Betacellulin

BTC
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1IOX, 1IP0
Identifiers
Aliases	BTC, entrez:685, betacellulin
External IDs	OMIM: 600345; MGI: 99439; HomoloGene: 1309; GeneCards: BTC; OMA:BTC - orthologs
Gene location (Human) Chr. Chromosome 4 (human)[1] Band 4q13.3 Start 74,744,759 bp[1] End 74,794,523 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5 E2|5 44.78 cM Start 91,505,120 bp[2] End 91,550,853 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gastric mucosa bronchial epithelial cell ascending aorta retinal pigment epithelium right coronary artery skin of abdomen rectum popliteal artery transverse colon gallbladder Top expressed in mucous cell of stomach pyloric antrum epithelium of stomach medullary collecting duct skin of back retinal pigment epithelium cumulus cell skin of abdomen duodenum belly cord More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding phosphatidylinositol-4,5-bisphosphate 3-kinase activity protein tyrosine kinase activity epidermal growth factor receptor binding growth factor activity Cellular component integral component of membrane membrane plasma membrane extracellular region intracellular anatomical structure extracellular space clathrin-coated vesicle membrane Biological process positive regulation of urine volume positive regulation of fibroblast proliferation negative regulation of apoptotic process MAPK cascade positive regulation of cell differentiation positive regulation of cell population proliferation positive regulation of mitotic nuclear division positive regulation of cell division regulation of cell motility phosphatidylinositol phosphate biosynthetic process epidermal growth factor receptor signaling pathway ERBB2 signaling pathway peptidyl-tyrosine phosphorylation regulation of signaling receptor activity positive regulation of protein kinase B signaling signal transduction negative regulation of epidermal growth factor receptor signaling pathway membrane organization Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 685 12223 Ensembl ENSG00000174808 ENSMUSG00000082361 UniProt P35070 Q05928 RefSeq (mRNA) NM_001729 NM_001316963 NM_007568 RefSeq (protein) NP_001303892 NP_001720 NP_031594 Location (UCSC) Chr 4: 74.74 – 74.79 Mb Chr 5: 91.51 – 91.55 Mb PubMed search [3] [4]
Wikidata
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Betacellulin is a protein that in humans is encoded by the BTC gene located on chromosome 4 at locus 4q13-q21.^[5] Betacellulin was initially identified as a mitogen.^[6] Betacellulin, is a part of an Epidermal Growth Factor (EGF) family and functions as a ligand for the epidermal growth factor receptor (EGFR). The role of betacellulin as an EGF is manifested differently in various tissues, and it has a great effect on nitrogen signaling in retinal pigment epithelial cells and vascular smooth muscle cells. While many studies attest a role for betacellulin in the differentiation of pancreatic β-cells, the last decade witnessed the association of betacellulin with many additional biological processes, ranging from reproduction to the control of neural stem cells.^[6] Betacellulin is a member of the EGF family of growth factors. It is synthesized primarily as a transmembrane precursor, which is then processed to mature molecule by proteolytic events.

Structure

As shown on figure 1, the secondary structure of the human betacellulin-2 has 6% helical (1 helices; 3 residues) 36% beta sheet (5 strands; 18 residues). The mRNA of betacellulin contains six exons in which is 2816 base-pair long.^[6] The mRNA was translated into 178 amino acids, and different regions of the amino acid are responsible for different function.^[6] The first 31 amino acids are responsible for the signal peptide (Figure 2, exon 1), the 32nd to 118th amino acids are responsible for the extracellular region (Figure 2, exon 2 and 3), the 65-105 amino acids are responsible for the EGF-like domain (Figure 2, exon 3), the transmembrane domain is from amino acids 119-139 (Figure 2, exon 4), the cytoplasmic tail is from amino acid 140-178 (Figure 2, exon 5).^[6]

• 
  Figure 1. NMR Structure of Human Betacellulin-2
• 
  Figure 2. The transcription and translation product of betacellulin gene

Function

As a typical EGFR ligand, betacellulin is expressed by a variety of cell types and tissues, the post-translation of the betacellulin can ectodomain shedding, and the proteolytic release the soluble factors can bind and activate the homodimer or heterodimer of the ERBB receptors. The membrane-anchored form of the betacellulin can activate the epidermal growth factor receptor (EGFR).^[7] Betacellulin stimulates the proliferation of retinal pigment epithelial and vascular smooth muscle cells but did not stimulate the growth of several other cell types, such as endothelial cells and fetal lung fibroblasts.^[8]

Tissue distribution

The mRNA coding for betacellulin was found to be slightly higher compared in the rat sciatic nerve segment after nerve damage, suggesting that betacellulin can play a role in peripheral nerve regeneration. Immunohistochemistry has been used to look for betacellulin expression in Schwann cells. Treating cells with betacellulin recombinant protein can be used to investigate the role of betacellulin in managing Schwann cells. A co-culture assay can also used to assess the effect of Schwann cell-secreted betacellulin on neurons.^[9]

Mouse BTC is expressed as a 178-amino acid precursor. The membrane-bound precursor is cleaved to yield mature secreted mouse BTC. BTC is synthesized in a wide range of adult tissues and in many cultured cells, including smooth muscle cells and epithelial cells. The amino acid sequence of mature mouse BTC is 82.5%, identical with that of human BTC, and both exhibit significant overall similarity with other members of the EGF family.

Clinical significance

The transcription factor signal transducer and activator of transcription 3 (STAT3) was identified as the therapeutic target for glioblastoma.^[10]

References

Further reading

External links

• Betacellulin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.