Property Summary

NCBI Gene PubMed Count 42
PubMed Score 681.62
PubTator Score 69.33

Knowledge Summary


No data available


  Differential Expression (14)

Disease log2 FC p
urothelial carcinoma -1.500 4.8e-02
psoriasis -4.200 2.2e-243
posterior fossa group B ependymoma 2.100 3.6e-06
Atopic dermatitis -4.200 1.0e-08
intraductal papillary-mucinous adenoma (... 2.300 5.9e-04
intraductal papillary-mucinous carcinoma... 1.700 1.1e-02
intraductal papillary-mucinous neoplasm ... 1.700 4.5e-02
colon cancer -2.700 4.0e-04
lung cancer -2.000 3.6e-05
interstitial cystitis -1.500 3.3e-03
nasopharyngeal carcinoma -1.300 5.5e-03
spina bifida -2.420 2.9e-02
Breast cancer -1.400 1.1e-04
pituitary cancer 1.500 1.6e-04

Protein-protein Interaction (167)

Gene RIF (27)

24629040 CXCL8 production from lung cancer cells could be initiated by an autocrine mechanism or external sources of BTC.
24092824 Data suggest that BTC (betacellulin), AREG (amphiregulin), and EREG (epiregulin) induced prostaglandin E2 production by induction of COX-2 (prostaglandin-endoperoxide synthase 2) through MAP kinase signaling in granulosa cells.
22183345 BTC has properties of increasing retinal vascular leakage that could contribute to the development of diabetic retinopathy.
20530572 Data suggest a novel receptor-independent role for betacellulin intracellular-domain fragment signaling due to its ability to inhibit cell growth in vitro.
20165885 These are the first data that demonstrate an influence of betacellulin upon mesenchymal stem cells and the first to implicate HIF-alpha in betacellulin-mediated proliferation.
18508082 These results indicate the possibility of designing BTC mutants, which have an activity of inducing differentiation only, without facilitating growth promotion.
17962208 1st report of BTC expression in breast cancer. Its expression was lower in lobular breast cancers than in ductal carcinomas.
17895248 the ADAM10 prodomain inhibits betacellulin shedding, demonstrating that it could be of potential use as a therapeutic agent to treat cancer.
17525275 In vivo, EGFR signaling is hyperactive in tumor cells of skin SCC but not of BCC, and in nearby asymptomatic epidermis of both tumor types. Hyperactivation is due to upregulation of EGFR ligands AREG, HBEGF and TGFA, and downregulation of BTC
17479438 Variants in the betacellulin gene do not play a major role in the development of type 2 diabetes in an Amish Caucasian populations
16869959 Observational study of gene-disease association. (HuGE Navigator)
16869959 Failure to confirm a role for nonsynonymous coding variants of betacellulin in the propensity to type 2 diabetes or to impaired insulin secretion in African American subjects.
16683131 Observational study of gene-disease association. (HuGE Navigator)
16683131 intron 4 T-4 allele in the betacellulin gene is associated with lower risk of type 1 diabetes mellitus and may interact with human leukocyte antigen
16306376 Observational study of gene-disease association. (HuGE Navigator)
16306376 -226A/G polymorphism of the BTC gene may contribute to the development of diabetes.
15936459 Observational study of gene-disease association. (HuGE Navigator)
15936459 Genetic variations in the protein-coding region of the human BTC gene are unlikely to be a major contributor to development of type 2 diabetes.
15793259 Observational study of gene-disease association. (HuGE Navigator)
15793259 To determine if mutations in the betacellulin gene play a role in the development of type 2 diabetes, we screened subjects with type 2 diabetes for the presence of mutations.
15507448 shedding of precursor is mediated by ADAM10
15274392 Betacellulin is expressed in malignant fibrous histiocytoma and is a regulator of tumor growth.
15248827 BTC may play a pivotal role as a local growth factor in promoting the differentiated villous trophoblastic function via ErbB-1 in early placentas and in contributing to placental growth through EVT cell function via ErbB-4 in term placentas.
15192046 although BTC and EGF share overlapping signaling properties, the ability of BTC to enhance Erk activation occurs independent of Ras.
12768307 Betacellulin and heregulin/NDF-alpha are involved in epidermal morphogenesis and/or in maintenance of the differentiated phenotype.
12111392 The main structural properties of the model and the templates are compared and the hBTC conformation is closely similar to that of hTGFalpha.
12074582 The solution structure of the EGF-like domain of betacellulin has been determined using two-dimensional nuclear magnetic resonance spectroscopy

AA Sequence

CCHPLRKRRKRKKKEEEMETLGKDITPINEDIEETNIA                                    141 - 178

Text Mined References (45)

