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Protein

Dickkopf-related protein 4

Gene

DKK4

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 - Biological processi

Keywordsi

Molecular functionDevelopmental protein
Biological processWnt signaling pathway

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000104371.4
HGNCiHGNC:2894 DKK4
MIMi605417 gene
neXtProtiNX_Q9UBT3

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

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
ProteomicsDBi84056

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, 5 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
OMAiHARLRVC
OrthoDBiEOG091G0H13
PhylomeDBiQ9UBT3
TreeFamiTF330916

Family and domain databases

InterProiView protein in InterPro
IPR006796 Dickkopf_N
IPR023569 Prokineticin_domain
PfamiView protein in Pfam
PF04706 Dickkopf_N, 1 hit
PF06607 Prokineticin, 1 hit
ProDomiView protein in ProDom or Entries sharing at least one domain
PD059788 Prokineticin, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiDKK4_HUMAN
AccessioniPrimary (citable) accession number: Q9UBT3
Secondary accession number(s): Q3KNX0, Q9Y4C3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: May 1, 2000
Last modified: June 20, 2018
This is version 133 of the entry and version 1 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. 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

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