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Protein

Dickkopf-related protein 3

Gene

DKK3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 - Molecular functioni

  • co-receptor binding Source: GO_Central
  • receptor antagonist activity Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein
Biological processWnt 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

EuPathDBiHostDB:ENSG00000050165.17
HGNCiHGNC:2893 DKK3
MIMi605416 gene
neXtProtiNX_Q9UBP4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi27122
OpenTargetsiENSG00000050165
PharmGKBiPA27347

Polymorphism and mutation databases

BioMutaiDKK3
DMDMi311033372

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 212 PublicationsAdd BLAST21
ChainiPRO_000000722222 – 350Dickkopf-related protein 3Add BLAST329

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi26O-linked (GalNAc...) threonine1 Publication1
Glycosylationi28O-linked (GalNAc...) threonine1 Publication1
Glycosylationi96N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi106N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi121N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi204N-linked (GlcNAc...) asparagineSequence analysis1
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
ProteomicsDBi84024

PTM databases

GlyConnecti822
iPTMnetiQ9UBP4
PhosphoSitePlusiQ9UBP4
UniCarbKBiQ9UBP4

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000050165 Expressed in 230 organ(s), highest expression level in primary visual cortex
CleanExiHS_DKK3
ExpressionAtlasiQ9UBP4 baseline and differential
GenevisibleiQ9UBP4 HS

Organism-specific databases

HPAiCAB024949
HPA011868

Interactioni

Subunit structurei

Interacts with LRP5 and LRP6.By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi118013, 67 interactors
IntActiQ9UBP4, 10 interactors
MINTiQ9UBP4
STRINGi9606.ENSP00000314910

Structurei

3D structure databases

ProteinModelPortaliQ9UBP4
SMRiQ9UBP4
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni29 – 46O-glycosylated at one siteAdd BLAST18
Regioni147 – 195DKK-type Cys-1Add BLAST49
Regioni208 – 284DKK-type Cys-2Add BLAST77

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili40 – 84Sequence analysisAdd BLAST45

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi338 – 343Poly-Ala6

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

InterProiView protein in InterPro
IPR006796 Dickkopf_N
IPR039863 DKK-like
PANTHERiPTHR12113 PTHR12113, 1 hit
PfamiView protein in Pfam
PF04706 Dickkopf_N, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F6SYF8F6SYF8_HUMAN
Dickkopf-related protein 3
DKK3
364Annotation score:
E9PKW6E9PKW6_HUMAN
Dickkopf-related protein 3
DKK3
234Annotation score:
E9PHY3E9PHY3_HUMAN
Dickkopf-related protein 3
DKK3
183Annotation score:
E9PKK9E9PKK9_HUMAN
Dickkopf-related protein 3
DKK3
132Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05751649E → D. Corresponds to variant dbSNP:rs11544816Ensembl.1
Natural variantiVAR_030787335R → G8 PublicationsCorresponds to variant dbSNP:rs3206824Ensembl.1

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_001317149.1, NM_001330220.1
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

Similar proteinsi

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_001317149.1, NM_001330220.1
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
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118013, 67 interactors
IntActiQ9UBP4, 10 interactors
MINTiQ9UBP4
STRINGi9606.ENSP00000314910

PTM databases

GlyConnecti822
iPTMnetiQ9UBP4
PhosphoSitePlusiQ9UBP4
UniCarbKBiQ9UBP4

Polymorphism and mutation databases

BioMutaiDKK3
DMDMi311033372

Proteomic databases

EPDiQ9UBP4
MaxQBiQ9UBP4
PaxDbiQ9UBP4
PeptideAtlasiQ9UBP4
PRIDEiQ9UBP4
ProteomicsDBi84024

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
DisGeNETi27122
EuPathDBiHostDB:ENSG00000050165.17
GeneCardsiDKK3
H-InvDBiHIX0009450
HGNCiHGNC:2893 DKK3
HPAiCAB024949
HPA011868
MIMi605416 gene
neXtProtiNX_Q9UBP4
OpenTargetsiENSG00000050165
PharmGKBiPA27347
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IRWK Eukaryota
ENOG4111WWP LUCA
GeneTreeiENSGT00390000000221
HOGENOMiHOG000234342
HOVERGENiHBG004476
InParanoidiQ9UBP4
PhylomeDBiQ9UBP4
TreeFamiTF337340

Miscellaneous databases

ChiTaRSiDKK3 human
GeneWikiiDKK3
GenomeRNAii27122
PROiPR:Q9UBP4
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000050165 Expressed in 230 organ(s), highest expression level in primary visual cortex
CleanExiHS_DKK3
ExpressionAtlasiQ9UBP4 baseline and differential
GenevisibleiQ9UBP4 HS

Family and domain databases

InterProiView protein in InterPro
IPR006796 Dickkopf_N
IPR039863 DKK-like
PANTHERiPTHR12113 PTHR12113, 1 hit
PfamiView protein in Pfam
PF04706 Dickkopf_N, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiDKK3_HUMAN
AccessioniPrimary (citable) accession number: Q9UBP4
Secondary accession number(s): A8K1I2, D3DQW1, Q9ULB7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: November 2, 2010
Last modified: November 7, 2018
This is version 152 of the entry and version 2 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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