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Taxonomy and function of C1 protein kinase C homology domains
Open accessAbstract
C1 domains are compact α/β structural units of about 50 amino acids which tightly bind two zinc ions. These domains were first discovered as the loci of phorbol ester and diacylglycerol binding to conventional protein kinase C isozymes, which contain two C1 domains (CIA and C1B) in their N‐terminal regulatory regions. We present a comprehensive list of 54 C1 domains occurring singly or doubly in 34 different proteins. Many C1 domains and C1 domain‐containing proteins bind phorbol esters, but many others do not. By combining analysis of 54 C1 domain sequences with information from previously reported solution and crystal structure determinations and site‐directed mutagenesis, profiles are derived and used to classify C1 domains. Twenty‐six C1 domains fit the profile for phorbol‐ester binding and are termed “typical.” Twenty‐eight other domains fit the profile for the overall C1 domain fold but do not fit the profile for phorbol ester binding, and are termed “atypical.” Proteins containing typical C1 domains are predicted to be regulated by diacylglycerol, whereas those containing only atypical domains are not.
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“Prior studies indicate that the GEFH1 C1 domain does not bind diacylglycerol,21”
From Structural basis of microtubule-mediated signal transduction (2026) · cites this paper as [26]
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“The C1 domain, also referred to as phorbol esters/diacylglycerol-binding domain, is part of a group of zinc-finger proteins homologous to the conserved region 1 of protein kinase C.”
From Structural basis of microtubule-mediated signal transduction (2026) · cites this paper as [26]
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“The first retinoid form to be described to act in this way was retinol, which was reported to bind to different proteins from the serine/threonine kinase family, specifically rapidly accelerated fibrosarcoma (Raf) and protein kinase C (PKC), and function as a redox reagent [249,250].”
From Vitamin A Update: Forms, Sources, Kinetics, Detection, Function, Deficiency, Therapeutic Use and Toxicity (2021) · cites this paper as [250]
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Metadata
- Authors
- Hurley, J. H., Newton, A. C., Parker, P. J., Blumberg, P. M., & Nishizuka, Y.
- Affiliations
- National Institutes of Health (US)
- University of California San Diego (US)
- Biosignal Research Center, Kobe University (JP)
- Corresponding author
- Hurley, James H.
- Venue
- Protein Science
- Publisher
- Wiley
- Published
- 1997-02
- Volume
- 6
- Issue
- 2
- Pages
- 477-480
- ISSN
- 0961-8368 (ISSN-L)
- 1469-896X
- PMC
- PMC2143645
- OpenAlex
- W2010994547
- Cited by
- 362
- References
- 30
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 3 · 2023: 4 · 2022: 2 · 2021: 10 · 2020: 5 · 2019: 12 · 2018: 4 · 2017: 11 · 2016: 8 · 2015: 13 · 2014: 16 · 2013: 7 · 2012: 16
- FWCI
- 7.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Protein Science (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Keywords
- C1 domain, protein kinase C, phorbol ester binding, zinc-binding domain, protein domain classification
- MeSH terms
- Amino Acid Sequence, Animals, Humans, Molecular Sequence Data, Protein Kinase C, Sequence Homology, Amino Acid
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