical structure morphogenesis Source: ProtInc
  • negative regulation of aldosterone biosynthetic process Source: UniProtKB
  • negative regulation of anti-Mullerian hormone signaling pathway Source: ParkinsonsUK-UCL
  • negative regulation of canonical Wnt signaling pathway Source: BHF-UCL
  • negative regulation of cortisol biosynthetic process Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • regulation of transforming growth factor beta receptor signaling pathway Source: ParkinsonsUK-UCL
  • Wnt signaling pathway Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Wnt signaling pathway

Names & Taxonomyi

Protein namesi
Recommended name:
Dickkopf-related protein 3
Short name:
Dickkopf-3
Short name:
Dkk-3
Short name:
hDkk-3
Gene namesi
Name:DKK3
Synonyms:REIC
ORF Names:UNQ258/PRO295
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:2893. DKK3.

Subcellular locationi

GO - Cellular componenti

  • extracellular space Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA27347.

Polymorphism and mutation databases

BioMutaiDKK3.
DMDMi311033372.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 21212 PublicationsAdd
BLAST
Chaini22 – 350329Dickkopf-related protein 3PRO_0000007222Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi26 – 261O-linked (GalNAc...)1 Publication
Glycosylationi28 – 281O-linked (GalNAc...)1 Publication
Glycosylationi96 – 961N-linked (GlcNAc...)Sequence analysis
Glycosylationi106 – 1061N-linked (GlcNAc...)Sequence analysis
Glycosylationi121 – 1211N-linked (GlcNAc...)Sequence analysis
Glycosylationi204 – 2041N-linked (GlcNAc...)Sequence analysis
Disulfide bondi208 ↔ 220By similarity
Disulfide bondi214 ↔ 231By similarity
Disulfide bondi219 ↔ 265By similarity
Disulfide bondi241 ↔ 273By similarity

Post-translational modificationi

N- and O-glycosylated.3 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ9UBP4.
MaxQBiQ9UBP4.
PaxDbiQ9UBP4.
PeptideAtlasiQ9UBP4.
PRIDEiQ9UBP4.

PTM databases

iPTMnetiQ9UBP4.
PhosphoSiteiQ9UBP4.
UniCarbKBiQ9UBP4.

Expressioni

Tissue specificityi

Highest expression in heart, brain, and spinal cord.2 Publications

Gene expression databases

BgeeiENSG00000050165.
CleanExiHS_DKK3.
ExpressionAtlasiQ9UBP4. baseline and differential.
GenevisibleiQ9UBP4. HS.

Organism-specific databases

HPAiCAB024949.
HPA011868.

Interactioni

Subunit structurei

Interacts with LRP5 and LRP6.By similarity

Protein-protein interaction databases

BioGridi118013. 56 interactions.
IntActiQ9UBP4. 9 interactions.
STRINGi9606.ENSP00000314910.

Structurei

3D structure databases

ProteinModelPortaliQ9UBP4.
SMRiQ9UBP4. Positions 205-279.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni29 – 4618O-glycosylated at one siteAdd
BLAST
Regioni147 – 19549DKK-type Cys-1Add
BLAST
Regioni208 – 28477DKK-type Cys-2Add
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili40 – 8445Sequence analysisAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi338 – 3436Poly-Ala

Domaini

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

Sequence similaritiesi

Belongs to the dickkopf family.Curated

Keywords - Domaini

Coiled coil, Signal

Phylogenomic databases

eggNOGiENOG410IRWK. Eukaryota.
ENOG4111WWP. LUCA.
GeneTreeiENSGT00390000000221.
HOGENOMiHOG000234342.
HOVERGENiHBG004476.
InParanoidiQ9UBP4.
PhylomeDBiQ9UBP4.
TreeFamiTF337340.

