Receptor tyrosine-protein kinase erbB-4 is an
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
that in humans is encoded by the ''ERBB4''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
Alternatively spliced variants that encode different protein isoforms have been described; however, not all variants have been fully characterized.
Function
Receptor tyrosine-protein kinase erbB-4 is a
receptor tyrosine kinase
Receptor tyrosine kinases (RTKs) are the high- affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kin ...
that is a member of the
epidermal growth factor receptor family
The ErbB family of proteins contains four receptor tyrosine kinases, structurally related to the epidermal growth factor receptor (EGFR), its first discovered member. In humans, the family includes Her1 (EGFR, ErbB1), Her2 (Neu, ErbB2), Her3 (Er ...
. ERBB4 is a single-pass type I transmembrane protein with multiple
furin
Furin is a protease, a proteolytic enzyme that in humans and other animals is encoded by the ''FURIN'' gene. Some proteins are inactive when they are first synthesized, and must have sections removed in order to become active. Furin cleaves these s ...
-like cysteine rich domains, a tyrosine kinase domain, a phosphotidylinositol-3 kinase binding site and a
PDZ domain
The PDZ domain is a common structural domain of 80-90 amino-acids found in the signaling proteins of bacteria, yeast, plants, viruses and animals. Proteins containing PDZ domains play a key role in anchoring receptor proteins in the membrane to ...
binding motif. The protein binds to and is activated by
neuregulin
Neuregulins or neuroregulins are a family of four structurally related proteins that are part of the EGF family of proteins. These proteins have been shown to have diverse functions in the development of the nervous system and play multiple essen ...
s-2, -3 and -4,
heparin-binding EGF-like growth factor
Heparin-binding EGF-like growth factor (HB-EGF) is a member of the EGF family of proteins that in humans is encoded by the ''HBEGF'' gene.
HB-EGF-like growth factor is synthesized as a membrane-anchored mitogenic and chemotactic glycoprotein. A ...
and
betacellulin
Betacellulin is a protein that in humans is encoded by the ''BTC'' gene located on chromosome 4 at locus 4q13-q21. Betacellulin was initially identified as a mitogen. Betacellulin, is a part of an Epidermal Growth Factor (EGF) family and function ...
. Ligand binding induces a variety of cellular responses including mitogenesis and differentiation. Multiple proteolytic events allow for the release of a cytoplasmic fragment and an extracellular fragment.
Clinical significance
Mutations in this gene have been associated with cancer.
Other
single-nucleotide polymorphisms
In genetics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently larg ...
and a risk haplotype have been linked to
schizophrenia
Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social wit ...
.
Single-nucleotide polymorphisms
In genetics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently larg ...
in ERBB4 have also been found in a study of patients with familial
amyotrophic lateral sclerosis type 19.
Interactions
ERBB4 has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with:
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DLG4
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NRG1
Neuregulin 1, or NRG1, is a gene of the epidermal growth factor family that in humans is encoded by the ''NRG1'' gene. NRG1 is one of four proteins in the neuregulin family that act on the EGFR family of receptors. Neuregulin 1 is produced in num ...
,
*
STAT5A
Signal transducer and activator of transcription 5A is a protein that in humans is encoded by the ''STAT5A'' gene. ''STAT5A'' orthologs have been identified in several placentals for which complete genome data are available.
Structure
STAT5a s ...
,
and
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YAP1
YAP1 (yes-associated protein 1), also known as YAP or YAP65, is a protein that acts as a transcription coregulator that promotes transcription of genes involved in cellular proliferation and suppressing apoptotic genes. YAP1 is a component in th ...
.
References
Further reading
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External links
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{{Portal bar, Biology, border=no
Tyrosine kinase receptors