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Aliases for SCUBE3 Gene

Aliases for SCUBE3 Gene

  • Signal Peptide, CUB Domain And EGF Like Domain Containing 3 2 3 5
  • CUB Domain And EGF-Like Repeat Containing 3 2 3
  • CEGF3 3 4
  • Signal Peptide, CUB And EGF-Like Domain-Containing Protein 3 3
  • Signal Peptide, CUB Domain, EGF-Like 3 2

External Ids for SCUBE3 Gene

Previous HGNC Symbols for SCUBE3 Gene

  • CEGF3

Previous GeneCards Identifiers for SCUBE3 Gene

  • GC06P035231
  • GC06P035290
  • GC06P034902
  • GC06P035182
  • GC06P035282
  • GC06P035532
  • GC06P037760
  • GC06P038384
  • GC06P038974

Summaries for SCUBE3 Gene

Entrez Gene Summary for SCUBE3 Gene

  • This gene encodes a member of the signal peptide, complement subcomponents C1r/C1s, Uegf, bone morphogenetic protein-1 and epidermal growth factor-like domain containing protein family. Overexpression of this gene in human embryonic kidney cells results in secretion of a glycosylated form of the protein that forms oligomers and tethers to the cell surface. This gene is upregulated in lung cancer tumor tissue compared to healthy tissue and is associated with loss of the epithelial marker E-cadherin and with increased expression of vimentin, a mesenchymal marker. In addition, the protein encoded by this gene is a transforming growth factor beta receptor ligand, and when secreted by cancer cells, it can be cleaved in vitro to release the N-terminal epidermal growth factor-like repeat domain and the C-terminal complement subcomponents C1r/C1s domain. Both the full length protein and C-terminal fragment can bind to the transforming growth factor beta type II receptor to promote the epithelial-mesenchymal transition and tumor angiogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

GeneCards Summary for SCUBE3 Gene

SCUBE3 (Signal Peptide, CUB Domain And EGF Like Domain Containing 3) is a Protein Coding gene. Diseases associated with SCUBE3 include Lung Cancer. GO annotations related to this gene include calcium ion binding. An important paralog of this gene is SCUBE1.

UniProtKB/Swiss-Prot for SCUBE3 Gene

  • Binds to TGFBR2 and activates TGFB signaling. In lung cancer cells, could serve as an endogenous autocrine and paracrine ligand of TGFBR2, which could regulate TGFBR2 signaling and hence modulate epithelial-mesenchymal transition and cancer progression.

No data available for CIViC summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SCUBE3 Gene

Genomics for SCUBE3 Gene

Regulatory Elements for SCUBE3 Gene

Enhancers for SCUBE3 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH06G035160 0.8 dbSUPER 29.8 -52.4 -52379 3.0 BCOR SOX13 ZFP64 ARID4B ZMYM3 ZNF644 RAD21 YY1 GATA3 GATA2 SCUBE3 DEF6 UHRF1BP1 TCP11 GC06P041035
GH06G035164 1.3 Ensembl ENCODE dbSUPER 18 -48.3 -48285 2.1 ELF3 SOX13 TFAP4 FOXA2 SAP130 ZMYM3 MAX CEBPG YY1 GATA3 SCUBE3 C6orf106 TCP11 GC06P041035
GH06G035175 1 dbSUPER 16.9 -35.9 -35864 4.8 PKNOX1 ARNT ARID4B ZNF48 ZNF121 ZNF143 KDM4B MCM3 NFYC REST SCUBE3 DEF6 TCP11 GC06P041035
GH06G034951 1.3 Ensembl ENCODE 10.5 -260.1 -260070 4.4 FOXA2 MLX ARID4B YY1 ZNF121 FOS ZHX2 MIER2 PPARG KAT8 TAF11 UHRF1BP1 ANKS1A SCUBE3 SNRPC PIR53548 GC06P040140
GH06G035247 1.1 ENCODE dbSUPER 11.2 +34.2 34238 0.8 CTCF TAL1 BACH1 ZIC2 FOSL1 TCF12 ZNF316 POLR2A GATA2 EED DEF6 ZNF76 SCUBE3 TEAD3 TULP1 TCP11 PIR55616 GC06M037880
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around SCUBE3 on UCSC Golden Path with GeneCards custom track

Promoters for SCUBE3 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000196055 153 801 FEZF1 ZNF2 GLIS2 ZNF263 ZNF662 REST ZNF491 ZNF579 MAFF ZSCAN16

Genomic Location for SCUBE3 Gene

35,214,047 bp from pter
35,253,079 bp from pter
39,033 bases
Plus strand

Genomic View for SCUBE3 Gene

Genes around SCUBE3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SCUBE3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SCUBE3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SCUBE3 Gene