Family and domain databases

InterProiIPR006796. Dickkopf_N.
[Graphical view]
PfamiPF04706. Dickkopf_N. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9UBP4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQRLGATLLC LLLAAAVPTA PAPAPTATSA PVKPGPALSY PQEEATLNEM
60 70 80 90 100
FREVEELMED TQHKLRSAVE EMEAEEAAAK ASSEVNLANL PPSYHNETNT
110 120 130 140 150
DTKVGNNTIH VHREIHKITN NQTGQMVFSE TVITSVGDEE GRRSHECIID
160 170 180 190 200
EDCGPSMYCQ FASFQYTCQP CRGQRMLCTR DSECCGDQLC VWGHCTKMAT
210 220 230 240 250
RGSNGTICDN QRDCQPGLCC AFQRGLLFPV CTPLPVEGEL CHDPASRLLD
260 270 280 290 300
LITWELEPDG ALDRCPCASG LLCQPHSHSL VYVCKPTFVG SRDQDGEILL
310 320 330 340 350
PREVPDEYEV GSFMEEVRQE LEDLERSLTE EMALREPAAA AAALLGGEEI
Length:350
Mass (Da):38,390
Last modified:November 2, 2010 - v2
Checksum:i734504122B40AFEE
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti49 – 491E → D.
Corresponds to variant rs11544816 [ dbSNP | Ensembl ].
VAR_057516
Natural varianti335 – 3351R → G.8 Publications
Corresponds to variant rs3206824 [ dbSNP | Ensembl ].
VAR_030787

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS7808.1.
PIRiJC7188.
RefSeqiNP_001018067.1. NM_001018057.1.
NP_037385.2. NM_013253.4.
NP_056965.3. NM_015881.5.
XP_006718241.1. XM_006718178.2.
UniGeneiHs.292156.
Hs.731954.

Genome annotation databases

EnsembliENST00000326932; ENSP00000314910; ENSG00000050165.
ENST00000396505; ENSP00000379762; ENSG00000050165.
GeneIDi27122.
KEGGihsa:27122.
UCSCiuc001mjv.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS7808.1.
PIRiJC7188.
RefSeqiNP_001018067.1. NM_001018057.1.
NP_037385.2. NM_013253.4.
NP_056965.3. NM_015881.5.
XP_006718241.1. XM_006718178.2.
UniGeneiHs.292156.
Hs.731954.

3D structure databases

ProteinModelPortaliQ9UBP4.
SMRiQ9UBP4. Positions 205-279.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118013. 56 interactions.
IntActiQ9UBP4. 9 interactions.
STRINGi9606.ENSP00000314910.

PTM databases

iPTMnetiQ9UBP4.
PhosphoSiteiQ9UBP4.
UniCarbKBiQ9UBP4.

Polymorphism and mutation databases

BioMutaiDKK3.
DMDMi311033372.

Proteomic databases

EPDiQ9UBP4.
MaxQBiQ9UBP4.
PaxDbiQ9UBP4.
PeptideAtlasiQ9UBP4.
PRIDEiQ9UBP4.

Protocols and materials databases

DNASUi27122.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000326932; ENSP00000314910; ENSG00000050165.
ENST00000396505; ENSP00000379762; ENSG00000050165.
GeneIDi27122.
KEGGihsa:27122.
UCSCiuc001mjv.4. human.

Organism-specific databases

CTDi27122.
GeneCardsiDKK3.
H-InvDBHIX0009450.
HGNCiHGNC:2893. DKK3.
HPAiCAB024949.
HPA011868.
MIMi605416. gene.
neXtProtiNX_Q9UBP4.
PharmGKBiPA27347.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IRWK. Eukaryota.
ENOG4111WWP. LUCA.
GeneTreeiENSGT00390000000221.
HOGENOMiHOG000234342.
HOVERGENiHBG004476.
InParanoidiQ9UBP4.
PhylomeDBiQ9UBP4.
TreeFamiTF337340.

Miscellaneous databases

ChiTaRSiDKK3. human.
GeneWikiiDKK3.
GenomeRNAii27122.
PROiQ9UBP4.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000050165.
CleanExiHS_DKK3.
ExpressionAtlasiQ9UBP4. baseline and differential.
GenevisibleiQ9UBP4. HS.

Family and domain databases

InterProiIPR006796. Dickkopf_N.
[Graphical view]
PfamiPF04706. Dickkopf_N. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDKK3_HUMAN
AccessioniPrimary (citable) accession number: Q9UBP4
Secondary accession number(s): A8K1I2, D3DQW1, Q9ULB7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: November 2, 2010
Last modified: September 7, 2016
This is version 137 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.