Summary: Phorbol esters/diacylglycerol binding domain (C1 domain)
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C1 domain Edit Wikipedia article
|Phorbol esters/diacylglycerol binding domain (C1 domain)|
C1 domain of PKC-delta (1ptr) Middle plane of the lipid bilayer - black dots. Boundary of the hydrocarbon core region - blue dots (cytoplasmic side). Layer of lipid phosphates - yellow dots.
|SCOPe||2cpk / SUPFAM|
C1 domain (also known as phorbol esters/diacylglycerol binding domain) binds an important secondary messenger diacylglycerol (DAG), as well as the analogous phorbol esters. Phorbol esters can directly stimulate protein kinase C, PKC. The N-terminal region of PKC, known as C1, has been shown
Phorbol esters (such as PMA) are analogues of DAG and potent tumor promoters that cause a variety of physiological changes when administered to both cells and tissues. DAG activates a family of serine/threonine protein kinases, collectively known as protein kinase C (PKC). Phorbol esters can directly stimulate PKC.
The N-terminal region of PKC, known as C1, binds PMA and DAG in a phospholipid and zinc-dependent fashion. The C1 region contains one or two copies of a cysteine-rich domain, which is about 50 amino-acid residues long, and which is essential for DAG/PMA-binding.
The DAG/PMA-binding domain binds two zinc ions; the ligands of these metal ions are probably the six cysteines and two histidines that are conserved in this domain.
Human proteins containing this domain
AKAP13; ARAF; ARHGAP29; ARHGEF2; BRAF; CDC42BPA; CDC42BPB; CDC42BPG; CHN1; CHN2; CIT; DGKA; DGKB; DGKD; DGKE; DGKG; DGKH; DGKI; DGKK; DGKQ; DGKZ; GMIP; HMHA1; KSR1; KSR2; MYO9A; MYO9B; PDZD8; PRKCA; PRKCB1; PRKCD; PRKCE; PRKCG; PRKCH; PRKCI; PRKCN; PRKCQ; PRKCZ; PRKD1; PRKD2; PRKD3; RACGAP1; RAF1; RASGRP; RASGRP1; RASGRP2; RASGRP3; RASGRP4; RASSF1; RASSF5; ROCK1; ROCK2; STAC; STAC2; STAC3; TENC1; UNC13A; UNC13B; UNC13C; VAV1; VAV2; VAV3;
- Azzi A, Boscoboinik D, Hensey C (1992). "The protein kinase C family". Eur. J. Biochem. 208 (3): 547â€“557. doi:10.1111/j.1432-1033.1992.tb17219.x. PMID 1396661.
- Kikkawa U, Nishizuka Y, Igarashi K, Fujii T, Ono Y, Kuno T, Tanaka C (1989). "Phorbol ester binding to protein kinase C requires a cysteine-rich zinc-finger-like sequence". Proc. Natl. Acad. Sci. U.S.A. 86 (13): 4868â€“4871. doi:10.1073/pnas.86.13.4868. PMC 297516. PMID 2500657.
This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
Phorbol esters/diacylglycerol binding domain (C1 domain) Provide feedback
This domain is also known as the Protein kinase C conserved region 1 (C1) domain.
Knighton DR, Zheng JH, Ten Eyck LF, Ashford VA, Xuong NH, Taylor SS, Sowadski JM; , Science. 1991;253:407-414.: Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase. PUBMED:1862342 EPMC:1862342
Internal database links
|SCOOP:||C1_2 Filamin PHD PHD_2 Prok-RING_1 zf-C2H2 zf-H2C2_2 zf-PHD-like zf-RING-like zf-RING_15 zf-RING_16 zf-RING_2 zf-RING_9|
|Similarity to PfamA using HHSearch:||C1_2 zf-RING-like|
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR002219
Diacylglycerol (DAG) is an important second messenger. Phorbol esters (PE) are analogues of DAG and potent tumour promoters that cause a variety of physiological changes when administered to both cells and tissues. DAG activates a family of serine/threonine protein kinases, collectively known as protein kinase C (PKC) [ PUBMED:1396661 ]. Phorbol esters can directly stimulate PKC. The N-terminal region of PKC, known as C1, has been shown [ PUBMED:2500657 ] to bind PE and DAG in a phospholipid and zinc-dependent fashion. The C1 region contains one or two copies (depending on the isozyme of PKC) of a cysteine-rich domain, which is about 50 amino-acid residues long, and which is essential for DAG/PE-binding. The DAG/PE-binding domain binds two zinc ions; the ligands of these metal ions are probably the six cysteines and two histidines that are conserved in this domain.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Biological process||intracellular signal transduction (GO:0035556)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
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The members of this clan are all variations of the protein kinase C1 domain that is characterised by a rich cysteine and histidine content. The C1 domain is the N-terminal region of conservation found in protein kinase C domains. This domain is involved in binding many ligands, which include diacylglycerol, phorbol esters and zinc .
The clan contains the following 4 members:C1_1 C1_2 C1_4 ZZ
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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
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This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
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Curation and family details
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|Previous IDs:||DAG_PE-bind; C1;|
|Number in seed:||44|
|Number in full:||47816|
|Average length of the domain:||52.60 aa|
|Average identity of full alignment:||31 %|
|Average coverage of the sequence by the domain:||7.25 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||25|
|Download:||download the raw HMM for this family|
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How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:
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Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
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The tree shows the occurrence of this domain across different species. More...
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For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.
Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the C1_1 domain has been found. There are 62 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
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AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.