PMID Year Title
26871637 2016 Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.
25416956 2014 A proteome-scale map of the human interactome network.
24629040 2014 Regulatory mechanisms of betacellulin in CXCL8 production from lung cancer cells.
24440602 2014 The ABC of BTC: structural properties and biological roles of betacellulin.
24092824 2013 EGF-like growth factors induce COX-2-derived PGE2 production through ERK1/2 in human granulosa cells.
22183345 2012 Regulation of retinal vascular permeability by betacellulin.
20530572 2010 Sequential and gamma-secretase-dependent processing of the betacellulin precursor generates a palmitoylated intracellular-domain fragment that inhibits cell growth.
20165885 2010 Betacellulin inhibits osteogenic differentiation and stimulates proliferation through HIF-1alpha.
19740107 2009 Epidermal growth factor receptor ligands as new extracellular targets for the metastasis-promoting S100A4 protein.
18508082 2008 A betacellulin mutant promotes differentiation of pancreatic acinar AR42J cells into insulin-producing cells with low affinity of binding to ErbB1.
17962208 2008 ErbB/HER ligands in human breast cancer, and relationships with their receptors, the bio-pathological features and prognosis.
17895248 2007 The ADAM10 prodomain is a specific inhibitor of ADAM10 proteolytic activity and inhibits cellular shedding events.
17525275 2007 Differential ErbB1 signaling in squamous cell versus basal cell carcinoma of the skin.
17479438 2007 Betacellulin variants and type 2 diabetes in the Old Order Amish.
16869959 2006 Analysis of coding variants in the betacellulin gene in type 2 diabetes and insulin secretion in African American subjects.
16683131 2006 Association of a polymorphism in the betacellulin gene with type 1 diabetes mellitus in two populations.
16381901 2006 The LIFEdb database in 2006.
16306376 2005 A functional variant in the human betacellulin gene promoter is associated with type 2 diabetes.
16081630 2005 Betacellulin-delta4, a novel differentiation factor for pancreatic beta-cells, ameliorates glucose intolerance in streptozotocin-treated rats.
15936459 2005 Molecular scanning of the betacellulin gene for mutations in type 2 diabetic patients.
15793259 2005 The exon 1 Cys7Gly polymorphism within the betacellulin gene is associated with type 2 diabetes in African Americans.
15507448 2005 ADAM10 mediates ectodomain shedding of the betacellulin precursor activated by p-aminophenylmercuric acetate and extracellular calcium influx.
15489336 2004 From ORFeome to biology: a functional genomics pipeline.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15274392 Expression of betacellulin, heparin-binding epidermal growth factor and epiregulin in human malignant fibrous histiocytoma.
15248827 2004 Changes in the expression and cytological localization of betacellulin and its receptors (ErbB-1 and ErbB-4) in the trophoblasts in human placenta over the course of pregnancy.
15192046 2004 Differential activation of epidermal growth factor (EGF) receptor downstream signaling pathways by betacellulin and EGF.
12768307 2003 Proliferation-differentiation relationships in the expression of heparin-binding epidermal growth factor-related factors and erbB receptors by normal and psoriatic human keratinocytes.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12111392 2002 Human betacellulin structure modeled from other members of EGF family.
12074582 2002 Solution structure of betacellulin, a new member of EGF-family ligands.
11522793 2001 Novel betacellulin derivatives. Separation of the differentiation activity from the mitogenic activity.
11334053 2000 Identification of an alternatively spliced mRNA transcript of human betacellulin lacking the C-loop of the EGF motif and the transmembrane domain.
11254912 2001 Immunohistochemical localization of Betacellulin, a member of epidermal growth factor family, in atherosclerotic plaques of human aorta.
11076863 2000 DNA cloning using in vitro site-specific recombination.
10940639 2000 Structure-function and biological role of betacellulin.
10867024 2000 Ligand discrimination in signaling through an ErbB4 receptor homodimer.
10706134 2000 Epidermal growth factor-like ligands differentially up-regulate matrix metalloproteinase 9 in head and neck squamous carcinoma cells.
9662041 1998 Studies on the betacellulin receptor in pancreatic AR42J cells.
9528863 1998 Betacellulin-Pseudomonas toxin fusion proteins bind but are not cytotoxic to cells expressing HER4; correlation of EGFR for cytotoxic activity.
8919026 1996 Human betacellulin, a member of the EGF family dominantly expressed in pancreas and small intestine, is fully active in a monomeric form.
8570211 1996 Betacellulin activates the epidermal growth factor receptor and erbB-4, and induces cellular response patterns distinct from those stimulated by epidermal growth factor or neuregulin-beta.
8439318 1993 Cloning and expression of cDNA encoding human betacellulin, a new member of the EGF family.
8144591 1994 Recombinant human betacellulin. Molecular structure, biological activities, and receptor interaction.
7590736 1995 Mouse chromosomal location of three EGF receptor ligands: amphiregulin (Areg), betacellulin (Btc), and heparin-binding EGF (Hegfl).