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Protein

Dickkopf-related protein 4

Gene

DKK4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 4 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

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Wnt signaling pathway

Enzyme and pathway databases

BioCyciZFISH:ENSG00000104371-MONOMER.
ReactomeiR-HSA-201681. TCF dependent signaling in response to WNT.
R-HSA-3772470. Negative regulation of TCF-dependent signaling by WNT ligand antagonists.
R-HSA-5339717. Misspliced LRP5 mutants have enhanced beta-catenin-dependent signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Dickkopf-related protein 4
Short name:
Dickkopf-4
Short name:
Dkk-4
Short name:
hDkk-4
Cleaved into the following chain:
Gene namesi
Name:DKK4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:2894. DKK4.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi27121.
OpenTargetsiENSG00000104371.
PharmGKBiPA27348.

Polymorphism and mutation databases

BioMutaiDKK4.
DMDMi13124092.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 182 PublicationsAdd BLAST18
ChainiPRO_000000722519 – 224Dickkopf-related protein 4Add BLAST206
ChainiPRO_0000007226134 – 224Dickkopf-related protein 4 short formAdd BLAST91

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi145 ↔ 157By similarity
Disulfide bondi151 ↔ 166By similarity
Disulfide bondi156 ↔ 194By similarity
Disulfide bondi176 ↔ 202By similarity
Disulfide bondi196 ↔ 218By similarity

Post-translational modificationi

Appears to be not glycosylated.
Can be proteolytically processed by a furin-like protease.1 Publication

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond

Proteomic databases

PaxDbiQ9UBT3.
PeptideAtlasiQ9UBT3.
PRIDEiQ9UBT3.

PTM databases

PhosphoSitePlusiQ9UBT3.

Expressioni

Tissue specificityi

Expressed in cerebellum, T-cells, esophagus and lung.

Gene expression databases

BgeeiENSG00000104371.
CleanExiHS_DKK4.
GenevisibleiQ9UBT3. HS.

Organism-specific databases

HPAiHPA052916.

Interactioni

Subunit structurei

Interacts with LRP5 and LRP6.By similarity

Protein-protein interaction databases

BioGridi118012. 4 interactors.
STRINGi9606.ENSP00000220812.

Structurei

3D structure databases

ProteinModelPortaliQ9UBT3.
SMRiQ9UBT3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni41 – 90DKK-type Cys-1Add BLAST50
Regioni145 – 218DKK-type Cys-2Add BLAST74

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

Signal

Phylogenomic databases

eggNOGiENOG410IRWJ. Eukaryota.
ENOG410YHPI. LUCA.
GeneTreeiENSGT00390000007000.
HOGENOMiHOG000246998.
HOVERGENiHBG081443.
InParanoidiQ9UBT3.
KOiK02165.
OMAiARKGSQC.
OrthoDBiEOG091G0H13.
PhylomeDBiQ9UBT3.
TreeFamiTF330916.

Family and domain databases

InterProiIPR006796. Dickkopf_N.
IPR023569. Prokineticin_domain.
[Graphical view]
PfamiPF04706. Dickkopf_N. 1 hit.
PF06607. Prokineticin. 1 hit.
[Graphical view]
ProDomiPD059788. Prokineticin. 1 hit.
[Graphical view] [Entries sharing at least one domain]

Sequencei

Sequence statusi: Complete.

