BTC betacellulin [Homo sapiens (human)] - Gene

Summary

Official Symbol: BTCprovided by HGNC
Official Full Name: betacellulinprovided by HGNC
Primary source: HGNC:HGNC:1121
See related: Ensembl:ENSG00000174808 MIM:600345; AllianceGenome:HGNC:1121
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary: This gene encodes a member of the epidermal growth factor (EGF) family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the secreted growth factor. A secreted form and a membrane-anchored form of this protein bind to multiple different EGF receptors. This protein promotes pancreatic cell proliferation and insulin secretion, as well as retinal vascular permeability. Mutations in this gene may be associated with type 2 diabetes in human patients. [provided by RefSeq, Nov 2015]
Expression: Broad expression in skin (RPKM 3.9), esophagus (RPKM 3.5) and 18 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 4q13.3

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (74744759..74794523, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (78084851..78134624, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (75669969..75719733, complement)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Betacellulin regulates gap junction intercellular communication by inducing the phosphorylation of connexin 43 in human granulosa-lutein cells.
Title: Betacellulin regulates gap junction intercellular communication by inducing the phosphorylation of connexin 43 in human granulosa-lutein cells.
Betacellulin enhances ovarian cancer cell migration by up-regulating Connexin43 via MEK-ERK signaling.
Title: Betacellulin enhances ovarian cancer cell migration by up-regulating Connexin43 via MEK-ERK signaling.
Despite both ligands binding to the EGFR, BTC biases the EGFR to dimerize with ErbB3 to regulate the biologic response.
Title: Betacellulin (BTC) Biases the EGFR To Dimerize with ErbB3.
Our results suggest that betacellulin induces ovarian cancer migration and Slug-dependent E-cadherin down-regulation
Title: Betacellulin induces Slug-mediated down-regulation of E-cadherin and cell migration in ovarian cancer cells.
CXCL8 production from lung cancer cells could be initiated by an autocrine mechanism or external sources of BTC.
Title: Regulatory mechanisms of betacellulin in CXCL8 production from lung cancer cells.
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.
Title: EGF-like growth factors induce COX-2-derived PGE2 production through ERK1/2 in human granulosa cells.
BTC has properties of increasing retinal vascular leakage that could contribute to the development of diabetic retinopathy.
Title: Regulation of retinal vascular permeability by betacellulin.
Data suggest a novel receptor-independent role for betacellulin intracellular-domain fragment signaling due to its ability to inhibit cell growth in vitro.
Title: Sequential and gamma-secretase-dependent processing of the betacellulin precursor generates a palmitoylated intracellular-domain fragment that inhibits cell growth.
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.
Title: Betacellulin inhibits osteogenic differentiation and stimulates proliferation through HIF-1alpha.
These results indicate the possibility of designing BTC mutants, which have an activity of inducing differentiation only, without facilitating growth promotion.
Title: A betacellulin mutant promotes differentiation of pancreatic acinar AR42J cells into insulin-producing cells with low affinity of binding to ErbB1.

Submit: New GeneRIF Correction See all GeneRIFs (27)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-35798 (e-PCR)
- UniSTS:36941

SHGC-59577 (e-PCR)
- UniSTS:49741

D4S1633E (e-PCR)
- UniSTS:148571

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables epidermal growth factor receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables growth factor activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables receptor ligand activity	IDA Inferred from Direct Assay more info	PubMed
enables transmembrane receptor protein tyrosine kinase activator activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in ERBB2-EGFR signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in ERBB4-ERBB4 signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in cell population proliferation	IEA Inferred from Electronic Annotation more info
involved_in epidermal growth factor receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in epithelial cell apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of epithelial cell apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cell division	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cell population proliferation	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of fibroblast proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of mitotic nuclear division	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of urine volume	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in clathrin-coated endocytic vesicle membrane	TAS Traceable Author Statement more info
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
is_active_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: probetacellulin

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001316963.2 → NP_001303892.1 probetacellulin isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 3' coding region compared to variant 1. The encoded isoform (2, also known as BTC-beta or BTC-delta4) lacks the transmembrane domain and a portion of the EGF domain compared to isoform 1.

Source sequence(s)

AB109441, AC116645, BI552049, BX114471, S55606

UniProtKB/TrEMBL

A0A0S2Z3I5, H0Y8Q5

Related

ENSP00000421747.1, ENST00000512743.1
NM_001729.4 → NP_001720.1 probetacellulin isoform 1 preproprotein

See identical proteins and their annotated locations for NP_001720.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AB109441, AC116645, BX114471, S55606

Consensus CDS

CCDS3566.1

UniProtKB/Swiss-Prot

P35070, Q96F48

UniProtKB/TrEMBL

A0A0S2Z437

Related

ENSP00000379092.3, ENST00000395743.8

Conserved Domains (1) summary

PHA02887
Location:50 → 109

PHA02887; EGF-like protein; Provisional