Proteins for SCUBE3 Gene

  • Protein details for SCUBE3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Signal peptide, CUB and EGF-like domain-containing protein 3
    Protein Accession:
    Secondary Accessions:
    • A8K5A3
    • Q5CZB3
    • Q86UZ9
    • Q8NAU9

    Protein attributes for SCUBE3 Gene

    993 amino acids
    Molecular mass:
    109282 Da
    Quaternary structure:
    • Forms homooligomers and heterooligomers with SCUBE1. Interacts with TGFBR2 through the CUB domain; this interaction does not affect TGFB1-binding to TGFBR2.
    • Sequence=BAC03798.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

    Alternative splice isoforms for SCUBE3 Gene


neXtProt entry for SCUBE3 Gene

Post-translational modifications for SCUBE3 Gene

  • N-glycosylated.
  • Proteolytic cleavage produces a CUB-containing C-terminal fragment that retains the ability to bind to TGFBR2. This reaction is catalyzed in vitro by MMP2 and, to a lesser extent, by MMP9.
  • Glycosylation at isoforms=2417, isoforms=2464, isoforms=2685, Asn756, and isoforms=2785
  • Modification sites at PhosphoSitePlus

Other Protein References for SCUBE3 Gene

No data available for DME Specific Peptides for SCUBE3 Gene

Domains & Families for SCUBE3 Gene

Suggested Antigen Peptide Sequences for SCUBE3 Gene

Graphical View of Domain Structure for InterPro Entry

genes like me logo Genes that share domains with SCUBE3: view

No data available for Gene Families and UniProtKB/Swiss-Prot for SCUBE3 Gene

Function for SCUBE3 Gene

Molecular function for SCUBE3 Gene

UniProtKB/Swiss-Prot Function:
Binds to TGFBR2 and activates TGFB signaling. In lung cancer cells, could serve as an endogenous autocrine and paracrine ligand of TGFBR2, which could regulate TGFBR2 signaling and hence modulate epithelial-mesenchymal transition and cancer progression.

Gene Ontology (GO) - Molecular Function for SCUBE3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005509 calcium ion binding IEA --
GO:0005515 protein binding IPI 15234972
genes like me logo Genes that share ontologies with SCUBE3: view
genes like me logo Genes that share phenotypes with SCUBE3: view

Animal Models for SCUBE3 Gene

MGI Knock Outs for SCUBE3:

Animal Model Products

  • Taconic Biosciences Mouse Models for SCUBE3

CRISPR Products

miRNA for SCUBE3 Gene

miRTarBase miRNAs that target SCUBE3

Inhibitory RNA Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for SCUBE3 Gene

Localization for SCUBE3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SCUBE3 Gene

Secreted. Cell surface.

Subcellular locations from

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SCUBE3 gene
Compartment Confidence
extracellular 5
plasma membrane 3
endoplasmic reticulum 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for SCUBE3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005615 extracellular space IBA --
GO:0005886 plasma membrane TAS --
GO:0009986 cell surface IDA,IEA 15234972
genes like me logo Genes that share ontologies with SCUBE3: view

Pathways & Interactions for SCUBE3 Gene

SuperPathways for SCUBE3 Gene

No Data Available

Gene Ontology (GO) - Biological Process for SCUBE3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007165 signal transduction IBA --
GO:0022617 extracellular matrix disassembly TAS --
GO:0030154 cell differentiation IBA --
GO:0045880 positive regulation of smoothened signaling pathway IEA --
GO:0051260 protein homooligomerization IDA 15234972
genes like me logo Genes that share ontologies with SCUBE3: view

No data available for Pathways by source and SIGNOR curated interactions for SCUBE3 Gene

Drugs & Compounds for SCUBE3 Gene

No Compound Related Data Available

Transcripts for SCUBE3 Gene

Unigene Clusters for SCUBE3 Gene

Signal peptide, CUB domain, EGF-like 3:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Alternative Splicing Database (ASD) splice patterns (SP) for SCUBE3 Gene

ExUns: 1 ^ 2a · 2b ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20 ^ 21 ^ 22 ^ 23 ^ 24a · 24b ·
SP1: -
SP2: - -
SP3: - - -

ExUns: 24c

Relevant External Links for SCUBE3 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for SCUBE3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for SCUBE3 Gene

mRNA differential expression in normal tissues according to GTEx for SCUBE3 Gene

This gene is overexpressed in Artery - Aorta (x15.0), Thyroid (x10.1), and Artery - Tibial (x8.5).