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

Q9UBT3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVAAVLLGLS WLCSPLGALV LDFNNIRSSA DLHGARKGSQ CLSDTDCNTR
60 70 80 90 100
KFCLQPRDEK PFCATCRGLR RRCQRDAMCC PGTLCVNDVC TTMEDATPIL
110 120 130 140 150
ERQLDEQDGT HAEGTTGHPV QENQPKRKPS IKKSQGRKGQ EGESCLRTFD
160 170 180 190 200
CGPGLCCARH FWTKICKPVL LEGQVCSRRG HKDTAQAPEI FQRCDCGPGL
210 220
LCRSQLTSNR QHARLRVCQK IEKL
Length:224
Mass (Da):24,876
Last modified:May 1, 2000 - v1
Checksum:i45F8EBC476961357
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti93M → L in BAA33438 (Ref. 2) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF177397 mRNA. Translation: AAF02677.1.
AB018005 Genomic DNA. Translation: BAA33475.1.
AB017788 mRNA. Translation: BAA33438.1.
BC107046 mRNA. Translation: AAI07047.1.
BC107047 mRNA. Translation: AAI07048.1.
CCDSiCCDS6130.1.
RefSeqiNP_055235.1. NM_014420.2.
XP_011542790.1. XM_011544488.2.
XP_016868805.1. XM_017013316.1.
UniGeneiHs.159311.

Genome annotation databases

EnsembliENST00000220812; ENSP00000220812; ENSG00000104371.
GeneIDi27121.
KEGGihsa:27121.
UCSCiuc003xpb.4. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF177397 mRNA. Translation: AAF02677.1.
AB018005 Genomic DNA. Translation: BAA33475.1.
AB017788 mRNA. Translation: BAA33438.1.
BC107046 mRNA. Translation: AAI07047.1.
BC107047 mRNA. Translation: AAI07048.1.
CCDSiCCDS6130.1.
RefSeqiNP_055235.1. NM_014420.2.
XP_011542790.1. XM_011544488.2.
XP_016868805.1. XM_017013316.1.
UniGeneiHs.159311.

3D structure databases

ProteinModelPortaliQ9UBT3.
SMRiQ9UBT3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118012. 4 interactors.
STRINGi9606.ENSP00000220812.

PTM databases

PhosphoSitePlusiQ9UBT3.

Polymorphism and mutation databases

BioMutaiDKK4.
DMDMi13124092.

Proteomic databases

PaxDbiQ9UBT3.
PeptideAtlasiQ9UBT3.
PRIDEiQ9UBT3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000220812; ENSP00000220812; ENSG00000104371.
GeneIDi27121.
KEGGihsa:27121.
UCSCiuc003xpb.4. human.

Organism-specific databases

CTDi27121.
DisGeNETi27121.
GeneCardsiDKK4.
HGNCiHGNC:2894. DKK4.
HPAiHPA052916.
MIMi605417. gene.
neXtProtiNX_Q9UBT3.
OpenTargetsiENSG00000104371.
PharmGKBiPA27348.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IRWJ. Eukaryota.
ENOG410YHPI. LUCA.
GeneTreeiENSGT00390000007000.
HOGENOMiHOG000246998.
HOVERGENiHBG081443.
InParanoidiQ9UBT3.
KOiK02165.
OMAiARKGSQC.
OrthoDBiEOG091G0H13.
PhylomeDBiQ9UBT3.
TreeFamiTF330916.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000104371-MONOMER.
ReactomeiR-HSA-201681. TCF dependent signaling in response to WNT.
R-HSA-3772470. Negative regulation of TCF-dependent signaling by WNT ligand antagonists.
R-HSA-5339717. Misspliced LRP5 mutants have enhanced beta-catenin-dependent signaling.

Miscellaneous databases

GenomeRNAii27121.
PROiQ9UBT3.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000104371.
CleanExiHS_DKK4.
GenevisibleiQ9UBT3. HS.

Family and domain databases

InterProiIPR006796. Dickkopf_N.
IPR023569. Prokineticin_domain.
[Graphical view]
PfamiPF04706. Dickkopf_N. 1 hit.
PF06607. Prokineticin. 1 hit.
[Graphical view]
ProDomiPD059788. Prokineticin. 1 hit.
[Graphical view] [Entries sharing at least one domain]
ProtoNetiSearch...

Entry informationi

Entry nameiDKK4_HUMAN
AccessioniPrimary (citable) accession number: Q9UBT3
Secondary accession number(s): Q3KNX0, Q9Y4C3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: May 1, 2000
Last modified: November 2, 2016
This is version 127 of the entry and version 1 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 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. 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.