DKK1

Protein identityUniProt · HPA

UniProt accession

O94907

Gene

DKK1

Ensembl

ENSG00000107984

Chromosome

10

Canonical length

266 aa

Protein class

Predicted secreted proteins

Secretome location

Secreted in other tissues

OverviewNCBI Gene

This gene encodes a member of the dickkopf family of proteins. Members of this family are secreted proteins characterized by two cysteine-rich domains that mediate protein-protein interactions. The encoded protein binds to the LRP6 co-receptor and inhibits beta-catenin-dependent Wnt signaling. This gene plays a role in embryonic development and may be important in bone formation in adults. Elevated expression of this gene has been observed in numerous human cancers and this protein may promote proliferation, invasion and growth in cancer cell lines. [provided by RefSeq, Sep 2017]

Canonical amino-acid sequenceUniProt

266 residues, UniProt reviewed canonical sequence.

>O94907|DKK1
     1  MMALGAAGAT RVFVAMVAAA LGGHPLLGVS ATLNSVLNSN AIKNLPPPLG GAAGHPGSAV
    61  SAAPGILYPG GNKYQTIDNY QPYPCAEDEE CGTDEYCASP TRGGDAGVQI CLACRKRRKR
   121  CMRHAMCCPG NYCKNGICVS SDQNHFRGEI EETITESFGN DHSTLDGYSR RTTLSSKMYH
   181  TKGQEGSVCL RSSDCASGLC CARHFWSKIC KPVLKEGQVC TKHRRKGSHG LEIFQRCYCG
   241  EGLSCRIQKD HHQASNSSRL HTCQRH

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DKK1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.55

Highest tissue expression

46 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DKK1.

Disease | ImmuneIEDB

Conditions an epitope on DKK1 was assayed in.

• lung non-small cell carcinoma B cell
• invasive ductal carcinoma T cell
• multiple myeloma T cell

ReferencesPubMed · IEDB

Publications for DKK1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.73

gnomAD pLI

0.17

gnomAD missense Z

0.18

DepMap mean gene effect

-0.12

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• canonical Wnt signaling pathway
• cell morphogenesis
• embryonic limb morphogenesis
• endocardial cushion development
• endodermal cell differentiation
• face morphogenesis
• forebrain development
• hair follicle development
• heart induction
• heart valve development
• learning or memory
• limb development
• mesoderm formation
• motor learning
• negative regulation of apoptotic process
• negative regulation of BMP signaling pathway
• negative regulation of canonical Wnt signaling pathway
• negative regulation of cardiac muscle cell differentiation
• negative regulation of mesodermal cell fate specification
• negative regulation of neuron projection development
• negative regulation of ossification
• negative regulation of SMAD protein signal transduction
• negative regulation of transcription by RNA polymerase II
• negative regulation of Wnt signaling pathway
• positive regulation of gene expression
• positive regulation of JNK cascade
• positive regulation of Wnt signaling pathway, planar cell polarity pathway
• regulation of dopaminergic neuron differentiation
• regulation of neuron apoptotic process
• regulation of receptor internalization
• regulation of synaptic transmission, glutamatergic
• response to retinoic acid
• synapse pruning
• Wnt signaling pathway involved in somitogenesis
• negative regulation of presynapse assembly
• negative regulation of Wnt-Frizzled-LRP5/6 complex assembly
• positive regulation of midbrain dopaminergic neuron differentiation
• positive regulation of Wnt signaling pathway, calcium modulating pathway
• regulation of endodermal cell fate specification

Molecular functions

• co-receptor binding
• growth factor activity
• low-density lipoprotein particle receptor binding
• receptor antagonist activity

Cellular components

• early endosome membrane
• extracellular region
• extracellular space
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Dickkopf, N-terminal cysteine-rich
• Dickkopf related protein 1-4
• Dickkopf-related protein 1/2/4, C-terminal subdomain 2
• Dickkopf-related protein 1/2/4, C-terminal subdomain 1
• Dickkopf N-terminal cysteine-rich region
• Dickkopf-related protein 1/2/4, C-terminal subdomain 2
• Dickkopf-related protein 1/2/4, C-terminal subdomain 1
• Dickkopf-related protein 1, second cysteine-rich domain
• Dickkopf-related protein 1, N-terminal domain

KeywordsUniProt

• Developmental protein
• Disulfide bond
• Glycoprotein
• Secreted
• Signal
• Wnt signaling pathway

InteractionsUniProt · HPA

Protein binding partners of DKK1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• KREM1
• LRP6
• KREMEN1
• LRP5