Protein differential expression in normal tissues from HIPED for SCUBE3 Gene

This gene is overexpressed in Bone marrow mesenchymal stem cell (68.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for SCUBE3 Gene

Protein tissue co-expression partners for SCUBE3 Gene

NURSA nuclear receptor signaling pathways regulating expression of SCUBE3 Gene:


SOURCE GeneReport for Unigene cluster for SCUBE3 Gene:


mRNA Expression by UniProt/SwissProt for SCUBE3 Gene:

Tissue specificity: Highly expressed in osteoblasts. In normal lung, mainly expressed in bronchial epithelial cells. Tends to be up-regulated in lung cancer cells.
genes like me logo Genes that share expression patterns with SCUBE3: view

Primer Products

No data available for Evidence on tissue expression from TISSUES and Phenotype-based relationships between genes and organs from Gene ORGANizer for SCUBE3 Gene

Orthologs for SCUBE3 Gene

This gene was present in the common ancestor of animals.

Orthologs for SCUBE3 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia SCUBE3 34 35
  • 99.61 (n)
(Bos Taurus)
Mammalia SCUBE3 34 35
  • 93.29 (n)
(Canis familiaris)
Mammalia SCUBE3 34 35
  • 93.15 (n)
(Monodelphis domestica)
Mammalia SCUBE3 35
  • 91 (a)
(Mus musculus)
Mammalia Scube3 34 16 35
  • 90.16 (n)
(Rattus norvegicus)
Mammalia Scube3 34
  • 89.69 (n)
(Ornithorhynchus anatinus)
Mammalia SCUBE3 35
  • 83 (a)
(Gallus gallus)
Aves SCUBE3 34 35
  • 79.18 (n)
(Anolis carolinensis)
Reptilia SCUBE3 35
  • 82 (a)
(Danio rerio)
Actinopterygii scube3 34 35
  • 70.91 (n)
fruit fly
(Drosophila melanogaster)
Insecta CG32373 35
  • 22 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 37 (a)
Species where no ortholog for SCUBE3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for SCUBE3 Gene

Gene Tree for SCUBE3 (if available)
Gene Tree for SCUBE3 (if available)

Paralogs for SCUBE3 Gene

Paralogs for SCUBE3 Gene

(3) SIMAP similar genes for SCUBE3 Gene using alignment to 1 proteins:

genes like me logo Genes that share paralogs with SCUBE3: view

Variants for SCUBE3 Gene

Sequence variations from dbSNP and Humsavar for SCUBE3 Gene

SNP ID Clin Chr 06 pos Sequence Context AA Info Type
rs193920941 Uncertain significance 35,245,288(+) CTACC(C/T)GGGCA intron-variant, upstream-variant-2KB, reference, missense
rs1000014997 -- 35,228,146(+) ATGAG(C/G)TTCAG intron-variant
rs1000066808 -- 35,214,368(+) GCCCT(C/T)CCCTG utr-variant-5-prime
rs1000107771 -- 35,248,083(+) ACCAG(A/G)GAAGA intron-variant
rs1000140749 -- 35,235,942(+) CACAG(-/T)CCCAG intron-variant

Structural Variations from Database of Genomic Variants (DGV) for SCUBE3 Gene

Variant ID Type Subtype PubMed ID
esv2759419 CNV loss 17122850

Variation tolerance for SCUBE3 Gene

Residual Variation Intolerance Score: 8.71% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.18; 51.97% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for SCUBE3 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SCUBE3 Gene

Disorders for SCUBE3 Gene

MalaCards: The human disease database

(1) MalaCards diseases for SCUBE3 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
lung cancer
  • lung cancer, protection against
- elite association - COSMIC cancer census association via MalaCards

Relevant External Links for SCUBE3

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
genes like me logo Genes that share disorders with SCUBE3: view

No data available for UniProtKB/Swiss-Prot and Genatlas for SCUBE3 Gene

Publications for SCUBE3 Gene

  1. SCUBE3 is an endogenous TGF-beta receptor ligand and regulates the epithelial-mesenchymal transition in lung cancer. (PMID: 21441952) Wu Y.Y. … Yang P.C. (Oncogene 2011) 3 4 64
  2. The role of height-associated loci identified in genome wide association studies in the determination of pediatric stature. (PMID: 20546612) Zhao J. … Grant S.F. (BMC Med. Genet. 2010) 3 46 64
  3. Many sequence variants affecting diversity of adult human height. (PMID: 18391951) Gudbjartsson D.F. … Stefansson K. (Nat. Genet. 2008) 3 46 64
  4. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T. … Sugano S. (Nat. Genet. 2004) 3 4 64
  5. A novel secreted, cell-surface glycoprotein containing multiple epidermal growth factor-like repeats and one CUB domain is highly expressed in primary osteoblasts and bones. (PMID: 15234972) Wu B.-T. … Yang R.-B. (J. Biol. Chem. 2004) 3 4 64

Products for SCUBE3 Gene

Sources for SCUBE3 Gene

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